When the Patient Is Also an Experiment : Feds find fault with UCLA schizophrenia study
Few of the miracle drugs and treatments we take for granted today would have been possible without ultimately testing them on humans. But the process by which that was done, at least by today’s prevailing ethic, was often abusive. For 40 years starting in 1932, the U.S. Public Health Service studied 399 black men with syphilis in Alabama to compare their health with 401 men who did not have the disease. The doctors let them die without telling them they were part of a study and without treating them--even after penicillin came along. And during the 1940s and 1950s numerous Americans were the unwitting subjects of classified studies on the effects of radiation.
UCLA SUICIDE: It is unlikely such lapses could occur today. But medicine is still vexed by the issue. On Wednesday a federal agency rebuked UCLA for an experiment in which researchers removed schizophrenic patients from medication; some later had severe relapses and one committed suicide. The agency said the patients were not properly advised of the risks.
Nearly 20 years ago, Congress passed a law to protect human subjects. It resulted in rules requiring each university and hospital to establish a board to evaluate research proposals and make sure each subject gave “informed consent.” But those boards have operated with varying effectiveness and little federal oversight. It took Robert Aller, the father of one of the UCLA subjects, years of pressure on Congress and publicity to get the federal Office of Protection From Research Risks to probe the matter.
The UCLA affair offers a good case study of the dilemma facing modern medical experimenters. Many patients with debilitating diseases volunteer to take personal risks to advance knowledge. And the UCLA researchers had good intentions. Schizophrenia medicines like Prolixin have bad side effects including involuntary movements and muscular stiffness. They wanted to devise strategies for taking patients off medication for extended periods.
During one such period, Aller’s son Gregory threatened his parents and suffered hallucinations. Another patient off medication, Antonio Lamadrid, jumped to his death from a UCLA building. The federal rebuke faults the written consent form, which did not specify how severe the relapses could be. The researchers maintain that they gave this information orally and say the study included a “clinical override” by which they “immediately evaluated” subjects who displayed psychotic symptoms and recommended medicine. That is hard to square with the Aller and Lamadrid cases, though one of the researchers, Dr. Keith H. Nuechterlein, a psychologist, says that patients often refuse medication and it is difficult to determine clinically how severe a relapse is.
UCLA has agreed to strengthen its procedures, making changes in the informed-consent forms, adding a “subject representative” to the internal review board and setting up a monitoring system to oversee studies in which researchers are responsible for both research and care of subjects.
EMPTY EXERCISE: That is good, but it may take more. Alexander M. Capron, professor of law and medicine at USC, says that review boards often approve studies on the basis of the researchers’ reputations and patient consent becomes a hollow ritual. And the boards operate on an “assurance” model, meaning that the federal government, which supports most biomedical research, accepts the judgments without review unless a problem crops up later.
Some medical ethicists argue against doing research in which known treatments are withheld and the patient is certain to regress during the study. We disagree. But there must be much better oversight, improved patient consent and closer monitoring of subjects to ensure that they can be rescued from the kind of untoward results that marred the UCLA experiment.