Adaptive trials in low back pain and osteoarthritis: How common are they and when should they be used? A systematic review from ClinicalTrials.gov

This registry-based systematic review aimed to investigate the use and applicability of adaptive designs in ongoing low back pain (LBP) and osteoarthritis (OA) trials and discuss emerging opportunities of adaptive designs in the field, in light of the expected advantages and possible challenges.

We searched ClinicalTrials.gov for records of ongoing studies in chronic LBP or OA. The applicability of adaptive designs for the included trials was assessed based on the ratio of primary endpoint length to recruitment length, considering a ratio below 0.25 as an indicator of potential feasibility. Meeting this ratio means there may be opportunities to implement adaptations that improve trial efficiency and benefit participants yet to be recruited.

Overall, 579 clinical trials were included (135 trials in LBP and 447 trials in OA, with three overlapping studies among the two conditions). A ratio below 0.25 was observed in 89 (66%) LBP trials and 256 (57%) OA trials, suggesting they could potentially benefit from an adaptive design. However, only two (1.5%) out of 135 LBP trials and eight (1.8%) out of 447 OA trials reported an adaptive design, with the most common types being dose escalation studies (67%), followed by group-sequential designs (22%), and master protocols (11%).

The use of adaptive designs in LBP and OA clinical trials is rare, although many trials would benefit from using this innovative approach to trial conduct. Researchers should be encouraged to consider the benefits and challenges of employing an adaptive design to plan future trials.