Timing of consent into a multicenter randomized controlled traumatic brain injury clinical trial conducted under exception from informed consent [abstract]
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Study Objective: Clinical trials conducted under the Exception from Informed Consent (EFIC) Guidelines (21 CFR 50.24) require investigators to attempt prospective consent if possible before enrolling patient under EFIC. Investigators subsequently obtain consent for continued participation for patients enrolled under EFIC when a legally authorized representative (LAR) becomes available. The objective of this study is to describe the timing of patient enrollment into a traumatic brain injury study conducted under EFIC. Methods: This study is a post hoc analysis of prospectively collected data from a randomized, controlled traumatic brain injury clinical trial evaluating the effectiveness of progesterone vs. placebo on patients 18 years and older who have sustained a moderate to severe brain injury (GCS 4-12). The study protocol required study drug to be started within 4 hours from time of injury. Research teams had 60 minutes from
patient arrival to the facility to make meaningful contact with an LAR before enrolling the patient under EFIC. If an LAR was identified and at the facility within 60 minutes of arrival, the study team attempted to obtain prospective consent. If no LAR was identified within that timeframe, patients were enrolled under EFIC and subsequently consented for continued participation at a later time. Descriptive statistics for the patient population were tabulated, and time from injury to randomization and study drug start were calculated for the EFIC and consent groups. Time to consent intervals and Kaplan-Meier curves for the EFIC and LAR consent groups were also calculated. Results: A total of 882 patients were randomized between April 2010 and October 2013 (442 progesterone, 440 control). Patient demographics were balanced between groups, with a median age of 35 years, 73.7% male, 15.2% black, and a median GCS of 7. The most frequent mechanism of injury was a motor vehicle crash. Six hundred fifteen patients were enrolled under EFIC (69.7%). Median time from injury to consent was 2 hours, 55 minutes (IQR 2:25-3:30) hours for patients enrolled with prospective consent. Patients enrolled under EFIC had a median time from injury to consent for continued participation of 19 hours (IQR 5:14-23:26). The median time from injury to randomization for the EFIC group was lower compared to the consent group [2:45 (IQR 2:19-3:13) versus 3:15 (IQR 2:42-4:08)], as was time from injury to study drug initiation [3:37 (IQR 3:10-3:57) versus 3:54 (IQR 3:31-4:01)]. For the prospective consent group, the cumulative prospective consent rate at 1, 2, 3, and 4 hours from time of injury was 1%, 8%, 56%, and 100%, respectively. Conclusions: As expected, a larger number of patients were enrolled under EFIC, and patients enrolled under EFIC had faster time to randomization and study drug start compared to patients enrolled under consent. For patients enrolled using traditional prospective consent, the vast majority were enrolled between 2 and 4 hours from time of injury. The range of time to subsequent consent for patients enrolled under EFIC was broad.