Regulators encouraged by Hopkins

`Extraordinary effort' expended on reviews of medical studies

But concerns persist

2 experiments draw agency's criticism, 1 involving children

November 10, 2001|By Tom Pelton | Tom Pelton,SUN STAFF

A federal agency yesterday praised Johns Hopkins medical institutions' efforts to improve the safety of medical experiments, but found significant ethical problems in at least two studies.

The Office of Human Research Protection said the Hopkins medical school and its affiliated institutions should be commended for overhauling their internal review boards since the death June 2 of a volunteer in an asthma experiment.

But as part of continuing scrutiny of Hopkins' experiments, the agency discovered flaws in a hormone study and a cocaine experiment, according to a letter released yesterday.

A study of hormones in children with a rare genetic bone disease should never have been approved because children were subjected to unacceptable risks, the agency said. Volunteers began enrolling in the study this year.

The study's researchers, led by Dr. Michael A. Levine, provided parents with consent forms that failed to warn about potentially serious side effects, including heart irregularities, according to the agency.

In a second experiment, scientists studying drug cravings provided up to $700 to cocaine addicts to persuade them to come to the lab, where researchers used imaging equipment to scan their brains.

The money is a problem because addicts are a "vulnerable population" who might have felt coerced by the financial offer, according to the letter by Patrick J. McNeilly, oversight coordinator at the federal agency.

"OHRP is concerned that the [review board] failed to recognize the vulnerability of drug abusing populations and the possibility of coercion or undue influence to participate by offering a large payment," McNeilly wrote.

It was not clear yesterday if the two experiments would continue or be altered because of the agency's findings.

Hopkins officials have until Nov. 30 to reply to the regulators' report and declined to discuss either study yesterday. "Nobody is available to comment," said Hopkins spokesman Gary Stephenson.

The agency's report also found minor problems in the internal review process for several other experiments, but its overall tone was not negative. The federal agency praised the "extraordinary effort" by Hopkins to "enhance its system for protections of human subjects."

In June, 24-year-old Ellen Roche died after inhaling an experimental chemical in an asthma study at Hopkins' Bayview Medical Center.

In reviewing that case, federal regulators found systematic flaws in Hopkins' system for monitoring experiments and suspended federally funded research involving humans for four days in July. Besides the medical school and Bayview, the shutdown included the Kennedy Krieger Institute and the Applied Physics Laboratory.

Since then, Hopkins has doubled its number of internal review boards, increased training for all board members, and pledged to re-review thousands of experiments to make sure they are safe.

But the federal agency said Hopkins' re-review of its experiments missed some problems - including the consent form used in the hormone study and the cash used in the cocaine experiment.

The hormone research criticized by the agency was led by Levine, an endocrinologist at the Johns Hopkins Children's Center. He studies dwarfism and other rare genetic mutations that affect the size of children and warp their bones.

In the federally funded study, Levine is examining the molecular basis for the unusual hormone levels in children with McCune Albright syndrome, a genetic condition that causes early puberty, skin discoloration and deformity of the legs, arms and skull, according to the National Institutes of Health.

Levine, who declined to comment for this article, failed to adequately inform the volunteers of the side effects of substances used in the study, which include L-dopa, a drug often used to treat trembling associated with Parkinson's disease, and GnRH, a hormone, according to the federal report.

The consent form signed by parents only said the drugs may leave the subjects "feeling sick to your stomach, dizzy or slightly warm."

The forms did not say that falling blood pressure, cardiac irregularities, anxiety attacks and blood clots were also risks of the experiment, the federal agency found.

The agency said the study's risk level appeared to violate federal regulations meant to protect children.

"OHRP is concerned that the above referenced research appears to be more than a minor increase over minimal risk ... and therefore is not approvable under HHS regulations," the report said.

The agency also criticized the review of a cocaine study, led by Dr. Dean F. Wong, a professor of radiology and psychiatry. The experiment used brain scanning equipment to monitor the levels of dopamine, a chemical messenger, in the brains of cocaine addicts.

During a review Aug. 8 of the experiment, the Hopkins medical school's review board concluded that there was no ethical problem with providing $600 to $700 to drug addicts to compensate them for two to four days of volunteering, according to the agency.

Ethicists not involved with the study said yesterday that there are no general prohibitions against providing money to drug addicts to entice them to enroll in studies.

"You can't have these types of studies without money," said Leonard Glantz, professor of health law at Boston University's School of Public Health. "It's unlikely you'd get drug addicts or anybody else to come in for a study without offering them cash."

The federal agency also cited some minor problems with Hopkins' review of experiments. In some cases, the report said, review board members failed to read descriptions of the experiments before the board meetings.

Occasionally, the review boards have lacked expertise to review experiments that demand specialized knowledge, federal regulators said.

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