Do the Ends Justify the Means in Human Research?

Thu, 5 Sep 2002

A moral struggle is taking place in which research stakeholders–including medical institutions that profit from biomedical research, and their emissaries in government oversight agencies–argue that ethics should be breached to further the interest of research. Patients’ rights advocates–such as human rights and disability groups–argue that the rights of living individuals must be protected—-including the right not to be subjected to experimentation without voluntary, informed, comprehending consent.

The Bureau of National Affairs reports (below) that government proposals to protect vulnerable (in this case) elderly patients from experiments that expose them to greater than minimal risk, should be prohibited–unless they have executed an advanced directive giving their consent for future research. Dr. Dave Wendler, head of the Vulnerable Populations Unit at the National Institutes of Health Department of Clinical Bioethics, argues AGAINST these proposals because he suspects “few patients would file research advance directives (RADs)…” Indeed, when Dr. Wendler asked 150 patients with a family history of Alzheimer’s whether they would want to participate in research if they got ill, 80% said they would–but only 20% returned a RAD to Wendler. Does this bioethicist propose to disregard their freely made choice and recruit them for experimental research without their consent?

Public Citizen urged the Secretary of HHS to stop a large-scale government-sponsored Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT) because it “is not only useless, but dangerous and should be stopped.” Public Citizen said the drugs in question are inappropriate and the lengthy duration of the study poses health risks to the subjects and no benefit. this underscores the vulnerability of the elderly to experiments that are against their best interests. http://printerfriendly.abcnews.com/printerfriendly/Print?fetchFromGLUE=true&GLUEService=ABC

Similarly, The Alliance for Human Research Protection (AHRP), filed complaints with The Office of Human Research Protections about a government-sponsored acute respiratory distress study (ARDS) that had been conducted on 861 incapacitated patients. In its response to the complaint, OHRP acknowledged that the experiment had been conducted without legally valid informed consent at ALL 12 major research centers. The study was halted but it is not clear whether 37 patients died because the experiment was not suspended sooner for statistical purposes. See: http://www.researchprotection.org/ethical/CaromeARDS082802.html

AHRP is especially concerned that OHRP has recently adopted a policy of blacking out information from its letters of determination in order to shield institutions that the agency found to have violated ethical standards. OHRP’s action undermines rather than protects the safety of human subject. The correct link to OHRP’s Aug 2 blacked out letter is: http://ohrp.osophs.dhhs.gov/detrm_letrs/YR02/aug02b.pdf

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THE BUREAU OF NATIONAL AFFAIRS September 4, 2002

Human Subject Protection Advance Directive, Minimal Risk Mandate Could Hamper Vulnerable Subject Research

Proposals being considered by federal regulators to protect vulnerable research subjects unable to consent to study participation could, if implemented, have a chilling effect on research, according to Dr. Dave Wendler, head of the Vulnerable Populations Unit at the National Institutes of Health Department of Clinical Bioethics.

The Department of Health and Human Services Office for Human Research Protections is considering requiring Alzheimer’s disease patients and other vulnerable subjects to consent to research while still mentally competent, Wendler said, and banning them from studies that pose greater than minimal risk.

But institutional review boards (IRBs) interpret “minimal risk” narrowly and, if the ban was implemented, would be reluctant to approve a vulnerable subject’s participation in any study that involved more than a one-time blood draw regardless of scientific merit, he said.

Also, although most people want to specify medical preferences before they become ill, few file clinical advance directives. Wendler said he suspects the same would happen in research; few patients would file research advance directives (RADs) even if they wanted to participate in trials.

The research community must work now to block RAD and minimal risk proposals or “we will be stuck with whatever we wind up with for a long time,” Wendler suggested. He said his office plans to present its concerns to OHRP shortly.

Wendler spoke Aug. 28 at an NIH grand round meeting. NIH enrolls a significant number of vulnerable patients in its studies.

Making the Case. To gauge how IRBs would apply minimal risk standards to vulnerable subjects, Wendler and colleagues asked about 200 IRB chairs to classify commonly used research procedures according to risk. Preliminary findings indicate that:

• 81.4 percent of IRB chairs thought one-time blood draws posed minimal risk;

• 48.4 percent classified sex surveys as minimal risk;

• 44.2 percent said magnetic resonance imaging was minimal risk;

• 23.4 percent classified allergy skin testing as minimal risk;

• 14.9 percent classified one blood draw per week for 24 weeks as minimal risk;

• 8.5 percent said an electromyogram was minimal risk;

• 7.5 percent considered pharmacokinetic testing minimal risk; and

• 2.1 percent ranked lumbar punctures as minimal risk.

“Minimal risk standards get interpreted conservatively in practice,” Wendler concluded, noting that one-time blood draws were the only procedures the majority considered minimal risk. Following a minimal risk standard, at least half of IRBs would reject studies involving the other procedures, he predicted.

“There’s a lot you can do with a blood draw, but there’s a whole heck of a lot you cannot do,” he said.

To gauge the impact of requiring RADs for vulnerable patient research, Wendler asked 150 patients with family history of Alzheimer’s disease if they would want to participate in research if they came down with the disease.

Over 80 percent said “yes,” even if the study was risky. Eighty-eight percent agreed that they should document that preference and name a surrogate decisionmaker in advance. However, only 20 percent of patients filled out and returned research advance directives Wendler mailed to them.

Although patients wanted to participate in research, he concluded, they just never got around to filling out the form.

“So, if we require advance directives, you will bar a lot of people who would want to be in research,” he said. “We should not require that informed consent be documented in a research advance directive.”

Who Is Vulnerable? Wendler cautioned against considering patients vulnerable just because they perform poorly on mental status or IQ tests or because they are terminally ill.

“What you worry about is whether that person can give informed consent to the protocol,” he said, not overall functioning.

Testing gives some insight. High scoring patients usually can understand the protocol and give consent while very low scores indicate the inability to do so. Patients who score in the middle must be assessed individually, Wendler said.

Some terminally ill cancer patients can think clearly about their best interests, for example, and decide if they should participate. Others are overwhelmed by their circumstances and less likely to be able to do so.

To gauge understanding, Wendler suggested asking patients to explain studies in their own words and their reasons for joining them.

NIH asks Alzheimer’s patients to designate surrogate decisionmakers at the time of enrollment, and investigators periodically reconsent patients to make sure they still want to participate. As the disease progresses, staff rely more heavily on surrogates to make the call, Wendler explained.

By M. Alexander Otto

Copyright 2002, The Bureau of National Affairs, Inc., Washington, D.C.

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http://printerfriendly.abcnews.com/printerfriendly/Print?fetchFromGLUE=true&GLUEService=ABC NewsCom Alzheimer’s Study May Harm Patients, Group Says

Sept. 4 — By Maggie Fox, Health and Science Correspondent

WASHINGTON (Reuters) – A big government-sponsored trial aimed at seeing if painkillers can reduce the risk of Alzheimer’s disease is not only useless, but dangerous and should be stopped, a consumer’s group said on Wednesday.