post-licensing evaluation of pharmaceuticals...2006/01/26 · 3 dr. med. annette zentner, mph dept....
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Post-licensing evaluation of pharmaceuticals
An international comparison
Dr. Annette Zentner MD, MPHDept. Health Care Management
Technische Universität Berlin, Germany
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Agenda
• Pharmaceutical regulation in industrialised countries
• Pharmaceutical evaluation– aspects– Process– methods
• Conclusionshtt
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Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Pharmaceutical regulation in industrialised countries
Austria Germany Sweden United KingdomNegative List
Austria France Ireland New ZealandPublic Price NegotiationUnited KingdomPublic Profit Control
Australia Belgium Denmark Finland GreeceItaly Canada Luxembourg The NetherlandsPortugal Sweden Switzerland Spain
Public Price Setting
Australia Belgium Denmark Germany France New Zealand The NetherlandsNorway Sweden Spain
Reference Pricing
Australia Austria Canada FranceThe Netherlands Norway New ZealandSweden Switzerland
Positive List
Pharmaceutical evaluation
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Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Rationale behind post-licensingevaluation
0
5
10
15
20
25
1986
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
Truly innovative substances
Therapeutically relevantsubstancesMee-too preparations
Source: Schwabe and Paffrath 2004
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Criteria for marketingauthorisation
• Safety• Pharmaceutical Quality• Efficacy
No comparison with already availabletreatment options
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Who is in charge for post-licensing evaluation of drugsin industrialised countries?
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
National drug evaluating institutions and their advisory bodies
Austria Federation of Austrian Social Insurance Institutions/Drug Evaluation Commitee
(Hauptverband der Österreichischen Sozialversicherungsträger/Heilmittel-Evaluierungs-Kommission)
Australia Pharmaceutical Benefits Advisory Committee/Economic Sub-Committee
Belgium National Institute for Sickness and Invalidity Insurance/Commission for Reimbursement of Medicines
(Institut national de l’assurance maladie-invalidité/Commission de réimboursement des médicaments)
Canada PMPRB - Patented Medicine Prices Review Board/Human and Veterinary Drug Advisory Panels
CDR - Canadian Expert Drug Advisory Committee/Common Drug Review-Directorate at Canadian
Coordinating Office for Health Technology Assessment
Finland Pharmaceuticals Pricing Board (Lääkkeiden hintalautakunta)
France Economic Committee for Health Products/Transparency Commission
(Comité économique des produits de santé/Commission de Transparence)
Germany Federal Joint Committee/Institute for Quality and Efficienty in Health Care
(Gemeinsamer Bundesausschuss/Institut für Wirtschaftlichkeit und Qualität im Gesundheitswesen)
The Netherlands Health Care Insurance Board/Committee for Pharmaceutical Aid
(College voor zorgverzekeringen/Commissie Farmaceutische Hulp)
Norway Norwegian Medicines Agency (Statens Legemiddelverk)
New Zealand Pharmaceutical Management Agency/Pharmacology and Therapeutic Advisory Committee
Sweden Pharmaceutical Benefits Board (Läkemedelsförmånsämnden)
Switzerland Swiss Federal Office of Public Health/Confederal Drug Commission
(Bundesamt für Gesundheit/Eidgenössische Arzneimittelkommission)
United Kingdom National Institute for Clinical Excellence
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Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Establishing comparativepost-licensing evaluation
2003 2004
IQWiGHEKPBAC
CEDAC
1987
PMPRB
1994
EAK
PPB
1999
CT
1996
CFH
2002
NoMA
2000
PHARMAC
PBBNICE
Example Australia
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The pathwayof a new drug
in Australia
Example France
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Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Price negotions according to
no improvement: no inclusion of the product on the positive list
ASMR VI
no improvement but a lower treatment costASMR V
minor improvementASMR IV
modest improvementASMR III
great improvement in terms of efficacy and/or reduction of side effects
ASMR II
major therapeutic progressASMR I
Amélioration du Service Médical Rendu-Classification
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Drug Review Bodies: Roleand Structure
advisory-typebodies
regulatory-typebodies
AT AU BE CH DE NL
NO UK
FI NZSE
CAFR
• Physicians• Health economists• Pharmacists, clinicalpharmacologists• Epidemiologists• Government/insurancefund representatives• Consumers (AU, SE, UK)• Industry (UK)
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Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Which pharmaceuticals aresubject to evaluation?
• all newly licensed (AT, AU, NL)
• those with new chemical substances (CA [CDR])
• all patented (CA [PMPRB])
• all newly licensed for outpatient care (FI)
• newly licensed prescription drugs for outpatient care (FR)
• new and “old” prescription drugs (SE)
• specific products according to priority setting(UK)
Aspects of pharmaceuticalevaluation in industrialised
countrieshttp:/
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Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Criteria for Assessment and Decision-Making
XXR&D
XXXXXEquity considerations
XXXXXXXXXBudget impact
XGovernment priorities
XX
XXX
AT
X
X
XXX
AU
X
XXX
BE
X
X
XXX
CA
XX
CH
XX
DE
XXX
FI
X
X
XX
FR
XX
XXX
NL
XXX
NO
X
X
XXX
NZ
X
XXX
SE
Public health impactCommunity need
Availability of therapeutic alternativesPharmacological/innovative characteristics
Cost-effectivenessPatient benefitTherapeutic benefit
Criteria
XX
XXx
UK
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
H T A R E P O R TD efin ition of the P olicy Q uestion(s)
B ackground inform ation / D eterm ination of the sta tus of the technology
D efin ition of the research questions
Safety
Sources of data
A ppraisal o fev idence
S yn thesis ofev idence
E fficacyE ffectiveness
S ources of data
A ppraisal o fev idence
S ynthesis ofev idence
P sychologica lS ocia l
E th ica lSources of data
A ppraisal o fev idence
S yn thesis o fev idence
O rgan isationP rofessional
S ources of data
A ppraisal o fev idence
Syn thesis ofev idence
E con om ical
S ources of data
A ppraisal o fev idence
S ynthesis ofev idence
C onclusions / R ecom m endationsF IN A L H T A R E P O R T
D raft elaboration
E xternal R eview
H T A P ro tocol
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Process of pharmaceuticalevaluation in industrialised
countries
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Who provides and analyses thedata?
AT, CA (PMPRB), CH, FI, FR: Assessments are mainly based on a definite number of clinical or economic studies which are submitted by pharmaceutical companies. Systematic reviews are preferred but not required.
CA (CDR), NZ, SE, UK: Review bodies themselves perform systematic review of clinical and economic evidence independently of studies and data provided by companies.
AU, NO, NL: Review bodies check and validate data provided by industry. Manufacturers are required to submit a comprehensive summary of the drug’s effectiveness and cost-effectiveness data that is based on a systematic search and synthesis of published and unpublished evidence.
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Example Sweden
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Evaluation process at PBB
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Example England and Wales
Evaluation process at NICE
Assessment
Appraisal
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Methods for pharmaceuticalevaluation in industrialised
countries
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
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Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Everything is relative...Comparator
• “common practice” in most countries (i.e. most frequently prescribed medicine or most prevalent non-pharmaceutical treatment)
• best available treatment (e.g. FI, NO, NZ, UK)
• least expensive therapeutic alternative (e.g. CA, FR, NZ)
Choice of comparator iscrucial for result of
assessment! Methologicalguidelines require close
adherance
Choice of comparator iscrucial for result of
assessment! Methologicalguidelines require close
adherance
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Study designs
• preferably “head-to-head” randomized controlled trials (direct comparisons)
• majority favours final outcome parameters (change in mortality, morbidity, quality of life) and studies in “natural” and country specific setting
• cost-utility analyses are most frequently recommended, required in AU, NZ, UK; quality-adjusted life years (QALYs) required as outcome in 4 countries
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Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Australia (PBAC)-benefit versus harm versus costs
More
alike
?less
lessalikemoree f f e c t i v e n e s s
Toxicity
cost
-effe
ctive
ness
-/
utilit
y-an
alysis
cost-minimisation-
analysis
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Final outcomes versussurrogatparameters
source:PBAC
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Efficacy• explanatory trials• highly selected populations• comparator: placebo
• outcomes: clinical, morbidity, mortality, adverse effects
• ‘what it says on the packet’
Effectiveness• pragmatic trials• few exclusions• comparator:
‘current (best) practice’
• outcomes: patient-focused, down-stream resources
• ‘the real life effect’
Evidence GapEvidence Gap
LicensingLicensing
Post-LicensingPost-Licensing
Efficacy versus effectiveness
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Methodology: Details
Methodologies further differ on:sub-group analysis, time horizon, preferredoutcome parameter (clinical, patient benefit, combined), use of „community effectiveness“ data(mostly preferred), indirect comparisons (mostlyno), instruments to measure quality of life, perspective of economic analysis, costs included in analysis, calculation of drug costs, incrementalanalysis, discounting (0%-15%), use of modellingtechniques, sensitivity analysis, dealing withmissing and unreliable data …
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Dealing with missing orunreliable data
Far better an approximate answer to the right question, which is often vague,
than an exact answer to the wrong question, which can always be made
precise.
Tukey JW, 1962http:/
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Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Methodological approaches
• inclusion of various study designs and expert opinion (RCT is not a dogma)
• indirect comparisons• modelling
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Restrictions for use of pharmaceutical
to specific indications, type and severity of diseases or conditions, populations (e.g. age, sex), therapeutic strategies (e.g. first line, second line treatment), treatment settings (e.g. inpatient/ outpatient care, general/specialist care), prescribers (e.g. only specialists; FI, NZ) or pre-authorisation through sickness fund (AT, BE)
attempt to target limited resources to populations that are likely to benefit most (or to those for whom evidence is available)
attempt to target limited resources to populations that are likely to benefit most (or to those for whom evidence is available)htt
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Example United Kingdom
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Recommendations of NICE
source: Rothgang 2004
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Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Conclusion I:Criteria and Process
...it follows a systematic, evidence-based, comparative approach,...it is independently performed and supplemented by other criteria in thedecision-making process
Post-licensing evaluation of drugs is a valuable policy tool
IF...
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Conclusion II:Methodological Challenges
...decision-makers are aware of itsmethological strenghts and limitations,...it is repeated according to gain in new evidence.
Post-licensing evaluation of drugs is a valuable policy tool
IF...
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Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Conclusion III:Policy Challenges
...it has reliable impact on rewardingmanufacturers in terms of fullreimbursement and/or free or premiumpricing,...if potential for international collaboration to increase transparency and acceptability is increasingly used.
Post-licensing evaluation of drugs is a valuable policy tool
IF...
Dr. med. Annette Zentner, MPHDept. Health Care Management,
Technische Universität Berlin, Germany
Thank you for your attention!
More details are available:Zentner A, Velasco-Garrido M, Busse, R. Methods for
comparison of pharmaceuticals – an international review. GMS Health Technol Assess 2005; 1:Doc09 (20051115) (abstract and executive summary in English)
www.egms.de/en/journals/hta/2005-1/hta000009.shtmlhttp:/
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