The current system for protecting people participating in clinical drug trials is outdated and needs to be overhauled, according to an article in the Journal of the American Medical Association (JAMA).

"Serious concerns have been raised regarding the processes by which the safety of participants in clinical trials is currently monitored," wrote senior author Dr. Jeremy Sugarman, director of the Center for the Study of Medical Ethics and Humanities at the Duke University Medical Center. "All the players in the system recognize that patient safety is a critical issue that must be addressed."

While no one knows exactly how many people are harmed from adverse events during clinical trials, Dr. Sugarman and Duke co-authors Drs. Michael Morse and Robert Califf revealed that some trials have generated several hundred "adverse event reports."

However, despite a law requiring these reports, many drug and biotechnology company researchers fail to file properly.

In certain cases it is not clear precisely what adverse event reports must be reported, how rapidly they must be reported, who shoulders the main responsibility for reporting or to whom completed reports must be submitted, the authors said.

Clinical trials are tests in which limited numbers of people use new or experimental medications and medical devices to ascertain their safety and efficacy. Only after the medications and devices are tested can they obtain approval from the federal Food and Drug Administration for broad-based use.

When patients become worse during the course of the trial, it's often impossible for the researcher to determine whether the treatment being tested is at fault.

There needs to be a way to understand whether an adverse event is caused by a problem from the drug under study or was brought about by a natural course of the disease for which the patient is being treated, the researchers noted.

"People in clinical trials are generally sick or are already being treated for a disease. The experts on a data monitoring committee must be able to quickly discern between natural occurrences or actual effects of the disease and what is a truly harmful effect of a study drug," said Sugarman.

Data monitoring committees recently have been required in all federally funded late-phase studies. Traditionally, they report each individual adverse event occurring in a clinical trial, but this practice has made it difficult for review boards to accurately evaluate the events, particularly when the trial is being conducted at multiple sites throughout the country and, even more so, when studies involve international study sites.

"Simply put, communication between all parties involved in clinical trials must be improved," Sugarman stated. "Communication must be better between the IRBs (Investigational Review Boards), the data monitoring committees and the sponsors of studies. The information must be condensed and better compiled for enhanced communication."

Trial sponsors, usually drug and biotechnology companies, often possess considerable information from other studies about adverse events, the authors said. However, "sponsors such as pharmaceutical companies often do not disclose to researchers data on the true meaning of adverse events," the study noted.

The authors also advised that safety parameters should be established at the outset of each study. They said data monitoring committees should provide a simple, understandable report to each IRB at appropriate and regular intervals indicating that the safety parameters have not been exceeded and that there are no reasons, based on evolving information concerning the risks and benefits, that the study should not continue.

Finally, the authors urged preventing sponsors from being the sole monitor of a trial, thus removing all potential conflicts of interest.

SOURCES: "Monitoring and Ensuring Safety During Clinical Research," Journal of the American Medical Association (JAMA), Vol. 285 No. 9, March 7, 2001.

"JAMA article calls for overhaul of clinical trials to improve patient safety," Duke University, March 7, 2001.