Every other day, Adil Shamoo says he gets an inquiry about something untoward in a clinical trial.

Shamoo, whose day job is professor of molecular biology, epidemiology and preventive medicine at the University of Maryland’s School of Medicine, is also the founder of Citizens for Responsible Care and Research (CIRCARE).

CIRCARE is an advocacy organization for anyone concerned about potential misconduct in a clinical trial. It provides ways to resolve a potential problem or bring it to wider attention. Shamoo is as concerned about patient risks in investigator-initiated trials as in industry-sponsored research.

Patient Advocate

The recommended first form of action? Shamoo and other CIRCARE volunteers advise working though the system, contacting the sponsor. If it’s a researcher reaching out to CIRCARE, Shamoo suggests calling a supervisor, then a monitor. Next move? Contacting the institutional review board (IRB).

“If all this fails, then we point them to how to file a complaint to the FDA or OHRP (Office for Human Research Protections),” says Shamoo, formerly chair of the department of biochemistry and molecular biology at the University of Maryland.

The Media Option

Often, though, it’s too late. “Usually by the time they come to us, they have already exhausted the internal system, or it is too late for that, and the research is already published,” he laments. In that case, CIRCARE may recommend going to the press, says Shamoo.

As editor-in-chief of the journal Accountability in Research, Shamoo has been exploring ethics in research since 1990, when then-Congressmen Al Gore and Ted Weiss conducted hearings on scientific fraud, producing the report “Are Scientific Misconduct and Conflict of Interest Hazardous to Our Health?”

At the time, Shamoo was a bench scientist. It wasn’t the report’s findings that captured his attention. It was the dismissive response of the medical establishment.

‘A Bunch Of Lunatics’

“The reaction struck me,” says Shamoo. “They said, ‘This is trivial. This is not important.’ They wrote articles saying: ‘These are a bunch of lunatics who are exaggerating.’ They said, ‘Science is self-correcting, therefore we shouldn’t worry about it.’ ”

Shamoo insists science is not self-correcting. One interest of his is informed consent in pediatric research, which was an outgrowth of a 1997 fenfluramine study of 34 boys, a project run under the auspices of the New York Psychiatric Institute.

Close to Home

Another pivotal personal experience was raising a child with schizophrenia. When his teenage son was diagnosed with the condition in 1986, Shamoo began paying attention to the mentally ill as clinical trial subjects. He says he’s alarmed that some psychiatrists participating in clinical trials abruptly take patients with schizophrenia off medicines that work in order to test new drugs.

What else is wrong with the present system? For starters, the adverse-events reporting system in the U.S., he says, offers a circuitous, murky and voluntary path to let the government know about a drug safety problem. The inadequacies of trial-specific and so-called spontaneous Medwatch systems have been debated by academic experts and politicians for years, but not fixed—even after last fall’s user fee legislation.

“Human subjects don’t know what to report,” Shamoo says. “The principal investigator doesn’t know what to report; most are not educated on the ethics and regulatory requirements in clinical trials. There is no uniform definition of what an adverse reaction is, and what is to be reported, and when. The chain of reporting is all broken.”

Indifferent IRBs

And the institutional review boards (IRBs)? Shamoo says they can’t be counted on. Each varies greatly in its performance. He’s watching the for-profit IRB sector closely, as this letter to a journal suggests.

Not only that, but Shamoo asserts that a “patchwork of regulation” in the U.S. only protects about 70 percent of the people who participate in research. The remaining 30 percent—participating in research that takes place prior to the investigational new drug application (IND) stage—aren’t protected by the government.

That is in sharp contrast to regulations for research on animals. “If you do experiments on animals in your basement,” Shamoo notes, “they can come and arrest you. That is not a fact in humans.”

Volunteer Compliance

Innovators doing pre-IND research on humans often choose to comply with the same regulations to which they are bound in post-IND projects, says Shamoo. But they have no obligation to do so. By his count, millions of research subjects may be unprotected because 164 major universities and other research institutions don’t follow the post-IND rules.

Is the answer more regulation? Or education? Both, says Shamoo.

He’s in favor of the proposed National Human Subjects Protection Act. The bill would impose uniform and mandatory reporting of all adverse events, as well as mandatory ethics and regulatory compliance training for principal investigators, coordinators and monitors. The overall goal? To close gaps in the current regulatory regime.

So far, though, the bill is stalled on Capitol Hill. Shamoo says he has hope that when a new president takes over early next year, the bill will have a chance.

Maryland Out in Front

In the meantime, he hopes that laws could change at the state level. In 2002, his own state of Maryland passed a law requiring that all research using human subjects must adhere to federal regulations.

At the time the bill was proposed, says Shamoo, the public was very much in favor of it. (A healthy human subject in an asthma trial at Johns Hopkins University had just died.) The bill sailed through as sponsors “didn’t have the normal lobbying effectiveness,” he says.

Shamoo just hopes it won’t take similar circumstances to get laws passed in other states or at the national level.

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