Re-randomization increased recruitment and provided similar treatment estimates as parallel designs in trials of febrile neutropenia

Abstract

Objective: Re-randomization trials allow patients to be re-enrolled for multiple treatment episodes. However, it remains uncertain to what extent re-randomization improves recruitment compared to parallel group designs or whether treatment estimates might be affected.

Study design and setting: We evaluated trials included in a recent Cochrane review of granulocyte colony-stimulating factors for patients with febrile neutropenia. We assessed the recruitment benefits of re-randomization trials; compared treatment effect estimates between re-randomization and parallel group designs; and assessed whether re-randomization led to higher rates of non-compliance and loss to follow-up in subsequent episodes.

Results: We included 14 trials (5 re-randomization and 9 parallel group). The re-randomization trials recruited a median of 25% (range 16-66%) more episodes on average than they would have under a parallel-group design. Treatment effect estimates were similar between re-randomization and parallel group trials across all outcomes, though confidence intervals were wide. The re-randomization trials in this review reported no loss to follow-up and low rates of non-compliance (median 1.7%, range 0-8.9%).

Conclusions: In the setting of febrile neutropenia, re-randomization increased recruitment while providing similar estimates of treatment effect to parallel group trials, with minimal loss to follow-up or non-compliance. It appears to be safe and efficient alternative to parallel group designs in this setting.

Keywords: Clinical trials; Febrile neutropenia; Poor recruitment; Randomized controlled trials; Re-enrolment; Re-randomization.