The new england journal of

Review Article

Dan L. Longo, M.D., Editor Enduring and Emerging Challenges of Informed

Christine Grady, Ph.D.

nformed consent is a widely accepted legal, ethical, and regula- From the Department of , Na- tory requirement for most and health care transactions. Nonetheless, tional Institutes of Health Clinical Center, Bethesda, MD. Address reprint requests the practice of informed consent varies by context, and the reality often falls to Dr. Grady at the Department of Bioeth- I ics, National Institutes of Health Clinical short of the theoretical ideal. Contemporary developments in health care and call for renewed efforts to address the enduring and emerging challenges Center, Bldg. 10/1C118, Bethesda, MD 20892, or at ­cgrady@​­nih​.­gov. of informed consent, such as what information should be disclosed, how it should be disclosed, how much the persons providing consent should understand, and how N Engl J Med 2015;372:855-62. DOI: 10.1056/NEJMra1411250 explicit consent should be. Copyright © 2015 Massachusetts Medical Society. The moral force of consent is not unique to health care or research. Integral to many interpersonal interactions and well entrenched in societal values and juris- prudence, consent can render actions morally permissible that would otherwise be wrong. For example, with consent it is fine to borrow a person’s car or draw blood, but these actions without consent are considered theft or battery.1 Recent research conducted by Facebook and OkCupid, which made use of user information and gener- ated arguments about whether the general consent given when joining a social network suffices as consent for such research or whether express consent is required,2,3 illustrates both how deeply rooted the idea of consent is in society and the changing landscape in which it may apply.

Ethical and Legal Foundations Consent is a long-standing practice in some areas of medicine, yet only in the last century has informed consent been accepted as a legal and ethical concept integral to medical practice and research.4 Informed consent, in principle, is authorization of an activity based on an understanding of what that activity entails and in the absence of control by others.5 Laws and regulations dictate the current informed- consent requirements, but the underlying values are deeply culturally embedded — specifically, the value of ’ and their right to define their own goals and make choices designed to achieve those goals.5 This right applies to all types of health-related interventions, including life-sustaining inter- ventions. An early President’s Commission report noted, “Informed consent is rooted in the fundamental recognition . . . that adults are entitled to accept or reject health care interventions on the basis of their own personal values and in furtherance of their own personal goals.”6 Although informed consent is widely accepted in the United States and in many other countries, this understanding — and, indeed, the focus on an individual right to self-determination — varies according to culture. Cultural differences manifest in both the practice of informed consent — that is, what is told to whom and who makes decisions — as well as in an understanding of the normative underpinnings of informed consent as respect for individual autonomy. Persons in

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many cultures, both in the United States and ests and whether to authorize or refuse it. Persons around the world, rely on their families and should have the capacity to understand the infor- sometimes on their communities for important mation and should be in a position to make and decisions, and this may be the norm in cultures to authorize a choice about how to proceed. Nei- that stress the relationship of individuals to oth- ther medical nor research interventions should ers and the embeddedness of individuals within commence until valid consent has been obtained, society. Commentators and empirical evidence except under limited circumstances (e.g., emer- have shown that culture influences moral values gencies). When a or is and that other key values such as loyalty, compas- a child or an adult who is not capable of providing sion, and solidarity may be more dominant than informed consent, permission for medical care or autonomy in some cultures.7 Respecting persons research is often sought from a substitute deci- includes respecting their cultural values and may sion maker, such as a parent or legally autho- require adapting the specifics of information dis- rized proxy. closure or obtaining authorization for treatment Most accept that in practice, particular aspects or research accordingly. Yet respecting cultural of informed consent vary by context, and both values does not negate the need to respect the scholars and practitioners continue to debate persons for whom care or research is being con- these aspects — such as the scope and level of sidered or the need to implement respectful and detail provided and the methods of disclosure,12,13 appropriate procedures. As Gostin points out, whether and how to assess comprehension, what “Vast personal, cultural, and social differences will constitutes necessary and sufficient understand- perennially pose challenges to meaningful dia- ing for valid consent,14 approaches to assessing logue among physician, patient, and family; it is persons’ capacity to consent and steps taken when the regard, consideration, and deference shown the they lack that capacity,15 how to know when patient that remains the hallmark of respect for choices are sufficiently voluntary,16 and issues persons.”8 The World Medical Association Declara- concerning the documentation of consent.17 tion of Lisbon on the Rights of the Patient em- Consent for an elective surgical procedure dif- phasizes that everywhere have a right to fers from that for a simple routine blood test or information and to self-determination.9 The Dec- from a complicated research study, for example. laration of Helsinki and other international codes Cultural, socioeconomic, and educational factors of research ethics similarly emphasize the cen- can also influence the process and practice of in- trality of informed consent in the context of re- formed consent, as can different decision-making search globally.10 practices and norms related to the role of indi- vidual autonomy.18 Gaps between Furthermore, in practice, emphasis is often and Practice given to the written documentation of consent, despite wide agreement that consent requires more Informed consent is a process of communica- than a signature on a form. Faden and Beauchamp tion between the health care provider or investi- acknowledge that there are two common and gator and the patient or research participant that starkly different meanings of informed consent: ultimately culminates in the authorization or re- autonomous authorization by a patient or re- fusal of a specific intervention or research study. search participant and institutionally or legally According to the American Medical Association, effective authorization, determined by a complex “Informed consent is a basic policy in both eth- web of prevailing rules, policies, and social prac- ics and law that physicians must honor . . . .”11 tices.5 The latter meaning, which is not necessar- The process involves multiple elements, including ily accompanied by autonomous decisions, may disclosure, comprehension, voluntary choice, and overemphasize written documentation and risk authorization. In theory, physicians and investi- communication, and it serves to help protect pro- gators disclose understandable information to viders and institutions from liability. patients and research participants to facilitate A substantial body of literature corroborates informed choice.4 These persons use this infor- a considerable gap between the practice of in- mation to deliberate and decide whether the in- formed consent and its theoretical construct or tervention offered is compatible with their inter- intended goals and indicates many unresolved

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Challenges of Informed Consent conceptual and practical questions.19-22 Empirical ethical goals of consent.40 More provocatively, evidence shows variation in the type and level of some suggest a need to revisit the concepts and detail of information disclosed, in patient or re- the contours of acceptable consent, noting that search-participant understanding of the informa- current notions of informed consent may be out- tion, and in how their decisions are influenced.23 dated41 or that we may be expecting too much of Physicians receive little training regarding the consent.42 Clearly, there is a need for continued practice of informed consent, are pressed for time consideration of the normative and practical as- and by competing demands, and often misinter- pects of informed consent in an attempt to rec- pret the requirements and legal standards. Patients oncile practice with the theoretical ideal. Several often have meager comprehension of the risks and contemporary trends in health care and research alternatives of offered surgical or medical treat- accentuate this need, as described in Table 1. ments,24 and their decisions are driven more by trust in their doctor or by deference to authority Changing Models of Health than by the information provided.25,26 Informed Care and Research consent for research is more tightly regulated and detailed,27 yet research consent forms continue to Informed consent is one among several important increase in length, complexity, and incorporation challenges that have arisen as health care institu- of legal language, making them less likely to be tions and practitioners adopt robust learning read or understood.28,29 Studies also show that models that hybridize patient care with research research participants have deficits in their un- and evidence generation to efficiently integrate derstanding of study information, particularly of improved prevention, treatment, and care-deliv- research methods such as randomization.30 Re- ery methods. The models include the Institute of search participants, who are often patients with Medicine Learning Health Systems, continuous illnesses, frequently misunderstand the way in quality improvement, comparative effectiveness which research is distinct from individualized trials, pragmatic clinical trials, and practice-based clinical care, and some worry that this “therapeu- research, among others.43,44 Accompanying the tic misconception” can invalidate informed con- of these models are debates about how sent.31 The federal regulations require most re- specific the disclosed information should be, about search informed-consent documents to include a when express prospective consent is necessary or standard set of informational elements and to be when routine disclosure or notification might approved by an institutional review board before suffice, and about how closely consent for these use.27 However, recent controversy over a study of activities should resemble a research model of in- neonates, the Surfactant, Positive Pressure, and formed consent.45,46 Conventionally, information Oxygenation Randomized Trial (SUPPORT) study, disclosure differs between clinical and research illustrates that even when these requirements informed consent in detail, formality, and level are adhered to, reasonable people disagree about of prior review; these differences are often justi- the adequacy of the information presented on the fied by differentiating the primary goal of clini- consent forms.32,33 cal care — helping the patient — from the pri- Various strategies to improve patient under- mary goal of clinical research — generating standing in informed consent have been evaluated. useful knowledge.47,48 With more recently em- Studies show that patients understand risk bet- braced learning paradigms, these goals are con- ter when physicians are taught communication verging, or at least the boundaries are shifting.49 strategies.34,35 Decision aids and decision-making Some argue that in the context of learning activi- tools36 and a focus on shared decision making also ties, “research-like” written informed consent enhance patients’ understanding and satisfac- may be ethically unnecessary, overly burdensome, tion.37,38 When time is spent explaining informa- and likely to thwart improvement efforts.50,51 Dis- tion about the study, the participants’ under- agreement remains, however, about the right con- standing of research seems to improve.39 Practical sent model for these clinical and research learning strategies, such as synthesizing and simplifying activities, and high-profile cases have spurred information and using technological tools and controversy.52,53 One argument against research- nonphysician providers to explain the research, like consent presumes that many learning activi- have been suggested as ways to help achieve the ties — for example, evaluating the importance

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The new england journal of medicine Proposed Strategies ing; consent to be governed, more evi - more governed, be to consent ing; con - giving persons what dence about strategies alternative know, to want sent to consent consent; dynamic or broad science of enhancement governed; be literacy data of deidentification governed; be to samples and profession - health of training and pacity presenting to approaches creative als; friends trusted involving information; discus - consent in members family and studying making; decision and sions decision substitute for paradigms new making Integrated consent, shared decision mak - decision shared consent, Integrated information; present to technology of Use consent consent; ; Broad ca - of assessment effective and Respectful Enduring Questions and Challenges search participants often do not understand the understand not do often participants search infor - Complex them. to provided information difficult more be may interventions and mation limit - of setting the in especially understand, to literacy. science and health ed future regarding be to need process consent answer the Does specimens? or data of uses deidentified are specimens or data the differ if oversight? to subject are projects future if or Capacity assessed. occasionally only is consent re - or patient a when only questioned be may physician the with disagrees participant search deci - substitute for standards The researcher. or differ - are and jurisdiction by vary makers sion decisions. research and clinical for ent mation for valid consent in various contexts? various in consent valid for mation in - present or disclose to way best the is What but comprehensive sufficiently be to formation ele - contextual the are What overwhelming? not amount, appropriate the determine that ments disclosure? of format and complexity, Empirical evidence shows that patients and re - and patients that shows evidence Empirical the in provided information the does specific How to capacity the and adults, for assumed is Capacity What is the appropriate amount and detail of infor - of detail and amount appropriate the is What Emerging Questions and Challenges understanding should be sought when obtaining con - when sought be should understanding se - genetic as (such technologies complex for sent complex and voluminous by characterized quencing) of variants (e.g., uncertainty substantial information, impli - and findings, incidental significance), unknown relatives? blood for cations broad or unspecified an for consent provide to pant a to consent to or research future possible of range governance? of system or program con - of incapable is person a that indicate not do se people elderly of numbers increasing the senting, yet disor - other and dementia of prevalence increasing and care clinical both in professionals that suggest ders to capacity person’s a consider should research in and capacity. assess to how in trained be and consent and tools efficient and respectful for need a is There decision promoting capacity, assessing for processes friends, and families involving appropriately making, deci - substitute using and values, cultural respecting appropriate. when makers sion lar to research informed consent or clinical informed clinical or consent informed research to lar to given be should information much How consent? (if circumstances what Under advance? in participants suffi - consent express than rather notification is any) cient? When can consent be ethically waived or altered? What information is important to patients and research or patient a for acceptable ethically it Is participants? unspeci - an for consent provide to participant research activities? of range broad or fied How should information be presented, and what level of level what and presented, be information should How partici - research or patient a for acceptable ethically it Is per dementia and capacity, mental diminished age, Older Should informed consent for these activities be more simi - more be activities these for consent informed Should nologies, such as next- as such nologies, se - genetic generation quencing biologic or data clinical specimens population aging an preva - in increase and dementia of lence tems, pragmatic trials, pragmatic tems, improve - quality and ment Current Trends in the Health Care and Research Landscape That Have an Effect on Enduring and Emerging Challenges in Informed Consent. Informed in Challenges Emerging and Enduring on Effect an Have That Landscape Research and Care Health the in Trends Current 1. Table Adoption of complex tech - complex of Adoption of use future for Consent with changes Demographic Selected Current Trends in Health Care sys - care health Learning

858 n engl j med 372;9 nejm.org February 26, 2015 The New England Journal of Medicine Downloaded from nejm.org at NIH Libary on February 26, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved. Challenges of Informed Consent of repeat laboratory tests or how well health care uncertain significance and secondary and inci- providers use a checklist — add little or no risk dental findings, and the implications for blood for patients already receiving care, involve de- relatives present substantial challenges.64,65 Com- tails of slight interest to patients, and have over- prehensively explaining in advance the elements all goals that patients support. Some would ex- necessary for obtaining informed consent, such tend to learning activities a “simple” consent or as the expected risks, benefits, and likely outcomes notification paradigm that is used for certain of sequencing, can be difficult because of the sheer clinical interventions, usually when the risks are volume and inherent uncertainty of the informa- low and patients are not likely to have strong tion generated. Further, the level and type of de- preferences between treatment options or when tails presented in an informed-consent process there is only one logical choice.54 The SUPPORT may appropriately differ between the clinical and study, for example, brought to the forefront the research contexts, as well as according to popula- unresolved question of the extent to which re- tion or setting. For example, the type of informa- search in which participants receive standard tion and the way it is disclosed to informed healthy medical care or the care that they would rou- consumers who purchase direct-to-consumer ge- tinely receive outside the study poses “research nomic analysis may vary from that for ill patients risks” that require review by an institutional re- seeking clinical diagnosis and treatment.66 view board and comprehensive disclosure of these In all settings, determining how to present risks in a research informed-consent process.55-57 complex scientific information is further compli- Further research and dialogue will help guide cated by the low prevailing rates of science and decisions about how much disclosure is neces- .67 It has been suggested that in sary in different learning contexts, the extent to certain circumstances, it may be acceptable to ask which risk to participants matters in these deci- people to consent to an oversight mechanism sions, how we should think about risk presented that serves to evaluate specifics (i.e., consent to by research involving standard medical interven- be governed) rather than to consent to specific tions, the role of patient preferences, and which, details42; there may also be a need for ongoing if any, activities can proceed without explicit pro- communication processes that allow the incorpo- spective consent. Crucially, these efforts should ration of changing information and changed ex- include identifying what patients, research partici- pectations over time.43 Engaging patients in the pants, providers, and others care about in various identification of suitable consent mechanisms or contexts. in the development of mechanisms of dynamic consent are additional strategies that have been 68,69 Consent and Emerging suggested. Similar consent strategies have been Technologies proposed for research involving biologic speci- mens and data. Inspired by the story of Henrietta A second challenge to informed consent emerges Lacks (whose tumor gave rise to HeLa cells but from the complexity and uncertainty of the infor- whose permission to use her tumor cells for mation generated by advanced technologies and research was not sought),70 scientists and policy- expanded research opportunities. For instance, makers are investigating and discussing models next-generation genomic sequencing technologies, of consent to identify those that are both ethi- such as whole-genome sequencing, which allow cally and practically suitable for the future use the quick and increasingly inexpensive detection of of samples and data.71,72 variation in the human genome, are rapidly be- ing adopted into clinical research and routine Changing Demographics clinical practice.58 Although the routine imple- mentation of genomic sequencing into standard A third contemporary challenge to informed con- clinical practice may be premature, turning back sent emerges from expected sociodemographic may be difficult.59,60 Many recommend a robust trends. The U.S. population will become consid- informed-consent process for the use of genomic erably older and more racially and ethnically di- sequencing technologies.61-63 Yet the complexity, verse over the next few decades, with an expected volume, and density of generated health infor- doubling of the number of persons 65 years of age mation, the anticipated discovery of variants of or older and an even more dramatic increase in

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the number of the “oldest old” (85 years of age or can wax and wane, so patients should remain older).73,74 Persons older than 65 years of age gen- involved in treatment decisions to the extent that erally use more health care services, have a higher it is possible. Creative and applicable methods of prevalence of chronic diseases, and more often information disclosure are also necessary for per- have declining physical and cognitive function sons whose capacity is diminished, as well as for than do those who are younger.75 The number of the increasing numbers of patients who are not people with Alzheimer’s dementia is also expect- primarily English speakers. ed to more than double by 2050 and to increase Despite the enduring and emerging challenges more dramatically among the oldest old.76 Prepar- of informed consent in health care and research, ing for these realities and their effect on health consent is recognized as morally transformative care is critical. For informed consent, they suggest authorization, making certain activities permis- the need for respectful, effective, and efficient sible that otherwise would be wrong. Assiduous methods of both ascertaining whether persons efforts to clarify and fine-tune concepts, expec- have the capacity to consent for themselves and tations, practices, and the critical role of context facilitating decision-making processes for those are necessary to bridge the gap between the re- who do not. Although many elderly persons, in- alities of informed consent and the ideal. Contin- cluding some with dementia, retain the capacity ued exploration through research, public dialogue, to give informed consent for certain treatment and creative approaches will help address the ethi- decisions, others do not. Clinicians, who often cal permissibility and public acceptability of new lack training in assessing capacity, do not always models of consent, such as allowing consent for recognize incapacity and may question a patient’s a broad set of activities, sometimes with an ex- capacity only when they face a risky decision or plicit system of governance over specifics; recog- when the patient disagrees with their recom- nizing the validity of joint approaches to consent mendations.77 Cultural understandings of health and decision making; refining processes to re- and illness can also sometimes play a role when spect those who cannot consent for themselves; patients disagree with clinical recommenda- and finding creative, practical, and respectful ways tions. Assessing capacity and identifying appro- of presenting information and supporting decision priate and legally acceptable alternative decision making tailored to each context. Respecting and makers or processes take time and resources and promoting the informed choices of patients and often receive short shrift in a busy clinical or re- research participants or persons acting on their search setting. Assessing the reasoning capacities behalf remain of paramount importance, despite of persons from cultural backgrounds that are not the challenges of varied and changing contexts, well understood by clinicians can also pose consid- altered capacity, limited health literacy, complex erable challenges. Clinicians and investigators interventions, and shifting boundaries between should be taught to assess capacity and should health care and learning. Continued persistent and be provided with validated and useful tools78 and thoughtful efforts to bring the theoretical and the resources to help resolve difficult or border- practical realities of informed consent closer to- line cases. Joint decision-making approaches that gether are essential. support the existing capacity of each patient but The views expressed are those of the author and do not neces- involve friends and family members have been sarily reflect those of the Clinical Center, the National Institutes recommended, because even “autonomous” deci- of Health, or the Department of Health and Human Services. sions are often made together with trusted loved Disclosure forms provided by the author are available with the 79,80 full text of this article at NEJM.org. ones. Patients may have the capacity for cer- I thank Alan Wertheimer and David Wendler for their review tain decisions but not for others, and capacity of an earlier version of the manuscript.

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860 n engl j med 372;9 nejm.org February 26, 2015 The New England Journal of Medicine Downloaded from nejm.org at NIH Libary on February 26, 2015. For personal use only. No other uses without permission. Copyright © 2015 Massachusetts Medical Society. All rights reserved. Challenges of Informed Consent

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