Ethics stifling research? Some Britons say 'yes'

Delays in American trials over bad science

Some researchers in the UK have renewed debate over the limits placed on medical research by ethics regulations, saying ethical red tape is "stifling" advances in medicine. But ethicists in the United States say the argument is nothing new and that the review process for clinical trials protects both human subjects and research.

Clinical researchers at Britain's Leeds University wrote in the August issue of British Medical Journal that oppressive paperwork, restrictions barring approaching subjects who haven't previously opted in to being test subjects, and stifling rulings by ethics committees have deterred researchers and stopped trials before they even begin.

The United States does not have identical "opt in" requirements, but restrictions and delays, particularly when it comes to trial reviews by institutional review boards (IRBs), often draw criticism from researchers. But, research ethicists say clinical trials in general in this country are not often thwarted by ethical requirements or fears of risks to trial participants.

"I've never seen a protocol rejected by an IRB simply because it carried risk," says Kenneth A. Richman, PhD, associate professor of philosophy and health care ethics at Massachusetts College of Pharmacy and Health Sciences in Boston. "The main issue is whether the risk is worth it. Primarily, protocols are rejected when the science isn't good."

Slow process not due to ethical restrictions

Richman agrees that the review process for clinical trials can be extremely slow at times, but usually not on the grounds that the trial is ethically flawed.

"Sometimes it's a risk-benefit analysis," he explains. "Sometimes if it's referred or conditionally approved, the IRB looks for revisions to the [informed] consent form to make it clearer or more accurate; but even when I have reviewed protocols with an IRB that looks at clinical trials, the only reason for rejection is usually that the science isn't good.

"It's not just an ethical issue."

Richman says in his work with IRBs and clinical trials, he has not gotten the sense that the process has slowed recently.

"It is a case of there being hoops to go through, and that does slow things down, but that's just the research game," he says. "That's just the way it works."

Karen J. Maschke, PhD, associate for ethics and science policy for The Hastings Center in Garrison, NY, says the argument that ethics impedes research is not new.

"That exact same argument was made in the United States in the 1970s [when the] Tuskegee syphilis study [came to light]," she says, and again in New York in a study of chronic diseases among hospitalized patients at a Jewish hospital, when the trial subjects had not given consent to be included in the study.

"In my experience, no one has pointed to any good, empirical evidence that research has been stifled by ethical requirements," she adds.

Some researchers have experienced delays because of the IRB review process, she concedes, "but that's an institutional issue with their own IRBs, not an ethical issue."

PolyHeme study drew attention in U.S.

Recently, a U.S. study examining the effectiveness and safety of a blood substitute, PolyHeme (Northfield Laboratories), drew fire for what some ethicists said was overstepping informed consent bounds.

The PolyHeme study, which is ongoing, compares use of the PolyHeme blood substitute to traditional saline in trauma patients who can unknowingly receive the experimental product because of a federal regulation that waives informed consent requirements for trauma or emergency patients under certain circumstances.

The oxygen-carrying PolyHeme fluid is intended for use in ambulances to prevent death before a patient can receive blood in an emergency room. However, the study allowed patients to continue receiving PolyHeme for up to 12 hours after arrival at the hospital. In an open letter published in the on-line version of The American Journal of Bioethics in early 2006, a panel of ethicists said while the use of PolyHeme is justifiable outside the hospital setting, patients should be given blood once they arrive at the hospital and are matched for donor blood.

"Studies like [the PolyHeme study] put pressure on the key fault lines in research ethics," Richman states. "We desperately want data on how to help trauma patients, but we also believe that patients should not be enrolled in studies without their explicit permission. Ethicists call this a conflict between beneficence and respect for persons."

While most research involves this conflict to some degree, Richman adds, "each study has to be examined in the context of available data and applicable guidelines, and people are concerned that scientists and review committees got it wrong in the case of the PolyHeme study."

Political pressures influence trials

More so than ethical restrictions, Richman says, the political climate in the United States is a bigger threat to clinical research.

"I'm more concerned about people turning away from research on stem cells and HIV due to the political climate," he says.

Prior to the mid 1970s, many drugs and pharmaceutical products were tested on prison inmates who were paid to participate in trials. Revelations of abuse at some prisons led to new regulations that said prisoners can participate only in trials that pose minimal risk, but an Institute of Medicine report presented in August recommends that trials with greater risks be conducted in prison populations if there are potential benefits to prisoners.

Ethicists are split over the potential benefits among prison populations, which suffer disproportionate rates of HIV and hepatitis C infections, and the risk posed when incarcerated, often functionally illiterate subjects are asked to consent to participate in trials.

"With the IOM report on prisoners, there are two responses to that," Richman suggests. "One is, 'Look at this report — it is broadening ethics oversight by suggesting that research on prisoners be reviewed by an ethics board'; and the other is, 'Oh no. They say it's OK to research on prisoners again.'"

In cases such as the PolyHeme trial, where anyone in one of the research locations could become a subject simply by being hit by a car or suffering other traumatic blood loss outside a hospital, Richman says the question of boundaries of consent become a bit fuzzy.

"The interesting [ethical] cases are the ones in between being clearly permissible and clearly impermissible," he adds.

Sources

For more information:

  • Kenneth A. Richman, PhD, associate professor of philosophy and health care ethics, Massachusetts College of Pharmacy and Health Sciences, 179 Longwood Avenue, Boston, MA 02115. Phone (617) 732-2927.
  • Karen J. Maschke, PhD, associate for ethics and science policy; editor, IRB: Ethics & Human Research, The Hastings Center, 21 Malcolm Gordon Road, Garrison, NY 10524. Phone (845) 424-4040.