Abstract
The proceedings of the 16th annual Conference on Statistical Issues in Clinical Trials appear in this issue of Clinical Trials, a tradition beginning in 2010.1–15 The proceedings include invited papers from our speakers along with edited morning and afternoon panel discussions, with audience members, both in-person and online, offering additional perspectives.
Table 1 lists our speakers and panelists. Dr. Pamela A. Shaw delivered closing remarks which are summarized here. Our overview speaker, Dr. Frank Bretz, considered in-depth some of the difficult issues in designing a dose-finding trial and, in particular, the challenging issues with identifying dose when the shape of the underlying dose-response curve is unknown. He touched on adaptive designs, multiplicity, and frameworks for maintaining valid inference and preventing overfitting to data in the context of efficient adaptations. Dr. Joyce Cheng advocated reform of many aspects of dose-finding trials in oncology, particularly with the new therapies coming online. She noted that there may be multiple doses sitting in the efficacy zone for targeted therapies at the same time as there may be late-occurring toxicities. Dr. Cheng described the need to consider efficient designs and possibly adaptive designs, but coming from the regulatory perspective, also maintaining rigorous type-one error control. Dr. Ying Yuan introduced several efficient statistical designs and strategies for dose-finding in early phase trials and described some of their advantages and limitations. One example involved pooling data from one trial phase into the next, where information from both phases can be used for more efficient inference. A second involved the idea of backfilling to generate additional information on safety, tolerability, and preliminary activity on a range of doses below the maximum tolerated dose. Finally, in the morning, Dr. Mandy Jin provided insights into seamless phase II/III designs with again the idea of pooling information to allow information to accumulate in order to make effective decisions in the setting of multiple endpoints. The morning concluded with a panel/audience discussion led by Drs. Ken Cheung and Elizabeth Garrett-Mayer.
2024 University of Pennsylvania conference on statistical issues in clinical trials: optimizing dose selection across the clinical trials spectrum.
The afternoon involved novel topics and applications. Dr. Weng Kee Wong described how looking into other fields and finding innovations from engineers and computational science gives new insights into the challenges central to optimal study design. His paper delves into the world of metaheuristics and particle swarm optimization as it applies to dose-finding (and other) design problems. In the challenging setting of drug combinations, Dr. Pavel Mozgunov gave a concrete example of some of the struggles in introducing more complex designs to our collaborators, particularly in the context of combination therapies. Dr. Michael Kosorok presented SMART designs (dynamic treatment regimens) that typically involve adaptations of multiple interventions but also have potential for use in the context of non-traditional dose-finding. Finally Dr. Yunda Huang talked about novel issues in dose-finding in the context of infectious disease, specifically HIV prevention, vaccines and monoclonal antibodies. Panelists Drs. Anna Heath and Kelley Kidwell closed the day with intriguing questions.
We hope you enjoy these thought-provoking papers and edited transcripts of the panelists’ comments and audience discussions.
Footnotes
Acknowledgements
The authors thank the hard-working program committee including Drs. Susan Ellenberg, Jonas Ellenberg, Michael Harhay, Wei-Ting Huang, Yimei Li, Devan Mehrotra and Pamela Shaw and our Administrative Director, Ms. Marissa Fox, for outstanding logistical support. The Department of Biostatistics, Epidemiology and Informatics at the Perelman School of Medicine, University of Pennsylvania, provided the conference facility and logistical support, and the American Statistical Association and the Society for Clinical Trials provided in-kind support for the conference. Additional financial support was provided by Merck & Co. They thank the reviewers who carefully read and provided excellent comments on the papers presented here.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
