|Adaptive Trial Design 1: An Overview......
Adaptive Trial Design 1: An Overview
Adaptive trial design refers to a clinical trial methodology that allows trial design modifications to be made after patients have been enrolled in a study, without compromising the scientific method. In order to maintain the integrity of the trial, these modifications should be clearly defined in the protocol.
When designed well, an adaptive trial empowers sponsors to respond to data collected during the trial. This is achieved by re-focusing the trial in a way that maximises the impact of each subject’s contribution. Examples of adaptive trial designs include dropping a treatment arm, modifying the sample size, balancing treatment assignments using adaptive randomisation or simply stopping a study early for success or failure.
In a standard trial, safety and efficacy data are collected and reviewed by a monitoring board during scheduled interim analyses. However, aside from stopping a study for safety reasons, very little can be done in response to that data. Often, a whole new study must be designed to further investigate key trial findings.
In an adaptive trial, the sponsor might have the option of responding to interim safety and efficacy data in a number of different ways, including narrowing the trial focus or increasing the patient population. An example of narrowing the trial focus includes removal of one or more of the treatment arms based on predetermined futility rules. Alternatively, if the data available at the time of the review do not allow for a clear decision between utility and futility, it might be decided to expand the enrolment of patients on one or more treatment arms beyond the initially targeted sample size.
Another example of adaptive design is the response-adaptive. In a response-adaptive setting, patients are randomised to treatment arms based on the response to treatment of previous patients. In a response adaptive trial, real-time safety and efficacy data can be incorporated into the randomisation strategy in order to influence subsequent adaptive randomisation decisions on a patient-by-patient basis. An example of response-adaptive randomisation is “play-the-winner”, which assigns patients to treatment arms that have resulted in fewer adverse events or better efficacy.
As these examples demonstrate, the adaptive design concept can be utilised in a number of different ways to increase trial flexibility. In a well-designed adaptive trial, that flexibility can result in lower drug development costs, reduced time to market and improved patient safety. Cost reduction is achieved by stopping unsuccessful trials earlier, identifying successful trials sooner, dropping unnecessary treatment arms or determining effective dose regimens faster.
Time to market can be accelerated by identifying successful trials sooner and reducing, or removing entirely, the lead time between trial phases, especially Phases II and III. Patient safety is improved because adaptive trials tend to reduce exposure to unsuccessful treatment arms (which are dropped early), and increase access to effective treatment arms (via response adaptive randomisation).
Article written by: Eva Miller, Manager of Biostatistical Services, Stephane Deleger, West Coast Business Development Manager, and Jim Murphy, Vice President of Business Development and Marketing at Interactive Clinical Technologies, Inc (ICTI)
The authors can be contacted at firstname.lastname@example.org
Full paper can be accessed at: http://www.pharmaceutical-int.com/article/implementing-and-managing-adaptive-designs-for-clinical-trials.html