ims accesspoint - november 2011

IMS HEALTH ECONOMICS AND OUTCOMES RESEARCHOUTCOMES - Issue 1 Page 1

Volume 2, Issue 3NOVEMBER 2011

IMS HEALTH ECONOMICS & OUTCOMES RESEARCH

News, views andinsights from

leading experts in HEOR

The era of ‘prove it works’

Validating the IMSCORE Diabetes Model

Chris Blanchettepresents a noveldata linkagetechnique for CERPage 30

Xavier Badia andNúria Lara Surinachconsider challengesof studies in AsiaPage 16

Dana Morlet-Vigierand Arnaud Troubaton impact of drugreform in France Page 8

Real-world evidence drives agenda

US senior drug costs defy expectations

ACCESSPOINT

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‘Prove it works’The growing need for real-world evidenceheralds a new era for pharmapage 12

Planning for observationalresearch in AsiaEmerging markets offer challenges andbenefits for primary data collectionpage 16

Capturing the real world in real timeTechnological advancements extend capabilitiesof IMS LifeLink™ EMR database in Europe page 20

News, views and insights from leading experts in HEORIMS HEALTH ECONOMICS & OUTCOMES RESEARCH

ACCESSPOINT

Validating the modelMajor updates to IMS CORE

Diabetes Model are undergoingrigorous validation

page 34

Extending theoutreach of HEOR

In the age of the empowered consumer,

we consider the implications of DTC engagement in Europe

page 38

AccessPoint - Issue 3 Page 1

WELCOME CONTENTSWelcome to the third issue of ACCESSPOINT, a twice-yearlyreview of news and insights from our international HEORexperts at the IMS Consulting Group – sharing theprograms that are expanding our contribution to globalhealth and the real-world research that is enabling moreinformed, evidence-based decision making.

As we approach the end of 2011, we can reflect on a year of impetusand innovation in pharmaceutical markets around the world: inFrance, the culmination of a drug safety scandal has triggered aradical reassessment of pharmaceutical regulation with majorimplications long-term (page 8); in the U.S. and Europe,concentrated pressure on the demands of information is driving newinitiatives in healthcare datasets from both the public and privatesector, enabling more and better evidence generation (page 25); inthe dynamic emerging Asian markets, converging trends are creatinga need for different approaches to observational research (page 16);and globally, the imperative for real-world evidence is signaling thestart of a new “prove it works” era for pharma (page 12).

Already, the call for more rigorous outcomes research and evidenceof comparative effectiveness is fuelling novel techniques andtechnology refinements that will transform our ability to evaluateand analyze the value of medicines: sophisticated data linkageapproaches promise more holistic patient-level research (page 30);technical enhancements are extending the potential of IMS LifeLink™EMR datasets in Europe (page 20); and advanced methodologies areproving the feasibility of extrapolating data across multiple markets(page 48). Underpinning it all is the growing need to ensure thatour value messages reach out and resonate with a broader audience(page 38).

Leveraging the potential of these new developments will be key tomeeting the changing demands of the market. IMS is committedto accelerating understanding based on sharper, more effective use ofinformation and continued innovation. Our global team of highly-qualified, multi-disciplinary HEOR researchers andconsultants works with government agencies, academic leaders (pages 2, 5) and our unparalleled global data assets to advanceevidence-based healthcare in critical and pioneering areas. Majorenhancements to the IMS CORE Diabetes Model (page 4), whichare now undergoing extensive validation (page 34) underscore ourresolve to capture the very latest scientific and technical advances.And findings from our analyses continue to provide importantinsights into policy impact (page 43) and the key dynamics that areshaping the future landscape (page 7).

I hope you find this issue of ACCESSPOINT informative and timely aswe look forward to the opportunities and challenges ahead in 2012.

AccessPoint is published twice yearly by the Health Economics& Outcomes Research team of the IMS Consulting Group.VOLUME 2 ISSUE 3. PUBLISHED NOVEMBER 2011.

IMS HEALTH® 7 Harewood Avenue, London NW1 6JB, UKTel: +44 (0) 20 3075 4800 • [email protected]/heor

©2011 IMS Health Incorporated or its affiliates. All Rights Reserved.

“We are moving from a year of impetus andinnovation to a new era of transformation”

Jon ResnickVICE PRESIDENT AND GLOBAL LEADER, HEORIMS CONSULTING [email protected]

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NEWS SECTION2 McGowan collaboration for HEOR in

regenerative medicine3 Budget impact model for pharmacy setting4 New IMS CORE Diabetes Model goes live!5 Towards best practice modeling in COPD6 IMS Pharma Policy Analyzer to launch in Spain7 IMS Institute explores latest dynamicsINSIGHTS8 DRUG REFORM IN FRANCE Safety scandal triggers major review12 REAL-WORLD EVIDENCE

The era of ‘prove it works’ 16 OBSERVATIONAL RESEARCH IN ASIA

Challenges in emerging markets 20 EUROPEAN EMR DATA

Capturing the real world in real time 25 IMS ISPOR SYMPOSIUM

New horizons for patient-level data 30 PROBABILISTIC DATA LINKAGE

Novel technique for comparative research34 IMS CORE DIABETES MODEL

Robust validation after major enhancements38 COMMUNICATION AND OUTREACH

Implications of DTC advertising43 MEDICARE PART D

Why seniors’ drugs costs are going downPROJECT FOCUS48 CHEMOTHERAPY-INDUCED ANEMIA

Adapting country-specific data 50 BREAST CANCER Understanding real-world persistenceIMS CONSULTING GROUP OVERVIEW52 Locations, expertise, LifeLink™


NEWS | REGENERATIVE MEDICINE

Discussions are underway tocooperate on further initiatives thatwill underscore the importance ofhealth economics in regenerativemedicine and advance its applicationin this pioneering field

Regenerative medicine offers tremendous potential for tissue and organ repair.A new collaboration taps IMS HEOR expertise for pioneering research.

IMS partners with McGowan Instituteto advance HEOR analysis inregenerative medicine

IMS HEOR is to design and conduct independentcost analyses for the development, administration,treatment and follow-up of regenerativeinterventions in two studies being conducted underthe Limb Salvage and Regenerative MedicineInitiative. These have been instigated by theMcGowan Institute for Regenerative Medicine, aUniversity of Pittsburgh Medical Center programand world-renowned leader in the emerging fieldof regenerative tissue research.

The studies will investigate the use of biologic scaffolds formuscle tissue regeneration in patients suffering from massiveloss of skeletal muscle tissue, and allogenic human dermalfibroblasts for remodeling scar contractures. IMS will provideindependent health economic (HE) analyses of these efficacystudies. The key sub-tasks to be performed by IMS are thecalculation of cost per subject and comparison of costs forthe new interventions versus standard of care.

NEW COLLABORATIONThe input from IMS HEOR forms part of a new collaborationbetween IMS Government Solutions and the McGowanInstitute for Regenerative Medicine to bring the promise ofgroundbreaking medical advances to U.S. Service memberswho have been severely wounded in combat. This centers onan initiative funded by the Office of the Secretary ofDefense–Office of Technology Transition (OSD-OTT) to testand implement new approaches to skeleto-muscleregeneration, cranio-facial reconstruction and scarcontracture remodeling for wounded soldiers.

McGowan medical staff will apply their expertise in tissueengineering and cellular therapies for a group of 100 veteransreturning from Iraq and Afghanistan. IMS HEOR will workwith the IMS Government Solutions team to provide dataanalysis, outcomes research and benchmarking services,including establishing a baseline for monitoring patientresponses, tracking recovery patterns and advancing newapproaches in clinical translation. Among other uses,information from these analyses will provide historical datafor similar future efforts of this kind.

PROMOTING IMPORTANCE OF HEOR Discussions are also underway between IMS HEOR, the IMSInstitute, IMS Government Solutions and the PTEI Center forRegenerative Medicine Economics at the University ofPittsburgh, to cooperate on further initiatives that willunderscore the importance of health economics inregenerative medicine and advance its application in thispioneering field. •

For further information on this initiative, please contactRichard Chapman, Principal HEOR, IMS Consulting Group, U.S.,[email protected]


IMS PHARMACY BUDGET IMPACT MODEL | NEWS

Understanding budget impact is key for rational decision making. A new modeling initiative from IMS supports analyses in the pharmacy setting.

IMS pharmacy budget impact modelenables new insights for a widerange of stakeholders

IMS HEOR and the Payer Solutions unit of IMSHealth are collaborating to develop a standardizedmodel framework to estimate the pharmacy budgetimpact (BI) of adopting or diffusing a newtherapeutic intervention. This will initially coverthe U.S. with plans for global expansion.

Budget impact analyses (BIA) are an essential component ofa comprehensive economic assessment of a healthcaretechnology. They are increasingly required by nationalregulatory agencies and managed care organizations toestimate the economic consequences of introducing a newdrug or technology within a specific setting of care.

The IMS initiative reflects growing recognition that despitenational and local guidelines for developing BIAs there arestill opportunities to address hurdles to their optimal use,such as:

• Payer skepticism of BIAs developed by manufacturers

• Opaque (or lack of) benchmarks to evaluate budget impact

• Inefficient practice of developing models de novo tosupport new products/analyses

FLEXIBLE, MULTI-USE STANDARDIZED SOLUTION The turnkey modeling solution developed by the collaborativeIMS team is a flexible, multi-use and standardized frameworkto enable multiple analyses across therapeutic areas. It ispre-populated with proprietary data on prescription drug useand drug prices to establish national (or regional)benchmarks for comparison.

All model screens are presented in logical fashion andinclude: informational screens, user input screens(population, market basket, drug prices and contracting) andresults and sensitivity analyses. Users may select defaultdata sources and assumptions and override all inputs toperform exploratory scenario analyses.

Members of the development team, which includes expertsfrom the IMS Center of Excellence for Health EconomicModeling, believe the BI model’s standardized platform andanalytic scope will facilitate BIAs by companies and payers alike.

Users will include those who manage and plan for healthcarebudgets such as administrators of insurance plans, healthcaredelivery organizations or employers, as well as manufacturersof new pharmaceutical or healthcare interventions. •

For further information on the IMS Pharmacy BudgetImpact Model, please contact Julie Munakata, PrincipalHEOR, IMS Consulting Group, U.S., [email protected]

ERRATUMPutting the P into Outcomes Research. Badia X, Donatti C, Makin C. AccessPoint, 2011; 1(2):31-35.

Figure 2 on page 34 of this article, depicting a PRO Framework, should contain the followingacknowledgement: Source: Doward L, Gnanasakthy A, Baker, M. Patient-reported outcomes: Looking beyond the label claim.Health and Quality of Life Outcomes, 2010; 8:89.

We apologize for this unintentional omission.


NEWS | IMS CORE DIABETES MODEL

Significant enhancements strengthen robustness of IMS CORE DiabetesModel, bringing new analytic possibilities for diabetes decision support.

New version of IMS CORE Diabetes Model goes live!

The IMS CORE Diabetes Model (CDM) is widelyrecognized as the leading economic model ofdiabetes. With the prevalence of diabetescontinuing to grow at alarming rates around theworld, its critical insights into the long-termclinical and economic outcomes of new therapeuticinterventions are key to identifying optimalapproaches to managing this disease.

In a move that reflects our ongoing commitment toinnovation in the field of diabetes and ensuring that the CDM remains the best economic evaluation tool available, weare delighted to announce the recent launch of Version 8.0.With significant scientific and technical updates, togetherwith enhancements to the model interface, the new versionoffers both augmented capabilities and an improved end-userexperience.

The updates include new clinical information and/ormodifications to reflect alternative or fresh assumptions inthe modeling process, such as new relationships of riskfactors, the integration of more recent clinical data indiabetes, and structural changes that broaden the model’sscientific scope.

KEY STRUCTURAL CHANGESAmong the principal structural modifications to the modelare: a new treatment-to-target approach, the ability toleverage real-world patient-level data in the model, and theextension of probabilistic sensitivity analysis.

1. New treatment-to-target approach

This newly added feature captures HbA1c efficacy datafrom clinical trials where titration algorithms were appliedto treat patients to target levels. In such trials, HbA1cefficacy data is normally expressed in terms of thepercentage of patients who reached a target HbA1c value.The treatment-to-target approach allows the user tospecify treatment efficacy in terms of a pre-defined HbA1ctarget (eg, ADA target of 7%) and a percentage of patientswho reach the target. It has been integrated into themodel alongside the standard approach to define HbA1cefficacy in the CDM (mean change from baseline). Usershave the option to choose either approach in thetreatment setting of the model (Figure 1).

2. New patient-level analysisThe CDM performs patient-level simulations on the basisof mean cohort properties such as age, duration ofdiabetes, physiological parameter levels and baselinecomplication rates. A subset of those parameters mightbe subjected to random sampling in order to incorporatecohort heterogeneity, but also the uncertainty relating tothe parameter assumptions. In Version 8.0, real-worldpatient-level data that might come from clinical trialpopulations or patient registries can be applied directlyin the model. Records of patient-level data can beuploaded into the model and applied as an alternative tothe Cohort module settings to describe the patientcharacteristics of the cohort to be simulated.

In addition, data for treatment effects can be likewiseincluded in the patient-level dataset. The option ofapplying real-world patient-level data to explore theparameter uncertainty is important, since parameters mayhave an underlying covariance structure that might notbe reflected by random assignment of patientcharacteristics and/or treatment effects.

3. Extension of probabilistic sensitivity analysis The CDM uses Monte Carlo simulations, together with a non-parametric bootstrapping approach, to capture parameteruncertainty, enabling the imprecision of cost-effectivenessresults to be assessed. The process involves sampling withreplacement from distributions for input parameters foreach bootstrap iteration of the analysis.

...continued opposite

FIGURE 1: TREATMENT SECTION OF THE IMS CORE DIABETESMODEL WITH FOUR NEW VARIABLES AND THE OPTION TOCHOOSE BETWEEN “TREATMENT TO TARGET” AND“CONVENTIONAL (MEAN CHANGE)” APPROACH


COPD MODELING | NEWS

COPD burden demands robust health economic support.

In the previous version of the model, cohort baseline values(age, duration of diabetes and baseline physiologicalparameter levels) and the treatment effects on physiologicalparameter levels were subject to random sampling. Incompliance with guidelines from NICE, the list of parametersthat are subjected to random sampling has been extended toincorporate transition probabilities for cardiovascular events,health state utilities and event dis-utilities, as well as directand indirect costs. In addition, the distribution type appliedto sample treatment effects has been changed from normaldistribution to a beta distribution. The beta distributionrequires an upper and lower limit for input parameters. Betadistributions were chosen because they enable the definitionof a distribution to prevent inconsistent or illogical valueswithout altering the mean or standard deviation.

IMPROVED CAPABILITY AND USER EXPERIENCEIn addition to the structural changes, Version 8 of the CDMalso brings enhancements to calculation speed and userexperience to ensure that diabetes model simulations can

be set up, performed and analyzed in an efficient andseamless way.

We are confident that the changes and new featuresincorporated into the Version 8.0 update will strengthen therobustness of the IMS CORE Diabetes Model and enable agreater range of analyses to be undertaken. Feedback to datehas been extremely positive and we encourage and welcomecomments from all users as they gain experience with thenew update. •

For further information on the IMS CORE Diabetes Modelupdate, please contact David Grant, Senior Principal HEOR,IMS Consulting Group, U.K., [email protected]

A full validation of the new model version is now underway (see article on page 34 of this issue) and

the results will then be submitted for peer-reviewed publication.

Chronic obstructive pulmonary disease (COPD) isbecoming a serious concern for global publichealth. Reflecting the need for more and better real-world evidence in this disease, on 24 September Yevgeniy Samyshkin and Yumi Asukaifrom IMS HEOR were invited speakers at an expertconference on COPD modeling.

Hosted by Maureen Rutten van Mölken of iMTA (ErasmusUniversity) and featuring guest speaker Andrew Briggs ofGlasgow University, the meeting took place in Amsterdam,alongside the 2011 European Respiratory Society AnnualCongress.

The conference reflects concern about the growing burden ofCOPD – highlighted at a recent high-level meeting of the UNGeneral Assembly – and the need to better understand thevalue of different treatments. Affecting millions of peopleworldwide – many of whom remain undiagnosed – thisdebilitating lung condition is predicted to be the thirdleading cause of death by 2030.1 It has long been associatedwith elderly males, but with new research revealing asignificant impact on the working population, its economictoll is considered likely to increase considerably.2

Promoting best practice COPD modelingWIDE-RANGING INPUT IMS was invited to present our models alongside other leadersin this field such as Professors Briggs and van Mölken andSixten Borg from the Institute of Health Economics (IHE).Approximately 30 attendees from industry and academia wereinvited to observe, with representation from all the majorpharma companies active in COPD. Presentations drew on richand varied expertise, ranging from the clinical experience ofa COPD specialist to the technical insights of a financialmodeler considering issues around model validation.

Speakers discussed key methodological and implementationissues in modeling COPD and the potential value of creatinga benchmark or reference case for COPD models. Furtherdiscussion focused on:

• Approaches to describing disease progression• Relevance of GOLD system in classifying disease severity& progression

• Impact of disease exacerbations• Limitations of existing COPD models and datasets• Potential data that would help the modeling to betterreflect clinical reality

The group offers an exciting opportunity to develop bestpractice in COPD modeling and set benchmarks that futureanalyses will need to meet. Further gatherings are plannedto address the strengths and weaknesses of existingapproaches and develop an agenda for advancing the qualityof analyses and data available in this area. •

New CDM goes live ...continued from previous page

1WHO World Health Statistics, 2008 Accessed Oct 13, 2011http://www.who.int/whosis/whostat/EN_WHS08_Part1.pdf2COPD: The New Workplace Epidemic. Fletcher MJ, van der Molen T,Barnes N, Walsh J. Updated September 2011. Education for Health.


NEWS | IMS PHARMA POLICY ANALYZER

FIGURE 1: HOME PAGE OF IMS PHARMA POLICY ANALYZER

Spain’s ever changing regional policies are a major challenge for marketaccess in this country. A new on-line tool from IMS Barcelona enables moreinformed strategic decision making.

IMS Pharma Policy Analyzer prepares to launch in Spain

With 17 autonomous regions, each having theirown pharmaceutical policies, Spain presents oneof the most complex environments for achievingsuccessful market access. Multiple stakeholders anddisparate rules in primary and secondary care mustbe addressed against a background of ongoingchanges to the current pharmaceutical policies.Understanding the direction of new developmentsand leveraging them to best effect requires thevery latest intelligence – at both a national andregional level.

IN-DEPTH, UP-TO-DATE INFORMATION IMS Pharma Policy Analyzer is a new, web-based tool whichcharts, captures and clarifies the current policies governingmarket access in the different regions of Spain (Figure 1).Updated every four months, it brings together into a singlesource, critical, current information on four key panel areas:

1. Regional Policies

2. Regional Stakeholders

3. National Healthcare System: Organization and Legislation

4. Benchmarks

continued opposite

1. Regional Policies: Covers all regional policies about theevaluation, selection, acquisition, purchase, prescriptionand dispensing by region, prescription and dispensingchannel, and type of drugs. It also contains stakeholderrelationship diagrams per region and the impact ofpolicies on market access and the decision making process.

2. Stakeholder Dataview: Provides name, surname,department, position and main activities of the regionalstakeholders, by region.

3. National Healthcare System: Organization andLegislation: Describes official national pricing andreimbursement policies for pharmaceuticals, all nationalpharmaceutical legislation in chronological order, and theterritorial organization of healthcare provision by region.

4. Benchmarks: Enables comparisons of economic dataacross regions on the basis of: socio-demographicindicators, economic indicators, healthcare budgets,healthcare and pharmaceutical expenditure andpharmaceutical market indicators. All data is extractedfrom multiple, official Spanish sources.

Additional sections include a glossary, main links, latestchanges and SOPs to further clarify the complexities of the Spanish pharmaceutical market. An example of the detail provided by Pharma Policy Analyzer is shown in Figure 2 (opposite page).

SINGLE REFERENCE, MULTIPLE BENEFITS Health economics and outcomes research experts at the IMSConsulting Group in Barcelona, who have spent many monthsdeveloping and fine-tuning Pharma Policy Analyzer, areconfident of its value as a definitive, single reference whenpreparing for market access on a regional basis in Spain.

With detail that would be time-consuming to generate perse, it enables a fast understanding of the policies that impactmarket access and the implication of changes as new policiesare implemented, as well as the ability to develop andimprove relationships with key stakeholders.


IMS INSTITUTE INSIGHTS | NEWS

FIGURE 2: IMPACT OF REGIONAL POLICIES FOR HOSPITALDRUGS WITH THERAPEUTIC EQUIVALENTS IN ANDALUSIA

The benefits of Pharma Policy Analyzer are expected toextend beyond market access to medical affairs, marketing,health policy and outcomes research, in facilitatingoptimal decision making and product positioning in the market.

IMS Pharma Policy Analyzer is scheduled for launch at theend of 2011. •

For further information on IMS Pharma Policy Analyzerplease contact Xavier Badia, Global Leader ObservationalOutcomes Research and Senior Principal HEOR, IMS Consulting Group, Spain, [email protected] or Ana Vieta, Engagement Manager HEOR, IMS Consulting Group, Spain, [email protected]

IMS Pharma Policy Analyzer, Spain...continued from previous page

IMS Institute for Healthcare Informatics explores key dynamics that are shaping the future of healthcare.

Weekly insights accelerateunderstanding of latest trends

Since its launch early in 2011, the IMS Institute for Healthcare Informatics has confirmed the strengthof its research agenda with a series of comprehensive publications and podcasts, and relevant, objectiveweekly insights into the leading issues that impact healthcare worldwide.

Recent topics covered include:

• Cost savings from generics in the United StatesSupporting a study published by the GenericPharmaceutical Association (GPhA), research from theInstitute reveals the cost savings generated by dispensingfor generic versions of brand name drugs in the U.S. overthe past decade.

• Growth of non-communicable diseases As the UnitedNations discusses prevention and control of four majornon-communicable diseases – cancer, diabetes, COPD andcardiovascular disease – the Institute details the dynamicsdriving growth and spending of medicines in these diseaseclasses globally.

• Spending and growth for NCEs Pharmaceuticalmanufacturers are pursuing more targeted therapies totreat diseases afflicting smaller patient populations. Newtherapies and their impact on spending on medicinesglobally over the next five years are discussed.

• Impact of antivirals used for the 2009 H1N1 influenzapandemic A paper co-authored by the CDC and IMS on theimpact of antiviral medicines used during the 2009 H1N1influenza pandemic, finds approximately 10,000 influenza-related hospitalizations were prevented because of the useof these medicines during the pandemic.

• Spending and growth for global therapies While spending on most therapies for chronic conditionswill be lower over the next five years, there will becontinued growth for specialty medicines targeted towardcancer, autoimmune disease, multiple sclerosis and HIV.This trend is explored, with reference to the top 20 globaltherapy classes and their spending growth through 2015.

Further information on these and other insights from theIMS Institute, presented with commentary from ExecutiveDirector, Murray Aitken, can be accessed from the Institutewebsite at www.theimsinstitute.org, along with details ofthe Institute's range of research activities. •

IMS HEALTH ECONOMICS & OUTCOMES RESEARCHPage 8 IMS HEALTH ECONOMICS & OUTCOMES RESEARCH

INSIGHTS | DRUG REFORM IN FRANCE

A radical review of drug assessment inFrance, triggered by the high-profilewithdrawal of the anti-diabetic Médiator,paves the way for potentially game-changingpharmaceutical legislation. With every aspectof the evaluation process now under scrutiny,we consider the far-reaching implications forpricing and market access in this country.

The authors:

Dana Morlet-Vigier, MD is Principal HEOR, IMS Consulting Group, France. [email protected]

Arnaud Troubat, PHARMD, MBA, MHEM is Principal HEOR, IMS Consulting Group, [email protected]


DRUG REFORM IN FRANCE | INSIGHTS

The scandal involving Servier’s diabetes drug Médiator(benfluorex hydrochloride) has shaken the veryfoundations of the French healthcare system - quality,efficiency and equal access - and triggered nationaldebate on the healthcare system, pharmaceuticalregulation and market access. The drug has beenassociated with severe cardio-pulmonary adverse eventsand hundreds, if not thousands, of deaths. Added to thisare accusations of weakness on the part of the Frenchregulatory agency, AFSSAPS, for failing to addresspharmacovigilance signals over the course of many years.Following a number of official reviews, reforms were putforward by Health Minister Xavier Bertrand in June,2011. Corresponding draft legislation is currently beingexamined in parliament.

In spite of the media onslaught following the scandal, andcalls from official audit bodies for radical and deepreforms for market access and reimbursement, Bertrand’sproposals represent relatively limited changes. This mayhave come as something of a relief for stakeholders. But,even if the proposed reforms are quite minor, theirimpact may yet be quite radical and even more so as theParliament discusses at the same time the PLFSS 2012(Social Security Finance Bill, voted every year).

The changes under discussion in parliament with respectto these two laws will impact four key areas: stakeholderrelationships, prescribing, real-world evidence needs andhealth economics.

1. STAKEHOLDER RELATIONSHIPS

The Médiator affair has only served to exacerbate thelong-held perception of “abnormally close” linksbetween pharmaceutical manufacturers, regulatoryauthorities and prescribers in France. The government’sreaction represents a very serious attempt to sever thisassociation. Moving forward these relationships will bemuch more tightly controlled.

The key reforms currently being discussed in Parliamentare as follows:

• Expert Charter: Key opinion leaders (KOLs),whose credibility was seriously shaken by the falloutfrom Médiator, obliged to publicly declare allpotential “conflicts of interest”, and regulatoryagencies to have the ability to control.

• Sunshine Act: Manufacturers obliged to fullydisclose all payments/financial concessions made tohealthcare professionals, including doctors, nurses,medical students, patient associations, etc.

• ANSM: AFSSAPS, the French drug regulatoryagency, whose reputation has been severely damagedby the Médiator scandal, will be renamed theNational Agency for Drug Safety (ANSM). ANSMwill assume new powers and play a centralcoordinating role. ANSM to have the right todemand comparative data when licensing NCEs.

• Off-label prescribing: Prescribers are to informANSM about off-label drug use (versus the drug’sofficial marketing authorization or prescribingguidelines issued by the High Authority for Health[HAS]) and, moreover, to also inform their patientsbefore prescribing.

The impact of these changes is potentially far-reaching:sponsored trials may suffer; KOL advice will becomedifficult to obtain; patients will have very limited accessto off-label drugs (even in the absence of other choices);and pharmaceutical companies will have to constantlymonitor the real-life use of their drugs.

2. PRESCRIBER RESPONSIBILITY

To date, there have been few restrictions on physicianprescribing in France, and few demand-side controls tolimit consumption. However, in future, much greateremphasis will be placed on appropriate (ie, medicallyappropriate and economically sound) prescribing.

Proposed changesAlong with increased sanctions reinforcingpharmacovigilance obligations, physicians will berequired to officially inform their patients when they

Drug reform in FranceA TOUGHER WORLD FOR PHARMACEUTICALS?

The scandal involving Servier’sdiabetes drug Médiator has shakenthe very foundations of the Frenchhealthcare system - quality, efficiencyand equal access

continued on next page


prescribe off-label and follow enforced legislation onINN prescribing (mostly through the compulsory HAScertification of medical prescribing software). The “pay-for-performance” initiative will be extended to allGeneral Practitioners.

Hospital budget deficits are to be eliminated by 2012,with draft reform legislation introducing the possibilityfor prescribing controls to be enforced at the individualphysician level in hospitals. Hospital detailing was initiallyproposed to be confined to groups of physicians only, aproposal that has been fiercely discussed by Pharma andmay finally not be adopted – discussions are ongoing.Finally, there will be strict limits on spending growth fordrugs prescribed in hospitals and dispensed via retailpharmacies.

Potential impactThe primary goal of these measures is to rein inexpenditures by finally starting to tackle the “demand-side” of the market. While the actual changes could beperceived as minor, in practice they have the potential toresult in:

• Demand-side prescribing drivers in France replicating‘stricter’ EU countries

• Prescribers moving to distance themselves fromindustry contacts

• Increased uptake of ‘cheaper options’ and decreasinguptake of ‘perceived expensive’ drugs due to newprescriber price sensitivity

• Reduced off-label prescribing

• Collaborative agreements becoming more difficult toestablish.

3. REAL-WORLD EVIDENCE

The provision of real-world evidence (RWE), includingsafety and appropriate-use data, will become acompulsory requirement to ensure continued marketaccess (with a natural milestone at the mandatory five-year reimbursement reviews, but not restricted to this).Non-compliance may lead to loss of reimbursementand/or marketing authorization. The timelines forprovision of RWE data will be agreed beforereimbursement is granted.

This marks a significant change from the currentsituation. Requirements for post-marketing data haveexisted in France for some time, but demands for RWE(from either AFSSAPS or HAS) are not systematic andare not always met by manufacturers.

Another critical consideration for manufacturers is theproposed ANSM review of the risk-benefit profile of allexisting (in-market) drugs. Reviews will be prioritizedbased on medical benefit rating (SMR) – in other words,beginning with drugs judged to have an insufficient orweak SMR rating. RWE will be a key factor in thisprocess.

4. HEALTH ECONOMICS

In keeping with calls from numerous politicalstakeholders in France, health economics is set to have anincreased and more clearly defined role going forward.Indeed, the 2012 Social Security Finance Bill includesprovision for greater emphasis on these evaluations. Infuture, health economic data will be taken into accountby CEPS (the Pricing Committee) during the pricefixation process. The exact details are as yet unclear – butmay be known by as soon as the end of 2011.

What is clear is that the Commission for Economic andPublic Health Evaluation (CEESP), part of HAS, will begiven new authority to conduct health economic-basedassessments of individual drugs, and to providecorresponding advice to the CEPS as part of the initialprice fixing process. To date, the CEESP has focused ondisease area/therapeutic group reviews only, and has hadno involvement in pricing or market access decisions.

What this means is that budget impact modeling andcost-minimization from a national health insuranceperspective will become a “must” for all drugs, both atlaunch and for continued market access. The open use ofcost per quality-adjusted life year (QALY) or similarmetrics is nevertheless unlikely to happen in the shortterm as that would mean a significant political change.Nevertheless, it is expected that progressively the Frenchenvironment (stakeholders and public opinion) will bemore and more exposed to it.

Further, cost-effectiveness assessments of therapeuticstrategies as a whole are likely to become more systematic(with implications for prescribing guidelines). Cost-effectiveness data will have to be made available for pricefixation and price defense (throughout the lifecycle) inthe case of high-cost drugs such as cancer treatments.

If the proposed reforms are adopted,France will lead the European Unionin terms of real-world evidencecompulsory requirements

INSIGHTS | DRUG REFORM IN FRANCE

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FIGURE 1: PRICING AND REIMBURSEMENT ACCESS: PAST, PRESENT AND FUTURE


PRICE PRESSURE

Overall, these proposed reforms translate to graduallyincreasing pressure on drug prices, both at launch andacross the lifecycle, and significantly increasing constraintson reimbursement access (Figure 1).

Historically, almost all drugs for which applications havebeen submitted have been granted reimbursement inFrance. Listing was almost guaranteed, the only questionbeing at what price. However, the tide is turning. At least10 new (innovator) drugs have been rejected forreimbursement by the Transparency Commission (CT)since the beginning of 2011 (accounting for almost 25%of all submissions). The question now is one of “anyreimbursement at all?” Going forward, much greateremphasis will be placed on demonstrating first medicalbenefit (SMR) – actually focusing on the benefit-riskratio, rather than improvement in medical benefit(ASMR) against comparators. On the other hand, ANSMis given the right to request, if needed, comparative datafor licensing purposes. This brings some confusion overthe future roles of ANSM and HAS in market access.

PHARMA PREPARATION STRATEGIES

Despite the lack of finality over many details of the newregulations in France, the future obligations for theindustry are known and the key is for companies toanticipate these and begin their preparations now.

Those that are looking to get ahead of the changes shouldfocus on:

1. Being proactive: Collect real-world efficacy andsafety data rather than waiting for such demands,ideally beginning as soon as Phase III trials areavailable; bear in mind the increased emphasis onhealth economics in France and plan accordingly.

2. Knowing the data sources: Be aware of, and haveaccess to, relevant data sources.

3. Prioritizing activities: Examine the productportfolio and identify drugs with a high budgetimpact, a high likelihood of prescribing outside ofreimbursed indications, low incremental effectiveness,or safety issues, and direct efforts towards collating real-world evidence data for these products first andforemost.

LEADING THE WAY IN EUROPE

The Médiator affair has undoubtedly cut to the core ofthe established healthcare system in France. The outcomecould have been worse but if the proposed reforms areadopted, France will lead the European Union (EU) interms of real-world evidence compulsory requirementsand will be closing the gap with other EU countries interms of prescribing restrictions. Otherwise, it is businessas usual, with about €600 million in drug price cutsexpected for 2012 – the deepest wave of price cuts everseen in the country. •

Next 5 years?• Much more selective reimbursement• High price pressure (at access time)• Formal health economics for expensive therapeutic solutions?

• Prescription control at individual andhospital level based on restrictive guidelines

5 years ago• ASMR the name of the genre• ‘Standard’ price pressure• ‘Basic’ access restrictions

Today• SMR is now the key to gaining any access at all• Price cuts announced• Post-marketing data compulsory for continued access• Prescription control taking-off

-5 0 +5

DRUG REFORM IN FRANCE | INSIGHTS


INSIGHTS | REAL-WORLD EVIDENCE

The growing need for real-world evidence (RWE) tosupport a product throughout its lifecycle has endedthe era in which data was assembled purely for marketaccess. As more stakeholders outside the industrygenerate evidence themselves, manufacturers willincreasingly need to manage their own data packagesin dynamic and creative ways.

Vernon Schabert, PHD is Global Leader Retrospective OutcomesResearch and Senior Principal HEOR, IMS Consulting Group, [email protected]

The authors

Rob Kotchie, MCHEM, MSC is Principal HEOR, IMS Consulting Group, [email protected]

Jon Resnick, MBA is Vice President and Global Leader HEOR, IMS Consulting Group, U.S. [email protected]


REAL-WORLD EVIDENCE | INSIGHTS

Driving the industry into the ‘prove it works’ eraREAL-WORLD EVIDENCE SETS THE PACE

Broader than just observational data, real-world evidence(RWE) is data collected in actual practice for manypurposes and applied to prove or disprove a hypothesisthat may have nothing to do with its original remit.Although the concept of using RWE makes intuitivesense, in practice the quality of the underlying data,appropriateness of the research question for that data, andthe robustness of the methodology, affect whether or notto believe the outcome. Furthermore, the lack of trust indata generated by pharmaceutical companies results in ahigh bar and creates a real threat that healthcarestakeholders will use RWE to inform value decisionswithout the voice of the manufacturers.

MAJOR SHIFT

RWE represents a shift in the timing and use of data to inform the value of a product. Historically,pharmaceutical companies focused on pre-launchrandomized controlled trial (RCT) data to develop valuearguments and negotiate for market access. RWE isenabling continued scrutiny in the market among all keystakeholders – regulators, payers, healthcare providers,academics and patients. Traditional hurdles of efficacy,safety, quality, and value for money are extended as RWE enables conditional reimbursement and productreassessments. In effect, this shift will eventually force

manufacturers to continue lapping around the marketaccess and regulatory track (Figure 1).

This may sound far-fetched. However, stakeholders have always desired to understand whether the treatments they are using and paying for truly work inthe way they had expected. Now, technology and the proliferation of data enable them to do that, although barriers of trust and stakeholder alignment on appropriate use are slowing the pace. Nevertheless,this ‘prove it works’ era is happening, given budgetconstraints, safety concerns, a perceived slowdown ininnovation, and greater value for money scrutiny.

FIGURE 1: RWE WILL EXTEND THE COURSE AND FORCE PRODUCTS TO REVISIT HURDLES POST-LAUNCH

The former sprint to achieve pricing and market access...

RWE assessmentsextend the traditionalhurdles of efficacy, safety,quality, and value for money

Source: IMS Consulting Group

...now requires multiple laps around the trackwith conditional reimbursement and access

Over time, regulators will use RWE to revise product labels tohighlight safety concerns, and payersmay use RWE to revisit price, actupon conditional access, and informguidelines that influence or driveclinical practice



CHANGES REFLECTED IN KEY MARKETS

The era is beginning to manifest itself through specific regulatorand payer activities in several key markets, facilitated byregulator-mandated pharmacosurveillance programs (eg, RiskEvaluation and Mitigation Strategies [REMS] in the U.S.).Today, RWE primarily affects product label and uptake byinforming safety claims and appropriate use, respectively,although a future consensus is emerging and the evidence ofbroader applicability is building:

Effects on access: Evidence generated by registries in Sweden informs

product reassessments and has even improved access. Using datafrom its Rheumatoid Arthritis (RA) registry, the National Boardof Health and Welfare determined that early treatment withTNF-inhibitors was cost-effective. As a result, national RAguidelines prioritized early treatment with TNF-inhibitors.

Effects on price: AMNOG legislation in Germany specifies that product

prices are to be reassessed post-launch, with likely reduction inprice and impact on product use.

Effects on price and access:Similarly, in the U.K., value-based pricing may enable

post-launch outcomes to support revisions of price and access,and ultimately influence uptake.

Effects on price, access, and uptake: U.S. payers have signaled their intent to improve quality

and reduce costs by leveraging RWE through strategicacquisitions and establishment of research institutes. Forinstance, CVS Caremark plans to conduct comparativeeffectiveness research (CER) using its own anonymized claimsdata to inform guidelines, restrictions, and negotiations withmanufacturers.

Over time, regulators will use RWE to revise product labels tohighlight safety concerns, and payers may use RWE to revisitprice, act upon conditional access, and inform guidelines thatinfluence or drive clinical practice. Although the future will play out at different speeds across markets and channels, coreelements of lifecycle scrutiny will occur with certainty.

The market hasalready reached atipping point where the‘prove it works’ erawill transform thehealthcare industry

INSIGHTS | REAL-WORLD EVIDENCE



KEY ENABLERS

Four enablers shape the pace and strength of RWE in amarket:

1. Systems infrastructure and technology must be put inplace to facilitate logistics, data collection, and to makelinkages between different sources. Recent examplesinclude the General Practice Research Database(GPRD) data link between the primary care andhospital setting in the UK, and innovative solutionswith hospital administrations systems to harnesstechniques such as natural language processing andpredictive matching.

2. Defined methods (eg, propensity scoring) must beexploited and developed further.

3. Stakeholders must align around ways of ensuring thatdata and analyses are used appropriately, especiallywhen pharmaceutical companies are involved.

4. A legal and ethical framework creating a cleargovernance structure for the way in which data canbe used and by whom, is integral to facilitatinganalyses with real-world data. Freedom of informationfacilitates the growth and integration of RWE intodecision making but access to data and privacy lawsvary widely.

ADDRESSING THE CHALLENGESThe market has already reached a tipping point wherethe ‘prove it works’ era will transform the healthcareindustry. Manufacturers are no longer in a sprint to the‘finish line’ of launch. The industry now has to run on aperpetual track where the end of the race is never reallypassed (eg, payers will still care about RWE for a productafter patent expiry).

Manufacturers must begin to address these challengesstrategically and proactively; merely being reactive is aworst-case scenario. As one Italian payer recently advisedpharmaceutical companies: “Drive, do not follow.” Byincreasing efforts to play more strategically today,manufacturers have the opportunity to ‘shape the track’that defines the impact and role of RWE. Collectively,the pharmaceutical industry must articulate its vision forand broaden its role within RWE.

To win the race, organizations must refocus on enablinglifecycle evidence development:

• Secure a slot in the race:Work with stakeholdersto address concerns about the objectives of theanalysis, disclosing intended RWE studies at an earlystage (as for RCTs) and working with third-parties toremove bias concerns.

• Prepare with the end goal in mind: DevelopLifecycle Market Access (LMA) plans that focus onevidence generation early in the lifecycle and supporta coordinated RCT-RWE strategy. A winning visionmay require calculated risks that move beyondconventional paths.

• Get off to a good start: Leverage RCTs to gainpricing and market access by understanding payerquestions and concerns. Build confidence with payersby incorporating their questions around a product’sefficacy or safety into RWE planning while stillprotecting manufacturers’ interests.

• Maintain the pace: Remain focused post-launch onLMA by demonstrating and communicating value ina real-world setting and leverage RWE to improve thevalue proposition or further differentiate in acompetitive environment.

• Adjust to changing conditions: Stay flexible torespond to evolving market and competitive dynamics.

• Consider participating in relays: Build off others’RWE to help create a greater understanding of theeffectiveness of treatments and address broaderstakeholder questions.

• Continuous learning: Maintain support, refineapproaches, and transfer learnings to other assets.

To support this approach, manufacturers must reshape tobuild necessary skill sets and define ownership of RWEwithin their organizations. Too often, responsibility forRWE exists in siloed functions, deep in countries or withindividual brand teams, who cannot drive the broadercredibility and skill-development priorities. AcceleratingRWE is potentially disruptive, leading to new regulatoryand pricing & market access structures, increasing productevidence requirements and requiring changes in relativestakeholder power. However, taking an active role inRWE provides potential opportunities to optimizeportfolio assets, leverage internal efficiencies, and createa platform to build stronger stakeholder relationships. •

REAL-WORLD EVIDENCE | INSIGHTS


INSIGHTS | OBSERVATIONAL STUDIES IN ASIA

Converging trends are driving newrequirements for real-world studies in theemerging pharmaceutical markets,especially in Asia. As more companies facethe need to plan studies for observationalresearch in Asian countries, we considerthe challenges – and the advantages – ofprimary data collection in the region.

The authors:

Xavier Badia, MD, PHD, MPH is Global Leader Observational OutcomesResearch and Senior Principal HEOR, IMS Consulting Group, [email protected]

Núria Lara Surinach, MD, MSC is Principal HEOR, IMS Consulting Group, [email protected]


OBSERVATIONAL STUDIES IN ASIA | INSIGHTS

The rising demand for real-world data comparing therelative value of medical technologies has opened up newopportunities for outcomes research, with acorresponding increase in the collection of primary datathrough observational studies. Coming at a time whenmost of the major pharmaceutical manufacturers reportan increasing percentage of sales revenue from emergingmarkets, this is creating a need for real-world data – andconsequently for observational studies – in Asia.Understanding the issues, hurdles and benefits of runningobservational studies in the emerging Asian markets isfast becoming essential for pharmaceutical organizations.Companies looking to plan an observational study in thisregion will need to consider a number of fundamental,but critical, issues.

PILOT FEASIBILITY OF STUDY DESIGN AND REQUIRED DATA

One of the first things to consider when planning anobservational study in Asian markets is the feasibility of the chosen study design. Traditionally, observationalstudies can collect data in a cross-sectional way,retrospectively (based on medical chart review) orprospectively. However, in many Asian countries, medical records are invariably incomplete and often non-existent. This is especially apparent within primary care,making retrospective chart reviews a particular challengein this setting.

Another important issue is the type of data to becollected. Although a certain amount of clinical data canbe found in the medical charts, in some of the Asiancountries at least, information on healthcare resource usemay be scarce.

Thus, a first recommended step for companies is toundertake a small pilot study in each of the participatingcountries, in order to evaluate the feasibility of the desiredstudy design as well as the availability of data. Thisimportant preliminary activity is often overlooked, dueeither to time pressures or unwillingness to invest furthermoney in the project. Nevertheless, when planning anobservational study that includes clinical, economic orquality-of-life data in emerging Asian markets, a pilotstudy is highly cost-effective, avoiding both potentialdelays in field work and failure to meet the desired study outcomes.

PHYSICIAN RECRUITMENT

Another critical step for study implementation is physician recruitment. Often working inovercrowded conditions, with many patients to see in aday, doctors in emerging Asian markets have limited timeto dedicate to research. Securing their agreement to takepart in an observational study, especially a long,prospective investigation requiring follow-up over adefined period, can thus be difficult. When inviting studyparticipation, there is thus a need to contact a highnumber of physicians, making databases with lists ofpotential participants crucial. It is also important to offerphysicians some kind of incentive to partake in the studyapart from the economic one. Doctors tend to appreciatethe scientific value of the research and the possibility ofbeing part of the publication.

HEALTHCARE ORGANIZATION AND ACCESS

When considering the feasibility of certain studies, thestructure and organization of healthcare must betaken into account, particularly where there is noprovision for continuity in the patient-physicianrelationship. This lack of continuity can make patientfollow-up challenging especially outside the hospitalsetting where several physicians may be consulted for asingle disease episode. The same applies to physicians whofrequently move from one hospital/clinic to another ina short period of time.

Access to healthcare can also be an issue in somecountries, such as India, where only 10% of thepopulation is covered through health financing schemes.This is important in epidemiological studies as theprevalence of certain diseases measured at the physician’soffice is probably skewed towards more wealthy parts ofthe population with access to healthcare.

OBTAINING IRB APPROVAL

Before commencing field work and data collection, it isnecessary to obtain Institutional Review Board (IRB)approval (Figure 1). The lack of clear guidance onevaluating observational studies is creating a lot ofuncertainty in a number of countries (eg India, South Korea) in terms of the best way to proceed, andrequires an experienced local team.

Conducting real-world studies inemerging Asian markets CHALLENGES FOR OBSERVATIONAL RESEARCH



INSIGHTS | OBSERVATIONAL STUDIES IN ASIA

Despite the challenges,there are clearadvantages to conductingobservational studies inemerging Asian markets

FIGURE 1: ILLUSTRATIVE EXAMPLES OF THE IRB PROCESS IN INDIA, SOUTH KOREA AND TAIWAN

In India, there are 3-4 processes for obtaining IRB approval, takingapproximately 3-4 months.

HOSPITAL ETHICCOMMITTEE IRB DCGI

NOTIFICATION

Selectinstitutions andrecruit doctors

Receive approvalfrom ethiccommittee

Submit IRBapproval

Notify DCGI

Select institutionsand recruit doctors(Screeners)

Challenges: Alldocuments must beready and preparedfor recruitment

PUBLIC

PRIVATE

Not required

RECRUITMENT

Duration 30-35 Days 20-25 Days 25 Days

Note: PI is required to participate in necessary meetingsfor both ethic committee and IRB approval process

In South Korea, multiple-center IRB is required.

CLINIC LISTING HOSPITAL IRB

Challenges: “Skillful”introduction and persuasionprocess with hospital PI/Co-PIs are needed in the systemof dual-punishment*

Challenges: • Different requirements byeach hospital IRB committeeare expected and we haveto manage them includingprotcol modification byhospital

• Some hospital IRB officialsrefused to incorporate clinicphysicians in their IRB list

• Any change in the cliniclist should be reported andapproved by PI and each IRBcommittee even though it isincorporated as anattachment.

CLINIC

HOSPITAL PI, CO-PILISTING

Duration 20 Days 20 Days 60-75 Days

Develop Hospital PI, co-PI list that will bespecified in the hospitalIRB form

Submit IRBs to multiplecenters (target centers)and gain approval

Develop clinic list thatshould be included inhospital IRB submissionform

HOSPITAL

Taiwan requires separate IRB approval for hospitals and clinics.

JIRBHOSPITAL IRB

Duration150 Days 15-21 Days

Receive approval fromHospital IRB

HOSPITAL

CLINIC Receive approval

from JIRBNot required

Not required


* Dual punishment system:Providers as well as therecipients of an illegal rebate willbe subject to criminal penalities.


OBSERVATIONAL STUDIES IN ASIA | INSIGHTS

In some cases, observational studies are seen and treatedas randomized clinical trials (RCTs). Our experience hasshown that even pure observational epidemiologicalstudies, which do not measure any drug-related outcome,may be treated as RCTs, in the absence of specificguidelines and knowledge of observational research.

IndiaIn India, there are no set norms for including a physicianin a study. Government hospital physicians may mentionthe hospital Ethics Committee (EC) but later on agree forthe central EC. Much depends on how strictly the codeof conduct is followed in a particular hospital. A similarsituation arises with the contract for investigators. Everyhospital may try to insist on using their contract templatewhich quite often refers to terms more related to RCTsthan observational studies. For some study designs, it wouldbe advisable to opt first for a market research approach,thus avoiding some of these pitfalls. This situation clearlyunderscores the need to have an experienced team in placethat is able to manage the submission and maintain regularcontact with the IRB bodies.

South KoreaIn South Korea, current government regulations are limitedto clinical trials or post-marketing surveillance (PMS) tomonitor drug information, including adverse events. Thereare no formal regulations in the IRB process forobservational, non-interventional (of drug) studies in clinics.

The Korean Ministry of Health & Welfare (MHW)recommends the incorporation of clinics in the IRBapproval process of hospitals whose physicians areinvolved in the study. However, in studies involving manyclinic physicians, GH practitioners tend to hold backfrom taking a product investigator (PI) or co-PI role as itwould leave them responsible for the study: the currentsystem of dual punishment means providers as well as therecipients of an illegal rebate will be subject to criminalpenalties. Consequently, skillful communication with GHphysicians is extremely important.

Recently, the MHW has moved to set a regulation forpublic IRB in the case of small health centers or clinicswhere it is difficult to run an independent IRBcommittee. Draft guidelines have been published with aplan to enact the regulation in the next year.

DATA COLLECTION

Methods for data collection must be adapted to theparticular idiosyncrasies of each country. In certain Asianmarkets, the use of computers at physician-level is quitewell spread, while in other countries like India or China,for example, the recommendation is to collect the datausing pen and paper. In the case of physician surveys,telephone can be an option in some of the moredeveloped Asian markets, whilst in others a face-to-faceapproach is needed.

Real-world data includes patient-reported outcomes,which can be a challenge in Asian markets if PROquestionnaires have not been validated in the locallanguage. In some cases, translation into more than 10different languages could be required in a single countryin order to cover the entire population! Illiteracy can alsobe a problem, making the use of self-administeredquestionnaires problematic.

CLEAR BENEFITS

Despite the challenges, there are clear advantages toconducting observational studies in emerging Asianmarkets: lower costs, access to much higher patientnumbers, and in many countries a shifting spectrum ofdisease which increasingly resembles that of developedcountries, with growing emphasis on cardiovascular andmetabolic conditions. All the challenges can be overcomewith an experienced local team in each of the participantcountries that is able to adapt the study needs to theprevailing healthcare system. •


INSIGHTS | EUROPEAN EMR DATA

Increasing emphasis on real-world data has seen tremendous growth in the use of patient-level databases as their value in capturing clinical practice becomesincreasingly apparent. The IMS LifeLink™

Electronic Medical Records Database is amongthe most comprehensive of its kind in Europe,with new features and growing applicabilityacross a range of research applications.

The authors:

Massoud Toussi, MD, MSC, PHD is Medical Director HEOR, IMS Consulting Group, [email protected]

Nathalie Grandfils, MSC is Engagement Manager HEOR, IMS Consulting Group, [email protected]


EUROPEAN EMR DATA | INSIGHTS

Capturing the real world in real timeIMS LIFELINK™ ELECTRONIC MEDICAL RECORDS DATABASE IN EUROPE

WHY USE REAL-WORLD DATA?

There is a general consensus that randomized clinicaltrials (RCTs), with their small sample size, controlledenvironment and focus on short-term efficacy and safety,cannot deliver all the requisite information about the safeand effective use of a medicine at the time of launch.1Post-marketing evaluations must generally include asufficient number of exposed persons to detect adverseevents with a relatively low incidence rate. However,studies of this scale are expensive, challenging and time-consuming. Ironically, they are often needed quickly, toaddress immediate and serious regulatory, commercialand public health concerns.2

GROWING ROLE OF HEALTHCARE DATABASESIn recent years, the use of large healthcare databases forreal-world evidence has expanded significantly.Developed from the automatic electronic recording offilled prescriptions, professional services andhospitalizations,1 these databases enable long-termobservation of large study populations, allow forexamination of specific sub-populations, and offer arelatively inexpensive approach to addressing time-sensitive issues raised by decision makers.3 Moreover, ithas been proposed that when adequately controlled,observational studies produce similar results to RCTs.4,5

The strength of medical records databases lies in anumber of important advantages: the potential forproviding a very large sample size at relatively low cost;the absence of interviewer and/or recall bias; the lack ofneed to validate data against a source; and, mostimportantly, the possibility to study real-worldeffectiveness and utilization patterns.1 However, they arenot without their limitations: they can lack information

on some potential confounding variables such aslifestyle;2 there are uncertainties around the completionof their data because doctors use their software as theylike; they typically overlook non-prescriptionmedications; and they are unsuited for outcomes whichare poorly defined by standard classifications of disease.

IMS LIFELINK ELECTRONIC MEDICAL RECORDS DATABASEOne of the most comprehensive pharmacoepide-miological databases available in Europe is the IMSLifeLink Electronic Medical Records Database. This is alongitudinal patient database containing the electronichealth records of patients followed up by a representativepanel of physicians in France, Germany and the UK.Data are collected directly and continually during patientvisits, via medical office software and stored in a centraldatabase after de-identification.

The database has formed the basis of many studies and peer-reviewed scientific publications spanningepidemiology, pharmacoepidemiology, health economics,pharmacovigilance, pharmaceutical guidelines,compliance/persistence, prescribing behavior and drugapplications.i It allows longitudinal follow-up of all visitsby a patient consulting the same practitioner in the paneland is true to the principle of observational data collection:there is no intervention in the participating physicians’ workflow.

A number of key strengths bring particular advantagesfor the LifeLink Electronic Medical Records Database:

• Longitudinal with large time span: Patients andpractices can be analyzed in both a cross-sectional andlongitudinal way over a period of more than 20 yearsin Germany and the UK, and 14 years in France.

TABLE 1: LIFELINK ELECTRONIC MEDICAL RECORDS DATABASE COVERS AN EXTENSIVE PATIENT POPULATION


COVERAGE

Total country population (Millions)

Patients (Millions)

Physicians/practices

Prescriptions (Millions)

Data available since

UK GERMANY FRANCE

60

5

630/238

168

1991

82.5

13

3100/2500

77

1989

60.6

4.2

977/1013

42.5

1997

iA list of publications covering the use of IMS LifeLink Electronic Medical Records Database is available on request.



• Very large sample size: Approximately 22 million patientsrepresenting 287 million prescriptions are available at Europeanlevel for longitudinal analyses. Table 1 (page 21) shows thenumber of prescriptions, patients and physicians/practicescovered in the database, by country.

• Valid and representative: In a thorough evaluation,Becher, et al (2009)6 found the LifeLink Electronic MedicalRecords Database to be sufficiently representative and validin terms of panel of physician characteristics (age, region) andpatients (baseline characteristics, major pathologies and majordrug prescriptions) compared to the standard data obtainedvia official institutions in each country.

• Regularly updated and rapidly available: The databaseis updated monthly, with updates available 6 weeks after theend of a month in each country.

FROM DATABASE TO PROSPECTIVE STUDY DESIGN

Countering one of the principal shortcomings of databases –the absence of data that may be required for a study – a newfeature in the LifeLink Electronic Medical Records Databaseenables supplementary information to be captured throughadd-on questionnaires. The main value of these is in offeringretro/prospective designs to researchers, where part of the datais collected from the patient’s medical history and the rest byprospective follow-up.

Integrated into the usual medical software, the add-on screenquestionnaire pops up at the end of the consultation, based oncertain patient characteristics or whether a particular drug hasbeen prescribed. The physician is thus not influenced by a“study questionnaire” at the moment of prescribing, nor by anyprejudice relating to the patient’s willingness to participate inthe study, thereby reducing the risk of selection and self-selection bias. Also, it is now possible to add complete forms tothe standard patient record, allowing for prospective collectionof specific data for all patients.

Add-on questionnaires enable a wealth of supplementary datato be collected including:

• Disease severity or diagnosis scales

• Risk factors (eg, exposure to toxic agents in the past)

• Additional non-pharmacological therapies (eg, homeopathy,psychotherapy)

• Scales of evaluation of performance, observance, efficacy ofdrugs, etc

• Reasons for discontinuing therapy

• Information regarding hospitalizations, or consultation ofother practitioners

• Direct or indirect costs not usually found in patient records(eg, lost working days)

• Quality of life or patient satisfaction questionnaires


Ongoing investment inthe database is assured,reflecting a continuedcommitment to ensuringthe best availablepatient-level EMR data


EUROPEAN EMR DATA | INSIGHTS

Currently operational in France, with the possibility ofextensions to other countries, the “add-on” featureenhances the value of the database as a technical solutionto link to the physicians’ medical software – subject toprior acceptance and the approval of the regulatoryauthorities for each specific study.

RESEARCH APPLICATIONS

As enumerated by Schneeweiss and Avorn1, the researchapplications of patient record databases enable a betterunderstanding of many different aspects of healthcare,such as drug utilization, adverse drug effects or possibleunexpected beneficial drug effects and the impact ofchanges to health policy. They also support the efforts ofpharmaceutical manufacturers in demonstrating thebenefits of new medical technologies across a range ofanalyses. Examples of the way in which the LifeLinkElectronic Medical Records Database has informedresearch in each of these areas include:

Drug utilization and off-label useDrug utilization research is an essential part ofpharmacoepidemiology as it describes the extent, natureand determinants of drug exposure.7 In fact, the study ofreal daily dose, respect of the summary of productcharacteristics (SmPCs) and description of associatedprescriptions is important and often required by healthauthorities when assessing a medicine. A drug utilizationstudy using LifeLink Electronic Medical Records Databaseby Schröder-Bernhardi, et al (2004)8 provided valuableinsights into off-label drug use in primary care in Germany,with a focus on proton pump inhibitors and P-blockers.

Identifying adverse/beneficial drug effectsOne of the major domains of pharmacoepidemiology isresearch on the safety and beneficial effects of drugs. TheLifeLink Electronic Medical Records Database is widelyused in the context of Risk Management Plans requiredby the European Medicines Agency. There are manyexamples of its role in revealing potential safety issues,such as the findings of Star, et al (2010),9 who identifieda potential causal link between prescriptions ofantipsychotic medications and the occurrence ofpneumonia.

Understanding and informing health policy decisions Identifying the effects of delisting, withdrawal or changein prescription status is key to understanding the impactof policy changes on health systems, physicians andpatients. A study by Devaux, et al (2007)10 using theLifeLink Electronic Medical Records Database foundthat delisting mucolytic expectorants had no impact onthe cost of treatment for cough: many doctors hadreplaced the conventional expectorant treatments with

more expensive reimbursed classes but the overall costfor the health care system remained the same. This studyalso enabled the patients and physicians affected by thepolicy change to be characterized.

Studies of disease prevalence and incidence are alsoimportant for health policy decisions and are more time-and cost-effective when conducted via databases. Hsia, etal (2009)11 used the LifeLink Electronic Medical RecordsDatabase to investigate the prevalence of childhooddiabetes over an 8-year period in the UK. The authorsfound a significant increase in the prevalence of both type 1 and type 2 diabetes in children and adolescents inthe UK, providing valuable input for the funding anddesign of future services.

Demonstrating the benefits of medical innovationsRobust information supporting the benefits of medicalinnovations is increasingly needed for manufacturers tonegotiate optimal conditions for commercialization.These studies include, but are not limited to, theevaluation of cost-effectiveness, budget impact,persistence and observance, target populations byindication, and unmet medical need. Three recentexamples illustrate the use of LifeLink Electronic MedicalRecords Database in this context:

• Wade & Haring (2010)12 examined the economic andhuman costs of depression and the potential savingsassociated with improvement in patient adherence to treatment with antidepressants through the use of enhanced-care programs. They used LifeLinkElectronic Medical Records Database data as areference to compare the results of their study withreal life. The results indicated that enhanced-careprograms may lower costs associated with depressionand improve patient lives, providing a strong case forcompanies to establish such programs in associationwith their drug release.

Robust information supportingthe benefits of medical innovationsis increasingly needed formanufacturers to negotiate optimalconditions for commercialization




• Aballéa, et al (2008)13 compared treatment outcomesand cost associated with choice of fixed-dose inhaledcorticosteroid/long-acting beta-agonists for asthmamaintenance therapy, using LifeLink ElectronicMedical Records Database in Germany. The studyenabled a better understanding of cost-effectiveness oftwo different treatment choices in chronic asthma.

• Rathmann, et al (2007)14 studied the trends ofoutpatient prescription drug costs in diabetic patientsin Germany from 1994 to 2004. Using 46,017diabetic patients and 46,017 age and sex matchedcontrol subjects in 400 nationwide practices theyshowed that prescription drug costs among diabeticpatients increased 60% during the study period, whichwas twofold higher than the increase in non-diabeticpatients. Using the database, they were able tocorrelate growth in drug expenditure for diabetestreatment to progress in pharmacological therapy.

A VALID, REPRESENTATIVE RESOURCE

The validity and representativeness of the IMS LifeLinkElectronic Medical Records Database in retrospectivestudies has been demonstrated across a range of diseaseareas. The use of add-on questionnaires in conjunctionwith data collected from patient records is an importanttechnological advancement, enabling combinedretrospective and prospective designs – a particular benefitwhen research questions involve data that are notgenerally found in patient records. This is often the casewith studies requested by health and drug regulationauthorities, such as risk management plans, cost-effectiveness studies and outcomes research. Ongoinginvestment in the database is assured, reflecting acontinued commitment to ensuring the best availablepatient-level EMR, hospital and claims databases, notonly in Europe but also the Americas and emergingpharmaceutical markets of the world. •

1Schneeweiss S, Avorn J. A review of uses of healthcare utilization databases for epidemiologic research on therapeutics. J Clin Epidemiol. 2005, Apr;58(4):323–37. 2Strom BL, Kimmel SE. Textbook of Pharmacoepidemiology. 1st ed. John Wiley & Sons Ltd; 2006. 518 p.3Motheral B, Brooks J, Clark MA, Crown WH, Davey P, Hutchins D, et al. A checklist for retrospective database studies : Report of the ISPOR Task Forceon Retrospective Databases. Value Health. 2003, Apr;6(2):90–7. 4Benson K, Hartz AJ. A comparison of observational studies and randomized, controlled trials. N. Engl. J. Med. 2000, Jun 22;342(25):1878–86. 5Concato J, Shah N, Horwitz RI. Randomized, controlled trials, observational studies, and the hierarchy of research designs. N. Engl. J. Med. 2000, Jun22;342(25):1887–92. 6Becher H, Kostev K, Schröder-Bernhardi D. Validity and representativeness of the “Disease Analyzer” patient database for use in pharmacoepidemiologicaland pharmacoeconomic studies. Int J Clin Pharmacol Ther, 2009, Oct;47(10):617–26. 7World Health Organization. Introduction to Drug Utilization Research. WHO. Oslo, Norway: 2003. 8Schröder-Bernhardi D, Roth K, Dietlein G. Off-label use of proton pump inhibitors and P-blockers in general practices: An analysis using the DiseaseAnalyzer--mediplus patient database. Int J Clin Pharmacol Ther. 2004, Nov;42(11):581–8. 9 Star K, Bate A, Meyboom RH, Edwards IR. Pneumonia following antipsychotic prescriptions in electronic health records: A patient safety concern? Br JGen Pract. 2010, Oct;60(579):e385–9410Devaux M, Grandfils N, Sermet C. Deslisting of Mucolytics and Expectorants: What is the impact of general practioners’ prescribing? Institute forresearch and information in health economics: Questions d’économie de la Santé. 2007, Dec; (128).

11Hsia Y, Neubert AC, Rani F, Viner RM, Hindmarsh PC, Wong ICK. An increase in the prevalence of type 1 and 2 diabetes in children and adolescents:results from prescription data from a UK general practice database. Br J Clin Pharmacol. 2009, Feb;67(2):242–9

12 Wade AG, Häring J. A review of the costs associated with depression and treatment non-compliance: the potential benefits of online support. Int ClinPsychopharmacol. 2010 Sep;25(5):288–96

13Aballéa S, Cure S, Vogelmeier C, Wirén A. A retrospective database study comparing treatment outcomes and cost associated with choice of fixed-doseinhaled corticosteroid/long-acting beta-agonists for asthma maintenance treatment in Germany. Int. J. Clin. Pract. 2008, Dec;62(12):1870–9

14Rathmann W, Haastert B, Icks A, Giani G. Trends in outpatient prescription drug costs in diabetic patients in Germany, 1994-2004. Diabetes Care. 2007Apr;30(4):848–53.



IMS ISPOR SYMPOSIUM | INSIGHTS

The authors

Vernon Schabert, PHD is Global Leader Retrospective OutcomesResearch and Senior Principal HEOR, IMS Consulting Group, U.S. [email protected]

Alongside key developments in healthcare,new enhancements to public- and private-sector datasets are transforming the collectionand management of patient-level data in theU.S. An IMS Symposium at the 16th AnnualInternational Meeting of ISPOR explored theprogress of these initiatives in enablingfaster, more transparent outcomes research.

New horizons for patient-level data

This article summarizes presentations from the IMS Symposium: New Patient-Level Data from Sentinel, ACA and Recent CommercialEndeavors: Implications for Outcomes Research, held during theISPOR 16th Annual International Meeting in Baltimore, May 2011.Chair: Gregory Hess, MD, MBA, MSC, VP HEOR and Chief MedicalOfficer, SDI Health. Speakers: Joshua Benner, PharmD, SCD, Fellow atthe Brookings Institution and Managing Director, Engelberg Center forHealth Care Reform and Vernon Schabert, PHD, Senior Principal HEOR, IMS Consulting Group.

Joshua S Benner, PHARM D, SCDis Fellow at the Brookings Institution andManaging Director at its Engelberg Centerfor Health Care Reform, Washington D.C. [email protected]


INSIGHTS | IMS ISPOR SYMPOSIUM

New innovations in patient-level health data from bothpublic- and private-sector initiatives have the potential tosignificantly extend the perceived utility of healtheconomics and outcomes research (HEOR) in the U.S.Along with traditional medical claims data, Mini-Sentinelis combining Electronic Health Records (EHRs), detailedhospital data and more, for over 70 million patients; theAffordable Care Act and American Recovery andReinvestment Act have provided funding to expand andautomate routine medical care data capture as well as ameans, through the Patient-Centered Outcomes ResearchInstitute (PCORI), for directing these initiatives to improveoutcomes research. Commercial datasets are also beingenhanced and expanded.

CONCENTRATED PRESSURE

These advances reflect a number of importantdevelopments that are increasing the evidence demandsfor pharmaceutical market access decisions: greaterawareness of the gaps between efficacy and effectivenessin the real world; the move towards conditional pricing& market access; more frequent requirements for riskevaluation & mitigation strategies; the economicconsequences to manufacturers of pursuing personalizedmedicine product strategies; the growing need to addressemerging markets in launch strategy; and the increasingthreat from biosimilars outside the U.S. This concentratedpressure on the information required from data calls forhigher standards of completeness, greater clinical detail,a wider geographic reach, and a broader scope of carethan has so far been available.

PUBLIC-SECTOR INITIATIVES

The Engelberg Center for Health Care Reform at theBrookings Institution is developing and helping toimplement various practical, data-driven policy solutionsthat will enable better evidence on the safety andeffectiveness of medicines and the value of the healthcaredelivered to patients. Several of these initiatives, involvingpublic and private partners, aggregate and leverage datawhich is already being collected in the routine deliveryof care.

1. FDA’s Sentinel Initiative

The Sentinel Initiative was launched in 2008 to augmentthe Agency’s current safety surveillance capabilities.Today, the “Mini-Sentinel” pilot system can access theelectronic, integrated claims records of 71 million patients

in the U.S. For 10 million of these patients, claims arealso linked to electronic medical records (EMRs). Thesystem includes 88 hospitals and a number of device anddisease registries. Similar efforts, including the EU-ADRProject and PROTECT, are taking place in Europe.

In January 2011, the pilot system was declared open forbusiness with work commencing on the first surveillanceproject examining a potential association betweensaxagliptin and acute myocardial infarction (AMI).

The Sentinel system is a practical demonstration of ascalable distributed database network which makesrespectful use of patient-level data with the help of acommon data model that allows one executable query tobe implemented across the network. It will not onlyprovide better tools for monitoring medical productsafety but also additional resources for others developingevidence from similar data. It offers a model fordeveloping transparent protocols and provides ongoingmethods development for quantifying and reducing biasin exposure outcome associations that might also berelevant to comparative effectiveness research (CER) andother inferential analyses.

Sentinel also develops standardized definitions of severalhealth outcomes of interest, such as AMI, including thevalidation of claims-based definition of those healthoutcomes against medical charts. Perhaps mostimportantly, the system is helping to build capacity forconducting safety analyses on existing databases at over100 different participating institutions – capacity that can alsobe used to conduct other forms of evidence development.

2. Investment in data sources for CER

Research from the Engelberg Center in 2010 found thatmore than half of the US$1.1 billion funding allocatedto CER supported new evidence development andsynthesis through expanded capacity to conductobservational studies. Initiatives to expand the CER datainfrastructure include:

• Multi-Payer Claims Database with the underlyinggoal of making Medicare, Medicaid and private payerclaims data more readily available to individualresearchers. A further goal is the creation of asustainable ecosystem where data owners find it intheir interest to share their data and partner withresearchers.

New horizons for patient-level dataIMPLICATIONS FOR OUTCOMES RESEARCH



• New distributed databases providing access toclaims data and EMRs by linking individual primarycare practices.

• Product and disease registries enabling thecollection of information that is unavailable fromclaims or EMRs, such as implanted devices or patient-reported outcomes. Some of these registries can alsobe linked to claims databases to further broadenavailable information.

3. Quality of care: Improving measurement and reporting

The promotion of high-quality, high-value care alsorequires the ability to measure and report on theperformance of individual providers. Efforts in this areafocus on facilitating the coordination of care by providingdoctors and other healthcare providers with timely,comprehensive information on each patient, and to assistnew payment models, such as Accountable CareOrganizations (ACOs), by attributing patients and theiroutcomes to the providers who should be accountablefor them.

Three notable projects that are helping to addressingbarriers to effective performance measurement are theHealth and Human Services (HHS) National Strategy forQuality Improvement, the HHS Beacon CommunityProgram, and the Robert Wood Johnson FoundationHigh-Value Health Care Project. Collectively, theseprograms are accomplishing three important goals:

1. Developing methods for aggregating consistent datafrom multiple payers in a distributed network thatprotects patient privacy and the proprietary data of thepayers.

2. Filling gaps and measures in important areas likecancer care.

3. Piloting new measures that will help providersbenchmark the costs of care they provide to patientswith specific conditions.

A distributed approach to addressing data aggregationchallenges for quality measurement and reporting hasbeen proposed by Roski and McClellan of Brookingsi.The distinguishing feature of this is a feedback loop toprovide the results of quality measurement to consumers,not just doctors and payers. The goal here is to encouragegreater engagement in care and the use of high-quality,high-value providers by patients and consumers.

The results of pilot programs in Colorado and Floridasuggest that this approach is reliable, scalable andacceptable to both providers and payers.

Although these initiatives build on the work of many pastand ongoing efforts, the exciting progress being madetoday is that these are no longer disparate activitiesoperating in silos. However, further work is needed in anumber of areas:

1. Consistent use of health IT to transfer paper recordsto electronic formats and adhere to standards thatmake systems interoperable so that information can beaggregated and analyzed in a consistent manner.

2. Policies that protect privacy while supporting learningfrom the delivery of care.

3. Methodological best practices to reduce bias inexposure outcome associations when conductingobservational research.

4. Effective dissemination of the evidence, which is aclear, critical step in improving quality of care.

5. Payment and benefit reforms that can promote qualityand value among providers, patients and productmanufacturers.

APPLYING THE EVIDENCE

The evidence generated from ongoing projects will beused in a number of ways: for safety surveillance, CERand quality measurement reporting. Evidence fromSentinel will be directly considered by the FDA inregulatory decisions. Sentinel also has a history ofimpacting formulary decisions by payers and healthcaredelivery systems. CER will be considered in the contextof the overall body of evidence when making coveragedecisions and may be requested as a condition ofcoverage. Finally, for quality measurement, the evidencewill be used to reward providers who deliver high-quality, high-value care, as well as to inform benefit esignsthat can promote the use of such providers.

Although these initiatives buildon the work of many past andongoing efforts, the excitingprogress is that these are no longerdisparate activities

i Roski J. McClellan M. Health Affairs, 2011; 30 (4):682-9. See also: Higgins A, Zeddies T, Pearson SD. Health Affairs, 2011; 30 (4):673-81 continued on next page


INSIGHTS | IMS ISPOR SYMPOSIUM

PRIVATE-SECTOR INITIATIVES

In the private sector, the development of data sourceslargely reflects anticipated market needs. According toIMS Market Prognosisii, antineoplastics andimmunomodulators will be the leading growth marketover the next five years. These products include cancermedicines and other biologics, such as monoclonalantibodies, growth factors, disease-modifying anti-rheumatic drugs (DMARDs) and erythropoietin-stimulating agents.

This is not the landscape of ten years ago, when HEORwas primarily focused on CNS diseases and primary careconditions such as diabetes, endocrine and cardiovasculardisorders. Going forward, data demands will beincreasingly driven by market growth concentratedamong specialist-managed therapies. Although definingthe target populations for such therapies requires highly-specific clinical detail, research questions around thesetherapies will still require access to the full scope of care.New data sources must thus be able to address both thespectrum of care and specificity of clinical informationdemanded more frequently in specialty markets.

GROWING LINKAGE ACROSS SOURCES

Historically, databases have been developed by compilingmultiple instances of a single data type (eg, payer data,pharmacy records, EMRs). This has resulted in mostavailable sources having either a wide scope of care orsubstantial clinical detail, but not both (Figure 1).

Today, a growing number aim to link data across differentsources, for example: 1. Traditional payer data sources are being linked withhospital detail data enabling more specific informationaround the consequences of a hospitalization.

2. Traditional pharmacy data warehouses are trying tolink-up this information. The challenge withpharmacy data, especially in the U.S., is the absence ofdiagnostic information and the details of other clinicaltreatments that are provided. There has been an effortto take that pharmacy data and link it, for example,with claims data that might be available from a medicalswitch provider.

3. There have also been attempts to link pharmacy datawith EMR data and to some extent with lab results tohelp build a broader clinical history across the fullscope of care. In cancer therapy, for example, data fromoncology EMRs – which have rich detail foridentifying biomarkers, stage of disease and clinicalpathways – has been linked with broader informationfrom pharmacy data enabling insights beyond the care itself.

These advancements beyond the single-silo focus of dataare taking place in two ways: Firstly, through thetechnique of probabilistic matching, where independentdata sources are used to develop sense of care patterns,geographic location and other clues to match patients inthe hospitals with patients in claims data; and secondly,by creating an uncommon encryption mechanism andrelying on the strength of a trusted third party to ownthe encryption keys to match those data together.

BEYOND THE US

Most of these early efforts have been concentrated in theU.S., but more are now emerging elsewhere. Many ofthese ex-U.S. initiatives involve public/privatepartnerships or public academic or governmentinstitutions that have more legal and ethical flexibility injoining disparate data sources. Examples include thePHARMO Institute for Drug Outcomes Research in

Going forward, data demands willbe increasingly driven by marketgrowth concentrated amongspecialist-managed therapies

FIGURE 1: MOST COMMERCIAL DATA SOURCES TRADE-OFFSCOPE OF CARE VERSUS CLINICAL DETAIL

Source: IMS Symposium, ISPOR Baltimore, May 23, 2011

Payer

PCEMR

IP

Rx

Lab

Best Utility

High

Scop

e of

Car

e

Clinical Detail HighLow

Low

ii IMS Market Prognosis provides a five-year projection of growth at the country,regional and global level for health technology markets covering 80 percent of theindustrialized and emerging markets world.




the Netherlands, the Bremen Institute for PreventionResearch and Social Medicine (BIPS) database inGermany, and the Odense UniversityPharmacoepidemiological Database (OPED) inDenmark. The trade-off is that access may be difficult,particularly access by for-profit companies, who may betreated with suspicion by public-sector collaboratives.

CREATIVE LEVERAGING

While there may not yet be a commercially availablesource for matching every piece of information in everycountry, there are nevertheless options for leveragingprivate-sector databases (Figure 2). In the short andmedium term, there are two general strategies to leveragenot-yet-perfect data:

1. Creation of custom linkages among one or moreidentifiable or de-identified data sources. Identifiablesources may come from patient registries or payers andproviders with direct access to identifiers. In somecases, those can be linked to commercial data sourcesthrough probabilistic matching or commonencryption techniques, yielding data that meetsdemands for both clinical detail and scope of care.

2. Use of a modular approach, where real-world evidenceforms the basis of inputs to a decision model, or is usedas a portion of a Bayesian adaptive trial, to extend thevalue of data sources over time or across the scope of care.

BETTER DATA, RICHER RESEARCH

Recent advancements in the collection and managementof patient-level data from both public- and private-sectorinitiatives have a number of important implications forhealth economics and outcomes research:

1. Firstly, they mean more and better data for all, viamulti-payer networks that enable the scale of researchto be increased. This involves going beyond claimsdata to EHRs and registries, adding significantrichness to our research.

2. Secondly, they will create the opportunity for greatercollaboration through distributed database networks.They do, however, imply a need for researchers tocollaborate effectively with the owners of the data,whether they are in the government or private sector.

3. Thirdly, they will generate a need for more HEORinvestigators with new and different skills, includingexpertise in health IT, cryptography, patient privacy,ethics, epidemiology, health economics, biostatisticsand clinical decision analysis.

4. Finally, above all, growing emphasis on learning fromthe delivery of care provides a brighter future for, andvery high expectations of, HEOR scientists who aresure to play an increasingly important role inimproving healthcare by providing the evidence tosupport higher-quality, lower-cost care for patients andtheir populations.

However, simply having more and better evidence is notenough. Supporting efforts must address the need forconsistent use of health IT; policies that protect privacywhile supporting learning from delivery of care;methodological best practices; effective dissemination ofthe evidence; and payment and benefit reformspromoting quality and value among providers, patientsand manufacturers. •

FIGURE 2: LEVERAGING NOT-YET-PERFECT DATA

Source: IMS Symposium, ISPOR Baltimore, May 23, 2011

Analysis 1

Analysis 2

Analysis 3

CustomLinkages

ModularAnalyses

Source 1 Source 2 Source 3

Answer

HEOR scientists are sure to playan increasingly important role inimproving healthcare


INSIGHTS | DATA LINKAGE FOR CER

The ability to compare the relativeeffectiveness of different technologies andpractices is now imperative to meet thegrowing demand for more rigorous outcomesresearch. But, along with the many challengesthis brings, there is the need for new,advanced techniques to overcome thelimitations of existing data. Here we considerthe approach of data linkage in addressingthis critical issue.

The author

Christopher Blanchette, PHD, MS, MA is Principal HEOR, IMS Consulting Group, U.S. [email protected]


DATA LINKAGE FOR CER | INSIGHTS

Probabilistic data linkage A NOVEL TECHNIQUE FOR COMPARATIVE EFFECTIVENESS RESEARCH


DATA LIMITATIONSToday, there are only limited data available to conductcomparative effectiveness research. The two types thatexist are survey and secondary databases, both of whichhave their own particular shortfalls. Survey data have led to landmark studies that have shaped the currentpractice and treatment of many chronic diseases.However, these data are also traditionally limited inexternal validity, specificity of measurement on keyexposures and outcomes, and historically dated beyondapplication to current therapies.

Secondary databases, including administrative datacollected by the infrastructure of the healthcare system forthe purposes of payment for services, also have limitations.Administrative data are typically restricted to billing claimsand provide limited clinical detail to confirm disease. Theyare also often scarce on patient characteristics, such as raceand ethnicity, and on indigent and self-pay populations, aswell as lacking detail on patients’ perception of disease orthe impact of disease or treatment on humanisticoutcomes. Electronic medical record (EMR) systems,newly created to replace paper-based chart systems intracking clinical symptoms and disease, are still in the earlystages of development. Moreover, they are frequentlypositioned in silos of healthcare practice – traditionallyphysician practices with limited linkage to inpatientfacilities, other specialists or other physician services,emergency and acute services, and pharmacy services.

While each of these dataset types provides uniqueinformation, they lack a significant amount ofinformation about the patient and their treatments aswell. There are very few sources offering the completepicture of a patient. Those that do, often have their own drawbacks, such as geographic homogeneity, smallsample sizes or patient selection methods that limitgeneralization to real-world populations.

LEVERAGING THE BENEFITSUntil the ideal, complete source presents itself, there isan alternative: a method whereby researchers can leveragethe benefits of each individual type of data source,utilizing data linkage methods to fill in the gaps of onedatabase with the strengths of another. This approach waspresented at a workshop during the ISPOR 13th AnnualEuropean Congress in 2010. and preliminary results,demonstrating the application linking the twoadministrative databases, were discussed at a subsequentworkshop during the ISPOR 16th Annual InternationalMeeting in 2011.

MAKING THE LINKDatabase linkage methods generally employ bothdeterministic and probabilistic linking algorithms.1,2,3Deterministic linkage techniques can be applied whenboth datasets provide patient-identifying information thatcan be cross-matched between the two datasets. This isthe preferred form of data linkage because the focus ison matching the same patient from both datasets.

In the current climate with the regulatory and legal restraintson the use of personal health information (PHI) thisapproach is limited. In the absence of PHI, a probabilisticmethod may be applied. However, the focus is not onidentifying the same patient but rather on two matchingpatients with similar behavior and characteristics.4,5,6 Thegoal of both of these efforts is to identify the best methodfor pair-matching between datasets.

Probabilistic linking methods incorporate varyingstrengths of identifiers, depending on informationprovided by the identifier. Stronger weights are given tomatches for identifiers upon which matching is less likely.For example, matching on sex – male or female – is lesslikely to produce a matching of equivalent records thanmatching a record on the combination of birth-monthand year. Assigned weights are related to frequencies ofoccurrences of values in linked and unlinked pairs andalso to the designated level of agreement.7

The determination of agreement can be further definedinto subcategories: agreement (yes/no), or varying levelsof partial agreement (eg, matching of a date within 2 daysbefore/after, matching of data within a week before/after).Using probabilistic linking methods generally increasesthe sensitivity and specificity of models over a deterministicmethod in linking records from disparate datasets.

Propensity score methods are increasingly used to matchsimilar individuals in observational studies, along withother approaches to control for channeling bias.8,9 Thesemethods are similar to the approach used in probabilisticdata linkage. In propensity score matching, well-matchedpairs are closely matched on the predicted probability ofexperiencing the dependent variable using relevantcovariates. Matching techniques then employ a variety ofapproaches based on the predicted probability score(ranging from 0 to 1) including nearest neighbormatching heuristics, and often employing samplingwithout replacement.10,11


INSIGHTS | DATA LINKAGE FOR CER


In the absence ofcomplete data, theapproach offers a goodstart and paves the wayfor further examples ofthis type of linkagemethod to be explored

CASE IN PRACTICEComparative effectiveness of an inhaled corticosteroid/long-acting beta agonist combination versus an anti-cholinergic among commercially insured patients with COPD

STUDY DESIGN

The study used a historical cohort design. Patients aged 40 andolder with a principle or secondary diagnosis of COPD(International Classification of Disease, 9th Revision codes: 491,492 and 496) and at least three years of continuous enrollmentbetween January 1, 2004 and April 30, 2009 were selected fromDatabase A and Database B. The index date was assigned as thedate of the first claim (defined by a twelve month wash-outpre-index period) for the study drug, an inhaled-corticosteroid/long-acting beta agonist combination, or an anti-cholinergic. The effectiveness measure was risk of COPD-related hospitalization observed in the 12-month post-period and baseline characteristics were identified in the 12-month pre-index period.

PROBABILISTIC DATA LINKAGE METHOD

Steps taken to define and link the cohorts:

1. Restrict the samples to two cohorts in each database withsimilar pre-index and post-index time periods.

2. Pool data and develop a logistic regression modelpredicting the propensity to be in Database A usingoverlapping pre-index variables.

3. Match patients from both databases on the propensity score.

4. Impute Database A outcomes for matched controls from Database B.

5. Conduct comparative effectiveness study in each cohort(A, B, and A with imputed outcomes).

January 1, 2004 January 1, 2005 March 31, 2008 April 30, 2009

Time frame of analysis

Index Period

12-month pre-index

12-month post-index

STUDY DESIGN


DATA LINKAGE FOR CER | INSIGHTS

RESULTS

The event rate of hospitalizations in each cohort wasnearly identical as was the odds ratio and correspondingconfidence intervals from the adjusted logistic regressionmodels. This is not entirely surprising since theprobability of being in each cohort was determined bythe overlapping similarity in characteristics between thetwo cohorts, just as if the propensity score match wasused in a traditional cohort analysis.

CONCLUSIONS

The probabilistic linkage demonstrated that patients fromdifferent databases matched on similar pre-index characteristics may demonstrate similaroutcomes in the post-index period. The implications ofthese findings and this approach is significant as it callsinto question the case for linkage of simulated cohortsfrom varying databases – EMR and administrativedatasets, administrative datasets and surveys, EMR andsurveys, etc. Creation of simulated cohorts could helpexplain a more complete picture of patient outcomes andallow us to explore all sides of a patient experience –economic, clinical and humanistic through the use ofretrospective data analysis.

PAVING THE WAY FOR FURTHER EXAMPLESSeveral caveats are worthy of note with this method: the divergence of the measures between the databasesmay also cause a divergence in “like” patients therebyintroducing error in the outcomes assessment; care shouldbe taken to ensure that similar measures are used to buildthe logistic regression model to create the propensityscore; and the assumption is that probabilistic matchingproduces two individuals with similar attributes and notthe same individual. However, in the absence of completedata, this method appears to be a good start. Furtherexamples of this type of data linkage should be exploredwith various databases to determine the limitations. •

1da Silveira D, Artmann E. Accuracy of probabilistic record linkage applied to health databases: Systematic review. Revista de Saude Publica, 2009; 43:875-8822Jaro M. Probabilistic linkage of large public health data files. Statist Med, 1995; 14:491-4983Lyons R, Jones K, John G. The SAIL databank: Linking multiple health and social care datasets. BMC Med Inform Decis Mak, 2009; 9(3)4D'Agostino Jr R. Propensity score methhods for bias reduction in the comparison of a treatment to a non-randomized control group. Statist Med, 1998; 17: 2265-22815Rose S, van der Laan M. Why match? Investigating matched case-control study designs with causal effect estimation. Int J Biostat, 2009; 5:266Van der Laan M. Estimation based on case-control designs with known prevalence probability. Int J Biostat, 2008;4:1-177Mason C, Tu S. Data linkage using probabilistic decision rules: A primer. Birth Defects Research, 2008; 82:812-8218D'Agostino Jr R. Discussion of statistical and regulatory issues with the application of propensity score analysis to non-randomized medical device clinicalstudies. J Biopharmaceutical Stat, 2007;17:29-339Rosenbaum P, Rubin D. Reducing bias in observational studies using sub-classification on the propensity score. J Am Stat Assoc, 1984; 79:516-52410Gonzalez-Smith M, Storer J. Parallel algorithms for data compression. ACM, 1985; 32(2):344-37311Parsons L. Reducing bias in a propensity score matched-pair sample using Greedy Matching techniques. In: 26th Annual SAS User Group International Conference, 2001; 214-226

Pre-IndexIndex

Post-Index

Database A PS Match

Database B Imputation by match

Database A with imputedoutcomes from Database B

PROBABILISTIC DATA LINKAGE METHOD

Rate of Exacerbation Adjusted Results*

Data Treatment 1 Treatment 2 OR 95% CI

Database A 39.3% 46.3% 0.72 0.66 0.79

Database B 39.7% 47.1% 0.74 0.67 0.81

Database A with imputed outcomes 40.1% 46.8% 0.72 0.65 0.80

RESULTS

*Adjustment for age, geographic region, comorbidities and pre-indexutilization of health services and respiratory medications using logisticregression.


INSIGHTS | IMS CORE DIABETES MODEL

The IMS CORE Diabetes Model is recognizedby healthcare decision makers worldwide forits valuable insights into the long-term clinicaland economic outcomes of interventions fordiabetes. Recently updated with significantenhancements, it is now undergoing extensivevalidation to verify its new capabilities.

The authors:

Phil McEwan, PHD is an independent researcher with IMS HEOR, IMS Consulting Group, [email protected]

David Grant, MBA is Senior Principal HEOR, IMS Consulting Group, [email protected]


IMS CORE DIABETES MODEL | INSIGHTS

Validating the IMS CORE Diabetes Model

The IMS CORE diabetes model (CDM) is a policysupport simulation model that predicts expected long-term clinical events, health outcomes and costs associatedwith the management of Type 1 or Type 2 diabetesmellitus.1 The model has been used extensively toevaluate the cost-effectiveness of new diabetes therapies,although its capabilities extend well beyond technologyassessment. Increasingly, simulation models such as theCDM are being used to evaluate a range of issues fromcapacity and resource planning and trial design throughto optimal patient management strategies.

The CDM has recently undergone a major update: itscapabilities now include the ability to model individualpatient-level data and incorporate treat-to-target analysis.The probabilistic analysis module has also been updatedand improved. Demonstrating that the CDM is anaccurate representation of the system it is designed tosimulate is of fundamental importance. Individuals whoare developing, making and implementing decisions informed by the model’s analyses need to know that theCDM and its results are robust; such reassurance isachieved through model validation and verification.

RECORD OF ROBUST VALIDATION

The CDM has a robust validation pedigree. A majorvalidation exercise, published in 2004, demonstrated theoperational predictive validity of the model to 66epidemiological and clinical studies.2 Furthermore, theCDM’s development has been closely linked to the MountHood Challenges3,4 – forums for computer modelers ofdiabetes to compare predicted model output with datafrom clinical trials.

The fifth and most recent Mount Hood Challenge in 2010saw the CDM and seven other models simulate trials of alipid-lowering intervention (ASPEN); blood glucose-lowering intervention (ADVANCE); and blood pressure-and blood glucose-lowering intervention (ACCORD).The results of this meeting are to be published shortly;previous challenges have demonstrated that the CDMperforms well, particularly when predicting the relativebenefit of interventions.3,4

FIGURE 1: SCHEMATIC OUTLINING THE GENERALIZED MODEL DEVELOPMENT PROCESS (DASHED LINES) AND THE VALIDATIONAND VERIFICATION (CIRCULAR) ACTIVITIES CONDUCTED ALONGSIDE


Computer Programming & Implementation

Analysis & ModelingExperimentation

ComputerizedModel

ConceptualModel

Diabetes(Real World)

DATAVALIDITY

A RIGOROUS PROCESS FOR CONFIDENT USE

Source: Sargent RG. Verification and validation of simulation models. In: Proc 1996 Winter Simulation Conf., ed Charnes JM,Morrice DJ, Brunner DT, Swain JJ, 55-64. Piscataway, New Jersey: IEEE

ConceptualModel Validity

OperationalValidity

ComputerizedModel

Verification


INSIGHTS | IMS CORE DIABETES MODEL

CONCEPTUAL VALIDATION AND VERIFICATION

Figure 1 (page 35) is a graphical representation of the modeldevelopment process.5 The rectangular blocks represent themodeling problem and process; the diabetes box, the real-worlddiabetes phenomena; the Conceptual Model, the particularmathematical and logical representation of the real-worldsystem; and the Computerized Model is the physical(computer) implementation of the model.

The current validation of the CDM focuses on assessingconceptual model validity, verification and operational validity.Each of these is discussed in turn, below.

1. Conceptual model validityConceptual validity documents the model structure, logic andmathematical and causal relationships at the conceptual leveland includes the following items:

• UNDERLYING THEORIES AND ASSUMPTIONS: Theseare required for each module and sub-module to ensure thatthe model has face validity. This involves setting-out mechanisms within the model that control howdisease progression occurs, what modifiable and non-modifiable variables contribute to differential profiles ofdisease progression, and what specifications of treatmenteffects alter the course of disease progression.

• DEFINITION OF VARIABLES: All variables are requiredto be appropriate, justifiable and unambiguously defined. Forexample, all disease states and clinical endpoints, resourcedrivers and model and patient attributes must be clearlydelineated.

• MODEL CONTENT AND STRUCTURE: This requires ademonstration that the CDM is sufficiently complete toadequately undertake a diabetes economic evaluation,including documentation of areas where model structure isweak due to limited data availability.

• PARAMETER VALIDITY: The CDM contains approximately600 parameters. Of primary concern is an understanding ofpossible bias in the choice of parameters selected and thedegree of uncertainty associated with each. This is viewedagainst the importance of each parameter in driving theresults of the model – which may differ across modelapplications.

• PARAMETER SOURCE: While the source of parameter values is often limited by data availability, it isimportant to document the source and quality of parametervalues used in the model (eg expert opinion, literature, dataanalysis, calibration).


Individuals who aredeveloping, makingand implementingdecisions need to knowthat the CDM and itsresults are robust; such reassurance isachieved through modelvalidation andverification.


IMS CORE DIABETES MODEL | INSIGHTS

2. Model VerificationModel verification ensures that the programming andphysical implementation of the conceptual model havebeen completed correctly.

• IMPLEMENTATION: The choice of model designmust be justified, together with the software platformused to interface with the user (web interface) andperform the underlying calculations (compiled C++libraries). For the CDM, this requires justification of acohort-based micro-simulation with a compiled C++run-time library and web-based interface.

• VERIFICATION: Ensuring that the CDM operatesas intended is of fundamental importance to ensure itsvalidity and credibility. The following process has beenundertaken to verify the model:

• The major sub-programs within the core modelhave been built as stand-alone routines withinMicrosoft Excel to achieve two objectives:

1. Verify that the source codes used in thecompiled model are correct.

2. Facilitate the testing of each sub-routine, eg,assessing the effect that relevant input parameters(singularly and in combination) have on theresults predicted by each sub-routine.

• The CDM has been run under a variety ofscenarios and under simplified assumptions toensure that the model output is reasonable andinternally consistent with the output obtained fromthe analysis of individual sub-routines.

• The simulated trajectory of a patient over time isfollowed to facilitate the testing of model logic,timing of clinical events and the correct applicationof costs and dis-utilities.

3. Operational validityOperational validity asks whether the model’s behaviorpossesses the necessary accuracy required for its intendedpurpose across the domain of its intended use. It is anidealistic goal of validation to determine whether thesimulation model is good enough to make a decisionabout the system (eg, cost-effectiveness of new diabetestherapies) similar to that which would have been madehad it been feasible to experiment with real diabetespatients. This extends beyond the usual approach tovalidation where model output is compared to real-worldstudies – whether clinical trial, epidemiological study orobservational.

The Mount Hood Challenges have provided an excellent platform for assessing the operational validityof the CDM – pitching the model against other diabetesmodels with respect to reproducing the effects observedin long-term outcomes studies, cost-effectiveness analysis and model convergence.

CONCLUSION It is important to appreciate that simulation models arenot universally valid; they are designed for a specificpurpose and their validity requires assessment setagainst their intended use. Furthermore, the ultimategoal of credibility is achieved only when users haveenough confidence in the model to utilize it and relyon its output. Arguably, the IMS CORE DiabetesModel has already achieved this standard. The primaryobjective of the current validation process is to verifythe extent to which the most recent update hasimproved the model. Once this is completed, the keyelements of the validation will be submitted for peer-reviewed publication. •

1Palmer, et al. The IMS Core Diabetes Model: Projecting long-term clinical outcomes, costs and cost-effectiveness of interventions in diabetes mellitus(Types 1 and 2) to support clinical and reimbursement decision making. CMRO, 2004;20 (8 Suppl): 5-262Palmer, et al. Validation of the CORE Diabetes Model against epidemiological and clinical studies. CMRO, 2004; 20 (Suppl 1): S27-403Brown, et al. The Mount Hood challenge: Cross-testing two diabetes simulation models. Diabetes Res Clin Pract. 2000; 50 (Suppl 3):S57-644Computer modeling of diabetes and its complications. A report on the Fourth Mount Hood Challenge Meeting. The Mount Hood 4 Modeling Group.Diabetes Care, 2007; 30:1638-16465Sargent, R. G. Verification and validation of simulation models. In: Proc. 1996 Winter Simulation Conf., ed. Charnes JM, Morrice, DJ, Brunner DT andSwain JJ, 55-64. Piscataway, New Jersey: IEEE


INSIGHTS | COMMUNICATION AND OUTREACH

Health economics and outcomes research isa pivotal tool for decision makers but thereis work to be done in reaching out to abroader audience. In the age of theempowered consumer, we consider thecosts, benefits and policy implications of DTC engagement in Europe.

The author

Jacco Keja, PHDis Regional Leader EMEA HEOR, IMS Consulting Group. [email protected]


COMMUNICATION AND OUTREACH | INSIGHTS

“There are a number of benefits that would likely comefrom expanding our communications activities. The first isthat it would help us translate our research into concretepolicies - and help move health systems forward so thatdecisions better reflect evidence of value. Our work inpharmacoeconomics and outcomes research should resonatewith varied audiences, including payers, physicians, patients,and the media. The second likely benefit is an improvementin our own work. The practice of communicating well – toscientific audiences and to audiences unschooled in ourmethods - will help us shape and focus our analyses.”

These words were delivered by Peter Neumann asPresident of ISPOR in 20061 but they remain as validtoday within the broader context of health economicsand outcomes research (HEOR). Typically, HEORspecialists excel in science; where we can improve is in translating our work into practical policies. To this end, there is a need for deeper engagement withour stakeholders.

We are already making progress towards this goal: tenyears ago, the endpoint for most of our work was solid,scientific papers; five years ago, we had moved beyondthat, with value dossiers becoming the new pinnacle –albeit a rather static one, focused on launch. In recentyears, we have seen these documents become far moredynamic, constructed early in development andmaintained over the lifecycle, enabling gap analyses andinforming R&D on appropriate endpoints, studypopulations and relevant comparators, and those involvedin RWE generation, on requirements for data.

Alongside these developments, we have seen fledgingefforts by pharma to embed the value messages inmultichannel communications – and it is here whereHEOR embarks upon a higher level of communicationto healthcare providers and payers. But, as Peter stressedin his address, we cannot underestimate the importanceof educating “patients and the media” as well. This issueof outreach to a wider public audience is an interestingone as solutions can only be implemented and valued if the scope and dimensions of the problem arewell understood.

UNDERSTANDING THE ISSUES

As noted by PhRMA in 2008, efforts that form part ofpharmaceutical marketing and promotion have animportant role to play in educating and informingconsumers, helping to create awareness of diseases andtreatment options and empowering patients withinformation.2 This is particularly valid amid growingawareness of the need to “bring the patient back into thecenter of the conversation”.3 Although currentlypermissible only in the U.S. and New Zealand, direct-to-consumer advertising (DTCA) is reported to be thefastest growing form of pharmaceutical marketing.4 It isalso one of the most contentious, fuelling major concernsand policy discussions around the world. At the heart ofthis debate is the fundamental health economic questionraised by Block in 20075: What are the costs and benefitsattributable to DTCA for society as a whole? Morespecifically in this context, what is its value for healthcarein Europe - and what are the implications of proceedingin this direction?

COSTS AND BENEFITS

One of the main challenges in determining the costs andbenefits of DTCA in a European context is the dearthof studies in the academic literature evaluating how itmay directly impact healthcare in the region. The mostvocalized arguments against DTCA in the EU focus onconcerns that it may lead to increased drug expenditure,over-utilization of brands, the provision of misleading orfalse information, or patient safety issues.4 Advocates, onthe other hand, propose that DTCA can improve publichealth by increasing awareness about particular diseasestates and motivating patients to talk to their physicians.6

At the heart of these polarized views is the role of DTCAas a vehicle for information – something that has beenlong recognized by economists for its potential to impactnot only the immediate consumer, but also at a broader level, pharmaceutical prices, principal-agentrelationships and the overall functioning of healthcare markets.7

Extending the outreach of HEORHEALTHCARE VALUE AND POLICY IMPLICATIONS OF DTC IN EUROPE




As a conduit for information

As noted by Reinhardt, from a societal perspective thebenefits of pharmaceutical marketing activities such asDTCA lie in the utility of the information that can becommunicated to physicians and patients.8 Debatably,the argument in its favor hinges on the role of DTCA asa tool for health promotion. Matear and Dacin recognizethree areas where DTCA can serve as a vehicle forinformation: clinical, economic and consumer. However,their findings from a comprehensive review indicate littleor no consensus on its ultimate effects in this capacity.9

Opponents of DTCA have inferred that consumers arenot in a sufficiently knowledgeable position to assess itscomplexity and often place unjustified trust in adverts.10

However, a comprehensive review of evidence from U.S.surveys looking at the educational potential of DTCAwould appear to contradict this: more than 50% ofphysicians surveyed agreed that DTCA educates patientsabout health conditions and available treatments; andpatients felt that it improved their understanding ofdiseases and treatments and helped play a role in theirdecision making process.11 This is clearly an arearequiring further research.

Impact on pharmaceutical prices

One criticism levied at DTCA is that it mayinadvertently increase drug prices by driving up requestsfor the advertised product – with potentially seriousimplications for universal access to healthcare. Countriesbanning this form of promotion argue that it wouldreduce price sensitivity of demand for prescription drugsand consequently lead to negative welfare effects.12

It is interesting to note that the U.S. – where DTCAproliferates – pays, on average, one-third to a half morefor the same pharmaceutical drugs than other developedcountries with national healthcare systems.13 However,there is no substantial evidence in the current literaturethat shows a direct correlation or positive association ofhigh prices resulting directly from DTCA.13 Indeed, thefindings of a recent methodological study conducted byCapella, et al, utilizing data on brand medications in fivemajor therapy classes in the U.S., suggest that DTCAdoes not decrease price elasticity and thus does not leadto increases in the price of pharmaceutical prescriptiondrugs.14 While more research is needed to verify theseresults, there appears to be a growing body of evidencedisputing the assertion that DTCA has a price-risingimpact on pharmaceuticals.

Impact on physician-patient relationship

There is a view that DTCA may compromise orchallenge the traditional physician-patient relationship bycreating demand for an advertised drug,15 which in turnleaves physicians pressured to prescribe the productrequested.16 Physicians themselves have reported feelingless able to control the direction of treatment becausepatients have already decided on a medication17 orreceiving patient requests for advertised pharmaceuticalsthat in and of themselves may do very little to improvetheir overall health.18

However, these arguments only serve to underscore therecent paradigm shift in patient attitudes and the waythey gather information in today’s high-tech world. Witha far greater thirst for knowledge on matters of healthand wellness than previous generations, and thetechnology to seek it out, a growing number of patientsand consumers today consider mass media the mostimportant source of information, second only to theirhealthcare providers.19

Thus, DTCA may actually encourage patients to educatethemselves and become more active in managing theirown healthcare.18 As Harvard University economistMeredith Rosenthal has postulated: “It does not seemunrealistic that, however accidentally, DTCA could havea salutary effect, even if advertisements are misleading andfactually incorrect, simply by creating an opportunity fordiscussion with a physician”.20 It would also beinteresting to see if DTCA-educated patients are moremotivated and show an increased level of therapyadherence. Non-adherence is major healthcare issue.Even clinical trials report average adherence rates of only43 to 78 percent among patients receiving treatment forchronic conditions and of all medication-related hospitaladmissions in the U.S, 33 to 69 percent are due to poormedication adherence, with a resultant cost ofapproximately $100 billion a year.21,22

There appears to be a growing bodyof evidence disputing the assertionthat DTCA has a price-risingimpact on pharmaceuticals



COMMUNICATION AND OUTREACH | INSIGHTS

POLICY IMPLICATIONS IN EUROPE

DTCA, if used as a mediator of information, clearly hasthe potential to improve healthcare by increasing apatient’s right to take a proactive and informed role intheir health and treatment decisions. It may also have apositive welfare effect. Its ability to achieve this goal inEurope would depend, to a large extent, on the type ofstructure that could be established to oversee and policethe advertisement of pharmaceuticals to the public. Inthe U.S., the FDA has been severely criticized forshortcomings in this regard. Currently, EU law does notclearly distinguish between what is considered advertisingand the provision of non-promotional information onmedicines.23 However, ongoing discussions concerningthe potential revision of the absolute ban on DTCAwithin the EU Health policy framework may present anopportunity to do so.

Can objectivity be assured?

Some of the skepticism regarding DTCA in Europeconcerns the industry’s ability to offer objective and non-promotional information on its products withoutpromoting them.24 The EU framework banning DTCAfor prescription-only medicines is laid out in Article88(1) of Directive 2001/83/EC of 1992, the applicationof which resides with each member state.

In 2007, recognizing disparate interpretations of thisDirective across Europe, changes in public attitudestowards health and medical information, and theavailability of new channels such as the internet, the EClaunched a public consultation proposing a revisedframework for the provision of information onprescription drugs (not advertising) directly to consumersand patients. This was followed by a second consultationin 2008, maintaining the ban on DTCA, but opening upthe possibility for the pharmaceutical industry to providecertain information about prescription-only drugsthrough various multi-media channels. Most interestinglyreal-world evidence (RWE) was given a special position

in the original proposal, meaning that pharmaceuticalcompanies would be allowed to disseminate to the publicinformation on non-interventional studies (subject tocontrol by competent authorities prior to dissemination).

Recent developments

More recently, on 11 October, 2011, the EC adoptedrevised proposals amending those of 2008 and clarifyingthe information that pharmaceutical manufacturers canprovide to the public on prescription medicines. Thismakes provision for only certain information onprescription medicines (eg, from the label and packageinserts as well as trial information) to be providedthrough limited channels of communication (eg officialwebsites or printed information when specificallyrequested by the public) fulfilling recognized qualitycriteria (ie unbiased, evidence-based, factually correct,not misleading, and understandable) and verified bycompetent authorities prior to dissemination if it has notbeen approved before. It gives companies not only the rightbut also the obligation to make certain information available.The proposals also address pharmacovigilance issues.25

In general, the newer revised proposal seems to moveaway from a more patient- and reality-orientedframework, and regress back to a regulatory focus, eg, byreorienting the text from the right of marketingauthorization holders to make available someinformation, to the right of the patients to haveinformation. Another fundamental change is replacingthe original Article 100b text (“medicinal product-relatedinformation about non-interventional scientific studies,or accompanying measures to prevention and medicaltreatment, or information which presents the medicinalproduct in the context of the condition to be preventedor treated”) by text which is much more package insert-oriented where perhaps only the following text paves theway for RWE dissemination: Article 100g.: “other typesof information approved by competent authorities thatare relevant to support the proper use of the medicinalproduct.”

CONCLUSIONS AND IMPLICATIONS

The value of DTCA remains hotly debated, and asevidenced by the recent step back in the amendedDirective 2001/83/EC (as regards information to thegeneral public on medicinal products subject to medicalprescription and as regards pharmacovigilance) it seemsthat the old prejudice and political notions on thepotential negative impacts of DTCA are still dominant.

DTCA has the potential to improvehealthcare by increasing a patient’sright to take a proactive and informed role in their health and treatment decisions




1. Presidential Fireside Chat: ISPOR Initiatives in Communication and Outreach. http://www.ispor.org/news/articles/feb06/president.asp AccessedOctober 22, 2011

2. The Facts about Pharmaceutical Marketing and Promotion, PhRMA, 2008. Accessed October 22, 2011 athttp://www.phrma.org/sites/default/files/159/marketing_and_promotion_facts_071108_final.pdf

3. Landro L. The Informed Patient: Many Pills, Many Not Taken. Wall Street Journal, 10 October, 2011. Accessed October 22, 2011 athttp://online.wsj.com/article/SB10001424052970203388804576616882856318782.html

4. Liang BA, Mackey T. Reforming Direct-to-Consumer Advertising. Nature Biotechnology, 2011, 6 May; 29(5): 397-4005. Block AE. Costs and Benefits of Direct-to-Consumer Advertising: The Case of Depression. Pharmacoeconomics, 2007; 25(6):511-521.6. Hughes-Morgan M, Kendrick JL, et al. Strategic Change within the Pharmaceutical Industry: The Impact of Direct-To-Consumer Advertising for

Prescription Medicines. International Journal of Information Systems and Change Movement, 2010; 4(3): 246-257.7. Avery R, Kenkel D, et al. Health Disparities and Direct-to-Consumer Advertising of Pharmaceutical Products. Advances in Health Economics and Health

Services Research, 2008; 19: 71-94.8. Reinhardt, U E. An Information Infrastructure for the Pharmaceutical Market. Health Affairs, 2004; 23(1): 107-1129. Matear, M, Dacin PA. Marketing and Societal Welfare: A Multiple Stakeholder Approach." Journal of Business Research, 2010; 63: 1173-117810. Conners, A. Big Bad Pharma: An Ethical Analysis of Physician-Directed and Consumer-Directed Marketing Tactics." Albany Law Review, 2009;73(1):

243-248.11. Frosch D L, Grande D, et al. A Decade of Controversy: Balancing Policy With Evidence in the Regulation of Prescription Drug Advertising." American

Journal of Public Health, 2010; 100 (1): 24-32.12. Leeflang, PSH, Wieringa JE. Modeling the Effects of Pharmaceutical Marketing. Marketing Letters, 2010; 21: 121-133.13. Harter, T.D. In Sickness and in Health: Analyzing the Ethical Limits of the Marriage between Health Care and the Market in the United States. Philosphy.

Tennessee, University of Tennessee, 2010; PhD: 237.14. Capella ML, Taylor CR, et al. Do Pharmaceutical Marketing Activities Raise Prices? Evidence from Five Major Therapeutic Classes. Journal of Public

Policy & Marketing, 2009; 28(2): 146-161.15. Gellad, ZF, Lyles KW. Direct-to-Consumer Advertising of Pharmaceuticals. Am J Med, 2007;120: 475-480.16. Martinez, LS, Lewis N. The Role of Direct-to-Consumer Advertising in Shaping Public Opinion Surrounding Prescription Drug Use to Treat

Depression or Anxiety in Youth. J Health Communication,2009; 14(3): 246-261.17. Geyer, R. The Politics of EU Health Policy and the Case of Direct-to-Consumer Advertising for Prescription Drugs. Br J Politics & International

Relations, 2011; 13(4):586-602. Published online 23 May 2011.18. Matear, M, Dacin PA. Marketing and Societal Welfare: A Multiple Stakeholder Approach." Journal of Business Research, 2010; 63: 1173-1178.19. Austovoll-Dhalgren, A. Bottom-up Approach to Successful Implementation of Pharmaceutical Policy. Expert Review of Pharacoeconomics Outcomes

Research, 2009; 9(3): 193-195.20. Rosenthal, M B."Comment: The Economics of Direct-To-Consumer Advertising of Prescription-Only Drugs: Prescribed to Improve Consumer

Welfare." Journal of Health Services Research & Policy, 2004; 9(1): 39-42.21. Osterberg L, Blaschke T. Adherence to Medication. N Engl J Med, 2005;353:487-49722. Sabaté E. Adherence to Long-Term Therapies: Evidence for Action, WHO, 200323. Hancher L, Foldes ME. Push or Pull? Information to Patients and European Law. Tilec Discussion Paper No 2011-032, 16 June, 201124. Velo G, Moretti U. Direct-to-Consumer Information in Europe: The Blurred Margin Between Promotion and Information. Br J Clin Pharmacol, 2008;

66(5): 626-2825. Empowering the Patient: EC Wants Clearer Rules for Information on Prescription Medicines. EC Press Release. Accessed October 23, 2011 at

http://ec.europa.eu/health/files/patients/ip_10-2011/i11_1171_en.pdf

This article partially draws on a recent MSc Thesis by Rina Mae Acosta, "When Customer Relationship Matters:The Return on Investment of Direct-to-Consumer Advertising and Direct-to-Physician Marketing", working underDr Keja’s supervision to explore new models for calculating ROI of DTCA and DTPM.

For the industry and HEOR community, the imperativesare threefold:

1. We must step up our presence and become morevisible and audible in the relevant arenas and with therelevant audiences in order to balance the RCT-dominant views, taking care that RWE is appropriatelypositioned and valued.

2. More research is needed to determine the ROI andsocietal value of direct-to-patient communications.Current policies seem to draw heavily on politicalviews, undervaluing its positive potential. They alsoseem to over emphasize the fear of DTCAs from abudgetary impact perspective. There is a highlikelihood that these views are shortsighted given the

serious financial implications of poor or non-adherence to therapy as well as evidence that DTCAhas limited impacted on price elasticity. It is here, forexample, that a typical health economist view isneeded. One final thought on this is that perhapsDTCA may push the public to higher acceptance ofmedicine co-payment, thereby transferring part of theanticipated burden arising from the feared increaseduse of drugs, to the patients themselves.

3. Article 100g: Other types of information approved bycompetent authorities that are relevant to support theproper use of the medicinal product need further closescrutiny in order to understand their impact on theway we can communicate the findings of our work tothe wider community. •


MEDICARE PART D | INSIGHTS

When the Medicare Part D benefit became effective in2006, critics predicted a significant increase in theprice of seniors’ prescription drugs, and a consequentdramatic rise in Medicare expenditure. With figuresreleased in 2010 showing a substantial reduction inanticipated costs, researchers ask “What happened to senior drug Rx prices - and why?”

Summarized from: “Medicare Part D At Age Five: What Has Happened To Seniors’Prescription Drug Prices?” by Murray L Aitken, IMS Institute for HealthcareInformatics and Ernst R Berndt, MIT Sloan School of Management and NationalBureau of Economic Research.


The author

Murray Aitken, MBA is Executive Director, IMS Institute for Healthcare [email protected]

Medicare Part D: Not such a high price to pay?


INSIGHTS | MEDICARE PART D

Former Congressional Budget Office Director PeterOrszag has identified the “primary cause” of the costreduction reflected in the 2010 Medicare Trustees report,1as lower than expected bids submitted by prescriptiondrug plans offering coverage, stating “The bids are comingin and the pricing is coming in better than anticipated,and that is likely a reflection of the competition that’soccurring in the private market”.2 But what has enabledcompetitive prescription drug plans to offer unexpectedlower bids?

There are undoubtedly many reasons underlying thisdevelopment. In this analysis we have focused on one: thedeclining daily cost of therapy as patents expired andgenerics entered the market, and competitive prescriptiondrug plans relayed the cost savings to Part D beneficiaries.Specifically, we have examined trends in the average dailycosts (ADCs) of therapy over the five years since MedicarePart D came into effect, focusing on the ten therapeuticclasses which had the largest volume of Medicare Part Dprescriptions in 2006.

The analysis was enabled by access to IMS Medicare PartD prescription data from the IMS PlanTrak database; IMSHealth represents 100% of Part D plans, and combinedwith IMS’ National Prescription Audit (NPA), measuresthe prescription volume associated with those plans. TheNPA is projected to national levels, based on a sample ofretail and mail order outlets. Using data on the totalnumber of prescriptions dispensed, we identified the tentherapeutic classes in 2006 having the greatest MedicarePart D prescription volumes: lipid regulators, ACEinhibitors, calcium channel blockers, beta blockers, protonpump inhibitors (PPIs), thyroid hormone, angiotensin IIreceptor antagonists, codeine and combination products,antidepressants, and seizure disorders.

For each of the molecules in these ten classes, we useddata from IMS National Sales Perspective which tracksinvoices from wholesalers/manufacturers to retail and mailorder pharmacies. ADCs were computed using dispensingdata from the NPA. Based on annual Part D prescriptionquantity data from IMS PlanTrak, we constructed aweighted average aggregate ADC of therapy over theentire ten therapeutic classes, both monthly (Jan 2006–Dec 2010) and annually (2006-2010). The daily cost oftherapy calculations are thus interpreted as based onacquisition prices paid by pharmacies; they include

prompt payment discounts, but not discounts extendeddirectly to Part D beneficiaries, pharmacy margins andmanufacturer rebates paid to third-party payers such asMedicaid, private health benefit insurers and Part Dprivate prescription drug plans.

TRACK RECORD IN THE FIRST FIVE YEARS Our analysis shows that from the time of the MedicarePart D launch in 2006, through the end of 2010, onaverage over the ten largest volume Medicare Part Dtherapeutic classes, there has been a cumulative 30%decline in the annual ADC of therapy (Figure 1).

Cost declines occurred in four of the five cardiovascular-related classes, with the largest decline seen in calciumchannel blockers, and successively smaller declines inACE inhibitors, lipid regulators and beta blockers.Substantial daily cost declines also occurred in the CNSclasses of antidepressants and seizure disorders, and smallerdeclines within the PPIs (some of which are nowavailable in less costly OTC versions frequently notcovered by Medicare Part D, therefore understating pricedeclines experienced by seniors) and for the thyroid

Medicare Part D: Not such a high price to pay?

FIGURE 1: AN AVERAGE 30% REDUCTION IN THE DAILY COSTOF THERAPY OCCURRED WITHIN THE TOP 10 PART D CLASSESBETWEEN 2006 AND 2010

Source: IMS Institute for Healthcare Informatics; National Sales Perspectives;National Prescription Audit, Dec 2010

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hormone medicines, where there have been no patentexpirations for quite some time.

Negative compound annual growth rates were greater than 20%for the calcium channel blockers and ACE inhibitors (both ofwhich experienced generic entry in 2007); between 10% and20% for seizure disorder, antidepressants, and lipid regulators(with significant patent expirations in 2009, 2006 and 2006,respectively); and less than 10% among the PPIs, beta blockersand thyroid hormone products.

In contrast, daily cost of therapy increases occurred annuallyamong the angiotensen II receptor antagonists where only Cozaar/Hyzaar lost patent protection in 2010 andphysicians/consumers migrated towards the remaining Diovan,Avapro and Benicar brands. The only other class experiencing adaily cost increase is codeine and combination products, whichsimilarly experienced no patent expiries during 2006-2010.

One way of summarizing these various trends is to plot theaverage daily cost of therapy aggregated over the top tenMedicare Part D prescription volume classes, on a monthly basisfrom January 2006 through December 2010. This shows thatcoincidentally, between Jan 2006 and Dec 2010 the averagedaily cost of therapy in these classes declined by a third, from$1.50 to $1.00 (Figure 2, left half).

Overall, in the first 60 months of Medicare Part D, cumulativeADCs of therapy declined by greater than 50% within fourclasses (calcium channel blockers, ACE inhibitors, seizuredisorders, and antidepressants), between 30% and 50% amongthe lipid regulators and PPIs, and less than 20% for beta blockersand thyroid hormone products. In contrast, over the same timeperiod, the cumulative ADC of therapy increased by 11.9% forcodeine and combination products, and by 22.3% for theangiotensin II receptor antagonists, implying annualized averagecost increases of 2.9% and 5.2%, respectively.

The dynamics ofmedicine costs areaffected substantiallyby the impact of patent expiration

The cost declines observed in thefirst five years of Medicare Part Dcan be expected to continue. Inaggregate, over these ten classes, the2006-2015 decade is one ofsteadily decreasing ADCs of therapy



INSIGHTS | MEDICARE PART D


HISTORICAL QUIRK OR CONTINUING TREND? A natural question that arises is whether this general declinein ADC of therapy in the studied period is an historicaloddity which is unlikely to recur or a cost phenomenonthat is likely to continue for years to come.

To begin to address this issue, we have projected annual2011-2015 and monthly Jan 2011–Dec 2015 ADCs oftherapy for the same ten classes. This analysis is based on:IMS Institute current expectations for the timing of patentexpirations in each of the ten therapeutic classes; no new“blockbuster” drug launches from 2011-2015 in theseclasses; class-specific standard generic erosion curvesbenchmarked to 2006-2010 data; constant brand price andvolume growth equal to mean pre- and post-patentprotection expiration historical growth rates from 2006 to2010; constant form-strength distributions within theseclasses at 2010 values for the respective molecules3; and afall in generic prices consistent with standard historicgeneric erosion curves.

Over the entire ten therapeutic classes, the projected ADCof therapy falls from $1.00 per day in Dec 2010 by anadditional 35% to $0.65 (Figure 2, right half), resulting in acumulative -57% change between Jan 2006 and Dec 2015.

Between Dec 2010 and Dec 2015, the ADC of therapydrops by more than 40% in five of the ten classes: lipidregulators -50.8% (Lipitor patent expiry expected Nov2011); beta blockers -45.2% (Bystolic patent expiryexpected Dec 2012); PPIs -42.0% (Aciphex patent expiryexpected May 2013; Nexium Nov 2014); angiotensin IIreceptor antagonists -48.8% (Avapro patent expiry expectedMarch 2012, Diovan Sept 2012); and antidepressants -52.0% (Lexapro patent expiry expected March 2012;Cymbalta July 2014).

Average daily therapy costs are projected to increasemodestly between Dec 2010 and Dec 2015 for ACEinhibitors (18.2%), calcium channel blockers (13.9%),thyroid hormone products (3.8%) and seizure disorders(3.7%) classes, already heavily genericized with little, if any,expected patent expiry between 2011-2015, and to declinemodestly for codeine and combination products (-10.0%).Despite the modest expected price increases in these fourclasses, since 2006 all but codeine and combinationproducts will have experienced declines in ADC of therapy.ADC of therapy for the latter will have increased a penny.

BIG PICTURE: SUSTAINED DECLINES

The “big picture” pattern of sustained decline in ADCof therapy in the ten largest volume Medicare Part Dclasses over the entire period from Jan 2006 through Dec2015 can be seen visually by observing the steadilydownward sloping line in Figure 2. Despite some“bumps” triggered by patent expirations and substantialgeneric entry, the cost declines observed in the first fiveyears of Medicare Part D can be expected to continue.In aggregate, over these ten classes, the 2006-2015 decadeis one of steadily decreasing ADCs of therapy.

PATENT EXPIRATIONS, GENERIC SUBSTITUTION KEY DRIVERSOur analysis suggests that patent expiries and thesubstitution of generics for brands played a major role ineight of the ten classes experiencing declines in ADC oftherapy between 2006 and 2010. In aggregate, ADCsdeclined from $1.50 to $1.00 per day during this period. Given the anticipated expiry of patent protection between2011 and 2015, along with other continued marketdevelopment assumptions, and in the absence of newproduct surprises, we expect daily cost declines in aggregateover these ten therapeutic areas to continue over the 2011-2015 time period, with Part D prescriptions in Dec 2015costing on average $0.65 per day of therapy - a numbercoincidentally equal to the beneficiary age at whichMedicare Part D benefits currently become available.

FIGURE 2: SUSTAINED DECLINES IN AVERAGE DAILY COST OFTHERAPY BETWEEN JAN 2006 AND DEC 2015

Source: IMS Institute for Healthcare Informatics; National Sales Perspectives;National Prescription Audit, Dec 2010

COST

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2006 2007 2008 2009 2010 2011 2012 2013 20152014


Hence, when generic drug savings are taken intoaccount, ADCs of therapy for the top therapeutic classesin Part D will have fallen on a sustained basis between2006 and 2015. This reflects the Schumpeterian lifecycleprocess of “creative destruction” in biopharmaceuticalmarkets in which, over time, R&D investments producemedical advances with finite market exclusivity. Thesegenerate further funding for R&D, then make way forgeneric copies to be available at low costs for many years,enabling the savings and benefits of biopharmaceuticalsto flow to the next generation of medical advances.

The cost calculations in our analysis are based onacquisition prices paid by retail and mail orderpharmacies. Given the exclusions already noted, our dailycost of therapy trends might therefore differ from thoseactually experienced by Medicare Part D beneficiaries.Moreover, we focus on Part D prescriptions dispensed inthe retail and mail order environment; prices of specialtyand other drugs dispensed in the hospital and outpatientsetting may have differing trends.

Our 2011-2015 projections are based on IMS Instituteestimates of patent expiration for those brands still patent-protected in 2010, and on historic patterns in brand-generic erosion. To the extent that actual dates ofexpiration for patent protection and generic entry differfrom those expected by the IMS Institute, future brand-generic erosion curves differ from that observedhistorically, and new “blockbuster” products are launchedin these ten therapeutic classes, actual future daily cost oftherapy trends may differ from those projected in this study.

FURTHER REARCH WARRANTED

Useful future research suggested by this analysis involves amore detailed examination of changes since 2006 in thequantity of Medicare Part D prescription drugs dispensed(which according to the IMS Institute have increased 61% involume from 541 million prescriptions in 2006 to 871 millionin 2010) and the relationship between this increased access totherapies and the decline in the ADC of therapy over time.

This analysis shows that the dynamics of medicine costsare affected substantially by the impact of patentexpiration, which can generally be predicted several yearsin advance. Unlike medical devices, physician services andhospitalizations, the costs of medicines regularly declineby up to 90% following expiration of patent protection.The extent to which the price dynamics of thesemedicines are understood and incorporated into aggregatecost projections associated with new private or publichealthcare programs or policy initiatives is currentlyunclear to us, but the unique Medicare Part D experiencesuggests that new approaches to the aggregate costanalyses of medicines merit further scrutiny andconsideration to avoid substantial errors in estimatingfuture program costs. •

1. Medicare Trustees [2010], 2010, p189. Annual Report of the Boards of Trustees of the Federal Hospital Insurance and Federal Supplementary MedicalInsurance Trust Funds, 2010. Available online at https://www.cms.gov/ReportsTrustFunds/downloads/tr2010.pdf

2. As quoted in “CBO Lowers 10-Year Cost Estimate Of Medicare Prescription Drug Benefit”, 30 January 2007, available online athttp://www.medicalnewstoday.com/releases/ 61768.php, last accessed 9 June 2011

3. Hence, while new branded products in these therapeutic classes launched between 2006 and 2010 are included in the sample, potential new brandedproducts are not included in the 2011-2015 projections. A review of molecules in late-stage development in these therapeutic classes suggests that therewill be few if any blockbuster products launched in the 2011-2015 period.

New approaches to the aggregatecost analyses of medicines meritfurther scrutiny and considerationto avoid substantial errors inestimating future program costs



PROJECT FOCUS | CHEMOTHERAPY-INDUCED ANEMIA

Access to new therapeutic innovations is increasingly contingenton their economic value in relation to alternative interventions. Theability to demonstrate cost and health benefits based on usage inthe real-world setting is thus essential for supporting rationaldecision making – and successful product differentiation. This isespecially valid in complex and costly disease areas such asoncology, where new interventions that are perceived to beexpensive can add considerably to overall expenditures.

Analyzing longitudinal healthcare data, drawn from large medical,patient and health claims databases, affords unique opportunitiesto understand the clinical and economic outcomes associated witha particular intervention and the impact of events that may occurmore often with one drug compared to another. Today, increasinglysophisticated methodologies are extending the applications of thesedatabases further.

For one leading manufacturer of innovative therapeutics, theretrospective analysis of anonymized patient-level data, combinedwith advanced techniques for its extensive adaptation, provedpivotal in demonstrating superior product efficiency inchemotherapy-induced anemia (CIA) in multiple country settings.

BACKGROUND

CIA is a common complication of cancer treatment and itsassociated fatigue can significantly impact the quality of dailyliving. The use of erythropoiesis-stimulating agents (ESAs) toincrease inadequate hemoglobin (Hb) levels has been shown toimprove quality of life (QoL) and reduce the need for red bloodcount transfusions – a widely used intervention.1 Further, byimproving QoL, secondary to improving Hb, these agents may enablepatients to receive the correct doses of chemotherapy in a moretimely way than cancer patients who remain anemic.2

In 2006, having recently launched a new ESA, and given the cost-intensive nature of treatment for cancer, the company wantedto reach a better understanding of the costs associated with CIA.In particular it was keen to identify the potential for savingsthrough the use of its drug compared to competing agents. Theinitial focus was on Belgium, but an expansion to additionalEuropean markets was envisaged in a 3-4 year period. In IMS theyfound a partner with an expert global team that had extensiveexperience in the design and analysis of retrospective research,access to unparalleled patient-level assets and the ability tocollaborate seamlessly across multiple markets.

Advanced, innovativemethodologicaltechniques that adjustfor specific characteristicscan enable rigorousadaptations of dataacross a range ofgeographic settings.

Demonstrating cost savingsin chemotherapy-inducedanemia by extrapolatingcountry-specific data tomultiple markets

The Author: Mark Lamotte, MD is Principal HEOR, IMS Consulting Group, [email protected]

KEY INSIGHTS INTO COST AND OUTCOMES

The study was conducted using the IMS Hospital DiseaseDatabase (HDD), a longitudinal database containingindividual patient/admission-level data on diagnoses,procedures, and pharmaceutical products. Unique to Belgium,this includes information on 46 hospitals, representing 34%of day clinic visits and hospital beds in the country.Although focused on a different setting, in terms ofcompleteness and level of detail, HDD is comparable to theGP Research Database (GPRD) in the UK.

Applying propensity score matching using epidemiology andtreatment pattern-related variables to adjust for selectionbias, the IMS team was able to demonstrate the greaterefficiency of the company’s ESA due to shorter treatmentduration compared to competitor products. The study was thefirst real-life matched retrospective analysis comparing ESAs in terms of costs and outcomes.3

EXPLORING BROAD APPLICABILITY

In the follow-on analysis, IMS was asked to determine theapplicability of the Belgian findings to different settingsacross Europe, estimating differences in costs between ESAsby similarly adjusting for baseline characteristics usingpropensity score matching. However, when a literaturesearch revealed that no comparable databases to HDD existedin the relevant countries, it was clear that a differentapproach would be needed. Applying their extensive analyticexpertise, the IMS team focused on adapting the Belgiandataset, developing a rigorous methodology that involved:

1. Replacing Belgian unit costs with local unit costs fordrugs, daycare visits, hospitalization and bloodtransfusions for each country.

2. Validating epidemiology and treatment patterns by country,including gender/age distribution of the generalpopulation, use of ESAs and blood transfusions,incidence/distribution of cancer types, and use ofchemotherapy. Differences between countries were adjustedusing data from Eurostat, national cancer registries, IMSsales data, and reimbursement and treatment guidelines.

3. Weighting Belgian data to reflect treatment patterns inthe local setting based on calculations of totalchemotherapy sales in hospital (mg) for all countries.

Finally, adjusting for country-specific drug use and cancerincidence, the costs of the drugs were analyzed from thehealthcare payer perspective, using a mixed-effects modelstratifying for propensity score quintiles (Figure 1).

PROVEN FEASIBILITY OF DATA ADAPTATION

The demographic country profiles revealed broad similaritiesbetween all countries and Belgium in average age and genderdistribution. There were differences in cancer incidence butno major differences in the use of ESAs or the administrationof blood transfusions for chemotherapy patients. To reflectcountry-specific epidemiology, the relative weight of fourtumor types in the focus countries compared to Belgium wasused to adjust the original dataset. In all countries, total costsand anemia-related costs were lowest in patients receiving thecompany’s ESA compared with its competitors – findings thatwere fully in line with those of the Belgian analysis.

The results of the IMS analysis clearly demonstrate thefeasibility of adapting real-world, country-specific data toother clinical settings by adjusting for differences in patientcharacteristics, treatment strategies and costs.

By partnering with the IMS team on this work, the company was able to demonstrate the greater efficiency of its ESA in thehospital setting in multiple markets, with clear differentiationfrom competitor products based on compelling, real-worldevidence. The results have been presented at major internationalconferences including ISPOR4, form the basis of scientific globaland country manuscripts and will enable the distillation of keymessages regarding the real-life costs and effects associatedwith treatment of CIA. •


CHEMOTHERAPY-INDUCED ANEMIA | PROJECT FOCUS

FIGURE 1: ANALYSIS OVERVIEW

1.

2.

3.

4.

INITIAL PATIENT SAMPLEIMS Hospital Disease Database, January 2003 - June 2005Cancer patients, receiving chemotherapy and ESA darbepoetin alfa (n = 539) - epoetin-α (n = 1,594) - epoetin-β (N = 380)

PROPENSITY SCORE MATCHINGDarbepoetin alfa (n = 429) - epoetin-α (n = 1,584) - epoetin-β (N = 380)

COUNTRY-SPECIFIC COSTSOn propensity scores matched patients, replace Belgian costs with:• Drug costs (replace unit cost)• Procedures cost (replace on DRG level)• Hospitalization cost (calculate DRG country-specific day-cost and multiply with length of stay)

POPULATION WEIGHTS

5. FINAL WEIGHTING1. Final weight: Drug weight x Cancer weight2. Final normalized weight: Final weight adjusted for sample

size per group (sum of weights has to equal sample size pertreatment arm)

1Rizzo JD, Seidenfeld J, Piper M et al. Erythropoietin: A paradigm for thedevelopment of practice guidelines. Hematology Am Soc Hematol EducProgram 2001; 10-30.2Khan FA, Shukla AN, Joshi SC. Anaemia and cancer treatment: Aconceptual change. Singapore Med J 2008; 49:759-764.3Spaepen E, Demarteau N, Van Belle S, Annemans L. Health economicevaluation of treating anemia in cancer patients receiving chemotherapy: A study in Belgian hospitals. The Oncologist, 2008; 13: 596-6074Duran A, Spaepen E, Lamotte M, Walter E, Lucioni C, Pinheiro B, Brosa M,Kutikova L, Pujol B, Annemans L. Cost analysis of anemia treatment witherythropoiesis-stimulating agents (ESAs) in cancer patients receivingchemotherapy: A multi-country approach. ISPOR 16th AnnualInternational Meeting, Baltimore, MD, 21-25 May, 2011

Drugs:• On molecule level, assess thenational ratio of Belgiumsales.

• Average of molecule ratiosper patient is ‘chemotherapyweight’.

• The higher the ratio, thehigher the patient usescountry-specificchemotherapy, the moreweight the patient receives.

Cancer incidence:• For 4 major cancer types(breast, lung, female genital,hematological), assess theratio of the incidence ofCountry vs Belgium.

• The higher the ratio, thehigher the patient has acountry-specific cancer, themore weight the patientreceives.

Adjust on country-specific drug and cancer incidence using sample weighting:


PROJECT FOCUS | BREAST CANCER

Ensuring that patients derive the maximum benefit from the use ofa medical intervention is key to supporting the achievement ofoptimal outcomes. However, a product’s use may be influenced byprescribed co-medications, particularly within the context ofcomplex regimens such as oncology treatment protocols. This canbecome a particular challenge for manufacturers, as evolvingtreatment options can influence real-world practice patterns, oftenwith unintended consequences for established products.

Companies looking to gain a clearer perspective of the way theirproducts are being used by physicians and the impact of changingpreferences for protocols of care, have come to appreciate theimportant role of anonymized healthcare databases. With their largepatient cohorts, direct relevance to the general population, and theability to track the real-world use of medicines over time, thesepowerful datasets bring unique insights into prescribing behavior,emerging trends, and the issues that are driving – or potentiallyundermining – the optimal use of a drug.

FINDING THE EVIDENCE

A top U.S. biopharmaceutical company with a leading breast cancertreatment (trastuzumab) wanted to reach a better understanding ofthe drug’s real-world use within the context of two differentregimens – anthracycline-based (AB) and non-anthracycline-based(NAB). Breast cancer is the fifth leading cause of death worldwide1

making efforts to inform its optimal treatment critical. Trastuzumabis indicated for a sub-group of women with HER2-positive tumors,suggesting more aggressive disease and significantly shortenedsurvival. Its addition to adjuvant therapy has been found to reducethe risk of death in these patients.

When anecdotal reports suggested a change in physician preferencesfor adjuvant breast cancer protocols, the company commissionedIMS HEOR to both confirm this apparent finding and determine theimplications for the use of trastuzumab in this setting. In particular,it was keen to explore issues around patient persistence as thesewould clearly influence potential outcomes.

Having partnered with IMS on a number of previous economicevaluations in oncology using the IMS LifeLink™ Health Plan ClaimsDatabase (HPC), the company trusted both the rigor of the analysesand strength of the underlying data. LifeLink HPC is one of the mostcomprehensive datasets of longitudinal patient-level medical andpharmaceutical claims available. Incorporating claims from 80health plans across the U.S., it enables granular analyses acrossmultiple dimensions, including patterns of care, resource use, and

Retrospective cohortanalyses leveraginglarge healthcaredatabases can yieldimportant insights foroptimal drug usewithin emergingpreferences for care.

Understanding real-worldpersistence in adjuvantbreast cancer patients

The Authors: Vernon Schabert, PHD is Global Leader Retrospective OutcomesResearch and Senior Principal HEOR, IMS Consulting Group, [email protected]

Elise Pelletier, MS is Engagement Manager HEOR, IMS Consulting Group, [email protected]


medical costs, and comparisons across a range ofdemographic variables such as age, gender, in-patient and out-patient diagnoses and procedures,concomitant therapy and co-morbidities.

UNDERSTANDING THE TRENDS

The goal of the IMS team was to identify annual trends inthe use of trastuzumab in the U.S. over the previous four-year period and to compare levels of persistence in ABversus NAB protocols. They began by screening claimsrecorded in LifeLink HPC to identify the study cohort: womenaged 18 years and over with an early stage primary diagnosisof breast cancer, evidence of surgery for their disease, andevidence of trastuzumab used in one of the two treatmentregimens. Nearly 600 patients were found to fulfill the study’sdetailed selection criteria, 550 of whom were included in thefinal analysis. These patients were then followed todetermine duration of use, defined from the time of firstclaim for the drug (index) to the earliest of: discontinuation,metastasis, end of health plan enrollment or 360 days afterthe index claim.

Persistence was compared across regimens using Kaplan-Meier survival curves and the Cox proportional hazards model.The primary independent variable was the protocol in whichthe drug was used, with additional variables including patientcharacteristics.

REVEALING THE BENEFITS

The results of the IMS analysis2 provided important real-worldconfirmation of a shift towards greater use of the NABprotocol in the U.S. over the study period, thus confirmingthe anecdotal reports. A further revelation was that patientspersisted longer on therapy within the NAB regimen,providing support for its preferential use over the AB regimen(Figure 1). In a therapy area where precise patient subgroupdefinitions often yield very small cohorts, the large LifeLinkHPC database cohort gave the client increased confidence inthe findings compared to databases available elsewhere.

Given that patients derive maximum benefit from theirmedications when they are persistent over the long term,these findings have important clinical and economicimplications. They have been presented at several keynote oncology conferences and a manuscript is beingprepared for publication to support their wider disseminationand advance the understanding of optimal treatment for thisimportant disease. •

BREAST CANCER | PROJECT FOCUS

1WHO Factsheet 297, February 2011. Accessed at http://www.who.int/mediacentre/factsheets/fs297/en/index.html, October, 20112Lalla D, Pelletier EM, Goodman S, Brammer M, Schabert VF. Trastuzumab treatment patterns among patients diagnosed with adjuvant breast cancer:Results from a U.S. claims data analysis. European Multidisciplinary Cancer Congress, Stockholm, Sweden, 23-27 September, 2011.

FIGURE 1: KAPLAN-MEIER ANALYSIS OF THE PROPORTION OFPATIENTS PERSISTENT WITH TRASTUZUMABTHERAPY: AB vs NAB

Source: Lalla D, Pelletier EM, Goodman S, Brammer M, Schabert VF.Trastuzumab treatment patterns among patients diagnosed with adjuvantbreast cancer: Results from a U.S. claims data analysis.

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

30 60 90 120 150 180 210 240 270 300 330 360

SURV

IVAL

DIS

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N FU

NCTI

ON

Days

AB Group (N=291)

NAB Group (N=259)

IMS HEOR | OVERVIEW

Page 52 IMS HEALTH ECONOMICS & OUTCOMES RESEARCH

The IMS Consulting Group HEOR unit is a multi-disciplinary,global team with proven success and publication experiencein virtually all therapy areas and more than 40 countriesworldwide, including emerging economies in Central andEastern Europe, Latin America and Asia. Our bibliographyextends to more than 2000 references.

Our leading experts combine rigorous scientific researchwith a customer-focused consulting model to help you:

• Address growing HTA requirements nationally, regionally and locally

• Build powerful health economic support throughdisease modeling and outcomes evaluations

• Create enduring value propositions across the productlifecycle supported by scientific evidence

• Develop innovative solutions to real-world market needsthat leverage both bespoke observational researchand access to our unparalleled medical, hospital and patient-centered pharmaceutical databases.

HEOR STRATEGY &DETERMINING VALUE

DEMONSTRATINGVALUE

COMMUNICATINGVALUE

Strategy EvidenceDevelopment Communication

Our integrated approach – spanning world-leading skills instrategy, evidence development and value communications –is reflected in all of our work.

Revealing true product value

The IMS Consulting Group offers a spectrum of world-class expertise inHEOR to deliver the local excellence you need.

REALIZE

COMMUNICATE

DEMONSTRATE

DETERMINE

IMS HEOR brings unrivalled experience and specialistexpertise to help you determine, demonstrate, communicateand realize product value.

IMS HEOR BIBLIOGRAPHY

Please ask us for a copy ofour current bibliographycovering publications from2008-2011 or access theonline catalog of more than2000 references atwww.imsheorbibliography.com

IMS HEOR ONLINE

Visit us online at www.imsconsultinggroup.com/heor

LOCATIONS | IMS


IMS HEOR office locations

Global scope, local expertise

IMS HEOR experts are located in 17 countries worldwide and they havepublished on projects completed in more than 40 countries on all continents.

YOUR PRIMARY CONTACTS:Dr. Michael NelsonRegional Leader AmericasHealth Economics & Outcomes ResearchIMS Consulting Group1725 Duke Street, Suite 510Alexandria, VA 22314USATel: +1 703.837.5150Email: [email protected]

Dr. Jacco KejaRegional Leader EMEAHealth Economics & Outcomes ResearchIMS Consulting Group7 Harewood AvenueLondon NW1 6JB, UKTelephone: +31 (0) 631 693 939Email: [email protected]

NORTH AMERICAREGIONAL HEADQUARTERS200 Campus DriveCollegeville, PA 19426USATel: +1 610.244.2000

UNITED STATES1725 Duke StreetSuite 510Alexandria, VA 22314USATel: +1 703.837.5150

The Arsenal on the Charles311 Arsenal StreetWatertown, MA 02472USATel: +1 800.783.6362

CANADA303 Terry Fox DriveSuite 300Ottawa K2K 3J1, OntarioCanadaTel: +1 613.599.0711

LATIN AMERICAREGIONAL HEADQUARTERSInsurgentes Sur # 23755th Floor, Col. TizapanMexico City D.F. - C.P. 01090 MexicoTel: + 52 (55) 50.62.52.00 ext 5269

EUROPEREGIONAL HEADQUARTERS7 Harewood AvenueLondon NW1 6JBUnited KingdomTel: +44 (0) 20 3075 4800

BELGIUMMedialaan 381800 VilvoordeBelgiumTel: +32 2 627 3211

FRANCE91 rue Jean Jaurès92807 Puteaux cedexFranceTel: +33 1 41 35 1000

GERMANYHefnersplatz 1090402 NürnbergGermanyTel: +49 911 24270 6300

Max-Lebsche-Platz 3281377 MünchenGermanyTel: +49 (0)89 45 79 126411

ITALYViale Certosa 220155 MilanoItalyTel: +39 02 69 78 6721

SPAINDr Ferran, 25-2708034 BarcelonaSpainTel: +34 93 749 63 00

SWEDENSveavägen 155/Plan911346 StockholmSwedenTel: +46 8 508 842 00

SWITZERLANDTheaterstr. 44051 BasleSwitzerlandTel: +41 61 204 5071

UNITED KINGDOM7 Harewood AvenueLondonNW1 6JBUnited KingdomTel: +44 (0)20 3075 4800

ASIA PACIFICREGIONAL HEADQUARTERS

10 Hoe Chiang Road Keppel Towers #23-01/02Singapore 089315 Tel: +65 6227 3006

AUSTRALIALevel 5, Charter Grove29 - 57 Christie StreetSt Leonards, NSW 2065AustraliaTelephone: +61 2 9805 6800

CHINA7/F Central TowerChina Overseas PlazaJianguomenwai Avenue, Chaoyang DistrictBeijing 100001ChinaTel: +86 10 8567 4255

KOREA9F Handok Building735 Yeoksam1-dongKangnam-ku Seoul135-755S. KoreaTel: +82 2 3459 7307

TAIWAN8th FloorNo 2, Tun Hwa South RoadSection 1Taipei 10506TaiwanROCTel: +886 2 2721 5337

FOR FURTHER INFORMATION: email [email protected] or visit www.imsconsultinggroup.com/heor

harmaceutical companies worldwide rely on LifeLink to drive patient-centered decisions – from the first explorator

IMS | EXPERTISE


Renée J. G. Arnold, PHARM D• Dr. Renée Arnold is Principal at the IMS Consulting Group in the U.S., with particular expertise in theuse of technology to collect and/or model real-world data to facilitate rational decision making byhealthcare practitioners and policy makers.

• Renée was previously President and CEO, Arnold Consultancy & Technology where she developed andoversaw outcomes research for the pharmaceutical, biotech and device industries as well as federalgovernment programs. Her distinguished career in health economics and outcomes research includesroles as President and co-founder of Pharmacon International, Center for Health Outcomes Excellenceand Senior VP and Medical Director at William J Bologna International.

• Founding member and former Chair of the Education Committee of ISPOR, Renée has several adjunctappointments and is the author of numerous articles on pharmacoeconomics and cost-containmentstrategies. She holds a Doctor of Pharmacy degree from the University of Southern California in Los Angeles.

Xavier Badia, MD, MPH, PHD• Dr. Xavier Badia is Global Leader Observational Outcomes Research, and Senior Principal HEOR at theIMS Consulting Group in Spain.

• A founder of Health Outcomes Research Europe, Xavier has extensive experience in consulting andresearch outcomes, patient-reported outcomes, and effectiveness and cost-effectivenessevaluations. A respected scientific speaker and member of EuroQol since 1993, he serves on severalinternational advisory and editorial boards and has published over 150 peer-reviewed papers.

• Xavier holds an MD, a PhD in Medicine, and a Master’s in Public Health and Health Economics fromthe University of Barcelona.

Expertise in depthWe apply unrivalled experience and specialistexpertise to help our clients meet the demands ofan increasingly complex global, regional and localpharmaceutical landscape.

IMS has one of the largest global teams of expertsin health economics, outcomes research andmarket access of any organization in the world. Ourhighly-qualified consultants and researchers havemulti-disciplinary experience and proven skillscovering all key therapy areas.

Our experts have extensive capabilities in a widerange of health economic & outcomes researchdisciplines in industry, consulting, government andacademia, with a global grasp, local experience,and a unique, inside perspective of key marketaccess issues.

The strength of ourability to support

clients in healthcaredecision making for

HEOR andmarket access is

built on the qualityof our global team

OUR SENIOR TEAM

ry questions that drive clinical development to tactical sales planning for mature brands.

EXPERTISE | IMS


Nevzeta Bosnic, BA• Nevzeta Bosnic is Principal at IMS Brogan in Canada, where she manages projects to meet the broadspectrum of client needs in the Canadian pharmaceutical market.

• Formerly Director of Economic Consulting at Brogan Inc, Nev has led many strategic consulting,policy and data analyses for pharmaceutical clients, government bodies and academic institutions inCanada. She has extensive knowledge of public and private drug plans across the country and in-depth expertise and experience on the drug reimbursement process.

• Nev holds a Bachelor’s degree in Business Economics from the School of Economics and Business atthe University of Sarajevo, Bosnia-Herzegovina.

Karin Berger, MBA• Karin Berger is Senior Scientific Consultant to IMS and previously Principal, Health Economics &Outcomes Research, at IMS in Germany with a particular focus on outcomes research, patient-reported outcomes, and cost-effectiveness evaluation analyses at a national and international level.

• Formerly Managing Director of MERG (Medical Economics Research Group), an independent Germanorganization providing health economics services to the pharmaceutical industry, universityhospitals and European Commission, Karin has more than 14 years experience in the healtheconomics arena. She lectures at several universities, has published extensively in peer-reviewedjournals, and regularly presents at economic and medical conferences around the world.

• Karin graduated as Diplom-Kaufmann (German MBA equivalent) from the Bayreuth University,Germany, with a special focus on health economics.

Richard H. Chapman, PHD• Dr. Rick Chapman is Principal, Health Economics & Outcomes Research at the IMS ConsultingGroup in the U.S., directing the design and analysis of economic evaluations and healthoutcomes studies addressing a range of client issues.

• Formerly a Senior Director at ValueMedics Research, and Research Associate at the Center for RiskAnalysis, Rick has considerable experience in designing and conducting cost-effectiveness analyses,and particular expertise in the methodological quality of health economic analyses, medicationadherence and patient-reported outcomes, including quality of life and patient preferences.

• Rick holds a PhD in Health Policy (Decision Sciences) from Harvard University and an MS inHealth Policy and Management from the Harvard School of Public Health.

Joe Caputo, BSC• Joe Caputo is Principal, Health Economics & Outcomes Research at the IMS Consulting Group in theU.K., leveraging more than 15 years experience in the pharmaceutical sector to help clients addressthe challenges of global reimbursement and market access throughout the drug developmentprogram. He has led numerous projects involving payer research, value dossiers, local market accessmodels and HTA submissions.

• With a background that spans industry roles in drug development, sales & marketing and UK &global health outcomes, and consulting in health economics, Joe has wide-ranging knowledge ofthe drug development process at both local and international level and a unique understanding ofevidence gaps in light of reimbursement and market access requirements.

• Joe holds a BSc in Applied Statistics and Operational Research from Sheffield Hallam University, UK.

Christopher M. Blanchette, PHD, MS, MA• Dr. Chris Blanchette is Principal, Health Economics & Outcomes Research at the IMS ConsultingGroup in the U.S., bringing extensive experience in retrospective database research andobservational studies with particular emphasis on respiratory diseases.

• Chris was previously Director of Clinical & Outcomes Research at the Lovelace Respiratory ResearchInstitute, where he led a team of 50 people conducting clinical research, biostatistics, andoutcomes research programs. He also spent time in market access and R&D health economics atGlaxoSmithKline, most recently as Director for Health Data Analytics, and was formerly a researcherat the Premier Hospital Alliance and Agency for Healthcare Research and Quality.

• In addition to serving in leadership positions for ISPOR and several respiratory disease associations,Christopher is on the editorial board of the Journal of Medical Economics and advisory board of CurrentMedical Research and Opinion. He holds a PhD in Pharmaceutical Health Services Research and an MS inEpidemiology from the University of Maryland, and an MA in Medical Sociology from the University of North Carolina.

IMS | EXPERTISE


Jacco Keja, PHD• Dr. Jacco Keja is Regional Leader, EMEA, Health Economics & Outcomes Research, at the IMSConsulting Group, drawing on deep expertise in global market access, operational and strategicpricing, and health economics and outcomes research.

• Jacco’s background includes four years as global head of pricing, reimbursement, health outcomesand market access consulting services at a large clinical research organization and more than 13 years experience in the pharmaceutical industry, including senior-level international and globalroles in strategic marketing, pricing and reimbursement and health economics.

• Jacco holds a PhD in Biology (Neurophysiology) from Vrije Universiteit in Amsterdam, a Masters inMedical Biology, and an undergraduate degree in Biology, both from Utrecht. He is also visitingProfessor at the Institute of Health Policy & Management at Erasmus University, Rotterdam.

Rob Kotchie, MCHEM, MSC• Rob Kotchie is Principal, Health Economics & Outcomes Research at the IMS Consulting Group in theUK, with particular expertise in health economics, outcomes research, evidence-based medicine andreal-world evidence.

• Previously with ZS Associates, Rob specializes in the design and roll-out of global pharmacoeconomicmodels, the production of health technology assessment dossiers and the use of retrospective databaseanalytics. He has a strong focus on the areas of cardiovascular medicine, oncology, respiratory andmental health, in addition to organizational design and market access capability assessments.

• Rob holds a first class honors degree in Chemistry from the University of Oxford and an MSc inInternational Health Policy & Health Economics from the London School of Economics.

David Grant, MBA• David Grant is Senior Principal and Global Leader, Strategic & Applied Health Economics &Outcomes Research, at the IMS Consulting Group in the U.K., specializing in reimbursement andmarket access, environmental analysis, prospective and retrospective data collection andcommunications for product support.

• A co-founder and former Director of Fourth Hurdle, David’s experience spans 10 years in healtheconomics and outcomes research consulting, and 15 years in the pharmaceutical industry, includingroles in clinical research, new product marketing and health economics in the U.K. and Japan.

• David holds a degree in Microbiology and an MBA from the London Business School.

Frank-Ulrich Fricke, PHD, MSC• Dr. Frank-Ulrich Fricke is Principal, Health Economics & Outcomes Research at the IMS Consulting Groupand Professor for Health Economics, Georg-Simon-Ohm University of Applied Sciences, Nuremberg inGermany, with a focus on health economic evaluations, market access strategies and health policy.

• Formerly a Managing Director of Fricke & Pirk GmbH, and previously Head of Health Economics atNovartis Pharmaceuticals, Frank-Ulrich has conducted health economic evaluations across a widerange of therapeutic areas, developing a wealth of experience in pricing, health affairs and healthpolicy. As a co-founder of the NIG 21 association, he has forged strong relationships with healtheconomists, physicians and related researchers working in the German healthcare system.

• Frank-Ulrich holds a PhD in Economics from the Bayreuth University, and an MBA equivalent fromthe Christian-Albrechts-University, Kiel.

Mandy Chui, MBA• Mandy Chui is Regional Practice Leader, Pricing & Market Access at IMS in the Asia Pacific,helping clients formulate growth strategies, optimize price and reimbursement, and addressissues in business model, sales force and marketing optimization.

• In a career spanning more than 15 years at IMS Health, including roles as Country Principal forChina and Director of Area Sales & Marketing in Singapore, Mandy has developed an exceptionalunderstanding of Asian market dynamics and an extensive network of major stakeholdercontacts in this rapidly evolving region. She has also authored various publications on Chinaand emerging markets.

• Mandy holds an honors degree in Biology from the University of Hong Kong and an MBA fromMcGill University, Montreal.

EXPERTISE | IMS

Adam Lloyd, MPHIL, BA• Adam Lloyd is Global Leader Health Economic Modeling and Senior Principal, Health Economics &Outcomes Research at the IMS Consulting Group in the U.K., where he leads the economic modelingpractice with a particular focus on economic analysis and the global application of economic tools tosupport the needs of local markets.

• A former founder and Director of Fourth Hurdle, and previously Senior Manager of Global Health Outcomesat GlaxoWellcome, Adam has extensive experience leading economic evaluations of pre-launched andmarketed products, developing submissions to NICE and the SMC, decision-analytic and Markov modeling,and in the use of health economics in reimbursement and marketing in continental Europe.

• Adam holds an MPhil in Economics, and a BA (Hons) in Philosophy, Politics and Economics from theUniversity of Oxford.

Charles Makin, MS, MBA, MM, BS• Charles Makin is Principal, Health Economics & Outcomes Research at the IMS Consulting Groupin the U.S. focusing on naturalistic trials, adherence interventions, chart abstractions, patient-reported outcomes and other studies involving primary data collection.

• During a career that includes senior roles at the UnitedHealth Group and Wellpoint, Charles hasled numerous studies involving database analyses, economic modeling, multi-country patientregistries, systematic literature reviews and survey-based research.

• Charles holds a BS in Pharmacy from the University of Pune, India, an MS in PharmacyAdministration from Purdue University, Indiana, U.S. and an MBA in Marketing Management anda Master’s in Management, both from Goldey Beacom College, Delaware, U.S.


Mark Lamotte, MD• Dr. Mark Lamotte is Principal and Group Manager, Health Economics & Outcomes Research atthe IMS Consulting Group in Belgium with responsibility for the content and quality of allhealth economic evaluations conducted by his team.

• A physician by training (cardiology), Mark spent a number of years in medical practice beforejoining Rhône-Poulenc Rorer as Cardiovascular Medical Advisor and later becoming ScientificDirector at the Belgian research organization, HEDM. He has since worked on more than 150projects, involving expert interviews, patient record reviews, extensive modeling and reportwriting across a wide range of therapy areas, and authored many peer-reviewed publications.

• Mark holds an MD from the Free University of Brussels (Vrije Univeristeit Brussel, Belgium) andis fluent in Dutch, French, English and Spanish.

Won Chan Lee, PHD• Dr. Won Chan Lee is Principal, Health Economics & Outcomes Research at the IMS Consulting Groupin the U.S., specializing in prospective and retrospective health economics research.

• Over the course of his career, Won has completed numerous international economic evaluationsemploying a variety of analytical methods across a range of diseases and geographies. His expertiseincludes econometric database analysis, quality of life assessment and advanced economic modelingto establish the economic and humanistic value of new and existing therapeutic interventions.

• Won holds a Master’s in Economics from the University of Grenoble II, and a PhD in Economics fromthe Graduate Center of the City University of New York.

Claude Le Pen, PHD• Dr. Claude Le Pen is a member of the strategic committee of IMS France and Professor of HealthEconomics at Paris-Dauphine University providing expert economic advisory services to theconsulting practice.

• A renowned economist, leading academic, and respected public commentator, Claude has servedas an appointed senior member of several state commissions in the French Ministry of Health andis an expert for a number of parliamentary bodies, bringing a unique perspective and unparalleledinsights into the economic evaluation of pharmaceutical technologies at the highest level.

• Claude studied Business Administration in HEC Business School in Paris and holds a PhD inEconomics from Panthéon-Sorbonne University.

IMS | EXPERTISE


Dana Morlet-Vigier, MD• Dana Morlet-Vigier is Principal and Team Leader, Health Economics & Outcomes Research at the IMSConsulting Group in France, applying in-depth expertise and extensive experience in pharmaceuticalpricing, reimbursement and market access to help clients meet the growing challenges of today’sincreasingly complex product launch process.

• A medical doctor and INSEAD executive, Dana’s background spans 15 years in pharmaceuticals andincludes roles in R&D, commercial, market access, strategy and government affairs atGlaxoSmithKline, Organon and 3M Pharma. She has worked on numerous pricing and reimbursementnegotiations and designed and implemented national and international Phase II, III and IV studiesacross a wide range of therapy areas.

• Dana holds an MD from Bucharest Medical University, Romania and the Paris-Cochin Faculty, Paris, France.

Julie Munakata, MS• Julie Munakata is Principal, Health Economics & Outcomes Research at the IMS Consulting Group inthe U.S., with a particular focus on global economic modeling, value development planning, andsurvey data analysis.

• An accomplished researcher and author of more than 25 original articles, Julie has extensiveexperience in managing clinical trials, health economic studies and decision analytic modeling work,gained in senior roles at ValueMedics Research LLC, the VA Health Economics Resource Center andStanford Center for Primary Care & Outcomes Research, and Wyeth Pharmaceuticals.

• Julie holds an MS in Health Policy and Management from the Harvard School of Public Health and aBS in Psychobiology from the University of California, Los Angeles.

Joan McCormick, MBA• Joan McCormick is Principal at IMS Brogan in Canada, leading a team providing strategic adviceto companies with new products coming to market and ongoing consultation on the rules forexisting drugs post launch.

• Formerly Head of Price Regulation Consulting at Brogan Inc, Joan has supported many majorpharmaceutical companies with the preparation of pricing submissions to the PatentedMedicine Prices Review Board (PMPRB), gaining extensive insights into the operation of theCanadian pharmaceutical market.

• Joan holds a Bachelor’s degree in Life Sciences from Queen’s University in Kingston, Canada,and an MBA from the University of Ottawa, Canada.

Eva Marchese, PHD• Dr. Eva Marchese is Principal, Pricing & Market Access at the IMS Consulting Group in Italy,with a particular focus on market access, regulatory, pharmacovigilance, pricing andreimbursement, and health economics and outcomes research.

• An experienced consultant and founding partner of S&M Consulting, Eva has been involved inseveral ministerial committees at the Italian Ministry of Health, looking at cost evaluation andanalysis of day surgery procedures. She was previously Professor of Public Management andPolicy at Bocconi-SDA, the foremost Italian Business School, and a contracted Research Fellowat the Centre for Research on Healthcare and Social Management at Bocconi University.

• Eva holds a PhD in Public Management from the Parma State University, and a degree inBusiness Administration from Bocconi University in Milan.

Frédérique Maurel, MS, MPH• Frédérique Maurel is Principal, Health Economics & Outcomes Research at the IMS Consulting Groupin France, with a particular focus on observational research and health economics studies.

• A skilled consultant and project manager, Frédérique has extensive experience in the economicevaluation of medical technologies gained in roles at ANDEM, Medicoeconomie, and AREMIS Consultants.

• Frédérique holds a Masters degree in Economics – equivalent to an MS – and completed a post-graduate degree equivalent to an MPH with a specialization in Health Economics at the Universityof Paris-Dauphine (Paris IX) as well as a degree in Industrial Strategies at the Pantheon-SorbonneUniversity (Paris I).

EXPERTISE | IMS

Vernon Schabert, PHD• Dr. Vernon Schabert is Global Leader Retrospective Outcomes Research and Senior Principal at the IMSConsulting Group in the U.S., leading the assessment and validation of patient-reported outcomes (PRO)instruments, retrospective analyses of claims and survey databases, and primary data collection surveys.

• A founder and former President of Integral Health Decisions, Inc, Vernon has extensiveexperience in conducting claims analyses, creating custom administrative databases,developing business intelligence software, and leading national quality research projects,gained in roles with Thomson Reuters, Strategic Healthcare Programs LLC, and CIGNAHealthCare. His expertise spans numerous disease areas and diverse topics including medicationadherence, in-patient safety and outcomes in post-acute care.

• Vernon holds a PhD in Personality and Social Psychology from Stanford University and a BA inPsychology from Princeton University.

Michael Nelson, PHARM D • Dr. Michael Nelson is Regional Leader, Americas, Health Economics & Outcomes Research at the IMS Consulting Group in the U.S., with particular expertise in retrospective database research,prospective observational research, health program evaluation, and cost-effectiveness analysis.

• During a career that includes leadership roles in HEOR at PharmaNet, i3 Innovus, SmithKlineBeecham, and DPS/UnitedHealth Group, Mike has gained extensive experience in healthinformation-based product development, formulary design, drug use evaluation, and diseasemanagement program design and implementation.

• A thought leader in health economics for more than 20 years, Mike holds a doctorate in Pharmacyand a Bachelor of Science degree, both from the University of Minnesota College of Pharmacy. Healso served as an adjunct clinical faculty member at the University of Minnesota whilst in clinicalpharmacy practice.

Olaf Pirk, MD, PHD• Dr. Olaf Pirk is Senior Scientific Consultant to IMS and previously Principal, Health Economics & OutcomesResearch in Germany, with a particular focus on health technology assessment, healthcare systemresearch, health policy and health economic modeling across a range of countries and therapeutic areas.

• Formerly a Managing Director of Fricke & Pirk GmbH, Olaf has considerable pharmaceutical industryexperience gained in roles within health economics, pricing, health policy, marketing and clinicalresearch. As a co-founder of the NIG 21 association, he has forged strong relationships with healtheconomists, physicians and related researchers working in the German healthcare system.

• Olaf holds an MD and PhD in Medicines from the Medical University of Lübeck.

Jon Resnick, MBA• Jon Resnick is Vice President and Global Leader Health Economics & Outcomes Research at the IMS Consulting Group, advising pharmaceutical and biotech companies on a wide range of strategic,pricing and reimbursement issues.

• A former Legislative Research Assistant in Washington DC and member of the Professional Healthand Social Security staff for the U.S. Senate Committee on Finance, Jon combines public policyand industry expertise to provide a unique grasp of the healthcare market place. He has co-authored several major U.S. healthcare initiatives, including proposals to reform managed care.

• Jon holds an MBA from the Kellogg School of Management, Northwestern University, where hemajored in Management and Strategy, Finance, Health Industry Management, and Biotechnology.


Karl-Johan Myrén, MSC• Karl-Johan (Kalle) Myrén is Principal, Health Economics & Outcomes Research at the IMS Consulting Group, with responsibility for the Nordic region. He has extensive expertise inglobal and affiliate pricing, market access, reimbursement and health economics and a deepunderstanding of many different national healthcare systems.

• Karl-Johan’s career spans more than 13 years experience in global health economics gained inroles at the Swedish Institute of Health Services Development, Astra Zeneca and Eli Lilly,latterly as Senior Area Health Economist coordinating and managing health economic activitiesfor the European middle-sized (EMS) countries, including the Nordic markets, Belgium,Switzerland, the Netherlands and Portugal.

• Karl-Johan holds an MSc in Economics and a BSc in Mathematics from the University of Stockholm.

he best results were seen from adherence programs involving medical professional to patient contact on a

egular basis


IMS | EXPERTISE

Núria Lara Surinach, MD, MSC• Dr. Núria Lara is Principal, Health Economics and Outcomes Research at the IMS Consulting Group inSpain, where she leads the Outcomes Research group in the design and coordination of local andinternational observational and patient-reported outcomes studies.

• A former practicing GP and clinical researcher, Núria’s experience spans roles in outcomes researchat the Institute of Public Health in Barcelona and in Catalan Health Authorities, and consultingpositions within the pharmaceutical and medical device industries focusing on medical regulatoryand pricing affairs, pharmacoeconomics and market access strategies.

• Núria holds an MD (specializing in Family and Community Medicine in Barcelona), and a Master’s inPublic Health from the London School of Hygiene and Tropical Medicine and London School of Economics.

Meng Zhang, MBA• Meng Zhang is Principal, Pricing & Market Access at IMS in China, applying evidence-basedanalytics to help clients address key business issues in global pricing, product launch readiness,market opportunity assessment and product portfolio optimization.

• During the course of his career in the U.S. and China, Meng has developed extensive expertisein pricing and reimbursement, new market entry, competitive analysis and corporate strategicplanning, in consulting roles at SDI Health and Accenture, business development at J&J, andas a professional representative at Xian-Janssen Pharmaceutical Ltd in China.

• Meng holds a degree in Biology from Nanjing University, a Master’s in Biochemistry from theUniversity of New Brunswick, Montreal and an MBA from the Wharton School of the Universityof Pennsylvania, with a major in Healthcare Management.

Massoud Toussi, MD, MSC, PHD • Dr Massoud Toussi is Medical Director, Health Economics & Outcomes Research at the IMSConsulting Group in France, where he brings in-depth knowledge of methodological andoperational aspects of clinical research to assure the quality of interventional, observationaland database studies.

• A medical practitioner, Massoud was previously Head of Global Clinical Research Operations atCegedim. His background includes roles at the French High Authority for Health (HAS) andvarious CROs as Project Lead, Scientific Manager and Operations Director. He has also used hisextensive knowledge of IT tools and pharmacovigilance to define a new service process in drugsafety signal detection and transmission.

• Massoud holds an MD from Mashad University in Iran, an MSc in Medical Informatics andCommunication Technology from Paris IV, and a PhD in Medical Informatics from Paris XIIIUniversity. He also holds a diploma in Transcultural Psychiatry from Paris Nord University.

Arnaud Troubat, PHARM D, MBA, MHEM• Arnaud Troubat is Principal, Health Economics & Outcomes Research at the IMS ConsultingGroup in France. He has extensive consulting experience and special expertise in thedevelopment of registration dossiers and market access strategies across a large number oftherapeutic areas.

• A pharmacist by training, Arnaud began his career at the French pharmaceutical industryassociation (LEEM), supporting members in understanding and interpreting the changingeconomical environment in France. He then spent a number of years in pharmaceutical affairsat ICI, leading regulatory work on registration submissions and reimbursement strategies,before subsequently moving into consulting. Most recently, he was Director at Carré-CastanConsultants, managing a team working for a wide range of pharmaceutical companies.

• Arnaud holds a Doctor of Pharmacy degree and an MBA from IAE Paris and a Master’s in HealthEconomics and Management from Paris-Dauphine University.

IMS | LIFELINK

Your business models have changed. So have the metrics thatkeep the healthcare industry moving forward. Today, a patientperspective is a must.

Through the global IMS LifeLink™ program, we provide apowerful patient lens to drive focus and alignment acrossyour business, deepening your understanding of criticalpatient, physician and payer dynamics. LifeLink allows youto identify the right patient segments early on, in order togain competitive advantage in today’s complex environment.

We make a patient-centered perspective simple – byintegrating patient-level intelligence into our industry-leading offerings and giving you expert consultants whoapply it to your key issues.

IMS LifeLink provides insights of primary research with thebenefits of secondary – lower cost, repeatable, faster and alarger sample size.

IMS LifeLink has everything you need to succeed in apatient-centered universe.

POWERING A PATIENT PERSPECTIVE

We make a patient perspective easy, with familiar tools,integration into our industry-leading offerings and expertconsultants who apply patient insights to your business issues.

A PARTNER YOU CAN TRUST

Pharmaceutical companies worldwide rely on LifeLink to drivepatient-centered decisions – from the first exploratoryquestions that drive clinical development to tactical salesplanning for mature brands. They are recognizing significantbenefits, such as:

• Better global decision making through consistent insightsacross all brands and across the product lifecycle

• Improved internal alignment with consistent patientsegments defined across research & development andcommercial functions

• Enhanced communication with healthcare payers andother stakeholders with the use of a consistent patientview and common language

• Faster and more accurate views across three keydimensions: patients, payers and prescribers

• Confidence working with a partner who is committed todriving new metrics for new business models

Powering a patient perspective

Pharmaceutical companies worldwide rely on IMS LifeLinkTM to drive patient-centered decisions – from clinical development to mature brands.


CANADA • Longitudinal Rx

UNITED STATES• Longitudinal Rx

• Health Plan Claims Database

• Health Plan Claims Database

• Longitudinal drug utilization data(Oncology, hospital)

• Oncology Analyzer

EUROPE • Longitudinal Rx (Belgium, Germany, Netherlands, UK)

• Anonymized Patient-Level Data from Electronic Medical Records (France, Germany, Italy, UK)

• Hospital Disease Database (Belgium)

• Oncology Analyzer(France, Germany, Italy, Netherlands, Spain, Turkey, UK)

ASIA • Oncology Analyzer (China, Japan, Korea, Taiwan)

• Longitudinal Rx (Japan, South Korea)

AUSTRALIA • Longitudinal Rx • Longitudinal Patient Database

(Sweden)

AN UNPARALLELED ARRAY OF ANONYMIZED PATIENT-LEVEL DATA WORLDWIDE

©2011 IMS Health Incorporated or its affiliates. All Rights Reserved.

Reveal True Product Value

Developing products that are fit to succeed in the ‘real world’ requires a sharp scientific focus.

The IMS Consulting Group Health Economics & Outcomes Research unit is a multi-disciplinary,global team — with proven success in more than 40 countries worldwide.

Our team of leading experts combines rigorous scientific research with a customer-focusedconsulting model to help you:

Address growing HTA requirements Build powerful health economic support Create enduring value propositions Develop innovative solutions for real-world market needs

Next time you need HEOR support, consider the IMS perspective.

? [email protected]

? UK + 44 (0)20 3075 4800, US +1 (703) 837-5150, AsiaPac +86 10 8567 4255, Latin America + 52 (55) 50.62.52.00

? www.imsconsultinggroup.com/heor

ims accesspoint - november 2011

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