Survival of the Fittest Drug Label

Several FDA initiatives are aiming to make prescription-drug labeling more clear, informative, accessible, and consistent.

FDA's proposed rule to revise the overall format of prescription-drug labeling, which was released in December 2000, has been receiving a lot of attention lately. However, it is only one of several initiatives under way to make prescription-drug labeling more clear, more informative, more accessible, and more consistent for healthcare practitioners.

A draft guidance on the content and format of the "Adverse Reactions" section of prescription-drug labeling appeared in June 2000. Other guidances revising the requirements for "Clinical Pharmacology" and "Warnings/ Precautions" sections are in the works, as is a proposed rule to revamp the pregnancy subsection of the labeling, according to the agency.

On July 9, 2001, another aspect of this effort emerged, as the agency released a draft guidance on the "Clinical Studies" section of labeling for prescription drugs and biologics. The document can be viewed at, and written comments may be submitted to the agency until October 9.

The guidance aims to help firms de-cide which studies should be included in the "Clinical Studies" section of the labeling, how individual studies should be described, and how data should be presented. It also points out the advertising and promotional implications of the information in the section.

Studies that should be included are those that provide primary support for effectiveness, raise important issues about the limitations of effectiveness, and contribute efficacy data not otherwise provided. Studies that imply effectiveness for an unapproved indication, comparative efficacy, or safety claims not supported by substantial evidence, or that are not adequate and well controlled should not be included.

The focus should be on efficacy data as opposed to safety data, which is typically described in the "Adverse Reactions" section. Evidence supporting effectiveness, a description of the populations studied and end points measured, and a list of the important limitations of the available evidence should be included.

More detail should be included when the study responses are of critical health importance, when the study results represent a significant advance in treatment, when the study enrolled a very specific patient population and the results may not be applicable to other groups, when the results are not typical of what would be expected for the drug class and indication, or when an unfamiliar end point is used. Less detail is needed when the drug appears to have effects typical of its class or when the clinical end points measured are not readily applicable in clinical practice.

The end points presented should be essential to establishing the effectiveness of the drug (or showing its limitations) and should provide valid information about the activities of the drug.

Comparative data should not be used, unless they are from an adequate and well-controlled study that can support a comparative claim, or if the comparator data contribute information that is essential to a clinician's understanding of the effects of the drug at hand.

When describing a study, include information such as the level of blinding, type of controls, duration, method of allocation, and use of a run-in period. The dose, regimens, and titration procedures should be identified for each trial arm. The study population should be described in a way that identifies the characteristics that are important to understanding how to interpret and apply the study results.

When a detailed summary of findings is needed, elements such as the number of patients enrolled and completed, number discontinued and reasons for those, number not progressing to a certain phase, the absolute difference of the treatment effect, and a confidence interval to describe the uncertainty of the treatment effect should be included.

A summary statement about treatment effects in age, gender, and racial subgroups should also be included.

The summary section should be carefully scrutinized to ensure that it does not imply claims that are not adequately supported. Avoid vague, misleading, ill-defined, easily misunderstood, or promotional wording. For example, list the actual size or amount instead of saying "large" or "small," and provide the confidence interval instead of saying "significant."

An appendix to the document illustrates how to present graphs and tables within the labeling. The agency encourages using such graphics.

Written comments should be sent to the Division of Drug Information (HFD-240), Center for Drug Evaluation Research, FDA, 5600 Fishers Ln., Rockville, MD 20857, or to the Office of Communication, Training, and Manufacturers Assistance (HFM-40), Center for Biologics Evaluation and Research, FDA, 1401 Rockville Pike, Rockville, MD 20852–1448.

No votes yet