The trials within cohorts design facilitated efficient patient enrollment and generalizability in oncology setting

Abstract

Objectives: The trials within cohorts (TwiCs) design aims to improve recruitment efficiency. We conducted the first TwiCs in radiation oncology and described efficiency of the design and generalizability of the results.

Study design and setting: In two radiotherapy centers, patients with rectal cancer were asked to participate in a prospective cohort study and to provide broad consent for randomization and patient-reported outcomes (PROs). Consenting patients who met the trial criteria were randomized directly after cohort enrollment. The intervention arm was offered a radiotherapy boost. We evaluated acceptance rate, its impact on sample size, and compared clinical characteristics between trial participants and patients of the Dutch national cancer registry.

Results: 128 of the 200 eligible patients (64%) were randomized. Sixty-two patients did not consent (in time) to cohort participation, to broad randomization, or to PROs. Of the 64 patients in the intervention arm, 52 (81%) accepted the intervention. During the trial, the acceptance rate dropped temporarily, after which sample size was adapted. Trial patients were comparable in age, comorbidity, and disease stage to the national rectal cancer population.

Conclusions: The TwiCs design is feasible, allows enrollment of a high proportion of randomizable patients, with positive impact on trial efficiency and generalizability of results in a clinical oncology setting.

Trial registration: ClinicalTrials.gov NCT01951521.

Keywords: Clinical trial; Patient recruitment; RCT; Study design; Trials within cohorts.