Which of the following ethical violations were committed in the Tuskegee study?

1.1.3 The Tuskegee Syphilis Experiment

The Tuskegee Syphilis Experiment[19] was a clinical study conducted between 1932 and 1972 in Tuskegee, Alabama, by the United States Public Health Service. Four hundred Afro-American sharecroppers, most of them illiterate, were studied to observe the natural progression of untreated syphilis up to their eventual death by the disease.

This experiment aroused controversy and led to changes in the legal protection of the patients involved in clinical studies. Subjects involved in this experiment did not give their informed consent; they were not informed of their diagnosis and were told that they were being treated for “bad blood.” They were also told that if they participated in the study, they would be given free medical care, free transportation to the clinic, free meals, and free burial insurance in the case of death. Subjects were also warned to avoid penicillin treatment, which was already in use with other patients nearby.

In 1932, when the study began, treatments for syphilis were very toxic, dangerous, and had questionable effectiveness. Part of the purpose of the study was to determine if the benefits of the treatment compensated its toxicity and to recognize the different stages of the disease to develop treatments adapted to each of those stages. Doctors recruited 399 black men, supposedly infected with syphilis, to study the progress of the disease for the 40 following years. A control group of 201 healthy men was also studied to establish comparisons.

In 1947, penicillin had become the treatment of choice for syphilis. Before this finding, syphilis frequently led to a chronic, painful disease, and it eventually caused multiple organ failure. Instead of treating the subjects of the study with penicillin and concluding it or establishing a control group to study the drug, the scientists in charge of the Tuskegee experiment hid the information on penicillin from the subjects in order to continue studying how the disease spread and eventually led to death.

The study continued until 1972 when it was leaked to the press, thus bringing it to an end. By then, 28 of the 399 patients had died from syphilis and another 100 from related medical complications. In addition, 40 patients’ wives were infected and 19 children contracted the disease when being born.

The Tuskegee experiment led to the Belmont Report [9] of 1979 and the creation of the National Human Investigation Board, as well as the request for the creation of institutional review boards (IRBs).

17.2.3 Distrust of the Research Process

While most relevant to the Black community, any discussion about distrust of the research process should include the lasting after-effects of the Tuskegee syphilis experiments, arguably “the most infamous biomedical research study in US history” [18]. Note that these experiments ended only in 1972, when many of the patients diagnosed with cancer today were already adults. Such distrust is reinforced by a health system which is perceived to continue to discriminate against those of lower socioeconomic status [19]. Lack of knowledge and misconceptions about use of placebos also go hand-in-hand with distrust.

INFORMED CONSENT PROCEDURES

In general, informed consent procedures must be legally effective and sufficient to allow the potential subject to consider whether or not to participate and should minimize the possibility of coercion or undue influence. Information should be provided in understandable language, and there should be no exculpatory language that either waives or appears to waive the subject’s legal rights or releases or appears to release investigator, sponsor, or institution from liability of negligence. Failures to properly obtain informed consent are well known and have hurt the ability to get some populations in society to participate, for example, the deliberate infection of children in the Willowbrook experiments or the distrust the African-American community has in light of the Tuskegee syphilis experiment. Several excellent websites provide detailed reviews of major cases in the history of research ethics (see Table 13.8).

TABLE 13.8. Websites of interest for good clinical practice and research ethics

Sources: Adapted from Center for Drug Evaluation and Research, FDA Time Line: Chronology of Drug Regulation in the United States (www.cder.gov); Milestones of FDA History (www.fda.gov/oc/history); International Conference on Harmonization (www.ich.org).

To ensure adequate informed consent, patients should know and understand the reasons for the treatment and their participation and the benefits, risks, and alternatives to participation. But there are no guarantees in attempts to meet these standards. Modern medical interventions are complicated and highly technical. As such, the onus is on the investigator to ensure adherence to this standard. The necessary elements of an informed consent form are listed in Table 13.5 and involve elements of information, comprehension, and volunteerism. In neuroemergencies the ability to obtained informed consent from the patient is typically compromised by their disease, making it important to ensure that a legally authorized representative is appropriately consulted (11–17).

TABLE 13.5. Elements of the informed consent form

Source: Code of Federal Regulations, 45 CFR 46.116. See also, 21 CFR 50.25.

Informed consent is documented by the use of a written consent form preapproved by the IRB and signed by the person obtaining the consent and the subject or the subject’s legally authorized representative after ample opportunity is provided to read and understand content. A copy of the informed consent form is given to the person signing the form on behalf of the subject. If information regarding the study, its conduct, and associated risks and benefits are provided orally, a short form written consent document can be used, stating that the elements of informed consent required by 45 CFR 46.116 have been presented orally to the subject or the subject’s legally authorized representative. An independent witness is required when this method is used to obtain consent. The independent witness must be someone with no direct involvement with the study. If a written summary of the information provided orally is provided, only the short consent form itself is to be signed by the subject or the representative. The witness signs both the short consent form and a copy of the summary, and the person actually obtaining consent also signs a copy of the summary. A copy of the summary is given to the subject or the representative, in addition to a copy of the short consent form.

“Vulnerable” populations have been an explicit consideration in the regulations and guidelines surrounding the informed consent process. Children, prisoners, pregnant women, mentally disabled persons, and economically or educational disadvantaged persons are considered vulnerable populations. In general, neuroemergency populations should also be considered vulnerable, especially during the acute period of their disease. Often, for a considerable time during the lengthy recovery characteristic of neuroemergencies, the patient remains vulnerable (16,17).

2.1 Recognition of Need

The practice of research on humans is, of course, long standing. Even a quick review of medical history reveals countless examples of this. However, the formal idea and regulation of “human subjects research” is recent and was, like many such reforms, generated by a controversy. Serious ethical issues arising from the Tuskegee syphilis experiments in 1972 caused a moral outrage [1–3]. Congress was moved to act and in 1974 passed the National Research Act, which established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. From 1974 to 1978, the commission issued several reports related to biomedical and behavioral research with human subjects, culminating in 1979 with their final, formal report known as the Belmont Report, named after the conference room in which they met [4]. The Belmont Report summarized the basic ethical principles and corresponding guidelines that the commission recognized for the conduct of human experimentation. Principles and codes addressing the conduct of human subject research have existed in various forms and have been followed by a variety of organizations since the mid 1940s, but the Belmont Report has arguably had the greatest effect on human subject research protections in the United States.

The Belmont Report’s ethical principles and guidelines address key areas of concern following the aforementioned Tuskegee syphilis study. Officially known as the Tuskegee Study of Untreated Syphilis in the Negro Male, the study was sponsored by the United States Public Health Service and was conducted between 1932 and 1972. As the title suggests, the study aimed to follow the progression of untreated syphilis in the human body with a target study population of black males. Subjects infected with syphilis, and some who were not infected, were recruited into the study with the promise of medical care, free food, and burial insurance. The subjects were not informed of the true nature of the procedures to which they agreed and were told only that they were being treated for “bad blood” [1–3]. The researchers deliberately withheld penicillin and other treatments that were developed during the course of the study from the subjects so they could monitor and document the progression of the disease. As both a direct and indirect consequence, subjects experienced psychological/cognitive distress, physical deficiencies, and even death. Further, the disease may well have been transmitted to sexual partners and children born to research participants.

The core principles and practices identified in the Belmont Report were central to the public outcry regarding the overall conduct of this research and the treatment of the research subjects: patient autonomy, lack of informed consent, the direct harm done to subjects due to withholding medical care, and the unequal/inequitable distribution of research risks on one segment of the population. The Belmont Report identified three key ethical principles for the practice of human subject research: respect for persons, beneficence, and justice. Emerging from these three principles were three guidelines for their implementation or actualization: informed consent, assessment of risk and benefit, and equitable sharing of the burdens and benefits of research [4,5].

Respect for persons specifically addresses patient autonomy and requires that, as autonomous beings, subjects should be afforded the right to be informed of the procedures being performed in the research in which they are asked to participate and that their participation be voluntary. The Belmont Report describes an autonomous human being as one capable of self-determination and consideration of a variety of choices based on information provided to them. The full application of this principle, through informed consent, involves the provision of all relevant information, the confirmation that this information is comprehended and understood, and the ensuring of voluntary participation, or not, based on the potential subject’s choice.

Just as the autonomy of each person is recognized, the commission also recognized the necessity of protections for persons with diminished autonomy. Individuals who are incapacitated, ill, mentally disabled, immature, or are otherwise vulnerable to undue influence or coercion may have diminished autonomy requiring special care when including them in research—known as “vulnerable populations.” This care involves ongoing evaluation of their awareness of the consequences of participation, assessment of the subjects’ voluntariness, and protections to prevent coercion. It is the responsibility of the researchers to ensure patient autonomy is preserved and potentially to remove a subject from research if this cannot be established.

Beneficence refers to the prospective risks and harms that a research subject may face by participating in a study with the prospective benefits that may arise from the research for either the subject or, more generally, society with the development of new knowledge. For the Belmont committee, it addressed the direct harm done to the subjects in the Tuskegee syphilis study. By withholding medical care, specifically penicillin, the participants in this study were denied care that otherwise would have been available to them were they not research subjects. Penicillin was established as the standard treatment for syphilis in 1947, approximately 15 years after the initiation of this study; however, the subjects were denied this treatment, and the study continued for another 25 years. For these subjects, participation was actually maleficent, which is contrary to the very precepts of the practice of medicine and the principle of beneficence. The Belmont Report extends this precept of medicine into human subject research with the two prongs of beneficence: 1) to do no harm to subjects; and 2) if harm/risk is unavoidable, to maximize benefit while minimizing possible harm. The report acknowledged that individual research subjects may not directly benefit from their participation, but their inclusion in the study must still be justifiable in consideration of the benefits to be gained and possible risks. An evaluation should be made of the ratio of potential risks to potential benefits. There is, of course, some tension between this and the principle implicit in respect for persons. Respect for persons and autonomy require that researchers do not treat subjects as “means” to an “end,” but the assessment of risks/harm against possible benefits implies some dimension of this, especially when there is no direct benefit for the subjects and the only benefits are advancement of knowledge. The practice of informed consent, however, is designed to mitigate this tension.

The principle of justice addresses the unequal distribution of the burdens and risks of participation in research on subject populations in general, as illustrated by the inequitable inclusion of only the black male population in the Tuskegee syphilis study. This principle seeks to address the fairness of the distribution of research risks and possible benefits and to prevent injustice. There is no question that the rural black male population was exploited and manipulated in this study. Similarly, prisoners, the poor, and institutionalized individuals have been exploited in various other research studies throughout the last 100 years. The Belmont Report breaks down the equal treatment of human research subjects using five prongs: (1) to each person an equal share; (2) to each person according to individual need; (3) to each person according to individual effort; (4) to each person according to societal contribution; and (5) to each person according to merit. By evaluating the subject population in this way, the burdens of research can be distributed in an equitable manner, with no single population being exploited to address a medical condition that affects all populations or even specific other populations, as may have been the case with testing of medicines for human immunodeficiency virus/acquired immune deficiency syndrome among African populations that probably would not have had access to such medicines even if proved effective.

The Rise of the Patient Autonomy Model of Care

Medical Ethics arose as a discipline in response to serious medical and scientific misconduct at the expense of patients and study subjects. Two events that were pivotal in the development of the discipline of medical ethics, and that gave impetus to placing respect for autonomy at the center of the patient–doctor relationship are the ‘God Committee’ in Seattle and the Tuskegee syphilis experiment.

The God committee was created after the development of the first dialysis machines, in the early 1960s. A group of laypeople was chosen to determine who would receive dialysis and thus live, and who would be denied this treatment and then die of end-stage renal failure (Jonsen, 2007). Many of the criteria they used have been judged as both discriminatory (for example, favoring married over single persons, church going over nonreligious) and utilitarian (for example, how many children would be left behind to be supported by the state). News of the criteria used by the committee to select who would receive this scarce treatment option provoked outrage among both ethicists and the general public (Jonsen, 2007).

The Tuskegee experiment was a longitudinal observational study of 399 Black men in Alabama infected with syphilis (2011b). They were observed as study subjects without treatment from 1932 to 1972. Effective treatment for syphilis was developed in 1947, but the study subjects were not told of their condition, and treatment was never offered. When the study was made public, one of the researchers defended the men's lack of treatment saying that,” The men's status did not warrant ethical debate. They were subjects, not patients; clinical material, not sick people” (2011a). The Belmont Commission was established in response to the outcry over the Tuskegee syphilis experiment. A group of researchers, philosophers, and theologians met over a 4 year period and in 1979 produced the Belmont Report (Ryan and Al, 1979). It established the Office for Human Research Protections and led to the development of Institutional Research Boards that would be established wherever human research is conducted within this country. The board also established principles, which it believed would be useful guidelines for determining whether a proposed study involving humans was ethical. These three principles were respect for persons, beneficence, and justice. The description of ‘respect for persons’ however was immediately equated with ‘respect for autonomy’ which is how this principle has since been understood:

Respect for persons incorporates at least two basic ethical convictions: first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection. The principle of respect for persons thus divides into two separate moral requirements: the requirement to acknowledge autonomy and the requirement to protect those with diminished autonomy.

An autonomous person is an individual capable of deliberation about personal goals and of acting under the direction of such deliberation. To respect autonomy is to give weight to autonomous persons' considered opinions and choices while refraining from obstructing their actions unless they are clearly detrimental to others. To show a lack of respect for an autonomous agent is to repudiate that person's considered judgments, to deny an individual the freedom to act on those considered judgments, or to withhold information necessary to make a considered judgment, when there are no compelling reasons to do so.

Ryan and Al, 1979

Given its nature as a response to serious ethical lapses, it is not surprising that ‘respect for autonomy’ became the central principle guiding the doctor–patient relationship. This ascendency continued with the publication of Beauchamp and Childress's Principles of Biomedical Ethics, beginning with its first edition in 1979. This text has been central to medical education and medical ethics (Beauchamp and Childress, 1979). Its four principles are based upon the three principles of the Belmont Report, but nonmaleficence is made a separate principle in this work, rather than being subsumed under the principle of beneficence as it is in the Belmont Report.

The focus of Principles of Biomedical Ethics is the four principles that they determined are most central to resolving biomedical questions and dilemmas; it is not the doctor–patient relationship. For this reason, Beauchamp and Childress do not explicitly describe the doctor–patient relationship wholly in terms of autonomy, but Robert Veatch does in The Patient-Physician Relation (Veatch, 1991). Here, the principle of respecting patient autonomy is translated into a guiding standard for conduct in the clinical encounter. Veatch's contract theory of the doctor–patient relation takes the autonomous selfhood of both the physician and the patient as the starting point for his description of the proper clinical relation:

If it is true that medical ethics involves the stances of lay people as well as health professionals, and that patients (or their surrogates) are often healthy enough to be substantially autonomous agents, then the patient–physician relation ought to be one in which both parties are active moral agents articulating their expectations of the interaction, their moral frameworks, and their moral commitments. The result should be a partnership grounded in a complex contractual relation of mutual promising and commitment.

Veatch, 1991

Furthermore, Veatch argues that the contract, or partnership, model is most compatible with modern medicine, in part because it can accommodate the increasingly common circumstance in which the patient and doctor are strangers to one another (Veatch, 1991).

Veatch defends the need for his model precisely in an aspect of the clinical encounter that others consider a problem of modern medicine that needs to be remedied, rather than accepted. Many see the lack of continuity and enduring relationships between doctors and patients as a problematic and unfortunate emerging norm in clinical settings. But Veatch argues that there are potential advantages to a ‘stranger–physician relationship,’ over one where patient and physician share a friendship or mutual knowledge of one another. One problem with the physician-as-friend model that is avoided by a more distant contract model is that the physician-as-friend may presume knowledge that is incorrect, or worse, try to speak for the patient based upon the closeness of the relationship. It is certainly true that once a physician has spoken for a patient, given the social power of the physician's voice, it is hard for a patient to regain her standing and correct the physician's conclusions. But it seems equally true that details not shared by the patient, because the relationship is too distant, also may produce decisions that do not reflect patient preferences.

Veatch breaks with Beauchamp and Childress in that he places respecting patient autonomy over the principle of beneficence in the medical setting. Whereas PBE regards the four principles as having equal value, so that only in an actual individual clinical case can one principle override another, Veatch places autonomy permanently over ‘producing good’ for the patient (Veatch, 1991). Furthermore, Veatch argues that maintenance and respect for physician autonomy is crucial in a well-functioning clinical encounter, and he believes that approaching the relation as a ‘contract’ offers the best way of respecting both parties.

The only problem Veatch identifies with a model based upon autonomy is its potentially excessively individualistic focus that may obscure the fact that physicians must sometimes choose to balance social justice concerns over the needs of an individual patient. Veatch writes that:

If a clinician has entered into a partnership with a patient in which he or she is constrained by a promise to protect that person's rights and welfare, it would appear that any pressure to have the clinician reduce expenditures is really a pressure to violate that promise.

Veatch, 1991

It is outside the scope of this work to fully review the debate regarding the physician role in the doctor–patient relationship when there is a conflict between what is best for the patient and what is cost-effective or financially responsible. Paul Ricoeur, however, places issues of social justice outside the center of the doctor–patient relation, but within the domain that physicians must consider in medical decision-making (Ricoeur, 2007). That is, although a physician's primary concern must be the patient at that moment, the physician must not lose sight of the larger community of patients, and some consideration must at times be given to preventing a harm to others, if treatment to one potentially leaves others without care. Although this is a relatively underdeveloped consideration in the developed world currently, it is becoming an important issue globally, and medical ethics will increasingly have to contend with this balancing of individual and community needs.

In Veatch's most recent book, Patient, Heal Thyself, he takes the more radical step of suggesting that the doctor–patient relationship should, in a sense, be a nonrelation. His argument has four parts.

OVERVIEW OF TRADITIONAL BIOETHICS

Key United States population -African American women

Historically African Americans have a well-earned mistrust of the medical community due to its long history of abuse, exploitation, and experimentation. Famous examples include the Tuskegee Syphilis Experiment, where the United States Public Health Service (USPHS) experimented on 600 Black or Negro male poor sharecroppers while wilfully pretending to provide them medical care for tertiary stage Syphilis.39,40 The USPHS justified the unethical experiment as necessary to advance medical procedures and therapies for the public good. The use of Negroes as test subjects was rationalized because they were stereotyped as sexually promiscuous, intellectually inferior, and unable to manage their economy and healthcare.39,40 Unfortunately, this mistrust remains and today still serves as an effective barrier to medical care that further contributes to the increased incidence of trichomoniasis and other diseases.

Structural racism manifests by generating and reinforcing institutional and public policies and practices that negatively affect African American women's health based solely on race. Examples of these predisposing African American women to negative health disparities such as higher STD rates include reduced access to healthcare facilities such as clinics, hospitals, and other health-related services due to racial segregation. Also significant is the historical lack of racial, ethnic, and gender diversity in senior-level hospital executive leadership, healthcare providers (nurses, doctors, physician assistants), and social workers. This lack of diversity in healthcare leadership and clinicians translates to a power differential where White healthcare professionals, mostly men, make critical policies and decisions for the Black female patients about access to patient advocacy, clinical treatment, management, and quality of care.41

Cultural and linguistic competence is defined as the collective of congruent behaviors, attitudes, and policies that come together in a system, agency, or among professionals that enables effective work in cross-cultural situations.35 Although progress has been made regarding diversity-related training, there is still no federally mandated national gold standard for cultural competence training that mandates standards, practices, attitudes, and policies among healthcare providers and leadership.35 The lack of a national standard severely impedes effective communication with Black and African American women, especially vulnerable and low SES.11,35,42 Black women deserve a safe place to receive preventative, routine, and critical healthcare services; however, recent socio-demographic studies have quantified and provided evidence-based research of their collective experiences of receiving inferior standards of care, being ignored, and mistreated by healthcare providers regardless of income, education level and SES.43,44

Although trichomoniasis is ubiquitous in all races and ethnicities, research has suggested that African American or Black women have a higher incidence of trichomoniasis than Caucasian (White), non-Black Hispanic, and Asian women. For example, a 2015 (CDC) report showed that 13% of African American women were affected compared with 1.8% of non-Hispanic white women. Surprisingly, middle-aged women of forty years and older have a greater risk of T. vaginalis infections.45,46

Studies found a higher incidence of trichomoniasis among African American women engaging in high-risk sexual behaviors. These behaviors include, but are not limited to, lower use of barrier prophylactics, multiple sex partners, concurrent relationships, and either used drugs or have intercourse with men who use drugs, including alcohol.47,48 Their findings are still congruent with other researchers who have found that trichomoniasis is endemic in Black women who are long-term drug users.

A US-based study demonstrated that trichomoniasis was more common in the subpopulation of African American women who have sex with women than African American women who have sex with women and men at a prevalence of 25.0% vs. 13.5%, and P= 0.04, respectively. These findings indicate that bisexual women are at a significantly higher risk due to having sex with men than women who only have sex with women.49

Summary

This article will examine whether courts should have the power to decide to withdraw life-sustaining treatment over the objection of surrogate decision-makers. In doing so, I consider the ways in which giving courts this power might be better for individual patients, but worse for family members and other stakeholders who must live on after the patient's death. I also examine some of the cultural and historical reasons that handing such power over to courts or other government agencies may be seen as unthinkable in the United States, namely, moral transgressions like the Tuskegee Syphilis Experiments, which have given the public significant reasons to be wary of government intervention in healthcare and life-or-death decisions. Drawing on the Charlie Gard and Alfie Evans cases, bioethical theory, political philosophy, and my experiences as a clinical ethicist, I conclude that courts should not have the power to withdraw life-sustaining treatment over surrogate objection in most cases because doing so creates significant chaos, fear, and distress in patients and their families, and that taking positive stances on end of life issues violates the principles of liberal democracy, under which intimate decisions about the unknown should be left to patients and their surrogates. Unless surrogates are preventing a patient who is very likely to be physically suffering or who wishes to die from doing so, giving courts such power is likely to create significant moral distress that could be avoided or solved by facilitating transparent communication.

Willingness to Participate

Eligibility and access barriers assume, to some extent, willingness of patients to participate in clinical trials. However, attitudes toward clinical trial participation vary from ‘generally favorable,’79 to the perception of ‘last resort.’80 Distrust of the US health care system might be a major factor influencing African American clinical trial participation.81,82 The Tuskegee Syphilis Experiment, an infamous clinical trial conducted between 1932 and 1972 by the US Public Health Service to study the natural progression of untreated syphilis in rural African American individuals in Alabama, might still resonate in the African American community.5,81,83 Indeed, in a small survey of African American patients with prostate cancer, a major concern cited for inclusion in prospective studies was the Tuskegee study aftermath.84 One study noted that 22% of non-Caucasian patients, most of whom were African American, believed that they had been treated in clinical trials without their knowledge, compared with 9% of Caucasian patients (P = .032),73 highlighting that distrust in the health care system remains prevalent. Lack of trust is also a major factor influencing prostate cancer treatment in African American patients.71 For example, in the North Carolina Prostate Cancer Outcomes study (this state has one of the broadest racial disparities for prostate cancer with mortality being almost 3-fold greater in African American vs. Caucasian patients), the mean Physician Trust Score was significantly lower for African American (86.1; n = 207) versus Caucasian (89.8; n = 348) participants.85 Updated findings of this study together with those from the North Carolina-Louisiana Prostate Cancer project noted that mistrust and racism were the most important cultural factors to negatively affect the satisfaction of African American men with health services.86

The importance of perceived benefit might also be a factor. In one study, a similar proportion of Caucasian and non-Caucasian patients, most of whom were African American, were interested in learning about clinical trials, but non-Caucasian patients more often required a >50% chance of benefitting before they would participate (64% of African American compared with 45% of Caucasian patients; P = .03).73