Informed Consent

Administering informed consent in app-mediated research presents a number of unique challenges.^{Reference Doerr21} From an ethical perspective, an electronic informed consent process may have certain advantages. Owing to the unique character of the smartphone interface, for example, prospective participants working through an electronic consent form might be prompted to take the consent process more slowly, leading to more careful contemplation of the contours of a study protocol.^{Reference Wilbanks22} At the same time, electronically administered consent processes do not usually permit direct engagement with the research team. This limits opportunities for prospective participants to ask questions or receive clarification on elements of the study. To address this, researchers have developed techniques that attempt to address these concerns, for example, by administering quizzes that test the level of a participant’s informedness.^{Reference Doerr, Suver and Wilbanks23}

In the international app-mediated research context, the challenges presented by informed consent are potentially more acute. Studies that recruit participants in multiple countries, for example, may have to account for vastly different cultural expectations and levels of health literacy than might be expected in a higher income setting.^{Reference Zawati24} It may be especially challenging for researchers to confirm that prospective participants are informed when both a consent process and associated confirmatory quiz must be designed to account for potentially great cultural difference among participants. Nontraditional researchers may be particularly poorly equipped to manage these considerations. Absent institutional support, for example, the design of a culturally calibrated consent process may be difficult.

Beyond that, there might be a general concern about the adequacy of consent in app-mediated studies conducted by nontraditional researchers. Ensuring that citizen-led studies, in particular, are administering ethically adequate informed consent may be particularly challenging when such research is internationally dispersed. It may be difficult, moreover, to determine which informed consent models are applicable to international app-mediated research. Ensuring that standards are clear and accessible to study designers will be an increasingly complex and critical ethical issue.

Privacy

The protection of user privacy in app-mediated research is another serious ethical consideration. Recent work has found, for example, that smartphone applications with health related functions routinely share user data with third parties, including for-profit corporate entities, without oversight or transparency.^{Reference Grundy25} Despite collecting large volumes of personally identifiable and potentially sensitive health information, a number of health apps do not provide even basic privacy assurances or protections.^{Reference O’Loughlin26} While the most sophisticated app-mediated studies are likely to have participant privacy protections in place,²⁷ the same is not assured in the case of research conducted by nontraditional researchers.

From an international perspective, the consequences of unforeseen or uncontrolled data sharing may be particularly serious. For one thing, unregulated researchers may share, or be compelled to share, collected information with government agencies or other third parties. This risk that foreign entities may have access to a participant’s personal health information appears to be heightened when research arrangements cross borders. The risk of this kind of sharing, especially if not contemplated in informed consent documents or disclosed prior to the study, could potentially cause deep harm to participant privacy. Information shared with state agencies, for example, could be used for discriminatory effect in administrative proceedings.

Commercialization

While mobile health research has been given much attention as a promising development in medical science, with the potential to advance knowledge and lead to improved disease treatment and management,^{Reference Hamine28} it is also part of a more complex, lucrative commercial system. Smartphone applications with health-related functions form a large and growing industry. By some estimates, that industry is worth at least $23 billion.²⁹ App-mediated studies are being increasingly conducted by researchers outside of the academy, many of whom may have the commercialization of research results as a primary motive of their work. This raises a number of policy questions. Whether and how the potential commercialization of research results is communicated to participants during the informed consent process, for example, is an important ethical consideration.^{Reference Spector-Bagdady30} Additionally, the potential for the commercialization of app-mediated research results might raise trust issues in the interactions between researchers and participants. It is well-documented in the biobanking context that participants are generally less trusting of commercial researchers than university-affiliated researchers.^{Reference Caulfield and Murdoch31} As app-mediated research among nontraditional researchers grows, it will be important to find mechanisms that ensure participant trust and robust informed consent.

For app-mediated research conducted internationally, the above policy considerations will be even more pressing. Issues of participant trust, for example, might be exacerbated when research is conducted by a foreign entity.^{Reference Sheikh and Hoeyer32} Ensuring transparency in the informed consent process, both about who is conducting the research and how results may be used, will play a critical role in maintaining the delicate trust between researchers and participants. At the same time, there is an emerging consensus among researchers, including those who are university-affiliated, that commercializing study results is the most promising way to bring innovations into public use and may even constitute an ethical responsibility.^{Reference Holloway and Herder33} This suggests that the continued commercialization of research results might be inevitable, underscoring the urgency of accounting for such trends in our assessment of international app-mediated studies.

Research Ethics

Requirements for ethics review are a primary mechanism through which medical research is regulated. International research generally complicates the applicability of such requirements, and this is almost certainly true in the case of app-mediated research as well. It may be unclear where such projects should be submitted for ethics approval, whether research ethics committee decisions would apply across jurisdictions, and whether it is possible to enforce existing rules against non-scientist researchers. Where ethics review is sought at multiple sites, there is a profound risk that the process will be inefficient and costly.^{Reference Humphreys, Trafton and Wagner34} Conventional ethics review systems, moreover, will sometimes be at odds with the structure of citizen science projects.³⁵ These factors suggest that requirements for ethics approval for international app-mediated studies carried out by nontraditional researchers is likely to be complicated and unclear.

Against this backdrop, some have proposed a “safe harbor” framework of ethics equivalency for biomedical research across jurisdictions.^{Reference Dove, Knoppers and Zawati36} On this model, international ethics review may be harmonized according to “globally transposable research ethics norms and principles.”³⁷ This would be facilitated by an international compact and the creation of an agency formed to facilitate ethics review for multisite international studies. While this sort of approach would potentially help address some of the difficulty in managing ethics approval for international app-mediated studies, it is only one approach. As smartphones become more centrally important research tools, it will be necessary to develop clear and consistent approaches to ethics approval.

Informed Consent

The informed consent implications of app-mediated research are likely to be modulated by several international policy documents. The World Medical Association’s Helsinki Declaration, for example, is perhaps the most influential international research ethics document.^{Reference Carlson, Boyd and Webb45} While it does not explicitly contemplate app-mediated research and is primarily addressed to physicians, its broad statement of research ethics principles may be a helpful guide for nontraditional researchers conducting app-mediated studies as well. In recent years, some have argued that citizen scientists could help to promote the public trust and increase the credibility of their work by adhering to the participant protection standards detailed in the Helsinki Declaration.^{Reference Puhan46} The Declaration sets out specific requirements for securing informed consent, including that prospective participants are “informed of the aims, methods, sources of funding, any possible conflicts of interest, institutional affiliations of the researcher, the anticipated benefits and potential risks of the study.”⁴⁷

These informed consent requirements, of course, are not uniquely present in the Helsinki Declaration. The CIOMS Guidelines likewise maintain that researchers have an obligation to obtain the informed consent of prospective participants.⁴⁸ Notably, the Council for International Organizations of Medical Sciences (CIOMS) stresses that informed consent should only be obtained after all necessary information about the research project has been communicated. Unaffiliated or otherwise nontraditional researchers should clearly disclose their status as citizen or commercial scientists in the informed consent process. Sources of funding should similarly be clearly disclosed during recruitment in order to avoid real or perceived conflicts of interest.

Privacy

The privacy implications of mobile health are pervasive. The United Nations Special Rapporteur on the Right to Privacy’s Task Force on Privacy and the Protection of Health Data has specifically addressed such issues in draft recommendations on the protection of health data. These draft recommendations clarify that the “the same legal protection and confidentiality applicable to other health-related data processing.”⁴⁹ The recommendations stress that individuals who use mobile apps for health data processing must have the privacy implications of such use explained to them prior to engaging with the application.⁵⁰ The Helsinki Declaration, notably, stresses the importance of protecting the “life, health, dignity, integrity, right to self-determination, privacy, and confidentiality of personal information of research subjects.”⁵¹ Article 24 of the Declaration specifies that “every precaution must be taken to protect the privacy of research subjects and the confidentiality of their personal information.”⁵² In light of the particular risks associated with app-mediated research, as we outlined above, the protection of the privacy interests of participants should be a central consideration in the design of app-mediated studies.

Like the World Medical Association, the Organization for Economic Cooperation and Development (OECD) has taken a recent interest in the growth of mobile health technologies. In October 2016, it issued the results of an expert consultation on mobile health held as part of the OECD-Harvard Global Health Institute Workshop.⁵³ This document contemplates health research directly on several points. In particular, the OECD identifies the central importance of maintaining relationships of trust among stakeholders, including in the provision of health services and the conduct of health research. In this regard, ensuring privacy is intimately related to maintaining the public’s trust.⁵⁴

Commercialization

The issue of commercialization in international policy norms is often framed explicitly in terms of informed consent. The CIOMS Guidelines, for example, specify in Guideline 1 that the commercial intentions of health researchers should be disclosed in the course of securing participant informed consent.⁵⁵ Importantly, article 12 of the Helsinki Declaration specifies that “medical research involving human subjects must be conducted only by individuals with the appropriate ethics and scientific education, training and qualifications.”⁵⁶ The CIOMS in its International Ethical Guidelines for Health-related Research Involving Humans takes a similar position.

In Guideline 1, for example, the CIOMS Guidelines describe the importance of having properly trained scientific personnel and of communicating the qualifications of researchers to prospective participants during the informed consent process.⁵⁷ This may serve to restrict the class of citizen scientists capable of conducting research that complies with international ethics norms. For private entities conducting app-mediated research for primarily commercial purposes, it may be difficult to assess researcher qualifications. While institutional affiliation may provide some measure of assurance of researcher qualification when the institution in question is a university, the same does not appear to be true in the case of less traditional research entities. The OECD, likewise, points to the importance of transparency and accountability in health research.⁵⁸ For app-mediated studies, the overriding ethical consideration on the issue of commercialization may be that participants are adequately informed about what will happen to the fruits of the study in question.

Research Ethics

The Helsinki Declaration takes a fairly strict approach to ethics review. Article 23, for example, requires that research protocols involving human subjects “must be submitted for consideration, comment, guidance and approval to the concerned research ethics committee before the study begins” and that the committee have “the right to monitor ongoing studies.”⁵⁹ The reviewing committee must be transparent, independent, and must not be influenced by the researcher or the researcher’s institution. The CIOMS Guidelines go somewhat further, describing requirements for the formation of an ethics committee. The Guidelines state clearly that “all proposals to conduct health-related research involving humans must be submitted to a research ethics committee to determine whether they qualify for ethical review and to assess their ethical acceptability.”⁶⁰ In the case of international research, the Guidelines require coordination between ethics committees in different countries. Such committees “should establish efficient communication” mechanisms for the coordination of research ethics review.⁶¹

Despite the clarity of such guidelines, questions remain about the obligations of nontraditional researchers to obtain research ethics approval. A citizen researcher might not know to which research ethics committee their project is best submitted. On this measure, industry self-regulation might be determinative, at least on the question of whether ethics review is required. Persons using the ResearchKit platform to develop app-mediated studies, for example, are required to obtain research ethics approval before posting their study, irrespective of whether there is a regulatory obligation to do so.^{Reference Glaser62}