HTA and Post-Launch Studies

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EXPLORING THE FUTURE OF RE FOR DRUGS IN EUROPE ELEMENTS AFFECTING THE FUTURE OF RE IN EUROPE? Baseline factors Payers continue to face austerity pressures Decision making by Payer / HTA bodies remains at national / subnational level Patient expectations continue to rise Key Factors Assessed New pharmaco-vigilance regulation (PAES and PASS) Adaptive Licensing (AL) Assessment of clinical evidence by HTA bodies/payers at launch Key Factors Assessed (continued) Demand for post-launch RE studies by HTA bodies/payers Coordination between regulatory and HTA bodies Infrastructures to conduct RE research Methodologies to analyse RE evidence Use of Patient Reported Outcomes (PROs) Relationship between FDA and EMA Personalised medicine Commissioning and funding RE studies

EUROPE CRITICAL KEY FACTORS IDENTIFIED -- DEFINITIONS TOP TWO CRITICAL KEY FACTORS Regulatory change: New pharmaco-vigilance regulation enables the EMA to seek efficacy data in addition to safety (at first authorisation or post-authorisation) in order to inform a benefit-risk assessment of a medicine. Adaptive Licensing: prospectively planned, flexible approach to regulation with iterative phases of evidence gathering to reduce uncertainties followed by regulatory evaluation and license adaptation HTA change: Assessment of clinical evidence by bodies/payers at launch identifying incremental effectiveness of a new medicine (compared to current practice) based on clinical trial data and modelling techniques Demand for post-launch RE studies by HTA bodies/payers Studies requested by HTA bodies/payers to demonstrate benefits in real world setting SECOND TWO CRITICAL KEY FACTORS Coordination between regulatory and HTA bodies: Interaction between regulatory and HTA bodies can in principle cover one or more of: the offering of scientific advice both pre- and post-launch leading to the possible coordination and/ or agreement on evidence requirements (e.g. type of study design and type of end points to be included) Infrastructure and methods: The extent to which: improvements in research infrastructures and in the availability of data are made robust methodologies to analyse evidence produced by RE studies will be developed and agreed by key stakeholders THREE RESULTING SCENARIOS Three scenarios, operating fundamentally on a logic of increasing Europe an co-ordination.. Scenario 1: Status quo Little regulatory change. No HTA agreement on methods for clinical assessment, and post-launch studies requested in some countries. Limited regulatory and HTA coordination either pre or post launch. Scenario 2 Some changes Post-authorisation efficacy studies (PAES) implemented. Convergence of HTA methods for clinical assessment but HTA ability to request post-launch studies constrained by role of regulatory. Some regulatory and HTA coordination pre-launch Scenario 3 Major changes; high-trust environment Integrated regulatory system, including AL, applied to a variety of drugs. Convergence of HTA methods for clinical assessment and coordination for demand of postlaunch studies (often linked to conditional reimbursement schemes). Joint regulatory and HTA thinking for pre-and post- launch.

SOME CHANGE SCENARIO MOST LIKELY Regulatory: Post-authorisation efficacy studies (PAES) implemented CMA used as now in limited cases HTA bodies/payers: Convergence of methods for clinical assessment Ability to request post-launch studies constrained by regulatory PAES role Regulatory and HTA bodies/payers dialogue: Some coordination pre-launch but not post-launch Infrastructures and methods: Increased use of disease registries in some countries Progress in EHRs Limited methods development Industry is responsible for financing and conducting studies Limited opportunity to identify subgroups/biomarkers pre-launch MOVEMENT TOWARD HARMONIZATION IN EUROPE Most Likely Scenario AL applied to a variety of drugs Joint HTA and EMA coordination for pre-and post- launch Coordination across HTA bodies in demand for P-L studies, often linked to CED, P4P schemes Greater HTA and EMA coordination pre-launch Disease registries in some countries, and progress in EHRs Collaborations across large registries Full use of EHRs Good progress in methods Public-private partnerships have a major role Post-authorisation efficacy studies (PAES) implemented Most Conducive To RE Scenario

COMMONALITIES BETWEEN US AND EU MOST LIKELY SCENARIOS FOR CER AND RE Payers/HTA bodies will still require RCTs for initial market access Payers/HTA bodies will impose greater demands on CER/RE for market access, specifically: How does this work in my population? How does this compare with existing alternatives? Payers/HTA bodies will impose greater demands on CER/RE for preferential tier placement/favorable pricing How does this affect resource use and cost? Data rich environment in the US, but conducive for conduct of RCTs in only select systems, largely for observational research Progress on the development of patient/disease registries and on cross country registries in the EU, but doubts remain over methods FDA and EMA both seeking to achieve earlier licensing of products, albeit FDA has no interest in adaptive licensing whilst the EMA is seeking to implement this DIFFERENCES BETWEEN US AND EU MOST LIKELY SCENARIOS FOR CER AND RE US Focus is on increased capacity to conduct CER Focus on integration to increase incentives and ability to look for value FDA looks favourably on active comparators, may still require placebo Limited interaction between FDA and payers Payers/providers will do some of their own research Focus on patient-centered research prominent EU Focus is on differences between national HTA bodies requirements Payers already have HTA processes to identify value EMA and HTA bodies demanding active comparators Structured interaction between EMA and HTA bodies including parallel advice Requirement to develop RWE is expected of industry Patient influence is a less important driver

QUESTIONS How plausible do you find this description of the future? Is it consistent with trends you see taking shape now? How much might happen by 2020? In terms of their effects on future CER and RE, do the US and EU futures create any synergies? Conflicts? Opportunities?