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Mass Tort Update
PART III. ABUSES OF INFORMED CONSENT AND RESPONSES TO THE ABUSES
A. Abuses:
The atrocities committed by the Nazi doctors sentenced during the Nuremberg Trial, in the name of science, served as the modern starting point for the medical ethics dialogue on human experimentation. During World War II, doctors tortured and mutilated imprisoned individuals, often resulting in death. They submerged concentration camp inmates in freezing water to test how long these individuals could survive. Other subjects suffered mutilation at the hands of surgeons. These people were used merely as means to an end. The Nazi doctors justified their experimentation with the goal of advancing science. The Nuremberg Code was formulated as a response to the Doctors Trial. The code consisted of ten rules, or the ten commandments of ethical human research. The code established standards to use in evaluating the study s scientific value and purpose in eight of its rules. The remaining two rules focused on obtaining informed consent.
In the United States, violations of the Nuremberg Code occurred before, during, and after the Doctors Trial. The Public Health Service (PHS) ran the infamous Tuskegee Syphilis Study between 1932 and 1972. The study took place in rural Macon County, Alabama, a community of poor African-Americans. The study s goal was to observe and to categorize the natural history of syphilis in order to determine if the disease progressed differently in blacks and whites. The subjects were 399 black men with syphilis, and 201 control subjects. These men were never informed that they were part of a study, and therefore, they never consented to be in the study. In the 1940s, when penicillin became available, these men were not treated. In fact, the PHS went to great lengths to prevent the subjects from obtaining treatment. Although peer reviewed medical literature published parts of the study, there was never an objection from the medical community. Tuskegee openly violated the absolute requirement of informed consent in the Nuremberg Code. The study had a flawed ethical and scientific basis, which did not satisfy those requirements of the Code. The Tuskegee example made it clear that society cannot rely on those in positions of authority, specifically physicians, to act in the best interest of subjects.
The beneficence of physicians cannot be relied on in the research arena. The Tuskegee physicians/researchers exhibited no respect for the autonomy of their subjects, but rather used their professionalism to exploit subjects. Even after its exposure, some of these physicians continued to defend the study. These subjects lived in the poor, rural, segregated south, they were obedient to authority, and they were vulnerable. The study was their only access to health care therefore, even if the subjects consented to the study, their consent was not voluntary.
Events from the Jewish Chronic Disease Hospital in Brooklyn demonstrate how physicians/researchers often put research above the best interest of patients. At this hospital, physicians injected cancer cells into twenty-two elderly and debilitated patients without the patients knowledge or consent. The study s goal was to examine how quickly the patients could reject the cancer cells. Physicians performed these injections using an experimental protocol, to advance scientific knowledge, with no intention of treating the patients and the hospital approved the study.
Prisoners are another vulnerable class that has often been subject to experimentation. Consent obtained from prisoners is not voluntary and informed because these individuals are a captive population, eager to earn whatever money possible. The situation of confinement makes it impossible for prisoners to make a decision based on free will. The prisoners might receive special benefits for research participation that can ease their quality of life. They might feel obligated to participate, in which case the experiments erode their ability to exercise autonomy. The Department of Health and Human Services restricted experimentation on prisoners in 1978 under guidelines for Protection Pertaining to Biomedical and Behavioral Research Involving Prisoners as Subjects.
B. Case Law:
The case law pertinent to the violation of informed consent in experimentation consists of relatively few tort cases. In Burton v. Brooklyn Doctors Hospital, doctors treated a premature infant a high concentration of oxygen as part of a study to determine if lower concentrations of oxygen than normally given were sufficient to prevent brain damage while preserving the baby s eyesight. The doctors made no attempt to get informed consent from the baby s parents. The hospital running the experiment performed prior studies showing that high concentrations of oxygen given to premature infants caused blindness. The Appellate Division of the New York Supreme Court found that no medical reason existed for giving a child high oxygen, except for the random allocation process required by the study. The court also found that the physicians improperly failed to inform the parents of the risks, and held in favor of the plaintiff.
The medical profession argued that investigators guided by ethical concerns and the beneficence of physicians will guide researchers. Violations of that protection of patients, such as those in Burton, are not as rare as one might suppose. In 1966, Henry Beecher, a prominent anesthesiologist from Harvard, published a landmark article in the New England Journal of Medicine. In this article, Beecher outlined his concerns about the ethics of medical research. He detailed twenty-two studies that violated informed consent, using them as examples of how the push for evidence-based medicine increased ethically wrong behaviors in medical research. Prior to general application of new procedures, researchers experimenting with subjects are required to show the benefit of the new therapies. Beecher expressed concern that newly available sums of money for research, coming from hospitals and the National Institutes of Health, could increase the ethical and informed consent violations in human research. In discussing the issue of consent, Beecher pointed out that a patient will almost always consent to any request their physician makes. However, most patients will not agree to jeopardize [their] health or [their] life for the sake of science. To protect the patient/subject, Beecher suggested investigators always strive for fully informed consent, and clarify that the patient/subject is participating in an experiment. Beecher deemed the second safeguard the more reliable of the two, which would be the presence of an intelligent, informed, conscientious, compassionate, responsible investigator.
Beecher did well to identify the issues at such an early stage in the race for medical advancement. The funding for Medical Studies through federal programs, including the National Institutes of Health, increased dramatically since the publication of Beecher s article. Perhaps of greater concern is the current trend for research funding from private sources, such as medical device manufacturers and pharmaceutical companies, who are funding increasing amounts of research. Privately funded human research trials are often joint ventures with academic institutions or private physicians. This private research leads to increased pressures on physicians/researchers, who now must recruit subjects to fulfill their obligations to outside agencies. The financial stakes are increased as federal funding is becoming harder to obtain. To continue to remain academically productive, physicians/ researchers are driven to join forces with companies, whose goal is to promote a specific product. It is unlikely that the investigator remain independent and unbiased in the face of financial pressures. Even if the physicians/researchers could remain unbiased, treating physicians should never suggest that a patient participate in such a study. They could not fulfill the requirements for obtaining informed consent, even after disclosing their interests fully. Specifically, the physicians relationships with their patient would interfere with the patient/subject s ability to make a free and informed decision. These and other potential problems in informed consent and human experimentation led to federal legislation for regulating scientific investigation. The response to investigators breaches of ethics predominantly occurred through the federal legislature.
C. Responses:
The response to breaches in medical research ethics began with the Nuremberg Code, which formed the basis for much of the law on human research ethics and regulation. Eight of the rules in the Nuremberg Code addressed the ethics of a research project itself, and focused on the scientific validity and safety of the proposed investigation. These criteria were best determined by scientists who understand the study s science and the methodology. The two remaining rules focused on informed consent, and thereby empowered the subject by protecting human rights. No longer was the research subject at the mercy of the investigator because the researcher had the affirmative duty to make certain that the subject is truly informed. The investigator could not delegate this responsibility with impunity. Rule number one addressed the requirements of informed consent, and Rule number nine required that the subject have the right to terminate the experiment. For the first time, these rules suggested that the research subject should be empowered with respect to participation in studies, and no longer rely solely on the ethics of researchers. The Nuremberg Code made the requirement of informed consent inviolate. There was no balancing of personal autonomy with the benefit of scientific research to society as a whole, and there were no exceptions to the prerequisite of informed consent. Based on the evidence in the Doctors Trial, it was clear to the world that society could not rely on the ethics of researchers, particularly physicians, to protect the best interest of human research subjects. The authors of the Code gave research subjects the power to consent after full disclosure and to terminate the research at will.
The World Medical Association (WMA) introduced the Declaration of Helsinki in 1964. In the introduction, the WMA defines the acceptable purposes of human research as the improvement of diagnostic, therapeutic and prophylactic procedures and the understanding of the etiology and pathogenesis of disease. The Declaration of Helsinki makes a distinction between therapeutic and non-therapeutic research. The requirement of informed consent is explored in Basic Principle #9 of the Declaration of Helsinki. Basic Principle #10 applies specifically when the subject is in a dependent relationship with the investigator. If the Declaration of Helsinki is applied, the voluntariness of the patient/subject s consent is lost. In such a situation, the patient s consent is invalid until an independent physician, not engaged in the investigation, obtains the patient s informed consent.
Unfortunately, Part II of the Declaration of Helsinki, dealing with clinical research, erodes the right of autonomy of the subject in therapeutic research. In research, the risks and benefits to be gained by experimental treatment are to be weighed against the risks and benefits of applying the standard treatment. In other words, every patient should receive the best-proven treatment, even the control group. In Basic Principle #5, the requirement of obtaining informed consent may be waived entirely if the physician considers it essential not to obtain informed consent. Often referred to as the therapeutic privilege, this concept is usually used in the context of medical treatment. Unfortunately, by permitting the physician to get around consent in research, the Declaration endorses a standard of informed consent that falls below the common law standard for consent to treatment.
Under the common law concept of therapeutic privilege, if the treating physician believes, in the specific circumstances of the particular patient, that informing the patient of the risks will be harmful, the physician need not obtain consent. Under the privilege, the process of obtaining informed consent must cause harm to the patient, not the patient s refusal to consent. The privilege will not apply when the patient rejects an intervention suggested by the physician. If the interpretation of therapeutic privilege is that broad, the exception would swallow the rule, and the requirement of informed consent in treatment could always give way to the beneficence of physicians. In research, however, there is no known benefit to withholding informed consent from the subject, and therefore, the concept of therapeutic privilege is not valid. Instead, if the process of obtaining consent may injure the patient, then the subject should not be recruited for research.
The recent October 2000 revision of the Declaration of Helsinki removes this exception. Under the revised Declaration, the investigator, in potentially therapeutic experiments, can no longer decide for the subject whether consent is necessary. The revised Declaration further requires that separation of treatment and research should be made clear to the patient, although it describes no method to effectuate this requirement. The current revision also strengthens and clarifies the stance that placebo arms, or control groups receiving no treatment, are not ethical, unless no alternate accepted treatment exists. All patients must receive the best, known treatment and receive full disclosure of all the physician s relevant financial interests. In the remainder of the Declaration of Helsinki, the WMA delineates the ethics of the research itself.
To rely solely on the physician / investigator s beneficence and ethics in research would violate the Nuremberg Code. The distinction between research and treatment fundamentally concerns the unknown. While research involves interventions with unknown outcomes, the outcomes in medical research, as defined by the Belmont Report, are already accepted and known. Whether the research is therapeutic or purely non-therapeutic, the benefit is unknown. Therefore, the requirement of maintaining a subject s autonomy is fundamental, and informed consent should be a requirement.
Research, in contrast to treatment, is further described as a rigid protocol for the advancement of knowledge and the potential benefit of society at large. The protocol is not varied based on the individual needs of subjects. This protocol is in contrast to treatment, where the intervention is tailored to the individual patient s best interest. If the initial action proves unbeneficial for the individual, then the physician reassesses the treatment and changes course. In this manner, the best interest of the patient directs the suggested treatment. For research, particularly protocol-driven research, the individual is treated as part of a larger group. The assignment of subjects to protocols is not directed by the subjects best interest. The research protocol cannot be altered even if another course might be better. The constraints of research are consequently much more rigid than those of treatment.
This distinction between research and treatment is not always clear. Nancy King suggests, in Hastings Center Report, that this distinction should be dropped and the standard for informed consent should be the same in both categories. King s solution involves a meaningful discussion between the patient/subject and the physician/investigator. However, her analysis fails to consider the intent-based distinction between research and treatment. In The Regulation of Human Experimentation in the United States-A Personal Odyssey, Jay Katz also voices concern that the research-treatment distinction may allow investigators to label interventions as treatment, when they are, in fact, experimental. I submit that the difference between research and standard treatment is not difficult in most instances. Medical malpractice is based on the physician s deviation from the standard practice. Juries make this distinction on a regular basis, thus, it would seem plausible that we could make the same differentiation between research and treatment prospectively. Therapeutic experimentation, however, is an oxymoron because treatment and experimentation are distinct. Experimental interventions cannot be treatment until they become standard practice, and then, by definition, are no longer experimental.
Physicians who participate in clinical trials run by industry are well aware that these are experiments and not proven therapies; that is the reason for the study. The exception to the rule is the study physician acting alone, who tries a novel treatment for a particular ailment with no other intentions but to cure the patient. The ethical guidelines of the American Medical Association (AMA) stipulate that research on human subjects must be organized and protocol driven, so that valid scientific results can be obtained. Novel treatments by individual physicians would fail this test. These new treatments are not research; furthermore, the ethics and legal standing of a particular novel treatment depends on the particular treatment s acceptance in the medical community, and the adequacy of informed consent. Unfortunately, the implementation of novel treatments without further research may lead to ineffective treatments becoming accepted practice. The later sections of this paper will discuss the importance of the physician/researcher s intent and its relationship to the inviolate nature of informed consent in research.
D. Federal Regulation:
The government produced little regulation on research ethics until 1962. Until this time, the responsibility for the regulation of research and ethics rested on research institutions and investigators. This standard was analogous to the professional standard of disclosure, in informed consent for treatment, prevalent at that time. The beneficence of physicians was assumed to carry over into the realm of research. Society continued to rely on the professionalism of physicians to protect the autonomy, health, and well-being of the individual subjects of human research. The multiple infamous transgressions of individual autonomy in the name of research had yet to move the federal government to action. Interestingly, beginning in the 1940s, the Department of Defense and the Atomic Energy Commission devoted time and effort to discussing the ethics of experimentation. The Armed Forces Medical Policy Council, in 1952, adopted ethical principles from the Nuremberg Code as guidelines for research into atomic, biologic, and chemical warfare.
The debate over regulation of research grew as the press disclosed blatant violations of research ethics to the public. The first step in regulating research was in 1953 with the opening of the National Institutes of Health s (NIH) Clinical Center. The NIH set up loose guidelines for subject consent, but these rules only applied to research performed in the Clinical Center and not to outside research funded by NIH. The restrictions were very limited, and applied solely to research with an unusual hazard. The consent requirement only applied to volunteer subjects, who had no possibility of benefiting from the research. Therefore, the regulations did not apply to patients. In 1962, the FDA began regulating clinical drug investigations, requiring proof of therapeutic efficacy in addition to the safety of the study. The FDA relied upon the constitutional power of the Commerce Clause to regulate all such investigations, regardless of the funding source. The FDA s regulations applied to new drugs and to investigational devices.
In 1966, the NIH, under the Public Health Service, issued a statement requiring prospective review of all proposed research funded by the Department of Health Education and Welfare. Congress codified these rules into federal regulations, with the most recent significant revision in 2005. These regulations, often referred to as the Common Rule, required institutional review boards to prospectively evaluate proposed human research. The role of these institutional review boards (IRBs) is to decentralize the control of research project oversight. Idealistically, IRBs exist to protect the subject s rights and autonomy. Practically, IRBs members are primarily from the institution performing the research. The regulatory requirement is that IRBs have, at minimum, five members but only one member must be from outside the parent institution.
The federal regulations applied only to research funded, or specifically regulated, by federal agencies. This restriction contradicted the FDA regulatory scheme, which applied more broadly, but applied only to investigational drugs and devices. In all other respects, the rules applied by the FDA are essentially the same as those applied to federally funded research. The section of the federal regulations on informed consent does not define this term nor does it delineate the process of obtaining consent. Instead, the federal regulation lists eight general elements of informed consent and outlines a method of documentation for it once obtained.
Section 46.117 also lists exceptions to the requirement of informed consent. Under this section, the requirements of informed consent may be waived if certain requirements are met, including if the research poses only minimal risk. The potential subjects do not decide if the risk is minimal, the decision is made for them. In fact, subjects never have the opportunity to evaluate the risk s magnitude in deciding whether or not to participate in experimentation. This fact usurps the autonomy of the subjects, thereby violating the absolute requirement of informed consent in the Nuremberg Code. The exceptions to the requirement of informed consent in the Common Rule are set forth in 45 C.F.R. § 46.116, part d, and are as follows:
These exceptions put the decision of what information to disclose in the hands of the investigators or the reviewing IRBs. These rules subsume the individual s free choice in the name of science.
The members of the IRB are almost all members of the institution applying for federal funding. Thus, do the regulations put Dracula in charge of the blood bank ? This utilitarian approach to the advancement of science and medical treatment restricts the fundamental rights of bodily integrity and autonomy. Such balancing of benefits does not occur unless the opposing interest is a compelling state interest. The advancement of science and the acquisition of knowledge are not compelling state interests because they do not remediate immediate harms. To balance all possible benefits to society against the rights of individuals, exceptions can always be found for obtaining informed consent. The advancement of science does not override individual autonomy; therefore, there should be no balancing of a societal benefit against the risk to the individual.
The federal regulation serves to protect the institutions conducting the research, perhaps even more so than the subjects. The IRBs are not required to supervise consent, nor are there any guidelines for the process of obtaining consent. The regulation is very vague in its description of informed consent. The circumstances of obtaining informed consent are required to give the subject sufficient opportunity to consider whether or not to assent, and to minimize the possibility of coercion and undue influence. The regulation provides no clarification of what this process entails, nor are there guidelines for IRBs in evaluating compliance. The requirement of understanding for informed consent is not adequately addressed in the current federal regulation. The concept of voluntariness required for informed consent is given even less consideration in the Common Rule. Only the very general guidelines given above address that consent must be voluntary.
The current system of insuring the protection of research subjects is inadequate. IRBs play only a cursory role in reviewing studies. The definition of minimal risk is vague and relies on the IRB s definition, and not on national reviews or standards. The IRBs role in reviewing the scientific value of the study perhaps is adequate, but that will not be discussed in this paper. The ability of an IRB to sufficiently protect the patient s autonomy does not exist in the current system. A recent study shows that some IRBs only spend one or two minutes reviewing each study. Most IRBs in the U.S. consist primarily of scientists; therefore, the reviewing institutional body is similarly situated to the scientists/physicians who plan to conduct the study. The process of review can thus be equated to the early common law of informed consent in treatment. The early rule was the physician (professional) rule of disclosure, based on what the reasonable physician would disclose to their patient. As outlined above, the reasonable patient standard now replaces the professional standard with regard to disclosure.
The courts applied and ethicists suggested an analogous standard to use in research, or the reasonable subject standard of disclosure. This rule is not followed with IRBs. In other countries IRBs, or their equivalent, are made up of a much larger percentage of community members. For example, in the Dutch system, half of the IRB consists of non-scientist community members. Australia has a similar system, requiring a broader representation of laypersons on their review boards than in the U.S. The Department of Health and Human Services, Office of Inspector General suggested a large percentage of the IRBs should consist of laypersons from the community. The larger number of community members makes the board better able to assess what information the reasonable subject would require in order to make an informed decision regarding whether to participate in a study or not. The criticism of these community IRBs is that the members cannot understand the science or the value of the research. This criticism, in a nutshell, exemplifies the problem with the current system and the prevalent attitude in the scientific community. If the potential subject cannot at some level understand the science, as well as the risks and benefits of the study, voluntary informed consent would be impossible to obtain. However, the subject s understanding should not be viewed as an obstacle to scientific and medical progress, but as an integral part of human subject research. Understanding is necessary to maintain individual autonomy and the integrity of the medical and scientific communities.
The criticism that the lay public may accept scientific studies with unacceptable scientific validity would make community review boards (CRBs) inadequate. That criticism presents a very different argument from an assertion that CRBs cannot understand the science enough to evaluate the adequacy of disclosure. By setting up a dual review system, the government would solve the valid concern that unacceptable science may pass by the CRBs. The first review would be by a scientific review board, not unlike our current IRBs. They would evaluate the merit of the study on scientific grounds. If the study passed this first review, only then would it go on to review by the CRB consisting of primarily laypersons. To be valid, the laypersons should be the same make-up as the potential subjects of the experiment. The layperson CRB would determine the adequacy of disclosure and the process of consent.
Unfortunately, the increased funding available from governmental and private sources makes it more difficult for IRBs to adequately evaluate studies. IRBs are over burdened, and their current membership is inadequate to represent the interests of patients. Changes in the membership of the boards, and the addition of supervision of the process of informed consent should be instituted.
In 1995, President Clinton created the National Bioethics Advisory Commission, which released a draft report in December of 2000. The report detailed inadequacies in the federal oversight of human subject research and recommended major changes. At publication, the current administration of President George W. Bush and Congress has not yet acted on this report. The recommended changes included (among others):
Congress should create an independent office to oversee human research. Currently the Office for Human Research Protection (OHRP) is under the Department of Health and Human Services.
At minimum half of the members of IRBs must be from outside the institution. At minimum half are to be non-scientists.
All research should be covered, not only federally funded research.
University review boards should supervise the informed consent process under certain situations.
In the National Bioethics Advisory Commission s (NBAC) draft policy they extensively outlined the history and reasoning for revamping the current federal scheme of research regulation. However, the piecemeal current system is failing in many respects.
Much of the newly proposed regulation is based on the principles set forth in the Belmont Report. The National Research Act of 1974, established the National Commission for the Protection of Human Subjects of Biomedical and Behavior Research (National Commission). The National Commission presented the Belmont Report to Congress in 1978 and published it in 1979. The major thrust of this report identified three basic ethical principles and applied these principles to research. These rules are: 1) respect for persons, 2) beneficence, and 3) justice. Respect for persons is the underlying ethical principle behind informed consent. Beneficence is translated into a risk verses benefit analysis for the subject. Justice was initially only applied to the selection of participants. A broader use of justice in experimentation now applies to those who will benefit from the research project, in relation to those who take the risk. This balance is particularly relevant in international studies, where the drug studied may not be available to the population who participates in the investigation.
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