Analysis on the Current Status and Ethics Review Key Points of Electronic Informed Consent / 中国医学伦理学

Informed consent is one of the key elements to protect the rights and welfare of the patients or research subjects. With the development of electronic information technology, the diversity and convenience brought by the electronization makes the electronic informed consent (E-Consent) come into being. European and American countries have begun to apply E-Consent in the field of clinical trials, established a relatively perfect E-Consent platform and software system, and initially formed the guiding principles and recommendations of E-Consent. However, the implementation of E-Consent is still less in China, and there is no targeted legal basis and guidelines for ethical review. Therefore, this paper explored the implementation potential of E-Consent domestically by analyzing the application scenarios, advantages and disadvantages, and feasibility of E-Consent, and tried to establish the practical ethic review points of E-Consent based on the basic principles of ethical principles, to ensure that clinical trials have an appropriate E-Consent process.

Electronic informed consent: effects on enrolment, practical and economic benefits, challenges, and drawbacks-a systematic review of studies within randomized controlled trials.

BACKGROUND: Enrolment is one of the most challenging aspects of conducting clinical trials, preceded by the process of informed consent (IC). Different strategies to improve recruitment in clinical trials have been used, including electronic IC. During COVID-19 pandemic, barriers to enrolment have been evident. Although digital technologies were acknowledged as the future of clinical research and potential advantages were shown for recruitment, electronic informed consent (e-IC) has not yet been globally adopted. The purpose of this review is to investigate the effect of using e-IC on enrolment, practical and economic benefits, challenges, and drawbacks when compared to traditional informed consent, through a systematic review. METHODS: Embase, Global Health Library, Medline, and The Cochrane Library databases were searched. No limit was set for publication date, age, sex, or study design. We included all studies within a randomized controlled trial (RCT), published in English, Chinese or Spanish, evaluating the electronic consent process used in the parent RCT. Studies were included if any of the three components ((i) information provision, (ii) participant's comprehension, (iii) signature) of the IC process was designed as electronic, whether administered remotely or face-to-face. The primary outcome was the rate of enrolment to the parent trial. Secondary outcomes were summarized according to the various findings reported on the use of electronic consent. RESULTS: From a total of 9069 titles, 12 studies were included in the final analysis with a total of 8864 participants. Five studies of high heterogeneity and risk of bias showed mixed results on the efficacy of e-IC on enrolment. Data of included studies suggested e-IC could improve comprehension and recall of study-related information. Meta-analysis could not be conducted due to different study designs and outcome measures and the predominantly qualitative findings. CONCLUSION: Few published studies have investigated the impact of e-IC on enrolment and findings were mixed. e-IC may improve participant's comprehension and recall of information. High-quality studies are needed to evaluate the potential benefit of e-IC to increase clinical trial enrolment. TRIAL REGISTRATION: PROSPERO CRD42021231035 . Registration date: 19-Feb-2021.

Comparative analysis of multiple models of electronic informed consent in clinical research / 中华医学科研管理杂志

Objective:To provide decision-making support for electronic informed consent selection and promotion in clinical research, and lay a possible theoretical foundation for better protection of subjects′ rights and interests, as well as promotion of clinical research quality and efficiency.Methods:This paper summarized the relevant laws and regulations of electronic informed consent, analyzed the advantages and challenges of the application of electronic informed consent in clinical research, sorted out several common electronic informed consent modes in domestic clinical research, explored their operational processes and applications, and discussed their advantages and limitations.Results:At present, three electronic informed consent modes were mainly used in domestic clinical studies. Each had their own advantages and limitations in terms of convenience of operation, data security, privacy protection of subjects, cost input, popularization degree and so on.Conclusions:Electronic informed consent needs continuing improvement of relevant laws and regulations and the joint efforts of all stakeholders engaged in clinical research. The sponsor and the researcher should take full consideration of the cost, safety, security, feasibility, and ofters, and make the selection according to the actual needs of the research.

Challenges and Suggestions for Improvement of the Electronic Informed Consent System in Clinical Application / 中国医学伦理学

The electronic informed consent (eIC) system is a product of modernization development of electronic and intelligent technology. In the context of COVID-19, the eIC system can adapt to the epidemic prevention and control requirements, showing its time-space advantages. By introducing the concept, form and the use of eIC system, this paper analyzed the challenges of acceptance, understanding, consent and information security faced by the eIC system. Based on this, some suggestions were put forward, including strengthening the training of the relevant personnel involved in the eIC system, enhancing and improving the functions of the eIC system, and perfecting the relevant laws and regulations of the eIC system, so as to provide reference for the future research and application of eIC.

Supervision of Electronic Informed Consent in International Clinical Research and Its Implications for China / 中国医学伦理学

At present, China is still in the exploratory stage in the field of electronic informed consent (eIC), and relevant policies, regulations and application guidelines have not yet been established and improved. While the traditional informed consent supervision system is difficult to meet the needs of the innovative development of eIC, such as subject privacy and data security. Through sorting out and analyzing the legal norms and construction system of eIC supervision in Europe and the United States, combined with the current development status, problems, and challenges of eIC in China, this paper targeted proposed the path to construct the supervision of eIC in clinical research in China from the aspects of restricting the signing form and process of eIC, adjusting the ethical review paradigm of eIC, enhancing the strength of eIC ethical review, improving the construction of eIC legal system, and strengthening the training of relevant researchers.

Electronic informed consent criteria for research ethics review: a scoping review.

BACKGROUND: The research shows a growing trend in using an electronic platform to supplement or replace traditional paper-based informed consent processes. Instead of the traditionally written informed consent document, electronic informed consent (eConsent) may be used to assess the research subject's comprehension of the information presented. By doing so, respect for persons as one of the research ethical principles can be upheld. Furthermore, these electronic methods may reduce potential airborne infection exposures, particularly during the pandemic, thereby adhering to the beneficence and nonmaleficence principle. This scoping review aims to identify the ethics related criteria that have been included in electronic informed consent processes and to synthesize and map these criteria to research ethics principles, in order to identify the gaps, if any, in current electronic informed consent processes. METHODS: The search was performed based on internet search and three main databases: PubMed, SCOPUS and EBSCO. PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation guideline was used to report this work. RESULTS: Of 34 studies that met the inclusion criteria, 242 essential original constructs were collated, and 7 concepts were derived. Digital content showed the highest percentage of collated original constructs (27%, n = 65) followed by accessibility (24%, n = 56), comprehension engagement (18%, n = 43), autonomy (14%, n = 34), confidentiality (11%, n = 25), language (5%, n = 13), and parental consent (1%, n = 2). Twenty-five new items were synthesized for eConsent criteria which may provide guidance for ethical review of research involving eConsent. CONCLUSION: The current study adds significant value to the corpus of knowledge in research ethics by providing ethical criteria on electronic informed consent based on evidence-based data. The new synthesized items in the criteria can be readily used as an initial guide by the IRB/REC members during a review process on electronic informed consent and useful to the future preparation of a checklist.

Rethinking informed consent in the time of COVID-19: An exploratory survey.

Background: Owing to the infectious nature of COVID-19, alternative solutions, such as electronic informed consent (eIC), needed to be implemented to inform research participants about study-related information and to obtain their consent. This study aimed to investigate stakeholders' experiences with alternative consenting methods as well as their views on any regulatory or legal guidelines for eIC implementation in clinical research. Results may serve as the cornerstone to rethink the informed consent process in clinical research. Materials and methods: This study consisted of an online survey among three stakeholder groups across European Union (EU) Member States and the United Kingdom. The stakeholder groups included (i) investigators, (ii) data protection officers (DPOs) or legal experts working in the pharmaceutical industry, academia, and academic biobanks, and (iii) ethics committee (EC) members. Data collection occurred between April and December 2021. The data collected were analyzed using descriptive and inferential statistics. Results: The online survey was completed by 191 respondents, of whom 52% were investigators. Respondents were active in 24 out of the 27 EU Member States and the United Kingdom. The majority of each stakeholder group considered validated electronic methods moderately or extremely useful to re-consent previously enrolled research participants upon study amendments or to obtain consent from COVID-19 patients. Nevertheless, this exploratory survey identified that only 13% of DPOs/legal experts, 26% of investigators, and 41% of EC members had experience with eIC. In addition, results suggest that the legal acceptance of eIC across EU Member States and the United Kingdom is variable and that a definition of eIC, issued by national law or policy, is rarely available. The results also showed that the COVID-19 pandemic brought additional challenges to inform participants and to obtain their consent; for example, related to travel restrictions. Conclusion: A number of alternative consenting methods were recommended, for example by the European Medicines Agency, to ensure clinical study continuation during the COVID-19 pandemic. Although stakeholders support the use of eIC in clinical research, it seems that the experience with eIC is low. To harmonize eIC practices as much as possible, further investments in multi-stakeholder, multi-national guidance are needed.

Developing and Implementing Electronic Consent Procedures in Response to Covid-19 Restrictions.

The Covid-19 pandemic resulted in unprecedented restrictions on many public, private, and workplace activities throughout the United States and elsewhere. When restrictions were imposed, we were conducting a type III hybrid effectiveness-implementation trial in 10 pediatric trauma centers. In response to several pandemic-based restrictions, we had to develop procedures for engaging with potential research participants while limiting nonclinical, in-person interactions. This manuscript describes the procedures and challenges of obtaining electronic informed consent and assent in a multisite trauma center-based research study. We developed, tested, and trained staff to implement three options for obtaining informed consent. Twenty-five participants were enrolled in the effectiveness-implementation multisite trial during the first six months of utilization of the consent options, with eleven of these individuals enrolled using hybrid or electronic consent procedures. The challenges we identified involving electronic consent procedures included confusion over who would complete the electronic consent process and difficulties reconnecting with families. Lessons learned can strengthen electronic consent and assent procedures for future studies. More research is needed to further strengthen this process and increase its utilization.

Characteristics of Electronic Informed Consent Platforms for Consenting Patients to Research Studies: A Scoping Review.

Informed consent process assures that research study participants are properly informed about the study prior to their consent. Due to the increasing significance of electronic informed consent (eIC) platforms, particularly during the COVID-19 pandemic, we conducted a scoping review of eIC systems to address the following characteristics: 1) technological features of current eIC platforms, 2) eIC platforms usability and efficacy, and 3) areas for future eIC research. We performed a literature search using publically available PubMed repository, where we included studies discussing an eIC platform or multimedia educational module given to patients prior to signing a consent form. In addition, we tracked first author, year of publication, sample size, study location, eIC procedure, methodology, and eIC's comparison to paper consent. Our results showed that with a few noted exceptions, electronic consent improves patient usability, satisfaction, knowledge, and trust scores when compared to traditional paper consent.

Digitizing the Informed Consent Process: A Review of the Regulatory Landscape in the European Union.

Background: Rapid technological advancements are reshaping the conduct of clinical research. Electronic informed consent (eIC) is one of these novel advancements, allowing to interactively convey research-related information to participants and obtain their consent. The COVID-19 pandemic highlighted the importance of establishing a digital, long-distance relationship between research participants and researchers. However, the regulatory landscape in the European Union (EU) is diverse, posing a legal challenge to implement eIC in clinical research. Therefore, this study takes the necessary steps forward by providing an overview of the current regulatory framework in the EU, relevant to eIC. Methods: We reviewed and analyzed the key EU regulations, such as the EU General Data Protection Regulation (GDPR) and the Clinical Trials Regulation (CTR). We investigated the legality of eIC in several EU Member States, Switzerland, and the United Kingdom. To this end, we contacted the medicines agencies of various countries to clarify the national requirements related to the implementation and use of eIC in clinical research. Our research was complemented by comparing the legal acceptance of eIC between the EU and the United States. Results: In the EU, a distinction must be made between eIC for participation in clinical research and eIC for processing the participants' personal data, complying respectively with requirements laid down by the CTR and the GDPR. On a national level, countries were classified into three groups: (1) countries accepting and regulating the use of eIC, (2) countries accepting the use of eIC without explicitly regulating it, and (3) countries not accepting the use of eIC. As a result, the regulation of eIC through laws and guidelines shows a large variety among EU Member States, while in the United States, it is harmonized through the Code of Federal Regulations. Conclusion: Various requirements must be considered when implementing eIC in clinical research. Nevertheless, requirements across the EU Member States may differ significantly, whereas, in the United States, efforts have already been made to achieve a harmonized approach.

Framework and Practical Guidance for the Ethical Use of Electronic Methods for Communication With Participants in Medical Research.

Online communication with participants, including online recruitment, electronic informed consent, and data communication, is one of the fields to which information and communication technology (ICT) has been applied in medical research. Online communication provides various benefits, especially for genome research and rare disease research. However, ethical challenges that are derived from or exacerbated by online communication need to be addressed. Here, we present an overview of such ethical issues and provide practical guidance for the ethical implementation of ICT. We specify the ethical issues in the context of using online communication for medical research by an analysis based on the eight ethical principles for clinical research. Informed by this ethical context, we then develop a novel framework for the governance of medical research involving ICT, which consists of eight categories: five research processes (ie, design of research, recruitment, informed consent, data communication, and dissemination and return of results) and three overarching perspectives related to multiple processes of research (ie, access to research and online dialog, community involvement, and independent review). Finally, we present a practical guidance chart for researchers, patient partners, independent reviewers, and funding agencies. We believe that our study will contribute to the ethical implementation of online communication in medical research.

Analysis on the Current Status and Ethics Review Key Points of Electronic Informed Consent / 中国医学伦理学

Informed consent is one of the key elements to protect the rights and welfare of the patients or research subjects. With the development of electronic information technology, the diversity and convenience brought by the electronization makes the electronic informed consent (E-Consent) come into being. European and American countries have begun to apply E-Consent in the field of clinical trials, established a relatively perfect E-Consent platform and software system, and initially formed the guiding principles and recommendations of E-Consent. However, the implementation of E-Consent is still less in China, and there is no targeted legal basis and guidelines for ethical review. Therefore, this paper explored the implementation potential of E-Consent domestically by analyzing the application scenarios, advantages and disadvantages, and feasibility of E-Consent, and tried to establish the practical ethic review points of E-Consent based on the basic principles of ethical principles, to ensure that clinical trials have an appropriate E-Consent process.

Electronic informed consent information for residual newborn specimen research: findings from focus groups with diverse populations.

We developed a video and an app for obtaining consent about allowing newborn blood spots (NBS) to be used as biospecimen resources for biobanking. Newborn screening programs test for treatable diseases and leave residual biospecimens that can be used in future research activities. We conducted focus groups and interviews with three diverse communities to determine (a) how well the consent tools worked and (b) participant familiarity with NBS. Participants preferred the video and noted that they were unaware that NBS could be used for future research. Providing information about how biospecimens could be used was a key issue.

Awareness and Collaboration Across Stakeholder Groups Important for eConsent Achieving Value-Driven Adoption.

BACKGROUND: While the shift to digital technologies is pervasive across multiple industries, the informed consent process for clinical trials remains largely paper-based. Given the inefficiencies in the traditional process and the increasing complexity of clinical studies, the current approach at times may raise challenges with respect to quality, compliance, participant understanding, and trial retention. Electronic informed consent (eConsent) is an enabling clinical technology to potentially address these issues by using multimedia components to create an interactive participant experience and improve data quality. METHODS: The TransCelerate eConsent Initiative conducted a multifaceted engagement approach to better understand the perceptions, experiences, and concerns of impacted stakeholders, including participants, sites, ethics committees, and health authorities. RESULTS: While all stakeholders were supportive of the use of multimedia components to deliver study information, several stakeholder-specific concerns were noted. Participant feedback, as collected through surveys (n = 3045) and an advisory board (n = 10), suggests that some participants may have data privacy concerns and a diversity of preferences for multimedia presentation. Site interviews (n = 9) suggest concerns related to additional operational activities and potential for technology failure. Health authorities' feedback, through nonbinding meetings, was geographically varied; ethics committee feedback, through interviews, suggests concern over impact on operational process changes. CONCLUSIONS: While the appetite for eConsent is increasing, involved stakeholders and industry must continue to raise awareness, communicate, and collaborate to develop appropriate technological capabilities, regulatory pathways, and operational processes to clear the path for mainstream use of eConsent.

The Application of Electronic Informed Consent / 中国医学伦理学

The application of electronic informed consent has the advantages of speeding up the recruitment of subjects, helping the less educated to understand research and recruit groups, facilitating direct communication between subjects and researchers, minimizing human omissions and errors, and effectively improving the efficiency of clinical research. However, there are also some challenges, such as privacy, ethical censorship, hardware costs and so on. On the basis of the above discussion, this paper believed that electronic informed consent, as a new form, would provide a more powerful tool for clinical research in an era full of opportunities and challenges, with research value and potential.

Building clinical trials around patients: Evaluation and comparison of decentralized and conventional site models in patients with low back pain.

Clinical trials are slow and costly, built around the research centers that study local participants. Building clinical trials around patients in their homes and community through remote visits and monitoring could enhance recruitment and increase convenience for participants. This study evaluated different trial settings, a decentralized arm via telemedicine center (virtual study conduct), a conventional arm via health clinic (onsite study conduct) and a mixed model arm. Acute low-back pain patients (20-65 years) were recruited to this non-interventional trial in Switzerland. The study consisted of a screening period and a 2-week data collection period using direct data capture (eSource), electronic informed consent form (eICF), electronic diary (eDiary) and wearable actigraphy sensor. A higher number of patients were enrolled in the decentralized arm (N = 18) compared to the conventional arm (N = 5) and none in the mixed model arm. The decentralized arm consisted of a diverse population with increased participation from rural areas. In the decentralized arm 89% of enrolled patients completed the study compared to 60% in the conventional arm. All the patients reported satisfaction with the use of eICF, eDiary and remote visits; whereas patients reported a lower level of satisfaction with the wearable sensor. The decentralized setting was operationally feasible and well accepted by patients. Faster recruitment and improved access to patients was observed in the decentralized arm. This study supports broader adoption of the decentralized model in clinical trials, though further investigations in larger interventional trials are needed to confirm the benefits from this patient-centric approach.

Molecular Tumor Boards: Ethical Issues in the New Era of Data Medicine.

The practice and development of modern medicine requires large amounts of data, particularly in the domain of cancer. The future of personalized medicine lies neither with "genomic medicine" nor with "precision medicine", but with "data medicine" (DM) (big data, data mining). The establishment of this DM has required far-reaching changes, to establish four essential elements connecting patients and doctors: biobanks, databases, bioinformatic platforms and genomic platforms. The "transformation" of scientific research areas, such as genetics, bioinformatics and biostatistics, into clinical specialties has generated a new vision of care. Molecular tumor boards (MTB) are one response to these changes and are now providing better access to next-generation sequencing (NGS) and new cancer treatments to patients with inoperable or metastatic cancers, and those for whom the usual treatment has failed. However, MTB face a crucial ethical challenge: maintaining and improving the trust of patients, clinicians, researchers and industry in academic medical centers supported by private or public funding rather than providing genetic data directly to private companies. We believe that, in this era of DM, appropriate modern digital communication networks will be required to maintain this trust and to improve the organization and effectiveness of the system. There is, therefore, a need to reconsider the form and content of informed consent (IC) documents at all academic medical centers and to introduce dynamic and electronic informed consent (e-IC).

Building the Partners HealthCare Biobank at Partners Personalized Medicine: Informed Consent, Return of Research Results, Recruitment Lessons and Operational Considerations.

The Partners HealthCare Biobank is a Partners HealthCare enterprise-wide initiative whose goal is to provide a foundation for the next generation of translational research studies of genotype, environment, gene-environment interaction, biomarker and family history associations with disease phenotypes. The Biobank has leveraged in-person and electronic recruitment methods to enroll >30,000 subjects as of October 2015 at two academic medical centers in Partners HealthCare since launching in 2010. Through a close collaboration with the Partners Human Research Committee, the Biobank has developed a comprehensive informed consent process that addresses key patient concerns, including privacy and the return of research results. Lessons learned include the need for careful consideration of ethical issues, attention to the educational content of electronic media, the importance of patient authentication in electronic informed consent, the need for highly secure IT infrastructure and management of communications and the importance of flexible recruitment modalities and processes dependent on the clinical setting for recruitment.

Web-based trial to evaluate the efficacy and safety of tolterodine ER 4 mg in participants with overactive bladder: REMOTE trial.

INTRODUCTION: Participatory patient-centered, web-based methods could streamline and improve the convenience of clinical trial participation. We used an entirely web-based approach to conduct a randomized, placebo-controlled, Phase 4 (REMOTE) trial under an Investigational New Drug (IND) application to evaluate tolterodine extended release (ER) 4 mg for overactive bladder. METHODS: The trial was designed to replicate previous clinic-based trials of tolterodine ER but was conducted via the web from one clinical site overseen by physicians. Participants were recruited via the web, screened for eligibility using web-based questionnaires, had laboratory testing in their community, and entered a run-in phase requiring bladder e-diaries. Informed consent was obtained using an interactive web-based method with physician countersignature. Study medication was shipped directly to participants. RESULTS: With a goal of 283 randomized participants, 5157 registered on the trial website. Of 456 who passed initial screening, identification verification, and signed consent, 237 passed additional medical screening and were countersigned by the investigator. After laboratory testing, 118 entered the placebo run-in; only 18 passed e-diary assessments and were randomized to treatment. At week 12, the mean change from the baseline in micturitions/24 hours (primary endpoint) was -2.4 for tolterodine ER versus -0.8 for placebo [treatment difference (95% CI): -1.6 (-3.9, 0.6)]. CONCLUSION: The REMOTE trial is the first entirely web-based trial conducted under an IND application. The efficacy observed was consistent with results from conventional trials. With simplification of multi-step screening and testing, web-based trials or their component parts should provide a participant-friendly approach to many clinical trials.