Identifying a Need for Greater Protection of Human Research Participants in Clinical Drug Trials
Jennifer Y. Thornhill
If you are planning to be a volunteer in a clinical drug trial, you want to be aware of all of the possible risks and benefits of participating. But what if study investigators fail to give you an accurate run-down of foreseeable consequences?
Kirsten Scheer Bauer believes that the study investigators of the clinical drug trial, Antihypertensive and Lipid Lowering to Prevent Heart Attack Trial (ALLHAT), failed to adequately inform her father, Scott Scheer, of all of the possible risks of participating in their study. The Office for Human Research Protections—a United States federal division that aims to protect volunteers in research conducted or supported by the U.S. Department of Health and Human Services—also found that the written materials ALLHAT provided to volunteers fell short of sufficiently addressing foreseeable study risks. Bauer says this failure, as well as other research oversights, ultimately cost her father his life.
Throughout her grieving, Bauer says she has remained hopeful that her father’s story will inspire greater oversight protection for human research subjects.
Nearly five years since her father’s death, Kirsten Scheer Bauer’s emotions remain raw. Her father, Dr. Scott Scheer, died unexpectedly at the age of 62. On the night of his death, Scheer had asked his wife to put his briefcase in the car—his plan was to head to work in the morning. Later in the evening of July 15, 2001, Scheer collapsed in his home from a pulmonary embolism (a blood-clot in his lung).
Scheer’s death is suspected to be linked to drug-induced lupus—a side-effect caused by long-term use of certain medications. Scheer’s blood-clotting may also have been a result of end-stage glomularnephritis (kidney failure), which he also acquired as a side-effect to medication. The causal medication in each of these cases was hydralazine, a drug Scheer had been taking for nearly three years, as a subject in the Canada-U.S. clinical drug trial, ALLHAT. ALLHAT involved nearly 42,000 subjects, enrolled at approximately 500 study sites. Scheer was one of about 30 subjects enrolled at the Lankenau Medical Research Center in Wynnewood, Pennsylvania.
“In life, my father wanted to make a contribution to science as a participant in a research study,” Bauer said in a recent presentation at a national ethics conference in Ottawa, Ontario, “I hope that his death prompts improvements in human research protection.”
The consent form Scheer signed on May 19, 1997—when he first agreed to be a participant in the cholesterol-lowering arm of ALLHAT—never mentioned hydralazine-induced lupus or kidney failure as possible risks. In fact, the five-page form never mentioned hydralazine at all.
Scheer’s consent form specified exactly four blood pressure medications—the purpose of the study was to test the performance of an older drug against that of three newer medications. To draw a comparison, study subjects were randomly and blindly assigned to take dosages of one of the four medications. Although the consent form indicated that “other drugs” may be used, the language was vague: “If necessary,” the form reads, “other drugs may be used in combination with my assigned study medicine, in order to lower my blood pressure to a satisfactory level.” The consent form neither names these “other drugs,” nor their potential risks.
“There were very little risks portrayed on the informed consent,” Bauer says, “very minimal and 
annoying things like having an upset stomach. The real risks were not represented.”
OHRP also found the risks included on ALLHAT’s informed consent documents to be lacking. Just over a month after her father’s death, Bauer contacted this division of the U.S. federal health department to voice concerns about her father’s case and the possibility that other study subjects may be unknowingly experiencing hydralazine-induced risks. Since ALLHAT had received federal funding, OHRP was in a position to investigate the drug trial.
In a letter from OHRP (and addressed to the President of Lankenau Medical Research Center), the Compliance Oversight Coordinator for OHRP writes, “OHRP finds that the informed consent documents . . . failed to adequately address . . . any reasonably foreseeable risks and discomforts to the subject.”
The happy times Bauer shares with her family—including her son, who is now two-years-old and can be seen in this photo playing with a train set—often serve as heartbreaking reminders that her father is no longer here to be a part of her happiness.
Photo credit: Kirsten Scheer Bauer
Kirsten Scheer Bauer says there were other oversights in her father’s case. Bauer says the medical investigator team failed to respond to her father’s medical symptoms, including the pin-prick skin rash her father had reported just weeks prior to his death. Instead, it was a physician Scheer had consulted on July 9, 2001, (outside of ALLHAT) who recognized the severity of Scheer’s physical warning signs. The physician recommended that Scheer stop taking hydralazine.
Bauer says after her father told the clinical research coordinator for ALLHAT that he would be discontinuing the hydralazine as per his doctor’s instructions, the coordinator proceeded to send study medication to Scheer via Federal Express, continuing to treat Scheer as an ALLHAT participant. Scheer died that same week.
According to the Lupus Foundation of America, Inc. web site, hydralazine (also called Apresoline) is one of the known drugs currently in use that may lead to drug-induced lupus.
Bauer’s story illustrates the need for increased protection of human research subjects.
Scheer’s family has taken civil action in this case, filing a wrongful death lawsuit in a Philadelphia state court. The suit names (among others) Lankenau hospital and the study investigators.
Other than civil action, there is little recourse for clinical drug trial subjects (or their family members) in instances when drug trials go wrong. For federally funded or conducted health research projects in the U.S., one may contact OHRP. This division has the authority to stop or demand corrective action.
Michael McDonald, the Maurice Young Chair of Applied Ethics at the University of British Columbia says there is no equivalent body to the OHRP in Canada.
Although there is no Canadian system of oversight to ensure consistent standards for human research protection, in a 2004 Royal College Outlook article, authors Ken Davey, Barbara McGillivray and Richard Carpentier point out for clinical trials of new drugs, medical devices, or natural health products, Health Canada requires a research ethics board approval. The authors also indicate “Health Canada has developed an inspection program for clinical trials.”
In a special issue of the Health Law Review, McDonald 
concludes that protection of human subjects is not an optional goal in health research. McDonald further concludes that achieving this goal requires persistence: “The challenge then is to adequately demonstrate to research subjects that ‘we’ (researchers, sponsors and regulators) are doing a good job of protecting their interests and rights. We have a long way to go in this country before we can truthfully say that we are doing this. Honest recognition that we have a problem of ethical legitimacy is the first essential step towards effectively remedying the situation.”
Kirsten Scheer Bauer has collected a stack of documents—the informed consent form that her father signed to drug trial subject is among these. While this paper trail has provided insights into her father’s death, it has done little to bring comfort to the Scheer family.
Photo credit: Kirsten Scheer Bauer
Shortly after her father’s death, Kirsten Scheer Bauer recalls her mother asking her which of her father’s personal possessions she would like to have.
“I choose a red, cozy sweater” says Bauer.
At the time, Bauer was five months pregnant with her first child—a baby girl and the first grandchild in the Scheer family. Throughout her pregnancy, Bauer says she wore the sweater as a tangible reminder of her father. When she had her son two years later, Bauer relied on her father’s sweater as a continued source of comfort.
“I remember one night I put the red sweater right in the crib with [my son],” Bauer says of a night she had been unable to soothe her restless baby boy, “he snuggled into it and I remember thinking how I wish [my father] were here.”
For more information:
Health Canada listing of national and international ethics resources (which includes a link to the Office for Human Research Protections)
National Council on Ethics in Human Research
National Council on Ethics in Human Research Newsletter
International Listing of Selected Human Research Ethics Norms, Organizations, & Resources
