The ethics of clinical research on human subjects has a rich history that belies its relatively recent development in the mid-twentieth century, marked by publications such as the Nuremberg Code , Henry Beecher’s landmark 1966 paper “Ethics and Clinical Research” , the Belmont Report , and the Declaration of Helsinki . In some universities and medical schools, ethics and professionalism courses can reduce medical ethics to the principles of beneficence, nonmaleficence, respect for persons, and justice . A similar strain of reductionism happens when students are merely given historical examples of egregious violations of human decency, such as the US Public Health Service Syphilis Study at Tuskegee or the more recently exposed US Public Health Service Sexually Transmitted Diseases Inoculation Study of 1946-48, which took place in Guatemala . Any tendency toward this kind of reductionism should be resisted, however, because a rich and full understanding of research ethics requires contextualization within historical, social, and cultural frameworks. The enterprise of biomedical research continues to be shaped by modern challenges, expectations, and social values. In this issue of the AMA Journal of Ethics, several authors explore current ethical issues in research and cull important lessons from the past to inform the future of biomedical research design and clinical practice.
I had the privilege of speaking with Robert Levine, MD, co-author of the Belmont Report and consultant for landmark regulations guiding the ethics of research on human subjects. In the podcast, Dr. Levine shares his experiences as the chair of various committees and his opinions on ongoing issues in the field of clinical research ethics. We discuss how the overemphasis in the literature on conflicts of interest, a phenomenon seen previously with informed consent, gives a false impression to new scholars in the field that this is the only topic of importance in modern clinical research ethics.
Several articles this month do discuss informed consent, particularly issues that stem from legislative or technological changes. In the health law piece, Richard Weinmeyer, JD, MPhil, MA, gives an overview of changes proposed to the Common Rule , which confers regulatory protections to research subjects who are members of vulnerable populations. Concisely, the proposed changes suggest new standards for informed consent processes and suggest how research review processes might be streamlined and made more efficient . In the policy forum section, Stephanie Alessi Kraft, JD, Kathryn Porter, JD, MPH, Benjamin S. Wilfond, MD, and the Research on Medical Practices Group explore unintended implications of the Office for Human Research Protections (OHRP) draft guidance redefining research risks surrounding informed consent.
One reason informed consent is discussed so frequently in this issue is that research has always relied on the participation of volunteers, often healthy subjects who are assuming some risk to themselves, or, in some cases, their loved ones. The cases in this issue explore the tensions between mitigating risk to individual subjects and maximizing benefit to the broader population of future patients. Spencer Phillips Hey, PhD, and Robert D. Truog, MD, comment on the case of a guilt-ridden physician who questions her decision to encourage a patient to enroll in a clinical trial. This highlights the value and necessity of the principle of clinical equipoise—the medical community’s genuine uncertainty as to the efficacy of each arm of a clinical trial—for considering whether and when it is ethically justifiable for patients to become subjects. Erin P. Williams, MBE, and Jennifer K. Walter, MD, PhD, MS, explore the issues of justice and coercion in a case in which researchers must decide how much to compensate subjects for trial participation. In their case commentary, Armand H. Matheny Antommaria, MD, PhD, and Kristen Stanley Bramlage, MD, discuss conflicts of interest and therapeutic misconception when enrolling pediatric patients in a clinical trial.
As with the patient-physician relationship, unchecked paternalism is now regarded as inappropriate in researcher-subject relationships. As our contributors explain, in recent decades public responses to the research enterprise have changed. Susan Lederer, PhD, explores changes in media representation of research-associated deaths, contrasting former attitudes with recent highly publicized cases that have shaken public trust in clinical research. Elizabeth Bromley, MD, PhD, Loretta Jones, MA, ThD, Marjorie S. Rosenthal, MD, MPH, Michelle Heisler, MD, MPH, Julie A. Sochalski, PhD, RN, Deborah Koniak-Griffin, RNC, EdD, Cristina Punzalan, MPH, and Kenneth Wells, MD, MPH discuss the new National Clinician Scholars Program’s focus on multidisciplinary teams and community-based participatory research, which addresses health needs in communities and incorporates nonmedical leadership into the setting of research priorities. And Paige E. Finkelstein provides an overview of the Food and Drug Administration’s expanded access process, through which people with life-threatening illnesses can apply for access to investigational drugs.
Another ethical issue in research is how study results are discussed among scientists and whether or not they are publicized. Daniel L. Shaw and Joseph S. Ross, MD, analyze new policies aimed at increasing transparency about clinical trial results and discuss the benefits of promoting a culture of open data and collaboration among researchers. Turning to how results are communicated to the public, Ivan Oransky, MD, shares his views on the irresponsible media representation of medical research outcomes and the incentives that lead both journalists and researchers to overstate claims of significance.
These and other challenges are a result of the adaptation of clinical research ethics to changing regulations and scientific and cultural norms. This issue of AMA Journal of Ethics attempts to raise awareness—and spark dialogue—about how clinical research ethics is transforming.
Nuernberg Military Tribunals. The Medical Case. Washington, DC: US Government Printing Office; 1949:181-182. Trials of War Criminals before the Nuernberg Military Tribunals under Control Council Law No. 10; vol 2. http://www.loc.gov/rr/frd/Military_Law/pdf/NT_war-criminals_Vol-II.pdf. Accessed October 23, 2015.
- Beecher HK. Ethics and clinical research. N Eng J Med. 1966;274(24):1354-1360.
National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont report: ethical principles and guidelines for the protection of human subjects of research. April 18, 1979. http://www.hhs.gov/ohrp/policy/belmont.html. Accessed October 21, 2015.
World Medical Association. WMA Declaration of Helsinki—ethical principles for medical research involving human subjects. Revised October 2013. http://www.wma.net/en/30publications/10policies/b3/index.html. Accessed October 23, 2015.
- Reverby SM. “Normal exposure” and inoculation syphilis: a PHS “Tuskegee” doctor in Guatemala, 1946-1948. J Policy Hist. 2011;23(1):6-28.
Federal policy for the protection of human subjects; notices and rules. Fed Regist. 1991;56(117):28002-28032. Codified at 7 CFR sec 1c; 10 CFR sec 745; 14 CFR sec 1230; 15 CFR sec 27; 16 CFR sec 1028; 22 CFR sec 225; 24 CFR sec 60; 28 CFR sec 46; 32 CFR 219; 34 CFR sec 97; 38 CFR sec 16; 40 CFR sec 26; 45 CFR sec 46, 690; 49 CFR sec 11 (2015). http://www.hhs.gov/ohrp/policy/frcomrul.pdf. Accessed November 5, 2015.
Federal policy for the protection of human subjects; proposed rules. Fed Regist. 2015;80(173):53933-54060. To be codified at 6 CFR sec 46; 7 CFR sec 1c; 10 CFR sec 745; 14 CFR sec 1230; 15 CFR sec 27; 20 CFR sec 431; 22 CFR sec 225; 28 CFR sec 46; 29 CFR sec 21; 32 CFR sec 219; 34 CFR sec 97; 38 CFR sec 16; 40 CFR sec 26; 45 CFR sec 46, 690; 49 CFR sec 11. http://www.gpo.gov/fdsys/pkg/FR-2015-09-08/pdf/2015-21756.pdf. Accessed October 20, 2015.