Ethical Considerations of Electronic Consent in Stroke Clinical Trials

By Stacey Kusterbeck

Growing numbers of researchers are using electronic informed consent (eConsent) in clinical trials. However, it was unclear how eConsent affected enrollment in acute ischemic stroke studies. A group of researchers analyzed eConsent adoption in the Multi-arm Optimization of Stroke Thrombolysis (MOST) trial.¹ Of 514 participants enrolled from 2019 to 2023, 174 were consented through eConsent. More than half of the 57 sites used eConsent at least once, and those sites had higher median enrollment than non-eConsent sites.

Medical Ethics Advisor (MEA) spoke with Christopher Streib, MD, MS, one of the study authors and stroke division director at the University of Minnesota about important considerations for researchers regarding eConsent.

MEA: From an ethical standpoint, why is it important for stroke researchers to enroll as many patients as possible in clinical trials?

Streib: I believe that academic stroke programs should have a fundamental commitment to enrolling patients in clinical trials and making clinical trial recruitment part of standard clinical practice.

First, there may be an advantage to our patients who are enrolled in clinical trials. Patients in stroke trials are much less likely to be lost to follow-up compared to stroke patients who are not participating in clinical trials. The trial infrastructure may also provide participants more rigorous follow-up and increased opportunities for risk factor control to prevent recurrent stroke. Those opportunities are not always readily available within our healthcare system.

Second, we need to ensure that we are approaching every eligible patient and offering them the opportunity to participate in clinical trials. It is important that we, as clinicians, don’t have selection bias. We know that, historically, trials have not always represented our stroke population in terms of sex, race, and socioeconomic status, leading to questions of generalizability.

Third, by enrolling patients in clinical trials at a high rate, we answer important questions in stroke care and can improve patient outcomes most efficiently.

MEA: What are ethical concerns if informed consent processes are overly burdensome for participants and research staff?

Streib: We need to design trials so that offering clinical trial participation to all eligible patients is feasible for the participants, research coordinators, and clinical teams. To do this, clinical trial infrastructure should be modernized. Until five years ago, for acute stroke trials I would fax 20-page consent forms to legally authorized representatives so that their loved one could participate in emergent stroke studies. Often, the legally authorized representative would have to drive somewhere get the fax, sign it, and send it back. This alone leads to ethical and practical issues.

For an acute stroke trial, the informed consent process is occurring on one of the worst days of the legally authorized representative’s life. I remember calling a family located in Nigeria to tell them their young family member had had a devastating stroke. He was eligible for a clinical trial studying the treatment of malignant cerebral edema and they wished to participate. They provided their verbal consent, but I told them that they would need to physically sign the trial’s informed consent form. They provided an email address, and I expected them to be able to print the form, sign it, and fax it back in about 30 minutes. It was 3 a.m. there and it took them three hours to complete. I have no idea what logistical hurdles participating in the clinical trial caused them, but I do know they spent much of that time driving somewhere to get the paperwork and send it back.

Clinical trials should be rigorous — not difficult. We must take responsibility for minimizing the burden of participating in clinical trials. Minimizing the research burden is also important for the clinical team and research staff. Turnover among research coordinators severely impacts clinical trial recruitment and completion. Finally, clinical teams are already suffering significant burnout without adding more time-consuming responsibility to their roles.

MEA: What are some ethical implications if eConsent is used in stroke trials?

Streib: In acute stroke trials, many patients lack capacity to consent for themselves. They may be aphasic or they do not clearly understand the risks of participation. For patients without capacity, informed consent must be obtained from a legally authorized representative. eConsent enables us to deliver the consent forms rapidly through email or text. Because eConsent makes it easier to deliver, sign, and return the consent form, more time can be spent on a discussion of potential risks and benefits and ensuring that all of their questions are asked and answered.

An additional important factor in acute stroke trials is that the interventions are most likely to be very time-dependent. If we delay the study intervention considerably while documenting informed consent, the individual participant becomes less likely to benefit from the intervention and the trial becomes less likely to be positive.

MEA: Where do things stand currently with eConsent?

Streib: Just like anything in medicine, change can be slow. We’ve really been at the forefront of pushing eConsent locally and the NIH [National Institutes of Health] StrokeNet [a Stroke Trials Network] has been pushing this also. But to really enact change, you need data, which is why we completed our study.

When we looked back at MOST, the sites that used eConsent enrolled more patients. This is most likely because they were able to reach legally authorized representatives [who] were not present locally. Informed consent that was completed “remotely” was common using eConsent and virtually non-existent when using paper consent forms.

We calculated that these remote enrollments using eConsent shortened the duration of the study by approximately eight months, which is a huge cost savings. There were also significantly less data clarification requests and unanticipated events (i.e., protocol deviations) with eConsent, compared to traditional paper consent forms. By making studies more efficient, it’s easier on the clinical team, research team, and participants. By completing studies more quickly (and many stroke studies are never completed due to recruitment issues), we can advance stroke care more efficiently.

Another fundamental reason that eConsent is needed is that currently nearly all stroke trials are completed in academic centers or tertiary hospitals, which have the research infrastructure to consent and enroll patients. We accept this reality because that is how it has always been, but it’s actually highly problematic. We generalize our trial results to all stroke patients. But the majority of stroke patients are not treated at academic stroke centers, and the treatment that they need may actually be quite different.

For example, there is compelling data that patients at smaller hospitals may benefit from thrombolysis (i.e., the stroke “clot-buster” medication) during transport to a tertiary stroke center where they will undergo thrombectomy. However, we cannot study this intervention currently because we are unable to enroll a high volume of rural stroke patients in clinical trials. Some sites, like our own, have begun to enroll remote patients in clinical trials through telemedicine and eConsent.

Infrastructure to support remote enrollment more broadly will enable us to design entirely new stroke trials. We need to conduct trials that are applicable to stroke patients across the entire country, with the ability to study many different stroke treatment paradigms in order to improve clinical outcomes.

MEA: What are important considerations, in terms of institutional review board (IRB) approval, for stroke researchers who are designing study protocols including eConsent?

Streib: It is important to work together with your local IRB. About five years ago, we discussed consent using telemedicine for informed consent with our IRB. Because video consent was new at that time, there were trials that allowed phone consent but not video consent. To be compliant with the study, you could already be on camera with the patient for their clinical stroke treatment, but then you were supposed to turn off the camera for informed consent. This is an example of very basic workflows that need to be updated for eConsent.

As we developed eConsent, we initially took a written consent form and then just replicated that form within REDCap. That way, we could deliver an identical consent form electronically — and this has been most palatable to the IRB. However, we are getting away from the idea of replicating paper consent and looking at how we can improve it. Not only does eConsent make remote enrollment easier, it actually results in fewer protocol deviation and fewer data clarification requests. There are some eConsent forms now that include a link to a video that may explain the study and the methodology (e.g., randomization and blinding) in a manner that is easier to comprehend than through written text.

MEA: What are misconceptions about eConsent, or arguments against using it?

Streib: There are quite a few concerns regarding eConsent adoption. Although our study results are only from a single stroke trial, I hope our findings can begin to allay many of them.

First, there is concern that eConsent will favor enrollment of privileged patients with internet access and a smartphone. That really doesn’t seem to be the case. In our experience, smartphones and internet access are relatively widely available. A related concern is that the elderly would not be enrolled because they would be less proficient with eConsent. We actually found that relatively more elderly patients were enrolled when eConsent was used. This is likely because we were able to reach their legally authorized representatives, typically their children, who did not live locally. In the past, patients who did not have local legally authorized representatives were unlikely to be enrolled in clinical trials due to the inability to obtain informed consent with paper.

We were also able to look at diversity. There was no hint that eConsent was associated with any changes in patient demographics. Finally, there is concern that the burden of eConsent for families or research teams is overwhelming. Because eConsent is a new process, there is certainly a learning curve. However, our findings do not support that eConsent workflows are problematic.

MEA: What are current barriers to eConsent?

Streib: Trying to use eConsent locally as an individual investigator or program will remain difficult. eConsent should be written into trial protocols as a standard workflow. StrokeNet also supports eConsent and utilizes a central IRB, which makes adoption easier for many stroke trials. In addition, StrokeNet provides a centralized eConsent platform through REDCap, that each site can use. eConsent is often not supported to this degree within individual trials.

While I would say most IRBs are receptive to eConsent, this will vary by institution. From a regulatory standpoint, the IRB must be confident that the eConsent platform meets Part 11 Compliance with the FDA [Food and Drug Administration]. This can lead to many requirements of individual institutions or stipulations on which eConsent platforms can be used.

Finally, there are some institutions that still view eConsent as a temporary solution to clinical trials during COVID, which limited in-person interaction. Some of the original IRB allowances for eConsent related to COVID are being withdrawn, meaning that eConsent needs local re-approval. We hope the data from our study can help support the use of eConsent as a routine, established practice.

MEA: Given all the benefits of eConsent, what about ethical concerns if eConsent is not used?

Streib: If you have a small study and every single patient needs to follow up in person locally, there is probably no issue. I do think that in broader clinical trials not using eConsent will unnecessarily slow recruitment and potentially cause problems with generalizability. For time-sensitive interventions, slowing informed consent decreases the probability that a participant may benefit and that a trial will be “positive” for demonstrating an improved outcome.

Finally, we must be able to study stroke interventions that could specifically benefit patients treated outside academic and tertiary stroke centers. We currently do not have the capability to directly study directed treatment designed for this patient population. Although these are my concerns from a stroke perspective, I suspect they are broadly applicable across many medical disciplines.

Overall, the conversation needs to change from trying to use eConsent to replicate paper consent forms, to using eConsent as a tool that allows us to obtain and document informed consent reliably and quickly, even when participants or legally authorized representatives are in a different geographic location.

eConsent has the potential to allow us to do conduct clinical research in a way that is more integrated into clinical care, and broadly applicable to our stroke population. Right now, we are on the tip of the iceberg.

Stacey Kusterbeck is an award-winning contributing author for Relias. She has more than 20 years of medical journalism experience and greatly enjoys keeping on top of constant changes in the healthcare field.

Reference

1. Davis SI, Staugaitis A, Rines I, et al. Electronic informed consent in the Multi-Arm Optimization of Stroke Thrombolysis trial. Stroke. 2025;56(7):1681-1688.