Post-hoc analyses of a large, randomised clinical trial have revealed the potential advantages associated with electronic informed consent (eConsent) in acute ischaemic stroke studies, including increased enrolment rates and improved adherence to consent documentation.
These findings were recently published in the journal Stroke by lead author Iris Davis (University of Cincinnati, Cincinnati, USA), corresponding author Christopher Streib (University of Minnesota, Minneapolis, USA), and colleagues.
“EConsent […] was associated with higher individual site enrolment, higher remote consent rates, and improved consent documentation adherence, over paper consent,” Davis et al write, concluding their paper. “Our study outlines the potential advantages of eConsent adoption in future acute ischaemic stroke clinical trials and stroke research networks.”
Davis et al begin their paper by noting that obtaining timely informed consent represents a “key barrier” in acute ischaemic stroke clinical trial recruitment—and, while eConsent may have the capacity to optimise recruitment by enabling electronic delivery and documentation of the informed consent process, it remains both “limited and understudied” in these types of trials.
The researchers therefore set out to conduct a post-hoc analysis of eConsent adoption within the MOST trial, a Phase 3 trial evaluating the potential benefits of two different blood-thinning medications alongside standard-of-care intravenous thrombolysis (IVT) in adult ischaemic stroke patients. Late-breaking data from MOST were presented at last year’s International Stroke Conference (ISC; 7–9 February 2024, Phoenix, USA) and have been published in full in the New England Journal of Medicine, ultimately revealing no significant 90-day clinical benefits with either argatroban or eptifibatide as compared to placebo treatments.
For their subsequent analyses of MOST, Davis et al reviewed study databases to ascertain whether participants were enrolled using conventional paper consent forms or eConsent. Additionally, they determined whether the participant or their legally authorised representative provided informed consent in person, or if they were located remotely. Participants were then assigned to one of four informed consent modalities: paper (in person), paper (remote), eConsent (in person), and eConsent (remote). The authors also note in their Stroke publication that study sites had the freedom to use paper consent or eConsent for each enrolment.
Outlining the results of their research, Davis et al state that eConsent was utilised for 173 (93 in person, 80 remote) of a total of 514 participants (33.7%), while the remaining 341 (337 in person, four remote) involved more traditional, paper-based consent. Of the 57 sites enrolling patients in the MOST trial, 32 (56.1%) utilised eConsent at least once—and those sites enrolled a higher number of study participants as compared to non-eConsent sites (median 7.5 vs 3, respectively; p<0.001). Overall, eConsent was also completed remotely on a significantly more frequent basis than paper consent (46.2% vs 1.2%, respectively; p<0.001). Thus, in the authors’ view, this difference in recruitment may be explained, in part, by increased enrolment opportunities for remote patients when eConsent is used.
“It is worth emphasising that fewer than 1% of participants were consented remotely using paper,” Davis commented, speaking exclusively to NeuroNews. “Examples of this scenario would be delivering a consent form to, and back from, a potential participant or their surrogate via fax machine, or by scanning it and sending via email. Before eConsent, this was the only method of obtaining consent from a patient or their surrogate when they were not physically in the same location as the researcher—which happens often in the acute research setting. The small number of consents obtained remotely using paper compared to using eConsent highlights the fact that electronic management and delivery of informed consent forms is a more practical and simple solution.”
EConsent may be especially important to facilitate the participation of rural stroke patients in clinical trials.
According to the authors, findings on demographic diversity of participants were similar between the in-person eConsent and in-person paper consent groups, as were median baseline neuroimaging-to-randomisation times (58.5 vs 55 minutes, respectively). And, “importantly”, consent documentation adherence was superior in the analysis’ in-person eConsent cohort as compared to its in-person paper consent cohort with decreased rates of data clarification requests (44 vs 81, respectively, per 100 participants) and a notable reduction in reportable unanticipated events (six vs 25, respectively, per 100 participants).
“The three most common reportable, consent-related issues in MOST were missing HIPAA [Health Insurance Portability and Accountability Act] documentation, using the incorrect version of the consent form, and using the incorrect person during the consent process—for example, not using an impartial witness when required,” Davis explained. “These types of issues where the informed consent process is incomplete or inadequate—according to human subjects research regulations—must be reported to the overseeing institutional review board [IRB], because they have the potential to impact the rights of participants.”
When asked to comment on the possibility of eConsent holding comparable benefits in other types of stroke trials—for example, those evaluating thrombectomy procedures, thrombolytic drug treatments, triage protocols, or artificial intelligence (AI) solutions—Streib affirmed that its advantages are likely to be “generally applicable”.
“The ability to connect clinicians, research teams, and patients or their legally authorised representatives in order to rapidly obtain informed consent addresses a common barrier in clinical trials studying time-sensitive interventions,” he told NeuroNews.
Streib’s view is that, while multiple remaining hurdles need to be overcome to achieve broader integration of eConsent into today’s stroke trials—and stroke trials of the future—the benefits of doing so could be significant.
“Centralised eConsent requires additional research infrastructure to manage the eConsent system and that can be considerable,” he stated. “There are also additional regulatory layers, including those within IRBs, who must approve the use of eConsent for a trial. Some institutions’ IRBs still either do not allow eConsent or considerably restrict its use.”
These processes and barriers are still being navigated to determine optimal eConsent implementation, according to Streib.
“EConsent may be especially important to facilitate the participation of rural stroke patients in clinical trials,” he added. “This is a huge priority in stroke clinical research and something we are actively working to address.
“Rural hospitals typically lack onsite clinical research teams, making trial enrolment nearly impossible. This is problematic because rural stroke patients may have different risk factors and different treatment needs. For example, a neuroprotectant medication that slows the progression of stroke would be of huge benefit to rural patients whose definitive treatment is delayed until they can be transferred to a larger, urban stroke centre.”
“Today, electronic approaches commonly replace conventional methods of paper documentation in healthcare, and in clinical research, to better manage medical data maintenance and access. EConsent provides a contemporary solution to documenting informed consent in clinical trials for patients, researchers, and healthcare systems,” Davis commented. “As discussed in our paper, we found key advantages of implementing eConsent to be increased enrolment opportunities and improved regulatory compliance. A shift towards using eConsent over paper consent could improve the efficiency of stroke trials by providing more patients the opportunity to participate, and by decreasing the regulatory reporting burden on research teams.”
