Study Selection
The search strategy conducted in all four databases retrieved 9069 records which were imported to Covidence for title and abstract screening. Duplicates were automatically removed by the system. From the resulting 8355 records, a total of 286 references were included in full-text review. Two reviewers assessed the articles independently. The first reviewer assessed 286 articles, and the second reviewer assessed 192 articles (94 remaining articles at full-text stage were assessed only by one reviewer). Twelve studies were included in the final analysis. Study selection and reasons for exclusion are shown in the Study Flow diagram in Figure 1. Expanded table of all included studies is shown in Additional File – Appendix 4.
Study Characteristics
A summary of the main characteristics of included studies is shown in Table 1.
TABLE 1 SHOULD BE INSERTED HERE
Study Design and Country
From a total of 12 included studies, six were conducted in the United States (39-44), two in the United Kingdom (45, 46), one each in Gambia (47), Uganda (48), Canada (49), and one, conducted globally, reporting results from 23 different countries (50).
Study design of all included studies were SWAT, i.e., studies within parent RCTs. Six studies within trials were RCTs (40, 41, 45-47, 49) and six were observational studies (39, 42-44, 48, 50).
Health Topic and Setting
Parent studies of included trials addressed different health topics such as depression (2 studies), infectious diseases (3 studies), stroke (1 study), prenatal education (1 study), chronic obstructive pulmonary disease (COPD) (1 study), spine surgery (1 study), breast cancer (1 study), prelabour rupture of membranes (1 study) and prevention of behavioral problems in young children (1 study). Health care settings varied from hospitals, remote community, outpatient clinics, community-based clinics, general practices, physician’s offices and patient´s homes. All studies were published between 2005 and 2020, except one that was published in 1997 (49).
Study Participants
Studies varied in their participants’ characteristics as they targeted selected groups (Table 1). Mean age was reported in 10 studies, ranging from 27 to 73 years (39-46, 49-50). Two studies did not provide mean age of participants (47-48). Six studies included men and women (39, 41-43, 45, 47). Four studies included only women (40, 48-50). One study did not exclude men in its criteria but represented only female perspective (44) and another study included parents aged ≥18 years with child aged between approximately 12 and 36 months (46).
Level of education was reported in nine studies, with three reporting no formal education in the majority of their sample (45, 47, 48). The remaining six studies reported educational level ranging from university to college education (40) (43-44) (46) (49-50).
Recruitment method
Eight of the 12 studies reported their method of recruitment of participation as face-to-face. Other studies reported methods of recruitment were by phone (39, 42), online (50), and by phone and letter (45).
Sample Size
In total, 8864 people participated in the 12 included studies. Number of participants analyzed per individual study ranged from four to 4214.
Type of Intervention and Comparator
Intervention type by IC component:
Nine out of the 12 included studies only evaluated the first component of the IC process, i.e., electronic information given to trial participants. In these studies, electronic information was provided in different ways, for example, as an aid to the paper IC form (40, 41, 43, 45, 46, 49) and as standalone electronic information (44, 47, 48). Formats for providing information varied from multimedia tool, slide show, video, and telemedicine (computer-enabled audio-visual communication). Three studies (39, 42, 50) had all three components of the IC form carried out electronically. No studies evaluated an intervention pertaining to only the second component of IC: participant comprehension. When electronic components of IC were provided, they were done both remotely (39, 42, 45, 46) and on-site/face-to-face (40, 41, 43, 44, 47-49).
Comparator
Traditional IC (face-to-face information and paper written consent) was the pre-defined comparator in this systematic review. Eight studies had traditional IC (39-42, 45-46, 47, 49) as the comparator. Other comparators were used in two studies: standard information read out by researcher (48) and pre- and post-intervention comparison in patient’s preference (43). Two studies (44, 50) did not include a comparator.
Most studies with a comparator included two arms. One trial (48) included three arms. All comparisons are listed as follows:
First component of IC (electronic information giving):
- Video information vs written versions in local languages or verbal presentation of the written IC given by trained study staff who were native speaker of the local language (47)
- Slideshow using illustrated text on a flip chart vs video vs standard researcher-read information (48)
- Video as an aid to paper IC vs written IC (40, 46)
- Telemedicine (computer-enabled audio-visual communication) as an aid to paper consent vs written IC (41)
- Written IC with access to a multimedia information resource vs written IC (45)
- Video decision aid as part of their IC process (before and after comparison in treatment preference) (43)
- Video vs written IC (49)
- Educational video vs no comparator (44)
All three components of IC were electronic
- Automated online IC vs no comparator (50)
- Videoconferencing vs written IC in person (42)
- Online IC vs written IC(39)
Study Outcomes
Five studies (44-46) provided data on the primary pre-defined outcome—rate of enrolment. For the secondary pre-defined outcomes, one study described the economic cost of using e-IC but none reported quantitative outcomes on the practical benefits or challenges of implementing e-IC. There was narrative information reported on the acceptability to potential participants. There were outcomes reported by studies that were not anticipated in the protocol: participant´s comprehension of information, effect on changes in treatment preferences by participants, experience of e-IC by users, participant and researcher attitudes towards method of recruitment, number of participants responding to the trial invitation, intention to participate in a clinical trial, and retention rates. Outcomes were varied and were measured in different ways. Some studies utilized questionnaires administered through computers, surveys sent by emails, electronic multiple-choice options, and in-person or telephone interviews.
Summary of outcomes is shown in Table 2.
TABLE 2 SHOULD BE INSERTED HERE
Quality Assessment
The quality of included studies varied. All six RCTs included in this review (40, 41, 45-47, 49) were assessed using the Cochrane Risk of Bias tool, and overall, they were judged to be at moderate-to-high risk of bias. Graphical summary of the risk of bias of included RCTs are shown in Figure 2 and Figure 3. Complete assessment of risk of bias using the Cochrane risk of bias table is detailed in Additional File - Appendix 5 and 8.
The assessment of risk of bias for non-randomised studies was performed using the CASP checklist (36). Templates for the Case Control and Cohort risk of bias are available in Additional File - Appendix 6 and 7. Overall, studies were judged as high risk of bias as there was not sufficient information to perform a detailed assessment. There were a mixture of secondary analyses, case control studies, cohort studies and studies that lacked objective outcome measures (Additional File - Table 3 and Appendix 8).
Primary Outcome
Five studies provided data on the predefined primary outcome — rate of enrolment, defined as the proportion of invited potential participants enrolled and/or the number of participants recruited in a given period (e.g., month).
Effect on Recruitment Rate
Two studies showed no statistically significant improvement in recruitment rate following an intervention when compared to written IC as controls. These interventions were written IC with access to a multimedia resource [OR 0.84, 95% CI 0.58 to 1.22] (45) and computer-enabled audio-visual communication as an aid to paper consent [56% vs. 69%, p=0.142] (41).
One study showed that an intervention group using a video aid to paper ICF was less likely to take part in the main clinical trial when compared to written IC (OR = 0.25, CI = 0.10–0.62, p = 0.003) (46).
Weston et al. showed a significantly larger proportion of participants expressing willingness to participate in a future trial when they have received the video intervention compared to those that received written IC (61.9% vs. 35.4%, x2 = 6.3; df = 1; P =0.01) (49). Swain et al. showed that a video intervention resulted in a statistically significant increase of participant enrolment to a clinical trial by 7% post-intervention when compared to the enrolment rate pre-intervention in a previous year (13.5% of 200 participants enrolled post-intervention, 6% enrolled pre-intervention, p< 0.001) (44).
Secondary Outcomes
Economic costs
Jolly et al. (45) estimated an additional six people would be recruited per 1000 approached at a cost of £100 per additional patient with the use of an online multimedia intervention which consisted of study-specific information, generic information on e.g., confidentiality, informed consent, randomization and videos of participants’ experiences. The cost of the online multimedia intervention was estimated £2500 (45, pp. 4). We contacted the authors for the paper by Afolabi et al (47), which stated the economic summary of their multimedia intervention was available by correspondence. No reply has been received at the time of writing this report.
Other secondary outcomes
The predefined secondary outcomes relating to the practical benefits, challenges of implementing e-IC, and acceptability of e-IC to potential participants were not universally reported by all of the studies. Some studies reported findings relevant to these outcomes, so we have provided a descriptive and narrative summary of what we felt were relevant to these outcomes.
Patient Comprehension and Understanding
Five studies (40, 41, 47, 48, 50) measured patient´s comprehension and understanding of the information as their primary outcome.
Afolabi et al. (47) reported better comprehension of study information, measured using an IC comprehension questionnaire, at baseline, day seven and day 14 in the group that received video information when compared to the group that received written versions in local languages or verbal presentation of the written IC by trained native language-speaking staff (score at day 14: 64%v 40%, p=0.035). Barrera et al. (50) reported that, with the use of an automated IC process for an online trial, a high proportion of participants (n = 1,179) showed a correct understanding of the study’s purpose (86.1%) and correctly identified two of three of the study’s benefits (74.6%). 56% correctly identified some or all of the potential risks of participation (50, pp. 5). Rothwell et al. (40) found that using a video presentation on an iPad, followed by a paper copy of the consent form may improve understanding of some aspects of a trial: “the alternatives to participation in this study” (4.88 ± 0.42 vs. 4.37 ± 1.10, p = .047); “who to contact if you are upset because of participation in this study” (4.41 ± 0.80 vs. 4.03 ± 1.40, p = .002); “Whom you should contact if you have questions or concerns about this study” (4.34 ± 0.97 vs. 4.13 ± 1.33, p = .009); and “Overall, how well did you understand this study when you signed the consent form” (4.72 ± 0.58 vs. 4.63 ± 0.67, p = .019) (40, pp. 5). Qualitative interviews in this study supported that the video was easy to understand and improved participants’ attention.
Bobb et al. (41) found that comprehension of consent using telemedicine (computer-enabled audio-visual communication as an aid to paper consent) was not inferior to standard face-to-face written consent, measured using a modified quality of informed consent instrument (QuIC) (QuIC scores 74.4 ± 8.1 vs. 74.4 ± 6.9 on a 100-point scale, p = 0.999).
Ditai et al. (48) reported no statistically significant difference on the QuIC tool at 48 hours after consenting to any of the three models of IC: i) Slideshow using illustrated text on a flip chart, ii) an approved study video iii) standard researcher-read information. Most participants in this study preferred the slide-show message (63%, 19/30), compared with 20% (6/30) for the video message and17% (5/30) for the standard model.
Weston et al. (49) found no differences in knowledge about the perinatal trial after receiving a video intervention when compared to written IC but they did find an increase in the retention of knowledge 2-4 weeks later by women in the video intervention group.
Acceptability to participants and user experiences
Mattock et al. (46) reported positive feedback on the usefulness of a video aid in addition to paper IC in all participants. All 17 participants interviewed found information easy to understand and informative but also commented on additional questions that needed discussing over the phone. Participants in the video group described material as introductory whilst those in standard consent group described the standard information as comprehensive. Participants and researchers found that an initial email contact increased participant´s receptivity to the study and engagement in the trial. Researchers also reported a better understanding of randomization by participants who watched the video.
Haussen et al. (39) reported acceptability of the use of an entirely electronic IC process to remotely obtain IC from the legally authorized representative (LAR) of stroke patients being enrolled into a clinical trial of neurointervention—the DAWN trial (39, pp.1). The LARs surveyed in this study reported no reservation in using this e-IC process via Research Electronic Data Capture (REDCap) platform, a secure/Health Insurance Portability and Accountability Act compliant data management platform, developed by the Vanderbilt University. This was used to create an online IC form, which could be accessed on a webpage. The investigator held discussion with the LAR of the potential participant over the telephone. Once agreed to be enrolled, LAR was sent a text message with a link to the webpage to complete the online IC form, which had the capability of capturing the LAR’s electronic signature.
Bobb et al. (41) identified no significant barriers in the use of telemedicine (computer-enabled audio-visual communication) as an aid to paper consent from its qualitative survey. It reported that video was easy to understand and was better at holding patient´s attention than a paper-based approach would have.
Other Outcomes
Changes in treatment preferences
Lurie et al. (43) found that watching video information prior to enrolment to a clinical trial comparing surgical and non-surgical treatments for spinal diseases led to a shift in treatment preference compared to non-watchers (37.9% vs 20.8%, p < 0.0001). These shifts were balanced and did not demonstrate any overall shift towards or away from surgery.
Invitation response and retention rates
Jolly et al. (45) found no effect on the proportion of people responding to study invitation (OR = 1.02, 95% CI 0.79 to 1.33) or retention in the trial at 6 (ORs 0.84, 95% CI 0.57 to 1.22) and 12 months after randomisation with the use of a multimedia information resources as an addition to written IC when compared with written IC only (ORs 0.80, 95% CI 0.54 to 1.18).
Study by Swain et al. (44) showed an increase of 14% (p< .001) in the proportion of patients expressing likelihood to enroll in a trial for breast cancer after the use of an educational video in a survey of attitudes and intention to enroll in therapeutic clinical trials.
Assessing intervention fidelity
Jolly et al. (45) did not report the number of participants who used the link to access the multimedia resource which was part of the intervention, so it was unclear how many participants actually used the resource.
Study by Mattock et al. (46) utilized an entirely remote e-IC process to obtain IC from LAR. However, it was not possible to ascertain whether the LAR actually read the online IC. It was unclear how much time the LARs or patients were given to decide about trial participation.