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Highlights
- •We found a rapid increase in platform trials since the last review, coinciding with the COVID-19 pandemic.
- •Platform trials have now been utilised in more diverse areas of medicine, whereas it was previously dominated by oncology and infectious diseases.
- •We provide the most updated review of platform trials to-date, including methodological aspects of platform trials and also provide readers with an introduction to platform trials by the way of examples throughout the paper.
- •As platform trials become more prevalent, this review can help clinicians and researchers understand platform trials and compare the different approaches taken by successful and unsuccessful models.
Abstract
Introduction
Adaptive platforms allow for the evaluation of multiple interventions at a lower cost and have been growing in popularity, especially during the COVID-19 pandemic. The objective of this review is to summarize published platform trials, examine specific methodological design features amongst these studies and hopefully aid readers in the evaluation and interpretation of platform trial results.
Methods
We performed a systematic review of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and clinicaltrials.gov from January 2015 to January 2022 for protocols or results of platform trials. Pairs of reviewers, working independently and in duplicate, collected data on trial characteristics of trial registrations, protocols, and publications of platform trials. We reported our results using total numbers and percentages, as well as medians with interquartile range (IQR) when appropriate.
Results
We identified 15,277 unique search records and screened 14,403 titles and abstracts after duplicates were removed. We identified 98 unique randomized platform trials. Sixteen platform trials were sourced from a systematic review completed in 2019, which included platform trials reported prior to 2015. Most platform trials (n=67, 68.3%) were registered between 2020-2022, coinciding with the COVID-19 pandemic. The included platform trials primarily recruited or plan to recruit patients from North America or Europe, with most subjects being recruited from the United States (n=39, 39.7%) and the United Kingdom (n=31, 31.6%). Bayesian methods were used in 28.6% (n = 28) of platform RCTs and frequentist methods in 66.3% (n = 65) of trials including 1 (1%) that used methods from both paradigms. Out of the twenty-five trials with peer reviewed publication of results, seven trials used Bayesian methods (28%) and of those, two (8%) used a pre-defined sample size calculation while the remainder used pre-specified probabilities of futility, harm, or benefit calculated at (pre-specified) intervals to inform decisions about stopping interventions or the entire trial. Seventeen (68%) peer reviewed publications used frequentist methods. Out of the seven published Bayesian trials, seven (100%) reported thresholds for benefit. The threshold for benefit ranged from 80% to >99%.
Conclusion
We identified and summarized key components of platform trials, including the basics of the methodological and statistical considerations. Ultimately, improving standardization and reporting in platform trials require an understanding of the current landscape. We provide the most updated and rigorous review of platform trials to date.
Article info
Publication history
Accepted:
February 2,
2023
Received in revised form:
January 26,
2023
Received:
September 20,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Contributions: TP, DZ and BR conceived the study idea. SC, EC, NK, GL, RV, and JM helped collect screen and collect data. CY, EG, SM, AH and BR provided content expertise. BR and DZ contributed equally to supervising the study. TP is the data guarantor.
Declaration of interests
☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:
Tyler Pitre reports financial support was provided by McMaster University.
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.
