FDA fine-tuning its position on trials controlled by placebo.(Placebos)

PHILADELPHIA -- A clinical trial characterized as a "medical experiment" is perhaps the most inflammatory accusation being made in the courts today, and the fuel for this fire is placebo-controlled trials, attorneys told CBI Dec. 4.

In clinical trials law suits, plaintiffs' attorneys are asking pointed questions about why a placebo control was used, and thus treatment withheld from a particular subject, when a comparator trial might have yielded the information necessary for drug approval.

A key reason is that FDA is seen to be a proponent of placebo-controlled trials. But speakers argued that this largely is an industry misperception, and that a careful examination of regulatory language is in order to more fully discern the agency's position on placebo-controlled trials.

"The industry operates with the assumption that FDA expects a placebo-controlled study for approval," said Frederick Rom, with Womble Carlyle Sandridge & Rice PLLC. "[FDA's] specific language is different, however."

While FDA generally is more amenable to placebo controls than indicated in international guidelines, agency thinking is changing due to heightened interest in clinical trials conduct, and "they're beginning to look more closely at when a placebo is appropriate," Rom said.

The core document on this issue is the Declaration of Helsinki, a statement of ethical principles from the World Medical Assn. that provides guidance to physicians and other participants in medical research involving human subjects. Originally adopted in 1964, it forbade placebo trials where an existing best therapy was available, but was amended in 2000 and 2002 to collectively allow placebo-controlled trials in investigations of "minor conditions" where patients are not subject to "additional risk or serious or irreversible harm," and "extreme care" is exercised in the goals and design of the trial.

"This is not law, but plaintiffs argue that this is the international standard," Rom said. Other documents that plaintiffs' attorneys rely upon include the Nuremberg Code and the Belmont Report, he said.