Background The pilot use of a smartphone platform for electronic informed consent (e-Consent) in large vessel occlusion acute stroke (LVOS) trials has recently been reported. The degree of satisfaction from Legal Authorized Representatives (LARs) with regard to this process remains to be established.
Methods A single-center study evaluating the experience of LARs with the use of e-Consent in a LVOS randomized trial of an investigational drug administered within 12 hours of last known normal was carried out. A structured survey was used to evaluate the experience of the LARs with the e-consenting process.
Results From February to November 2018, 60 consecutive patients were e-Consented. Of these, 53 LARs completed the survey. The median (IQR) age of the patients was 63 (53–70) years, baseline/discharge National Institutes of Health Stroke Scale score was 17 (12–20)/3(1–12), and 45% were independent at discharge. The survey was applied in person in 43% of cases and via telephone in 57%. Median LAR age was 48 (39–59) years, 64% were female, and a multi-ethnic composition was observed. Forty percent of LARs had less than tertiary level of education (high-school or less). Regarding the e-Consent, 98% of LARs reported to be ‘clear’ and 83% felt ‘very comfortable’ in signing. The overall experience was ‘excellent/good’ in 91%. Despite the positive general impression regarding the use of e-Consent, 12 LARs (22%) would have preferred paper consent. Multivariable 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 baseline ASPECTS score (OR 0.63, 95% CI 0.41 to 0.96; p=0.03) were independently associated with preference for paper consent.
Conclusions e-Consent was overall very well perceived by LARs in a randomized clinical trial of LVOS. A minority of proxies, who were more commonly less formally educated, would have preferred paper consenting.
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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.
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.
The primary outcome was the rate of LARs who would have preferred standard paper consent. Univariate analysis was performed and variables with a level of significance <0.1 were included in a multivariable logistic regression. Continuous variables were reported as mean±SD or median (IQR) and categorical variables were reported as proportions. Between-group comparisons for continuous/ordinal variables were made with the Student t-test/Mann–Whitney U test and for categorical variables using the χ2 test. Statistical analyses were performed using STATA-14 (Stata Corp, College Station, Texas, USA).
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).
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).
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.
Contributors DCH: Study conception, design of the work, acquisition of data, statistical analysis, interpretation of data, drafting of the manuscript. LC, SD, GMR, ARA, MS, LS, KMS, MRF: Data acquisition, critical revision of manuscript. KR: Statistical analysis, critical revision of manuscript. RN: Design of the work, interpretation of data, critical revision of manuscript. All authors gave final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests DCH: Consultant for Stryker and Vesalio; Viz-AI: stock options. RN: Principal Investigator, Stryker Neurovascular (DAWN trial - no compensation, Trevo-2 trial), Cerenovus/Neuravi (ENDOLOW trial - no compensation); consultant to Stryker Neurovascular; steering committee member, Stryker Neurovascular (no compensation), Medtronic (SWIFT trial, SWIFT Prime trial - no compensation), Cerenovus/Neuravi (ARISE-2 trial - no compensation); angiographic core lab, Medtronic (STAR trial); executive committee member, Penumbra (no compensation); physician advisory board, Cerenovus/Neuravi, Phenox, Anaconda, Genentech, Biogen, Prolong Pharmaceuticals, Allm Inc.(no compensation), Viz-AI; stock options, Viz-AI.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The unpublished data from this dataset are held by Grady Memorial Hospital/Emory University and DCH/RN. Requests for data sharing would be required to be discussed with them directly.
Patient consent for publication Not required.