Off-Label Prescribing: A Call for Heightened Professional and Government Oversight

Abstract

Off-label prescribing is an integral part of contemporary medicine. Many patients benefit when they receive drugs or devices under circumstances not specified on the label approved by the Food and Drug Administration (FDA). An off-label use may provide the best available intervention for a patient, as well as the standard of care for a particular health problem. In oncology, pediatrics, geriatrics, obstetrics, and other practice areas, patient care could not proceed without off-label prescribing. 1 When scientific and medical evidence justify off-label uses, physicians promote patients' interests by prescribing products off label.Off-label prescribing can also harm patients, however. The potential for harm is greatest when an off-label use lacks a solid evidentiary basis. A 2006 study examining prescribing practices for 169 commonly prescribed drugs found high rates of off-label use with little or no scientific support. 2 Researchers examining off-label use in U.S. children's hospitals concluded, "[W]e still have incomplete knowledge about the safety and efficacy of many medications commonly used to treat children across a range of drug classes and clinical diagnoses." 3 More than half the respondents in a survey of academic medical centers reported that innovative off-label prescribing raised concerns in their institutions, such as lack of data, costs, and unfavorable risk-benefit ratios.4 When substantial uncertainty exists about off-label applications, patients are at risk of receiving harmful or ineffective treatments.Legal authorities recognize physicians' discretion to prescribe products off label. 5 In the existing regulatory framework, once the FDA approves a product for marketing, physicians may prescribe it for indications or patient populations not included on the label. They may also prescribe drugs at dosages or using methods of administration not specified on the label. 6 Omission from the approved label does not mean that the FDA disapproves of an off-label use, it simply indicates that the agency has not reviewed that use. Of course, like other parts of medical practice, off-label prescribing can lead to malpractice liability if it fails to conform to accepted standards of care. 7 In a perfect world, all uses of drugs and devices would be supported by solid research. The existing regulatory system fails to impose this high standard, however, and the private sector often lacks incentives to conduct rigorous evaluations of off-label uses. In the current situation, the medical community has primary responsibility for determining when off-label prescribing is appropriate for patients. But appropriate off-label prescribing can be challenging for physicians today, because of time pressures, information overload, and the involvement of industry in research and education about off-label uses.Responsible off-label prescribing requires physicians to: (1) evaluate whether there is sufficient evidence to justify an off-label use; (2) press for additional information and research when NIH Public Access

Off-Label Use of Rituximab in a Multipayer Insurance System

“…As more scrutiny is placed on off-label prescription regulation, 14,15 it is important to examine population-wide medication use to document what is currently considered standard prescription practice and to analyze what proportion of such use is supported by scientific evidence. It would be worthwhile to compare these usage patterns with those in a single-payer system, such as Veterans Affairs, staff model HMO systems, or Medicare to determine whether a particular system is more effective at monitoring off-label usage and limiting it to diagnoses with sufficient evidence in the postapproval setting.…”

Outpatient Department – A Prospective Study at a Tertiary Care Teaching Hospital

“…Clinicians can prescribe off-label or unlicensed drugs provided they are aware about the benefits of such prescribing in certain special conditions. 25,26 To ensure that children are not exposed to unnecessary risks, controlled paediatric clinical trials are required for drugs to determine the most appropriate dose in children of different age groups.…”

Ten Common Questions (and Their Answers) About Off-label Drug Use

“…37 As peer-reviewed published evidence focusing on a drug's off-label use grows over time, new standards of practice involving the off-label use of a drug begin to develop. 38 To help determine whether the standards of practice are being met when prescribing medications for OLDU, physicians should first ask themselves several questions 38,45,46 : (1) Does the native drug have FDA approval? (2) Has the off-label use been subjected to substantial peer review?…”