The Trials within Cohorts design faced methodological advantages and disadvantages in the exercise oncology setting

Abstract

Objectives: The Trials within Cohorts (TwiCs) design is an alternative for pragmatic randomized controlled trials (RCTs) and might overcome disadvantages such as difficult recruitment, dropout after randomization to control, and contamination. We investigated the applicability of the TwiCs design in an exercise oncology study regarding the recruitment process, representativeness of the study sample, contamination, participation, and dropout.Methods: The Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA) Fit TwiCs evaluates an exercise intervention in inactive breast cancer patients. Eligible patients participating in the prospective UMBRELLA were identified and randomized. Patients randomized to the intervention (n 5 130) were offered the intervention, whereas controls (n 5 130) were not informed.Results: Fifty-two percent (n 5 68) accepted the intervention. Because this rate was lower than expected, a larger sample size was required than initially estimated (n 5 166). However, recruitment of 260 patients was still completed by one researcher within 30 months. Unselective eligibility screening and randomization before invitation improved representativeness. Disadvantage of the design might be inclusion of ineligible patients when cohort information is limited. Furthermore, the design faced higher noncompliance in the intervention group, but prevention of contamination.Conclusion: The TwiCs design improved logistics in recruitment and prevented contamination, but noncompliance due to refusal of the intervention was higher compared with conventional pragmatic exercise oncology RCTs, which may dilute the estimated intervention

The impact of the COVID-19 pandemic on quality of life, physical and psychosocial wellbeing in breast cancer patients and survivors – a prospective, multicenter cohort study

“…The present study was conducted within the ongoing prospective multicenter Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA). 16,17 Since 2013, the UMBRELLA cohort included patients ≥ □ 18 years old, who were referred from six hospitals in the Utrecht region to the Department of Radiation Oncology of the University Medical Center Utrecht (UMCU), the Netherlands. Inclusion criteria were histologically proven invasive breast cancer or ductal carcinoma in situ (DCIS), and the ability to understand the Dutch language (written and spoken).…”

The adapted Zelen was a feasible design to trial exercise in myeloma survivors

“…Reporting an alternative study design similar to Zelen, Gal et al. used a “trials within cohort RCT” within an exercise oncology setting [ 27 ]. In the first stage, participants enroll in a cohort study and provide broad consent to be approached for any experimental interventions or to be a control for multiple studies that may be undertaken during the cohort study period.…”

“…Gal et al. reported no contamination, and this design also mitigates patient distress because they remain unaware of the interventions unless they are selected [ 27 ]. This design is suggested to overcome the ethical disadvantages of the Zelen design and provides advantages over traditional study designs, and researchers may want to explore this as an alternative to the Zelen design.…”

Pain Response After Stereotactic Body Radiation Therapy Versus Conventional Radiation Therapy in Patients With Bone Metastases—A Phase 2 Randomized Controlled Trial Within a Prospective Cohort

“…1,2 Palliative radiation therapy (RT) is a proven effective and widely accepted treatment modality for metastatic bone pain. 3,4 Pain response after conventional RT (cRT) is similar in patients treated with single-fraction (8 Gy in 1 fraction) and multifraction (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) Gy in 5-10 fractions) RT. 1,5,6 It has been suggested that dose escalation, and more specifically dose escalation per fraction, could improve pain response in patients with metastatic bone pain.…”