Ethical Considerations during the Informed Consent Process for Acute Ischemic Stroke in International Clinical Trials

Abstract

We sought to investigate the experiences of researchers in existing active-control trials in acute ischemic stroke comparing investigational therapy to tissue plasminogen activator (tPA) in order to identify the approaches and challenges in obtaining informed consent. Out of 401 articles evaluated, 14 trials met inclusion criteria. Trial representatives were contacted to complete a survey concerning the consent process. None of the 14 trials published materials related to the informed consent process. Trials with 75% to 100% of patients directly consented had shorter door-totreatment (DTT) times than trials that directly consented less than 50% of patients. Trials that had translators available (for recruiting participants who were not native speakers in the local language) and translated consent documents had longer DTT times. The study findings suggest that differences in the standards of informed consent internationally may allow more patients with moderate strokes to provide direct consent without delaying DTT time. Future trials should emphasize transparency to the public and scientific community in the informed consent process. KEYWORDS human research ethics, human subjects research, acute ischemic stroke, informed consent, randomized controlled trials, literature review

Protocol for Deferral of Consent in Acute Stroke Trials

“…In light of recent experiences with trials such as ESCAPE and SPOTLIGHT, we sought to develop a protocol for implementing deferral of consent that could serve as a set of best practices to be followed while still meeting standards for ethics review. (34) Beginning from ethical first principles and recent scholarship, and extending through an iterative process involving stroke trialists, patient partners, and research ethics experts, (24,36) we designed a protocol for deferral of consent and implemented it in the AcT trial. AcT is the first trial that we are aware of to follow a specific protocol for the use of deferral of consent.…”

“…This would ensure transparency and allow for peer review. 36 The use of deferral of consent should be assessed within an ethical framework such as the substitute consent model proposed by Largent et al 18 or the model we have proposed. 39 Step 4: Support physician-patient communication with scripts and other aids, and with training in how to use them.…”

“…Beginning from ethical first principles and recent scholarship, 24 , 36 and extending through an iterative process involving stroke trialists, patient partners, and research ethics experts, we designed a protocol for deferral of consent and implemented it in the AcT trial. AcT is the first trial that we are aware of to follow a specific protocol for the use of deferral of consent.…”

“…The development of scripts and training to support physician-patient communication, especially during the enrollment process, could lead to more efficient, transparent, and consistent communication. 3 , 36 The use of scripts or aids would standardize the information given to patients, a potential issue given the increasing commonality of multisite, multinational trials. It would also reduce the cognitive burden on the enrolling physician by providing a procedure to follow and reduce the potential liability of researchers by ensuring all patients are given the requisite information in a consistent fashion.…”