Characterization of medical device randomized controlled trials with adaptive designs
Publication: Journal of Comparative Effectiveness Research
Abstract
Aim: Adaptive designs are frequently used in drug randomized controlled trials (RCTs). However, their use in medical device RCTs remains unclear. We aimed to characterize medical device RCTs with adaptive designs. Materials & methods: We searched for adaptive RCTs in the following databases: ClinicalTrials.gov, International Clinical Trials Registry Platform and the International Standard Randomised Controlled Trial Number registry. Adaptive design keywords and medical device corporation names were used as terms to search the trial records registered between 1 January 2000 and 18 October 2024 in the databases. The annual number and proportions of adaptive trials were analyzed, and characteristics such as design type, sponsor, therapeutic area, trial stage and regulatory status were summarized. Results: Overall, 105 adaptive RCTs were identified from ClinicalTrials.gov, accounting for 2.112 per 1000 trials in 49,721 medical device clinical trials registered in ClinicalTrials.gov during the period. The average annual number of adaptive RCTs per 1000 clinical trials was the highest (8.55 ± 11.65) during 2005–2010, reduced to 3.33 ± 2.35 during 2011–2016, and significantly decreased to 1.29 ± 0.85 during 2017–2024 (p = 0.011). The most common adaptive designs were group sequential design (GSD, 50.5%), sample size reassessment (SSR, 17.1%) and investigating both superiority and non-inferiority (10.5%). Most RCTs were sponsored by the private sector (62.9%), conducted in Europe/North America (95.2%), in the field of heart disease (46.7%) and post-market trials (76.2%). Compared with pre-market RCTs, post-market RCTs showed more diverse adaptive designs such as response-adaptive randomization and adaptive enrichment. Conclusion: The average annual proportions of adaptive medical device RCTs in ClinicalTrials.gov has reduced in the last 10 years. The most-used adaptive designs in medical device RCTs are GSD, SSR and investigating both superiority and non-inferiority.
Shareable abstract
Adaptive medical device RCTs allow preplanned trial modifications and may be more efficient and better protect patients than conventional ones. Of the 105 medical device adaptive RCTs identified from ClinicalTrials.gov, GSD, SSR and investigating both superiority and non-inferiority are the most-used adaptive designs.
Plain language summary
What is this article about?
An adaptive design allows changing the study design of an ongoing clinical trial based on accumulating study data. Using adaptive designs can potentially increase trial efficiency, better protect patients and improve stakeholder acceptability of the trial. To better understand whether adaptive designs are used in medical device randomized controlled trials (RCTs), we identified and characterized adaptive medical device RCTs from public clinical trial databases.
What were the results?
We identified 105 adaptive RCTs from 49,721 medical device clinical trials registered in ClinicalTrials.gov (2000–2024). The average annual number of adaptive RCTs per 1000 clinical trials decreased significantly from the highest (8.55 ± 11.65) during 2005–2010 to the lowest (1.29 ± 0.85) during 2017–2024 (p = 0.011). The most common adaptive designs were group sequential design (GSD, 50.5%), sample size reassessment (SSR, 17.1%) and investigating both superiority and non-inferiority (10.5%). A GSD allows possible early stopping the trial for success or futility based on the results from analyzing accumulated data in an ongoing trial (interim analysis results). A SSR design allows adjusting the sample size based on interim analysis results. Most of the 105 adaptive RCTs were sponsored by the private sector (62.9%), in the field of heart disease (46.7%) and post-market trials (76.2%).
What do the results mean?
Adaptive designs appear not to be used commonly in medical device RCTs. GSD, SSR and investigating both superiority and non-inferiority are the most-used adaptive designs. Approaches to enhance the understanding of adaptive designs and encourage the adoption thereof in medical device clinical trials should be further developed.
Supplementary Material
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© 2024 The authors. This work is licensed under the Attribution-NonCommercial-NoDerivatives 4.0 Unported License
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Received: 29 January 2024
Accepted: 6 November 2024
Published online: 9 December 2024
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Characterization of medical device randomized controlled trials with adaptive designs. (2024) Journal of Comparative Effectiveness Research. DOI: 10.57264/cer-2024-0011
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