Evidence-Based Medicine for Guiding Better CareJeffrey Rose, MDSenior Vice President, Clinical StrategyHearst HealthS E P T E M B E R 1 7 , 2 0 1 8

The Need for Evidence-Based Practice

Sources:1.Berwick DM and Hackbarth AD. Eliminating waste in US health care. JAMA. 2012 Apr 11;307(14): 1513–6. 2.McGlynn, et al, The Quality of Health Care Delivered to Adults in the United States, N Engl J Med 2003; 348:2635-2645 3.Tsugawa Y, Jha AK, Newhouse JP, Zaslavsky AM, Jena AB. Variation in Physician Spending and Association with Patient Outcomes. JAMA Intern Med. Published online

March 13, 20174.Dartmouth Atlas of Healthcare, http://www.dartmouthatlas.org/5.Building a Safer Health System 2000 Institute of Medicine: To Err Is Human Washington, DC. National Academies Press and6.James JT. A new, evidence-based estimate of patient harms associated with hospital care. J Patient Saf. 2013 Sep;9(3):122-8.7.Makary MA, Daniel M. Medical error - the third leading cause of death in the US. British Medical Journal 2016;353:i21398.Sackett DL, Rosenberg WM, Gray JA, et al. Evidence-based Medicine: What It Is and What It Isn’t. BMJ. 1996 Jan 13; 312(7023):71-2.

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►Wasteful Care 30% of all healthcare delivered in the US is inappropriate or

wasteful1

►Unwarranted Variations in Care Only 55% of appropriate healthcare services are delivered to

patients2

Nationwide, there are marked variations in services, costs, effectiveness of care and physician spending without rational explanation, within hospitals and across geographies and venues of care for normalized conditions and procedures3,4

►Harm Caused by Healthcare There are startling levels of harm and more than 70,000

deaths occur each year due to medical errors4,5,6,7

MODERN EVIDENCE-BASED MEDICINE:“The conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients”8

Sources:1.Bastian H, Glasziou P, Chalmers I. Seventy-Five Trials and Eleven Systematic Reviews a Day: How Will We Ever Keep Up? PLoS Med 2010 Sep 21;7(9): e1000326.

https://doi.org/10.1371/journal.pmed.10003262.Allen D, Harkins KJ. Too much guidance? Lancet. 2005 May 21-27;265(9473)1768 3.Paul G. Shekelle, MD, PhD Clinical Practice Guidelines, What’s Next, August 9, 2018. doi:10.1001/jama.2018.96604.Ioannidis, JP. Evidence-based medicine has been hijacked: a report to David Sackett. J Clin Epidemiol. 2016 May;73:82-6. 5.Prasad V, Vandross A, Toomey C, et al. A Decade of Reversal: An Analysis of 146 Contradicted Medical Practices. Mayo Clin Proc. 2013 Aug; 88(8):790-9.6.Prasad V, Cifu A, Ioannidis JPA. Reversals of established medical practices: evidence to abandon ship. JAMA. 2012;307(1):37-38.

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►Volume and Velocity More than 6 million articles are published every year, and approximately 75 randomized controlled trials

and 11 systematic reviews are published every day1

Even as this mass of information was condensed and consolidated into guidelines, those guidelines themselves, created by hosts of governing groups and specialty medical societies, became overwhelming2

►Quality, Transparency, and Conflicts of Interest Problems include variable methods of guideline gradation and assessment, qualifications and biases of

guideline developers, and variable guideline publication based on positivity or negativity of study outcomes and based on funding sources for studies or affiliation rewards of guideline authors3,4

►Competing Recommendations and Evidence Churn A study of articles published in the New England Journal of Medicine over the course of a decade (2001-

2010) demonstrated that 17% of the studies testing a new practice showed it was no better or worse than the current practice.5

Of the studies testing an established practice, 40.2% showed the practice to be no better than what had preceded it. Continued use of widespread practices that are implemented “in error” because of weak or conflicting evidence may be wasteful and expensive, if not harmful to patients.5,6

Complexities of Medical Evidence

Sources: 1.Guyatt, G, et al. Users’ Guides to the Medical Literature: A Manual for Evidence-Based Clinical Practice 3rd Ed. JAMA. 2.Bobb AM, Payne TH, Gross PA. Viewpoint: Controversies surrounding use of order sets for clinical decision support in computerized provider order entry. J Am Med Inform Assoc. 2007

Jan-Feb;14(1):41-7.3.Ozdas A, Speroff T, Waitman LR, et al. Integrating 'best of care' protocols into clinicians' workflow via care provider order entry: impact on quality-of-care indicators for acute myocardial

infarction. J Am Med Inform Assoc. 2006 March;13(2):188-96.4.Santolin CJ, Boyer LS. Change of care for patients with acute myocardial infarctions through algorithm and standardized physician order sets. Crit Pathw Cardiol. 2004 June;3(2):79-825.Kawamoto K, Houlihan CA, Balas EA, et al. Improving clinical practice using clinical decision support systems: a systematic review of trials to identify features critical to success. BMJ

2005 Apr 2;330(7494):765.6.Fonarow GC, Abraham WT, Albert NM, et al. Influence of a performance-improvement initiative on quality of care for patients hospitalized with heart failure: results of the Organized

Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure (OPTIMIZE-HF). Arch Intern Med 2007;167:1493-502.7.Burstin HR, Conn A, Setnik G, et al. Benchmarking and quality improvement: the Harvard emergency department quality study. Am J Med 1999 Nov;107(5):437-49.8.Grol R. Successes and failures in the implementation of evidence-based guidelines for clinical practice. Med Care 2001 Aug;39(8 Suppl 2):II46-54.9.Grilli R and Lomas J. Evaluating the message: the relationship between compliance rate and the subject of a practice guideline. Med Care 1994 Mar;32(3):202-13.10.Osheroff JA, Teich JM, Levick D, et al. Improving outcomes with clinical decision support: an implementer's guide (Kindle Locations 19-21). Chapter 1, Evidence Base for CDS Value,

HIMSS. Kindle Edition.11.Tierney WM. Controlling costs with computer-based decision support: an ax, a scalpel, or an illusion? JAMA Intern Med 2013 May 27;173(10):909-10.

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A G G R E G AT I O N A N D A P P R A I S A L

E M B E D D I N G I N T H E C L I N I C A L W O R K F L O W

Making the Evidence Actionable

Three Principles1:►Optimal clinical decision making requires

awareness of the best available evidence►Evidence-based medicine evaluates the totality of

evidence and provides guidance to decide whether evidence is more or less trustworthy, based on systematic summaries

►Evidence alone is never sufficient to make a clinical decision: it is a complement to clinical judgment

►Research has demonstrated that guideline programs, order sets, protocols, and other clinical decision support formats can help to improve safety, efficiency, and clinical outcomes when adherence is achieved.2,3,4,5,6

►Unfortunately, studies show that guideline adherence by clinicians ranges only from 50% to 67%.7,8,9

►Similar lukewarm results have been observed with evidence-based clinical decision support efforts, which seems to indicate that influencing clinical and industrial behavior remains problematic.10,11

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OUR NETWORK OUR REACH1 OUR MISSION

85%of discharged patients

205 Millioninsured individuals

70 Millionhome health visits

3.2 Billiondispensed prescriptions

3 8 Y E A R S in the health information industry

P I O N E E R Sof new and leading solutions

I N D E P E N D E N Tunbiased, evidence-based

To guide the most important care moments by delivering vital information into the hands of everyone who touches a person’s health journey

1 Annually in the United States

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Copyright © 2017 IQVIA. All rights reserved.

“Becoming the Best: Recent Developments

in Evidence-Based Medicine”

September 17, 2018

Mitch DeKoven, MHSASenior Principal – Health Economics/

Outcomes ResearchIQVIA

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A better world

More effective health delivery

Focus on value and outcomes

Improved health

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Imagine if every healthcare decision was the right decision for you

Bigger picture, bigger data, more precise insights and outcomes

Bre

adth

of i

nsig

hts

Volume and diversity of needed data

Diagnosis & Treatment

Plan

VS.

Diagnosis & Treatment Plan

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The main sources of data relevant to health…are everywhere

13

*Source: Harvard Business Review (2012)

The promise of big data is exciting

Increasing potential to have more data Proven value of using it

5%

6%

Additional growth of companies applying data-driven decision making compared to

competitors*

Productivity

Profitability

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The promise of big data is exciting (cont’d)

Clinical trials are designed around the patient

Treatment costs reflect the value they bring

Precision medicines find their way to the right patient

Predictive analytics prevent medical errors

Every medical decision is informed by evidence

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Payers and Regulators see the value of Real-World Evidence

FDA“The more widespread use of RWE can make our medical product development process more efficient…. This will ultimately help us achieve better outcomes, and safer and more efficient use of expensive technology.”

Scott Gottlieb, MD, FDA Commissioner

https://www.fda.gov/NewsEvents/Speeches/ucm576519.htm

EMA needs RWE to support adaptive approval pathways

EMA

Intensive monitoring of patients

Additional indication(s)

Num

ber o

f Pa

tient

s

Intensive monitoringof patients

Initial Approval of niche indication

Time

FULL APPROVAL

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Using RWE for more sophisticated site selectionCASE STUDYBetter execution

• Faster recruitment by understanding treatment patterns

• Reduces costs by selecting better sites and reducing non-recruiting sites

Two sites “look” the same

353 Total Crohn’s Patients

IQVIA can “see” actual available patients

Eligible Crohn’s Patients

SITE A SITE B

363

12516

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Finding patients in rare disease

*Group defined as top 5% of undiagnosed rare disease patients

0.01%

5.20%

Without themodel

With the model

Making diagnosis possibleDiagnosis rates for high-risk patients*

CASE STUDY

Rare Diseases

• Machine learning: 100+ medical and demographic predictors of 100M patients

• Physician and patient data: Identifying doctors with high-risk patients to increase diagnosis

• New tools: Increase screening, diagnosis

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Evidence hubs in NFLCASE STUDYEvidence infrastructure

DATA COLLECTION• Novel application of registry technology• Electronic medical record system• Focus on customized medical staff training

ANALYSIS AND INSIGHTS• Incidence and trends in injury occurrence• Injury prevention analyses

REPORTS• Specialty reports• Published findings• Updates to league

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Data anonymised

, extracted,

linked, and

harmonized across

sources

MS patients under routine clinical management

Network of public & private neurology practices

Quantitative MRI data• Whole/regional

atrophy• T1, T2, Gd

lesion activity & volume

Structured EMR data • Comorbidities• Treatment patterns• Clinical assessments

(EDSS, relapse, symptoms)

Structured MRI+EMR Real World Dataset

Generation of novel observational research

studies in MS

Collect and link existing MRI and clinical data in the real world

Multiple SclerosisCASE STUDYEvidence platforms

Generating Robust Evidence to Support Innovation

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What is StrataGraft?

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•Off-the-shelf availability; being studied as an option to reduce the need for autologous skin graft harvesting

•Shelf life enables on-site or on-demand availability

•Multli-layer skin substitute in development for the treatment of severe burnsFully developed, multi-layered epidermisDermal fibroblasts in collagen-rich matrix

•Creates physical barrier•Cryopreserved to maintain viability and biological

activity

StrataGraft’s clinical trials builds on evidence-based approach to severe burn care

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Substantial evidence supports early excision

and grafting as best approach, but adoption

is not universal