Adaptive Clinical Trial Design Software

Are Adaptive designs more efficient?

Adaptive designs allow clinical trials to be more flexible by utilising results accumulated in the trial to change the trial’s course. Trials with an adaptive design are usually more efficient, informative and can be more ethical than trials that have a traditional fixed design because they often make better use of resources such as time and money, and may require fewer participants.

Adaptive designs can also be potentially less efficient than a fixed term trial or simple adaptive design if designed poorly. For example, sample size re-estimation designs lead to higher average sample sizes for minimal success rate increases or adaptive selection designs which include additional arms with minimal prior chance of succeeding.

Overall, adaptive designs when properly considered and well-planned have considerable scope for increasing trial efficiency but the additional flexibility could mean more opportunities for making poor design decisions.

Recommended:
An Introduction to Adaptive Clinical Trial Designs

What is a Group Sequential Design?

Group sequential designs are the most widely used type of adaptive trial in confirmatory Phase III clinical trials. Group sequential designs differ from a standard fixed term trial by allowing a trial to end early based on pre-specified interim analyses for efficacy or futility. Group sequential designs achieve this by using an error spending method that allows a set amount of the total Type I (efficacy) or Type II (futility) error at each interim analysis. The ability to end the trial can help reduce costs by creating an opportunity to get early approval for highly effective treatments and abandoning trials that have shown very poor results thus far.

What is the assessment of futility in clinical trials?

The term 'futility' refers to the inability of a clinical trial to achieve its aims, such as, ending a clinical trial when the interim results suggest that it is highly unlikely to achieve statistical significance. This can save resources which can then be used in other more promising studies.

Recommended:
An Introduction to Adaptive Clinical Trial Designs

What is sample size re-estimation (SSR)?

Sample size r-estimation (SSR) is a type of adaptive trial where one can change the sample size if required. Sample size determination is a pre-trial process that will be conducted on the basis of inherently uncertain planning parameters (e.g. variance, effect size) and thus changing the sample size based on improved interim estimates for these parameters is an obvious adaptation target.

SSR can ensure that sufficient power is obtained for promising results in an underpowered study or could ensure more patients receive the superior treatment or transition directly from one trial phase to another. Combined this may reduce the use of resources and time or improve the likelihood of success of the trial.

There are two primary types of SSR: Unblinded SSR and Blinded SSR. The main differences between these designs are that they differ on whether the data is blinded or not and the planning parameter targeted to for an improved interim estimate.

Recommended Viewing:
Blinded Sample Size Re-Estimation in Clinical Trials

What is conditional power?

Conditional power is the probability that the trial will reject the null hypothesis at a subsequent look given the current test statistic and the assumed “true”  parameter values, which are usually assumed to equal their interim estimates or their initial planning values. 

What is predictive power?

Predictive power (also known as Bayesian Predictive Power) is the conditional power averaged over the posterior distribution of the effect size. It is commonly used to quantify the probability of success of a clinical trial. It has been suggested as a superior alternative to conditional power as it treats the “true” estimates as uncertain rather than fixed.

Recommended:
An Introduction to Adaptive Clinical Trial Designs