Informed Consent Requirements May Hinder Innovation in Stroke Treatments
Acute stroke is a common condition. “Yet we are still using a treatment — tPA — that was tested in a clinical trial published in 1995,” says William Meurer, MD, a professor in the departments of emergency medicine and neurology at the University of Michigan.
Newer, and perhaps better, drugs could be designed. Even small improvements in outcomes would help thousands of patients. “But the structural problems of doing a study in patients with an emergency condition are inhibiting progress,” Meurer says. “Basically, the current setup is likely preventing innovation in this area.”
There is enthusiasm for some alternative approaches, such as removing clots via an endovascular procedure. However, many strokes are either too small or arriving at hospitals without the setup to remove clots. “As such, we are systematically being dissuaded — by pharma, investigators, and academia — from finding a reperfusion drug that can open more vessels and cause less bleeding,” Meurer argues.
Meurer and colleagues identified 14 clinical trials comparing investigational therapy to tPA, and surveyed researchers from those studies about the consent process.1 None of the authors published materials used for informed consent. Studies with 75% or more of patients directly consented reported shorter door-to-treatment times than studies in which fewer than half of patients were directly consented. “Communities with diversity of preferred languages may require agile research teams — and the growing availability of on-demand video translators may help speed up the consent process,” Meurer offers.
The goal is to treat patients with stroke as soon as possible, as early as 15-20 minutes after arrival. “It seems unlikely that the full consent process can occur within the time scales needed in most cases,” Meurer observes.
Considering that, Meurer says prospective informed consent for replacement treatments for tPA probably is not feasible. “IRBs and regulatory bodies should consider the changing scope of acute stroke care, and collaborate with investigators to design studies that can ethically answer important questions and allow innovation and progress in the field,” Meurer says.
Ethical informed consent with a focus on the individual study participant is important. “However, the current structure of review does not weigh the impact on all future stroke patients, who may continue to have access to the only approved drug treatment, now nearly 30 years old,” Meurer argues.
Tenecteplase (TNK) has been studied extensively, showing several advantages over tPA (e.g., easier administration, probably less bleeding, and probably slightly better ability to open blood vessels).2 “Despite essentially no residual concern that TNK is worse than tPA, this very incremental replacement has not been widely adopted,” Meurer says.
Several required elements of informed consent may not be relevant, says Meurer, such as follow-up procedures or information on privacy protections, which are not unique to the study, when considering a one-time dose of a potentially life-changing medication. “Both IRBs and regulatory bodies should consider more dialogue with investigators who perform high-stakes research under very tight timelines,” Meurer advises.
Research ethics standards typically require consent from prospective participants for interventional research. “However, these same standards also recognize that some research would be impossible if prospective consent from the participant was required,” says Stacey Page, PhD, chair of the Conjoint Health Research Ethics Board at the University of Calgary Cumming School of Medicine.
Page and colleagues recently examined ethical justification for deferred consent for a study of acute ischemic stroke.3 Alterations of the normal informed consent process, says Page, “require trade-offs between ethics principles.”
Researchers are obligated to protect people who are vulnerable, incapacitated, and unable to exercise an informed choice. Researchers also are obligated to prevent inequities that would arise if such people could never be involved in research.
“When the previously incapacitated person regains capacity, or when a surrogate decision-maker is found, consent should be sought for the continued participation of that person in the research,” Page underscores.
1. Bellomo T, Fokas J, Tsao N, et al. Ethical considerations during the informed consent process for acute ischemic stroke in international clinical trials. Ethics Hum Res 2022;44:14-25.
2. Dong Y, Sui Y, Cheng X, Wang DZ. Is tenecteplase ready to replace alteplase to treat acute ischaemic stroke? The knowns and unknowns. Stroke Vasc Neurol 2022;7:1-5.
3. Faris H, Dewar B, Dowlatshahi D, et al. Ethical justification for deferral of consent in the AcT trial for acute ischemic stroke. Stroke 2022;53:2420-2423.
IRBs and regulatory bodies should consider the changing scope of acute stroke care, and collaborate with investigators to design studies that can ethically answer important questions and allow innovation and progress in the field.
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