Optimizing clinical trial design using prospective cohort study data: a case study in neuro-urology

Abstract

Study design: Simulations using data from a prospective cohort study.

Objectives: To illustrate how prospective cohort data can be employed in randomized controlled trial (RCT) planning to assess feasibility and operational challenges, using TASCI (Transcutaneous tibial nerve stimulation in patients with Acute Spinal Cord Injury to prevent neurogenic detrusor overactivity: a nationwide randomized, sham-controlled, double-blind clinical trial) as a case study.

Setting: Spinal cord injury (SCI) rehabilitation centers in Switzerland.

Methods: TASCI is nested in the multicenter Swiss Spinal Cord Injury Cohort Study (SwiSCI), which prospectively includes patients with acute SCI. In simulations, data from 640 patients, collected by SwiSCI, were used to investigate different scenarios of patient eligibility and study consent, as well as the performance of the randomization list. Descriptive analysis was used to describe the population of interest and the simulation results; multivariable logistic regression analysis was performed to identify predictors of discharge within the TASCI intervention time period.

Results: The recruitment target of 114 patients is obtainable within the originally envisioned 3-year time period under the most favorable recruitment scenario examined. The distribution of the primary prognostic factor produced imbalance in the randomization lists and informed further discussion of the cut-off values used in stratification. Influxes of patients resulted in overlapping intervention periods for multiple participants, which guided resource allocation. Early discharge was related to the primary prognostic factor and study center, but is only anticipated in about 8% of participants.

Conclusions: Prospective cohort data are a very valuable resource for planning RCTs.

Conflict of interest statement

Statement of Ethics:

Ethical approval was granted by all responsible ethics committees: Ethics Committee of Northwest/Central Switzerland (PB 2016-00183), Ethics Committee Vaud (032/13), and Ethics Committee Zürich (2013-0249). We certify that all applicable institutional and governmental regulations concerning the ethical use of human volunteers were followed during the course of this research.

Conflicts of Interest:

The authors declare that there are no conflicts of interest.

© 2020. The Author(s), under exclusive licence to International Spinal Cord Society.

Figures

Figure 1

Simulation flowchart. * = assignment to treatment groups is identical for all centers; LEMS = lower extremity motor score; SwiSCI = Swiss Spinal Cord Injury Cohort Study; TTNS = transcutaneous tibial nerve stimulation.

Figure 2

LEMS: distribution in the patient population, and imbalance in the simulations. Distribution of LEMS in the population of patients eligible for TASCI (A) and across study centers, grouped according to LEMS Model 1 (B). In simulations, imbalance was seen in the middle LEMS categories across all models, but was especially pronounced in Model 1 (C). LEMS models represent different cut-off values that are categorized based on the percent probability of urinary continence and complete bladder emptying one year after SCI: Model 1: 66% (LEMS 33-50) (black in B); Model 2: 75% (LEMS 36-50); or Model 3: 80% (38-50). LEMS = lower extremity motor score.

Figure 3

Description of patient flow. 3A – Number of eligible patients in the intervention window per day, in all study centers. 3B-F – In simulations, count of the mean number of weeks with a given number of participants receiving the TTNS intervention, in all four centers (B) and in each individual study center (C-F, centers 1-4, respectively), under the most favorable recruitment rate scenario. N = number; TTNS = transcutaneous tibial nerve stimulation.