Adaptive Studies: What Are They And How Can You Benefit From Them?

Adaptive studies (or adaptive clinical trials) is a relatively new term. They have been around for about 40 years; however, it wasn’t until 2004 that the FDA released the Critical Path Initiative that adaptive studies took shape. It called for more innovative designs to be used to improve study efficiencies.

Adaptive studies help decrease cost and time. By allowing for flexibility into the study, researchers may identify errors in the trial sooner and move on the right path. This adaptability is what makes the difference. By doing so, they cut the time spent on the study, and therefore, reducing costs.

In the article titled Adaptive design clinical trials: Methodology, challenges, and prospect, by Rajiv Mahajan and Kapil Gupta, they state that:

 [...] the pharmaceutical industry is gradually coming to realize that the classically structured clinical trial does not offer enough flexibility to make use of continuously emerging knowledge that is generated as the trial progresses.

 In other words, the knowledge researchers acquire throughout the trials is vast; however, the structure of the study does not allow researchers to make use of it entirely.

What are Adaptive Studies or Adaptive Clinical Trials?

Adaptive clinical trials are those that have protocol amendments, meaning one can modify them at specific points of the study. Researchers define these changes at the beginning of the study; they are not to be done at random or at any point. Investigators take the data acquired during the interim analysis and make decisions based on those results.

The greater flexibility of adaptive approaches allows investigators to address more involved clinical issues, such as patient heterogeneity, treatment scheduling, and combination therapies, in a single study.

Alexia Iasonos & John O'Quigley.

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What are the critical concerns with adaptive trial/study designs?

1. Conventional trials remain as the primary design
   Adaptive studies are a huge benefit for researchers. Nonetheless, some stick to more traditional ways of conducting their investigations. A study in which one either accepts or rejects the hypothesis stated at the beginning. This leads to black and white thinking, not recognizing there might be other paths or even better ones. Adaptive studies allow for modifications and give flexibility to the study. Besides, with adaptive studies, one can test many treatment arms simultaneously, unlike with conventional trials. Proffering adaptive studies the advantage.
   
   
2. Adaptive study designs require constant adaptations
   A frequent use case is dose-finding (finding the proper dose administered). The treatment is a variable continually changing and being adapted to test the minimum dose required for the drug to affect, and the maximum tolerable dose. This means the data monitoring committee needs to meet regularly to make the proper adaptations. Without the appropriate EDC, this could not happen.
   
   
3. Adaptive designs may cause bias
   In adaptive designs, researchers may analyze, and in fact are encouraged to, interpret data during the interim analysis. The knowledge of early data is what is so great about adaptive designs, it does, however, give space for bias. Since researchers know the trends of the study, they adopt the plan the best they can with those results. This may be a problem since they are now biased towards the research. By analyzing the data so early, researchers can now influence the remainder of the trial. That is why an early open discussion is so important, as well as following the FDA and EMEA’s approach, to reduce the bias as much as possible.
   
   

How does Teamscope make it more accessible?

Real-time data analysis

Having data analysis in real-time is crucial. According to Mahajan and Gupta:

[...] quick and reliable electronic data collection would seem to be mandatory for a trial that is dependent on constant updating.

As the trials take place, new knowledge is acquired, and therefore further theories arise. Being able to have that information allows for time optimization and, therefore, a decrease in costs.

Teamscope allows for powerful graphs

The ability to use graphs as the study progresses is incredibly beneficial. Data required throughout the research is essential. The use of charts can help the study as a visual aid as well as an immediate source of results.

Conclusion

Adaptive studies are beneficial for clinical trials; however, many researchers are reluctant and chose more conventional designs over the new more innovative ones. One of the reasons this happens is the constant need for adjustments in adaptive studies. Without the proper platform, these adaptations would be very complicated to make. EDC’s such as Teamscope not only make this a possibility but also make it an easy task. Another reason some researchers chose the traditional designs is the difficulty interpreting data. Teamscope’s real-time data analysis provides researchers on-demand access to statistical analysis, allowing them to have the visibility over the insights that an adaptive workflow requires.

References:

1. Gottlieb K. (2016) The FDA adaptive trial design guidance in a nutshell - A review in Q&A format for decision makers. PeerJ Preprints 4:e1825v1https://doi.org/10.7287/peerj.preprints.1825v1
2. Mahajan, R., & Gupta, K. (2010). Adaptive design clinical trials: Methodology, challenges and prospect. Indian Journal of Pharmacology, 42(4), 201–207. http://doi.org/10.4103/0253-7613.68417
3. Adaptive clinical trial. (2017, September 23). In Wikipedia, The Free Encyclopedia. Retrieved 20:18, February 1, 2018, from https://en.wikipedia.org/w/index.php?title=Adaptive_clinical_trial&oldid=802022701
4. Iasonos, A., & O’Quigley, J. (2014). Adaptive Dose-Finding Studies: A Review of Model-Guided Phase I Clinical Trials. Journal of Clinical Oncology, 32(23), 2505–2511. http://doi.org/10.1200/JCO.2013.54.6051
5. FDA (2010). Guidance for Industry: Adaptive Design Clinical Trials for Drugs and Biologics.