Current Practices, Challenges, and Statistical Issues With Product Safety Labeling

Abstract

Prescribing health care professionals are dependent on product labels to give them the information they need to appropriately prescribe drugs and monitor patients. A well-constructed label with accurate, meaningful, and easy-to-understand information is important for understanding the benefit–risk profile of the compound. Statisticians are uniquely qualified to help. Historically, statisticians have played a major role in defining the efficacy information provided in the label. Similar leadership is needed to develop safety information for products. Statisticians should play a key role in making sure that the safety information from clinical trials is accurate and provides adequate information to health care professionals regarding the likely and potential effects of a drug. In this regard, giving careful thought to (a) the way safety information is defined and collected, (b) the way in which different adverse events (AEs) are categorized and combined over multiple studies, (c) the statistical methods used to analyze the safety data, and (d) the tables and graphs in which safety information is presented is needed. We have touched on aspects of each of these in this article. Though product labeling has improved greatly in the past 20 years, there are still many issues that need statisticians’ leadership and thought processes. In this article, we consider some of the important issues and make recommendations to address them. These include passive versus active elicitation of AEs, grouping of terms for labeling purposes, definitions of treatment-emergent AEs, meta-analytical principles, and analytical methods for estimating incidence and rates. Consideration of these issues can benefit health care professionals and ultimately patients who take medicines.

Key Words:

• Adverse reaction
• Causation
• Core data sheet
• Summary of product characteristics
• United States package insert