Enhanced trial efficiency of the novel "contemporaneous control recapture" parallel-cohort RCT design: Methods and application in the CRITICAL-Kids-TP trial
Clinical trial published in Contemporary clinical trials (2025)
Abstract
The efficiency and generalizability of the traditional randomized clinical trial (RCT) design are reduced by the exclusion of otherwise eligible participants who decline randomization or undergo early withdrawal due to missed protocol-specified windows for randomization and/or first dose of the investigational drug. These limitations are particularly challenging for RCTs targeting rare diseases. In this report, we describe a novel adaptation to the previously-described "parallel-cohort RCT design", in which these up-front losses in an RCT are recaptured into a parallel, non-randomized, contemporaneous control cohort that augments the randomized controls. We also outline various statistical approaches employed to assure congruence of this non-randomized control group to the control arm of the randomized population, prior to analysis. Lastly, we describe the application of the "contemporaneous control recapture" parallel-cohort RCT design in the CRITICAL-Kids-TP trial (www.clinicaltrials.gov; NCT06628778), a proposed phase 3 trial of pharmacological thromboprophylaxis versus usual care (no pharmacological thromboprophylaxis) in critically ill adolescents.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
The efficiency and generalizability of the traditional randomized clinical trial (RCT) design are reduced by the exclusion of otherwise eligible participants who decline randomization or undergo early withdrawal due to missed protocol-specified windows for randomization and/or first dose of the investigational drug.
Why This Matters for Hirudotherapy
This methods paper describes a novel 'contemporaneous control recapture' adaptation of the parallel-cohort RCT design, in which otherwise-eligible participants who decline randomization or miss protocol windows are recaptured into a non-randomized contemporaneous control cohort that augments the randomized controls, with statistical approaches to confirm congruence before analysis; it illustrates the design in the planned phase 3 CRITICAL-Kids-TP trial of pharmacological thromboprophylaxis versus usual care in critically ill adolescents. It is relevant to ASH's clinical-evidence mission as a template for how rigorous trials of thromboprophylaxis can be made more efficient and generalizable, especially for rare or hard-to-enroll populations, which is precisely the constraint facing any future controlled study of hirudotherapy. The caveat is that this is a trial-design and protocol description, not results: it reports no efficacy or safety outcomes and concerns conventional pharmacologic thromboprophylaxis, not leech therapy.
Citation
Enhanced trial efficiency of the novel "contemporaneous control recapture" parallel-cohort RCT design: Methods and application in the CRITICAL-Kids-TP trial.
Sochet AA et al. · Contemporary clinical trials, 2025
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