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Platform trials: full steam ahead?

Platform trials: full steam ahead?

01 May 2021

James Wason, Professor of Biostatistics, RDS North East and North Cumbria

Background

Clinical trials provide the highest quality evidence on the benefits and harms of new healthcare interventions. Nevertheless, the cost of conducting clinical trials is high, and increasing(1).

New approaches for designing, conducting and analysing clinical trials are playing an important role in improving their efficiency. Improved efficiency means reducing the cost and time taken without compromising level of evidence provided. One way to do this is through combining (what used to be) several clinical trials testing related questions into a single platform trial.

What are platform trials?

Different researchers have used the term platform trial in subtlety different ways. Generally, it is a clinical trial that has the following properties (see figure):

  1. New treatment arms can be added during the trial;
  2. A shared control arm is used, which each treatment arm is compared to;
  3. An adaptive design(2) is used, allowing changes to be made, e.g. dropping less promising arms from the trial.

Diagram of a platform trial

Put simply, platform trials evaluate multiple treatments for a single disease, adding and dropping arms as they progress.

A famous example of a platform trial that uses all three of the above properties is the STAMPEDE trial in prostate cancer(3). STAMPEDE started over a decade ago and is still ongoing. It has rigorously evaluated several new treatments, leading to changes in standard of care. Several methodology articles have been published by STAMPEDE investigators to help other researchers implement the same idea in other disease areas(3).

Platform trials have become more prominent during the COVID-19 pandemic. Several UK and international platform trials were set up and started recruiting in record time. High-quality evidence from these trials has contributed substantially to the prevention and treatment of COVID-19.

Advantages, challenges?

Each property of the platform trial listed above provides advantages compared to the traditional way of conducting clinical trials:

  1. Adding new treatment arms into an existing trial is generally much easier than starting a new trial from scratch. A new intervention in a platform trial benefits from the sites already opened, meaning maximum recruitment speed.
  2. A shared control group reduces the number of patients needed to be allocated to the control group, leading to lower sample size required.
  3. An adaptive design means fewer patients are allocated to less effective arms on average.

These advantages are highly relevant to funders. A platform trial efficiently answers multiple research questions that would otherwise require several traditional trials to be run. This can make a platform trial excellent value for money compared with running several separate trials.

Despite these advantages, platform trials are complex and often have had enthusiastic researchers who were willing to work to overcome challenges. Challenges include regulatory acceptance(4), issues to do with trial management(5), data management(6) and statistical properties(7). Successful platform trials in various clinical areas have shown these can be overcome.

How the RDS can help

Many of the regional NIHR Research Design Services have access to expertise in design of platform trials. Where local expertise is not available, researchers can be referred to experts in other regions. Further support can be sought through RDS links to the UKCRC network of Clinical Trials Units (https://www.ukcrc-ctu.org.uk/) and the Trials Methodology Research Partnership (https://www.methodologyhubs.mrc.ac.uk/about/tmrp/).

Conclusion

Platform trials have demonstrated great potential for improving efficiency of evaluating healthcare interventions. Despite some challenges, it is likely their use will continue to increase in a variety of clinical areas.

References

  1. DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: New estimates of R&D costs. J Health Econ. 2016;47:20–33.
  2. Pallmann P, Bedding AW, Choodari-Oskooei B, Dimairo M, Flight L, Hampson LV, et al. Adaptive designs in clinical trials: why use them, and how to run and report them. BMC Med. 2018;16(1):29.
  3. http://www.stampedetrial.org/
  4. Collignon O, Gartner C, Haidich A-B, Hemmings RJ, Hofner B, Pétavy F, et al. Current Statistical Considerations and Regulatory Perspectives on the Planning of Confirmatory Basket, Umbrella, and Platform Trials. Clin Pharmacol Ther. 2020;107(5):1059–67.
  5. Schiavone F, Bathia R, Letchemanan K, Masters L, Amos C, Bara A, et al. This is a platform alteration: A trial management perspective on the operational aspects of adaptive and platform and umbrella protocols. Trials. 2019;20(1):264.
  6. Hague D, Townsend S, Masters L, Rauchenberger M, Van Looy N, Diaz-Montana C, et al. Changing platforms without stopping the train: experiences of data management and data management systems when adapting platform protocols by adding and closing comparisons. Trials. 2019 May 29;20(1):294.
  7. Lee KM, Brown LC, Jaki T, Stallard N, Wason J. Statistical consideration when adding new arms to ongoing clinical trials: the potentials and the caveats. Trials. 2021 Dec;22(1):1–10.

Note: This article was written as part of a RDS national priority initiative to encourage the use of innovative research methods. This initiative is planning whether developing training materials in this area would be of interest to researchers. The author would appreciate hearing from individuals who have a view on this.

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