The Informed Consent Process and the Use of the Exception to Informed Consent in the Clinical Trial of Diaspirin

Abstract

Abstract. In the clinical trial of diaspirin crosslinked hemoglobin (DCLHb), optimal therapy required the immediate enrollment of patients with severe, uncompensated, traumatic hemorrhagic shock. When it was not feasible to obtain prospective consent, an exception to informed consent was used according to FDA regulation 21 CFR 50.24. Objectives: To examine the informed consent process and the use of the consent exception and consent to continue (CTC), and to describe the patients for whom this process was used. Methods: This was a multicenter, randomized, controlled, single-blinded efficacy trial of DCLHb as an adjunct to standard therapy in the treatment of severe, traumatic hemorrhagic shock. Patients with unstable vital signs or a critical base deficit were treated, with a primary study endpoint of 28-day mortality. Results: During the 11-month study period, 112 patients were randomized in 18 U.S. trauma centers, and data from 98 of the infused patients were analyzed. Prospective consent was obtained from two patients, three family members, and one legally authorized representative (LAR) (6%). Consent to continue was requested for 89 patients (89%), and full participation was granted for 87 of these patients (98%). Consent to continue was provided by 54 (98%) of the 55 patients approached. The mean number of days for family/LAR CTC was 1.1 Ϯ 3.8 days, and 50% of the time it was obtained on the day of study enrollment. Patient CTC was obtained in an average of 13 Ϯ 23 days, with a median of four days. Patients treated in this protocol were more likely to have sustained penetrating trauma than the overall trauma patient population treated in these trauma centers (44% vs 21%, p = 0.002). Conclusions: Informed consent in this study of an emergent therapy most often involved the use of the consent exception and consent to continue, the latter of which occurred in a timely manner. Nearly all of those who were approached for CTC approved full participation in the study, suggesting acceptance of the process outlined in the new regulations. Patients treated in a hemorrhagic shock clinical trial may differ from the general trauma patient population.

Variation of community consultation and public disclosure for a pediatric multi-centered “Exception from Informed Consent” trial

“…13,22,23,25 Some recommend that the amount of required community consultation or public disclosure activities should be based on the incremental risks of a study. 10,34,35 Although most EFIC studies have the potential to enroll anyone from the entire community, some studies are more likely to enroll patients with a particular risk factor and thus may be targeted.…”

Randomized, controlled trials as minimal risk: An ethical analysis*

“…Although the potential for psychological harm is real, few patients/surrogates have opted to discontinue participation in RCTs that have been carried out without informed consent in recent years, and investigators have not reported adverse reactions from patients or their surrogates (37)(38)(39)(40)(41)(42). However, little data exist about the specific responses of research participants and/or their families on learning about research that was conducted in the absence of informed consent.…”

Exception from informed consent for emergency research

“…Moreover, identifying potential subjects a priori or their legally authorized representatives (LARs) in a timely fashion may not be practical in most circumstances. 2,3 …”