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Challenges in Cancer Clinical Trials
Published in Wei Zhang, Fangrong Yan, Feng Chen, Shein-Chung Chow, Advanced Statistics in Regulatory Critical Clinical Initiatives, 2022
Since platform trials allow multiple interventions to be explored simultaneously, usually multiple arms will be incorporated with a single experimental therapy assigned to each arm and a common control arm designed to facilitate the comparisons between new investigational agents and standard of care. Considering the dependence among multiple arms and relatively small sample size within each arm, statistical model that is able to borrow information across multiple arms is demanded. Bayesian Hierarchical Model (BHM) firstly proposed by Thall et al. (2003) could be used to fit this purpose. However, this model will lack power and inflate Type I error when treatment effect across multiple arms is heterogeneous. To solve this problem, Jiang et al. (2020) proposed Optimal Bayesian Hierarchical Model (OBHM) to trade-off power and Type I error through a utility function and maximize this utility function by considering homogeneous or heterogeneous treatment effects.
Rare Diseases Drug Development
Published in Shein-Chung Chow, Innovative Statistics in Regulatory Science, 2019
In practice, master protocol is intended for the addition or removal of drugs, arms, and study hypotheses. Thus, in practice, master protocols may or may not be adaptive, umbrella, or basket studies. Since master protocol has the ability to combine a variety of logistical, innovative, and correlative elements, it allows learning more from smaller patient populations. Thus, the concept of master protocols in conjunction with adaptive trial design described in the previous section may be useful for rare diseases clinical investigation although it has been most frequently implemented in oncology research. For rare diseases drug development, a platform trial with master protocol is often considered. A platform trial is an exploratory multi-arm clinical trial evaluating one or more treatments on one or more cohorts (or populations) with an objective to screen and identify promising treatments in connection with some cohorts for further investigation (see also Table 18.3). Note that a platform trial is typically followed by confirmative studies further investigating potential arms identified by the screening outcomes.
Basket Trials at the Confirmatory Stage
Published in Zoran Antonijevic, Robert A. Beckman, Platform Trial Designs in Drug Development, 2018
We have alluded in the Preface to this volume to differences in preferred terminology among authors. The terminology in this chapter is as follows: a platform trial is any trial that is capable of studying either multiple drugs or multiple disease entities simultaneously (Figure 3.1). Basket trials and umbrella trials study either multiple disease entities or multiple drugs, respectively.
Building the foundation for a community-generated national research blueprint for inherited bleeding disorders: facilitating research through infrastructure, workforce, resources and funding
Published in Expert Review of Hematology, 2023
Margaret V. Ragni, Guy Young, Glaivy Batsuli, Emily Bisson, Shannon L. Carpenter, Stacy E. Croteau, Adam Cuker, Randall G. Curtis, Michael Denne, Bruce Ewenstein, Amber Federizo, Neil Frick, Kerry Funkhouser, Lindsey A. George, W. Keith Hoots, Shawn M. Jobe, Emily Krava, Christopher James Langmead, Roger J. Lewis, José López, Lynn Malec, Ziva Mann, Moses E. Miles, Emma Neely, Ellis J. Neufeld, Glenn F. Pierce, Steven W. Pipe, Lisa R. Pitler, Leslie Raffini, Kathaleen M. Schnur, Jordan A. Shavit
Identifying, procuring, and managing the diverse, sustainable funding and other resources and recruiting, retaining, and training the workforce necessary to facilitate the prioritized inherited BDs research requires specific expertise, building upon successful models and innovating novel initiatives. Scientifically well-designed research studies, quality and uniform data collection, aligned and integrated sources and databases, use of technological advances to mine maximum information from existing records, and identification of the most meaningful metrics and predictive models all must be explored [42,43]. Innovations such as adaptive platform trials, embedding trials in medical records, and de-centralizing trial participation also offer opportunities to optimize the platforms and study designs that underpin research.
A narrative review on drug development for the management of antimicrobial- resistant infection crisis in Japan: the past, present, and future
Published in Expert Review of Anti-infective Therapy, 2022
Takahisa Ohashi, Masahito Nagashima, Nobuko Kawai, Norio Ohmagari, Kazuhiro Tateda
The first sincere attempt against COVID-19 was to conduct a huge number of clinical trials. However, the traditional phase 3 study design required independent patient enrollment in each study to test a single hypothesis. This traditional strategy led to sharing of the limited number of patients among multiple clinical trials and a delay in patient recruitment. Throughout the COVID-19 pandemic, significant progress has been made in expanding research networks and leveraging key innovations in the clinical trial design. Adaptive platform trials, for example, allow researchers to validate multiple interventions for a single disease simultaneously by comparing them with a single common control group [62,63]. Adaptive platform trials also allow modifications and adjustments as the trial progresses by adding or removing treatments and updating the trial design [62,63]. Facilitation of clinical trials through international networks and collaboration and an adaptive platform design is achieved for COVID-19 in the RECOVERY (NCT04381936) [64], WHO SOLIDARITY (ISRCTN83971151; NCT04315948) [65], the Adaptive COVID-19 Treatment Trial (NCT04280705) [66,67], and the Accelerating COVID-19 Therapeutic Interventions and Vaccines initiative announced in April 2020 [68].
Clinical care and therapeutic trials in PLS
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2020
Mary Kay Floeter, Deborah Warden, Dale Lange, James Wymer, Sabrina Paganoni, Hiroshi Mitsumoto
Platform trials are trials where multiple investigational products are tested in the context of a single disease (multiple drugs > one disease) (38,42). These trials are “perpetual” in that they have no defined end date and leverage an infrastructure that remains open long-term to accommodate new experimental agents (42). The design of these trials is often adaptive: it is possible to continue to refine the trial design over time to include more efficient measures of disease progression as they become available (43). Furthermore, platform trials represent an opportunity to collect bio-samples and data using coordinated processes thus enabling disease-focused scientific discovery projects. This model has already been adopted by the ALS community with the launch of the HEALEY ALS Platform trial (44). The HEALEY ALS Platform Trial is testing multiple investigational products (both in parallel and sequentially). This collaborative trial is also facilitating the systematic collection of longitudinal bio-samples to support biomarker discovery efforts. Thus, in addition to evaluating promising investigational products, the trial is also a source of data and samples that will, in turn, contribute to our understanding of ALS mechanisms and help develop better outcome measures and biomarkers. The establishment of a PLS platform would help accelerate drug development and provide critical learnings for this understudied disease.