Are human research subjects safe enough? - Ethical Aspects

Physician Executive, July-August, 2003 by Richard E. Thompson

Medical science owes much to countless contributions of committed and competent clinical investigators.

But only those willing to trample human rights resist reasonable restrictions on risks to which human research subjects are exposed.

Imagine a world where randomized clinical trials and double-blind studies using human subjects are not linchpin parts of medical research. Applications of new knowledge and technology would be haphazard and dangerous. We would never learn whether good results and bad are due to new treatments or extraneous factors.

Penicillin, paxil, patent medicines and magic potions would be on drugstore shelves alongside ginseng and St. John's wort. U.S. Food and Drug Administration controls and prescriptions would be meaningless. Why bother?

How would we know what to approve and prescribe and what not to? The daring act of consulting a physician would be even more dangerous than it already is.

Safety concerns

Human research must continue. But important popularized and politicized questions about safety of human research subjects must be answered.

In one poll, 83 percent of Americans agree that new drugs should be tested in humans but only 24 percent are very confident that patients in clinical trials are not treated as guinea pigs. (1)

There is nothing new about failing to safeguard the safety of human research subjects. In fact, teachers of 21st century principles-based neo-ethics use some classic examples to illustrate the age-old conflict between utilitarian concern for the common good, the concepts of human rights and personal autonomy, and virtues such as justice, fairness and truthfulness.

For example:

* During World War II, Nazi physicians experimented on concentration camp inmates. As a medical student, I watched a magnificent fluoroscopic study of the swallowing mechanism. As an aside, we were told that this excellent teaching tool was confiscated from the Nazis, that the fluoroscopy time far exceeded well-known safe limits for exposure to X-rays and that the subject undoubtedly died of throat or thyroid cancer within a few years.

* In Georgia in 1932, U.S. researchers began the now infamous Tuskegee syphilis study to better understand the long-term course of untreated syphilis. They enrolled 400 black men and 200 controls, most poorly educated, and did not inform the study subjects of available treatments. The study continued until 1972. In early years of the study, available treatments (arsenic and bismuth) were not very effective. But penicillin was discovered in 1940 and found to cure syphilis. This knowledge was withheld from the study group.

* In the 1970s, in the Danish Obesity Project, clinical researchers wanted to compare the effects of jejunoileal bypass with medical treatment of morbid obesity. Some patients in the medical treatment group were told that surgery was not an option because liver biopsy findings showed fatty infiltration. That was not true.

Horror stories

Exploitation of human research subjects is more common now than in previous times, or else better exposed. Either way, the number of contemporary horror stories is unacceptable. Two recent publicly exposed cases blew this issue wide open.

In 1999 at the University of Pennsylvania, a 19-year-old patient with OTC (ornithine transcarbamylase) deficiency died during a trial of gene therapy. The vector adenovirus used to deliver the therapeutic gene into the patient's bloodstream may have attacked his liver, causing the fulminate hepatitis and accompanying complications that led to his death.

In 2001 at Johns Hopkins, a researcher wanted to understand why some people respond to inhaled irritants by developing asthma and some don't. He enlisted healthy volunteers to inhale a chemical irritant, hexamethonium. One of the volunteers, a technician at the Johns Hopkins Asthma and Allergy Center, died. Allegedly, researchers meant well but failed to adequately research the toxic properties of hexamethonium.

Sometimes a medical scientist hot on the trail of a breakthrough discovery can become a zealot. Nothing must stand in his or her way. Nothing. Colleagues believe that is what happened to the principal investigator in a study approved by the University of Oklahoma that was stopped in 2000 after a nurse reported abuse of human subjects.

The greatest danger to human subjects is today's definition of legitimate research. Clinical investigators may be financially tied to a company not interested in testing a theory, but rather in marketing products.

In Nebraska in 1998, for $460, college students ingested the active ingredient of a popular insecticide spray. The purpose was to defuse accusations that the chemical is harmful to humans. No one was hurt. But studies in which investigators are paid to reach a dictated conclusion are not research. Rather, they are _____. Actually, we need a new term for what they are because such studies are definitely not clinical research.

Efforts to protect human research subjects began in 1946 when the Nuremberg Code was Written as a guideline for the Nuremberg Military Tribunal that tried Nazi leaders accused of war crimes. (2) Subsequent efforts (3,4) built on this beginning.