Abstract P5-18-02: The cohort multiple randomized controlled trial is a feasible and patient-acceptable design for pragmatic evaluation of multiple interventions, with potential for improved recruitment and generalisability: The UMBRELLA experience

Introduction: The randomized controlled trial (RCT) is the gold standard for evaluation of effectiveness of new interventions. In oncology, however, RCTs are often complicated by logistic challenges, slow recruitment, limited generalisability, and strong patient9s and doctor9s preferences for new interventions. At the University Medical Center Utrecht (the Netherlands), we implemented an innovative alternative to the classic RCT: the cohort multiple randomized controlled trial (cmRCT). The cmRCT serves as a multi-trial facility and has the potential to improve recruitment and generalisability. Methods: We initiated the 9Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation (UMBRELLA)9 at the department of radiation oncology. UMBRELLA is a large prospective cohort of breast cancer patients, for whom we capture clinical data (patient and tumor characteristics, treatment, imaging, toxicity, recurrence and survival). Patients provide Patient Reported Outcome Measures (PROMs) on quality of life, pain, fatigue, anxiety and depression, physical activity and cosmetics. For each intervention to be tested, a subcohort of eligible patients is identified within UMBRELLA. From this subcohort, a random sample of patients is selected and offered the intervention (which they can accept or refuse). Patients from the subcohort, who are not randomly selected, receive standard care, serve as controls, and are not informed about the trial. Outcomes of patients offered the intervention are compared to those of patients receiving standard care. This process can be repeated (simultaneously) for multiple experimental interventions. Results: Since October 2013, some 1000 patients have been enrolled in UMBRELLA. In order to make the design suitable for the clinical oncology practice, we developed a tailored informed consent procedure. First, we ask patients to enroll in the cohort and to provide PROMs. In addition, patients give broad consent to be either randomly selected to receive experimental interventions or to serve as control without further notice. In a second stage, at the initiation of a trial within the cohort, informed consent to receive the experimental intervention is sought in those randomly selected to receive the intervention. After completion of the trial, aggregated results are shared with all patients. Participation in UMBRELLA is 90%, and 90% of enrolled patients give broad consent for randomization. PROMs return rates vary from 70-90%. In September 2015, the first trial will be initiated, which aims to evaluate the impact of exercise programs on quality of life of inactive survivors. Preliminary inclusion and participation rates of this trial will be presented in December. Conclusion: High participation rates, high PROM return rates and high levels of broad informed consent for randomisation within UMBRELLA indicate that this innovative design is feasible in the oncology practice, acceptable for patients and likely to provide generalisable results. Results of trials within UMBRELLA need to confirm whether cmRCT is indeed an acceptable alternative for classic pragmatic RCTs. Citation Format: Verkooijen HM, Young Afat D, van den Bongard D, van Vulpen M, May AM, van Gils C. The cohort multiple randomized controlled trial is a feasible and patient-acceptable design for pragmatic evaluation of multiple interventions, with potential for improved recruitment and generalisability: The UMBRELLA experience. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-18-02.