Analysis:

Ultimately, I agree with Miller et al. that the moral principles which govern clinical medical practice should not be confused with the moral principles which should govern clinical medical research. While the Principles of Non-Maleficence [1], Clinical Equipoise [2], and Beneficence [3] ought to be strictly observed within the context of clinical practice, the differences in purposes, methodology, and costs of clinical practice compared to clinical research make it clear that they are not the same and should not be treated as such. But I am also sympathetic, at least in part, to Freedman et al. in that there is still room for significant improvement. As a result, I seek to argue for a kind of middle ground in this particular debate.

My only objection to the Principle of Clinical Equipoise, in general, is that the terms “scientific” and “clinical” that denote the specific kind of merits for which physician-investigators look when justifying the utility of clinical research is too narrow. At least one other category, socio-economic, should be added to the principle. To justify this claim, a realistic hypothetical scenario can provide an instance in which the Principle of Equipoise is actually detrimental to patients and society as a whole and should thus be applied on a case by case basis.

Imagine a situation in which there is but one prescription drug for a certain medical condition. Regarding this medical condition, it is extremely common, painful though not terminal, and is found among the entire population of a particular nation. Regarding the prescription drug used to combat this medical condition, it has taken a large team of pharmacists, doctors, and scientists years of research to develop, has cost billions of dollars to produce, and, because of the complex and complicated process by which the drug is produced, is only affordable for those patients who have vastly superior health care coverage.

Furthermore, the majority of the population suffers from living in conditions of abject poverty and, as a result, does not have access to the superior health care coverage necessary to afford the prescription drug. Many people suffer unnecessarily and the detrimental effects for the people, as well as the society in which they live, multiply exponentially over time. 

Moreover, the use and efficacy of this prescription drug to treat that medical condition has been thoroughly praised and documented throughout the contemporary medical and scientific literature. As a result, testing a new prescription drug against the original would constitute an impermissible waste of the latter. The overall cost of conducting such competitive or comparative research between the two could not be justified from an economic perspective.

Here is a situation which, arguably, would violate the Principle of Equipoise. Since the original prescription drug has been shown to be extremely effective and there is little to no disagreement among experts in the field of medicine, there seems to be no reason for more research to take place. But perhaps there is another type of merit in such medical research, aside from being either scientific or clinical. Perhaps by conducting such research, the investigators can discern whether a newly released prescription drug similar in chemical nature to the original but with the same physiological effects can be utilized, especially if this alternative is produced through a less expensive process, thereby reducing the price of and increasing the availability of the drug for those poorer people who did not have the means to pay for it but who needed it nonetheless. As a result, the Principle of Equipoise seems to be a relative, rather than an absolute, concept whose application depends on the greater context in which it is set. Moreover, there are other grounds, besides merely scientific or clinical merit that can justify the use of human test subjects in randomized controlled trials.

Yet the assumption upon which the Principle of Clinical Equipoise is based, that continued research on an already understood topic or proven treatment or medicine is wasteful or unnecessary, is dubious. If the study of evolutionary biology, and specifically epidemiology, has shown us anything, it is that newer, less understood organisms are regularly appearing on life’s horizon. Take, for example, certain detrimental bacteria. There have been several documented cases in which bacteria have become completely resistant to antibiotic treatments. Some of these cases have developed rather rapidly. As a result, it would seem foolhardy to assert that just because there is one or two or even 43 treatment options for a particular medical condition, that there needs to be no further research. Those treatment options could, potentially, become obsolete or ineffective in a short matter of time or could only be effective for certain demographics from its origins. Thus, continual research into a topic is almost always justified, regardless of the availability of existing treatment.

Connotative Expectations

Next, there is a semantic peculiarity that continues to aggravate the debate. The relevant part of this problem comes from the terminology of “physician-investigators” and “patient-subjects” (Miller, 111). While it is more truthful to state that the physicians who conduct medical research are both physicians and investigators, this seems to create some confusion about the role he or she is expected to play within the context of randomized controlled trials. Should they focus more on healing or investigating? What is the appropriate balance? Similarly, the term “patient-subject” implies that the person who has volunteered for a particular randomized controlled trial expects to or should benefit (or at least not get worse) from some sort of treatment given by the physician-investigator in question.

But because the ultimate goal of randomized controlled trials is not to provide treatment to patients, but to generate and refine contemporary medical knowledge, the term “physician” and the labeling of human volunteers as “patients” should be entirely eliminated. Those investigators who engage in randomized controlled trials, for at least as long as the trials are being conducted, should not be considered doctors or physicians since they are, first and foremost, researchers and scientists. Similarly, those subjects who engage in the same should not be considered patients since they are, for at least as long as the trials are being conducted, first and foremost, volunteers and/or test subjects. Since the roles are different, the titles or terms utilized should be too. This, in turn, will help eliminate further confusion and encourage the acceptance of Miller et al.’s ethical paradigm for clinical research.

Commiseration via Monetary Compensation

Finally, if physicians are worried about the potentially unjustifiable risks to benefits ratio within clinical research, one possible solution is to offer human participants monetary compensation for their time and (potential) suffering, if no positive consequences result from the experimental treatment. Put another way, if a subject’s health does not improve after receiving treatment during clinical research or, conversely, if a subject is moderately to greatly harmed from receiving treatment, then a subject should be awarded monetary compensation from the responsible party (parties). Two main criteria would determine the warrant and amount for such compensation: pain and time (intensity and duration).

For one, subjects should be compensated for the amount of time for which they volunteer. Depending on the duration of the clinical research in question, these subjects could miss work, family engagements, jury duty, and, perhaps, actual medical appointments. As a result, if the experimental treatment they receive does not ameliorate their condition, they should be compensated monetarily since they have given up time that they could have used on something else, for results that never materialized.

Next, subjects should be compensated for the pain they suffer as a result of the experiment’s design in clinical research. The measurement of this pain would include quantitative, qualitative, and temporal dimensions. Quantitatively, pain would be measured by the number of body parts or areas of the body in which pain occurred. For example, if a subject suffered from pain in his heart, toes, and shoulder, as opposed to just his shoulder, he would receive more monetary compensation. Qualitatively, pain would be measured by location; the more vital the body part, the higher the compensation. For example, a bruised shin that resulted from clinical research would not receive as much compensation as a collapsed lung. In addition, pain would be measured by intensity; the stronger or sharper the pain, the higher the compensation. Temporally, pain would be measured by its duration; the longer the pain persists, the higher the compensation.

In Sum…

So long as the previously enumerated conditions for clinical research, as listed by Miller et al., are met and so long as the subject is informed about and consents to the process (reserving the right to stop participating at any time), that provides sufficient basis for utilizing the compensation system developed here. This system would not only offset the risks to benefits ratio, but also it would also allow (and justify) further exploration via clinical research. Potentially controversial treatments and health conditions could be carefully monitored yet explored nonetheless, greatly expanding the knowledge base of medicine and improving medical care universally.

NOTES:

[1]: “Nonmaleficence means non-harming or inflicting the least harm possible to reach a beneficial outcome.” https://www.medscape.com/viewarticle/811079_5

[2]: “Clinical equipoise is an important concept concerning the state of knowledge about a particular research topic (67). In essence, it demands that true ambivalence toward the efficacy of a novel therapy exists among researchers. It serves as a minimum requirement to justify the investigation of a hypothesis, because any therapy believed by consensus to be efficacious should not be denied research subjects based on the principle of beneficence, whereas a therapeutic investigation considered harmful to subjects would violate the principle of nonmaleficence.” https://www.sciencedirect.com/topics/medicine-and-dentistry/clinical-equipoise

[3]: “[T]he principle of beneficence is understood as an abstract norm that includes derivative rules such as “Do no harm,” “Balance benefits against risks,” and “Maximize possible benefits and minimize possible harms.” This principle is satisfied in the research context by intentionally refraining from causing injury and by assuring that risks stand in reasonable relation to probable benefits. As one major demand of beneficence, the National Commission required that during the course of the ethical review of research protocols there be arrayals of data pertaining to benefits and risks and of alternative ways of obtaining the benefits (if any) sought in the research. It also demanded that systematic and nonarbitrary presentations of risks and benefits be made to subjects, as part of the informed consent process, and that assessments of risks and safeguards be considered by ethics committees when they evaluate whether research protocols are justified.
The National Commission demanded that, to fulfill obligations of beneficence, research subjects not be asked or allowed to consent to more risk than is warranted by anticipated benefits and that forms of risk incommensurate with participants’ previous experience not be imposed in the case of groups such as children.” https://plato.stanford.edu/entries/principle-beneficence/#BeneBiomEthi 

Tagged: compensation, Health, health care, Human Subjects, Medical Ethics, medical testing, Medicine, Principle of Clinical Equipoise, Principle of Therapeutic Beneficence, Principle of Therapeutic Nonmaleficence, quality, quantity