Researcher regains privileges, but with restrictions

Researcher regains privileges, but with restrictions – medical researcher Abraham Mittelman

John Henkel

A New York doctor who violated federal law in treating melanoma patients with experimental drugs is eligible once again to conduct clinical trials. But he can do them only under rigid restrictions and oversight by FDA and the medical center where he performs the studies.

Abraham Mittelman, M.D., a medical researcher with Westchester County Medical Center in Valhalla, N.Y., regained some research privileges last December after being barred from doing studies for six months. He had signed a consent agreement with FDA in June 1995, concerning previous clinical trial violations, ranging from dispensing unauthorized drugs to inadequately protecting the welfare of trial subjects.

By signing the agreement, Mittelman waived his right to a hearing and obligated himself to follow a detailed plan before working in clinical trials again.

Mittelman’s research centered on using biological drugs called monoclonal antibodies to threat more than 400 patients with advanced malignant melanoma, a deadly form of skin cancer. Monoclonal antibodies have been shown to be valuable in medical diagnostics, but their worth in disease treatment is unproven. FDA has approved several monoclonals for diagnostics but none for treatment.

“The way he did these studies, it’s impossible to know if the drugs he was testing really worked,” says Pat Holobaugh, FDA consumer safety officer.

FDA first suspected the infractions in October 1992, when a reviewer for the agency’s Center for Biologies Evaluation and Research noticed in a routine review that Mittelman was testing a drug without an approved investigational new drug (IND) application. FDA must approve INDS before researchers can begin testing drugs in clinical trials.

In January 1993, Margaret Sarles, investigator in FDA’s White Plains (N.Y. resident post, followed up on the IND discrepancy by interviewing Mittelman and examining his records relating to the monoclonal antibodies. For three months, Sarles gathered evidence showing that Mittelman had repeatedly violated regulations governing proper conduct in clinical studies of investigational new drugs.

Violations cited in the consent agreement included:

* failing to submit an IND application for an investigational drug

* administering an unapproved drug to humans

* failing to protect the safety and welfare of patients by using deficient consent forms

* administering to patients an unapproved biological reagent labeled “for laboratory use only”

* failing to maintain adequate records on the distribution of investigational drugs

* neglecting to maintain sufficient case histories of patients in the trials shipping investigational new drugs to Italy, Argentina and Greece without FDA authorization

* violating “clinical holds.” (FDA places clinical holds on investigational new drugs when there are concerns about their safety and other factors. A clinical hold forbids researchers to test the drug in clinical trials until the concerns are resolved. FDA found that Mittelman violated clinical holds on monoclonal antibodies by administering the drugs to 14 patients between 1988 and 1991, and to eight patients between 1991 and 1992.)

Under the consent agreement, Mittelman agreed to withdraw from every clinical study he was managing for six months and to notify all sponsors in writing that he was doing so. He also had to return to sponsors or destroy any investigational drugs in his possession.

Mittelman may now perform clinical trials under the following conditions, which remain in effect for the next three years:

* He cannot participate in more than three clinical studies with more than 20 patients at a time, and he cannot serve as the sole principal investigator.

* He must collaborate with a senior clinical investigator, approved by FDA, in reviewing the clinical trials every 60 days to ensure that Mittelman complies with FDA regulations and the consent agreement.

* He cannot store or control any investigational drugs or biologics. To ensure data accuracy, he must personally review each case report form before submitting it to the sponsor.

After three years, Mittelman can ask FDA to lift the restrictions.

COPYRIGHT 1996 U.S. Government Printing Office

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