The benefits and practical feasibility of utilising ‘adaptive’ designs in clinical trials are currently being investigated by biostatisticians, and it’s hoped that they could be used in investigating diseases as diverse as tuberculosis, malaria and Alzheimer’s.
Adaptive trials allow pre-planned adaptation during the course of the trial in order to maximise its success and the World Health Organization (WHO) have also shown an interest in using the technique in its vaccine trials.
‘Since 1948, the gold-standard for clinical trials has been the double–blind randomised and controlled clinical trial. A trait of such trials is that they are static – the key elements driving the design are specified in advance and do not change. An obvious problem with this approach is that the planning of such trials is based on a fixed set of assumptions. Incorrect choices for these parameters can lead to trials which are under-powered or over-powered, and both of these outcomes are ethically questionable and undesirable.
Adaptive trials employ methodologies that allow study sponsors to monitor the data being gathered during the course of a trial with the objective of implementing a pre-planned adaptation to maximise the success of the trial.
Perhaps the simplest adaptive designs utilise interim analyses, long associated with group sequential trials, to test the assumptions of trials and to make decisions about their future conduct. For example, at an interim if the patient-to-patient variability is much larger than anticipated at the planning stage, the sample size can be increased to ensure that the trial has the desired power. Conversely, if the estimated effect size at the interim is non-existent or much smaller than required then the trial can be stopped for so-called futility. A number of large pharmaceutical companies have implemented such strategies with considerable savings.
A second area for consideration is in phase II dose-response studies. In adaptive dose-finding studies the post promising doses are followed, with ineffective doses being dropped. These designs allow a wider range of doses to be investigated without unduly increasing the number of patients studied.’
The use of many of these designs is being considered outside of the pharmaceutical industry. The WHO has shown an interest in their use in vaccine trials and in diseases such as tuberculosis, HVC and malaria. It is also hoped that adaptive strategies will play a role in developing treatments for diseases such as Alzheimer’s.