aalborg universitet effect of nurse-led medication reviews ... · dan greenberg, phd ben-gurion...

Aalborg Universitet

Effect of nurse-led medication reviews - an interventional study

Sørensen, Ann Lykkegaard; Poulsen, Birgitte Klindt; Nielsen, Lars Peter; Lisby, Marianne;Mainz, JanPublished in:Value in Health

Publication date:2013

Document VersionEarly version, also known as pre-print

Link to publication from Aalborg University

Citation for published version (APA):Sørensen, A. L., Poulsen, B. K., Nielsen, L. P., Lisby, M., & Mainz, J. (2013). Effect of nurse-led medicationreviews - an interventional study. Value in Health, 16(7), A554. [PMH72].

General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright ownersand it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.

? Users may download and print one copy of any publication from the public portal for the purpose of private study or research. ? You may not further distribute the material or use it for any profit-making activity or commercial gain ? You may freely distribute the URL identifying the publication in the public portal ?

Take down policyIf you believe that this document breaches copyright please contact us at [email protected] providing details, and we will remove access tothe work immediately and investigate your claim.

Downloaded from vbn.aau.dk on: September 08, 2020

https://vbn.aau.dk/en/publications/06be0404-2fdc-4666-a4c7-27a9d8ef85fb

VALU

E IN H

EALTH

VO

LUM

E 16 N

UM

BER

7 N

OVEM

BER

20

13

PA

GES A

323

– A73

6

ELSEVIER

IN HEALTH

Volume 16 Number 7 November 2013 ISSN 1098-3015

www.ispor.org

ISPOR 16th Annual European Congress November 2-6, 2013, Dublin, Ireland

ISPOR 4th Latin America Conference September 12-14, 2013, Buenos Aires, Argentina

Research Podium AbstractsResearch Poster Abstracts

EDITORIAL BOARD

Co-Editor-in-ChiefMichael Drummond, PhDUniversity of YorkHeslington, York, [email protected]

Co-Editor-in-ChiefC. Daniel Mullins, PhDUniversity of MarylandBaltimore, MD, [email protected]

Maiwenn Al, PhDiMTA - Erasmus University RotterdamRotterdam, The [email protected]

Chris Bingefors, PhD, MScUppsala UniversityUppsala, [email protected]

Joshua Cohen, PhDTufts CSDDBoston, MA, [email protected]

Jalpa Doshi, PhDUniversity of PennsylvaniaPhiladelphia, PA, [email protected]

Sheri Fehnel, PhD, MARTI Health SolutionsResearch Triangle Park, NC, [email protected]

Alex Z. Fu, PhDGeorgetown UniversityWashington, DC, [email protected]

Benjamin P. Geisler, MD, MPHHealth Care Value StrategiesSomerville, MA, [email protected]

Ron Goeree, MAPATH Research Institute, McMaster UniversityHamilton, ON, [email protected]

Dan Greenberg, PhDBen-Gurion University of the NegevBeer-Sheva, [email protected]

Teresa Kauf, PhDUniversity of FloridaGainesville, FL, [email protected]

Andrew Lloyd, DPhil, BScOxford Outcomes, Ltd.Oxford, [email protected]

Andrea Manca, PhD, MScUniversity of YorkYork, [email protected]

Paul Scuffham, PhD, BAGriffi th University - School of MedicineQueensland, Australiap.scuffham@griffi th.edu.au

Ya-Chen (Tina) Shih, PhD, MSUniversity of ChicagoChicago, IL, [email protected]

Ulla S. Skjoldborg, PhD, MANovo Nordisk A/SCopenhagen, [email protected]

David Veenstra, PhD, PharmDUniversity of WashingtonSeattle, WA, [email protected]

Allan Wailoo, PhD, BSc, MAUniversity of Sheffi eldSheffi eld, UKA.J.Wailoo@sheffi eld.ac.uk

EDITORIAL ADVISORY BOARDAlan Brennan, PhDUniversity of Sheffi eldSheffi eld, UKA.Brennan@sheffi eld.ac.uk

Andrew Briggs, DPhilUniversity of GlasgowGlasgow, [email protected]

John Hornberger, MD, MSCedar Associates, LLCMenlo Park, CA, [email protected]

Don Husereau, MSc, BScUniversity of OttawaOttawa, ON, [email protected]

Pablo Lapuerta, MDLexicon PharmaceuticalsPrinceton, NJ, [email protected]

Adrian Levy, PhDDalhousie UniversityHalifax, NS, [email protected]

Richard J. Milne, PhDUniversity of AucklandAuckland, New [email protected]

Peter Neumann, ScDTufts University School of Medicine,Boston, MA, [email protected]

Chris L. Pashos, PhDUnited BioSource CorporationLexington, MA, [email protected]

Shelby Reed, PhD, RPHDuke Clinical Research InstituteDurham, NC, [email protected]

Uwe Seibert, MD, MPH, MSc, ScDUniversity of Health Sciences,Medical Informatics & TechnologyHall i.T., [email protected]

Johan L. (Hans) Severens, PhDErasmus UniversityRotterdam, The [email protected]

Sean Sullivan, PhDUniversity of WashingtonSeattle, WA, [email protected]

Milton C. Weinstein, PhDHarvard School of Public HealthBoston, MA, [email protected]

MANAGEMENT ADVISORY BOARDJan Busschbach, PhD (Chair)Erasmus UniversityRotterdam, [email protected]

Maarten J. IJzerman, PhDUniversity of TwenteEnschede, The Netherlands [email protected]

Donald Patrick, PhD, MSPHUniversity of WashingtonSeattle, WA, [email protected]

EDITORIAL OFFICEManaging EditorStephen L. PrioriISPORLawrenceville, NJ, [email protected]

Editorial AssistantDanielle MrozISPORLawrenceville, NJ, [email protected]

CO-EDITORS

VOLUME 16 NUMBER 7 NOVEMBER 2013

ISPOR 16TH ANNUAL EUROPEAN CONGRESS RESEARCH ABSTRACTS

Research Podium Presentations – Session IA323 Health Care Expenditure or Reimbursement Studies – Biologics: BI1–BI4A323 Cancer Outcomes Research Studies: CA1–CA4A324 Conceptual Papers: CP1–CP4A325 Research on Methods – Modeling Studies: MO1–MO4A326 Patient Preference Studies: PP1–PP4

Research Podium Presentations – Session IIA326 Research on Methods – Clinical Studies: CL1–CL4A327 Cardiovascular Disease Outcomes Research Studies: CV1–CV4A328 Medical Device & Diagnostic Research: MD1–MD4A329 Pricing Studies: PR1–PR4A329 Research on Methods – PRO/QOL Studies: QL1–QL4

Research Poster Presentations – Session IDisease–Specifi c Studies

A330 Individual’s Health – Clinical Outcomes Studies: PIH1–PIH6A331 Individual’s Health – Cost Studies: PIH7–PIH29A335 Individual’s Health – Patient-Reported Outcomes & Patient Preference Studies: PIH30–PIH51A339 Individual’s Health – Health Care Use & Policy Studies: PIH52–PIH62A340 Infection – Clinical Outcomes Studies: PIN1–PIN16A343 Infection – Cost Studies: PIN17–PIN112A361 Infection – Patient-Reported Outcomes & Patient Preference Studies: PIN113–PIN126A363 Infection – Health Care Use & Policy Studies: PIN127–PIN140A366 Respiratory-Related Disorders – Clinical Outcomes Studies: PRS1–PRS11A368 Respiratory-Related Disorders – Cost Studies: PRS12–PRS42A373 Respiratory-Related Disorders – Patient-Reported Outcomes & Patient Preference Studies: PRS43–PRS56A376 Respiratory-Related Disorders – Health Care Use & Policy Studies: PRS57–PRS64A377 Systemic Disorders/Conditions – Clinical Outcomes Studies: PSY1–PSY6A378 Systemic Disorders/Conditions – Cost Studies: PSY7–PSY50A386 Systemic Disorders/Conditions – Patient-Reported Outcomes & Patient Preference Studies: PSY51–PSY63A388 Systemic Disorders/Conditions – Health Care Use & Policy Studies: PSY64–PSY81

Research Poster Presentations – Session IIDisease–Specifi c Studies

A392 Cancer – Clinical Outcomes Studies: PCN1–PCN37A398 Cancer – Cost Studies: PCN38–PCN148A418 Cancer – Patient-Reported Outcomes & Patient Preference Studies: PCN149–PCN173A423 Cancer – Health Care Use & Policy Studies: PCN174–PCN221A431 Diabetes/Endocrine Disorders – Clinical Outcomes Studies: PDB1–PDB23A435 Diabetes/Endocrine Disorders – Cost Studies: PDB24–PDB72A444 Diabetes/Endocrine Disorders – Patient-Reported Outcomes & Patient Preference Studies: PDB73–PDB103A449 Diabetes/Endocrine Disorders – Health Care Use & Policy Studies: PDB105–PDB128

Research Poster Presentations – Session IIIHealth Care Use & Policy Studies

A453 Health Care Use & Policy Studies – Consumer Role in Health Care: PHP1–PHP5A454 Health Care Use & Policy Studies – Diagnosis Related group: PHP6

VALUE IN HEALTH 16 (2013)

A455 Health Care Use & Policy Studies – Drug/Device/Diagnostic Use & Policy: PHP8–PHP50A462 Health Care Use & Policy Studies – Equity and Access: PHP51–PHP62A464 Health Care Use & Policy Studies – Formulary Development: PHP63–PHP64A464 Health Care Use & Policy Studies – Health Care Costs & Management: PHP65–PHP143A477 Health Care Use & Policy Studies – Health Care Research & Education: PHP144–PHP158A479 Health Care Use & Policy Studies – Health Technology Assessment Programs: PHP159–PHP190A485 Health Care Use & Policy Studies – Population Health: PHP191A485 Health Care Use & Policy Studies – Prescribing Behavior & Treatment Guidelines: PHP192–PHP195A486 Health Care Use & Policy Studies – Quality of Care: PHP197A486 Health Care Use & Policy Studies – Regulation of Health Care Sector: PHP198–PHP205A487 Health Care Use & Policy Studies – Risk Sharing/Performance-Based Agreements: PHP206–PHP210A488 Health Care Use & Policy Studies – Conceptual Papers: PHP211–PHP235

Disease–Specifi c StudiesA492 Gastrointestinal Disorders – Clinical Outcomes Studies: PGI1–PGI10A494 Gastrointestinal Disorders – Cost Studies: PGI11–PGI38A499 Gastrointestinal Disorders – Patient-Reported Outcomes & Patient Preference Studies: PGI39–PGI45A500 Gastrointestinal Disorders – Health Care Use & Policy Studies: PGI46–PGI51A501 Sensory Systems Disorders – Clinical Outcomes Studies: PSS1–PSS8A503 Sensory Systems Disorders – Cost Studies: PSS9–PSS35A508 Sensory Systems Disorders – Patient-Reported Outcomes & Patient Preference Studies: PSS36–PSS47A510 Sensory Systems Disorders – Health Care Use & Policy Studies: PSS48–PSS58

Research Poster Presentations – Session IVDisease–Specifi c Studies

A512 Cardiovascular Disorders – Clinical Outcomes Studies: PCV1–PCV34A518 Cardiovascular Disorders – Cost Studies: PCV35–PCV115A532 Cardiovascular Disorders – Patient-Reported Outcomes & Patient Preference Studies: PCV116–PCV142A536 Cardiovascular Disorders – Health Care Use & Policy Studies: PCV143–PCV168A541 Mental Health – Clinical Outcomes Studies: PMH1–PMH17A544 Mental Health – Cost Studies: PMH18–PMH47A550 Mental Health – Patient-Reported Outcomes & Patient Preference Studies: PMH48–PMH56A551 Mental Health – Health Care Use & Policy Studies: PMH57–PMH73A554 Muscular-Skeletal Disorders – Clinical Outcomes Studies: PMS1–PMS20A558 Muscular-Skeletal Disorders – Cost Studies: PMS21–PMS70A567 Muscular-Skeletal Disorders – Patient-Reported Outcomes & Patient Preference Studies: PMS71–PMS89A571 Muscular-Skeletal Disorders – Health Care Use & Policy Studies: PMS90–PMS109

Research Poster Presentations – Session VResearch on Methods Studies

A574 Research on Methods – Clinical Outcomes Methods: PRM1–PRM18A578 Research on Methods – Cost Methods: PRM19–PRM39A581 Research on Methods – Databases & Management Methods: PRM40–PRM59A585 Research on Methods – Modeling Methods: PRM60–PRM113A595 Research on Methods – Patient-Reported Outcomes Studies: PRM114–PRM186A608 Research on Methods – Statistical Methods: PRM187–PRM208A612 Research on Methods – Study Design: PRM209–PRM217A613 Research on Methods – Conceptual Papers: PRM218–PRM243

Disease–Specifi c StudiesA618 Neurological Disorders – Clinical Outcomes Studies: PND1–PND12A620 Neurological Disorders – Cost Studies: PND13–PND37A624 Neurological Disorders – Patient-Reported Outcomes & Patient Preference Studies: PND38–PND53A627 Neurological Disorders – Health Care Use & Policy Studies: PND54–PND66A630 Urinary/Kidney Disorders – Clinical Outcomes Studies: PUK1–PUK4A631 Urinary/Kidney Disorders – Cost Studies: PUK5–PUK24


A634 Urinary/Kidney Disorders – Patient-Reported Outcomes & Patient Preference Studies: PUK25–PUK32A635 Urinary/Kidney Disorders – Health Care Use & Policy Studies: PUK33–PUK36

Research Poster Presentations – Session IDisease-Specifi c Studies (contd.)

A636 Individual’s Health--Cost Studies: PIH16

A637 ISPOR 16TH ANNUAL EUROPEAN CONGRESS DISCLOSURE INFORMATION

A649 ISPOR 16TH ANNUAL EUROPEAN CONGRESS RESEARCH ABSTRACTS AUTHOR INDEX

ISPOR 4TH LATIN AMERICA CONFERENCE RESEARCH ABSTRACTS

Research Podium Presentations – Session IA665 Budget Impact Studies: BU1–BU4A665 Cardiovascular Disease Outcomes Research: CV1–CV4A666 Health Care Expenditure Studies: HC1–HC4A667 Health Technology Assesment Studies: HT1–HT4A668 Infectious Disease Studies: IN1–IN4

Research Podium Presentations – Session IIA668 Cancer Outcomes Research: CA1–CA4A669 Formulary Development and Publication of Cost Studies: FD1–FD3A670 Pricing Studies: PR1–PR4A670 Cost, Risk Factor & Universal Coverage Studies: RF1–RF4A671 Trends in Health Care Studies: TR1–TR4

Research Poster Presentations – Session IHealth Care Use & Policy Studies

A672 Health Care Use & Policy Studies – Consumer Role in Health Care: PHP1A672 Health Care Use & Policy Studies – Drug/Device/Diagnostic Use & Policy: PHP2–PHP9A673 Health Care Use & Policy Studies – Equity and Access: PHP10–PH15A674 Health Care Use & Policy Studies – Formulary Development: PHP16A674 Health Care Use & Policy Studies – Health Care Costs & Management: PHP17–PHP42A678 Health Care Use & Policy Studies – Health Care Research & Education: PHP43–PHP46A679 Health Care Use & Policy Studies – Health Technology Assessment Programs: PHP47–PHP49A679 Health Care Use & Policy Studies – Patient Registries & Post-Marketing Studies: PHP51A679 Health Care Use & Policy Studies – Population Health: PHP52A680 Health Care Use & Policy Studies – Quality of Care: PHP53–PHP55A680 Health Care Use & Policy Studies – Regulation of Health Care Sector: PHP56–PHP62A681 Health Care Use & Policy Studies – Conceptual Papers: PHP63–PHP68

Disease-Specifi c StudiesA682 Cancer – Clinical Outcomes Studies: PCN1–PCN5A683 Cancer – Cost Studies: PCN6–PCN24A686 Cancer – Health Care Use & Policy Studies: PCN25–PCN30A687 Diabetes/Endocrine Disorders – Clinical Outcomes Studies: PDB1A688 Diabetes/Endocrine Disorders – Cost Studies: PDB2–PDB20A688 Diabetes/Endocrine Disorders - Patient-Reported Outcomes & Patient Preference Studies: PDB21–PDB22A691 Diabetes/Endocrine Disorders – Health Care Use & Policy Studies: PDB23–PDB26A692 Gastrointestinal Disorders – Clinical Outcomes Studies: PGI1A692 Gastrointestinal Disorders – Cost Studies: PGI2–PGI7A693 Gastrointestinal Disorders – Patient-Reported Outcomes & Patient Preference Studies: PGI8A693 Gastrointestinal Disorders – Health Care Use & Policy Studies: PGI9A693 Mental Health – Clinical Outcomes Studies: PMH1–PMH5A694 Mental Health – Cost Studies: PMH6–PMH9A695 Mental Health – Patient-Reported Outcomes & Patient Preference Studies: PMH10A695 Mental Health – Health Care Use & Policy Studies: PMH11–PMH14


A696 Sensory Systems Disorders – Clinical Outcomes Studies: PSS1A696 Sensory Systems Disorders – Cost Studies: PSS2–PSS7A697 Urinary/Kidney Disorders – Clinical Outcomes Studies: PUK1–PUK2A697 Urinary/Kidney Disorders – Cost Studies: PUK3–PUK13A699 Urinary/Kidney Disorders – Patient-Reported Outcomes & Patient Preference Studies: PUK14–PUK15

Research Poster Presentations – Session IIResearch on Methods

A699 Research on Methods – Clinical Outcomes Methods: PRM1A699 Research on Methods – Cost Methods: PRM3–PRM4A700 Research on Methods – Databases & Management Methods: PRM5–PRM8A700 Research on Methods – Modeling Methods: PRM9–PRM10A701 Research on Methods – Patient-Reported Outcomes Studies: PRM11A701 Research on Methods – Statistical Methods: PRM12–PRM14A701 Research on Methods – Study Design: PRM15A702 Research on Methods – Conceptual Papers: PRM16

Disease-Specifi c StudiesA702 Cardiovascular Disorders – Clinical Outcomes Studies: PCV1–PCV12A704 Cardiovascular Disorders – Cost Studies: PCV13–PCV30A707 Cardiovascular Disorders – Patient-Reported Outcomes & Patient Preference Studies: PCV31–PCV32A707 Cardiovascular Disorders – Health Care Use & Policy Studies: PCV33–PCV40A708 Individual’s Health – Clinical Outcomes Studies: PIH1–PIH4A709 Individual’s Health – Cost Studies: PIH5–PIH11A710 Individual’s Health – Patient-Reported Outcomes & Patient Preference Studies: PIH12–PIH17A711 Individual’s Health – Health Care Use & Policy Studies: PIH18–PIH19A712 Infection – Clinical Outcomes Studies: PIN1–PIN3A712 Infection – Cost Studies: PIN4–PIN19A715 Infection – Health Care Use & Policy Studies: PIN20A715 Muscular-Skeletal Disorders – Clinical Outcomes Studies: PMS1A715 Muscular-Skeletal Disorders – Cost Studies: PMS2–PMS18A718 Muscular-Skeletal Disorders – Patient-Reported Outcomes & Patient Preference Studies: PMS19–PMS20A719 Muscular-Skeletal Disorders – Health Care Use & Policy Studies: PMS21–PMS25A720 Neurological Disorders – Clinical Outcomes Studies: PND1–PND2A720 Neurological Disorders – Cost Studies: PND3–PND13A722 Neurological Disorders – Patient-Reported Outcomes & Patient Preference Studies: PND14–PND16A722 Neurological Disorders – Health Care Use & Policy Studies: PND17A723 Respiratory-Related Disorders – Clinical Outcomes Studies: PRS2–PRS3A723 Respiratory-Related Disorders – Cost Studies: PRS4–PRS11A724 Respiratory-Related Disorders – Health Care Use & Policy Studies: PRS12–PRS15A725 Systemic Disorders/Conditions – Clinical Outcomes Studies: PSY1–PSY4A726 Systemic Disorders/Conditions – Cost Studies: PSY5–PSY11A727 Systemic Disorders/Conditions – Patient-Reported Outcomes & Patient Preference Studies: PSY12–PSY13A727 Systemic Disorders/Conditions – Health Care Use & Policy Studies: PSY14–PSY18

A729 ISPOR 4TH LATIN AMERICA CONFERENCE DISCLOSURE INFORMATION

A732 ISPOR 4TH LATIN AMERICA CONFERENCE RESEARCH ABSTRACTS AUTHOR INDEX

Editorial Offi ce. Value in Health, ISPOR, 505 Lawrence Square Blvd. South, Lawrenceville, NJ 08648.

ISPOR Offi ce. Marilyn Dix Smith, RPh, PhD, Executive Director, 505 Lawrence Square Blvd. South, Lawrenceville, NJ 08648. Tel: (609) 586-4981, Fax: (609) 586-4982, E-mail: [email protected], Web site: http://www.ispor.org/valueinhealth_index.asp.

CUSTOMER SERVICE (orders, claims, online, change of address): ElsevierHealth Sciences Division, Subscription Customer Service, 3251 Riverport Lane,Maryland Heights, MO 63043. Tel: (800) 654-2452 (U.S. and Canada); (314)447-8871 (outside U.S. and Canada). Fax: (314) 447-8029. E-mail:[email protected] (for print support);[email protected] (for online support). Address changesmust be submitted four weeks in advance.

YEARLY SUBSCRIPTION RATES: United States and possessions: Individual$276.00; Institution $599.00. All other countries (prices include airspeeddelivery): Individual $276.00; Institution $599.00. To receive student/resident rate, orders must be accompanied by name of affi liated institution, date of term and the signature of program/residency coordinator on institution letterhead. Orders will be billed at the individual rate until proof of status is received. Current prices are in effect for back volumes and back issues.

Further information on this journal is available from the Publisher or from thisjournal’s website (http://www.elsevier.com/locate/jval). Information on otherElsevier products is available through Elsevier’s website (http://www.elsevier.com).

Author inquiriesFor inquiries relating to the submission of articles (including electronicsubmission where available), visit http:/www.elsevier.com/authors. The site alsoprovides the facility to track accepted articles and set up e-mail alerts to informyou of when an article’s status has changed, as well as detailed artwork guidelines, copyright information, frequently asked questions, and more. Pleasesee Information for Authors for individual journal. Contact details for questionsarising after acceptance of an article, especially those relating to proofs, areprovided after registration of an article for publication.

English language help service: Upon request, Elsevier will direct authors toan agent who can check and improve the English of their paper (before submission). Please contact [email protected] for further information.

Reprints. For queries about author offprints, e-mail [email protected]. To order 100 or more reprints for educational, commercial, orpromotional use, contact the Commercial Reprints Department, Elsevier Inc.,360 Park Avenue South, New York, NY 10010-1710. Fax: (212) 462-1935; [email protected]. Reprints of single articles available online may beobtained by purchasing Pay-Per-View access for $31.50 per article on the journalwebsite http://www.elsevier.com/locate/jval.

Copyright © 2013, International Society for Pharmacoeconomics and OutcomesResearch (ISPOR). Published by Elsevier Inc.

This journal and the individual contributions contained in it are protected undercopyright by International Society for Pharmacoeconomics and Outcomes

Research, and the following terms and conditions apply to their use:PhotocopyingSingle photocopies of single articles may be made for personal use as allowedby national copyright laws. Permission of the Publisher and payment of a fee isrequired for all other photocopying, including multiple or systematic copying,copying for advertising or promotional purposes, resale, and all forms ofdocument delivery. Special rates are available for educational institutions thatwish to make photocopies for non-profi t educational classroom use.Permissions may be sought directly from Elsevier’s Rights Department inOxford, UK: phone +44 (0) 1865 843830, fax +44 (0) 1865 853333. Requests may also be completed online via the Elsevier homepage (http://www.elsevier.com/authors/obtaining-permission-to-re-use-elsevier-material).In the USA, users may clear permissions and make payments through the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, USA; phone: (978) 750-8400, fax: (978) 750-4744, and in the UK through the Copyright Licensing Agency Rapid Clearance Service (CLARCS), 90 Tottenham Court Road, London W1P 0LP, UK; phone: (+44) 20 7631 5555; fax: (+44) 20 7631 5500. Other countries may have a local reprographic rights agency for payments.Derivative WorksSubscribers may reproduce tables of contents or prepare lists of articlesincluding abstracts for internal circulation within their institutions. Permission ofthe Publisher is required for resale or distribution outside the institution.Permission of the Publisher is required for all other derivative works, includingcompilations and translations.Electronic Storage or UsagePermission of the Publisher is required to store or use electronically anymaterial contained in this journal, including any article or part of an article.Except as outlined above, no part of this publication may be reproduced, storedin a retrieval system or transmitted in any form or by any means, electronic,mechanical, photocopying, recording or otherwise, without prior writtenpermission of the Publisher.Address permissions requests to: Elsevier Rights Department, at the fax ande-mail addresses noted above.Abstracting and IndexingValue in Health is indexed in Index Medicus/MEDLINE, Current Contents/Social &Behavioral Sciences, SciSearch/SCI Expanded, Social Sciences Citation Index,International Pharmaceutical Abstracts, Embase/Excerpta Medica, SciVerseScopus and PsychInfo/Psychological Abstracts, and Journal Citation Reports/Science Edition (Thomson ISI).NoticeNo responsibility is assumed by the Publisher or the International Society forPharmacoeconomics and Outcomes Research for any injury and/or damage topersons or property as a matter of products liability, negligence or otherwise,or from any use or operation of any methods, products, instructions or ideascontained in the material herein. Because of rapid advances in the medicalsciences, in particular, independent verifi cation of diagnoses and drug dosagesshould be made.Although all advertising material is expected to conform to ethical (medical)standards, inclusion in this publication does not constitute a guarantee orendorsement of the quality or value of such product or of the claims made of itby its manufacturer.

VA L U E I N H E A LT H 1 6 ( 2 0 1 3 ) A 3 2 3 – A 6 3 6

Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

Avai lable onl ine at www.sc iencedirect .com

journal homepage: www.elsevier .com/ locate / jva l

ISPOR 16TH ANNUAL EUROPEAN CONGRESS RESEARCH ABSTRACTS

RESEARCH PODIUM PRESENTATIONS – SESSION I HEALTH CARE ExPENDITURE OR REIMBURSEMENT STUDIES – BIOLOGICS

BI1ADHERENCE AND RESOURCE USE AMONG PATIENTS TREATED wITH BIOLOGICS. FINDINGS FROM THE BEETLE STUDy (BIOLOGICAL DRUGS: EvALUATION OF ECONOMICS, TREATMENTS, AND LABELING IN REAL-wORLD SETTING)Degli Esposti L., Sangiorgi D., Buda S.CliCon Srl, Ravenna, ItalyObjectives: Systemic administration of anti-TNF alpha leads to an anti-inflamma-tory and joint protective effect in pathologies such as rheumatoid arthritis, psoriasis, Crohn’s disease. The aim of this study was to assess adherence to therapy and stay on treatment (no switches or interruptions) of patients treated with biologics accord-ing to therapeutic indication and to calculate health care resources consumption (drugs, outpatient services, hospitalizations). MethOds: An observational retrospec-tive cohort analysis based on 5 Local Health Units administrative databases was conducted. Patients who filled at least one prescription for anti-TNF alpha between January 1, 2009-December 31, 2011 were included. Patients were followed-up for one year. Patients were defined as adherent if they had > 80% of follow up period covered by drugs dispensation. Results: A total of 1219 patients were analyzed, 47% male, age 49.6±14.6. Patients affected by rheumatoid arthritis were 36%, psoriasis 31%, Crohn’s disease 10%, psoriatic arthritis 7%, ulcerative colitis 3%, ankylosing spon-dylitis 3%, diagnosis not available 11%; 420 (34%) were treated with Adalimumab, 615 (50%) Etanercept, 184 (15%) Infliximab. Among the 94% of patients who did not switch, patients treated with Infliximab seemed to have the highest rate of adherent patients across all indications: 51%, vs. 27% Etanercept and 23% Adalimumab; at the multivariable logistic regression model, Infliximab resulted a protective predictor of non adherence for all indications (OR ranged from 0.08 to 0.43). For patients who started a first-line biological drug, stay on treatment was 73% for Infliximab, 67% Etanercept, 64% Adalimumab. The mean annual expenditure for each patient in analy-sis was € 11,120; in particular, non-pharmacological expenditure was € 988 for adherent and € 1,255 for non-adherent patients; at the multivariable generalized linear model, Infliximab was associated with the lowest cost for all indications. cOnclusiOns: Patients treated with Infliximab were associated to higher adherence and stay on treatment and lower costs, as compared to Adalimumab and Etanercept.

BI2wHAT ARE THE KEy DRIvERS OF REIMBURSEMENT FOR BIOSIMILARS? AN ExAMINATION OF REIMBURSEMENT PROCESSES AND RECOMMENDATIONS ACROSS NINE COUNTRIESde Silva S.U., Smith T.A., Bending M.W.Mapi, London, UKObjectives: Biosimilars are biotherapeutic products that are similar in terms of quality, safety and efficacy to an already licensed reference biotherapeutic product. The first biosimilar (Omnitrope) received EU regulatory approval in 2006; since then, 14 biosimilars have received marketing authorisation. This study examined the dif-ferences in the approaches to reimbursement of biosimilars in countries using HTA to inform decision-making. MethOds: Four biosimilar medicines were selected to provide sufficient documentation in seven European countries, South Korea and Australia. Regulatory approval and HTA reimbursement decision documents were identified and a qualitative analysis of the processes, recommendations by indica-tion, evidence and key decision drivers was undertaken to explain differences in recommendations across countries. Results: Twenty-one different indications were appraised; 90% of appraisals were ‘recommended’, 9% ‘recommended with restrictions’, and 1% were ‘not recommended’. The Netherlands and Germany accepted ‘clinical comparability’ to the originator as sufficient evidence for auto-matic reimbursement. Sweden and France were the only countries to appraise and to recommend for all indications. Scotland and Wales recommended all biosimilars but restricted indications in some cases. Agencies accepted the notion of clinical comparability and extrapolation across indications when appraising the evidence. A cost-minimisation analysis and budget impact analysis were key economic decision drivers. A full cost-effectiveness analysis was only requested by NICE. Other factors influential in recommending reimbursement were: lobbying, dual reimbursement processes, and other reimbursement mechanisms. cOnclusiOns: As the market for biosimilars continues to grow, it is imperative that specific HTA reimbursement processes are developed for assessing biosimilars. This includes further research on how different drug classes should be considered; especially pertinent due to the increase in biosimilars for monoclonal antibody-based drugs, which differ from the

ABSTRACTS

product classes (erythropoietin, white blood cell stimulators, growth hormone and insulins) currently dominating the market.

BI3DIFFERENCES IN APPROACH TO BIOSIMILARS: NICE vERSUS SMC RECOMMENDATIONSIzmirlieva M., Ando G.IHS, London, UKObjectives: Several biosimilar products have been approved for marketing in the European Union, but their market penetration remains slow. Lack of clear reimburse-ment guidance could be one of the reasons for this slow penetration. This study exam-ines how many, if any, biosimilar products have been assessed in the UK by NICE and by the SMC and to what extent recommendations by the two HTA organisations are consistent. MethOds: Secondary research was conducted, including a review of all NICE and SMC final guidance and of guidance in progress by NICE to compare the HTA process outcome and issues raised by the two HTA agencies. Results: NICE has issued only one final guidance for a biosimilar product (Omnitrope) and has another guid-ance in progress (for epoetin including biosimilars). The SMC has issued guidance for 4 biosimilar versions of filgrastim (Ratiograstim, TevaGrastim, Zarzio and Nivestim), 2 biosimilar versions of epoetin (Binocrit and Retacrit) and 1 version of somatropin (Omnitrope). All SMC guidance for biosimilars issued to date has been positive. The NICE guidance for Omnitrope is positive despite some reservations about the economic model. cOnclusiOns: Considering the limited overlap between NICE and SMC deci-sions (only one drug - Omnitrope - was considered by both agencies), it is difficult to assess consistency in the SMC approach compared to NICE’s approach at this stage. Based on the biosimilars HTA guidance by NICE and the SMC to date, a cost-minimisa-tion analysis may be acceptable for biosimilars even if such an approach - in the absence of a full cost-effectiveness model - might be rejected for an originator product. Both HTA agencies recommend that prescribing for biosimilars should be by brand name to avoid automatic substitution in the pharmacy.

BI4IMPACT OF ExCLUSIvE HOSPITAL DISTRIBUTION OF BIOSIMILAR ON DRUG HEALTH CARE BUDGETRémuzat C.1, Vataire A.L.2, Cetinsoy L.2, Aballea S.1, Toumi M.31Creativ-Ceutical, Paris, France, 2Creativ-Ceutical, PARIS, France, 3University Claude Bernard Lyon 1, Lyon, FranceObjectives: There is an increased trend in shifting biologics distribution to exclu-sive hospital pharmacy channel. Although it looks obvious that such process will generate savings through tenders at regional or national level such policy conse-quences were not clearly quantified. We used a model developed for EU commission to assess the consequences of such policies on biosimilars for selected EU countries (model developed for the European Commission for the project”EU Pharmaceutical expenditure forecast” http://ec.europa.eu/health/healthcare/key_documents/index.en.htm). MethOds: We built a model to assess policy scenarios impact on pharma-ceuticals reference forecast for seven EU Member States (France, the UK, Germany, Poland, Portugal, Greece and Hungary). We tested the impact of shifting biosimilar distribution to hospital channel on pharmaceutical industry revenue, Health insurers budget and society cost. Results: For the period 2012-2016 the savings of biosimilars (based in million Euros) for Health insurance will be for: UK 2,023; GE 1,127; FR 1,634; PL 200; GR 19; PO 272; HU 29. The extra savings by shifting of the biosimilars distribution to exclusive hospital pharmacy will be: for UK 353; GE 3,392; FR 1,684; PL 37; GR 206; PO 65; HU 176. The difference is relatively small for UK, although significant. However, it is considerable for Germany and France (around 3 and 2 time original saving). Similar fig-ures (revenue loss) are seen for pharmaceutical companies. cOnclusiOns: Although the impact of such policy varies from one country to one another based on initial pro-portion of biosimilar distributed through hospital and level of discount over branded products, this policy appears to have a substantial impact on drug expenditures and might contribute to sustainability of health insurance in EU countries. Germany and France might benefit dramatically from such policy.

CANCER OUTCOMES RESEARCH STUDIES

CA1RESPONSIvENESS OF THE EQ-5D IN ONCOLOGy: A META-ANALySISSmith A.B.1, Cocks K.1, Taylor M.2, Parry D.31University of York, York, UK, 2York Health Economics Consortium, York, UK, 3AstraZeneca UK, Macclesfield, UKObjectives: The EQ-5D is often employed in clinical trials to derive quality-adjusted life years for cost-utility analyses, and in comparisons of health-related quality of life across conditions. However, there are concerns that the EQ-5D is less

http://www.sciencedirect.comhttp://www.elsevier.com/locate/jval

A324 VA L U E I N H E A LT H 1 6 ( 2 0 1 3 ) A 3 2 3 – A 6 3 6

Objectives: To assess the economic burden of cancer by estimating years of poten-tial productive life lost (YPPLL) and costs of lost productivity due to premature can-cer-related mortality across Europe. MethOds: We derived the number of cancer deaths by sex for 23 of the most common cancer sites in 30 European countries from GLOBOCAN. YPPLL were calculated by multiplying the number of cancer-specific deaths for each productive age group (15-64) by standard life expectancy at the mid-point for each age group. Using the human capital approach, we multiplied standardised YPPLL for each individual by country- age- and gender-specific annual wages from age of death until retirement following adjustments for labour force participation and unemployment. Costs were expressed in 2008€ . Results: All cancer sites combined generated a total of € 150.9 billion in premature mortality costs in Europe in 2008. Western Europe accounted for almost half of the total, followed by Northern (21%), Southern (21%) and Central & Eastern Europe (9%). Findings contrasted with YPPLL where Central & Eastern Europe had the highest burden. Male costs exceeded female costs by 88% in Europe as a whole (male: € 98.4 billion; female: € 52.5 billion) and across all European regions. Lung was the most expensive site (€ 34.7 billion; 23% of total costs), followed by breast cancer (€ 13.6 billion, 9%), colorectal cancer (€ 12.1 billion, 8%), brain & CNS (€ 9.1 billion, 6%) and pancreatic cancer (€ 7.5 billion, 5%). According to premature mortality cost per death, testicular cancer was the most expensive site (€ 2.5 million per death), followed by brain & CNS cancer (€ 481,512) and Hodgkin lymphoma (€ 474,559). cOnclusiOns: Lost productivity costs due to cancer-related premature mortality are significant in Europe. Productivity costs provide an alternative perspective on the cancer burden on society and may inform cancer control policy decisions.

CONCEPTUAL PAPERS

CP1INCREMENTAL COST PER QUALITy-ADjUSTED LIFE yEAR GAINED? THE NEED FOR ALTERNATIvE METHODS TO EvALUATE MEDICAL INTERvENTIONS FOR ULTRA-RARE DISORDERSSchlander M.1, Garattini S.2, Kolominsky-Rabas P.3, Nord E.4, Persson U.5, Postma M.6, Richardson J.7, Simoens S.8, Sola Morales O.9, Tolley K.10, Toumi M.111University of Heidelberg, Wiesbaden, Germany, 2Mario Negri Institute for Pharmacological Research, Milano, Italy, 3University of Erlangen-Nuremberg, Erlangen, Germany, 4Norwegian Institute of Public Health, Oslo, Norway, 5The Swedish Institute for Health Economics, Lund, Sweden, 6Unit of PharmacoEpidemiology & PharmacoEconomics (PE2), Department of Pharmacy, University of Groningen, Groningen, The Netherlands, 7Monash University, Melbourne, Australia, 8KU Leuven, Leuven, Belgium, 9HITT, Barcelona, Spain, 10Tolley Health Economics, Buxton, UK, 11University Claude Bernard Lyon 1, Lyon, FranceObjectives: To critically appraise the problems posed by the systematic valua-tion of interventions for ultra-rare disorders using conventional health economic analysis methods. MethOds: An international group of clinical and health eco-nomic experts met in conjunction with the Annual European ISPOR Congress in Berlin/Germany, November 2012, to identify and deliberate underlying issues openly, adhering to the Chatham House rule. Results: The group reached a broad consen-sus, including: The complexities of research and development new treatments for ultra-rare disorders (URDs) may require conditional approval and reimbursement policies, such as coverage with evidence development agreements, but should not be used as a justification for showing surrogate endpoint improvement only. As a prerequisite for value assessment, demonstration of a minimum significant clinical benefit should be expected within a reasonable timeframe. Regarding the economic evaluation of interventions for URDs, the currently prevailing logic of cost effective-ness (using benchmarks for the maximum allowable incremental cost per quality-adjusted year, QALY, gained) was considered inappropriate since it does not capture well-established social preferences regarding health care resource allocation. Such social preferences include, but are not limited to, a priority for care for the worse of (related to initial health state), for those with more urgent conditions (the so called “rule of rescue”), a relatively lower priority based upon capacity to benefit, and a dislike against “all or nothing” resource allocation decisions that might deprive certain groups of patients from any chance to access effective care. cOnclusiOns: Alternative paradigms to establish the “value for money” conferred by interventions for URDs should be developed with high priority. Such methods should capture and reflect prominent societal value judgments, beyond efficiency as conventionally defined by QALY maximization under a budget constraint.

CP2THE MULTIMODEL ENSEMBLE APPROACH TO REDUCING STRUCTURAL UNCERTAINTy IN DECISION ANALyTICAL MODELLINGParham P.E.1, Hughes D.A.21Bangor University, Gwynedd, UK, 2Bangor University, Bangor, UKDecision analytical modelling represents an essential tool for undertaking health economic evaluation. Markov models provide a mathematical framework for such analyses, particularly in the context of assessing the cost-effectiveness of treat-ments for chronic diseases where economic outcomes are typically extrapolated beyond the duration of clinical trials. However, structural uncertainty is a key chal-lenge, to methodologists and decision makers alike, that has hitherto attracted insufficient attention. Best practice guidelines advocate the testing of structural assumptions through alternative modelling approaches or conducting scenario analyses. It should be recognised, however, that structural differences in model design represent a strength, rather than limitation, of the modelling process and in fields such as climate modelling, multi-model comparisons and ensemble pre-dictions have been used extensively as the basis for more robust policy decisions. Methods for combining models represents an emerging field in climate modelling, but the simplest approach is to treat all models equally and the mean of all model predictions has been shown to improve on the ‘best’ model predictions in numerous studies. A weighted multi-model approach may also be developed, but this remains an area of ongoing debate. To date, health economists have not fully embraced the potential of the multi-model paradigm to reduce structural uncertainty. In this work,

responsive to change particularly in oncology. Therefore the objective of this study was to determine the level of responsiveness of the EQ-5D in oncology. MethOds: A systematic review identified relevant articles reviewing responsiveness of the EQ-5D in adults (EMBASE, Medline). Effects sizes (ES) were calculated for the studies identified where not already reported. A meta-analysis was undertaken of the effect sizes: homogeneity of variance was assessed (fixed effects) and random effects models applied where there was significant heterogeneity. Responsiveness was also compared for improvement/deterioration in health status. Analyses were conducted in SPSS v18. Results: Data were available from 12 studies (3 breast, 2 prostate, as well as ovarian, lung and renal cancers) each with EQ-5D data at a minimum of 2 time points leading to a total of 45 entries. The overall unweighted ES was -0.26 (95%CI: -0.31 to -0.21), however there was significant heterogeneity in terms of effect sizes (Q(44) = 427.00, p< 0.001) which was accounted for using the random effects model (Q(44) = 39.58, p> 0.05). The overall weighted effect size (ES) was -0.17 (95%CI: -0.33 to -0.01). The weighted ES for improvement was 0.08 (95%CI: -0.02 to 0.18), and -0.52 (95%CI: -0.64 to -0.41) for deterioration. cOnclusiOns: There is considerable heterogeneity in the reported effect size of the EQ-5D. Responsiveness of the EQ-5D in oncology trials as measured by effect sizes is modest at best. The instrument appears to be more sensitive to deterioration in health status than to improvements. Further work will explore the ES of the EQ-5d in comparison with responsiveness of disease-specific measures and changes in health status.

CA2THE BURDEN OF CAREGIvING IN CANCER: THE STATUS OF CLINICAL RESEARCHFoster R.E., Bardos J.I., Wilson T.J., Hamerslag L., Kusel J.Costello Medical Consulting Ltd., Cambridge, UKObjectives: The responsibility of caring for cancer patients, often suffering from a magnitude of health problems, can result in a considerable burden for their caregiv-ers, both physically and psychologically. The objective of this study was to assess the status and extent of clinical research into the burden of caregiving for cancer patients. MethOds: ClinicalTrials.gov was searched for all cancer trials that con-sidered caregiver burden, using a matrix of search terms such as ‘carer’, ‘burden of care’ or ‘caregiver’. The impact of geographical location or cancer type on the pro-portion of trials assessing caregiver burden, the outcome measures used and the proportion of trials including caregiver burden as an outcome over time were inves-tigated. Results: From a total of 36,184 cancer-focused trials documented world-wide, 1,596 (4%) assessed caregiver burden. Outcome measures included caregiver quality of life (QoL), satisfaction with care and mood states. The impact of caregiver burden in cancer trials within different world regions varied, with the highest pro-portion of trials that considered caregiver burden located in Mexico (23%) and Asia (14-22%). Trials for five major cancer types (breast, lung, prostate, colorectal, liver) assessed caregiver burden at similar frequency (4-5%). Evaluation of completed tri-als demonstrated that the proportion of cancer trials considering caregiver burden increased from < 1% between 1997-2001 to 7% after 2012. cOnclusiOns: Fewer than 5% of all cancer trials documented worldwide have evaluated the impact of caregiver burden, although geographical variation does exist. The equal assess-ment of caregiver burden across cancer types may suggest that no single cancer type is considered to have a higher degree of caregiver burden. Interestingly, while the number of total cancer trials evaluating caregiver burden documented to date is relatively low, the incidence has increased over the last 15 years, suggesting that the growing importance of caregiver burden is being recognised.

CA3EMA APPROvAL OF DRUGS ON THE BASIS OF PIvOTAL NON-COMPARATIvE PHASE II TRIAL DATAMacaulay R.HERON Health, London, UKObjectives: The recent European Medicines Agency (EMA) approval of crizotinib has highlighted the potential for regulatory approval to be gained on the basis of pivotal non-comparative Phase II data. This research aims to determine the circumstances under which the EMA will approve submissions on this basis. MethOds: All publicly available European Public Assessment Reports (EPARs) were screened up to June 2013. Submissions that were based on pivotal Phase II data were identified and the acceptance decision, disease, and level of benefit were extracted. Results: Eight drugs (bevacizumab, bort-ezomib, crizotinib, dasatinib, everolimus, gefitinib, imatinib, ofatumumab) across ten indications been submitted to the EMA on the basis of pivotal non-comparative Phase II data. All submissions were for entry indications except imatinib, which was also submit-ted for two further indications on this basis. All, except crizotinib, were for indications with no alternative therapies and all were for onology indications except everolimus which was for subependymal giant cell astrocytoma (SEGA). All, except crizotinib, were EMA designated orphan medical products for these indications. One submission was rejected (bevacizumab), one was restricted (ofatumumab), and eight were approved. Top-line supportive Phase III data was only available in two submissions (crizotinib and everolimus). Overall response rates (ORRs) were the primary endpoints in all submis-sions except imantinib and dasatinib in leukaemia indications and everolimus in SEGA. Rejected drugs had ORRs of 47% (ofatumumab, rejected subpopulation) and 38% (beva-cizumab). Approved drugs had ORRs of 60% (crizotinib), 58% (ofatumumab, approved subpopulation), 40% (imatinib), and 35% (bortezomib). Despite low ORRs, imatinib was used to treat a disease with no licensed therapies (gastrointestinal stromal tumours), and bortezomib offered a 10% complete remission rate. cOnclusiOns: Pivotal Phase II data can support EMA approval if it demonstrates substantial clinical benefits for small patient populations with severe diseases that lack therapeutic alternatives.

CA4MEASURING THE COST OF LOST PRODUCTIvITy DUE TO PREMATURE CANCER-RELATED MORTALITy: A EUROPEAN OvERvIEwHanly P.1, Soerjomataram I.2, Sharp L.31National College of Ireland, Dublin, Ireland, 2International Agency for Research on Cancer, Lyon, Ireland, 3National Cancer Registry Ireland, Cork, Ireland

VA L U E I N H E A LT H 1 6 ( 2 0 1 3 ) A 3 2 3 – A 6 3 6 A325

administrative censoring, and data generating models. Combining the findings from our review and our simulation study, we made practical recommendations on the use of adjustment methods in HTA. Results: Our review demonstrates that adjustment methods make important limiting assumptions. Our simulation stud-ies show that the bias associated with alternative methods is highly associated with deviations from their assumptions. Our recommended analysis framework aims to help researchers find suitable adjustment methods on a case-by-case basis. The characteristics of clinical trials and the treatment switching mechanism observed within them, should be considered alongside the key assumptions of the adjustment methods. cOnclusiOns: The limitations associated with switching adjustment methods mean that different methods are appropriate in different scenarios. In some scenarios all methods may be prone to important bias. The data requirements of adjustment methods have important implications for people who design and analyse trials which allow treatment switching.

MO2USE OF REAL-wORLD EvIDENCE (RwE) TO vALIDATE A TRIAL-BASED HEALTH ECONOMIC MODELMunakata J.1, Li H.2, Luo R.3, Guo Y.3, O’Sullivan A.4, Duran A.5, Nelson M.61IMS Health, San Francisco, CA, USA, 2IMS Health, Alexandria, CA, USA, 3IMS Health, Plymouth Meeting, PA, USA, 4IMS Health, Waltham, MA, USA, 5IMS Health, London, UK, 6IMS Health, Alexandria, VA, USAObjectives: Decision makers often rely on health economic models populated with clinical trial data to inform initial assessments about treatment selection, coverage, and reimbursement. To date, there have been few (if any) published model re-analyses using real-world evidence (RWE). The purpose of this study is to 1) assess real-world health and economic outcomes associated with oral anticoagulant vs. low molecular weight heparin (LMWH) as prophylaxis for venous thromboembo-lism (VTE) in patients undergoing total hip (THR) or knee (TKR) replacement, and 2) compare results of a health economic model populated with clinical trial data vs. RWE. MethOds: Patients who underwent THR or TKR between July 2011 and June 2012 were identified in a US commercial insurance claims database. Patients were required to be continuously enrolled 3 months pre-/post-index and were excluded if treated with multiple anti-coagulants within 10 days post-index. A propensity score matching technique was employed to reduce selection bias. Patient characteristics, inpatient-related VTE events and health care costs were determined. A health eco-nomic model previously parameterized with clinical trial data was repopulated and reanalyzed using inputs derived from the claims study. Results: A total of 14,880 patients were identified (7,440 oral anticoagulant, 7,440 LMWH). In both groups, mean age was 59 and 53% were female. Compared with LMWH, oral anticoagulant use was associated with fewer symptomatic VTE events over 1-year. When repopu-lated with clinical inputs from claims data, the model projected similar VTE event differences as trial-based model (-0.023 vs. -0.015). Costs (per patient/year) in oral anticoagulant and LMWH groups were consistent across the trial-based model ($385 vs. $1,011), claims-based model ($437 vs. $1,290), and direct reported results from claims analysis ($506 vs. $1,125). cOnclusiOns: Use of RWE is a practical and objective way to validate a trial-based health economic model. Future work should consider study design issues and practical use of results.

MO3MULTI-STATE STATISTICAL MODELLING TO QUANTIFy AN INDIvIDUAL-BASED MICRO SIMULATION MODEL FOR RADIOTHERAPy TREATMENT IN LUNG CANCER PATIENTSBongers M.L.1, De Ruysscher D.2, Oberije C.3, Lambin P.3, Uyl-de Groot C.A.4, Coupe V.M.H.11VU University Medical Center, Amsterdam, The Netherlands, 2University Hospitals Leuven/KU Leuven, Leuven, Belgium, 3MAASTRO Clinic, Maastricht, The Netherlands, 4Erasmus University Rotterdam, Rotterdam, The NetherlandsObjectives: We developed an individual-based micro-simulation model for radio-therapy treatment in non small-cell lung cancer (NSCLC). The aim was to explore the suitability of multi-state statistical modelling in heath economics, as a tool to parameterize a simulation model that tracks clinical events over time, taking patient and tumour features into account. MethOds: The model contains the four clinical states ‘A: alive without local recurrence (LR) or metastasis (M)’, ‘LR’, ‘M’, and ‘Death’. Transition rates were estimated using multi-state statistical modelling, a technique that allows the simultaneous estimation of hazards for multiple transitions, taking covariates as well as the occurrence and timing of previous events into account. Each of the hazards from A to either LR, M and Death were adjusted for the presence of the other competing risks. Individual patients were simulated by repeatedly sampling a patient profile, consisting of patient and tumour characteristics. Subsequently, for each patient a pathway through the model was simulated. The internal validity of the model was verified by comparing intermediate simulation outcomes and overall survival under two different radiotherapy strategies to the original data used for estimation. Finally, the model was externally validated by comparing model outcomes to Dutch cancer registry data. Results: Model simulations for the two radiotherapy strategies demonstrated internal validity, with predicted probabilities for the occur-rence of LRs, Ms, deaths, and the occurrence of toxicities within 3 years that fell within the 95% confidence intervals of the data. The same was observed for the prediction of overall survival. Comparison of the model predictions to the Dutch cancer registry data showed a moderate fit. cOnclusiOns: Multi-state statistical modelling is a useful technique for obtaining the transition rates that are required for the quantifi-cation of a micro-simulation model. In future, our model will be used to evaluate the cost-effectiveness of individualized treatment strategies.

MO4BAyESIAN CALIBRATION METHOD TO ESTIMATE TRANSITION PROBABILITIES FOR A MARKOv MODEL BASED ON A CONTINUOUS OUTCOME MEASURE: APPLICATION IN PARKINSON’S DISEASENeine M.1, Briquet B.1, Mokdad C.E.1, Vataire A.L.2, Aballea S.11Creativ-Ceutical, Paris, France, 2Creativ-Ceutical, PARIS, France

we illustrate how this approach may be developed to a) simultaneously and system-atically compare health economic outcomes predicted by multiple Markov models; b) address the question of whether (and how) to weight different models within an ensemble based on different performance metrics and model skill scores; c) identify, quantify, and partition total uncertainty across a multi-model ensemble into different sources (for example, to highlight where future research priorities may optimally lie to further improve the robustness of policy recommendations through model improve-ment and data collection); and d) apply this approach to some real-world examples.

CP3THE GROwING ROLE OF QUALITATIvE INTERvIEwS IN HEALTH OUTCOMES RESEARCHGuillemot J.1, Gauthier A.1, Hass B.2, Basso F.3, Cognet M.11Amaris, London, UK, 2Boehringer Ingelheim GmbH, Ingelheim, Germany, 3Boehringer Ingelheim GmbH, Vienna, AustriaObjectives: Qualitative interviews, as tools for scientific evidence generation, are often excluded from consideration in health outcomes research. Lack of methodologi-cal rigour and the non-reproducibility and non-generalizability of results are often used to justify quantitative methodologies. Here we present an illustrative exam-ple of qualitative interviewing’s value within health outcomes research. In a study aiming to measure patient and physician preferences for hepatitis C treatments, a discrete choice experiment was designed and a systematic literature review was conducted. MethOds: To assess the comprehensibility and relevance of the ques-tionnaire as well as to estimate the value and preciseness of assumptions, pre-tests consisting of a questionnaire pilot followed by a semi-direct interview were con-ducted. The semi-direct interviewing followed rigorous methods, including defined themes assembled in a discussion guide and behavioural rules for the interviewer to promote axiological neutrality. Analytical methods using predefined codes for the interpretation enabled a systematic understanding of datasets. Results: The qualitative component mostly validated but sometimes challenged the theoretical assumptions of the discrete-choice experiment, which had been previously developed on the basis of the systematic literature review. Interviews shed light on occasional complexity and lack of comprehensibility of some questions. The qualitative analysis provided insights to patients’ and physicians’ experience of their treatment selection process. It included socio-psychological dispositions, like the aversion for work absen-teeism or the importance of social representation encouraging patients to prefer treat-ments which side effects would not affect their social capacities. cOnclusiOns: This method provided in-depth and structured feedback from a small group of patients and physicians. As health outcomes studies increasingly require to expand their level of detail and sensitivity by entering subjective fields of personal preferences, patients’ experiences and decision-making processes, there is a pressing need for conduct-ing qualitative micro-level studies prior to supporting broader, field-based studies.

CP4CONCEPTUAL AND PRACTICAL CONSIDERATIONS wHEN DEALING wITH MISSING UTILITy DATA IN LONGITUDINAL TRIALS, AND SUBSEQUENT USE IN COST-EFFECTIvENESS ANALySESWeston A.R.1, Brnabic A.1, Standfield L.B.21Optum, Sydney, Australia, 2Griffith University, Queensland, AustraliaPatient preference-based health-related quality of life measures (utilities) are a criti-cal input in cost-effectiveness analyses of pharmaceuticals and other health care technologies. Over recent years it has become more common for utility data to be collected alongside key clinical data within the pivotal Phase III trials. However, utility data are often not available for all patients throughout the entire course of the trial. The authors discuss the concept that there are unique characteristics of utility data that need to be considered when dealing with missing values, including the large inter-patient variability typically present at baseline. Missing data arise because i) patients become more ill and are less able to complete patient-reported instruments, ii) patients die during the course of the trial, or iii) patients are censored at later stages of the trial due to rolling recruitment. Whilst this is often a problem in oncology trials, it is also a consideration in other interventional and observational research designed to inform pharmacoeconomic evaluations. Situations where individual patient data are accessible and where only summary statistics are available are discussed. The practical considerations of how such re-analysed data should then be included within an economic model are discussed, given the manner in which utilities are incorpo-rated will vary depending on the nature of the health states used.

RESEARCH ON METHODS – MODELING STUDIES

MO1A GUIDE TO ADjUSTING SURvIvAL TIME ESTIMATES TO ACCOUNT FOR TREATMENT SwITCHING IN RANDOMISED CONTROLLED TRIALSLatimer N.R.1, Abrams K.R.2, Lambert P.C.2, Crowther M.J.2, Wailoo A.J.1, Morden J.P.3, Akehurst R.L.1, Campbell M.J.11University of Sheffield, Sheffield, UK, 2University of Leicester, Leicester, UK, 3The Institute of Cancer Research, Sutton, UKObjectives: Treatment switching is a common issue in clinical trials of cancer treatments – often patients randomised to the control group are permitted to switch onto the experimental treatment at some point during follow-up. In such circumstances an intention to treat (ITT) analysis will result in biased estimates of the overall survival advantage – and therefore the cost-effectiveness – associ-ated with the experimental treatment. Methods to adjust for switching have been used inconsistently and potentially inappropriately in health technology assess-ments (HTA). We present an analytical framework to guide analysts on the use of methods to adjust for treatment switching in the context of economic evalua-tions. MethOds: We conducted a review of methods used to adjust for treatment switching in HTA, and two rigorous simulation studies to assess the performance of adjustment methods in a range of realistic scenarios. We tested different simu-lated trial sample sizes, crossover proportions, treatment effect sizes, levels of


Intra class correlation coefficients between the countries were high: from 0.89 (England vs. US) through 0.99 (Canada vs. US). cOnclusiOns: This proof of con-cept study indicates that computer-based choice tasks for the EQ-5D-5L in the general population are feasible and parameter of the choice tasks estimates are generally consistent and logical, and the estimated values are largely consistent between the 4 countries.

PP3CAN THE USE OF SOCIAL MEDIA AND MOBILE APPS IMPROvE PATIENT KNOwLEDGE OF DISEASE AND HEALTH OUTCOMES? A SySTEMATIC REvIEwAbogunrin S., Martin A.Evidera, London, UKObjectives: The use of interactive social media (SM) based on Web 2.0 technology, e.g. Twitter, Facebook, MySpace; and mobile apps, is increasing but its role in improving patient knowledge of their disease and its management is unclear. We conducted a systematic review to assess the evidence for health benefits from SM. MethOds: We searched MEDLINE and EMBASE for relevant articles published in the last five years that used words synonymous with SM; patient, carer, or parents’ preferences, opinions or views; pharmacological interventions; and disease. We included comparative studies or systematic reviews on the use of any SM by patients, that measured differences in knowledge about disease, uptake of pharmacological interventions, or clinical outcomes from better management of disease. Articles were excluded if they reported only the use of SM by health care professionals, or if they were case studies, narrative reviews or expressed expert opinions. Results: We identified 3,232 unique abstracts, 24 of which reported the use of interactive, internet-delivered programs (n= 13), Facebook (n= 4), and mobile apps (n= 3) , for improving health outcomes of patients with cancer, or inflammatory, mental health, musculoskeletal, neurologic, ophthalmologic, or sexual health-related disorders. Patients receiving SM-based interventions showed improved knowledge of their disease, and better clinical outcomes compared with controls. Two additional studies reported on the use of SM aimed at increasing knowledge, and self-efficacy in parents of children with cystic fibrosis. Overall, the studies showed that SM-based interventions improved knowledge of disease and clinical outcomes com-pared with control groups. cOnclusiOns: Surprisingly little research has been con-ducted on the value of SM to aid and support patients. What evidence exists suggests that SM tools offer health benefits. fFrther work is needed to confirm these effects and to assess how best the tools might increase patients’ knowledge about disease, treatment adherence and clinical outcomes.

PP4THE IMPORTANCE OF PATIENT REPORTED OUTCOMES IN REIMBURSEMENT OF ORPHAN PRODUCTS IN EUROPELyons E.J.1, McGeagh J.1, Es-Skali I.J.2, Parmenter L.3, Nijhuis T.4, Boucher G.11Quintiles, Reading, UK, 2Quintiles Consulting, Hoofddorp, The Netherlands, 3Quintiles Outcome, Reading, UK, 4Quintiles, Hoofddorp, The NetherlandsObjectives: To determine the importance of patient reported outcomes (PROs) in the reimbursement of orphan drugs in Europe and identify any HTA authority preferences for particular PRO measures. MethOds: All 31 products assigned an orphan designation by the European Medicines Agency (EMA), between January 2009 and May 2013, were evaluated against the following criteria: approval for marketing, submission for reimbursement/price negotiation to NICE, SMC, G-BA, and HAS, presence or absence of PROs, approval or rejection of reimbursement application. Where available, HTA guidance documents resulting from the appli-cations were reviewed in detail to determine the impact of PRO measures on the reimbursement decision. Results: Of the 31 products assigned an orphan des-ignation, 26 were granted marketing authorisation by the EMA. Eleven products were submitted to NICE for reimbursement in England of which 7 submissions contained PROs and 6 were approved. In Scotland, 11 products were submitted for reimbursement to the SMC and of the 7 submissions containing PRO data, 3 were recommended for reimbursement. One submission is still pending. In Germany, 7 products were submitted to the G-BA of which 5 contained PROs and were allowed to enter into price negotiations. The French HTA authority, HAS, evaluated 20 sub-missions of which 9 contained PROs and 19 were approved. cOnclusiOns: The results of our assessment of EMA approved orphan drugs indicates that a great deal of variation exists across Europe with respect to the evaluation of orphan drugs for reimbursement or price negotiation. In some countries, reimbursement is largely independent of evidence of reported patient benefit while in others, where evidence of economic value is critical for success, robust PRO data are essential.

RESEARCH PODIUM PRESENTATIONS – SESSION IIRESEARCH ON METHODS – CLINICAL STUDIES

CL1A COMPARISON OF METHODOLOGIES FOR ESTIMATING SURvIvAL IN PATIENTS TREATED wITH SECOND-GENERATION TyROSINE-KINASE INHIBITORS (TKIS) FOR CHRONIC MyELOID LEUKAEMIA (CML)Pennington B.1, Batty A.J.1, Clifton-Brown E.21BresMed, Sheffield, UK, 2Pfizer Ltd., Tadworth, UKObjectives: NICE have previously recommended nilotinib, but not dasatinib, as a first-line (TA251) and second-line (TA241) treatment in chronic phase (CP) CML. Within these appraisals, different methods were used to estimate overall survival (OS). Bosutinib, a potent dual Src/Abl TKI, is undergoing a NICE appraisal in sec-ond-line or later CML (ID495). The objective is to review the OS methods used and assess their impact on cost-effectiveness and recommendations in CML apprais-als. MethOds: We identify the methodologies used for estimating OS in TA241 and TA251 and investigate the impact of using these to estimate OS for the TKIs, including bosutinib, in relapsed/refractory CML. Finally, we consider the implica-tions of the various methodologies on the cost-effectiveness results and recom-mendations in previous and future NICE assessments of TKIs for CML. Results: The base-case in TA241 used a surrogate relationship between response (MCyR) and OS

Objectives: Estimating transition probabilities for Markov models is challenging when the effectiveness of the studied intervention is measured using a continuous score, and only aggregate data by treatment are available. We developed a Bayesian calibration method to estimate transition probabilities and applied it in Parkinson’s disease (PD). MethOds: A previously published Markov model with health states corresponding to Hoehn and Yahr (H&Y) stages was adapted. Patient-level datasets were simulated to replicate results of clinical trials for different drugs, using the UPDRS scale to assess severity, and transition probabilities were estimated from simulated data to provide a reference case. Two calibrations methods were tested for obtaining transition probabilities without patient-level data. Firstly, the Solver tool of Excel was used, with the mean change in UPDRS score and associated variance as targets. Secondly, a Bayesian calibration was implemented in OpenBUGS to estimate the posterior distribution of transition probabilities, assuming the change in UPDRS score has a normal distribution, with observed mean and variance. All other model input parameters were taken from the original model. Results: With simulated patient-level data, the incremental cost (IC) was estimated at € -7,015 (95% credibility interval: € -23,953; € 5,977) and incremental QALYs (IQ) at 0.455 (0.112; 0.950). With calibration using the Solver tool, there was an infinity of solutions resulting in IC ranging from € -10,141 to € -8,206 and IQ ranging from 0.422 to 0.473. With calibra-tion using OpenBugs, the IC was estimated at € -6,852 (€ -24,244; € 6,448) and the IQ at -0.448 (0.108; 0.959). cOnclusiOns: Incremental costs and QALYs obtained using the Bayesian calibration and analysis of patient-level data were similarly distributed. Mean results obtained using the Solver tool were comparable, but no statistical distribution around results could be provided. This example suggests that the Bayesian calibration is a valid method to derive transition probabilities from continuous outcome measures.

PATIENT PREFERENCE STUDIES

PP1A METHODOLOGy FOR PREDICTING THE IMPACT OF COPAyMENTS ON THE UTILIzATION OF HEALTH TECHNOLOGIESSabatelli L.GLOB MOD, Barcelona, SpainObjectives: Copays (or copayments) for health-technologies, such as pharma-ceutical products, are used by governments and insurers to prevent moral hazard, reduce unnecessary utilization of resources, and contribute to the cost of health care. Nevertheless they may also reduce access to necessary care, and the financial protection associated with health insurance. In addition, from the perspective of the manufacturer, the introduction of copays may determine unexpected and abrupt falls in demand. The methodology here presented uses data extracted from surveys on product utilization and patient income, prior and after the introduction of copays in various countries and regions, to predict the potential impact of copays on the demand for a pharmaceutical product in a given country or region. MethOds: This approach uses multi-level multivariate regressions and a micro-economic model of demand (which assumes maximization of utility and preference independence) to anticipate changes in utilization (and therefore in demand) as a function of the amount of copay charges. Data from a computer simulation were used to test the method. Results: A non-linear relationship between copay and drug-consump-tion, determined by the combined effect of the amount charged and of the average population income was identified, predicting changes in aggregate demand and in income-specific demand. For instance: if we consider two countries both adopting a 1 Euro co-pay charge on a (not easily substitutable) product and whose average income differs by 20%, we expect the demand to be almost 3% lower in the country with the lower income than in the country with the higher income. cOnclusiOns: Under general market assumptions, it is possible to build models that estimate the potential impact of copay charges. These models can be used to help design health policies and market strategies.

PP2MULTINATIONAL CONSISTENCy OF A DISCRETE CHOICE MODEL IN QUANTIFyING HEALTH STATES FOR THE ExTENDED 5-LEvEL EQ-5DKrabbe P.F.M.1, Devlin N.J.2, Stolk E.A.3, Shah K.K.4, Oppe M.3, van Hout B.4, Quik E.H.1, Pickard A.S.5, Xie F.61University of Groningen, University Medical Center Groningen, Groningen, The Netherlands, 2Office of Health Economics, London, UK, 3Erasmus University Rotterdam, Rotterdam, The Netherlands, 4University of Sheffield, Sheffield, UK, 5University of Illinois at Chicago, Chicago, IL, USA, 6McMaster University, Hamilton, ON, CanadaObjectives: To investigate the feasibility of choice experiments for EQ-5D-5L states using computer-based data collection, and to examine the consistency of the estimated parameters values derived after modeling the stated preference data across countries in a multinational study. MethOds: Similar choice experi-ments were executed in Canada, England, The Netherlands, and United States (US). Interactive software was developed to standardize the format of the choice tasks across countries, except for England where face-to-face interviewers were used. The choice task required respondents to choose between two sub-optimal health states. A Bayesian design was used to generate 200 pairs of states that were randomly grouped into 20 blocks. Each respondent completed one block consisting of 10 pairs. A main-effect alternative-specific multinomial probit regression model was used to estimate regression coefficients and to derive values for each health state that capture the relative differences in levels between states. Results: In total there were 1775 respondents, at least 400 respondents from each country, who completed 17750 paired comparisons, resulting into 35500 assessed health states. The mean time to perform one choice task was between 29.2 (US) and 45.2 (England) seconds. All regression coefficients were statistically significant, except level 2 for Usual Activities in The Netherlands (p= 0.51). Three regression coefficients with illogical ordering were observed (The Netherlands: level 3 Pain/Discomfort, England: Level 3 Usual Activities & Pain/Discomfort). Predictions for the complete set of 3125 EQ-5D-5L states were similar for the four countries.

VA L U E I N H E A LT H 1 6 ( 2 0 1 3 ) A 3 2 3 – A 6 3 6 A327

Evaluation (GRADE) approach using the example of male human papilloma virus (HPV) vaccination Europe. MethOds: A pan-European multidisciplinary expert group was established to develop an extended GRADE framework that includes explicit assessment of cost-effectiveness, medical needs, and patient aspects, ethi-cal and social issues. Using an expert panel process, we assessed the feasibility of using this framework by applying it to male HPV vaccination in Europe. Studies were assessed using the specific framework tools; results and feasibility were discussed; and consensus was achieved through a modified Delphi method. Results: We identified three advisory committees (ACIP/USA; NACI/Canada; STIKO/Germany) using GRADE for vaccines assessment. Institutions handled data beyond vaccine efficacy and safety differently and did not formally grade economic evidence. We adopted the grading methodology of ACIP for the key factor ‘Benefits and Harms’ and developed modules for grading evidence type and quality of economic evalua-tions (‘Economic Evaluation’) and for systematically assessing epidemiology, disease burden and unmet medical needs, as well as ethical, social and patient aspects (‘Values and Preferences’). The feasibility test demonstrated that all framework components were feasible in the case of HPV vaccination. Overall evidence type for cost-effectiveness was low with uncertainty in results. Cost-effectiveness was best, when all HPV-related diseases and outcomes were included and when assum-ing low coverage in females and lower vaccine prices. cOnclusiOns: The GRADE approach is applicable in assessing vaccinations and was successfully applied to HPV vaccination in males. The assessment of benefits and harms can be extended by explicit assessment of the evidence on cost-effectiveness and other key fac-tors including unmet medical needs, and ethical, social and patient aspects. This extended framework can better inform policy- and decison makers.

CARDIOvASCULAR DISEASE OUTCOMES RESEARCH STUDIES

Cv1CHALLENGES IN MODELLING THE COST EFFECTIvENESS OF INTERvENTIONS IN CARDIOvASCULAR DISEASEBurgers L.T., Redekop W.K., Severens J.L.Erasmus University Rotterdam, Rotterdam, The NetherlandsObjectives: Modelling is essential in performing economic evaluations for various rea-sons. For example, modelling is necessary if extrapolation of short-term or intermediate results to long-term outcomes is required and numerous strategies need to be evaluated without direct evidence. However, modelling inherently poses challenges that need to be dealt with since models always represent a simplification of reality. The aim of this study is to identify and analyse the challenges in modelling the cost-effectiveness of cardiovascular disease (CVD) interventions. MethOds: A questionnaire was sent to 40 corresponding authors (systematically selected) of recent model-based economic evaluations of CVD interventions published in high-impact cardiovascular, health eco-nomics and general medical journals. Respondents were asked to provide their own challenges and also rank the importance of challenges identified using a pilot version of the questionnaire distributed to 7 experienced researchers. Furthermore, we analysed the discussion sections of the papers to identify unmentioned challenges. Solutions, if available, were based on input from the respondents and the recommendations of the ISPOR-SMDM task force. Results: The systematic literature search identified 1720 potentially relevant articles. The limit of 40 authors was reached after screening 294 titles and abstracts. Beside the challenge of lack of data, preliminary results show that it was difficult to obtain a sufficiently valid, precise and accurate cost-effectiveness estimate due, for example, to interrelating clinical outcomes or extrapolating from sur-rogate outcomes. Both challenges often exist in CEAs evaluating CVD prevention strate-gies. cOnclusiOns: The preliminary results of this study showed examples of CVD modelling challenges encountered during studies published in high-impact journals. Modelling guidelines do not provide sufficient assistance in resolving all challenges but it is probably unrealistic to expect this. Some of the reported challenges are specific to the type of intervention and disease, but most challenges are present in all types of interventions and diseases.

Cv2APPLICATION OF BEHAvIOURAL ECONOMICS TO THE UNDERSTANDING OF ADHERENCE: DOES AN INDIvIDUAL’S TIME PREFERENCE INFLUENCE ADHERENCE TO MEDICATIONS?Fargher E.A., Morrison V., Plumpton C.O., Hughes D.A.Bangor University, Bangor, UKObjectives: There is general support that individual time preference affects health-related behaviours. People with a high, positive time preference value their imme-diate health higher than future health, even if presented with extreme scenarios of intertemporal choice. We hypothesised that adherence to medication requires trade-offs between immediate and delayed health benefits. Patients with lower time preference rates may be more adherent to medication as they place a higher value on the future benefits of adherence. MethOds: Hypertensive adult patients across Europe were invited to complete a web-based survey that had been translated and piloted. Patients’ time preference was assessed (4-items) to calculate individual discount rates (%) in both short term (3-years) and medium term (6-years). Medication adherence was measured using the Morisky questionnaire (primary analysis) and the Medication Adherence Report Scale (MARS, secondary analysis). Sample size calculation, based on 5% one-sided confidence, assuming 30% non-adherence with Morisky measure indicated n= 323 per country. Missing data were imputed using multiple imputation in STATA. The significance of the association with adherence was assessed using the Wald test statistic. Results: 969 patients completed the questionnaire across England, Wales and Hungary, 79% of possible responses were observed. Short and medium term time preference rates in England, Wales and Hungary were in the expected directions, but the relationship was not statistically significant. Based on Morisky adherence - Wales (short): adherent 8.7%, non-adherent 9.4% (p= 0.541); (medium): adherent 4.7%, non-adherent 5.0% (p= 0.611). England (short): adherent 7.8%, non-adherent 9.5% (p= 0.163); (medium): adherent 3.7%, non-adherent 4.5% (p= 0.095). Hungary (short): adherent 19.0%, non-adherent 18.2% (p= 0.504); (medium): adherent 8.9%, non-adherent 8.6%

to derive OS estimates for nilotinib and dasatinib of 13.0 and 13.4 years respectively (second-line CP). Using the same approach for bosutinib gives an OS of 12.8 years (third-line CP). The base-case in TA251 used a cumulative approach, where OS is equal to the duration of treatments in the pathway. If this method is applied to the TKIs in second-line CML (TA241), OS is reduced to approximately 9.4 and 10.1 years for nilotinib and dasatinib respectively (second-line CP). Similarly, bosutinib OS (third-line CP) is also reduced using this method and a substantial increase in the ICER is seen. cOnclusiOns: There are methodological inconsistencies in NICE’s assessments of TKIs for CML. Applying the OS methodology from TA251 to TA241 may have led to nilotinib not being recommended for routine use in the NHS. The impact of new methodologies on previous appraisal results and recommendations should be considered when assessing the validity of a new approach.

CL2ADDRESSING HETEROGENEITy IN BASELINE RISK OF COPD ExACERBATIONS USING META-REGRESSIONCope S.1, Buckley F.2, Baldwin M.3, Kraemer M.4, Jansen J.21Mapi, Toronto, ON, Canada, 2Mapi, Boston, MA, USA, 3Novartis Pharmaceuticals UK Limited, Horsham, West Sussex, UK, 4Novartis Pharma AG, Basel, SwitzerlandObjectives: To evaluate differences across randomized controlled trials (RCTs) con-cerning interventions for moderate to severe chronic obstructive pulmonary disease (COPD) in terms of baseline exacerbation rates and the association with treatment effects by means of a network meta-analysis (NMA). This NMA is performed based on RCTs evaluating the long-acting bronchodilators indacaterol 75/150/300µg OD, salme-terol 50µg BID, formoterol 12µg BID, tiotropium bromide 18µg/5µg OD, and glycopyr-ronium bromide 50µg OD. MethOds: The rate of moderate or severe exacerbations was extracted from RCTs identified with a systematic literature review. A Bayesian NMA was used to synthesize the treatment effects of the different trials. The association between treatment effects and baseline exacerbation rate with placebo was assessed with a meta-regression model assuming a constant treatment-by-baseline risk interac-tion term. Results: Twenty-four RCTs were included that differed mainly in terms of smoking status, COPD severity, use of inhaled corticosteroids, exacerbation definition, and exacerbation history. Across the RCTs the rate of exacerbations per patient year for patients in the placebo arm ranged from 0.40 to 1.91. Baseline risk was negatively associ-ated with the rate ratios reflecting treatment effects across the RCTs. The coefficient for baseline risk was -0.35 (95% credible intervals: -0.49, -0.18). cOnclusiOns: Based on a NMA of RCTs regarding the efficacy of long-acting bronchodilators in terms of the rate of exacerbations per patient year, baseline risk of exacerbations acts as a significant treatment effect modifier and should be accounted for in the model.

CL3vALIDATION OF SURROGATE ENDPOINTS IN ADvANCED SOLID TUMOURS: SySTEMATIC REvIEw OF STATISTICAL METHODS, RESULTS, AND IMPLICATIONS FOR POLICy MAKERSCiani O.1, Davis S.2, Tappenden P.2, Garside R.3, Stein K.1, Cantrell A.2, Saad E.4, Buyse M.5, Taylor R.11University of Exeter, Exeter, UK, 2University of Sheffield, Sheffield, UK, 3University of Exeter, Truro, UK, 4Dendrix, Sao Paulo, Brazil, 5IDDI, Louvain-la-Neuve, BelgiumObjectives: Licensing and reimbursement of anticancer drugs should rely on evi-dence from patient-relevant endpoints such as overall survival (OS). Nevertheless, evidence from surrogate endpoints may also be useful, as it may expedite the regula-tory approval and coverage decisions of new therapies. It is therefore essential that candidate surrogate endpoints be properly validated. However, there is no consensus on statistical methods for such validation and on how the evidence thus derived should be applied by policy makers. MethOds: We review meta-analyses of thera-peutic interventions against advanced solid tumours published until December 2012 that quantified the statistical association between progression-free survival (PFS) or time-to-progression (TTP) and OS. We assessed the suitability of the two surro-gates using three current surrogate validation frameworks: Bucher’s framework, the German Institute of Quality and Efficiency in Health Care’s (IQWiG) framework and the Biomarker-Surrogacy Evaluation Schema (BSES3). Results: Thirty-one meta-analyses were included which employed a variety of statistical methods to assess surrogate validity. The strength of the association between PFS or TTP and OS was generally low. The level of evidence (observation-level vs. treatment-level) available supporting an association between PFS or TTP and OS varied considerably by cancer type, by evaluation tools and was not always consistent even within one specific cancer type. cOnclusiOns: Not in all solid tumours the treatment-level associa-tion between PFS or TTP and OS has been investigated. According to the IQWiG’s framework, only PFS achieved acceptable evidence of surrogacy in metastatic colo-rectal and ovarian cancer treated with cytotoxic agents, whereas in no indication did the two candidate endpoints achieve good evidence of surrogacy according to BSES3. Our study emphasises the challenges of surrogate-endpoint validation and the importance of building consensus on appropriate statistical techniques to exam-ine surrogacy and on the development of evaluation frameworks for policy makers.

CL4FRAMEwORK FOR EvIDENCE ASSESSMENT BASED ON GRADE AND APPLICATION TO HPv vACCINATION IN MALES IN THE EUROPEAN HEALTH CARE CONTExTSiebert U.1, Sroczynski G.2, Baker P.3, Borget I.4, Castellsagué X.5, Chapman R.6, von Knebel-Doeberitz M.7, Mortensen G.L.8, La Torre G.91UMIT – University for Health Sciences, Medical Informatics and Technology / ONCOTYROL / Harvard University, Hall i. T./ Innsbruck / Boston, Austria, 2UMIT – University for Health Sciences, Medical Informatics and Technology, Hall i.T., Austria, 3Men’s Health Consultant, Brighton, UK, 4Institut Gustave Roussy, Villejuif, France, 5L’Hospitalet de Llobregat, Barcelona, Spain, 6Evidera, London, UK, 7University of Heidelberg, German Cancer Research Center, Heidelberg, Germany, 8AnthroConsult, Aarhus C, Denmark, 9Sapienza University of Rome, Rome, ItalyObjectives: To develop and apply an extended framework for evidence assess-ment based on the Grading of Recommendations Assessment, Development and


large polyps, natural history of adenoma transition to cancer and importantly, adherence. CTC was found to be cost-effective in three studies, assuming the most favourable scenario. cOnclusiOns: CTC has the potential to be a cost-effective CRC screening strategy when compared to COL. There is a strong need for a differ-ential consideration of patient adherence and compliance to CTC and COL. Recent research shows that laxative-free CTC screening has the potential to become a viable alternative screening method for CRC as it can improve patient uptake of screening. This project is supported by the German Federal Ministry of Education and Research (BMBF) as part of the National Cluster of Excellence‚ Medical Technologies – Medical Valley EMN’ (Project grant No. 13EX1013B).

MD2MARKET ACCESS OF IMPLANTABLE MEDICAL DEvICES: EvIDENTIARy REQUIREMENTS ACROSS GLOBAL MARKETSChawla A.S.1, Spinner D.S.1, Ransom J.F.2, Doyle J.2, Faulkner E.C.11Quintiles Consulting, Durham, NC, USA, 2Quintiles Global Consulting, Hawthorne, NY, USAObjectives: With tightening health system budgets, medical devices (MDs) are being increasingly scrutinized for their impact on overall health care cost. The evi-dence bar for implantable MDs is particular high since most implantable devices are not reimbursed separately by payers, but via direct bundled payments to the provider. To characterize that trend, the objectives of this study were to: 1) Identify specific evidence criteria that maximally impact the payer decision, 2) Note differ-ences in HTAs across global markets, and finally 3) Outline differences in evidence requirements between drugs and devices. MethOds: A multimarket review of implantable MD HTAs and reimbursement decisions published from 2008-2013 was conducted. Identified by HTA W

aalborg universitet effect of nurse-led medication reviews ... · dan greenberg, phd ben-gurion...

Documents