Human guinea pigs

When people put their bodies on the line in medical trials, can they be sure that scientists aren't cutting corners or preoccupied with stock prices?

By Ivan Oransky

Aug. 2, 2001 | On May 4, Ellen Roche, a healthy 24-year-old woman, inhaled a drug known as hexamethonium as part of an experiment at Johns Hopkins University designed to figure out what nerves are at work in asthma attacks. Although approved by the Food and Drug Administration for intravenous use in patients with high blood pressure until 1997, the drug was known to cause serious lung problems and was never approved for inhalation. But Roche, a laboratory worker and veteran medical research subject, didn't know any of that, because the consent form the researcher, Dr. Alkis Togias, had her sign didn't mention it.

It seems that Togias had missed the lung toxicity in his review of the literature and didn't think the FDA's pulling of the drug from the blood pressure market was important enough to mention in the consent form. (A simple search on Google in July turned up reports of the drug's toxicity, and even if you can't believe everything you read on the Web, the search results, if Togias ever sought them, would have given him cause to investigate further.) Neither he nor the internal committee charged with reviewing the study deemed it necessary to apply to the FDA for approval to use the drug in the trial. Even when the first volunteer to take hexamethonium developed a cough, Togias ignored the symptom and failed to report it to the internal review committee, saying that it was a respiratory infection going around campus.

On May 9, Roche was admitted to Hopkins' intensive care unit, where she eventually needed a ventilator to breathe. She died on June 2.

"Hers was a truly noble act," said a Hopkins statement reporting the findings of an internal review on July 16. By emphasizing Roche's nobility, Hopkins implies that her death was akin to a casualty in a good war, a necessary loss of life on behalf of a greater cause. But in wars, soldiers know the risks. When information about other risks, like those attendant to Agent Orange, is suppressed, governments are rightly condemned. What makes Roche's death an unconscionable tragedy is that had Hopkins followed the rules and Roche known the risks, her untimely death might not have occurred. Hopkins said it was taking full responsibility for Roche's death, but it then laid the blame at Togias' feet, criticizing his work and pledging to improve its research review procedures. It thought that would be enough to placate the feds.

It wasn't. On July 19, the agency shut down all of the 2,400 or so federally funded human trials at the medical center. The response from Hopkins was a sputtering, angry press release that included the statement "We strongly believe that this action was taken in utter disregard of patients' health and potentially of life." To an outside observer, however, it would seem that it was Hopkins -- in approving Togias' protocol, including his utterly flawed consent form -- and not the government that was guilty of such utter disregard. (The funding was reinstated, with provisions for strict supervision, on July 23.)

While still taking "responsibility," Hopkins has also attempted to place the blame on the FDA's shoulders, saying that the agency had, by not responding to December 2000 and April 2001 letters requesting approval of Hopkins' recently revised research procedures, effectively bestowed that approval. That dishonest spin doctoring should be considered reprehensible in the face of the needless death of a healthy 24-year-old woman.

Next page: When doctors dream of stock prices, not clinical results