Szabolcs Barotfi Ph.D.

Transcription

1 Szabolcs Barotfi Ph.D.

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3 Manufacturer: Bayer Withdrawn in 2001 (4 years after registration) Financial loss: 1.2 bn $ Manufacturer: MSD Withdrawn in 2004 (5 years after registration) Financial loss: 2 bn $ Manufacturer: Pfizer Withdrawn in 2005 (1 year after registration) Financial loss: 2 bn $ Manufacturer: Roche Withdrawn in 1998 (1 year after registration) Financial loss: 2.9 bn $

4 What is it? Is less controlled Is diverse / colorful Is noisier Is subject to change Does not always follow the rules Has different people with different needs Late Phase Market authorization

5 Efficacy vs. Effectiveness Efficacy Effectiveness The extent to which medical interventions achieve health improvements under ideal circumstances. The extent to which medical interventions achieve health improvements in realpractice settings.

6 Real-World & Late Phase Research: Trends Global market landscape Increasing complex stakeholder landscape Increasing outsourcing rates Shift towards specialty drugs/personalized medicine Use of real-world data & analytics to drive decision making Reform driving progressive authorization Earlier interest in market access (earlier in product lifecycle) Integrate real-world and late phase planning and design within the overall context of Commercial and Medical Affairs Shift towards a patient-centric approach to validate clinical trial efficacy with real-world effectiveness and riskbenefit Focus on real-world cost effectiveness

7 Different stakeholders, different needs, different purposes Industry Regulators Payers Providers Patients Drug Candidates Market Access Meet commitments Add to the safety profile Evaluate efficacy to improve patient outcomes Prove value Secure reimbursement Enhance understanding of unmet patient needs Explore new indications Generate publications Detect safety signals Ensure long-term effectiveness Determine value and coverage Monitor usage within criteria Cost-effectiveness Obtain locally relevant evidence Advance science Improve care Ensure continued reimbursement Generate publications My own health what choices do I have? What are the risks/ benefits? Which treatment will improve my quality of life? Which treatment is safer, more convenient and affordable? Adapted from: Relative efficacy of drugs: an emerging issue between regulatory agencies and third-party payers. Eichler et al, Nature Reviews Drug Discovery 9, (April 2010)

8 Genomics Personalized Medicine Patient Reported Outcomes Convenience, Quality of Life Observational Research Safety, Effectiveness & Value Pragmatic Trials Randomized Controlled Trials Case Reports Expert Opinion Quality, Safety, Efficacy Physician Regulator Payer Patient S T A K E H O L D E R E X P A N S I O N

9 RCT are not well suited to answer all research questions: RCT Limitations Reality Generalizability Applicability Availability Data from RCTs do not always reflect real-world practice and outcomes due to atypical behavior & setting Protocol-driven behavior Narrowly defined study population May not be usual practice Data from RCTs cannot necessarily be assumed to apply to subpopulations not studied in those RCTs Data from RCTs do not answer questions of physician practice behavior and the resulting outcomes of that behavior. RCTs analysed by intent-to-treat, not how products are actually used Do not give insights into why clinicians may use products off-label or in risky situations As RCTs are costly to conduct there are a limited number of RCTs relative to the number of decisions that must be made RCTs alone cannot provide all the relevant information decision makers need to determine the relative risks and benefits when choosing the best treatment for a patient or weighing the implications of particular policies affecting medical therapies

10 Emphasis on lifecycle management of marketed products Dwindling product pipelines Diminished patent lines with generic erosion of brands Increasing regulatory pressures ( Post marketing commitments/post-authorization requirements ) New pharmacovigilance legislation will strengthen the legal basis for PASS & PAES New biological products in development Global health care payers are demanding product differentiation and evidence of strong economic value for pricing and reimbursement Need for targeted, fit for purpose, cost-effective study solutions Importance of designing studies with added value and increase ROI

11 The Approach The Question Assessor A Paradigm Shift Between Regulators & HTA Yesterday s Paradigm Today s New Paradigm Regulators Payers Regulators Payers Risk-benefit profile Safety, Efficacy, Quality Risk-benefit profile + Value Safety Comparative Effectiveness Cost vs. Health Benefit Risk-benefit profile Safety, Efficacy, Quality Comparative Effectiveness Risk-benefit profile + Value Long term safety / signal detection Cost vs. Health Benefit Randomised Controlled Trials Pragmatics Trials Observational Studies HEOR Randomised Controlled Trials Observational Studies HEOR Adaptive Phase IIIB & IV Trials Pragmatic Trials Observational Studies Meta-analysis Marketing Authorisation

12 Pre-launch Product Launch Phase IV Post-launch Natural history of disease burden of illness treatment patterns competitor products disease management To inform development, launch strategy, and market access Brand usage (on and offlabel) safety & effectiveness compliance, adherence, persistence treatment satisfaction quality of life comparative effectiveness disease management

13 What does it mean? Real World Research aims to capture this setting in the framework of a clinical study Objectives will vary Data needs will vary Type of study will vary Timepoint of data collection in a product lifecyle will vary Means of data collection will vary Data sources will vary Patients, physicians and stakeholders will vary often within the same project Safety, effectiveness, expanded access, quality of life Adverse drug reaction, patient reported outcomes Interventional vs observational Pre-launch, accompanying launch, post launch Site based vs direct to patient, survey, patient or site level data Primary vs secondary, site vs patient Diverse patient and physician population; study might aim to address regulatory, payers, providers, internal client needs

14 The Real-World Research Question can be Answered through Different Research Approaches Hybrid designs may capitalize on the speed, cost efficiency and strength of different methods Observational Interventional Study Study Prospective Retrospective Other terms include registry or non-interventional Usually described as studies Diagnosis and treatment according to usual clinical care Data source: existing data, new data, or both Need not involve a drug product (e.g. disease registry). Often described as trials Participants can be randomized to treatment and followed over time Often pragmatic or practical in design to mimic real-world clinical care Utilizing retrospective and prospective data to shorten time and cost Large Pragmatic Trial or Disease Registry Health Economic Study PRO Study Conducting sub-studies alongside larger simple prospective research endeavours

15 Supporting the Product Lifecycle & Evidence Generation Diversity of Real World & Late Phase Study Types Conducted Across the Product Lifecycle Preclinical R & D Clinical Phase Development Phase IIIa Phase I Phase IIb Phase registration III Submission for market approval Post-approval Phase IV Approval Registration Clinical Trials Interventional Safety and Efficacy Trials Pragmatic Trials Pre-Launch Observational Research (database research, registries, market surveys, etc) Post-Launch Prospective/Retrospective Observational Research Compassionate Use / Expanded Access Programs Post-Authorisation Safety Studies PRO Instrument Validation Value demonstration studies (HRQoL, HEOR, treatment satisfaction, etc) RWLP studies can start pre-approval (e.g. disease awareness), peri-approval (e.g. reimbursement comparator strategies) or post-approval (e.g. PASS).

16 Myth Observational studies only come to play post market launch Observational studies are scientifically less relevant than interventional clinical trials Their results are less robust It is much easier and faster to run observational studies and there is no planning required, as everything is flexible anyways There is no Ethics nor CA approval required for observational studies Data in observational studies is not clean. Reality Observational studies can also investigate the market that a product is supposed to be launched it. Studies would then focus on the disease/indication rather than a specific product. Observational studies are often scrutinized even more and address questions that might not be answered by clinical trials. Results are as robust as the methodology applied. Observational studies reflect real life and are therefore very diverse in terms of study population, site population, country requirements. Planning is often even more important and requires constant updates Observational studies follow the same rules for protection of data privacy and patient safety Data cleaning in observational studies uses a different approach, but focus is still on obtaining good quality data

17 Thank you! Contact details: Szabolcs Barotfi