Prioritizing Future Research on Off‐Label Prescribing: Results of a Quantitative Evaluation

Abstract

Background Drug use for indications not approved by the Food and Drug Administration exceeds 20% of prescribing. Available compendia indicate that a minority of off-label uses are well supported by evidence. Policy makers, however, lack information to identify where systematic reviews of the evidence or other research would be most valuable. Methods We developed a quantitative model for prioritizing individual drugs for future research on off-label uses. The base model incorporated three key factors, 1) the volume of off-label use with inadequate evidence, 2) safety, and 3) cost and market considerations. Nationally representative prescribing data were used to estimate the number of off-label drug uses by indication from 1/2005 through 6/2007 in the United States, and these indications were then categorized according to the adequacy of scientific support. Black box warnings and safety alerts were used to quantify drug safety. Drug cost, date of market entry, and marketing expenditures were used to quantify cost and market considerations. Each drug was assigned a relative value for each factor, and the factors were then weighted in the final model to produce a priority score. Sensitivity analyses were conducted by varying the weightings and model parameters. Results Drugs that were consistently ranked highly in both our base model and sensitivity analyses included quetiapine, warfarin, escitalopram, risperidone, montelukast, bupropion, sertraline, venlafaxine, celecoxib, lisinopril, duloxetine, trazodone, olanzapine, and epoetin alfa. Conclusion Future research into off-label drug use should focus on drugs used frequently with inadequate supporting evidence, particularly if further concerns are raised by known safety issues, high drug cost, recent market entry, and extensive marketing. Based on quantitative measures of these factors, we have prioritized drugs where targeted research and policy activities have high potential value.

Off-Label Use of Rituximab in a Multipayer Insurance System

“…Although there are concerns about the accuracy of drug compendia generally, 12 the Drugdex compendium has been used successfully in previous studies. 2 This study was limited by the lack of specificity in ICD-9 coding; the largest diagnostic code was Lymphomas, a broad entity that is presumed but not confirmed to reflect B-cell nonHodgkin's lymphoma. We addressed this by assuming that the Lymphomas group was evidence based to provide the most conservative estimate of off-label use.…”

“…2 Drugdex evaluates medication usage on the basis of three quality-oriented criteria, and three ordinal levels were used for offlabel indications (evidence-based, uncertain, and inadequate evidence) on the basis of the Drugdex assessment (see Table 1). …”

“…1 Physician survey studies suggest that off-label medication prescribing is common, totaling 21% of overall use among frequently used drugs. 2,3 Off-label usage in oncology is thought to be common and is defined as the use of medications for different types of cancer or for different doses or durations of treatment than were described in the FDA approval process, or as part of a nonapproved chemotherapy combination. 4 However, little is known about whether novel biologic agents, now widely used in oncology and other specialties, are administered within the range of evidence-based practices.…”

Restrictions On Pharmaceutical Detailing Reduced Off-Label Prescribing Of Antidepressants And Antipsychotics In Children

“…However, it carries the risk that patients will be exposed to uncertain benefits and the prospect of serious adverse effects. 5,6 For these and other reasons, federal law pro- hibits pharmaceutical companies from engaging in the direct promotion of drugs for unapproved uses. 4 Nonetheless, off-label promotion remains commonplace 7 and serves as one justification for AMCs' anti-detailing policies.…”

Cost and Utilization of Behavioral Health Medications Associated with Rescission of an Exemption for Prior Authorization for Severe and Persistent Mental Illness in the Vermont Medicaid Program

“…In addition, antidepressants, antipsychotics, and anxiolytics are increasingly being prescribed for off-label uses. 8 American pharmaceutical manufacturers are developing at least 300 new medications designed to treat the nearly 60 million Americans suffering from behavioral disorders. 9 Although the development of so many new medications to treat behavioral disorders is promising, states must still ensure that behavioral health programs are meeting the needs of their beneficiaries in a fiscally responsible manner.…”