Medical research has long held an exalted position in our modern society. It has been acclaimed for its significant achievements that range from the development of the Salk and Sabin vaccines for polio to the development of artificial organs. In order to determine their effectiveness and value, however, these new drugs and medical devices eventually are used on humans. The issue is, therefore, not only whether humans should be involved in clinical studies designed to benefit themselves or their fellow humans but also clarifying or defining more precisely the conditions under which such studies are to be permitted.

For example, consider the case of a 50-year-old female patient suffering from severe coronary artery disease. What guidelines should be followed in the process of experimenting with new drugs or devices that may or may not help her? Should only those procedures viewed as potentially beneficial to her be tried? Should experimental diagnostic procedures or equipment be tested on this patient to evaluate their effectiveness when compared to more accepted techniques, even though they will not be directly beneficial to the patient?

On the other hand, consider the situation of conducting research on the human fetus. This type of research is possible as a result of the legalization of abortion in the United States, as well as the technological advances that have made fetal studies more practical than in the past. Under what conditions should medical research be conducted on these subjects? Should potentially hazardous drugs be given to women planning to have abortions to determine the effect of these drugs on the fetus? Should the fetus, once aborted, be used in any experimental studies? Although these questions are difficult to answer, clinical researchers responsible for the well-being of their patients must face the moral issues involved in testing new equipment and procedures and at the same time safeguard the individual rights of their patients.

Case Study: Neonatal Intensive Care Unit (NICU)

Throughout time, low birth weight, oftentimes arising from premature birth, has been a major factor affecting infant survival. Underweight infants, who are typically classified as either low birth weight (LBW) (less than 1,500 g) or very low birth weight (VLBW) (less than 1,000 g), must be treated with the utmost caution and care in order to maximize their chances of survival. Advances in premature-infant medical care, such as improved thermoregulation and ventilation techniques, have greatly decreased the mortality rate among LBW and VLBW infants. Included in these advances was the creation of the NICU (Figure 2.2), where all the necessary equipment needed to sustain the life of the child could be kept conveniently in close proximity to one another.

One of the most important devices used in the NICU is the incubator. This device, typically molded of see-through plastic, is used to stabilize the body temperature of the infant. In essence, the incubator allows the medical staff to keep the new born warm without having to wrap it in

                                                  FIGURE 2.2 A Neonatal Intensive Care Unit.

blankets. The incubator also aids in preventing infection, as well as in stabilizing the humidity of the child’s environment. By keeping the temperature and humidity levels of the new-born’s environment static, the baby remains well hydrated and water loss is kept to a minimum.

A complication that many preterm infants suffer from is the inability to breathe normally on their own. The child may be completely unable to breathe for himself, or he may suffer from a condition known as apnea, where the breathing pattern is either aperiodic or irregular.

In these cases, children susceptible to an apneic event are closely monitored so if they stop breathing, nurses can rush to the bedside and wake them up. However, it is often minutes before the nurse can arrive at the scene. To facilitate the process of waking the infant experiencing an apnoeic event, biomedical engineers developed a tactile vibrator that when triggered by such an event vibrates against the infant’s foot and wakes her. In order to prove that the device is effective and safe, a human experiment must be initiated. In this case, the following questions need to be resolved:

1. Who is responsible for proposing the conduction of this study?

2. What should the process of approval of such a study include?

3. What should the policy be related to informed consent?

4. Should changes that were made in the device during the course of the study, which would alter the nature of the initially proposed device, be allowed?

Definition and Purpose of Experimentation

One may ask, what exactly constitutes a human experiment? Although experimental protocols may vary, it is generally accepted that human experimentation occurs whenever the clinical situation of the individual is consciously manipulated to gather information regarding the capability of drugs and devices. In the past, experiments involving human subjects have been classified as either therapeutic or nontherapeutic. A therapeutic experiment is one that may have direct benefit for the patient, while the goal of nontherapeutic research is to provide additional knowledge without direct benefit to the person. The central difference is a matter of intent or aim rather than results. Throughout medical history, there have been numerous examples of therapeutic research projects. The use of nonconventional radiotherapy to inhibit the progress of a malignant cancer, of pacemakers to provide the necessary electrical stimulation for proper heart function, or of artificial kidneys to mimic nature’s function and remove poisons from the blood were all, at one time, considered novel approaches that might have some value for the patient. In the process, they were tried and found not only to be beneficial for the individual patient but also for humankind. Nontherapeutic research has been another important vehicle for medical progress. Experiments designed to study the impact of infection from the hepatitis virus or the malarial parasite or the procedures involved in cardiac catheterization have had significant impacts on the advancement of medical science and the ultimate development of appropriate medical procedures for the benefit of all humans. In the mid-1970s, the National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research offered the terms practice and research to replace the conventional therapeutic and nontherapeutic distinction just mentioned. Quoting the commission, Alexander Capron in 1986 wrote the following:

The term practice refers to interventions that are designed solely to enhance the well-being of an individual patient or client and that have a reasonable expectation of success. In the medical sphere, practices usually involve diagnosis, preventive treatment, or therapy; in the social sphere, practices include governmental programs such as transfer payments, education, and the like.

By contrast, the term research designates an activity designed to test a hypothesis, to permit conclusions to be drawn, and thereby to develop or contribute to generalizable knowledge (expressed, for example, in theories, principles, or statements of relationships). In the polar cases, then, practice uses a proven technique in an attempt to benefit one or more individuals, while research studies a technique in an attempt to increase knowledge.

Although the practice/research dichotomy has the advantage of not implying that therapeutic activities are the only clinical procedures intended to benefit patients, it is also based on intent rather than outcome. Interventions are “practices” when they are proven techniques intended to benefit the patient, while interventions aimed at increasing generalizable knowledge constitute research. What about those interventions that do not fit into either category?

CASE STUDY: THE ARTIFICIAL HEART

In the early 1980s, a screening committee had been set up to pick the first candidate for the “Jarvik 7,” a new (at the time) artificial heart (Figure 2.3). It was decided that the first recipient had to be someone so sick that death was imminent. It was thought unethical to pick someone who might have another year to live when the artificial heart might well kill the patient immediately.

         FIGURE 2.3 The Jarvik-7 artificial heart, 1985.

1. Is this an example of nonvalidated practice?

2. Is informed consent still required?

A week after the operation, Barney Clark began having seizures from head to toe. Suffering a seizure, Clark’s unconscious body quivered for several hours. The seizures and spells of mental confusion continued throughout the next months. As a result, Clark expressed a desire to die. Although he did issue a positive statement during a videotaped interview, Clark was not a happy man, tethered to a huge machine, barely conscious, and in some pain. In March 1983, Barney Clark died of multiple organ collapse.

3. Discuss in detail the notions of “criteria for success” and quality of life in this case.

4. Barney Clark suffered a great deal. In response to this, who should be the responsible party in deciding what is right for the patient? When both sides hope for positive results, is it possible to make an unbiased decision based on what’s best for the patient?

One such intervention is “nonvalidated practice,” which may encompass prevention as well as diagnosed therapy. The primary purpose of the use of a nonvalidated practice is to benefit the patient while emphasizing that it has not been shown to be safe and efficacious. For humans to be subjected to nonvalidated practice, they must be properly informed and give their consent.