The quality of a clinical trial design is essential to ensure participant safety and obtain robust conclusions at the end of the trial. MultiHealth explains the advantages of adaptive design and how it is implemented.
The design of a clinical study corresponds to the methodology that defines how the study will be conducted to answer a medical research question. This design specifies the objectives, the study population, the interventions, the comparators, the evaluation criteria, and the duration of the study. Its purpose is to ensure the scientific validity, reproducibility, and reliability of the results while minimizing bias and guaranteeing patient safety. There are several types of designs, such as randomized controlled trials, observational studies, and longitudinal studies.
Greater flexibility guaranteed thanks to an adaptive design
Adopting an adaptive design makes it possible to anticipate changes to the planned clinical trial based on interim statistical results, without impacting the validity of the study itself. This means that changes can be planned prospectively based on analysis of the initial study data. Unlike a fixed design for the entire trial, as seen in "traditional" clinical studies, an adaptive design allows changes to be made at a given stage, while controlling the integrity of the trial. This must be provided for in the protocol and validated in advance by the regulatory authorities.
The defined changes can then be implemented based on the results of interim analyses carried out at pre-planned stages. No additional regulatory steps are necessary, as the changes or developments will have been approved by the authorities in advance. When properly implemented, adaptive plans can limit resource requirements, reduce the time needed to complete the investigation, and/or increase the chances of success.
Adaptive designs for medical devices
The FDA (Food and Drug Administration) has published an educational guide on adaptive designs specific to clinical investigations conducted for medical devices (1). This guide provides study sponsors with guidance on how to plan and implement adaptive designs for clinical studies when used in medical device development programs. In particular, it specifies that an adaptive model is generally feasible if the adaptation is intended to address a small number of endpoints and if the timing of the primary endpoint measurement is compatible with adaptation for the remainder of the investigation.
In practice, adaptive design will allow characteristics such as the number of patients, trial eligibility criteria, randomization rules, and endpoints to be modified during the course of the study.
A recent literature review took stock of the use of adaptive models in randomized controlled trials conducted in the field of medical devices between 2000 and 2024 (2). A total of 105 trials were identified, most of which (76.2%) were conducted after the device was placed on the market. The most common adaptive designs were sequential by group (50.5%) and sample size re-evaluation (17.1%).
Sequential design as an adjustment variable
Sequential group design incorporates interim analyses at several strategic points during the investigation to assess the efficacy or safety of a treatment. This design allows the study to be stopped early for defined groups of patients in cases of proven efficacy, proven ineffectiveness, or safety issues. This limits the number of patients exposed and reduces the time and cost of the trial.
Reassessment of sample size is an approach that allows the number of patients to be adjusted at predefined intermediate stages, based on data already collected, such as variance or event rate. This improves statistical power and reduces the risk of failure due to underestimating or overestimating the number of participants needed. This approach allows for mid-trial adjustments in trials where the effect of the treatment or management is significant but weaker than expected.
Increase trial efficiency while reducing time to market
The use of an adaptive design increases the efficiency of the trial, better protects patients, and improves the acceptability of the trial by stakeholders. In addition, it facilitates the timely evaluation and marketing of medical devices with a reasonable guarantee of safety and efficacy.
1 "Adaptive Designs for Medical Device Clinical Studies – Guidance for Industry and Food and Drug Administration Staff."
2 Su et al. Characterization of medical device randomized controlled trials with adaptive designs. J Comp Eff Res. 2024 Dec 9;14(1):e240011. doi: 10.57264/cer-2024-0011
