The Changing Face of Informed Consent

The Changing Face of Informed Consent

Christine Grady, R.N., Ph.D.

In the classic interaction in which informed consent is obtained for research, an investigator presents the potential participant with information regarding a new therapeutic, diagnostic, or prophylactic intervention and then asks the participant to read and sign a detailed written consent document. This traditional prototype is becoming outdated. Informed consent, which is ethically essential in most clinical research, respects persons’ rights to decide whether participation in the research is compatible with their interests, including their interests in protection from exploitation and harm.1,2 In the process of informed consent, participants are given an opportunity to understand relevant information about research participation and to make a voluntary choice.3 Required by ethical guidelines and regulations unless explicitly waived by institutional review boards,4-7 informed consent is thus a means of protecting the rights and welfare of participants while they contribute to the advancement of knowledge.

Over the past 50 years, the informed consent process has become increasingly regulated and standardized, while the challenges remain persistent and hard to overcome.8 Consent forms are increasingly long and complicated, obscuring important details, and are often designed to serve the interests of institutions and sponsors. Data show that participants often have a limited understanding of study information even when they have signed a consent form.8 Technological advances driving changes in research methods and information practices have influenced how we think about informed consent for research, which raises the possibility of new approaches to informed consent and innovative options for obtaining it.
Changing Research Methods

Unprecedented opportunities to answer important clinical research questions are available through the analysis of massive amounts of data (“big” data) in commercial, health care, research, and government databases, in social media and mobile devices, and in growing collections of biologic specimens and clinical and genomic data. Data are amassed quickly and easily, sometimes through passive technologies such as location-based mobile devices, through registries, or through systems of electronic health records or data and biospecimens collected for other purposes. Innovative studies are being developed that are conducted entirely through the Internet, as described below by Cummings and Rowbotham, or through the use of smartphone apps, as described below by McConnell and Ashley. Such research allows “access” to participants remotely without the constraints of time or location. Powerful technologies enable data mining and analytics, as well as the integration of data from multiple sources.

Is the classic written informed consent process and document appropriate for these research paradigms? The level of risk to participants is low and is usually thought to be primarily informational,9 which differs from the risks associated with traditional interventional clinical research; the researcher–participant relationship also differs. Some argue that although informed consent allows participants to decide about acceptable risks, it may be unnecessary for research that involves the mining of large data sets or the analysis of deidentified biospecimens, because risks are low, especially as compared with the risks of research on previously untested treatments. In addition, deidentification and privacy protections further attenuate any individual informational risk.10,11 Moreover, there is concern that requiring consent for low-risk research of this type could impede or make infeasible otherwise valuable research or could result in selection bias — that is, a situation in which persons who are willing to consent differ fundamentally from those who are not willing, thus jeopardizing the science.12,13

In the commercial marketplace, people use social media and mobile devices and contribute their data to large databases in innumerable ways, and they may be unaware of the multiple entities gathering and storing their data for future use. Persons are sometimes notified in general terms about various uses of their data, yet “[r]esearchers are rarely in a user’s imagined audience.”14 Reactions to certain research studies, such as the Facebook emotion experiment or OkCupid research,15-17 as well as empirical data, such as that gathered in association with Twitter’s population-level depression monitoring,18 provide evidence that some people feel strongly about being asked and may not consent to certain research uses.19

Research with biospecimens may pose risks that are different from those posed by research with either actively or passively gathered data, yet public and private researchers often use deidentified clinical biospecimens without consent.12 Requiring consent for the use of such samples could result in smaller, more highly selective pools of participant samples, which may impede publicly beneficial research or limit its validity. The debate about the need for and form of informed consent for research with stored biospecimens was revived by recent international discussions and proposed changes to the U.S. Common Rule (changes that were not ultimately accepted) that would have required written consent for all research use of biospecimens.20,21 Even those who favor requiring consent for biospecimen research disagree about whether consent should be broad for a wide range of future possible research or specific for each use, one-time or ongoing, and opt-in or opt-out.22-27

Other emerging clinical research paradigms, including pragmatic trials and learning health care systems — that is, systems in which interventions that are within the scope of standard practice are tested and data are gathered passively in an attempt to improve outcomes — have also provoked debate about appropriate methods of informed consent.28-31 Although more similar to the prototypical clinical trial, some of these studies pose low research risks, are more similar to quality-improvement studies than to interventional clinical research, and depend on collective participation for scientific validity. Features of some of these trials arguably permit less formal consent procedures, perhaps notification with opt-out and, in some cases, even waiver.31

In survey after survey, however, people report that they prefer to be asked and given a choice about research even if there is little risk to them.27,32-39 The challenge is finding practical, nononerous ways to respect persons’ choices that have minimal negative effects on the science. Information technology may provide new opportunities to implement informed consent with minimal intrusion.
Changing Information Technologies and Practices

Digital technology has transformed how people communicate, learn, and work; information is increasingly acquired and communicated online or through mobile devices. Society is gradually becoming paperless, and information is constantly at our fingertips. Health information is stored in electronic health records. Small tablet computers and smart phones are multiplying five times faster than the global population.40 Technological and societal changes in information practices present fresh opportunities for innovative implementation of informed consent. Apps, tablets, video, interactive computers, robots, personal digital assistants, mobile phones and smartphones, and wearable technology could help to modernize, alter, and improve methods of informed consent. Technologies permit broad standardization and easy updating of information, ready use of creative graphics, the means for remote interactive discussions, and documentation of the process. Investigators can use technologies to provide information, interact with participants, answer questions, and assess understanding on an ongoing basis. Available consent tool kits featuring visual interactive approaches aim to make informed consent more participant-centered and less focused on signing legal documents.41 Other tool kits allow researchers to create apps for medical research and include customizable visual consent templates.42 Technologies allow for methods of informed consent that are modern, green, interactive, and dynamic.43-46

Along with providing opportunities, adoption of digital and electronic methods of consent requires deliberation, evidence, and recognition of challenges (Table 1Table 1Components and Challenges of Informed Consent with Traditional Paper Forms and Electronic Methods.). Investigators and oversight bodies must still determine the appropriate content for disclosure. Replacing long, complex, technical written forms with long, complex, technical or legalistic electronic information pages would not represent progress. Indeed, very few persons read click-through agreements, a common notice-and-consent feature of computer and mobile device use, before clicking “agree.”48,49 Clicking an agreement box without engaging with the information would be the equivalent of signing a consent form without reading it. This approach to consent would probably do more to protect investigators and sponsors than to inform participants. Important additional challenges in digital consent interactions include verifying that the people who are consenting have the capacity to consent and are who they say they are (authentication). If informed consent aims to provide information that participants can use to make decisions, promoting informed consent will require the creative use of electronic technologies that are simple, easy to use, and in widespread and common use. The interactions need to be brief, engaging, informative about risks and benefits in a way that users can easily appreciate, and equipped with methods for authentication, as discussed below by Cummings and Rowbotham. Such approaches to obtaining consent could also reduce worries about possible selection bias.

Information technologies enable new ways of presenting information and transferring some control to participants even in research in which investigators and participants never meet, yet they do not resolve questions related to the necessity or adequacy of informed consent. As described below by Kang, regulations in India require consent interactions to be videotaped in order to enhance accountability, with the hope of improving the consent process and ensuring its adequacy.

Informed consent as a process that serves to respect autonomous choices and protect people from risks is not “one size fits all” and should be tailored to context. One-on-one interactive informed consent with detailed information about the purpose of a study as well as about its risks, benefits, and alternatives is necessary for high-stakes gene-transfer research, for example; however, in my view, it is unnecessary for studies that involve deidentified aggregate clinical data. For the latter, educating the public and notifying persons whose data will be used might sufficiently show respect without impeding the science.

Broad dialogue and empirical research should inform decisions about adopting new methods of obtaining informed consent and tailoring models of consent to changing research paradigms. Research is needed to examine whether and when any progress made through low risk–high reward research outweighs other issues, including the ethical reasons behind obtaining prototypical informed consent. Researchers should also investigate public views about informed consent for the use of big data and electronic consent methods, as well as methods promoting engagement with and comprehension of digital study information, methods of authentication and capacity assessment as part of digital consent, and the extent to which there is selection bias in research in which digital consent technologies are used. The ethical goals of informed consent and the importance of considering research context should guide us as we assimilate technology into research and the informed consent process and develop creative and effective evidence-based practices.

From the Department of Bioethics, National Institutes of Health Clinical Center, National Institutes of Health, Bethesda, MD. Address reprint requests to Dr. Grady at the Department of Bioethics, National Institutes of Health Clinical Center, National Institutes of Health, Bldg. 10, 1C118 Bethesda, MD 20892, or at cgrady@nih.gov.

The views expressed are those of the author and do not necessarily reflect those of the Clinical Center, the National Institutes of Health, or the Department of Health and Human Services.

I thank Frank Miller, Dave Wendler, and Carl Runge for their helpful comments.