W7: Statistical Challenges in HTA

Transcription

1 W7: Statistical Challenges in HTA Chair: Claire Watkins, Statistical Science Director, AstraZeneca Speakers: Keith Abrams, Professor of Medical Statistics, University of Leicester Nicholas Latimer, Research Fellow, University of Sheffield Marie Ange Paget, HTA Project Statistician, Eli Lilly ISPOR Europe, Dublin 2013 EFSPI HTA SIG European Federation of Statisticians in the Pharmaceutical Industry Health Technology Assessment Special Interest Group Collaborate and discuss strategies and methodology being applied in this area of research Exchange information and share case studies and statistical/analytical challenges faced in HTA research Keep abreast of new research and methodological developments Promote and highlight opportunities for statisticians to make a positive impact in HTA Interact with key opinion leaders in HTA research Organise and/or participate in workshops related to HTA Thanks to the SIG for helping to organise this session at ISPOR

2 Workshop Agenda Statistical Challenges in HTA Keith Abrams: Indirect Comparisons Nicholas Latimer: Treatment Switching Marie Ange Paget: Subgroup Analyses Panel Discussion W7- STATISTICAL CHALLENGES IN HTA Subgroup analyses Marie-Ange Paget HTA Project statistician (Eli Lilly, France) EU ISPOR Dublin 5 November 2013

3 Disclaimer The views expressed herein represent those of the presenter and do not necessarily represent the views or practices of Eli Lilly. This work is presented on behalf of the subteam of the EFSPI/PSI HTA working group: Chrissie Fletcher, Christy Chuang- Stein, Neil Hawkins, Carol Reid, Marie- Ange Paget 5 Agenda Introduction Subgroup analyses key principles to support Effectiveness analyses Cost-effectiveness analyses A case study Some recommendations 6

4 Introduction Subgroup analyses in cost-effectiveness are used by manufacturers and HTA authorities to understand key drivers of cost-effectiveness Pharmaco-economic guidances provide recommendations on how to assess patient heterogeneity However, there is a lack of consensus on which specific methods are most appropriate (Ramaekers, 2013) 7 Keys principles for subgroup analyses for clinical efficacy/effectiveness What are the statistical principles used in subgroup analyses? 8

5 Keys principles for subgroup analyses for clinical efficacy/effectiveness Subgroups pre-specification & definition Subgroup by treatment interaction Multiplicity issues Sensitivity analyses Replication Source of evidence Presenting and reporting subgroup results 9 Relevance for cost-effectiveness subgroup analyses Clinical effectiveness Cost-effectiveness Subgroups pre-specification Subgroup by trt interaction Multiplicity issues Sensitivity analyses Replication Source of evidence Presenting and reporting How relevant are these statistical principles for costeffectiveness subgroup analyses? trt: treatment

6 Relevance for cost-effectiveness subgroup analyses Clinical effectiveness Cost-effectiveness Sensitivity analyses Presenting and reporting Replication Source of evidence Subgroups pre-specifications Multiplicity issues Subgroup by trt interaction Extremely important Transparency Important All data sources Desirable Less important trt: treatment 11 A case study NICE (2006) reviewed 4 treatments for the treatment of Alzheimer s disease [TA111] Class Treatement EU marketing autorisation indication acetylcholine sterase (AChE) inhibitors N-methyl-Daspartate (NMDA) receptor antagonist Donepezil Galentamine Rivastigmine Memantine for mild to moderately severe Alzheimer s disease for moderately severe to severe Alzheimer s disease 12

7 Background All 3 AChE inhibitors were shown to be clinically effective in the overall study populations, but not deemed to be cost-effective for the group as a whole. Subgroup investigation (Appraisal Committee) to ascertain whether a subgroup of patients for whom the technologies were more cost effective 13 NICE (2006) recommendations Treatment EU marketing autorisation indication NICE (2006) recommendation Donepezil Galentamine Rivastigmine for mild to moderately severe Alzheimer s disease for patients with Alzheimer s disease of moderate severity Memantine for moderately severe to severe Alzheimer s disease Not recommended 14

8 4 years after NICE (2011) reassessed the 4 drugs with new randomized trials data [TA217] Clinical effectiveness analyses: No subgroup analyses by the technical assessment group as no RCT reported subgroup analyses by disease severity Cost-effectiveness analyses: The 2 manufacturer models: dominant in all severities with sensitivities analyses The technology assessment group: the 4 drugs are not cost-effectives irrespective of the severity 15 NICE (2011) recommendations Treatement EU marketing autorisation indication NICE (2011) recommendation Donepezil Galentamine for mild to moderately severe Alzheimer s disease As an option for managing mild, as well as moderate Alzheimer s disease. Rivastigmine Memantine for moderately severe to severe Alzheimer s disease As an option for managing moderate Alzheimer s disease in patients who are intolerant of or who have a contraindication to AChE inhibitors, and for managing severe Alzheimer s disease 16

9 Top suggested research priority Quality longer term RCTs (following CONSORT) to include mortality, time to institutionalization and HR QOL as outcomes and sufficiently powered for subgroup analysis by disease severity, response to treatment, behavioural disturbance and comorbidities. 17 What about our key principles? Sensitivity analyses Presenting and reporting Replication Source of evidence Subgroups pre-specifications Multiplicity issues Subgroup by trt interaction trt: treatment

10 Recommendations in costeffectiveness subgroup analyses Early planning in the design & analysis of confirmatory clinical studies Adherence of good statistical principles to provide Transparency in how subgroup are defined and when (planned vs post-hoc) Robustness of the subgroup results, and Quantification of the uncertainty Subgroup should also be clinically meaningful and relevant for reimbursement decision 19 References & Links EFSPI/PSI HTA Special Interest Group Christine Fletcher, Christy Chuang-Stein, Neil Hawkins, Marie-Ange Paget, Carol Reid. Subgroup Analyses in Cost-Effectiveness Analyses to Support Health Technology Assessments (submitted) Ramaekers BLT, Joore MA, Grutters JPC. How Should We Deal with Patient Heterogeneity in Economic Evaluation: A Systematic Review of National Pharmacoeconomic Guidelines Value in Health 16 (2013), pp Alzheimer's disease - donepezil, galantamine, rivastigmine (review) and memantine (replaced by TA217) (NICE TA111). National Institute for Health and Care Excellence. Sept Alzheimer's disease - donepezil, galantamine, rivastigmine and memantine (NICE TA217). National Institute for Health and Care Excellence. March

11 Key themes: Statistical Challenges in HTA Assumptions Awareness Evaluation Understanding impact Planning Design with the analysis in mind Payers and regulators # of statisticians with HTA expertise Discussion Panel Statistical Challenges in HTA Claire Watkins Keith Abrams Nicholas Latimer Mari Ange Paget