More Evidence that Food and Drug Administration (FDA) Regulatory Actions Fail To Protect the Public

A study published in the August 15, 2001 Journal of the American Medical Association (JAMA) adds weight to the evidence that Food and Drug Administration (FDA) regulatory actions fail to protect the public from preventable drug-induced injury.

The objective of the study was to evaluate the effect that “Dear Health Care Professional” letters and safety labeling changes had on physician compliance with a requirement for liver toxicity monitoring tests in patients taking the type-2 diabetes drug troglitazone (REZULIN). Elevation in liver enzymes is an early signal of potential liver toxicity.

More than three years ago, in the January 1998 issue of Worst Pills, Best Pills News, we listed troglitazone as Do Not Use because of its liver toxicity. More than two years later, in March 2000, the drug was removed from the market for this reason. The withdrawal was reported in the May 2000 issue of Worst Pills, Best Pills News.

The authors of the JAMA study compared the degree of physician adherence to the FDA’s liver function testing requirements in time periods representing four progressively more stringent changes in troglitazone’s professional product labeling. The new labeling changes were communicated to doctors in “Dear Health Care Professional” letters.

The time periods covered in the study were: 1.) April 1 to October 27, 1997, before testing was required; 2.) December 1, 1997 to June 30, 1998 during which time six blood tests were required during the first year of use of troglitazone; 3.) July 28, 1998 to January 26, 1999 when the number was raised from six to eight; and 4.) March 26 to September 24, 1999, when a patient was required to have 12 tests during the first year.

Some degree of liver function testing before starting troglitazone increased from 15 percent before any FDA monitoring requirements (time period 1) to 44.6 percent following the four separate FDA interventions. In the final time period, 33.4 percent of the patients had follow-up testing after one month of treatment, falling to 13 percent after five months of continuous use of the drug. Fewer than 5 percent of patients received all required liver toxicity monitoring tests.

The authors of the study concluded: “The FDA risk management efforts did not achieve meaningful or sustained improvement in liver enzyme testing.”

The troglitazone study follows a recent analysis of the effect of FDA regulatory action on the contraindicated prescribing and dispensing of the nighttime heartburn drug cisapride (PROPULSID). That study was published in the December 20, 2000 issue of the Journal of the American Medical Association.

We listed cisapride as a Do Not Use drug in the 1999 edition of our book Worst Pills, Best Pills because of numerous drug interactions that led to fatal heart rhythm disturbances. Cisapride was finally removed from the market in March 2000 after reports of at least 80 deaths and over 300 reports of heart rhythm abnormalities.

The cisapride researchers used prescription data from two managed care organizations and a state Medicaid program. The most striking finding was in the state Medicaid program. In the year prior to the June 1998 strengthening of cisapride’s black box warning, announced with a “Dear Health Care Professional” letter, 60 percent of patients were being given the drug even though it was contraindicated because of drug interactions or the patient’s medical condition. In the year following the strengthened warning, the proportion of patients receiving the drug in a contraindicated manner had hardly decreased at all—only from 60 to 58 percent.

The study’s conclusion was: “The FDA’s 1998 regulatory action regarding cisapride had no material effect on contraindicated cisapride use.”

The results of these two studies illustrate why the Public Citizen Health Research Group has supported a 1979 FDA initiative to require that pharmacists distribute scientifically accurate prescription drug information written in non-technical language to all patients receiving a new or refill prescription. It is becoming increasingly clear that informing physicians and pharmacists does little, if anything, to protect the public from preventable drug induced injury or death. We view the mandatory distribution of FDA-regulated written drug information as the only possible way of giving patients the information they need to protect themselves in a drug safety system that too often fails.

Tragically, the trade groups representing pharmacy and medicine, and the drug industry have been successful for over 20 years in preventing the FDA from implementing an old but vitally important program for patient safety.

What You Can Do

Before you take any new drug, ask your pharmacist for the drug’s FDA-approved professional product labeling, commonly referred to as the “package insert.” The information in this document can be life-saving, and if the technical jargon is hard to understand, ask your doctor.

DO NOT rely on the computer generated handouts given out by some pharmacies. This information is produced by unregulated commercial information vendors and is frequently out-of-date or omits important safety information.

You can find the latest drug safety labeling changes on the FDA’s web site at: www.fda.gov/medwatch/index.html.