NEW APPROACHES IN CLINICAL SCIENCE FOR DEVELOPING EVIDENCE

Transcription

1 SCT-QSPI\Regulatory Fall Innovation Workshop NEW APPROACHES IN CLINICAL SCIENCE FOR DEVELOPING EVIDENCE November 14-15, 2016 The Universities at Shady Grove Conference Center, Rockville, Maryland This multi-disciplinary two-day workshop brings together thought leaders and dynamic speakers from regulatory, government, industry, academia, and patient groups for direct and open discussions on recent innovations in the science and practice of clinical trials. DAY 1: EMERGING TRENDS IN CLINICAL TRIAL DESIGN AND ANALYSIS 7:30 Registration and Continental Breakfast 8:30 Welcome and Opening Remarks Janelle K. Charles, PhD; Division of Biometrics IV, OB/OTS, CDER/FDA & Joshua Chen, PhD; Sanofi Pasteur KEYNOTE ADDRESS BY DR. LYRIC JORGENSON DEPUTY EXECUTIVE DIRECTOR, WHITE HOUSE CANCER MOONSHOT TASK FORCE 8:40 9:20AM SESSION 1: ESTIMANDS CLINICAL OBJECTIVES, STATISTICAL METHODS AND MISSING DATA 9:20 AM NOON Organizers: Thomas Birkner, CDER/FDA; Ivan Chan, AbbVie; Joshua Chen, Sanofi Pasteur; Marc Walton, Janssen Research and Development Chairs: Thomas Birkner, FDA & Marc Walton, Janssen R&D An addendum to ICH E9 (Statistical Principles) is being currently drafted. The problem statement for this addendum focuses on the need to clarify what measure of treatment effect ( estimand ) is intended to be estimated in a clinical trial. A failure to clarify this has resulted in misalignment between trial objectives, design, conduct, and analysis and led to difficulties in interpretation. Confusion in regulatory submissions has arisen because the estimand is being implicitly defined as a consequence of the trial 1

2 design and statistical analysis methodology. This session will delve into the estimand topic from multiple angles (clinical trialist, patient, practicing clinician, statistician, and regulator). The first part of the session will include a presentation by a member of ICH E9 s addendum expert working group providing a background to the problem and describing the proposed structured estimand framework. This will be followed by a presentation discussing how different clinical scenarios (i.e., disease characteristics and therapeutic goals) lead to different clinical questions/trial objectives and subsequently different estimands. The first part of the session will conclude with statistical insights about the complexities in defining/choosing an estimator once the estimand of interest has been established. The second part of the session will consist of a panel including a patient representative, a regulator, and a practicing clinician who will be presented with several cases (i.e., disease characteristic and goal of treatment) and who will then share their perspective on what information (estimand) they want or need for the decisions they make in their role. The cases are then discussed by a clinical trialist elaborating on the difficulties of satisfying those likely differing demands within a single trial because of the differences in study design related to a specific estimand. The session will conclude with Q&A. 9:20 Randomized Clinical Trials: Why Estimands Matter Estelle Russek-Cohen, PhD; Director, Division of Biostatistics, OBE/CBER/FDA 9:45 If Selecting the Estimand is the Answer, What is the Question? The Interplay of Disease Features and Treatment Strategies Marc Walton, MD, PhD; Sr. Scientific Director, Quantitative Sciences, Janssen R&D 10:10 Estimands: A Recent Case-Study David Ohlssen, PhD; Team Lead, Advanced Exploratory Analytics, Novartis 10:35 MORNING REFRESHMENT BREAK & NETWORKING 10:55 PANEL DISCUSSION AND AUDIENCE ENGAGEMENT Panelists: Estelle Russek-Cohen, David Ohlssen, Marc Walton Thomas Permutt, PhD; Director, Division of Biometrics II/OB/OTS/CDER/FDA Robin A. Elliott, MA; Parkinson's Disease Foundation & World Parkinson Congress Steven A. Geller, MD FACP CPI; Medical Director, Centennial Medical Group 12:00 LUNCH 2

3 SESSION 2: CHALLENGES AND OPPORTUNITIES IN THE DESIGN AND IMPLEMENTATION OF BASKET AND PLATFORM TRIALS 1:00 4:00 PM Organizers: Susan Halabi, Duke University; José Pinheiro, Janssen R&D; David Stock, Bristol Myers Squibb; Lisa LaVange, OB/OTS/CDER/FDA Chairs: Susan Halabi, Duke University & Lisa LaVange, FDA Clinical trials have been traditionally designed to test the efficacy of a single compound on a particular group of patients. Increased advances in understanding the roles of molecular and genetic pathways in carcinogenesis are leading to the development of novel therapies that target these pathways. Traditional trials in oncology, however, are challenged by both the inter-patient and intra-patient molecular heterogeneity. Innovative trial designs, such as basket and platform trials, have been recently implemented in oncology and other therapeutic areas to overcome these barriers. In the context of oncology, basket trials typically test the effect of a therapy that targets a specific mutation across different cancers, while platform trials test the efficacy of multiple therapies across one or more types of patients. Both basket and platform trials have master protocols with multiple treatments, multiple molecular markers or multiple patient groups. These innovative trial designs have gained popularity due to their potential to identify effective therapies faster, and at a lower cost, than traditional designs. This session will focus on the statistical challenges in the design and logistical implementation of these trials. In addition, logistical issues related to the conduct and monitoring of such trials will also be discussed. Real life examples using both frequentist and Bayesian approaches will be provided. An assessment of where and when these designs may be an appropriate option will be discussed. 1:00 Design Issues and Challenges in Basket Trials (NCI MATCH trial) Richard Simon, PhD; Chief, Computational & Systems Biology Branch, National Cancer Institute 1:30 Platform Trials from a Bayesian Perspective Ben Saville, PhD; Statistical Scientist, Berry Consultants 2:00 The Challenges in Implementing Platform and Basket Trials to Guide Therapy: TAPUR Registry Richard Schilsky, MD; Senior Vice President & Chief Medical Officer, American Society of Clinical Oncology 2:30 AFTERNOON REFRESHMENT BREAK & NETWORKING 3:00 Discussant: Lisa LaVange, PhD; Director, Office of Biostatistics/OTS/CDER/FDA 3:30 QUESTION/ANSWER AND AUDIENCE ENGAGEMENT 4:30 WRAP UP DAY 1 3

4 DAY 2: LEVERAGING REAL WORLD EVIDENCE IN UNDERSTANDING MEDICAL PRODUCTS AND INTERVENTIONS 7:30 Registration and Breakfast 8:30 Welcome to Day 2 Janelle K. Charles, PhD; Division of Biometrics IV, OB/OTS, CDER/FDA & Joshua Chen, PhD; Sanofi Pasteur SESSION 3: REAL WORLD EVIDENCE SOURCES AND APPLICATIONS 8:40 11:40 AM Organizers: Li Chen, Amgen; Olga Marchenko, Quintiles; Renee Rees, CBER/FDA; John Scott, CBER/FDA Chairs: Olga Marchenko, Quintiles & John Scott, FDA This session will review and discuss sources and applications of Real World Evidence (RWE), specifically focusing on regulatory applications and industry/ academic centers applications using registries and Electronic Medical Record (EMR) systems. The first sub-session will cover a spectrum of evidence and examples of regulatory use of RWE: labeling changes, use of registries, and performance of comparative effectiveness research using Medicare data. A case study that provided important new information to be considered by policy makers recommending influenza vaccinations for elderly people will be presented and discussed. The second sub-session will discuss registries, registry-based clinical trials and trials using EMR system. Clinical Trial Transformation Initiative (CTTI) initiated a registry trials project the goal of which is to increase the practice of leveraging observational data registries to facilitate high quality clinical trials at lower costs. A member of this CTTI project will share experts view and give examples of existing registry trials. Case studies that include the use of EMR Systems and Health System Data in support of clinical trials together with barriers and solutions will be presented and discussed at this sub-session as well. SUB-SESSION #1: SOURCES, APPLICATIONS, AND REGULATORY PERSPECTIVES 8:40 Presentation Title to be Announced Benjamin Eloff, PhD; CDRH/FDA 9:00 Regulatory Application of Real World Data: How Do We Get Beyond Safety? Jonathan Jarow, MD; OMP/FDA 9:20 Potential use of vaccine effectiveness studies in Medicare for regulatory decisionmaking Hector Izurietta, PhD; Office of Biostatistics and Epidemiology, CBER/FDA 9:40 MORNING REFRESHMENT BREAK & NETWORKING 4

5 SUB-SESSION #2: REGISTRY-BASED CLINICAL TRIALS AND TRIALS USING ELECTRONIC MEDICAL RECORDS 10:00 Updates from CTTI working group on randomized registry trials Ted Lystig PhD, Director of Corporate Biostatistics, Medtronic 10:20 The VA s Point of Care Clinical Trial and Precision Oncology Programs Louis Fiore MD MPH, Executive Director, US Department of Veterans Affairs 10:40 PANEL DISCUSSION AND AUDIENCE ENGAGEMENT Panelists: Benjamin Eloff, Louis Fiore, Hector Izurietta, Jonathan Jarow, Ted Lystig 11:40 LUNCH SESSION 4: TRANSFORMING REAL WORLD DATA INTO EVIDENCE ACTIVE AND PASSIVE NETWORKED PATIENT ENGAGEMENT 12:40 4:00 PM Organizers: Janelle K. Charles, CDER/FDA; Michael Hale, Shire; Bo Li, CDER/FDA; Sally Okun, PatientsLikeMe; Yves Rosenberg, National Institutes of Health (NIH) Chairs: Michael Hale, Shire & Yves Rosenberg, NIH The purpose of this session is to review and discuss ways that Real World Data (RWD) are generated and collected, and potentially transformed into Real World Evidence (RWE). This session will consider some of the strengths, limitations, and key issues for these approaches to RWD. Those impact transformation methods, and interpretation potential. Current and future applications and other perspectives are discussed in two sub-sessions. The first sub-session will cover Social Media Listening and Patient Powered Research Networks. SML will primarily consider the passive gleaning of information from patient reported experiences in unstructured social media outlets (e.g., Twitter, Facebook). Beyond its potential for signal detection & safety surveillance applications, SML may offer the opportunity for insight into patient perspectives, product usage, and possibly new indications, among other potential uses. This will include a recent example where SML led to a product recall. This sub-session will also include an example of a wellknown and highly regarded Patient Powered Research Network which actively pursues data from their members using systematic data collection methods and tools, to enable the collection of meaningful patient generated data. The structure and discipline of this PPRN provide further application opportunities likely beyond the reach of passive source SML (e.g., effectiveness of sponsor REMS). The second sub-session will discuss Pragmatic Clinical Trials (PCT). The perspective for this session follows from the recent publication of Califf and Sugarman ( Exploring the ethical and regulatory issues in pragmatic clinical trials, Clinical Trials 2015, Vol. 12(5) ), where they defined PCTs as Designed for the primary purpose of informing decision-makers regarding the comparative balance of benefits, burdens and risks of a biomedical or behavioral health intervention at the individual or 5

6 population level. Elements of such trials were described by Luce et al (Ann Intern Med. 2009;151: ) as including clinically effective comparators, study patients with common comorbid conditions and diverse demographic characteristics, and providers from community settings. Primary and secondary outcomes are patient-centered, chosen to reflect what matters most to patients and clinicians. SUB-SESSION #1: SOCIAL MEDIA LISTENING IT IS HERE NOW 12:40 Social Media Listening for Drug Safety, has the time come? Greg Powell, PharmD, MBA; Director, Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline 1:00 How do patients power research networks? A look at a unique resource and some surprising uses Sally Okun, RN, MMHS; Vice President for Advocacy, Policy & Patient Safety, PatientsLikeMe 1:20 Exploration of Patient-Generated Health Data Sources: Overview of the PatientsLikeMe and FDA Research Collaboration Carol Pamer, BSPharm, MSc; Program Lead for Pharmacovigilance, Office of Surveillance and Epidemiology/CDER/FDA 1:40 AFTERNOON REFRESHMENT BREAK & NETWORKING SUB-SESSION #2: PRAGMATIC CLINICAL TRIALS ENABLING PCTS TO BE A ROUTINE PART OF OUR CLINICAL EVIDENCE 2:10 Pragmatic Trials: Thoughts from the NIH Michael S. Lauer, MD; Deputy Director for Extramural Research, NIH 2:30 Presentation Title to be Announced Alyson Karesh, MD; Director, Division of Clinical Trial Quality, OMP/CDER/FDA 2:50 PANEL DISCUSSION AND AUDIENCE ENGAGEMENT Panelists: Alyson Karesh, Michael Lauer, Sally Okun, Carol Pamer, Greg Powell Mark Levenson; PhD, Acting Director, Division of Biometrics VII OB/OTS/CDER/FDA 4:00 CLOSING REMARKS & ADJOURN WORKSHOP 6