The Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA): objectives, design, and baseline results

Abstract

PurposeIn oncology, RCTs are often beset by slow recruitment, limited generalizability, and strong preferences for interventions by patients and physicians. The cohort multiple randomized controlled trial (cmRCT) is an innovative design with the potential to overcome those challenges. In cmRCT, a prospective cohort serves as an infrastructure for multiple RCTs. We implemented cmRCT in a clinical breast cancer setting by creating UMBRELLA—a large prospective cohort of breast cancer and DCIS patients/survivors.MethodsFor all participants, clinical data and patient-reported outcomes (PROs, i.e., quality of life, fatigue, anxiety and depression, physical activity, work ability, and cosmetic satisfaction) are being collected at regular time-intervals for a period of 10 years. These data are being used both for observational and randomized studies. For each intervention to be tested against standard care, a subcohort of eligible patients is identified within UMBRELLA. From this subcohort, a random sample of patients is offered the intervention. Their outcomes are compared to the outcomes of patients receiving standard care.ResultsSo far, between October 2013 and July 2016, we have recruited 1308 participants. In this period, 1308/1486 (88%) patients who were invited for participation in UMBRELLA consented to cohort participation. Of these patients, 1138 (87%) gave broad consent for randomization to future interventions. Return rate for PROs at baseline were 80%, and varied from 67 to 74% during follow-up. Several observational studies—and the first randomized intervention study—are currently ongoing.ConclusionsResults from UMBRELLA show that this novel study design is feasible and acceptable to patients in a clinical breast cancer setting. We invite researchers who are interested in conducting randomized or observational studies within the UMBRELLA cohort to contact the UMBRELLA scientific advisory board.

Immediate and delayed autologous abdominal microvascular flap breast reconstruction in patients receiving adjuvant, neoadjuvant or no radiotherapy: a meta-analysis of clinical and quality-of-life outcomes

“…Current evidence for irradiating autologous abdominal flaps remains weak, involving only two moderate‐quality studies of the 12 included in this report. Future cohort studies should be designed and powered to take advantage of newly evolving study designs, such as multiple‐cohort RCTs or trials within cohorts. These designs permit collection of big data within registry or cohort platforms, and allow multiple synchronous randomized trials to be conducted in a cost‐effective manner.…”

The effects of exercise on the quality of life of patients with breast cancer (the UMBRELLA Fit study): study protocol for a randomized controlled trial

“…Therefore, the calculated number of subjects should be multiplied by (1-ρ 2 ), plus one extra subject per group [36], where ρ represents the correlation between baseline and follow-up outcomes. In our previous trials [34,35], we identified correlation of 0.4 between baseline and follow-up QoL. This leads to a final sample size of 83 patients per group (98*0.84 + 1).…”

“…Here, we determine a clinically relevant difference as a difference of 10 points [30]. A difference of 10 points is realistic because in a previous exercise trial in patients with cancer, QoL in the intervention group improved by 15.1 points (SD 17.7) and in the control group by 6.1 points (SD 17.1) using the EORTC-QLQ-30 after the 12-week intervention [34,35]. Therefore, using the control group data from the previous trial and the 10-point difference, we assume a 6-point increase in QoL in the control group and a 16-point increase in the intervention group, among patients who accept the intervention in this cmRCT.…”

Severe depression more common in patients with ductal carcinoma in situ than early-stage invasive breast cancer patients

“…This study was conducted within the prospective Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaLuAtion (UMBRELLA) [18]. UMBRELLA includes patients with invasive breast cancer and patients with DCIS, referred to the Department of Radiation Oncology of the University Medical Center (UMC) Utrecht for adjuvant radiotherapy.…”