Adaptive Designs in Clinical Trials

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Improving adaptive design use in practice

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:

  • 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

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Model-based early-phase trial design​

As healthcare becomes more personalised, we are seeing higher demand for complex and innovative designs in clinical trials. Many novel approaches to conducting dose-finding trials use advanced statistical modelling, requiring many design parameters to be specified in advance and extensive simulation studies to evaluate how well-suited a particular design is for our trial.

We are working on approaches to generate operating characteristics for complex model-based trial designs that require fewer assumptions and minimal or no simulations. We aim to improve the speed and quality with which early-phase trials are designed, and therefore increase the appropriate use of novel dose-finding methods in practice.

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Use of adaptive design​s in late phase intensive care trials

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. (1,2)

 

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?