Implementation of documented and written informed consent for clinical trials of communicable diseases: Lessons learned, barriers, solutions, future directions identified during the conduct of a COVID-19 clinical trial

Abstract

Background and objective The communicable nature of many infectious diseases, including SARS-CoV-2 creates challenges for implementing and obtaining regulatory-compliant written informed consent. The goal of this project was to identify and evaluate processes that address these barriers while maintaining clinical and research staff safety. Methods We reviewed Federal Drug Administration (FDA), World Health Organization (WHO), and VA Office of Research and Development (ORD) guidance about informed consent during the COVID-19 pandemic, and identified and pilot-tested several mechanisms for obtaining regulatory-compliant consent during our COVID-19 therapeutics clinical trial. Results Several processes were identified. These included a standard face-to-face consent with a plan for maintaining a paper copy of the signed consent form, a phone or video chat consent process that included taking a picture of the signed consent form or a screen shot of the signed document during a video chat, integration of the consent forms into software embedded within the electronic health record, and secure software programs with electronic signature. These processes are FDA-compliant but time-intensive, often requiring four or more hours of coordination between the clinical team, research staff, patients, and legally authorized representatives. Conclusions Future studies could evaluate how to improve efficiency, and whether some elements of the consenting process, such as the requirement for documented written signed consent, rather than a witnessed oral consent, is an acceptable standard for research participants with communicable diseases.

Subcutaneous sarilumab for the treatment of hospitalized patients with moderate to severe COVID19 disease: A pragmatic, embedded randomized clinical trial

“…After clarifications to the initial US Food and Drug Administration (FDA) guidance were issued [22], written documentation of informed consent was obtained from all participants or their legally authorized representative. Details of the informed consent processes, which were developed to minimize research staff exposure and also limit the use of personal protective equipment at a time when resources were scarce, are previously published [23].…”

“…Although the trial opened quickly, and the remote monitoring and embedding of group assignment and outcomes in the EHR proceeded well, the one time-consuming barrier to efficient conduct of the trial was the difficulty in obtaining signed documentation from severely ill patients of informed consent, as we described in detail elsewhere [23]. The pace of finding effective treatments, especially in emergency circumstances, would be greatly improved by a change in perspective of administrative and regulatory bodies.…”

Ethical challenges of prospective clinical trials during the COVID-19 pandemic

“…The informed consent process occurs before enrolling a patient in a clinical trial and allows for the investigator to provide the patient with education to assess the risks and potential benefits of a procedure or treatment [ 9 , 11 ]. The required elements of ‘(1) nature of the procedure, (2) the risks and benefits and the procedure, (3) reasonable alternatives, (4) risks and benefits of alternatives, and (5) assessment of the patient’s understanding of the elements 1 through 4’ must be documented, per the Joint Commission.…”

“…In 2020, the Federal Drug Administration (FDA) released nonbinding recommendations as part of guidance on the conduct of clinical trials during the ‘COVID-19 Public Health Emergency.’ Specifically, the FDA recognizes challenges that may arise, including but not limited to, ‘quarantines, site closures, travel limitations, interruptions to the supply chain from the investigational product’ [ 9 ]. The clinical trial’s consent process must be altered to comply with the pandemic’s limitations.…”

Reconsidering ‘minimal risk’ to expand the repertoire of trials with waiver of informed consent for research

“…The barrier we encountered was in the unnecessarily complicated informed consent process. 14 Ironically, our trial would not have qualified for the abbreviated consent process we advocate in this paper, because it conferred risk on participants. However, our additional experience serving on an IRB and participating in other clinical trials and in implementation science meant that we were primed to explore ways that pragmatic trials could be performed more efficiently without compromising ethics.…”