Introduction

The enrollment process in studies investigating diseases that require emergent treatment is challenging. This is particularly important in the setting of acute ischemic stroke (AIS), in view of the fact that the patients’ cognitive, motor, and speech functions are uniformly impaired and legal proxies are commonly not available at the time of presentation.1–3 Moreover, the Code of Federal Regulation 46.117 (Documentation of informed consent) requires a physical signature on the consent document for inclusion in randomized clinical trials (RCTs), generating additional time restraints for research teams. This may affect recruitment rates and impact the advancement of medical care through research.

We have recently reported the pilot use of a smartphone platform for electronic informed consenting (e-Consent) in acute stroke trials.4 The e-Consent was found to streamline the consenting process in a RCT involving patients with emergent large vessel occlusion strokes (LVOS). However, the perceptions of the legal authorized representatives (LARs) regarding this process were not evaluated. We here report the feedback provided by LARs after consenting for an LVOS RCT.

Methods

This is a single-center study evaluating the opinion of LARs after the use of e-Consent for a RCT comparing an investigational drug versus placebo in patients with LVOS presenting within 12 hours of last seen normal. The trial was discussed and offered to the LAR either via telephone or in person. The e-Consent was then sent to the LAR’s smartphone for review. The e-Consent design has been previously published.4 In summary, we used REDCap (Research Electronic Data Capture), a secure Health Insurance Portability and Accountability Act-compliant web-based platform designed for research data capture. This software was used to create a survey project located on a static URL that can be remotely accessed (via smartphone browser). Regardless of the geographical position of the proxy, a link to the URL was sent via text message to the LAR. The required actions included entering the LAR’s email address, names of the patient and LAR, selecting relationship status, and signing freehand in the touchscreen.

We designed a structured survey in order to evaluate the experience of the LARs with the consenting process, focused on their opinions regarding the e-Consent strategy (Supplemental Material). This survey was applied to each LAR at least 12 hours after enrollment. ‘Door-to-eConsent’ was defined as the time interval between patient arrival at our institution and consent being electronically signed by the LAR. The questionnaire was obtained as part of a quality control initiative; approval for retrospective data review was obtained by the local Institutional Review Board.

Results

From February to November 2018, 60 consecutive patients were consented for the trial. Fifty-five were enrolled and five were considered ‘screen failures’. All enrolled patients were consented with the use of e-Consent; paper consent was not used during the study period. Three LARs were unavailable for the survey, three patients died before the questionnaire could be applied, and one refused to participate, leaving 53 patients for the primary analysis.

All LARs who were approached for potential trial enrollment were able to successfully complete the e-Consent process. Thirty-three patients (62%) were transferred from other institutions for potential thrombectomy. This allowed 27/53 patients (53%) to be e-Consented before they arrived at the tertiary care center. The median Door-to-eConsent interval was −7 min (IQR −46 to 63). Table 1 shows the patients' and LARs’ demographics and perceptions about the e-Consent process. Nearly all LARs (98%) reported e-Consent to be ‘clear’; 83% felt ‘very comfortable’ in signing the e-Consent. The overall experience was ‘excellent/good’ in 91%.

Despite the positive general impression regarding the e-Consent, 12 LARs (22%) would have preferred paper consent. The proportion of LARs who considered the e-Consent clear was overall high and comparable with the group who preferred paper consent (98% and 100%, respectively; p=1.00). The proportion of LARs who felt very comfortable in signing the e-Consent was equivalent among the two groups (83% vs 83%; p=1.00). Multivariable logistic regression indicated that lower educational status (tertiary education or less: OR 5.09, 95% CI 1.02 to 25.48, p=0.04) and lower ASPECTS on baseline imaging (OR 0.63, 95% CI 0.41 to 0.96, p=0.03) were independently associated with the preference for paper consenting (table 2).

Discussion

We have shown that the use of e-Consent for patient enrollment in AIS trials is feasible and is associated with a positive perception by LARs. Preference for standard paper consent was not common, and was predicted by lower LAR educational status and by larger baseline ischemic core.

In 2015 the FDA released formal recommendations for investigators/Institutional Review Boards/sponsors on the use of electronic media in clinical trials. e-Consent aims to enhance access and to optimize enrollment. We have previously published our pilot data on the use of e-Consent for the enrollment of patients in a large vessel occlusion trial. We found that e-Consent was feasible and had the potential to enhance rates of enrollment and to reduce time to randomization. However, the main limitation was the fact that, despite the apparently good performance, the perceptions of the LARs on the process were lacking.4

Data on the use of e-Consent for trial enrollment remain scarce. An experiment evaluating the use of a computer-based consenting tool included 50 participants who were informed that the study did not aim to truly enroll them in a real blood pressure medication trial but only to understand their personal preferences. They reported that the computer/web-based slideshow approach was easier to use and more interesting than paper consenting.5 In a study involving the use of e-Consent via REDCap to facilitate the inclusion of pregnant women in a clinical trial, all of the 61 patients were able to complete the consenting process. In our real-world experience, the use of e-Consent in the setting of acute stroke research was feasible and well received. Approximately one-fifth of LARs would have preferred standard paper consenting. Interestingly, all these individuals considered the e-Consent to be clear and 83% felt very comfortable in signing the e-Consent form, indicating that although it may not have been an optimal experience, it was positive. This needs to be considered in face of the time constraints related to acute stroke treatment.

Lower educational status has been suggested as a potential barrier to the use of e-Consent.5 Our cohort was composed of a substantial proportion of LARs with lower educational status (40% high school or less), and we observed this was associated with a higher chance of preference for paper consent. It is unclear how lower baseline ASPECTS (larger ischemic core) was associated with preference for paper consent.

e-Consent in AIS trials will always be limited by the emergent nature of the discussion. It allows the integration of interactivity/multimedia features that can enhance comprehension,5 so technology vendors may be able to enhance the tools for simpler and more intuitive processes.6 This may benefit both LARs and patients who have less formal education and improve their experiences with e-Consenting.

This study has limitations, including the sample size and other unmeasured variables that could have influenced the LARs' perspectives towards the e-Consent. The strengths of this study include its use in a real-life RCT of AIS and the diversity of the LAR population (wide range of ages and multi-ethnic backgrounds).

Conclusion

e-Consent was overall very well perceived by LARs in a RCT of LVOS. A minority of proxies, who were more commonly less formally educated, would have preferred paper consenting. Technological e-Consent enhancements may help to address this important gap.