Abstract

Maaike Verweij¹, Maarten Burbach², Roxanne Gal³, Anne May³, Rieke van der Graaf⁴, Martijn Intven¹, Lenny Verkooijen¹

¹University Medical Center Utrecht, Radiation-Oncology, Utrecht, The Netherlands; ²University Medical Center Groningen, Surgery, Groningen, The Netherlands; ³Julius Research Center, Epidemiology, Utrecht, The Netherlands; ⁴Julius Research Center, Medical Humanities, Utrecht, The Netherlands

Trials within cohorts (TwiCs) is an efficient study design for evaluating multiple interventions in an oncology setting. TwiCs embeds pragmatic randomized trials within a cohort study. According to the staged-informed consent procedure for TwiCs, patients are asked for broad consent for future randomization upon cohort enrollment. This includes consent for use of medical data for comparative purposes if randomized to the control group of an embedded trial. If randomized to the intervention group, patients are asked to sign a second trial-specific consent. Patients in the control arm of TwiCs receive care as usual and are not explicitly notified that they take part in a clinical trial. In this study the opinion of patients who had served as control in TwiCs was asked, in order to assess the acceptability of the TwiCs design.

A survey was conducted among  patients with rectal or breast cancer who were randomized to the control arms of two TwiCs (resp. the  RECTAL-BOOST (RB) and UMBRELLA FIT (UF) trials). The survey questioned patient’s opinion of having served as control before and after providing the respective trial results. RB control patients were informed that a boost prior to chemoradiation did not result in a higher probability of pathological complete response. UF control patients were informed that an exercise program 12-18 months after breast cancer treatment resulted in less complaints of fatigue.

37 of 49 (76%) RB and 69 of 69 (72%) UF control patients completed the questionnaire. 54% of RB and 70% of UF did not remember providing broad consent for future randomization at median 4 (range: 2-5) resp.  5 (2-8) years after cohort enrollment.

Before providing the trial results, 51% of RB and 45% of UF indicated a positive opinion and 43% resp. 46% a neutral opinion on having served as control in a TwiC. 22% of RB and 13% of UF thought positively and 62% resp. 68% neutrally about not receiving a notification when serving as control.

The TwiCs design was accepted by the majority of patients who had served as control without explicit notification in TwiCs. Their opinion did not vary by underlying condition, type of intervention and trial outcome. Most patients did not remember their informed consent 2-8 years after cohort enrollment. Actively reminding cohort participants of the possibility of serving as control without explicit notification, might further reduce negative opinions on the TwiCs design.