One of the applications of information and communication technology (ICT) in medical research is a variety of online communications with participants, including recruitment, informed consent, and sharing of research results [1-4]. The use of the internet is expected to enable continuous communication without spatial restrictions [3]. This is especially beneficial in rare disease research because it is difficult to recruit a sufficient number of participants in geographically limited areas. As clarified by the Rare and Undiagnosed Diseases Study (RUDY) in the United Kingdom and Japan, digital platforms enable the effective recruitment of participants [5-7]. Additionally, the RUDY project demonstrated that digital technologies facilitate dialog and collaboration between patients and researchers [5-7]. This type of active patient involvement encouraged by digital tools is referred to as participant-centric initiatives [8,9]. Another research area where ICT use is expected to bring about significant change is human genome research. Since genome cohort studies such as the “All of US” study in the United States aim to recruit a large number of participants, registering and answering an online questionnaire should prove to be efficient and helpful for participants [10]. Moreover, long-term communication with participants is more important for genome research projects because the results of individual analyses can change as data are accumulated over time [11].

At the same time, online communication can raise new ethical challenges such as the digital divide, concerns about invasion of privacy, how to assure understanding of information for consent, and methods for authenticating participants [12-15]. To maximize the benefits of ICT, it is crucial to deal with such ethical challenges. Previous studies focused on individual ethical issues; however, there has been no attempt to provide an overview of the ethical issues that need to be addressed in implementing online communication with participants. Although some countries already have regulations or recommendations regarding electronic methods, such as guidance on the use of electronic consent released by the US Food and Drug Administration [16], their scope is limited. In Japan, the newly revised ethical guidelines for medical research established in 2021 include descriptions about online informed consent, but few details are specified. Therefore, the purpose of this viewpoint is to provide an overview of ethical issues and present a practical guide for implementing online communication in medical research.

We initially performed an analysis based on the eight ethical principles for clinical research proposed by Emanuel et al [17], referred to as the Emanuel Framework (EF). We specified the ethical issues in the context of online communication with participants through each principle of the EF: collaborative partnership, social value, scientific validity, fair participant selection, favorable risk-benefit ratio, independent review, informed consent, and respect for participants. The lead author (AK) carried out a literature search and both authors performed analyses. We then developed a new framework composed of the issues specified by the analysis, after receiving feedback from the researchers of the medical and genomics research projects under the same research program that funded this study, sponsored by the Japan Agency for Medical Research and Development (AMED). Finally, we propose a practical guide for researchers, patient partners, independent reviewers, and funding agencies.

Informed by the EF ethical analysis, we have schematically presented the interrelationships among the issues based on the actual processes of medical research and formulated a novel framework for the governance of medical research involving ICT (Figure 1).

The framework is designed for any research involving communication with participants, not for studies that involve digital technology in general (eg, research drawing on electronic medical records without any online communication with participants). The framework covers eight elements. The first five elements (left side of Figure 1) are the processes involved in medical research using ICT, which cover the design of research, recruitment, informed consent, data communication, and dissemination of progress and results, including the return of individual genomic analysis results. The other three elements (right side of Figure 1) are overarching perspectives. They cover access to research, community involvement, and independent review. In each category, benchmarks are described to show what issues are involved.

The “design of research” category includes the purpose and benefit of the use of electronic methods. In addition, it should be taken into account that online communication would affect scientific validity. This is especially true when recruitment and data communication through online systems are employed. The category of “recruitment” includes the issues related to risks when recruiting participants online. Researchers must consider that online recruitment would have additional risks for participants with vulnerabilities and that some of their data may be available before the participants have given consent. The category of “informed consent” includes the benchmarks associated with information presented online, the understanding of participants, and consent from the participant’s legally authorized representative. The category of “data communication” covers the situation in which participants manage their own data or when data are generated by the participants’ own devices. The category of “dissemination and return of results” includes the benchmarks related to not only individual participants but also the target community.

Security issues, digital divide, authentication of participants, and the risk of miscommunication are important factors in considering access to the research system and online dialog between researchers and participants. The “involvement of target population” category includes the benchmarks associated with the strategy and tools for “community” involvement, as well as sharing responsibility and benefits. The category of “independent review” includes the benchmarks regarding the procedures for independent review of DTP recruitment and competency of the reviewers.

Based on this framework, we present a practical guide in the form of a chart for researchers, patient partners, independent reviewers, and funding agencies (Figure 2). This guidance chart mainly consists of four steps: (1) meet the benchmarks in the category of independent review, (2) meet the benchmarks in the category of each research process where online systems are employed, (3) meet the benchmarks in the category of access to research, and (4) meet the benchmarks in the category of patient involvement.

Depending on the users of the chart, the first step is either step 1 or step 2. For independent reviewers and funding agencies, the first step is to ensure that the reviewers are competent to review this type of research using online communications with participants, especially from the perspectives of technology and privacy risks. In cases where they are not competent, they need to ask ICT experts for help and review the literature to address new ethical issues such as the means of symbolizing consent in the process of informed consent.

Steps 2 to 4 are for independent reviewers, funding agencies, researchers, and patient partners. In the second step, researchers should clarify the purpose, benefits, and effects of using electronic methods for each research process, as well as the impact of the planned adoption of electronic methods in terms of scientific validity. Subsequently, researchers and patient partners should address the ethical issues related to each research process where they plan to employ online systems for communication with participants, from recruitment to dissemination of research results. Concrete issues that need to be addressed can be found in the benchmarks in the framework categories shown in Figure 1. Independent reviewers should review each step by carefully examining the content of research protocols that address these ethical aspects.

The third and fourth steps focus on the overarching perspectives that need to be ensured in all of the processes of research projects. Even if a research project plans to employ online communication only for one process such as online informed consent, the ethical issues included in the category of access to research and online dialog, and involvement of the target population should be addressed.

For funding agencies, in addition to making sure that the relevant benchmarks are met, it is desirable to ensure that adequate funding is available for the costs of addressing ethical issues in each step, particularly in steps 1, 3, and 4. Regarding step 1, funding may be required to ask ICT experts for help and access to useful literature. In step 3, large investments are sometimes required to address security issues and to implement appropriate authentication systems.

As ICT becomes implemented and applied more widely, it is hoped that it will be used actively in medical research. In some countries, electronic methods are increasingly being employed in research projects. Online systems should be utilized carefully while keeping in mind the ethical considerations that have been described in this article. We believe that our ethical framework and the guidance chart can help to make electronic strategies ethically sound and acceptable.