Variation in time to notification of enrollment and rates of withdrawal in resuscitation trials conducted under exception from informed consent

Abstract

Importance: Emergency research is challenging to do well as it involves time sensitive interventions in unstable patients. There is limited time to obtain informed consent from the patient or their legally authorized representative (LAR). Such research is permitted under exception from informed consent (EFIC) if specific criteria are met, including notification after enrollment. Some question whether the risks of EFIC outweighs its benefits. To date, there is limited empiric information about time to notification (TTN) and rates of withdrawal in such trials.

Objective: To describe variation in TTN and rates of withdrawal among that patients enrolled in EFIC trials over a twelve-year period.

Design: We performed post hoc descriptive analyses of data from five trials conducted under EFIC.

Setting: Emergency medical services and receiving hospitals participating in the Resuscitation Outcomes Consortium in the United States and Canada.

Participants: Patients with out-of-hospital cardiac arrest or life-threatening traumatic injury.

Exposures: Notification strategies were specified at each site before initiation of enrollment by a local institutional review board. We monitored TTN within each site centrally throughout each study's enrollment period.

Outcomes: TTN was defined as time from randomization to first-reported notification of patient or LAR of enrollment. Withdrawal was defined as patient or LAR opt out of ongoing participation at the time of notification.

Results: Of 35,442 patients enrolled in five trials, 33,805 had cardiac arrest; and 1636 had traumatic injury. TTN varied overall and by patient outcome. Among those with cardiac arrest, TTN ranged from median (5%ile, 95%ile) of 6 (1,27) days to 28 (2, 53) days across sites. 0.3% of notified patients with cardiac arrest withdrew. Among those with traumatic injury, TTN ranged from 0 (0, 5) days to 36 (5, 68) days across sites. 7.7% of notified patients with traumatic injury withdrew.

Conclusions and relevance: There is large variation in TTN in trials conducted under EFIC for emergency research. This may be due to several factors. It may or may not be modifiable. Overall rates of withdrawal are low, which suggests current practices related to EFIC are acceptable to those who have participated in emergency research.

Keywords: Cardiac arrest; Randomized trials; Traumatic injury.