Abstract
This study aims to investigate the knowledge and attitudes of participants and potential participants in clinical trials toward electronic informed consent. We conducted a survey-based cross-sectional study in Hunan Province, China in March 2021. A total of 547 respondents were included in this study. All questions in an 8-item survey section assessing participants’ knowledge of electronic informed consent received correct answers from at least 70% of participants. In terms of attitude scores, most participants (86.3%) believed that electronic informed consent is more convenient than the paper-based version, and more than half (51.2%) believed that electronic informed consent could completely replace the paper-based version. Responses indicated that common concerns about electronic informed consent were its security and confidentiality, legal benefits, and implications for rights protection.
Keywords: Knowledge, attitude, electronic consent, informed consent, clinical trial
Introduction
Informed consent is a key component of the rights and protection of clinical trial subjects, as an application of the principle of respect for persons (National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 1979). The informed consent process for clinical research typically includes face-to-face interactions between researchers and participants, to review an informed consent document and prompt an individual’s decision about whether to participate (Hallinan, et al., 2016). In recent years, with the rapid development of information technology, an increasing proportion of clinical research is using electronic media to supplement or replace paper-based informed consent (Lentz, Kennett, Perlmutter, & Forrest, 2016). Electronic informed consent (eIC) is the process of using electronic systems and procedures to convey research-related information and obtain and record informed consent in research and clinical care — including the use of a variety of electronic media, such as text documents, images, audio and video materials, interactive websites, biometric devices, and card readers (US Food and Drug Administration [FDA],2016).
As eIC has grown in popularity, guidelines for its use have also emerged in various countries, beginning in recent years and accelerating during the COVID-19 pandemic. In 2020, many trials involving face-to-face communication with subjects were suspended due to pandemic restrictions, causing significant obstacles for research (Rai, & Frei, 2020). In response to this situation, the FDA issued industry guidelines for clinical trials in March 2020 stating that during the period when COVID-19 may cause research interruptions, clinical investigators and IRBs should consider changes to policy and procedures regarding informed consent and other research steps (FDA, 2020). In 2020, the European Medicines Agency of the European Union (EMA) issued “Guidance on the Management of Clinical Trials during the COVID-19 Pandemic,” which included a statement permitting use of eIC during the pandemic in EU member countries, “if in compliance with national legislation” (EMA, 2021).
In China, prior to the COVID-19 pandemic, eIC was rarely used in clinical research, and had only been attempted in other areas of medical practice, such as vaccination, and clinical medical record systems (Cong, Mu, & Rao, 2019). But new regulations and guidelines during the pandemic began to permit and regulate use of eIC, including for research. In 2020, a regulation entitled “Good Clinical Practice for Drug Clinical Trials (GCP)” permitted for the first time that electronic data including eIC could be used in drug clinical trials (National People’s Congress of the People’s Republic of China, 2020). And on July 2021, the Center for Drug Evaluation (CDE) in China published “Guidelines for the Management of Drug Clinical Trials during COVID-19 (Provisional),” which noted that many practical difficulties to implementation of clinical trials may arise during the pandemic, and permitted clinical trials to use remote technology such as remote eIC (CDE, 2021).
While governments have begun to permit eIC in clinical research under certain circumstances, many questions about how to implement eIC legally and ethically have yet to be addressed (Harvard catalyst, 2021). As such, studies have begun to emerge examining areas of eIC that need improvement and, in some cases, further regulation. Evaluations in the US and UK have shown that many research participants consider eIC easier to use, more interesting, and easier to understand than paper-based consent — but also that eIC may raise concerns such as accessibility for underrepresented populations, user-friendliness, and data security (Simon et al., 2018) (Skelton et al., 2020). Improved participant satisfaction with eIC is associated with trust-enhancing messages providing more background information, and interactive explanatory features (Skelton et al., 2020) (Golembiewski et al., 2021). However, a 2020 scoping review showed that although experts have identified benefits to eIC versus paper-based consent, research on effective strategies for overcoming barriers to eIC adoption is still far from comprehensive (Chen, et al., 2020).
Evidence suggests many researchers have reservations about using eIC for clinical trials in particular, with 67% of UK researchers in a 2016 survey stating they believed eIC was suitable only for observational research (Stevens, et al., 2016). However, at present, few studies have examined research participants’ knowledge and attitudes toward use of eIC specifically in clinical trials — despite the increased use of eIC for clinical trials during the COVID-19 pandemic. And to our knowledge, no evaluation studies of the use of eIC for research have yet been conducted in China. Considering that eIC is a relatively new method in China with potential for wider use to continue emerging from the pandemic, there is a need for further research in China on how research participants perceive eIC — particularly in the under-studied area of clinical trials. After searching and synthesizing previous research on eIC, and based on the current development status of eIC in China, we designed and implemented a self-developed questionnaire to investigate the knowledge and attitudes of clinical trial subjects and potential subjects in China toward eIC.
Methods
We conducted a cross-sectional study between March 19, 2021 and March 28, 2021 in Hunan Province in Central Southern China. The study included an online, self-administered, structured questionnaire. The questionnaire was developed by the research team, evaluated by four independent professionals with expertise in research ethics for content validity, and then finalized according to their feedback and comments.
Participants were then recruited to complete the finalized questionnaire if they were 18 years of age or older, and met one of two additional inclusion criteria: (1) had enrolled previously in clinical trials, or (2) had agreed to be contacted for clinical trial recruitment. Our reasons for these criteria were to select participants who had at least some familiarity with informed consent and clinical trials, and to investigate knowledge and attitudes toward eIC among those who might be most likely to encounter eIC in the future. An invitation to complete the online questionnaire by web link was sent out to potential participants through two channels: WeChat (a popular social media app in China), and 520, a clinical trial recruitment platform in Hunan Province. Individuals receiving the link included only those who had either formerly enrolled in clinical trials, or who had indicated willingness to be contacted through the platforms for clinical trial recruitment. The web link included a consent form and questionnaire that could be filled out online. After participants read and submitted the initial consent form, they could choose to complete the questionnaire. Questionnaires were returned anonymously; therefore, no information was available that could link the identity of participants to their responses. The questionnaire required approximately 20 minutes to complete.
The questionnaire consisted of four sections: demographic information, basic information, a knowledge survey, and an attitude survey. Descriptive statistics were used to summarize data collected in the demographic section of the questionnaire, which included gender, age, marital status, residential area, economic level, and educational background. The basic information section was a combination of single-answer-choice questions and multiple-answer-choice questions, divided into two parts: electronic device usage and clinical-trial-related experience. The electronic device usage part included questions about the frequency and duration of the participant’s electronic device usage, and the clinical-trial-related experience part included questions about the participant’s amount of previous experience participating in clinical trials, types of participation in clinical trials, and whether they had heard of the term “electronic informed consent.” The knowledge survey included questions about the correctness of eight statements about eIC, with options for participiants to mark each statement with “yes,” “no,” or “I don’t know.” Questions included statements about the concept, content, form, and legal effectiveness of eIC. The correct answer to all eight questions was “yes,” as all statements included about eIC were correct. We calculated a knowledge score for each participant by adding the total number of points, where “yes” answers were each counted as 1 point, while “no” or “I don’t know” answers were counted as 0 points. Therefore, the lowest possible knowledge score was 0 points, and the highest possible knowledge score was 8 points. Higher knowledge scores were considered to signify a higher level of knowledge about eIC.
The Electronic Informed Consent Attitudes Scale (eIC Attitudes Scale) is a 17-item, self-report attitude survey developed at the outset of this study. Questions measure participants’ attitudes toward eIC, with responses scored on a 5-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). Seven of the items were negatively worded and reverse scored (e.g. a score of 5 became 1, and vice versa) when calculating the total score of the eIC Attitudes Scale. The total possible score was between 17 and 85. A higher total score indicates more positive attitudes toward eIC.
Data was analyzed using SPSS 26.0. The internal consistency of the eIC Attitudes Scale was measured using Cronbach’s alpha coefficient. The Cronbach’s alpha coefficient for the reliability of the eIC Attitudes Scale was 0.806. It is generally believed that a Cronbach’s alpha coefficient greater than 0.7 indicates that a scale has satisfactory internal consistency (Waclawski, 2010).
The Cochrane formula (n = z2pq/e2) was used for sample size calculation, with the confidence interval 0.95 and a margin of error of 5%. The resulting minimum sample size was 385. Response data was processed using SPSS 26.0 (IBM, Chicago, IL, USA), with the dataset generated from all valid questionnaires. Questionnaires were considered valid if 100% of questionnaire items were completed; validity was ensured upon submission, through the use of survey software that required completion of all survey items in order for participants to submit responses.
Results
Participant demographics
The study questionnaire received a total of 547 responses, of which 429 were from Hunan Province and 118 were from other provinces. As the total number of individuals who had access to the survey link through the recruitment platforms is not known, a response rate could not be calculated. A complete description of participant demographics is displayed in Table 1. The number of male participants was 264 (48.3%), and urban residents accounted for 83.2% of participants. In terms of economic level, 21.0% of participants’ annual household disposable income per capita was low (<7,400 CNY), 15.5% were lower-middle income (7,400–16,000 CNY), 23.4% were middle income (16,000–25,000 CNY), 22.7% were upper-middle (25,000–39,000 CNY), and 17.4% were high income (39,000–75,000 CNY). In terms of current job status, the proportions of participants who were students, unemployed, full-time employed, and part-time employed were 16.8%, 6.6%, 66.9% and 9.7%, respectively. In terms of education level, the proportion of participants who were junior high school graduates and below accounted for 6.6%, while proportions of those who graduated from high school, undergraduate, and postgraduate education were 27.1%, 49.2%, and 17.2% respectively.
Table 1.
Participants demographic characteristics (n=547)
| Characteristics | N(%) |
|---|---|
| Age, years (mean±SD) | 33 ± 11 |
| Gender | |
| Male | 264 (48.3) |
| Female | 283 (51.7) |
| Residency | |
| Urban | 455 (83.2) |
| Rural | 92 (16.8) |
| Region | |
| Hunan Province | 429 (78.4) |
| Other provinces | 118 (21.6) |
| Current job status | |
| Student | 92 (16.8) |
| Unemployed | 36 (6.6) |
| Part-time employment | 53 (9.7) |
| Full-time employment | 366 (66.9) |
| Annual per capita household disposable income level | |
| Low (<7400 CNY) | 115 (21.0) |
| Lower-middle (7400 – 16000 CNY) | 85 (15.5) |
| Middle (16000 – 25000 CNY) | 128 (23.4) |
| Upper-middle (25000 – 39000 CNY) | 124 (22.7) |
| High (39000 – 75000 CNY) | 95 (17.4) |
| Level of education | |
| Less than high school | 36 (6.6) |
| High school | 148 (27.1) |
| College | 269 (49.2) |
| Postgraduate | 94 (17.2) |
| Length of time using smartphone/computer daily | |
| <1h | 15 (2.7) |
| 1–3h | 102 (18.6) |
| 3–6h | 184 (33.6) |
| >6h | 240 (43.9) |
| Frequency of difficulty during use of smartphone/computer | |
| Never | 270 (49.4) |
| Occasionally | 250 (45.7) |
| Often | 27 (4.9) |
| Previously participated in a clinical trial | |
| Yes | 170 (31.1) |
| No | 377 (68.9) |
| Types of participation in clinical trials a | |
| Drug clinical trials | 161 (79.7) |
| Medical device clinical trials | 12 (5.9) |
| Research initiated by the researcher | 28 (13.9) |
| Other | 1 (0.5) |
| Awareness of electronic informed consent | |
| Never heard of it | 237 (43.3) |
| Heard of it but not very familiar | 219 (40.0) |
| Heard of it and familiar | 91 (16.6) |
| Preferred device to use for electronic informed consent | |
| Mobile device (mobile phone/tablet) | 476 (87.0) |
| PC device (desktop computer) | 71 (13.0) |
More than one answer was possible
SD=Standard deviation
A total of 170 participants (31.1%) had enrolled in clinical trials previously. 43.3% of participants said that they had not heard of the term “electronic informed consent” before, 40.0% said they had heard of it but did not understand it well, and 16.6% said they had heard of it and understood it well. 87.0% of participants preferred mobile devices (mobile phones, tablets, etc.) as the device to use for eIC, and 13.0% preferred to use PC devices. 4.9% of people stated that they find it difficult to use electronic devices for daily tasks.
Knowledge of electronic informed consent
Regarding knowledge of eIC, participants had an overall median knowledge score of 8 (IQR 6–8). As shown in Table 2, all questions in the knowledge section of the questionnaire had an overall correct response rate of more than 70%. The majority of questions were answered correctly by more than 80% of participants, including questions on the reliability of eIC, diversity of forms of eIC, consistency of content with paper-based informed consent, diversity of communication methods, use of electronic signatures, and methods of information presentation. Relatively few participants knew about the location flexibility of eIC (73.1%) and the requirement for ethics review (77.5%).
Table 2.
Knowledge of electronic informed consent
| Question | Yes(%) |
|---|---|
| Electronic informed consent relies on electronic systems and procedures to convey research-related information, and obtain and record informed consent | 456(83.4) |
| The electronic media used for electronic informed consent can include many forms, such as electronic text, images, audio, video, interactive websites, biometric devices and card readers, etc. | 444(81.2) |
| The use of electronic informed consent needs to be reviewed and approved by an ethics committee. | 424(77.5) |
| The main content of electronic informed consent is the same as paper-based informed consent. | 442(80.8) |
| The electronic informed consent process can be carried out on-site at the research site (i.e., the investigator and the subject are in the same place), or remotely when the subject is not on the research site (i.e., the subject is at home). | 400(73.1) |
| When using eIC, the subject can communicate with the investigator on-site, or communicate remotely through electronic messages, telephone, video or real-time chat. | 439(80.3) |
| The electronic informed consent process can use electronic signatures to obtain the signatures of subjects or their legal representatives. | 439(80.3) |
| Electronic informed consent uses interactive electronic technologies such as diagrams, images, graphics, and videos to help subjects understand relevant information. | 456(83.4) |
Attitudes toward electronic informed consent
For the purposes of this description, we added together the percentages of “strongly agree” and “agree” responses from the attitude section of the questionnaire.
As shown in Table 3, most participants (86.3%) thought eIC is more convenient than paper-based consent. Nearly 70% of participants expressed a preference for eIC over paper-based consent, and more than half (51.2%) believed that eIC could completely replace paper-based consent.
Table 3.
Attitudes toward electronic informed consent
| Question | Strongly Agree (%) | Agree (%) | Not Sure (%) | Disagree (%) | Strongly Disagree (%) |
|---|---|---|---|---|---|
| Compared with paper-based informed consent, I prefer to use electronic informed consent. | 164(30.0) | 218(39.9) | 129(23.6) | 32(5.9) | 4(0.7) |
| I think using electronic informed consent would make me more willing to participate in clinical trials. | 152(27.8) | 160(29.3) | 175(32.0) | 49(9.0) | 11(2.0) |
| I think it is more convenient to use electronic informed consent, compared to paper-based consent. | 209(38.2) | 263(48.1) | 60(11.0) | 11(2.0) | 4(0.7) |
| I think electronic informed consent can completely replace the use of paper-based informed consent. | 119(21.8) | 161(29.4) | 158(28.9) | 90(16.5) | 19(3.5) |
| I think I would be able to decide more easily whether to participate in a trial using electronic informed consent, compared to paper-based consent. | 137(25.1) | 212(38.8) | 167(30.5) | 29(5.3) | 2(0.4) |
| Compared with paper-based informed consent, I would prefer to use interactive devices (such as computers or mobile phones) at the research site when using electronic informed consent. | 175(32.0) | 242(44.2) | 96(17.6) | 32(5.9) | 2(0.4) |
| Compared with paper-based informed consent, I prefer to participate in remote electronic informed consent (not at the research site). | 157(28.7) | 197(36.0) | 142(26.0) | 46(8.4) | 5(0.9) |
| I am worried that I am not proficient in the use of electronic equipment, and would not be able to adapt to using electronic informed consent. | 87(15.9) | 161(29.4) | 110(20.1) | 141(25.8) | 48(8.8) |
| I am worried that I would not be able to understand the research content (such as research purpose, research methods, research procedures, risks and benefits, etc.), when using electronic informed consent. | 104(19.0) | 181(33.1) | 133(24.3) | 100(18.3) | 29(5.3) |
| I have concerns about online communication or interaction with researchers during the electronic informed consent process. | 96(17.6) | 193(35.3) | 156(28.5) | 81(14.8) | 21(3.8) |
| I think that in the electronic informed consent process, it is better to be able to set up interactions with researchers (such as online question and answer, video explanation, etc.). | 180(32.9) | 255(46.6) | 91(16.6) | 17(3.1) | 4(0.7) |
| Compared with paper-based informed consent, I have concerns about the security and confidentiality of using electronic informed consent. | 143(26.1) | 256(46.8) | 109(19.9) | 34(6.2) | 5(0.9) |
| I think that electronic informed consent should include a more detailed introduction to privacy protection and data confidentiality measures than paper-based informed consent. | 219(40.1) | 265(48.5) | 48(8.8) | 13(2.4) | 2(0.4) |
| I can accept facial recognition, fingerprint recognition, electronic signature, and other technologies for the signing of electronic informed consent. | 167(30.5) | 271(49.5) | 71(13.0) | 33(6.0) | 5(0.9) |
| I think the use of electronic informed consent can better regulate the signing of informed consent and avoid errors and omissions. | 150(27.4) | 229(41.9) | 132(24.1) | 32(5.9) | 4(0.7) |
| I have concerns about the legal effectiveness and protection of my rights and interests as a research subject when using electronic informed consent. | 118(21.6) | 240(43.9) | 130(23.8) | 47(8.6) | 12(2.2) |
| I think that in my country, the relevant laws and regulations on electronic informed consent for clinical trials need to be further improved. | 196(35.8) | 271(49.5) | 68(12.4) | 10(1.8) | 2(0.4) |
In terms of electronic signature methods, 80.0% of people were willing to accept facial recognition, fingerprint recognition, and other electronic signature methods, and 69.3% believed that their signing of eIC would be more standardized than in the paper-based version. Nearly 60% of people believed that eIC would increase their willingness to participate in clinical trials, while 63.9% believed that it would be easier to decide whether to participate in a trial when using eIC, compared to paper-based consent.
When it comes to the specific scenarios in which eIC is used, participants were more willing to use interactive equipment on site (76.2%) and to engage in remote signing of eIC (64.7%) than to use paper-based consent. 45.3% of people were worried about their ability to use electronic devices, 52.1% expected to have difficulty understanding research content, and 52.9% expected to have difficulties interacting with researchers when using eIC.
In terms of other concerns about eIC, 72.9% of participants expressed concerns about its security and confidentiality, and 88.6% believed that eIC should include more detailed confidentiality explanations. In addition, 65.5% of people had concerns about legal and rights protection, and 85.3% believed that laws and regulations related to eIC still need to be further improved.
Factors associated with knowledge and attitudes
Tables 4 and 5 show the average (median) knowledge scores and average (mean) attitude scores from different groups of participants.
Table 4.
Factors associated with knowledge of electronic informed consent
| Variables | N (%) | Median (IQR) | a p-value |
|---|---|---|---|
| Total | 547 (100) | 8 (6–8) | N/A |
| Gender | |||
| Male | 264 (48) | 8 (5–8) | 0.233 |
| Female | 283 (52) | 8 (6–8) | |
| Residency | |||
| Urban | 455 (83) | 8 (6–8) | 0.440 |
| Rural | 92 (17) | 8 (4–8) | |
| Current job status | |||
| Student | 92 (17) | 8 (5–8) | 0.323 |
| Unemployed | 36 (6) | 7 (1–8) | |
| Part-time employment | 53 (10) | 8 (6–8) | |
| Full-time employment | 366 (67) | 8 (5–8) | |
| Annual per capita household disposable income level | |||
| Low (<7400 CNY) | 115 (21) | 8 (3–8) | 0.278 |
| Lower-middle (7400 – 16000 CNY) | 85 (16) | 8 (5–8) | |
| Middle (16000 – 25000 CNY) | 128 (23) | 8 (6–8) | |
| Upper-middle (25000 – 39000 CNY) | 124 (23) | 8 (6–8) | |
| High (39000 – 75000 CNY) | 95 (17) | 8 (7–8) | |
| Level of education | |||
| Less than high school | 36 (7) | 5 (0–8) | 0.000* |
| High school | 148 (27) | 8 (5–8) | |
| College | 269 (49) | 8 (6–8) | |
| Postgraduate | 94 (17) | 8 (7–8) | |
| Previously participated in a clinical trial | |||
| Yes | 170 (31) | 8 (6–8) | 0.192 |
| No | 377 (69) | 8 (6–8) | |
| Awareness of electronic informed consent | |||
| Never heard of it | 237 (43) | 7 (4–8) | 0.000* |
| Heard of it but not very familiar | 219 (40) | 8 (7–8) | |
| Heard of it and familiar | 91 (17) | 8 (8–8) | |
| Preferred device to use for electronic informed consent | |||
| Mobile device (mobile phone/tablet) | 476 (87) | 8 (6–8) | 0.293 |
| PC device (desktop computer) | 71 (13) | 8 (6–8) |
Mann-whitney test and Kruskal-Wallis test were used
Statistically significant
IQR = Interquartile range
Table 5.
Factors associated with attitudes toward electronic informed consent
| Variables | N (%) | Mean | SD | a p-value |
|---|---|---|---|---|
| Total | 547 (100) | 54.85 | 6.55 | N/A |
| Gender | ||||
| Male | 264 (48) | 56.01 | 6.87 | 0.000* |
| Female | 283 (52) | 53.78 | 6.08 | |
| Residency | ||||
| Urban | 455 (83) | 54.85 | 6.66 | 0.966 |
| Rural | 92 (17) | 54.88 | 6.12 | |
| Current job status | ||||
| Student | 92 (17) | 53.27 | 5.35 | 0.000* |
| Unemployed | 36 (6) | 54.17 | 5.07 | |
| Part-time employment | 53 (10) | 54.97 | 6.93 | |
| Full-time employment | 366 (67) | 57.26 | 6.10 | |
| Annual per capita household disposable income level | ||||
| Low (<7400 CNY) | 115 (21) | 55.42 | 5.43 | 0.440 |
| Lower-middle (7400 – 16000 CNY) | 85 (16) | 55.49 | 5.68 | |
| Middle (16000 – 25000 CNY) | 128 (23) | 54.27 | 6.72 | |
| Upper-middle (25000 – 39000 CNY) | 124 (23) | 48.48 | 2.46 | |
| High (39000 – 75000 CNY) | 95 (17) | 54.46 | 7.59 | |
| Level of education | ||||
| Less than high school | 36 (7) | 56.53 | 6.20 | 0.079 |
| High school | 148 (27) | 55.67 | 5.91 | |
| College | 269 (49) | 54.4 | 6.66 | |
| Postgraduate | 94 (17) | 54.22 | 7.24 | |
| Previously participated in a clinical trial | ||||
| Yes | 170 (31) | 56.89 | 7.18 | 0.000* |
| No | 377 (69) | 53.93 | 6.06 | |
| Awareness of electronic informed consent | ||||
| Never heard of it | 237 (43) | 54.21 | 6.35 | 0.114 |
| Heard of it but not very familiar | 219 (40) | 55.47 | 6.53 | |
| Heard of it and familiar | 91 (17) | 55.04 | 7.10 | |
| Preferred device to use for electronic informed consent | 0.706 | |||
| Mobile device (mobile phone/tablet) | 476 (87) | 55.1 | 6.50 | 0.021* |
| PC device (desktop computer) | 71 (13) | 53.18 | 6.82 |
Independent t-test and One-way ANOVA
Statistically significant
SD=Standard deviation
Differences in median knowledge scores by both education level and whether participants had heard of eIC were found to be statistically significant (p=0.000). The median knowledge score of participants with postgraduate education was 8 (IQR 7–8), while the median knowledge score of participants who graduated from junior high school and below was 5 (IQR 0–8). People who had previously heard of eIC and were familiar with it had a median knowledge score of 8 (IQR 8–8), and those who had never heard of it had a median knowledge score of 7 (IQR 4–8).
When comparing the mean attitude scores, males (56.01±6.87), people who preferred to use mobile devices for eIC (55.10±6.50), and people who had participated in clinical trials (56.89±7.18) had significantly higher mean attitude scores (p<0.05). Differences in mean attitude score by current job status were also found to be statistically significant (p<0.05).
Discussion
To our knowledge, this is the first published study to evaluate knowledge and attitudes toward eIC among participants and potential participants in clinical trials in China. Questionnaire respondents generally showed a high level of knowledge of eIC, with an overall median knowledge score of 8 (IQR 6–8) on a scale from 0–8, and positive attitudes toward eIC, with an overall mean attitude score of 56.85 (±6.55) on a scale from 17–85. Differences in median knowledge scores by both education level and whether respondents had heard of eIC were found to be statistically significant (p=0.000). On the eIC Attitudes Scale, differences in mean attitude score by gender, electronic device preference, former participation in clinical trials, and current job status were also found to be statistically significant (P<0.05).
Knowledge of electronic informed consent
According to the demographic survey, 43.3% of participants had never heard of eIC, and only 16.6% believed they were very familiar with it. While this finding suggests a low general awareness of eIC, participants had a high median score on the knowledge section of the questionnaire, and the percentage of participants who correctly answered questions about the content, methods and format of eIC was generally high. This may suggest that trial participants and potential trial participants generally know the content of eIC, but may not be familiar with the term “electronic informed consent,” and associated terminology. And while the rate of correct answers was generally high, there was a significant positive association between participants’ awareness of the term “electronic informed consent” and the median knowledge scores observed, with a median knowledge score of 7 (IQR 4–8) among participants who had never heard of eIC, 8 (IQR 7–8) among those who had heard of eIC but were not very familiar with it, and 8 (IQR 8–8) among participants who had heard of eIC and were familiar with it. This positive trend in scores suggests that increasing public awareness of the term “electronic informed consent” and associated terminology may be conducive to research participants in China using eIC while having a higher degree of knowledge about its content. And while there was no significant difference in average knowledge scores based on whether participants had formally participated in clinical trials, it was notable that participants who had previously participated in clinical trials had significantly higher mean attitude scores (14.89 compared to 11.93). Most participants (68.9%) had no experience participating in clinical trials and were considered potential subjects. Among the population who had participated in clinical trials, 79.7% had participated in drug clinical trials, accounting for the vast majority of the types of trials. This suggests former participants in drug clinical trials may be one group that is relatively more open to use of eIC in China, and that promoting the use of eIC may be most effective initially in the context of drug trials.
Each of the questions in the knowledge section of the questionnaire were answered correctly by over 80% of participants, except for two questions: those concerning location flexibility (73.1%) and ethical review (77.5%). Research on eIC suggests it can increase location flexibility for consenting participants, as it can often be carried out through a variety of both face-to-face and remote channels (Skelton, et al., 2020). The relatively lower proportion of participants who correctly answered the question about location flexibility suggests a need to promote awareness among potential clinical trial participants in China of the convenience that eIC can bring in the form of location flexibility, as this may increase accessibility for some participants. The results showing that less than 80% of participants answered correctly the question about ethical review also indicates it is necessary to increase subjects’ awareness of the need to check whether an eIC method has passed review by an Institutional Review Board (IRB) when participating in clinical trials. IRBs have a responsibility to check that informed consent processes in research are adequate, and are required to review methods of eIC used by researchers to ensure compliance with human subjects protection (FDA, 2016). It is important for clinical trial participants to be aware of the protections that they are entitled to as participants in research, and the role of IRBs in those protections. Relatedly, participants expressed concerns on the eIC Attitudes Scale about the protection of their rights and interests when using eIC (65.5% strongly agreed or agreed), and believed that China’s regulations on eIC need to be further improved (85.3% strongly agreed or agreed). This result aligns with the fact that China currently lacks detailed laws and regulations concerning the design and maintenance of eIC. Recent evidence in China suggests there is a need to both synthesize the existing informed consent laws and regulations into guidelines that can be implemented for eIC, and to further regulate electronic signature laws and regulations (Hu, et al., 2019). Our findings in this study lend further weight to these suggestions.
Attitudes toward electronic informed consent
Participants held predominantly positive attitudes toward eIC, believing that eIC is more convenient than paper-based informed consent (86.3%), and nearly 70% of participants were inclined to choose eIC over paper-based informed consent. These findings are consistent with previously published literature results. In a 2018 focus group study in the US, patients believed that eIC was easier to use and to understand than the paper-based version (Simon, et al., 2018). Another US study showed that eIC was relatively feasible and easy for participants to use for a trial, and was found to expedite enrollment of a representative sample (Phillippi, Doersam, Neal, & Roumie, 2018). In relation to overall positive attitudes toward eIC, a high proportion of participants in our study specifically stated eIC would increase their willingness to participate in clinical trials. This was consistent with previous research findings on the relationship between eIC implementation and participant enrollment in research. A 2016 US study showed that the number of people who consented to participate in a large, multi-hospital biological database increased during the period when the database first began implementing eIC for recruitment (Boutin, et al. 2016). Therefore, our results suggest eIC may be similarly efficacious in China’s context, for increasing participants’ ability and willingness to enroll in clinical trials.
Despite overall positive attitudes toward eIC, about half of participants (52.1%) expected to have difficulties understanding research content when using eIC, while another 24% indicated they were not sure whether they might have difficulties. This may indicate concerns about understanding research could be a barrier to use of eIC among potential clinical trial participants in China; however, this finding should be interpreted in light of both general research on informed consent, and research on eIC from other countries. Research on informed consent across formats suggests that participants often lack understanding of key aspects of research. The issue of inadequate understanding in informed consent has to some extent motivated the further development of eIC, because of new methods it offers for attempting to enhance participant understanding. Electronic features such as hyperlinked supplemental information, or quizzes on key research concepts have been found effective for improving participant understanding (Rothwell, et al., 2014) (De Sutter, et al., 2020). However, evidence is currently mixed on whether electronic or paper-based interventions to enhance understanding of informed consent are more effective (De Sutter, et al., 2020). And while many studies evaluating eIC in other countries have found eIC to achieve adequate participant understanding of research, evaluation studies are needed to test this and other aspects of eIC in China (De Sutter, et al., 2020).
Results on the attitude section of our questionnaire also indicated that participants had reservations about risks to security and confidentiality involved with eIC. While the majority of participants stated they were willing to accept technology-based identification methods associated with eIC such as facial recognition, fingerprint authentication, and electronic signatures (80.0%), participants also largely said that eIC should include more detailed information on privacy protection and data confidentiality measures than paper-based informed consent (88.6%). Similar concerns about data privacy and protection arose within focus group discussions in a US study on attitudes toward eIC (Simon, et al., 2018). Another US study showed that subjects had a higher degree of satisfaction with informed consent and a clearer understanding of research content when using eIC that presented information about both data protection measures and the training of researchers (Golembiewski, et al., 2021). The authors of this latter study speculated that presenting such information may have protected against distrust toward eIC that could have been heightened by news media coverage of data privacy issues during the study. It is similarly possible that participants’ attitudes toward eIC in our study were influenced in part by media coverage on data privacy issues in China.
In addition, 85.3% of participants thought that relevant laws and regulations on eIC need further improvement. This view aligned with a 2021 literature review of eIC use in China — which highlighted the importance for regulatory bodies to establish further laws and regulations protecting participant data and preventing data breaches, particularly while the development of eIC in China is still at an early stage (Dong, et al., 2021). In short, although eIC can increase convenience for subjects, concerns about security and privacy may be a barrier to the use of eIC, and need to be solved through technical, ethical, legal and other efforts as the use of eIC in research grows.
Factors associated with knowledge and attitudes
Another common concern among participants in our study was lack of confidence in the ability to use and communicate through electronic devices: 45.3% of participants worried about their ability to use electronic devices, and more than half expected to have difficulties in communication with researchers when using eIC (52.9%). Previous studies have relatedly raised concerns that eIC requires proficiency in the use of electronic devices, also known as digital literacy (Simon, et al., 2018). Indeed, low digital literacy can be a barrier to accessing health-related information in general, and can contribute to disparities in use of electronic health applications — an issue that has been highlighted especially acutely during the COVID-19 pandemic (Eruchalu, et al., 2021). Research shows that older adults, racial/ethnic minorities, and individuals with lower education level are less likely to engage with health applications such as online patient portals, even with adequate access to electronic devices and the Internet (Sarkar, et al., 2011). Concerning education level in particular, in a 2019 randomized trial in the US that evaluated effectiveness of different methods of eIC, participants with lower education levels reported lower satisfaction with eIC, subjective and objective understanding of the research, voluntariness, and trust in medical researchers, and were found to spend more time consenting (Harle, et al., 2019). Analysis of responses to our questionnaire showed that median knowledge scores increased with educational level, with a median knowledge score of 5 (IQR 0–8) for participants who graduated from junior high school and below, 8 (IQR 5–8) for participants with high school education, 8 (IQR 6–8) for college education, and 8 (IQR 7–8) for participants with postgraduate education. These results and related prior research suggest the need to pay attention to variation in participants’ digital literacy and education level in the design of eIC, including development of new content to improve both understanding and trust among participants.
There were also several other factors associated with average attitude scores toward eIC. Male participants in our study had a higher mean attitude score (56.01±6.87) compared to female participants (53.78±6.08). This may be related to a general tendency among women to be more cautious toward new technological innovations, compared to men (Mitra, Lafrance, & McCullough, 2001). In terms of current job status, the mean attitude scores of participants with full-time employment (57.26±6.10) and participants with part-time employment (54.97±6.93) were higher than those of students (53.27±5.35) and unemployed participants (54.17±5.07), and the part-time employed group scored significantly higher than the other three groups. This may be because employed groups have richer social networks and have more channels to access clinical trials and eIC; and compared with full-time employment, people with part-time employment tend to have more spare time and more urgent financial needs, such that compensation for clinical trials may be appealing. Future research should evaluate whether employed individuals may be more likely to be exposed to or accept eIC, and whether special efforts may be needed to promote or adapt eIC to other groups. Regarding electronic device preferences, participants who preferred to use mobile devices for eIC had a significantly higher mean attitude score than those who preferred PC devices. This may be due to the flexibility, portability, and convenience of mobile devices compared to PC devices, suggesting that it may be more possible to promote eIC among potential research participants who use mobile devices more regularly than PC devices.
Limitations
There are several limitations to this study that should be considered. Because this study used a convenience sample that was recruited mostly from within Hunan Province, generalizability of results may be limited. Our sample was also limited to individuals who had previously enrolled in clinical trials or who had indicated willingness to participate in clinical trials, which may have resulted in knowledge and attitude scores higher than the general population. In addition, as an electronic questionnaire was used in this study, individuals who do not use smartphones were largely filtered out. This may have been related to the results that 83.2% of respondents were from urban areas, the mean age of respondents was relatively young (33±11 years), and 66.3% had a college education or higher. These factors imply further limits to the generalizability of our results, in that our sample did not include many rural participants, older adult participants, or participants with lower education levels. As the use of eIC for clinical trials continues to grow, it will be important for future research to evaluate possible differences in knowledge and attitudes toward eIC among various sub-populations in China.
Best practices
To our knowledge, this study is the first to evaluate knowledge and attitudes toward eIC among human research subjects and potential subjects in China. Participants had a high average knowledge score and generally showed a high degree of willingness to accept eIC. Concerns about eIC were mainly related to issues of security, confidentiality and rights protection. Therefore, the results of this study may serve as a reference for research institutions, and government departments, and IRBs to formulate policies and uphold review standards that both promote eIC usage for clinical trials in China and address these areas of concern.
Research agenda
More in-depth research should be conducted to explore the applicability of eIC in different research contexts. Particular areas that need further investigation include how to address needs among specific groups of people, such as those with lower digital literacy, and which types of trials are more well-suited to the use of eIC. Given limitations on the diversity of the sample in this study, future research should examine knowledge and attitudes toward eIC particularly among rural and older participants. It also remains an open question for future research whether eIC has disadvantages that cannot be ignored compared to paper-based informed consent. In addition, research is needed to examine data handling and data confidentiality in the use of eIC. Further studies in these areas will contribute to the further establishment and improvement of eIC for research in China and on an international level.
Educational implications
The results of this study may inform training for ethics committee members and staff regarding criteria for adequate review of clinical trials using eIC, and related training for researchers on how to comply with IRB requirements and complete regulatory documents concerning eIC. Results may also inform education for the general public in China on the rights and protections of individuals participating in research, and the relative convenience of some aspects of eIC that may increase willingness of individuals to enroll in clinical trials. Lastly, the results of our study may serve as a reference for policymakers regarding the formulation of policies that both promote eIC and ensure that it is implemented ethically, with adequate protections for human subjects.
Funding
This work was supported by the Key Research and Development Project of Hunan Province in Changsha, China under award number 2020SK2010 and the National Institutes of Health Fogarty International Center Masters Level Bioethics Program at Central South University in Changsha, China under award number R25 TW007700.
Footnotes
Declaration of Conflicting Interests
The authors declare that they have no competing interests.
Publisher's Disclaimer: Disclaimer
Publisher's Disclaimer: This publication represents the views of the authors and does not reflect the official position or policy of Central South University, Hunan University of Chinese Medicine, or Yale University.
Ethical approval statement
This study was conducted following review and approval by the IRB of the Third Xiangya Hospital of Central South University (IRB approval number I 21020).
Availability of data and materials
Data used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data used and/or analyzed during the current study are available from the corresponding author on reasonable request.