Written Drug Information Sheets Distributed by Pharmacists Fail to Meet Minimum Quality Standards

The Food and Drug Administration (FDA) announced on June 18, 2002, the results of a national study to determine the extent of distribution and the quality of unregulated written drug information, known as “patient information leaflets” (PILs), produced by commercial information vendors to be disseminated by pharmacists to drug consumers when prescriptions are filled. The study’s results were appalling.

More than 1,300 PILs were evaluated, and not a single one of them met all of the nationally accepted guidelines. In fact, the highest mark in the survey went to a drug that contained 80 percent of the information that patients should be receiving, and the average leaflet provided only 50 percent of the minimum amount of information needed to enable a patient to use a drug. Incomplete drug information is misleading and thus potentially dangerous.

The study was conducted by researchers from the University of Wisconsin-Madison, School of Pharmacy on contract to the FDA. PILs were collected from a random sample of 384 community pharmacies. A total of 1,367 PILs for four drugs were evaluated: 1) atenolol (TENORMIN), a high blood pressure drug; 2) the popular cholesterol lowering agent atorvastatin (LIPITOR); 3) glyburide (DIABETA) used in the treatment of type-2 diabetes; and 4) nitroglycerin (NITROSTAT) used under the tongue for chest pain (angina).

Despite evidence to the contrary, in the data collected, the study incorrectly concluded that more than 90 percent of the PILs were scientifically accurate, up-to-date, and non-promotional.

“Scientifically accurate” was supposed to be a previously agreed-upon guideline by PILs producers defined as information consistent with or derived from the FDA approved professional product labeling. This FDA approved labeling is primarily addressed to physicians and pharmacists, and is quite technical in nature.

Table 1 shows the discouraging results of two areas of PIL evaluation: Contraindications and Precautions. This information is contained in the professional product labeling. Only about one-fifth of the atenolol PILs contained 80 percent or more of the required information about Contraindications. The score for atorvastatin was only 1.2 percent. None of the PILs for glyburide or nitroglycerin reached this level of information content. The results for Precautions were similar. Approximately one-fourth of the atorvastatin PILs reached the 80 to 100 percent level of information. The PILs for the other three drugs totally failed.

It is incomprehensible that the conclusion was reached that more than 90 percent of the PILs being distributed to consumers were “scientifically accurate.”

Focusing on the scientific accuracy of the PILs evaluated for the cholesterol lowering drug atorvastatin, the findings were alarming. There were more than 53 million prescriptions dispensed for this drug in 2001. Fewer than one percent of atorvastatin PILs (0.6 percent) cautioned about the drug’s interaction with gemfibrozil (LOPID). By contrast, atorvastatin’s professional product labeling warns of increased risk of a serious adverse reaction (rhabdomyolysis) that can lead to kidney failure when the drug is used in combination with drugs like gemfibrozil.

Only one-quarter of the atorvastatin leaflets warned consumers that blood tests are needed to monitor for possible liver failure. The drug’s professional product labeling recommends that function tests be performed prior to starting the drug, at 12 weeks following initiation of treatment, and after any elevation of dose, and semiannually thereafter.

Information about a drug’s Contraindications and Precautions can be life-saving for consumers.

The study was required under provisions of Public Law 104-180 passed in August 1996. The law’s primary purpose was to help develop a private sector plan acceptable to the Secretary of the Department of Health and Human Services to ensure that patients would receive scientifically accurate, useful written information about their prescription drugs. Public Citizen was a part of this process that developed the Action Plan for the Provision of Useful Prescription Drug Information (Action Plan) that was accepted by the Secretary on January 24, 1997.

The law required the Action Plan to meet the goals of the FDA’s 1995 proposed rule on “Prescription Drug Product Labeling: Medication Guide Requirements” relating to the mandated provision of FDA approved scientifically accurate written prescription information to consumers. For purposes of the Action Plan, “scientifically accurate” was defined as information consistent with or derived from the FDA approved professional product labeling. Also, pharmacists had to distribute scientifically accurate and useful written information, as defined in the plan, to 75 percent of individuals receiving new prescriptions by the year 2000 and to 95 percent by the year 2006. This proposed rule was strongly supported by consumer groups, including Public Citizen.

The FDA’s reaction to the study’s appalling results may be illegal and is clearly irresponsible. The agency made the following statement in its June 18, 2002 announcement of the study results:

Because the agency sees progress in meeting the goals set under Public Law 104-180, FDA will continue to work with private sector partners to improve the usefulness of patient information, and meet the goal for the year 2006, which calls for 95 percent of patients obtaining new prescriptions to receive useful written medication information at the time of dispensing.

During the development of the Action Plan there was no discussion, or was it the intent, to award partial credit to patient information leaflets. The standard was always that the evaluation of these leaflets would be dichotomous (acceptable/unacceptable) and that only those leaflets scoring 100 percent would be counted toward the distribution goal of 75 percent.

Both the Action Plan and the FDA’s 1995 proposed rule are clear on this point. The Action Plan says:

The written information that meets these guidelines—i.e., adheres to the criteria, includes the suggested components, and substantially conforms with the formatting suggestions here and in Appendix G—will be deemed “useful” information and will “count” toward the quantitative goals of the Plan.

The following appears in the agency’s 1995 proposed Medication Guide rule:

Each sample [PIL] will be scored on each criterion, using “acceptable’’ and “not acceptable’’ cutoff points. As mentioned, FDA believes that for a particular information sheet to be judged as acceptable overall, it must receive an acceptable rating on each of the individual components.

The private sector that produces and distributes these PILs has known since January 1997 exactly what was required. In March 2000, the FDA released the results of a pilot study also designed to determine the extent of distribution and the quality of unregulated written drug information leaflets, Evaluation of Written Prescription Information Provided in Community Pharmacies: An 8-State Study.

The release of these study results is the latest chapter in a sorry saga that stretches back to 1979 when the FDA first attempted to ensure that patients received objective, scientifically accurate information about the risks of prescription drugs. During the ensuing 23 years two themes have dominated the issue of providing useful written drug information to patients. First, the private sector has dogmatically maintained that their “initiative” would produce superior drug information for patients. This ideological hallucination should finally be put to rest with the release of the study results. Second, trade groups representing pharmacy and medicine, the drug industry and a member of Congress, Michael Crapo (R-ID), have successfully blocked efforts to ensure patients’ access to objective written drug information.

Public Law 104-180 requires that if the goals of the Action Plan are not achieved by the private sector, and by default the goals of FDA’s 1994 proposed Medication Guide rule, the Secretary of the Depart-ment of Health and Human Services shall seek public comment on other initiatives that may be carried out to meet such goals.

The FDA must follow the law and for the sake of the health of millions of prescription drug consumers sooner, not later.

What You Can Do

Do not rely on the quality of written information from a pharmacist’s computer system.

If you have been prescribed a drug that has not been covered in Worst Pills, Best Pills, the new Companion to Worst Pills, Best Pills or this newsletter, ask your pharmacist for a copy of the drug’s FDA-approved professional product labeling or “package insert.”

Follow the Health Research Group’s Seven Year Rule. You should wait at least seven years from the date of initial release to take any new drug unless it is one of those rare “breakthrough” products that offers documented therapeutic advantages over older proven drugs. New drugs are tested on a relatively small number of people before being released, and serious adverse effects or life-threatening drug interactions may not be detected until the new drug has been taken by hundreds of thousands of people. A number of new drugs have been withdrawn within their first seven years after release. Also, warnings about serious new adverse reactions have been added to the labeling of a number of drugs, or new drug interactions have been detected, often within the first seven years after a drug’s release.