by Liz Allen, Visiting Professor, Faculty of Life Sciences and Medicine, King’s College London and Quintiles, Early Clinical Development
What is a clinical trial?
Clinical trials are studies designed to evaluate the effectiveness and safety of potential new medicines. Clinical trials are divided into four phases (Phase I, II, III and real world late phase studies sometime called Phase IV).
Phase 1 requires a small number of subjects, usually healthy volunteers though more recently such studies involve small numbers of patients. As the development moves from phase to phase increasingly large numbers of patients become involved and the cost escalates. It is estimated that about 40% to 50% of drugs that enter phase III studies will fail, by which point a pharmaceutical company will have invested close to one billion pounds.
How is an adaptive trial different?
Adaptive clinical trial designs have been proposed as a means of more quickly determining the benefits and risks of a new medicine while continuing to help ensure patient safety.
Compared to ‘traditional’ clinical trials, adaptive clinical trials have a more flexible design, allowing trials to be modified depending on interim safety and efficacy results, giving an earlier indication of medicine efficacy and safety. Adaptive clinical trials maximise the contribution of each individual trial participant, potentially allowing fewer participants to be needed, thereby reducing costs. Patients also benefit in that drug doses that are proving to be ineffective or harmful can be either changed or stopped.
What are the pros and cons?
Adaptive design methods can be attractive due to their flexibility. They are particularly useful in early clinical development where the effective dose or most effective route of administration is not yet known. However, as adaptive clinical trials allow for changes during the trial, the statistical analysis of the results is more complex than in a traditional trial. Furthermore, there is a possibility of introducing bias into the study through the selective use of the best results and adapting the trial to only focus on positive outcomes.
There is no doubt that compared with traditional trials, adaptive clinical trials require greater communication and coordination between clinicians, trial managers, statisticians and those involved in the regulation process. However, the use of an adaptive design for clinical trials has the potential to bring new and safer medicines to market sooner and to provide earlier therapeutic benefits to more patients whilst reducing the exposure to less effective medicines.
Is it time for adaptive design?
While adaptive clinical designs pose many challenges, they also offer many potential benefits. Is now the time right to embrace adaptive clinical designs and grasp the opportunity to take a step forward from the traditional randomised controlled trial?