Outdated Prescription Drug Labeling: How FDA-Approved Prescribing Information Lags Behind Real-World Clinical Practice

Shea, Michael; Stewart, Mark; Dyke, Hugo Van; Ostermann, Linda; Allen, Jeff; Sigal, Ellen V.

doi:10.1177/2168479018759662

Cited by 8 publications

(10 citation statements)

References 11 publications

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“…In contrast to the study by Wagner et al, a recent study reviewed the indications listed in the NCCN Compendium for 43 cancer drugs that were approved between 1999 and 2011 and compared these with the FDA-approved indications [34]. Of the 253 off-label uses across the 43 drugs reviewed in the study, 91% were deemed a ‘well-accepted off-label use’ by the authors, meaning the drug received either a Category 1 or Category 2A NCCN Guidelines recommendation in that setting [1, 34]. Additionally, 65% of the off-label uses were for cancer types not represented in the FDA labeling at the time of analysis.…”

Section: Discussionmentioning

confidence: 99%

Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals

Kurzrock

Gurski²,

Carlson

et al. 2019

Annals of Oncology

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BackgroundA previous analysis of 113 National Comprehensive Cancer Network® (NCCN®) recommendations reported that NCCN frequently recommends beyond Food and Drug Administration (FDA)-approved indications (44 off-label recommendations) and claimed that the evidence for these recommendations was weak.MethodsIn order to determine the strength of the evidence, we carried out an in-depth re-analysis of the 44 off-label recommendations listed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).ResultsOf the 44 off-label recommendations, 14 were later approved by the FDA and/or are supported by randomized controlled trial (RCT) data. In addition, 13 recommendations were either very minor extrapolations from the FDA label (n = 8) or were actually on-label (n = 5). Of the 17 remaining extrapolations, 8 were for mechanism-based agents applied in rare cancers or subsets with few available treatment options (median response rate = 43%), 7 were based on non-RCT data showing significant efficacy (>50% response rates), and 2 were later removed from the NCCN Guidelines because newer therapies with better activity and/or safety became available.ConclusionOff-label drug use is a frequent component of care for patients with cancer in the United States. Our findings indicate that when the NCCN recommends beyond the FDA-approved indications, the strength of the evidence supporting such recommendations is robust, with a significant subset of these drugs later becoming FDA approved or supported by RCT. Recommendations without RCT data are often for mechanism-based drugs with high response rates in rare cancers or subsets without effective therapies.

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Section: Discussionmentioning

confidence: 99%

Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals

Kurzrock

Gurski²,

Carlson

et al. 2019

Annals of Oncology

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“…In the US, a bill was introduced in the senate in September 2018, called the "Making Objective Drug Evidence Revisions for New Labeling Act" or "MODERN Labeling Act," which could be relevant to drug repurposing (115th Congress (2017(115th Congress ( -2018, 2018). The not-for-profit organization Friends of Cancer Research started the initiative to address outdated generic product labels in the US (Friends of Cancer Research, 2018;Shea et al, 2018). The proposed bill aims to establish a process for the FDA to determine whether the labeling of generic medicines needs modifying, including medicines with relevant accepted uses in clinical practice (supported by evidence that could meet the standards for approval) that are not reflected in the approved labeling.…”

Section: Initiating Legislative Changes In Europementioning

confidence: 99%

On-Label or Off-Label? Overcoming Regulatory and Financial Barriers to Bring Repurposed Medicines to Cancer Patients

et al. 2020

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Repurposing of medicines has gained a lot of interest from the research community in recent years as it could offer safe, timely, and affordable new treatment options for cancer patients with high unmet needs. Increasingly, questions arise on how new uses will be translated into clinical practice, especially in case of marketed medicinal products that are out of basic patent or regulatory protection. The aim of this study was to portray the regulatory framework relevant for making repurposed medicines available to cancer patients in Europe and propose specific policy recommendations to address the current regulatory and financial barriers. We outlined two routes relevant to the clinical adoption of a repurposed medicine. First, a new indication can be approved, and thus brought on-label, via the marketing authorization procedures established in European and national legislation. Such procedures initiate a detailed and independent assessment of the quality and the benefit-risk balance of a medicinal product in a specific indication, benefiting both prescribers and patients as it reassures them that the scientific evidence is robust. However, the process of marketing authorization for new therapeutic indications entails a high administrative burden and significant costs while the return-on-investment for the pharmaceutical industry is expected to be low or absent for medicines that are out of basic patent and regulatory protection. Moreover, most of the repurposing research is conducted by independent or academic researchers who do not have the expertise or resources to get involved in regulatory procedures. A second option is to prescribe a medicine off-label for the new indication, which is managed at the national level in Europe. While off-label use could provide timely access to treatments for patients with urgent medical needs, it also entails important safety, liability and financial risks for patients, physicians, and society at large. In view of that, we recommend finding solutions to facilitate bringing new uses on-label, for example by developing a collaborative framework between not-for-profit and academic organizations, pharmaceutical industry, health technology assessment bodies, payers, and regulators.

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“…Most changes to drug labeling occur at the discretion of a drug manufacturer. However, certain disincentives—such as the cost of preparing supplemental applications or generic competition once a drug goes off patent—may discourage drug manufacturers from pursuing labeling changes . Differing regulatory requirements for reference listed drugs (RLDs; i.e., brand‐name drugs) and generic drugs contribute to outdated and inaccurate labeling over time.…”

Section: Challenges Of Outdated Oncology Drug Labelingmentioning

confidence: 99%

“…A white paper from Friends of Cancer Research noted that outdated prescribing information leads clinicians to rely on sources other than drug labeling to guide their decision making for patient treatment. It also reduces the FDA's ability to convey accurate and reliable information about drugs to patients and clinicians . Project Renewal aims to provide clinicians and their patients with the most accurate drug labeling by developing a process and criteria for updating prescribing information for longstanding oncology drugs, based on the breadth of experience the cancer community has accumulated with using these drugs.…”

Section: Project Renewalmentioning

confidence: 99%

“…A number of important drugs used to treat cancer—many of which serve as the backbone of modern chemotherapy regimens—have outdated information in their drug labeling . This prescribing information is intended to be an authoritative resource to ensure clinicians are equipped with the information necessary to safely and effectively prescribe drugs to their patients.…”

Section: Introductionmentioning

confidence: 99%

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Challenges and Opportunities to Updating Prescribing Information for Longstanding Oncology Drugs

et al. 2019

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A number of important drugs used to treat cancer—many of which serve as the backbone of modern chemotherapy regimens—have outdated prescribing information in their drug labeling. The Food and Drug Administration is undertaking a pilot project to develop a process and criteria for updating prescribing information for longstanding oncology drugs, based on the breadth of knowledge the cancer community has accumulated with the use of these drugs over time. This article highlights a number of considerations for labeling updates, including selecting priorities for updating; data sources and evidentiary criteria; as well as the risks, challenges, and opportunities for iterative review to ensure prescribing information for oncology drugs remains relevant to current clinical practice.

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Outdated Prescription Drug Labeling: How FDA-Approved Prescribing Information Lags Behind Real-World Clinical Practice

Cited by 8 publications

References 11 publications

Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals

Level of evidence used in recommendations by the National Comprehensive Cancer Network (NCCN) guidelines beyond Food and Drug Administration approvals

On-Label or Off-Label? Overcoming Regulatory and Financial Barriers to Bring Repurposed Medicines to Cancer Patients

Challenges and Opportunities to Updating Prescribing Information for Longstanding Oncology Drugs

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