Ethical Considerations In RCTs With Diabetic Patients
At the conferring of medical degrees, physicians take the Hippocratic Oath, in which they make a covenant to practice medicine to the best of their abilities. As the oath states, “I will apply, for the benefit of the sick, all measures (that) are required.” The physician has a duty to promote the patient’s best medical interests and therefore is obliged to advise the patient to receive the treatment that the physician prefers.
Although the driving force behind clinical research is the betterment of patient care, there is a substantial risk that physicians take by encouraging their patients to enroll in clinical trials. It becomes an even greater risk when the physician is also the researcher.
The aforementioned duty is what can create a barrier to the enrollment of patients in randomized clinical trials (RCTs). On one hand, patients may receive treatment they would otherwise not have access to getting. On the other hand, they may be randomized into the placebo group, which may or may not stall their medical therapy for weeks, even months. Although the Food and Drug Administration and Institutional Review Boards have many committees and regulatory procedures in place to ensure the protection of patient rights, there is still a moral dilemma that arises when a patient is randomized into the placebo group.
Assessing Our Obligations To Patients
When enrolling patients in clinical trials, physicians have two obligations to patients.1 The first obligation is to recommend the treatment that is, in the physician’s professional judgment, the best choice for the patient. With clinical trials, the placebo or the standard of care is what the medical community believes to be the “superior” treatment. Although the active treatment group may also seem superior, these judgments are tentative and have no real substantial evidentiary basis.
In current clinical research evaluating products for diabetic foot wounds, saline gauze or hydrogel is commonly used as the control even though many other products have been proven by well designed trials to be more effective.
Herein lies the physician’s dilemma: Is the fact that we are using a known inferior product as the placebo considered unethical?
In this example, however, these trials do offer an advantage to the placebo groups. Due to frequent return clinic visits, frequent debridement of the wounds occurs and this has been documented to increase the rate of wound healing.2 Although patients are receiving a product that is not the most optimal for the wound, the patient is still receiving focused care, which he or she may not be receiving otherwise if the patient was not involved in the trial.
The second obligation to patients is to obtain the patient’s informed consent. This is perhaps the saving grace for physicians involved in clinical research. Respect for a patient’s values is the core purpose behind the informed consent. The informed consent entails explicit explanation of: the goals of research; potential risks and benefits; reasonable alternatives to the recommended treatment; and the right to withdraw from the trial at any time.3 It is the responsibility of the researcher to educate the patients objectively and make them understand that involvement in the research may or may not be of personal therapeutic benefit.
Ultimately, the impetus should be in the patients’ hands. Patients themselves may place a greater value on participation in a study, which will contribute to medical progress and to the well being of patients in the future.
Evaluating The Potential Risks Of Clinical Trials To Patients With Diabetes
In patients with diabetes, as with any other immunocompromised patients, the risks of delayed wound healing increase threefold. More particularly with wound care, studies have documented an increased risk of infection, hospitalization and amputation directly proportional to the length of time a wound remains open.4 Wounds may or may not respond to certain therapies, and therefore have a higher chance of developing an infection.
One may ask: Is this a risk worth taking? Does one just abandon the efforts of clinical trials? Should randomized clinical trials be abandoned and should intermediate level evidence suffice? How can progress occur if there is no sound clinical evidence to support new therapies?
The involvement of patients with diabetes or any patients in clinical trials poses many risks, including physical and economic risks.5 Although many products being tested on diabetic wounds go through initial safety testing and are released on the human market only if they are found to have minimal associated risks, every patient will react differently to different products. With the new developing therapies, there are chances of discomfort or inconvenience.
Also, many studies have an initial screening period that may last anywhere from one to four weeks. During this time, no treatment occurs. This in many cases prolongs the time in which patients receive care. However, if one considers the chronicity of the wound or condition, this may just be a trivial amount of time.
Additionally, not all research studies offer patients financial support and thereby cause the patient to incur financial obligations. Typically, research studies require patients to have frequent clinic visits, which then require the patient to take time off from work and pay for transportation.
Many wound care studies require offloading, which limits the amount a patient can work and may even necessitate time off work. However, research trials do give the underinsured and/or economically disadvantaged patients the opportunity to have therapies they may otherwise not have access to or afford.
The dual role that a physician and researcher assumes when agreeing to participate in such trials can be problematic and risky. A conflict of interest may occur because the goal of carrying out important and valid research might conflict with the goal of acting in the best interests of the individual patient. While physicians have a duty to their individual patient, one can argue that physician researchers have a duty to a larger demographic of patients who may benefit from advances in medical knowledge.
It is important to ensure the protection of potentially vulnerable populations such as patients with diabetes or the economically disadvantaged, who may feel compelled to enroll in such studies due to a lack of options. Objective guidance from their physician can help patients make a decision but patients should feel comfortable with the decision they make and the position in which they are putting themselves. While the physician researcher has multiple interests, the primary interest should always be the patient and his or her best interests.
Dr. Siddiqui is a Diabetic Limb Salvage Fellow in the Department of Plastic Surgery at Georgetown University Hospital in Washington, D.C.
1. Marquis D. How to resolve an ethical dilemma concerning randomized clinical trials. N Engl J Med 1999; 341(9):691-693.
2. Sheehan P, Jones P, Caselli A, Giurini JM, Veyes A. Percent chance in wound area of diabetic foot ulcers over a 4-week period is a robust predictor of complete healing in a 12 week prospective trial. Diabetes Care. 2003; 26(6):1879-82.
3. Passamani E. Clinical trials – are they ethical? N Engl J Med 1991; 324(22):1589-1592.
4. Cardinal M, Eisenbud DE, Armstrong DG, Zelen C, Driver V, Attinger CE, Phillips T, Harding K. Serial surgical debridement: A retrospective study on clinical outcomes in chronic lower extremity wounds. Wound Rep Regen. 2009; 17(3):306-311.
5. Coleman CH, Menikoff JA, Goldner JA, Dubler NN. The ethics and regulation of research with human subjects. Newark, NJ: LexisNexis, 2005.