Is Informed Consent Broken?

doi:10.1097/MAJ.0b013e31822a6c47

The American Journal of the Medical Sciences

Volume 342, Issue 4, October 2011, Pages 267-272

https://doi.org/10.1097/MAJ.0b013e31822a6c47 Get rights and content

Abstract

For as long as the federal regulations governing human subjects research have existed, the practice of informed consent has been attacked as culturally biased, legalistic, ritualistic and unevenly enforced. Its focus on meeting the regulatory requirements is seen as undermining a truly ethical process that produces informed and voluntary participation in medical research. Recent changes in the clinical translational research enterprise, with large scale genomic and other data sharing made possible by advanced bioinformatic technologies, may further challenge this goal. Study participants are asked to consent to future studies with unspecified aims, broad data sharing policies and ongoing uncertainties regarding confidentiality protections and the potential benefit of incidental genomic research findings. Because more research is conducted under these new conditions, the very nature of the researcher-subject relationship is shifting and will require new governance mechanisms to promote the original goals of informed consent.

Section snippets

Overemphasis on Respect for Persons

The first critique of informed consent is its excessive focus on individual autonomy. The Belmont Report described 3 moral principles, which many argue are equally important and universally applicable.⁵ The emphasis on autonomy reflects unique features of American culture, and its attention to individual rights. When these standards are exported to international studies, in settings with different traditions, misunderstanding and conflicts often result. The best-known examples of this occurred

CHANGES IN CLINICAL TRANSLATIONAL RESEARCH

As describe above, scientific, technological and economic forces are reshaping the world of clinical research. Trial sponsorship by the pharmaceutical and biotech industry now plays a significantly larger role than NIH.³⁸ Trials themselves are also increasingly being conducted outside of academic medical centers, in private clinics and hospitals.³⁹ These changes in funding and organizational context have generated increased attention to conflicts of interest that may influence the conduct of

INFORMED CONSENT IN GENOMIC RESEARCH

A recent publication⁴² identified challenges to informed consent for an NIH-funded consortia of GWAS studies linked to patient electronic medical records. As introduced in the previous section, they are generated by evolving technologies that enable the collection and storage of large-scale data and specimens. Genomic research challenges our basic understandings of how to describe study purpose, potential risks of harm and potential benefits that may come from participation.

THE OLD MODEL OF INFORMED CONSENT—OUTDATED AND OBSOLETE?

What is clear is that as more research is facilitated by large data repositories, the very nature of the researcher-subject relationship is being transformed. Controversy over inadequacies in our current system of informed consent have implications for connections and disconnections between researchers and the communities from which subjects are drawn, researchers and IRBs that attempt to address challenging dilemmas in genomic research and researchers and medical institutions and providers who

ACKNOWLEDGMENTS

I thank Daniel Nelson, Chuck Lidz and an anonymous reviewer provided very helpful suggestions for an earlier version of this article.

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The translational research from “bench-to-bedside” poses several critical ethical challenges which have direct implication in the safety and dignity of the human study-subjects. These include presence of voluntary informed consent, therapeutic misconception, and clinical equipoise. Over years, a number of legislations have been created as a result of human atrocities on the pretext of biomedical research including the Nuremberg Code, the Declaration of Helsinki, the Common Rule, and the Belmont Report. Each of these have served as a milestone in the creation of the notion of voluntary informed consent, the core of ethics in translational research. Regulatory bodies like Institutional Review Boards also play a critical role in protecting human participants through prior and intermittent review of the ethical considerations of the research protocol.
Translational research in vulnerable neurologically injured patients adds specific challenges in terms of emergency research and the inability of subjects to comprehend. Waiver of informed consent, surrogate consent, and e-consents from legal representatives are often used in the place of voluntary informed consent. The recently introduced translational genomic research further adds to the complexities of protecting patient’s identity and large-scale data sharing. Finally, effective collaboration must be obtained between the researchers, scientists, review boards, funding agencies as well as the government bodies to ensure ethical conduct of scientifically rigorous translational research.
Randomized evaluation of trial acceptability by INcentive (RETAIN): Study protocol for two embedded randomized controlled trials
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The most common and conceptually sound ethical concerns with financial incentives for research participation are that they may (1) represent undue inducements by blunting peoples' perceptions of research risks, thereby preventing fully informed consent; or (2) represent unjust inducements by encouraging enrollment preferentially among the poor. Neither of these concerns has been shown to manifest in studies testing the effects of incentives on decisions to participate in hypothetical randomized clinical trials (RCTs), but neither has been assessed in real RCTs.
We are conducting randomized trials of real incentives embedded within two parent RCTs. In each of two trials conducted in parallel, we are randomizing 576 participants to one of three incentive groups. Following preliminary determination of patients' eligibility in the parent RCT, we assess patients' research attitudes, demographic characteristics, perceived research risks, time spent reviewing consent documents, ability to distinguish research from patient care, and comprehension of key trial features. These quantitative assessments will be supplemented by semi-structured interviews for a selected group of participants that more deeply explore patients' motivations for trial participation. The trials are each designed to have adequate power to rule out undue and unjust inducement. We are also exploring potential benefits of incentives, including possible increased attention to research risks and cost-effectiveness.
Click yes to consent: Acceptability of incorporating informed consent into an internet-based testing program for sexually transmitted and blood-borne infections
2017, International Journal of Medical Informatics
Citation Excerpt :
Twenty years ago, the most pressing concern with the above shift was that patients become aware of the use, confidentiality, and security of their online data. This continues to be a principal concern [14–17], but what wasn’t predicted then and is today’s reality, is the novel and emerging issue of increased autonomy of patients over access to medical procedures and making health care decisions, with no requirement for discussion with a HCP [18,19]. As described by Applebaum in 2007, “valid IC is premised on the disclosure of appropriate information to a competent patient who is permitted to make a voluntary choice” [20].
Autonomous use of online health care services without interaction with a health care provider challenges existing models for achieving informed consent (IC); current examinations of this issue have focused on commercial direct-to-consumer genetic testing. As IC is integral to publicly funded clinical testing services, we incorporated pre-test concepts necessary for IC in GetCheckedOnline (GCO), British Columbia’s online sexually transmitted and blood-borne infection (STBBI) testing service.
We assessed the acceptability of this IC step and its design options among potential users during usability testing of GCO.
English-speaking participants ≥ 19 years were recruited from Craigslist and among provincial STI clinic clients for usability testing of an early version of GCO, which included a consent webpage presenting 8 pre-test statements for review prior to completing testing. Participants were interviewed regarding their acceptability, perceptions, and understanding of the consent page; transcripts were analyzed thematically.
We conducted 13 interviews (9 males, 4 females; 9 self-identified as heterosexual; all had previously tested for STBBI). We identified three main themes: i) the meaning of IC (consent page viewed as important and for protection of individual and organization; participants demonstrated varying understandings of specific components); ii) the impact of previous experience on understanding IC (participants understood difference between online and in-person testing; IC concepts were better understood by participants with more testing experience); iii) the role of website design on achieving IC (design of page to disrupt speedy click-throughs was valued and demonstrated seriousness of the consent page).
Our careful attention to both content and design of the consent page of GCO was highly valued by potential users of the service, and effective in disrupting routinization of consent on websites. We argue that principles of IC apply equally in online self-testing programs as in clinical practice, and can be effectively achieved without detracting from the user experience.
Moral Duties of Genomics Researchers: Why Personalized Medicine Requires a Collective Approach
2017, Trends in Genetics
Advances in genome sequencing together with the introduction of personalized medicine offer promising new avenues for research and precision treatment, particularly in the field of oncology. At the same time, the convergence of genomics, bioinformatics, and the collection of human tissues and patient data creates novel moral duties for researchers. After all, unprecedented amounts of potentially sensitive information are being generated. Over time, traditional research ethics principles aimed at protecting individual participants have become supplemented with social obligations related to the interests of society and the research enterprise at large, illustrating that genomic medicine is also a social endeavor. In this review we provide a comprehensive assembly of moral duties that have been attributed to genomics researchers and offer suggestions for responsible advancement of personalized genomic cancer care.
"Watching time tick by...": Decision making for Duchenne muscular dystrophy trials
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This interview study explored clinicians' perspectives and parents' decision making about children's participation in Duchenne muscular dystrophy (DMD) clinical trials.
Data from semi-structured interviews conducted with clinicians and parents in U.S. or Canada were assessed using thematic analysis.
Eleven clinicians involved in ten trials and fifteen parents involved in six trials were interviewed. Parents described benefit–risk assessments using information from advocacy, peers, professionals, and sponsors. Strong influence was attributed to the progressive nature of DMD. Most expected direct benefit. Few considered the possibility of trial failure. Most made decisions to participate before the informed consent (IC) process, but none-the-less perceived informed choice with little to lose for potential gain.
Clinicians described more influence on parental decisions than attributed by parents. Clinicians felt responsible to facilitate IC while maintaining hope. Both clinicians and parents reported criticisms about the IC process and regulatory barriers.
The majority of parents described undertaking benefit–risk assessments that led to informed choices that offered psychological and potential disease benefits. Parents' high expectations influenced their decisions while also reflecting optimism. Clinicians felt challenged in balancing parents' expectations and likely outcomes. Prognosis-related pressures coupled with decision making prior to IC suggest an obligation to ensure educational materials are understandable and accurate, and to consider an expanded notion of IC timeframes. Anticipatory guidance about potential trial failure might facilitate parents' deliberations while aiding clinicians in moderating overly-optimistic motivations. Regulators and industry should appreciate special challenges in progressive disorders, where doing nothing was equated with doing harm.

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This study was supported by grants from the National Human Genome Research Institute: R01 HG02087 “The Social Construction of Benefit in Gene Transfer Research” (Henderson PI) 1999–2007 and P50 HG004488-01 “Center for Genomics and Society” (Henderson PI) 2007–2012.

This paper was part of the 17th Annual Thomas A. Pitts Memorial Lectureship held at the Medical University of South Carolina, October 29–30, 2010.

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Symposium ArticleIs Informed Consent Broken?

Abstract

Section snippets

Overemphasis on Respect for Persons

CHANGES IN CLINICAL TRANSLATIONAL RESEARCH

INFORMED CONSENT IN GENOMIC RESEARCH

THE OLD MODEL OF INFORMED CONSENT—OUTDATED AND OBSOLETE?

ACKNOWLEDGMENTS

Soc Sci Med

Ann Thorac Surg

Ann Thorac Surg

Genet Med

Genet Med

Racism and research: the case of the Tuskegee Syphilis Study,

Hasting Cent Rep

Secretary’s Advisory Committee on Human Research Protections

Against relativism: cultural diversity and the search for ethical universals in medicine

The ethical design of an AIDS vaccine trial in Africa

Hastings Cent Rep

Research and informed consent in Africa—another look

N Engl J Med

CIOMS International Ethical Guidelines for Biomedical Rsearch Involving Human Subjects

Fair benefits for research in developing countries

Science

Motivating donors to genetic research? Anthropological reasons to rethink the role of informed consent

Med Health Care Philos

Attitudes and beliefs of African Americans toward participation in medical research

J Gen Intern Med

Applying research ethics guidelines: the view from a sub-saharan ethics committee

J Empir Res Hum Res Ethics

The evolution of consent forms for research: a quarter century of changes

IRB

The Hydra

Hastings Cent Rep

Informed Consent: No easy read

Trust, the fragile foundation of contemporary biomedical research

Hastings Cent Rep

The invisible hand in clinical research: the study coordinator’s critical role in human subjects protection

J Law Med Ethics

The cultural calculus of consent

Clin Obstet Gynecol

Twenty-five years of therapeutic misconception

Hastings Cent Rep

Questing for grails: duplicity, betrayal and self-deception in postmodern medical research

J Contemp Health Law Policy

An approach to evaluating the therapeutic misconception

IRB

Symposium Article
Is Informed Consent Broken?