Prior to performing procedures, administering medications, or enrolling patients into clinical trials, physicians and other health care providers are required (both legally and ethically) to obtain “informed consent” from their patients. The concept of “informed consent” may have different meanings depending on the specific medical-legal situation under discussion. Generally speaking, factors such as a patient’s decision making capacity, understanding, voluntariness, and access to full disclosure of the procedure/treatment’s risks and benefits are assessed before obtaining an informed consent (Vaughn 2013). In performing clinical trials the concept of informed consent becomes important, not only from the patient authorization standpoint, but from the regulatory perspective as well.
Institutional Review Boards (IRBs) are responsible for making sure that research protocols adhere to certain basic ethical considerations. One of these considerations involves the type of incentives that a patient can receive for participating in a research trial. These incentives may become problematic when recruiting subjects who have limited resources. Do IRBs or other regulatory bodies provide adequate oversight to assure that the incentives offered by a clinical trial do not influence a patient’s ability to provide “un-constrained” informed consent? Here I examine two different cases and argue that study-sponsored incentives may potentially interfere and influence a resource-poor patient’s ability to provide informed consent. In addition, I will look at the arguments that may be used to support research in resource-poor settings.
Let us examine the following two cases:
CASE1: Ms. A is a 45-year-old female with poorly-controlled rheumatoid arthritis. She is currently uninsured, and is being followed in a county hospital clinic. She is unable to maintain gainful employment because of her disease, and often has difficulty paying for basic day-to-day living essentials such as food and electricity. Dr. Z, her rheumatologist, has been treating her with the Disease Modifying Anti-Rheumatic Drugs (DMARDs) available on the hospital formulary. Ms. A’s disease has proven to be recalcitrant to the medications that are available on the formulary. Ms. A does not have the ability to pay for the next level of therapeutic DMARDs. The county hospital is unable to provide Ms. A with the charity care needed to purchase any new medications, and there are no pharmaceutical company patient assistance programs available. Dr. Z is involved in a phase three clinical trial investigating RAX, a new DMARD, and offers Ms. A. enrollment. The new medication has many serious potential side effects. If she consents to be part of the clinical trial, Ms. A will receive $30 per clinical visit, transportation expenses, and administration of the study drug. After providing informed consent, Ms. A is enrolled into the clinical trial.
CASE2: Ms. B is a 45-year-old female with poorly controlled rheumatoid arthritis. She is currently employed and receives generous insurance and health benefits through her employer. She is seen in the faculty practice of a university hospital. Ms. B’s disease has been progressing despite the use of many “first-line” DMARDs. Her rheumatologist, Dr. Z offers her different treatment options including the ability to switch to a different class of DMARD that the insurance company will cover or enroll in the same phase three clinical trial that was offered to Ms. A. Ms. B will receive the same incentives as Ms. A if she decides to enroll. After contemplating her options, Ms. B. provides informed consent and is enrolled in the clinical trial.
In their essay, “The Concept of Informed Consent”, Faden and Beuchamp introduce two types of informed consent, sense₁ (also known as autonomous authorization) and sense₂. Sense₁ (also known as institutional authorization) consent is defined as when a “…patient or subject with substantial understanding and in the absence of control by others intentionally authorizes a professional…” to complete an intervention. Sense₂ consent refers to the “legal” requirements that must be fulfilled before informed consent is recognized. Let us assume that both Ms. A and Ms. B have completed all of the necessary paperwork that is required by the local hospital, the pharmaceutical company sponsoring the trial, and the state and federal authorities. In other words, sense₂ consent has been obtained from both women. Has Dr. Z obtained sense₁ consent from both women? Can Dr. Z ever truly obtain sense₁ consent from both women?
As stated earlier, one of the requisites for informed consent is that the individual provides voluntary authorization before enrolling in clinical research. Did Ms. A truly provide voluntary consent? There is no evidence that Dr. Z coerced her into the study. Although it was not mentioned in the cases, the clinical trial protocols have been examined by the county hospital’s and university’s IRBs. The $30 per visit stipend and parking expenses were seen as being consistent with other similar studies. Does Ms. A really have other options? We know that she is unemployed and has difficulty paying for basic living expenses. The county hospital has no available resources left to pay for Ms. A’s escalated therapy. Patient assistance programs that are often provided by pharmaceutical companies are not available in this case. Ms. A appears to have few remaining options. The study would provide her with a new DMARD that could help her debilitating disease, as well as a source of needed income.
However, if we contrast Ms. A’s case to that of Ms. B’s, we can see important distinctions. Ms. B does not necessarily need the resources of the clinical trial to escalate her therapy or to provide her with monetary incentives. She has the insurance coverage needed to obtain alternative medications as well as steady employment that provides her with a comfortable living. We could say that Ms. B has meaningful options. She does not have to rely on the clinical trial for improvement of her health and well-being. Ms. B seems to enter the clinical trial on a truly voluntary basis, while Ms. A, given her circumstances, seems to have few other options. When we look at Faden and Beuchamp’s definitions of sense₁ and sense₂ consent, it appears that both Ms. A and Ms. B satisfy the technical requirements for informed consent, while only Ms. B is able to give true “un-constrained” consent.
Unfortunately, the example of Ms. A is a story that is all too familiar to health care providers. At times, patients must make difficult decisions as they try to balance the needs of housing, feeding and caring for themselves and their families while maintaining their own health. Do health care providers and biomedical researchers have a moral obligation to identify and understand their patients’ socio-economic status prior to enrolling them into clinical trials?
I argue that researchers do have this obligation to their patients. For patients like Ms. A, clinical trials may provide them with another means of obtaining medications that they may not otherwise be able to obtain. Many of these medications, however, are experimental and do not have adequate safety data. In addition, if the studies are placebo controlled, there is no guarantee that a researcher’s patient will receive the study medication, as the patient may be randomized into the control group. In performing clinical trials in resource-poor settings, researchers should be aware of the barriers that their patients face in maintaining their health and well-being. Only then can they be assured that their patients are providing voluntary, “un-constrained” informed consent.
Some would argue that resource-poor patients may not need any more stringent requirements in providing sense₁ consent than those patients who are relatively resource-wealthy. One argument mentioned earlier in the essay, deals with the opportunity for resource-poor patients to obtain needed medications that they would not be able to obtain through other means. Proponents of this argument may claim that these patients should be admitted into clinical trials (with standard sense₁ consent) precisely because these patients are resource-poor and would not be able to have access to potentially useful medications without the clinical trial infrastructure. Another potential argument against more rigorous sense₁ requirements centers on the concept of paternalism. There is no shortage of examples of paternalism throughout the history of American (or world) medicine. Efforts have been made to recognize and eliminate paternalistic behavior among physicians and health care providers, and to have patients act as “shared decision makers” in their management and treatment of their disease. Those who take an “anti-paternalistic” approach to offering clinical trials to resource-poor patients may claim that those researchers that hesitate to enroll these patients are imposing their views on their patients and are not allowing them to fully participate in decisions involving their care.
The arguments against a more stringent view of informed consent are reasonable. It would be difficult to dispute the fact that many resource-poor patients who have been enrolled in clinical trials have received effective and innovative treatment for their disease. In addition, we cannot ignore the potential financial gains from which a resource-poor area may benefit by participating in clinical trials. These financial gains may theoretically be reinvested back into the research and health care infrastructure, and may allow these resource-poor facilities to treat future patients. In addition, the critique of paternalism is reasonable. Does this mean that these arguments overshadow the fact that patients, such as, Ms. A may not have any other alternatives but to enroll in clinical trials? When one has no other options, is she/he truly giving “voluntary” consent? Is there truly, as Faden and Beuchamp state, “absence of control by others”? Additionally, clinical researchers and health care professionals have the obligation to act in the best interests of their patients. This includes protecting patients from unproven therapies or interventions.
Clinical trials research has the potential to introduce novel therapeutic and technological innovations not only to patients, but to the biomedical community as a whole. It is important that the healthcare providers and administrators who are involved in these clinical trials be sensitive to the fact that the patients that they recruit may be doing so out of necessity rather than by choice. Ms. A clearly lacked the options that were available to Ms. B. Both are able to provide traditional sense₁ and sense₂ consent, but it is only Ms. B who is able to give “un-constrained” consent. The research community must be cognizant of these differences in consent and continue to strive to protect vulnerable populations, including the resource-poor. It is imperative that researchers consider their patients resources prior to obtaining consent. If research groups are unable to verify the “un-constrained” consent of their potential subjects, then, perhaps, these patients should not be considered for enrollment into clinical trials.
Beauchamp, Tom L. “Informed Consent: Its history, meaning, and present challenges.” Cambridge Quarterly of Healthcare Ethics no. 20 (2011): 515-23.
Faden, Ruth and Tom Beauchamp. A History and Theory of Informed Consent. New York: Oxford University Press, 1986.
Vaughn, Lewis. Bioethics: Principles, Issues and Cases. New York: Oxford University Press, 2013.