Did company go too far in subject recruitment?
Overnight stays blur boundaries, experts say
Subject recruitment is one of the more ethically troubling issues raised by the recent case in which a judge ordered that a teenager receive an investigational drug from PTC Therapeutics of South Plainfield, NJ.
The family of the 16-year-old muscular dystrophy patient, Jacob Gunvalson of Gonvick, MN, told Judge William J. Martini of the United States District Court in Newark, NJ, that they had a special relationship with PTC Therapeutics. Gunvalson's mother said that company officials had assured her early on that her son could take part in the PTC124 phase IIa trial.1
One reason why she felt this way was because a PTC Therapeutics' official had invited the Gunvalson family to stay in their home overnight, a practice that apparently wasn't unusual during the recruitment process. The judge appeared to sympathize with the Gunvalsons' claim that they had a relationship with PTC Therapeutics that went above and beyond the typical sponsor-subject relationship.1
PTC Therapeutics CEO Stuart Peltz acknowledges in an Aug. 20 media statement that company staff formed a close relationship with the Gunvalsons, as they did with other potential clinical trial participants.
"We believe the court may not have appreciated that PTC is a small, start-up company doing pioneering work to develop treatments for rare forms of muscular dystrophy and similar diseases," Peltz says.
"In contrast to big pharmaceutical concerns, it is quite natural for our team to form close relationships with patients and other members of the rare disease community," he adds. "In fact, on the very night Mrs. Gunvalson and her son were staying at the home of a PTC employee, another patient's parent was staying with her as well."
Peltz says the company has received awards from patient advocacy groups for these efforts.
Raise the red flags
This practice is very problematic from an ethical perspective, experts say.
"An IRB wouldn't have approved having patients stay at sponsor's homes," says Stephanie J. Zafonte, MSN, RN, CCRP, CQA, RAC, director of operations at George Washington University, biostatistic center, in Rockville, MD. Zafonte previously was the senior extramural regulatory analyst with the office of clinical research at the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) in Bethesda, MD.
"That's completely unethical, and the company should be held accountable for choices, whether they're forced to give the drug to the boy or not," Zafonte says. This could be seen as coercive during a recruitment process, he adds.
"It's an interesting recruitment process to invite someone into the home of the sponsor," says LaDale K. George, JD, a health care attorney with Foley & Lardner in Chicago, IL.
"I'd like to understand the rationale for intimate relationships with a patient because it appears to present a situation that could be interpreted, as in this case, as somewhat coercive and promising more than exclusion/inclusion criteria would entail," George says.
Mark S. Schreiner, MD, an associate professor of anesthesia in pediatrics at the University of Pennsylvania, says, "I think the sponsor should not have a personal relationship with subjects. At our hospital we had a similar experience with a company developing a drug for a rare condition. Someone high up in the company had two children with the condition. They wanted the children to receive the drug."
The children would have been the only subjects in the study. This case never even got so far as the IRB because the research institution felt that it was a conflict of interest and there wouldn't have been equitable selection, so the request wasn't approved, he adds.
The ethical way for clinical trials to recruit subjects is to have the process be objective and impersonal, the experts say.
"If you're a patient and you're seeking to obtain access to the clinical trial, there is a mechanism for doing that," George says. "You can identify where the investigator is located and then attempt to go through the investigator to gain access to the trial, or you can contact the company and the sponsor's process is to direct you to the investigator."
Any contact between the sponsor and the patient beyond the formal process could lead to misinterpretation of motive on the part of the sponsor or patient, he adds.
"This is where the subjects, as it appears to be the case here, believe they were entitled to some level of preference beyond what inclusion/exclusion criteria is mandated," George says. "And it appears to give the illusion of recruitment efforts beyond what an IRB has the responsibility for approving."
When the sponsor provided housing to the patient, it deviated from standard practice.
"Usually you arrange housing through the clinical trial site," Schreiner says. "The investigator is the one who has the relationship with the subject, not the sponsor."
There are some rare diseases in which parents and interest groups work with sponsoring companies directly, and these relationships might have some blurred lines, Schreiner notes.
"But I think that impacts the ability of the subjects to make a risk-benefit decision," he adds. "The prospective participants may be unduly influenced into taking part in a risky trial for altruistic reasons."
Blurred relationship lines can lead to research participants failing to understand that the investigational drug might not work at all and that the participant might not even receive the actual drug, but could be on the placebo arm.
"These families are in desperate situations," says Merit E. Cudkowicz, MD, an associate professor of neurology at Harvard Medical School and Massachusetts General Hospital in Charlestown, MA.
"These are horrible illnesses, and especially if it's your son whose sick you want to do everything you can."
Sponsors and investigators who do not follow ethical standards when interacting with potential research participants run the risk of bad outcomes, such as what has happened with the PTC124 court case.
"It appears that the behavior of the sponsor was misleading to the patient and their family," George says. "And if more appropriate boundaries were maintained then the family's impression of what they were being offered by the therapeutics company likely would have been very different."
Reference
- Grynbaum MM. Judge orders drug maker to provide experimental treatment to terminally ill teenager. NY Times. Aug. 21, 2008.
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