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Why use adaptive design in clinical trials? Let us quickly look at the advantages of adaptive designs in clinical trials and what they mean for you.
Given the high failure rates and the increased costs of clinical trials, researchers need innovative design strategies to best optimize financial resources and reduce the risk to patients.
The FDA defines an adaptive clinical trial design as “a clinical trial design that allows for prospectively planned modifications to one or more aspects of the design based on accumulating data from subjects in the trial.”
The FDA are encouraging sponsors to use adaptive clinical trials as a tool to reduce the risk and costs of a trial, while reducing the time it takes new drugs to reach patients - all while upholding strict standards. For more information about the FDA’s view on adaptive trials, you can check out our blog New FDA Guidance on Adaptive Clinical Trial Design.
What are the advantages of adaptive design in clinical trials?
Based on what the FDA has published in conjunction with what we consider a benefit to researchers, here are five advantages that adaptive design clinical trials may have over a fixed term trial.
Watch the video below or read on for more detail about these 5 high level advantages of adaptive design in clinical trials and how they can positively impact your research.
This video is an excerpt from our webinar The Advantages & Disadvantages of Adaptive Sample Size Re-Estimation.
The first advantage of adaptive design in clinical trials is the ability to make certain decisions earlier than would normally be possible. For example, with the correct adaptive trial design, researchers have the ability to observe and if there is strong evidence for or against the proposed treatment then it makes sense to act quickly upon their findings. This can lead to the following:
Stop the entire trial early
The very simplest and earliest type of adaptive design is a group sequential design. A group sequential design provides researchers with the opportunity to stop a trial early for either efficacy and/or futility. Some form of futility monitoring should be built into a phase 3 trial.
Drop underperforming treatments / doses early
Multiple treatments in phase I/II are often investigated. The ability to drop underperforming treatment/doses provides many benefits for time and costs savings. The continual reassessment method (CRM) is one such approach that while CRM is a Bayesian method of consistently learning about the dose-toxicity relationship after each cohort. It leans to adaptive design as a means of discovering the Maximum Tolerated Dose (MTD). CRM is most notably a common choice in adult oncology. In more recent and complex adaptive trials, the hypothesis can be changed based on this information.
Treatments within a trial may have negative side effects. Being able to move patients onto a higher performing drug sooner is a huge benefit to all involved in the trial.
A benefit of early decision making is the ability to reduce the costs of the clinical trial. This lower upfront cost can often reduce barriers to investment as there are some safeguards in place to avoid prolonging costly measures. The ways in that costs can be reduced can be grouped into the following:
Stopping for futility
The term 'futility' is used to refer to the inability of a clinical trial to achieve its objectives. This involves stopping a clinical trial when the interim results suggest that it is unlikely to achieve statistical significance which can save resources that could be used on more promising research.
Simultaneously test multiple treatments
The cost reduction from this is obvious and a great benefit of adaptive design.
This refers to better statistical efficiency in the clinical trial. The aim is to move as quickly as possible to those methods and treatments that are important.
Make changes based on the best evidence available
For example, if a trial is ongoing and it becomes evident that it is underpowered or that certain groups aren't really responding, the live data can be studied and the trial adapted to reflect this information.
Adaptive trial design allows you to answer more questions from your trial. So instead of focusing on a simple question such as treatment A vs treatment B, the trialists would now have the ability to further examine or ‘dig in’ to sub-population. This would not be possible in a traditional setting as it would be hard to justify and would be unlikely to receive funding.
Higher probability of getting the best treatment
Subjects are in favour of the idea that they will not unnecessarily be put into a placebo/control group through randomization, but upon analysis will be in the best group as the researchers understand it. This also helps in recruiting and retaining subjects.Sponsor funding
All of the points above combined with the FDA pushing for more adaptive trial designs due to their cost and time savings means that sponsors are also increasing their acceptance of adaptive design in clinical trial design.
Like any trial design, if not executed properly there can be some disadvantages. Below is a quick summary of the potential disadvantages of unblinded sample size re-estimation (SSR). However there are ways to overcome these with careful forward planning and reap the benefits of an adaptive design trial.
If you are exploring adaptive designs, one important factor is to select validated and trusted software that is designed for your adaptive trials.
nQuery has dedicated adaptive trial design functionality that contains a selection of sample size tables designed specifically for areas of adaptive design.
We recently hosted a webinar examining Advantages & Disadvantages of Adaptive Sample Size Re-Estimation. You can watch this webinar on demand by clicking the image below.
In this webinar you’ll learn about: