pharmacoeconomic evaluation in ireland

Pharmacoeconomic Evaluation in IrelandA Review of the Process

Lesley Tilson, Aisling O’Leary, Cara Usher and Michael Barry

National Centre for Pharmacoeconomics, St James’s Hospital, Dublin, Ireland

Abstract Objective: To describe the pharmacoeconomic assessment process in Ireland

and to provide examples of recent appraisals and the subsequent impact on

pricing and reimbursement decisions.

Method: The pharmacoeconomic appraisals conducted by the National

Centre for Pharmacoeconomics (NCPE) between September 2006 and

February 2009 were reviewed. The NCPE recommendations and subsequent

reimbursement decisions by the Health Service Executive (HSE) were recorded.

Recommendations made by the NCPE were compared with those of UK

agencies. The duration of the NCPE pharmacoeconomic process and the time

from marketing authorization to reimbursement was estimated. The budget

impact assessments from the pharmaceutical companies were reviewed and

compared for consistency.

Results: The NCPE conducted 12 single technology appraisals during the

study period. Eight of the medicines assessed were either recommended as a

cost-effective use of resources or recommended with certain restrictions, and

were funded by the HSE. Of the four medicines that were not considered cost

effective, two were reimbursed after a price reduction was negotiated and the

remaining two were not. The NCPE recommendations concurred with those

of the UK agencies for the majority of appraisals, with the exception of

sunitinib and lapatinib. The average duration of the NCPE process was

2.7 months. The average time from marketing authorization to reimburse-

ment was 7 months. The review of budget impact assessments highlighted a

high degree of variability between submissions.

Conclusions: The findings of this review highlight the efficiency of the phar-

macoeconomic process and the acceptance of the NCPE recommendations

by the HSE for pricing and reimbursement decisions. NCPE recommen-

dations broadly concurred with those of UK agencies for the majority of

appraisals.

Background

The population of Ireland increased from 3.92million to 4.24 million between 2002 and 2006,

representing an 8.1% increase over a 4-year peri-od.[1] From a 10-year perspective, Ireland’s popu-lation increased at an annual average rate of1.6% between 1996 and 2006. This is the largest

ORIGINAL RESEARCH ARTICLEPharmacoeconomics 2010; 28 (4): 307-322

1170-7690/10/0004-0307/$49.95/0

ª 2010 Adis Data Information BV. All rights reserved.

population growth in the EU. Although the pop-ulation is aging, in comparative terms it remainsrelatively young, with 11.1% of the populationaged >65 years.

Healthcare policy and expenditure is governedby the Department of Health and Children(DoHC) and administered through the HealthService Executive (HSE). Healthcare funding ismainly derived through taxation (75%), withprivate funding via insurance agents accountingfor 11% and patient co-payments the remainder.Total healthcare expenditure has increased con-siderably from h3.5 billion in 1997 to an esti-mated h15 billion in 2007. In 2007, expenditureon medicines under the Community DrugSchemes (approximately 85% of total pharma-ceutical expenditure) was h1.74 billion, a >5-foldincrease over the decade 1997–2007.[2]

The National Centre for Pharmacoeconomics(NCPE) was established in Ireland in 1998 withfunding from the DoHC. The aims of the centreare to promote expertise in Ireland for the ad-vancement of the discipline of pharmacoeco-nomics through practice, research and education.The NCPE appraises the cost effectiveness oftechnologies (medicines, diagnostics and devices)that may entail a high budget impact to the healthsystem, in response to requests from the HSE orthe DoHC. The NCPE also conducts pharma-coeconomic evaluations to inform public healthpolicy (e.g. universal infant pneumococcal vacci-nation) and prescribing in primary care (e.g. sta-tins for primary and secondary prevention ofcoronary heart disease).[3-5]

Ireland is a small country with a process thatdiffers from other countries for handling phar-macoeconomic evaluations. Similar to the UK,Ireland is often one of the countries of first launchfor new medicines in the EU and therefore the re-imbursement decision could be of interest to otherEU countries who may evaluate these medicines ata later stage. In this review we describe the phar-macoeconomic evaluation process in Ireland andprovide examples of recent appraisals and thesubsequent reimbursement decisions.

Reimbursement of Medicines in Ireland

There are a number of different reimbursementschemes in Ireland (e.g. General Medical Services[GMS], Drugs Payment [DP], Long-Term Illness[LTI] and High Tech Drugs Scheme [HTDS]),which are collectively referred to as the Commu-nity Drug Schemes. These four schemes accountfor 98% of prescriptions and 99% of expenditure inthe community setting. Prior to reimbursementunder the Community Drug Schemes, a medicinemust be included on a positive list.1

The GMS scheme is a means-tested scheme,and eligibility is dependent upon factors such asage, marital status, living alone or with familyand allowances. Individuals covered by the GMSscheme are entitled to full reimbursement ofprescription medications that are included on theGMS list of reimbursable items. Approximatelyone-third of the population is eligible for theGMS scheme and it accounts for about two-thirds of pharmaceutical expenditure in primarycare. Pharmacists are paid a flat fee per item fordispensing medicines on the scheme.

The DP scheme applies to Irish residents whoare not eligible for the GMS scheme. Individuals/families are required to pay a deductible of up toh120 in any calendar month for approved pre-scribed medicines and the HSE pays for the re-maining cost of medicines in any particular month.Individuals who have any of 15 listed chronic ill-nesses (e.g. diabetes mellitus and epilepsy) are alsoentitled to full reimbursement of drugs specific tothat condition under the LTI scheme. Pharmacistsare paid a percentage mark-up (20%) on the in-gredient cost as well as a dispensing fee per item onthe DP and LTI schemes.

The HTDS was introduced in 1996 to facili-tate the supply by community pharmacists ofcertain high-cost drugs e.g. oral chemotherapy,b-interferon and growth hormones. The priceof these high-cost drugs is paid directly to thewholesaler by the HSE and pharmacists are paida standard monthly patient care fee. There is alsoa separate scheme for dispensing methadone for

1 List of pharmaceuticals that may be prescribed at the expense of the healthcare payer (cf negative list).

308 Tilson et al.

ª 2010 Adis Data Information BV. All rights reserved. Pharmacoeconomics 2010; 28 (4)

opiate-dependent drug users, and pharmacistsare paid a monthly patient-care fee. Therefore,the reimbursement price of medicines in Irelanddepends on patients’ eligibility for reimbursementof prescription drugs. Indeed, the difference indrug costs between theGMS andDP/LTI schemescan result in a medicine being cost effective on onescheme, but not on the other. The CommunityDrug Schemes in Ireland are explained in greaterdetail in previous publications.[6,7]

Pharmacoeconomic Evaluation in Ireland

The requirement for pharmacoeconomic eval-uation for reimbursement of technologies inIreland is outlined in the agreement betweenthe Irish Pharmaceutical Healthcare Association(IPHA) and the HSE (IPHA/HSE Agreement).[8]

The requirement for pharmacoeconomic data isby agreement, rather than by statutory regula-tion. The Agreement came into effect on 1 Sep-tember 2006 and replaced the previous Agreement,which commenced in 1993, was renewed in 1997and extended in 2001. It outlines the supplyterms, conditions and pricing of medicines sup-plied to the health service in Ireland. The Agree-ment covers all medicines reimbursed under theCommunity Drug Schemes and all medicinessupplied to the HSE, State-funded hospitals andState agencies whose functions normally includethe supply of medicines.

Under the terms of the 2006 IPHA/HSEAgreement, the HSE reserves the right to assessnew and existing technologies (medicines, diag-nostics and devices) that may incur a high cost orhave a significant budget impact. What con-stitutes ‘high cost’ or ‘high budget impact’ has notbeen explicitly stated or defined. In the case ofnew medicines, assessments may be conductedprior to the reimbursement application but mustbe completed within 90 days. Evaluations areconducted in accordance with the existing agreedIrish Healthcare Technology Assessment Guide-lines (2000).[9] Prior to the current Agreement,pharmacoeconomic data were used on an in-formal basis in Ireland.

The pharmacoeconomic evaluation processincludes a number of key steps (figure 1):

� Products are formally referred to the NCPE bythe Products Committee of the CorporatePharmaceutical Unit of the HSE, whose respon-sibility it is to approve medicines for reimburse-ment under the Community Drug Schemes. TheCommittee meet on a monthly basis.

� Once the NCPE receives a request to conduct apharmacoeconomic assessment, representa-tives of the relevant pharmaceutical companyare invited to attend a meeting at which thedetails of the process, as well as the scope andrequirements for the evaluations, are outlined.

� The pharmaceutical company then prepares apharmacoeconomic submission, which includesevidence of the cost effectiveness and anestimate of the potential budget impact of theproduct in the Irish setting. The budget impactestimate is not part of the decision-makingprocess on cost effectiveness but it is intended togive the HSE an indication of the financialimplications should the product be reimbursed.

� The NCPE Review Group critically appraisesthe company submission. The Review Group isa multidisciplinary team comprising a clinician,

Product for pharmacoeconomic assessment selected byproduct committee (HSE)

Formal notification to pharmaceutical company andreferral to NCPE

Meeting between review group at NCPE and representativesfrom the pharmaceutical company

Formal submission of evidence of cost effectiveness, cost-effectiveness model and budget impact analysis from company

NCPE critical appraisal of company submission

NCPE appraisal sent to pharmaceutical company for comment

NCPE final appraisal sent to product committee (HSE)

Summary of NCPE appraisal posted on NCPE website

Product committee (HSE) make reimbursement decision

Fig. 1. Summary of the pharmacoeconomic process in Ireland.HSE =Health Service Executive; NCPE =National Centre forPharmacoeconomics.

Pharmacoeconomic Evaluation in Ireland 309


pharmacists, research scientist, health economistand statistician. This process includes an assess-ment of the modelling and data inputs providedby the manufacturer (as opposed to the NCPEdeveloping a model and preparing an assess-ment report themselves). Local expert clinicalopinion is sought by the Review Group regard-ing the place in therapy of the new medicine.

� The NCPE prepares a critical appraisal of thecompany submission with the systematic appli-cation of a ten-point checklist. The checklist wasdevised by Drummond et al.[10] and it is used toensure a consistent systematic approach isadopted to critically appraise each submission.The NCPE invite comments from the pharma-ceutical company prior to completion of thefinal appraisal.

� The final appraisal, which includes a recom-mendation of whether the technology may beconsidered cost effective from the HSE per-spective, is completed by the NCPE andsubmitted to the Products Committee (HSE).

� A summary of the final appraisal document isposted on the NCPE website. This includes arecommendation as to whether the technologywould be considered a cost-effective use ofresources.

� Products subject to an assessment are reim-bursed within 40 days of a positive reimburse-ment decision. Should reimbursement berefused, an appeal may be made to a desig-nated expert committee whose final decisionmay be made within a further 90 days and isaccepted as binding.[8]

Pharmacoeconomic Evaluation in OtherJurisdictions

The processes of selecting and appraising newdrugs vary between jurisdictions, both within theEU and other international settings. In this arti-cle, we compare our recommendations with thoseof the three UK bodies that evaluate cost effec-tiveness of drugs and medical interventions:the National Institute for Health and ClinicalExcellence (NICE), the Scottish MedicinesConsortium (SMC) and the All Wales MedicineStrategy Group (AWMSG). NICE, the inde-

pendent agency that provides guidance to the UKNHS on the use of technology, has two ap-proaches to completing technology appraisals: asingle technology (STA) and multiple technology(MTA) appraisal process. NICE MTAs take anaverage of 14 months and STAs are expected totake between 6 and 8 months.[11] One of the maindifferences between the STA and MTA processesis that under the STA process, the cost-effective-ness model provided by the manufacturer isreviewed, whereas under the MTA process anindependent model is developed.[11,12] NICE as-sesses both drugs and medical interventions, butit does not consider all drugs, only those that arereferred to it by the Secretary of State for Health.

In contrast, the SMC assesses and producesadvice on all new drugs but does not assess otherhealthcare interventions. The AWMSG appraisesnew high-cost medicines for which no NICEguidance is expected for at least 12 months.NICE guidance takes precedence over AWMSGguidance if the two differ.

The SMC and AWMSG processes put theburden of proof on the manufacturers and pro-vide more rapid recommendations based on areview of the manufacturers’ own models com-pared with the NICE MTA process. The NICESTA process is broadly similar, in terms of itstimelines, to the Scottish and Welsh processes.SMC aims to issue advice on all newly licensedmedicines within 12 weeks of products beingmade available. The SMC process does not in-clude the time for companies to prepare theirsubmission, whereas the NICE STA appraisalincludes this period.[11] The AWMSG processtakes approximately 6 months and can be timedso that the medicine can be endorsed for NHSWales as expediently as possible. This results inuse and funding of a medicine prior to NICEguidance or in its absence.

The objectives of this article are to assess therecommendations made by the NCPE and sub-sequent reimbursement decisions by the HSE.Furthermore, in cases where the NCPE haveevaluated the same drugs as NICE, SMC andAWMSG, the recommendations are comparedand reasons for any disagreements are discussed.Additional elements of this article include a review

310 Tilson et al.


of the time from marketing authorization (MA) toreimbursement and the duration of the pharmaco-economic appraisal process itself. Common issuesraised by the Review Group in the critical appraisalof company submissions are highlighted. Further-more, ancillary analysis of the estimated budgetimpact analyses (BIAs) submitted by the phar-maceutical companies is presented.

Methods

The pharmacoeconomic appraisals conductedby the NCPE between September 2006 andFebruary 2009 were reviewed. Details of the ther-apeutic indication of themedicine at the time of theevaluation, the chosen comparator for the cost-effectiveness evaluation and the setting/drugreimbursement scheme were collated for each ap-praisal. All medicines appraised by the NCPEduring the study periodwere categorized accordingto the NCPE recommendation, whether cost ef-fectiveness was demonstrated and whether theywere subject to an appeal. Subsequent reimburse-ment decisions by the HSE were recorded.

The evaluations of the drugs that were alsoappraised by the NICE, SMC and AWMSGwerereviewed and compared with the NCPE re-commendations. The date of publication of allappraisals was recorded.

The time from first MA to reimbursement wasestimated. The list of licensed human medicineson the Irish Medicines Board website[13] providesaccess to the date of first MA in Ireland and is apublicly available source of the data. The date ofinclusion of the medicine on the list of re-imbursable items was obtained from the productfiles of the Primary Care Reimbursement Service(PCRS). This list is updated on a monthly basis.

The duration of the pharmacoeconomic processwas estimated for each appraisal. The ‘start date’ isregarded as the date the NCPE receives the sub-mission from the pharmaceutical company. The‘finish date’ is regarded as the date that the NCPEsubmit their final appraisal of the company sub-mission to the Product Committee of the HSE.According to the IPHA-HSE Agreement, theprocess should take no longer than 90 days. TheNCPEReviewGroupmay request the company to

undertake certain changes to the pharmacoeco-nomic submission. For example, more extensivesensitivity analysis or alterations to key data inputsmay be required. The time taken by the companyto prepare and make amendments to the submis-sion is not included in the 90-day time limit (i.e.there is a ‘stop-clock’). The duration of the phar-macoeconomic process recorded in this reviewincluded the time for the company tomake amend-ments to their submission.

Common issues raised by the Review Group inthe critical appraisal of company submissions werehighlighted and the BIAs from the pharmaceuticalcompanies were reviewed and compared for con-sistency. The following information was extractedfrom the six BIAs that were reviewed.� Estimated budget impact. The submissions were

categorized according to whether by year 5 theintervention would be cost saving, low bud-get impact (<h0.5 million), medium budget im-pact (h0.5–2 million), high budget impact(>h2 million) or unclear. These ranges wereadopted arbitrarily from a study conducted bythe SMC[14] solely for the purpose of this reviewand are not representative of any classificationused by the HSE. The budget impact estimatewas based on assumptions regarding the num-ber of eligible patients who would be prescribedthe new drug and the drug acquisition cost.

� Method of calculating budget impact. The sub-missions were categorized according to whetherthey considered the impact on the drug budgetonly or the overall healthcare budget. If limitedto a drug budget perspective, the BIA will notanswer the broader health system questionsconcerning overall healthcare spending in thecontext of cost offsets. The drug budgetperspective may include reduced utilization ofdrugs due to replacement of current treatments,potential increase in certain drugs to manageadverse effects and impact on hospital day cases(e.g. for intravenous infusions).

� Treatment replacement assumptions. The in-clusion of potential cost offsets due to pro-ducts that will be replaced by the newmedicinewas considered in the review.

� Time horizon. The time horizon for BIAswas recorded. A survey of drug plan managers



in Canada indicated that 83% of respon-dents would find a time horizon of 3–5 yearsvaluable.[15] Time horizons that go beyond a fewyears are subject to considerable assumptions.

� Sensitivity analysis. There is considerableuncertainty in a BIA. A range of results shouldbe presented based on realistic scenariosregarding inputs and assumptions.

Results

Pharmacoeconomic AssessmentsConducted by the National Centre forPharmacoeconomics (NCPE)

Twelve pharmacoeconomic assessments wereconducted between September 2006 and Feb-ruary 2009. The products in table I are listed inchronological order from the date of notificationby the HSE that a pharmacoeconomic assess-ment was required. Six of the applications wereseeking reimbursement on the GMS and DPschemes, four applications were for the HTDS,one was for a HSE clinic/community scheme (foropiate-dependent drug users) and one was ahospital-only product.

The 2006 IPHA/HSE Agreement states thatnew or existing medicines may be subject to phar-macoeconomic assessment. Therefore, the processcan be initiated at any point in a product life cycle.There is currently only one example of an existingmedicine (glucosamine) where cost-effectivenessdata were requested to ensure continued re-imbursement. The appraisal of glucosamine is on-going and has not been included in this review. Allother pharmacoeconomic evaluations were ofnewly licensed medicines prior to reimbursementor funding in the hospital setting.

NCPE Recommendations and SubsequentReimbursement Decisions

NCPE Recommendations

Two-thirds (n = 8) of the medicines assessedwere recommended for reimbursement (table II).Of these, cost effectiveness was demonstrated forfive products, namely rivaroxaban, dabigatran,ambrisentan, lapatinib and rimonabant, and theywere not subject to restrictions. One of the med-

icines (rimonabant), which was recommendedwithout restriction, was found to be cost effectiveon the GMS scheme but not on the DP scheme.Medicines reimbursed on the DP scheme aresubject to a 20% mark-up on the ingredient cost,and medicine costs can be a major driver in thecost-effectiveness analysis.

Cost effectiveness was either borderline or notdemonstrated for three medicines (sunitinib,natalizumab and nilotinib). Sunitinib was re-commended on the grounds of innovation. Na-talizumab was restricted to specialist use only andnilotinib was restricted to those patients who didnot respond to second-line dasatinib therapy.Follow-up review was recommended for twomedicines (natalizumab and lapatinib) in view ofthe high level of uncertainty demonstrated in thecost-effectiveness analysis.

Two medicines (melatonin and grass pollen al-lergy vaccine [Grazax�]) were not recommendedby the NCPE on the grounds of insufficientclinical evidence. Buprenorphine/naloxone 4 : 1(Suboxone�) was not found to be cost effectivecompared with methadone in the maintenanceof opiate addiction. Cost effectiveness of chon-droitin sulfate was not demonstrated.

Summary of Reimbursement Decisions by theHealth Service Executive

In summary, six medicines were reimbursedon the Community Drug Schemes. A furthertwo medicines were reimbursed after a price re-vision (grass pollen allergy vaccine [Grazax�] andnilotinib). The role of the NCPE is to evaluate thecost effectiveness of new and existing technolo-gies. As part of this process, the NCPE examinethe relationship between drug price and theincremental cost-effectiveness ratio (ICER). How-ever, pharmaceutical price setting and negotia-tion is the responsibility of the HSE.

Natalizumab was restricted to prescribing byspecialists in the hospital setting in the rapidlyevolving severe multiple sclerosis subgroup only.Two medicines were not reimbursed on theCommunity Drug Schemes: chondroitin sulfateand melatonin. Finally, buprenorphine/naloxone4 : 1 (Suboxone�) was not recommended as analternative to methadone in the maintenance

312 Tilson et al.


treatment of opiate addiction and its use isrestricted to those patients for whom methadonetreatment is unsuitable.

Appeals

The pharmaceutical company has the right toappeal against the reimbursement decision. Ap-peals are heard by an expert panel, themembershipof which is agreed between the IPHA and theHSE.

There has only been one appeal for a medicine thatwas refused reimbursement to date. In this case,the cost effectiveness of chondroitin sulfate was notdemonstrated and the expert group agreed withthe NCPE recommendation and the subsequentreimbursement decision made by the HSE. Theexpert group included representatives from theDoHC, the pharmaceutical industry as well asindependent clinical experts.

Table I. Summary of pharmacoeconomic assessments from September 2006 to February 2009

Medicine (trade name,

manufacturer)

Therapeutic indication at time of evaluation Comparator Setting/drug scheme

Chondroitin sulfate

(Chondromel�, Clonmel)

This appraisal consisted of a systematic

review of the clinical evidence, which was

conducted by the NCPE

NA GMS/DP

Rimonabant (Acomplia�,

sanofi-aventis)

An adjunct to diet and exercise for treatment of

obese or overweight patients with associated

risk factor(s), such as type 2 diabetes mellitus

or dyslipidaemia

Diet and exercise alone GMS/DP

Sunitinib (Sutent�, Pfizer) Second-line treatment of patients with GIST

and mRCC

Best supportive care HTDS

Natalizumab (Tysabri�,

Biogen)

Highly active relapsing and remitting multiple

sclerosis that is (1) RES (2) SOT

Interferon b and

glatiramer acetate

Hospital only

Grass pollen allergy vaccine

(Grazax�, Menarini)

Prevention of seasonal grass pollen-induced

rhinoconjunctivitis

Symptomatic

medication against

grass pollen-induced

rhinoconjunctivitis

GMS/DP

Buprenorphine/naloxone 4 : 1(Suboxone�, Schering Plough)

Maintenance treatment of opiate addiction Methadone HSE clinics/community

scheme for opiate-

dependent drug users

Lapatinib (Tyverb�, GSK) Treatment of previously treated advanced or

metastatic HER2 positive breast cancer, in

combination with capecitabine

Weighted treatment

group including

trastuzumab (75%),

vinorelbine and

capecitabine

HTDS

Nilotinib (Tasigna�, Novartis) Treatment of chronic-phase CML in patients

for whom imatinib has failed

Dasatinib – the current

second-line treatment

HTDS

Rivaroxaban (Xarelto�, Bayer) Primary prevention of VTE after total hip and

knee replacement

Enoxaparin GMS/DP

Dabigatran (Pradaxa�,

Boehringer Ingelheim Ltd)

Primary prevention of VTE after total hip and

knee replacement

LMWH GMS/DP

Melatonin (Circadin�,

Lundbeck)

Short-term treatment of primary insomnia in

adults aged ‡55 years

Benzodiazepine and

benzodiazepine-like

drugs

GMS/DP

Ambrisentan (Volibris�, GSK) Functional class II or III PAH Bosentan and

sitaxentan

HTDS

CML = chronic myeloid leukaemia; DP =Drugs Payment; GIST = gastrointestinal stromal cell tumour; GMS =General Medical Services;

GSK =GlaxoSmithKline; HER2 =human epidermal growth factor receptor 2; HSE =Health Service Executive; HTDS =High Tech Drug

Scheme; LMWH = low-molecular-weight heparin; mRCC =metastatic renal cell carcinoma; NA =not applicable; NCPE=National Centre for

Pharmacoeconomics; PAH = pulmonary arterial hypertension; RES = rapidly evolving and severe; SOT = sub-optimally treated; VTE = venousthromboembolism.



Comparison of NCPE Recommendationswith Other Jurisdictions

Of the ten appraisals conducted by the NCPE(chondroitin sulfate was excluded because aneconomic evaluation was not submitted and ri-monabant was excluded because the product waswithdrawn), NICE appraisals were completed forfive of those products (four by the STA and oneby the MTA process), SMC evaluated all tenproducts and AWMSG evaluated two products(table III).

NCPE recommendations broadly concurredwith four of five NICE appraisals, eight of tenSMC appraisals and one of the two AWMSG ap-praisals. The AWMSG and SMC did not re-commend sunitinib (Sutent�), whereas the NCPEfound that sunitinib was not cost effective but itwas recommended on the basis of innovation.[16]

Sunitinib was recommended by NICE as first-linetreatment of metastatic advanced or metastaticrenal cell carcinoma (RCC) in patients who aresuitable for immunotherapy with an Eastern Co-operative Oncology Group status of 0 or 1. Theend-of-life QALY weighting approach was adop-ted in this MTA appraisal, as well as a pricingstrategy with the first cycle of sunitinib free ofcharge to the NHS.[17] Although the SMC andAWMSG did not recommend sunitinib, their

advice is now superseded by the NICE MTA. ANICE MTA recommendation will usually super-sede that of the SMC or AWMSG where the tworecommendations conflict, as the NICE process isconsidered more robust (involving the use of anindependent cost-effectiveness model) and to re-flect a larger evidence base because it takes place ata later stage in the product life cycle.

There were different appraisal outcomes forlapatinib (Tyverb�) between the NCPE and theNICE/SMC. The base-case cost per QALY of theNCPE evaluation of lapatinib was h12 230 whenusing a weighted comparators group.[18] Theweighted comparators group assumed 45% ofpatients received a combination of vinorelbine(Navelbine�) plus trastuzumab (Herceptin�), 30%received capecitabine (Xeloda�) plus trastuzumaband 25% received capecitabine or vinorelbinemonotherapy. The NCPE recommended reim-bursement of lapatinib by the HSE. The weightedcomparators approach assumed the majority ofpatients who would qualify for lapatinib would betaking trastuzumab plus vinorelbine or capecita-bine, with only a small number treated with cape-citabine or vinorelbine monotherapy. This reflectscurrent clinical practice in Ireland. By comparison,NICE concluded that the evidence available at thetime of the appraisal did not support the use of la-patinib within its licensed indication. NICE based

Table II. Summary of National Centre for Pharmacoeconomics (NCPE) recommendations (September 2006 to February 2009)

NCPE recommendations Number of

appraisals

Number of

appeals

Recommended

Cost effective on Community Drug Schemes (lapatinib, rivaroxaban, dabigatran, ambrisentan) 4

Cost effective on the GMS scheme but uncertainty regarding cost effectiveness on the DP/LTI scheme

as a result of higher drug costs (rimonabant)

1

Cost effectiveness not demonstrated but recommended on grounds of innovation (sunitinib) 1

Recommended with restrictions

Cost effectiveness borderline or not demonstrated (natalizumab, nilotiniba) 2

Not recommended

Cost effectiveness not demonstrated (chondroitin sulfate, buprenorphine/naloxone 4 : 1b) 2 1

Insufficient clinical evidence for use (grass pollen allergy vaccinea, melatonin) 2

Total 12 1

a Reimbursed after a price reduction was negotiated.

b Restricted to those for whom methadone treatment is not suitable.

DP =Drugs Payment; GMS =General Medical Services; LTI =Long-Term Illness.

314 Tilson et al.


Table III. Summary and date of NCPE, NICE, SMC and AWMSG recommendations

Drug NCPE NICE SMC AWMG

Sunitinib (Sutent�) Not cost effective for unresectable or

metastatic GIST or advanced or metastatic

RCC; recommended for reimbursement on

basis of innovation; Oct 2006

For RCC: recommended first line for pts

with advanced or metastatic RCC, who

are suitable for immunotherapy, with an

ECOG status of 0 or 1; Mar 2009 (MTA)

For GIST: recommended for pts with

unresectable and/or metastatic GIST,

who are resistant/intolerant to imatinib;

Sept 2009 (STA)

Not recommended for advanced

or metastatic RCC; Feb and Jul

2007

Not recommended for

unresectable or metastatic GIST;

Sep 2006. The economic case

was not demonstrated

Not recommended for

advanced or metastatic

RCC; Aug 2007

Clinical and economic

data were not sufficient to

recommend its use

Not recommended for

unresectable or metastatic

GIST – a submission was

not made to AWMSG; Feb

2008

Natalizumab (Tysabri�) Recommended as cost effective from

societal perspective only; Apr 2007

Cost effective and recommended for

the RES RRMS sub-group only; Aug

2007 (STA)

Re-submission. Accepted for

restricted use in RES RRMS sub-

group only; Sep 2007

NA

Buprenorphine/naloxone4 : 1 (Suboxone�)

Not recommended as a cost-effective

intervention; available on a restricted

basis; Nov 2007

NA Accepted for restricted use for pts

in whom methadone is not

suitable and the use of

buprenorphine is considered

appropriate; Feb 2007

Recommended for

restricted use in pts who

are unsuitable for

maintenance tx with

methadone; Jun 2008

Grass pollen allergy

vaccine (Grazax�)

Not recommended as a cost-effective

intervention on the grounds of insufficient

clinical evidence; Sep 2007

NA Not recommended – insufficient

clinical evidence and economic

analysis; Apr 2007

NA

Lapatanib (Tyverb�) Recommended for advanced and

metastatic HER2 positive breast cancer

based on weighted comparator group; Jan

2008

Not recommended for routine tx of

women with previously treated

advanced or metastatic HER2 positive

breast cancer; Apr 2009 (STA)

Not recommended for advanced

or metastatic breast cancer.

Economic submission not

sufficiently robust

Justification of the tx cost in

relation to health benefits was not

sufficient; Feb 2009

NA

Nilotinib (Tasigna�) Cost effectiveness not demonstrated;

reserved for chronic-phase CML pts for

whom imatinib has failed due to resistance

or intolerance and for whom second-line

therapy with dasatinib has also failed; Feb

2008

MTA of nilotinib and dasatinib for tx of

CML. Expected date: Apr 2010

STA for first-line tx of CML

Expected date: May 2011

Accepted for restricted use in

chronic-phase CML by those

resistant or intolerant to at least

one other therapy including

imatinib; Jun 2008

NA

Rivaroxaban (Xarelto�) Recommended for prevention of VTE in

adults after total hip or knee replacement;

Sep 2008

Recommended as an option for

prevention of VTE in adults after total

hip or knee replacement; Apr 2009

(STA)

Accepted for use for prevention of

VTE in adults after total hip or

knee replacement; Dec 2008

NA

Continued next page

Pharm

acoeco

nomic

Evalu

ationin

Ireland

315

ª2010AdisData

Inform

atio

nBV.Allrig

htsrese

rved.

Pharm

acoeconomics2010;28(4)

its decision on an incremental analysis of thecomparators, as opposed to the weighted com-parator approach.[19,20]

The NCPE recommendations were reportedearlier than the AWMSG and NICE for all drugs,with the exception of dabigatran. The NICE andNCPE reports for dabigatranwere published in thesame month. Five of ten SMC appraisals were re-ported earlier than the NCPE appraisals and fourwere reported later than the NCPE. The SMCconducted two sunitinib appraisals, one for gastro-intestinal stromal cell tumour (GIST), which wasreported earlier than the NCPE and one for RCC,which was later than the NCPE (table III).

Time to Reimbursement and Duration of thePharmacoeconomic Appraisal Process

Time to Reimbursement

Eight of the medicines subjected to a phar-macoeconomic assessment were reimbursed onthe Community Drug Schemes. The average timeto reimbursement for the eight medicines was6.1months (range 2–16months; median 5.5months;interquartile range [IQR] 3.75, 6.25 months). Theanomaly associated with the short turnaroundfor one particular medicine was as a result of thecompany submitting the cost-effectiveness ana-lysis 4 months prior to the granting of the MA.The NCPE report was submitted to the productcommittee of the HSE during the same monththat the MA was granted. In contrast, the phar-macoeconomic evaluation for a similar medicinewas submitted to the NCPE 4 months after thefirst MA was granted, resulting in a considerablylonger time to reimbursement.

Duration of Pharmacoeconomic Process

Eleven pharmacoeconomic assessments weresubmitted to the NCPE. The average duration ofthe pharmacoeconomic process was 2.7 months(range 1–6 months; median 2 months; IQR 1.75,4 months) including the time for the company tomake amendments to their submission.

Critical Appraisal of Company Submissions

The Review Group of the NCPE assess thecompany submissions using the systematicT

able

III.Contd

Drug

NCPE

NICE

SMC

AWMG

Dabigatran(Pradaxa�)

RecommendedforpreventionofVTEin

adultsaftertotalh

iporkneereplacement

surgery;Sep2008

Reco

mmendedasanoptionfor

preve

ntionofVTEinadults

aftertotalhip

orkn

eereplace

ment;Sep2008(STA)

Acceptedforuseforpreventionof

VTEin

adultsaftertotalhip

or

kneereplacement;Jun2008

NA

Melatonin

(Circadin

�)

Notrecommendedfortheshort-term

txof

primary

insomnia

inadultsaged‡5

5years

ongroundsofinsufficientevidence;Oct

2008

NA

Nosubmission–not

recommended;Aug2008

NA

Ambrisentan(Volibris�)

Recommendedforthetx

offunctional

classIIorIIIPAH;Feb2009

Drugsfortx

ofPAH(M

TA);date

tobe

confirm

ed

Restrictedto

prescribingby

specialists

inpts

withfunctional

classIIandIIIPAH;Nov2008

NA

AWMSG=AllWalesMedicinesStrategyGroup;CML=chronic

myeloid

leukaemia;ECOG=Eastern

CooperativeOncologyGroup;GIST=gastrointestinalstromalcelltumour;

HER2=humanepiderm

algrowth

factorreceptor2;MTA=multiple

technologyappraisal;NA=notassessed;NCPE=NationalCentreforPharm

acoeconomics;NICE=National

Institute

forHealthandClinicalExcellence;PAH=pulm

onary

arterialhypertension;pt=patient;RCC=renalcellcarcinoma;RES=rapidly

evolvingsevere;RRMS=relapsing

remittingmultiple

sclerosis;SMC=ScottishMedicinesConsortium;STA=single

technologyappraisal;tx

=treatm

ent;VTE=venousthromboembolism.

316 Tilson et al.


application of a ten-point checklist. It is un-realistic to expect every submission to satisfy allten points; however, the systematic application ofthese points allows the Review Group to assessthe strengths and weaknesses of individual studies.The NCPE recommend that the submissionsinclude Irish epidemiological, resource use, unitcost and utility data. In the absence of Irish data,the use of data from other jurisdictions (e.g. fromthe UK) should be clearly documented and jus-tified and an attempt should be made to quantifythe likely consequences of such an approachusing sensitivity analysis. The following are someof the common issues that are raised during thecritical appraisal:� Inappropriate comparator – the chosen com-

parator should reflect current best clinicalpractice in Ireland.

� Failure to include all available evidence – theassessment of the evidence of safety and efficacyshould be based on a systematic, reproducible,transparent, unbiased approach for the technol-ogies being compared. In addition, health utilityvalues obtained from the literature should bederived from a transparent, systematic search.

� Lack of transparency in summarizing theevidence – the methods used to analyse orcombine data should be clearly outlined andjustified, with the data provided in bothaggregated and disaggregated form.

� Assumptions that are not credible – forexample, extrapolation of effects beyond theend of a clinical trial require additional data(e.g. from long-term observational studies)and may also depend on several assumptions.There may be no unambiguous way to makesuch extrapolations, but it is expected that themethods and assumptions used should beconservative and transparent.

� Inappropriate cost data – for example, notallowing for wastage in drug cost calculationsor not including the most recent appropriateprice for the comparator drug. Currently,there are no agreed Irish cost models availableand it is acknowledged that there is a need tobe flexible regarding cost valuation. Wherepossible, it is preferred that Irish unit cost dataare used from sources including DRG data for

hospital admissions and data from localhospital finance departments.

� Inadequate sensitivity analysis – justificationfor the choice of variables and the plausibleranges, over which they are varied, is sought. Itis difficult to specify firm guidelines on whichparameters should be included in the sensitiv-ity analysis, beyond the fact that all variables,in principle, are potential candidates. TheReview Group routinely requests that a moreextensive sensitivity analysis is undertaken.Furthermore, an appropriate form of sensitiv-ity analysis should be used, e.g. probabilisticsensitivity analysis.

Budget Impact Analysis (BIA)

Of the 12 pharmacoeconomic assessmentssubmitted, four of the earlier submissions lackedany form of BIA, and a further two were excludedon the basis of insufficient information, allowingsix BIAs for review. The target populations in-cluded in the submissions represented all thoseeligible for treatment. The source and transpar-ency of data presented varied between submis-sions. In the absence of Irish epidemiologicaldata, non-Irish sources were frequently included,as well as estimates from the literature and as-sumptions based on expert opinion. The uptakerate of the new medicine was usually based on noparticular rationale and it is acknowledged thatthere are major challenges in anticipating theuptake rate of any new medicine.

The comparator included in the BIA should bethe same as the comparator included in the eco-nomic evaluation, i.e. current standard of care. Aforecasted version of the current market (includ-ing post-patent price cuts if necessary) should becompared with the forecasted version of themarket if the new product is reimbursed. This wasnot always clearly presented in the BIAs sub-mitted. Only one of the BIAs accounted for post-patent price cuts in the forecasted version of thecurrent market.

Five of the six products reviewed were esti-mated to incur a high budget impact, i.e.>h2 million by year 5 (year 3 for rimonabant), theexception being melatonin. These five BIAs were



each undertaken from the drug budget perspec-tive. The submission for melatonin includedboth a drug budget and a wider health serviceperspective, and estimated the potential costoffsets to the health service from nocturnalfalls that could be avoided. One of the BIAs didnot account for the reduction in costs associatedwith product replacement and this was deemedappropriate as the comparator was diet andexercise, which was consistent with the cost-effectiveness evaluation of this medicine.

A 5-year time horizon was adopted for allsubmissions, with the exception of rimonabant,which included a 3-year timeframe. Sensitivityanalyses included in the BIAs were basic and onlyone of the submissions included a series of de-terministic one-way sensitivity analyses, wherethe uptake rate was varied –20%, the cost of thedrug was varied according to the reimbursementschemes (e.g. GMS vs DP scheme) and the po-tential health service cost offsets were also varied.The sensitivity analyses for the other submissionswere limited to one alternative scenario analysis;for example, alternative comparators, or uptakerates or different drug reimbursement schemes(GMS vs DP).

Discussion

The 2006 IPHA/HSE Agreement representeda major change in the reimbursement of medi-cines in Ireland, as it allowed decision makers torequest and use evidence of the cost effectivenessof a new medicine in the reimbursement decision.

Reimbursement Decisions

One of the implications of using cost-effec-tiveness data in the decision-making process isthat there is a threshold ratio above which an inter-vention would not be considered cost effective.In practice, there is no fixed cost-effectivenessthreshold in Ireland above which an interventionwould not be considered cost effective, or belowwhich it would. Cost effectiveness is only onefactor that is considered in the decision-makingprocess. If a technology has an ICER that issignificantly higher than other technologies that

have been funded or reimbursed, other factorsneed to be taken into consideration. Sunitinib,for example, had an ICER of h57 280 per QALYand was funded on the basis of its innovativenature. Moreover, an ICER below that at whichmost interventions are funded is not a guaranteefor reimbursement, as demonstrated by the recentexample of the Health Technology Assessment ofthe human papillomavirus (HPV) vaccine.[21,22]

The ICER of vaccinating all 12-year-old girls wash17 383 per life-year gained (LYG), with thecost of the HPV vaccine plus administrationcosts in the first year of vaccination estimatedat h9.7 million. The corresponding figures forvaccinating 12-year-old girls plus catch-up to15-year-old girls resulted in an ICERof h52968 perLYG and a budget impact of h38.9 million in thefirst year of vaccination. Vaccination of 12-year-oldgirls was approved and the catch-up programmerejected. The introduction of the HPV vaccina-tion programme for all 12-year-old girls wassubsequently delayed, indicating that whilst theICER of a technology is an important consi-deration, budget impact may have a greater in-fluence over reimbursement and implementationdecisions.

The following factors also impact on theNCPE recommendation, in addition to estimatedcost effectiveness:� the level of uncertainty associated with the

clinical and cost-effectiveness information;� budgetary considerations (and constraints)

and the opportunity costs of investing in aparticular intervention;

� the particular features of the condition and thepopulation receiving the technology;

� the innovative nature of the technology;� the lack of, or inadequacy of, alternative

treatment options;� the wider societal costs and benefits.

Comparison of NCPE Recommendationswith Other Jurisdictions

The recommendations for the majority ofappraisals were broadly consistent betweenthe NCPE and other UK agencies, with theexceptions of lapatinib and sunitinib. Overall,

318 Tilson et al.


the NCPE recommendations were published inadvance of those of the NICE and AWMSGand half of the SMC appraisals. This could bebecause there is a time lag for technologies to bereferred to NICE and, in the case of Scotland, thereimbursement application to theHSEmay occurearlier in Ireland, thus triggering a more rapidinitiation of the process.

In this review we restricted our comparison tothe UK agencies and we did not explore the ap-propriateness of the recommendations made byeach agency. We did not compare the consistencyof implementation of recommendations of thedifferent bodies or their role in informing pricesetting directly or with more sophisticated ap-proaches (e.g. risk-sharing agreements). Futureresearch could compare and contrast the systemsof pharmacoeconomic appraisal and the outcomesof assessments, followed by an assessment of bestpractices among different international agencies.

Duration of the Pharmacoeconomic Process

The time from granting of the first MA to re-imbursement is variable across EU member statesand, traditionally, there has been only a short delayto reimbursement in Ireland. The 2006 IPHA/HSEAgreement confirms that new medicines, includingnew preparations and applications, granted anMA in Ireland will become reimbursable underthe Community Drug Schemes within 60 daysfrom the date of reimbursement application.Where a pharmacoeconomic assessment is re-quested, the 60-day rule does not apply. Accordingto the Agreement, the pharmacoeconomic processshould be completed within a 90-day period. Thisis an important component of the Agreement forthe pharmaceutical industry in terms of ensuringthat speed to market is maintained. It was notpossible to establish the true duration of the phar-macoeconomic appraisal process by the NCPE, asthe time for the company to make amendments totheir original submissions was included in thisestimate. The average duration of the pharmacoe-conomic process, including the time for the com-panies to make amendments to their submissions,was <90 days.

Pharmacoeconomic Evaluation of ExistingTechnologies

The 2006 IPHA/HSE agreement allows for newor existing technologies to be subjected to phar-macoeconomic assessment. All medicines includedin this review were deemed ‘new’ medicines, whichwere identified for pharmacoeconomic assessmentby the HSE at the time of reimbursement applica-tion. Glucosamine represents the first existingmedicine selected for pharmacoeconomic assess-ment, subsequent to reimbursement already beinggranted. It has been suggested that more focusshould be applied to identifying topics for potentialdisinvestment, so that ineffective and inefficientproducts and practices do not remain in the healthsystem and to free up resources for new innovativemedicines.[23]

The data required to ascertain the clinical andcost effectiveness of an intervention can fre-quently only be determined after practical appli-cation in the market. This is particularly true fornovel products undergoing a rapid assessmentprocess similar to the process at the NCPE. Onoccasion, the NCPE has strongly recommendedthat follow-up appraisals are conducted for par-ticular medicines in view of the uncertainty of theevidence at the time of the initial pharmacoeco-nomic assessment.

It is important to highlight that, to date,medicines that have undergone the review processmay obtain a widening of their licensed indica-tions. It is recommended that the cost effective-ness of these medicines and the associated budgetimpact should be re-evaluated for any new li-censed indications. Sunitinib, for example, iscurrently being investigated for a range of otherconditions, including breast and colorectal cancer(in addition to GIST and metastatic RCC). Riv-aroxaban and dabigatran are being investigatedfor atrial fibrillation and acute coronary syn-drome indications (an extension from their ve-nous thromboembolism indication). There is alsoa possibility that medicines that were not initiallyselected for pharmacoeconomic assessmentmay incur a high budget impact in the futurebecause of expanding indications. This maytrigger a pharmacoeconomic evaluation after



reimbursement has already been granted. A pro-cess of re-evaluation of pharmacoeconomic assess-ments would ensure the accuracy of assessmentsis maintained in the future. However, in practice,it is important that such re-evaluations do notlead to inefficiency, additional resource burdenand delayed access to treatments.

BIA

The potential budget impact of a new tech-nology is an important factor in the decision-making process. It is anticipated that BIAs willbecome increasingly important in the future dueto the constraints on resources. Although af-fordability is not a consideration in informingdecisions about cost effectiveness of medicines, itis a factor that is considered in the reimbursementdecision and in the decision to select a medicinefor pharmacoeconomic assessment.

This review highlighted that the BIAs are oftenbased on multiple assumptions that are madewithin the context of an unpredictable clinicaland financial environment. There are significantchallenges in estimating product uptake rate andthis is often based on no particular rationale.Prevalence and incidence data are often lackingin the Irish setting. Exploration of general trendsin drug utilization on the Community DrugSchemes and in the hospital setting could helpsupport improved techniques for estimatingbudget impact.

There are many factors that may influence theactual budget impact of a new medicine. For ex-ample, new safety information may affect pro-duct uptake rate. Restrictions in prescribing mayhave an impact on the BIA and this may not bereflected in the company submissions. Otherfactors that potentially influence uptake includethe potential for off-label use and future new in-dications. Future research should investigatewhether the estimated budget impact correlateswith actual expenditure. At the time of this re-view, it was too early to establish the true uptakeof many of the medicines that were subject topharmacoeconomic assessment.

There are a number of assumptions in BIAsthat are subject to uncertainty, particularly pre-

dictions of future practice after a new medicine isreimbursed. The International Society forPharmacoeconomics and Outcomes Research(ISPOR) principles for good practice for BIArecommend that a deterministic sensitivity ana-lysis should be reported.[24] It recommends that aseries of scenario analyses should be presented inthe same way that sensitivity analyses would beprovided for a cost-effectiveness analysis. Giventhe uncertainty associated with the data includedin BIAs, there should be a minimum requirementto include the uptake rate, number of eligiblepatients and treatment costs in a deterministicsensitivity analysis.

The potential budget impact can differ when itis viewed from different perspectives. The ma-jority of BIAs submitted to the NCPE were un-dertaken from the drug budget perspective.However, recommendations for the perspectiveof BIAs vary between settings. The ISPOR prin-ciples for good practice for BIA recommends thehealth service perspective, whereas the Canadianguidelines state the drug budget perspective.[15,24]

The development of guidance on requirementsfor BIAs would improve the consistency of datareceived from manufacturers and increase thevalue of this component of the submission. Astandard reporting format for BIAs would beof benefit to the pharmaceutical companiespreparing these reports and for the HSE in plan-ning their budgets. Our findings are consistentwith those of Orlewska[25] who reported thatmany published BIAs included in their reviewfailed to reach the desired quality. They recom-mend use of good research practice principles,as well as promotion of standardization andtransparency.

Conclusions

The 2006 IPHA/HSE Agreement represented amajor change in the method of reimbursement ofpharmaceuticals in Ireland. It allowed the HSE,for the first time, to request and use evidence ofcost effectiveness of medicines in the reimburse-ment decision. The majority of medicines thatwere subject to pharmacoeconomic assessmentby the NCPE were either recommended for

320 Tilson et al.


reimbursement or recommended with certainrestrictions.

It is anticipated that Ireland will continue toreward innovation in the pharmaceutical in-dustry and maintain speed to market access. Theaverage duration of the pharmacoeconomic pro-cess was 2.7 months, which is less than the 90-daytime limit specified in the IPHA/HSE agreement.Furthermore, these estimates include the timetaken by the company to make amendments tothe original submission, which is not included inthe 90-day time limit.

The review of the BIAs highlights the varia-bility of data included in the submissions. Thedevelopment of guidance for conducting BIAs, aswell as a standard reporting format, would be ofbenefit to pharmaceutical companies preparingthese estimates and lead to greater transparencyand reliability for the HSE in planning theirbudgets.

The NCPE recommendations were broadlysimilar to those of the other UK agencies. Fur-ther research on assessment of best practicesamong different international agencies would bevaluable.

In the future, there will be an ongoing demandto demonstrate value for money and it is expectedthat there will be an increase in pharmacoeco-nomic assessments of both new and existingtechnologies in Ireland.

Acknowledgements

No sources of funding were used to assist in the prepara-tion of this study. The authors have no conflicts of interestthat are directly relevant to the content of this study.

References1. Central Statistics Office. Census 2006: principal demo-

graphic results [online]. Available from URL: http://www.cso.ie/census/documents/Amended%20Final%20Principal%20Demographic%20Results%202006.pdf [Accessed 2009Nov 30]

2. Primary Care Reimbursement Service. Statistical analysis ofclaims and payments 2007. Finglas: Health Services Execu-tive [online]. Available from URL: http://www.hse.ie/eng/Staff/PCRS/PCRS_Publications/2007_Report.pdf [Accessed2009 Nov 30]

3. Tilson L, Usher C, Butler K, et al. Economic evaluation of auniversal childhood pneumococcal conjugate vaccinationstrategy in Ireland. Value Health 2008; 11: 898-903

4. Barry M, Heerey A. Cost-effectiveness of statins for thesecondary prevention of coronary heart disease in Ireland.Ir Med J 2002; 95: 133-5

5. Walshe V, Nash A, Barry M. Cost effectiveness of statintherapy for the primary prevention of coronary heartdisease. Ir Med J 2006; 99: 144-5

6. Barry M, Molloy D, Usher C, et al. Drug expenditure inIreland 1997-2007. Ir Med J 2008; 101: 299-302

7. Barry M, Tilson L. Recent developments in pricing and re-imbursement of medicines in Ireland. Expert Rev Pharmaco-economics Outcomes Res 2007; 76: 605-11

8. Agreement between the Irish Pharmaceutical HealthcareAssociation and the Health Services Executive on the sup-ply terms, conditions and prices of medicines supplied tothe health services September 2006 [online]. Available fromURL: http://www.hse.ie/eng/About_the_HSE/Whos_Who/IPHA_Agreement_2006.pdf [Accessed 2009 Mar 1]

9. National Centre for Pharmacoeconomics. Irish healthcaretechnology assessment guidelines 2000 [online]. Availablefrom URL: http://www.ncpe.ie [Accessed 2009 Mar 1]

10. Drummond M, Sculpher M, Torrance G, et al. Critical as-sessment of economic evaluation. In: Drummond M,Sculpher M, Torrance G, et al. Methods for the economicevaluation of health care programmes. 3rd ed. Oxford:Oxford Medical Publications, 2005: 27-53

11. Office of Fair Trading. Annexe B: review of NICE, SMC,and AWMSG, Feb 2007 [online]. Available from URL:http://www.oft.gov.uk/shared_oft/reports/comp_policy/oft885b.pdf [Accessed 2009 Apr 15]

12. DrummondM, Sorenson C. Nasty or nice? A perspective onthe use of health technology assessment in the UnitedKingdom. Value Health 2009; 12: S8-13

13. Irish Medicines Board [online]. Available from URL: http://www.imb.ie [Accessed 2009 Nov 30]

14. Scottish Medicines Consortium Evaluation Project Team.An evaluation of manufacturers’ budget impact estimateswith resource use over time in NHS Scotland 2008 [online].Available from URL: http://www.scottishmedicines.org[Accessed 2009 Mar 1]

15. Marshall D, Douglas P, DrummondM, et al. Guidelines forconducting pharmaceutical budget impact analyses forsubmission to public drug plans in Canada. Pharmacoe-conomics 2008; 26 (6): 477-95

16. National Centre for Pharmacoeconomics. A review of thecost-effectiveness of sunitinib under the High Tech DrugScheme in Ireland, October 2006 [online]. Available fromURL: http://www.ncpe.ie [Accessed 2009 Mar 26]

17. National Institute for Health and Clinical Excellence. Suni-tinib for the first line treatment of advanced and/or meta-static renal cell carcinoma, March 2009. NICE technologyappraisal guidance 169 [online]. Available from URL:http://www.nice.org.uk/nicemedia/pdf/TA169Guidance.pdf[Accessed 2009 Apr 15]

18. National Centre for Pharmacoeconomics. Cost effectivenessof lapatinib (Tyverb) for the treatment of women withpreviously treated advanced or metastatic HER2 posi-tive breast cancer, January 2008 [online]. Available fromURL: http://www.ncpe.ie/u_docs/doc_137.pdf [Accessed2009 Apr 15]



19. National Institute for Health and Clinical Excellence. La-patinib for the treatment of women with previously treatedadvanced or metastatic breast cancer: final appraisal de-termination, February 2009 [online]. Available from URL:http://www.nice.org.uk/nicemedia/pdf/BreastCancerLapatinibFAD.pdf [Accessed 2009 Jun 29]

20. National Institute for Health and Clinical Excellence. Breastcancer (advanced or metastatic): lapatinib appeal decision,July 2009 [online]. Available fromURL: http://www.nice.org.uk/guidance/index.jsp?action=download&o=44808 [Accessed2009 Nov 30]

21. Health Information and Quality Authority. Health Tech-nology Assessment of the role of human papillomavirusvaccines in reducing the risk of cervical cancer in Ireland2008 [online]. Available from URL: http://www.hiqa.ie[Accessed 2009 Mar 1]

22. Usher C, Tilson L, Olsen J, et al. Cost effectiveness of HPVvaccine in reducing the risk of cervical cancer in Ireland due

to HPV types 16& 18 using a transmission dynamic model.Vaccine 2008; 26: 5654-61

23. Department of Health and Children. Economies in drugusage in the Irish healthcare setting [online]. Available fromURL: http://www.dohc.ie/publications/pdf/economies_drug_usage.pdf [Accessed 2009 Jun 29]

24. Mauskopf J, Sullivan S, Annemans L, et al. Principles ofgood practice for budget impact analysis: report of theISPOR Task Force on good research practices – budgetimpact analysis. Value Health 2007; 10: 336-47

25. Orlewska E. Budget-impact analyses: a critical review ofpublished studies. Pharmacoeconomics 2009; 27 (10): 807-27

Correspondence: Dr Lesley Tilson, National Centrefor Pharmacoeconomics, St James’s Hospital, James’s St,Dublin 8, Ireland.E-mail: [email protected]

322 Tilson et al.


pharmacoeconomic evaluation in ireland

Documents