Medical researchers must learn from past mistakes
Changes in the air as trust in medical research falls
Early medical researchers were an ethical bunch, possibly because they had little choice. Many conducted experiments and tests on themselves (including one who snaked a catheter through his arm and into his heart, then climbed two flights of stairs to take an X-ray to prove a person could survive cardiac catheterization), because the researchers couldn’t bring themselves to do untested procedures on others.
"There was great attention to minimization of risk" to trial subjects, according to Jeremy Sugarman, MD, MPH, MA, deputy director of the Berman Bioethics Institute at Johns Hopkins University.
Today, many research programs find themselves fighting the notion that researchers are driven by financial motives, are puppets for pharma companies, or are willing to risk subjects to achieve the results they hope for.
Past violations of humane care still recalled
Nazi doctors who conducted torturous experiments on concentration camp prisoners "crossed all boundaries of civilized conduct." Western physicians adopted the Nuremberg code in 1947 as a direct result of the trials of those doctors after World War II, spelling out what was ethical conduct for carrying out medical research — obtain voluntary consent, benefits must outweigh risks, do animal experiments first, avoid suffering, protect subjects from harm. But at the same time, the U.S. Public Health Service, in trying to learn more about syphilis and justify treatment programs for blacks, withheld adequate treatment from a group of poor black men who had the disease.
The so-called "Tuskegee syphilis study" went on for 40 years, and by the time it reached widespread public knowledge, hundreds of men and their families had suffered the effects of untreated syphilis in exchange for meager funeral benefits. A class-action lawsuit filed by the National Association for the Advancement of Colored People (NAACP) in the 1970s ended in a settlement that gave more than $9 million to the study participants, and in 1997 President Bill Clinton apologized for the study on behalf of the country.
"Tuskegee violated almost every principle of the Nuremberg code," notes A. Cornelius Baker, a Washington, DC-based health policy consultant who has specialized in public policy regarding people with AIDS. "Think of the irony. [The syphilis study was going on] just after the revelation of the Nazi atrocities."
The Tuskegee study was not alone in shaping negative public opinion of clinical studies. In the Jewish Chronic Disease Hospital cancer experiments, live human cancer cells were injected into 22 chronically ill, debilitated non-cancer patients in 1963 without their consent to learn if foreign cancer cells would live longer in debilitated non-cancer patients than in patients debilitated by cancer. Severely retarded children at the Willowbrook State Hospital in New York were injected with hepatitis virus in the 1960s, with researchers going so far as to block admission to patients whose parents did not consent to the experiment. And in April 1999, research projects at the Veteran’s Administration West Los Angeles Medical Center were shut down after an investigation showed that not only was research being done on patients who had not given informed consent, but on patients who had expressly refused consent.
Sugarman says the "three pillars of protection" for study subjects — and for the credibility of studies themselves — are the investigators and sponsors, informed consent, and oversight.
Investigators and sponsors must ensure protection of the participants and credible results through scientific design of studies, responsible conduct of the research, and clear definition of the responsibilities of the researchers and sponsors.
The process and design of informed consent involves determining that a subject can give consent and is doing so voluntarily, and understands clearly what he or she is consenting to. The need for oversight is evident when looking at recent scandals in research programs that did not meet standards and that Sugarman says could have been avoided with independent, prospective review.
"The key to successful oversight often involves an independent group review," Sugarman suggests. "Attention to the ethics of research is essential to respecting those who choose to participate."
Conflict of interest was not a topic that received much public examination until 1999, when an Arizona teenager, Jesse Gelsinger, died within days of receiving an injection that was part of a gene therapy trial he had consented to. His death received national attention, which only grew as his father became more and more aware of the financial ties that pervaded the research sponsors and the researchers.
By 2001, 11 of the major medical journals in the United States had imposed requirements that contributors divulge all potential conflicts of interest, and in 2004, the Department of Health and Human Services issued its "Final Guidance Document — Financial Relationships and Interests in Research Involving Human Subjects: Guidance for Human Subject Protection" (available at www.hhs.gov/ohrp/humansubjects/finreltn/fguid.pdf).
"Ethics is pretty easy, really," Sugarman says. "If it doesn’t sound right, don’t do it."
Sources/Resources
- A. Cornelius Baker, community health advocate, Washington, DC. Phone: (202) 234-3661.
- Jeremy Sugarman, MD, MPH, MA, deputy director, Berman Bioethics Institute, Johns Hopkins University, Baltimore, MD. E-mail: [email protected].
- U.S. Department of Health and Human Services, Office for Human Research Protections (OHRP). On-line at www.hhs.gov/ohrp.
- Centers for Disease Control and Prevention, Atlanta, GA. "The Tuskegee Syphilis Study: A Hard Lesson Learned." Available at www.cdc.gov/nchstp/od/tuskegee/time.htm.
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