Disparity Between FDA Labelling and Clinical Practice

Overview of FDA Approval Process

A recent study has highlighted the significant gap between the FDA-approved labeling of prescription drugs and their application in real-world clinical settings. When new prescription drugs gain marketing approval in the United States, the Food and Drug Administration (FDA) provides essential drug-related information. However, as these drugs are used in practice, clinicians and researchers may discover new indications and safety evidence. If drug manufacturers do not submit this new information to the FDA, the original labeling becomes outdated.

Understanding Off-Label Use

Off-label use refers to the administration of prescription drugs for indications that differ from those approved by the FDA. As the official labeling becomes outdated, healthcare providers often turn to alternative sources for drug-related information.

The off-label use of anti-cancer prescription drugs is particularly prevalent. The National Comprehensive Cancer Network Drugs and Biologics Compendium (NCCN compendium) serves as the primary source of drug information for physicians, as it provides updated content based on rigorous evidence.

Study Analysis by Friends of Cancer Research

Researchers from the Friends of Cancer Research in Washington, DC, conducted an analysis of drug-related information for 43 anticancer prescription drugs. The goal of their study was to quantify the differences between FDA labeling and NCCN compendium labeling.

The researchers examined 43 anticancer drugs approved for marketing between 1999 and 2001, comparing the indications from FDA-approved labeling to those in the NCCN compendium. Their findings were recently published in Therapeutic Innovation & Regulatory Science.

Findings of the Research

Among the anticancer drugs studied, the researchers identified 99 FDA-approved uses compared to 451 indications listed in the NCCN compendium. Of the NCCN compendium indications, 198 were classified as on-label uses while 253 were off-label uses.

Notably, the NCCN compendium assesses the quality of evidence supporting off-label uses. The researchers categorized 231 off-label uses recommended by the NCCN compendium as “well-accepted off-label uses,” defined as those with high-quality clinical evidence (category 1 or 2A).

Public Health Implications

The significant disparity between FDA-approved uses and real-world clinical practice raises public health concerns. The FDA’s mission is to communicate accurate drug-related information to both the public and healthcare providers. However, outdated information may prompt physicians and patients to seek alternative sources. While the NCCN compendium provides high-quality evidence, other resources might recommend off-label uses with less robust support.

Challenges in Updating Drug Labeling

The FDA has acknowledged the importance of off-label uses and has made attempts to update prescription drug labeling. However, these efforts have previously faltered due to the voluntary nature of drug manufacturers’ responsibilities to provide updated information about drug effectiveness.

Conclusion

The substantial gap between FDA labeling of prescription drugs and actual clinical practice is a pressing public health issue. Accurate and updated prescription drug labels are vital for enabling healthcare providers and patients to identify drug indications backed by the highest quality evidence.

Written by Jessica Caporuscio, PharmD
Reference: Shea MB, Stewart M, Van Dyke H, et al. Outdated Prescription Drug Labeling: How FDA-Approved Prescribing Information Lags Behind Real-World Clinical Practice. Ther Innov Regul Sci. 2018