Description
Platform trials test multiple therapies in one indication, one therapy for multiple indications, or both. These novel clinical trial designs can dramatically increase the cost-effectiveness of drug development, leading to life-altering medicines for people suffering from serious illnesses, possibly at lower cost. Currently, the cost of drug development is unsustainable. Furthermore, there are particular problems in rare diseases and small biomarker defined subsets in oncology, where the required sample sizes for traditional clinical trial designs may not be feasible.
The editors recruited the key innovators in this domain. The 20 articles discuss trial designs from perspectives as diverse as quantum computing, patient’s rights to information, and international health.
The book begins with an overview of platform trials from multiple perspectives. It then describes impacts of platform trials on the pharmaceutical industry’s key stakeholders: patients, regulators, and payers. Next it provides advanced statistical methods that address multiple aspects of platform trials, before concluding with a pharmaceutical executive’s perspective on platform trials. Except for the statistical methods section, only a basic qualitative knowledge of clinical trials is needed to appreciate the important concepts and novel ideas presented.
Table of Contents
Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii
List of Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xv
Part I Overview of Platform Clinical Trials . . . . . . . . . . 1
1 I-SPY2: Unlocking the Potential of the Platform Trial . . . . . . . . . . . . . .3
Laura Esserman, Nola Hylton, Smita Asare, Christina Yau,
Doug Yee, Angie Demichele, Jane Perlmutter, Fraser Symmans,
Laura van’t Veer, Jeff Matthews, Donald A. Berry, and Anna Barker
2 The Challenges with Multi-Arm Targeted Therapy Trials . . . . . . . . .23
Ryan J. Sullivan and Keith T. Flaherty
3 Basket Trials at the Confirmatory Stage . . . . . . . . . . . . . . . . . . . . . . . . .37
Robert A. Beckman and Cong Chen
4 Harnessing Real-World Data to Inform Platform
Trial Design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .55
Daphne Guinn, Subha Madhavan, and Robert A. Beckman
5 Impact of Platform Trials on Pharmaceutical Frameworks . . . . . . . . .73
Zoran Antonijevic, Ed Mills, Jonas Häggström, and
Kristian Thorlund
Part II Stakeholders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
6 Friends of Cancer Research Perspective on Platform Trials . . . . . . . .85
Jeffrey D. Allen, Madison Wempe, Ryan Hohman, and Ellen V. Sigal
7 Regulatory and Policy Aspects of Platform Trials . . . . . . . . . . . . . . . .97
Rasika Kalamegham, Ramzi Dagher, and Peter Honig
8 Multi-Arm, Multi-Drug Trials from a Reimbursement
Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .119
Anja Schiel and Olivier Collignon
9 Highly Efficient Clinical Trials: A Resource-Saving Solution
for Global Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .125
Edward J. Mills, Jonas Häggström, and Kristian Thorlund
10 Decision Analysis from the Perspectives of Single and
Multiple Stakeholders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Robert A. Beckman, Carl-Fredrik Burman, Cong Chen,
Sebastian Jobjörnsson, Franz König, Nigel Stallard, and
Martin Posch
11 Optimal Approach for Addressing Multiple Stakeholders’
Requirements in Drug Development . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Zoran Antonijevic and Zhongshen Wang
Part III StatisticalMethodology. . . . . . . . . . . . . . . . . . . . 165
12 Primary Site Independent Clinical Trials in Oncology . . . . . . . . . . . 167
Richard M. Simon
13 Platform Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
Ben Saville and Scott Berry
14 Efficiencies of Platform Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Satrajit Roychoudhury and Ohad Amit
15 Control of Type I Error for Confirmatory Basket Trials . . . . . . . . . . 211
Cong Chen and Robert A. Beckman
16 Benefit-Risk Assessment for Platform Trials. . . . . . . . . . . . . . . . . . . . 231
Chunlei Ke and Qi Jiang
17 Effect of Randomization Schemes in Umbrella Trials
When There Are Unknown Interactions between
Biomarkers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
Janet J. Li, Shuai Sammy Yuan, and Robert A. Beckman
18 Combinatorial and Model-Based Methods in Structuring
and Optimizing Cluster Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
Valerii V. Fedorov and Sergei L. Leonov
Part IV Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
19 An Executive’s View of Value of Platform Trials . . . . . . . . . . . . . . . . 289
David Reese and Phuong Khanh Morrow
Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .295
