Comparing The Effectiveness Of New Drugs: Should The FDA Be Asking 'Does It Work' Or 'Does It Work Better'? Sean R. Tunis, MD, MSc

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1 Moderator Comparing The Effectiveness Of New Drugs: Should The FDA Be Asking 'Does It Work' Or 'Does It Work Better'? Sean R. Tunis, MD, MSc Center for Medical Technology Policy Baltimore, MD, USA COMPARING THE EFFECTIVENESS OF NEW DRUGS: SHOULD THE FDA BE ASKING DOES IT WORK OR DOES IT WORK BETTER? Sean Tunis MD, MSc June 4, 2012

2 First Plenary Session Participants Moderator/Speaker: Sean Tunis, MD, MSc, Founder & Director, Center for Medical Technology Policy, Baltimore, MD, USA Speakers: Mark B. McClellan, MD, PhD, Director, Engelberg Center for Health Care Reform, Senior Fellow, Economic Studies & Leonard D. Schaeffer Chair in Health Policy Studies, Brookings Institution, Washington, DC, USA Vicki L. Seyfert-Margolis, PhD, Senior Advisor, Science Innovation and Policy, Office of the Chief Scientist, Office of the Commissioner, U.S. Food and Drug Administration, Silver Spring, MD, USA The Propositions Regulatory agencies should place more emphasis on evidence of comparative effectiveness in pre market regulatory review. The efficiency of drug development and overall public health would improve if regulatory agencies encouraged pre market CER

3 High Hopes for CER Better information about the costs and benefits of different treatment options, combined with new incentive structures reflecting the information.is essential to putting the country on a sounder long term fiscal path. Peter Orszag, CBO (later OMB) Congressional Testimony, June 2007 PATIENT-CENTERED OUTCOMES RESEARCH INSTITUTE The Patient-Centered Outcomes Research Institute helps people make informed health care decisions and improves health care 1 delivery and outcomes by producing and promoting high integrity, evidence-based information that comes from research guided by patients, caregivers and the broader health care community

4 IOM s Features of CER (2009) Objective of directly informing clinical or health policy decision Compares at least 2 alternative, each with potential to be best practice Conducted in real world settings, with typical patients Measures outcomes important to patients Results at population and subgroup level A More Precise Proposition The current regulatory paradigm could be modified so that pre approval trials provided more information on: Results in patients with common co morbidities to the primary condition being treated Comparing risks and benefits of alternative tx Outcomes that are most relevant to patients and are used by clinicians in patient management More clinically relevant follow up duration

5 Example 1: Dementia ACP guideline developed in 2008 Reviewed 5 drugs approved by FDA based on significant improvement ADAS-cog Overall assessment was that evidence for clinical recommendations is weak No convincing active comparative studies Most outcomes in trials not used in routine clinical practice.and not clinically important Follow-up too short: generally less than 1 year. Example 2: Psoriasis Regulatory studies report scaling, thickness and extent of body surface area affected by plaques (PASI score) FDA does not currently allow other QoL / PRO measures on product labels Patients state that face and joint involvement had biggest impact on QoL Might justify addition of measure of face and joint severity as endpoints in future trials

6 Some Important Trade offs There are unavoidable trade off between maximal internal validity and improving external validity / generalizability E.g. studies done in real world patients / settings Active comparator trials, especially 3 arm trials, are more expensive and take longer Many PROs and QoL measures are less well validated than existing regulatory endpoints Early Advice on CER and Clinical Development Payer advisory boards Scientific advice from HTA group and payers Mostly outside the US, especially Europe Some pilots provide joint advice with regulators Sometimes includes multiple payer / HTA groups Challenges Limited ability for dialogue around complex study design issues Must work within existing regulatory framework

7 Objectives Green Park Collaborative To determine the feasibility of developing guidance documents with recommendations for the design of clinical studies in specific therapeutic areas that address the information needs of payers and HTA bodies Informed by existing regulatory guidance and current best practices in research methods To develop a draft guidance for Alzheimer s disease drugs as a proof of concept GPC Steering Group (partial list) Berit Mørland (HTAi) Sean Tunis (CMTP) Francois Meyer (HAS) Sue Hill (PBAC) Brian O Rourke (CADTH) Carole Longson (NICE) Finn Kristensen (EUnetHTA) Louis Jacques (CMS) Paulo Siviero (IMA) Marc Berger (United) Hans Georg Eichler (EMA) Bob Temple (FDA) David Grainger (Lilly) Brian Cuffel (Pfizer) Jens Grueger (Roche) Robert Dubois (NPC) Karen Facey (patient/citizen) Steve Pearson (ICER) Chris Henshall (advisor) Lloyd Sansom (advisor)

8 Life Sciences Advisory Group Recommendations in Process Selection of measures of cognitive performance and severity for study inclusion Use of biomarkers in patient selection, stratification and surrogate outcomes Duration of follow up in controlled portion of studies and after crossover to active therapy Inclusion of caregiver quality of a life as a measure of drug effectiveness

9 A More Precise Proposition The current regulatory paradigm could be modified so that pre approval trials provided more information on: Results in patients with common co morbidities to the primary condition being treated Comparing risks and benefits of alternative tx Outcomes that are most relevant to patients and are used by clinicians in patient management More clinically relevant follow up duration Contact Info x120 (D) (M)

10 Moderator Comparing The Effectiveness Of New Drugs: Should The FDA Be Asking 'Does It Work' Or 'Does It Work Better'? Sean R. Tunis, MD, MSc Center for Medical Technology Policy Baltimore, MD, USA