Adaptive Designs in Clinical Trials
Improving adaptive design use in practice
Team: Graham Wheeler, Victoria Cornelius, Akino Uda
Adaptive designs aim to make clinical trials more efficient by changing aspects of ongoing studies whilst ensuring that the statistical validity of the study is preserved. Possible adaptations may include adding and dropping treatment arms, changing the randomisation ratio, altering the dose or level of intervention administered, or focusing on a subgroup of patients most likely to benefit based on past trial data.
Barriers to adaptive design use have been identified, including lack of training opportunities and statistical support, availability of user-friendly software, funding and reliance on traditional and established practices. This project encompasses research focussed on:
Reporting quality of trial designs used in practice
Creating novel user-friendly software for adaptive designs
Developing simpler approaches to adaptive designs that require fewer assumptions and are more likely to be adopted intro practice
Improving knowledge transfer between statistical and clinical communities
Adaptive designs for platform trials
Team: Ed Waddingham, Victoria Cornelius, Mohammad Chehrazi
Recent years have seen the emergence of large-scale “platform” trials. In this type of study, the set of interventions to which a participant can be randomised can change over time. For example, interventions may be dropped if enough evidence has been accumulated to show they are ineffective or harmful, and promising new interventions that were unavailable or unknown at the design stage may be added.
Adaptations such as these help to ensure that platforms continue to address a relevant scientific question over longer periods than typical trials, as well as improving statistical efficiency. The ability of platform trials to assess multiple interventions under one protocol also results in operational economies of scale and hence more efficient research.
We are supporting the development of platform trials across several disease areas, evaluating the operating characteristics in each context under various modelled scenarios, and identifying optimal parameters and guidelines to facilitate the design of quality platform trials now and in the future.
Use of adaptive designs in late phase intensive care trials
Team: Leila Janani, Victoria Cornelius, Ellie Van Vogt, Kiarash Tanha, Laurent Billot
Intensive care-based randomised controlled trials present special challenges. They have exceptionally heterogeneous patient population which is hypothesised as a reason for the large proportion of negative trial results, especially where mortality is the primary endpoint.
Use of adaptive trials that undertake interim monitoring can offer an opportunity to stop early for futility or efficacy. This early stopping will improve the cost-benefit ratio of clinical trials in critically ill patients.
We are undertaking a systematic review to determine how many trials use adaptive designs to save recourses. In this project we will answer the following questions:
What designs are being used in late phase trials undertaken in intensive care?
What proportion of trials use an adaptive design, and what are the adaptive elements?
What methods are used for interim monitoring in trials?
Our protocol can be read here.