Off-label prescribing: Comparative evidence, regulation, and utilization

标签外处方：比较证据、监管和利用

• 批准号: 7785649
• 负责人: AARON SETH KESSELHEIM
• 金额: $ 15.92万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7785649
• 关键词: Off; label; prescribing; Comparative; evidence

DESCRIPTION (provided by the applicant): Off-label prescription of drugs is a routine practice among physicians. The Food and Drug Administration (FDA) approves new drugs based on their effectiveness for a particular indication, but once a drug enters the market, physicians can prescribe drugs for other indications that they deem appropriate. Sometimes, such prescribing is based on rigorous randomized trial data that has not (yet) led to formal FDA approval for a given indication; other off-label use is based on less well-established evidence. Because of concerns about cost and/or quality of care, payers in both the private and public sectors have sought to prohibit off-label use, limit its coverage, and/or require patients to assume an increasing fraction of its cost. Off-label drug use thus involves prescriptions that may or may not be sound therapy, that may involve unnecessary risk to patients, and that may be cost-effective or cost-ineffective-or a mix of all three. Though off-label use has been estimated to account for nearly three-quarters of the use of some drugs, the practice remains poorly understood. Few studies have detailed extent to which newly approved drugs are prescribed for off-label uses, or the evidence supporting such utilization. In addition, scant data exist regarding the patient or physician or drug characteristics that predict when an off-label use is more likely to occur. Though promotion of drugs for off-label uses is strictly regulated, there have been several recent high-profile instances of violation of these regulations. No studies have systematically evaluated the impact of marketing or other legal, regulatory, or financial forces on the practice of off-label drug use. We propose to develop a comprehensive scheme for studying off-label drug use to categorize the different types of off-label use and their clinical, economic, and policy implications. We will apply this typology to evaluate the frequency and patterns of off-label drug use in three important categories: oncology drugs, neuropsychiatric drugs, and drugs for other rare diseases. We will identify target drugs and review the medical literature, as well as expert opinion, regarding specific uses of each product to define the quality of evidence supporting each off-label use. We will then evaluate the characteristics of off-label drug use in large population databases of prescriptions and diagnoses, including Medicaid patients, Medicare patients, and those covered by a large health insurer. Using these datasets, we will use multivariable regression to determine predictors of use of specific off-label drugs for particular purposes, and identify characteristics of patients, physicians, and medications that are associated with off-label use. Finally, we will use time-trend analysis to determine the impact of changes in legal, regulatory, or financial factors that impact off-label use. A better understanding of the properties and predictors of off-label use can inform evidence-based prescribing of these products. Studying the benefit-risk-cost relationships associated with such uses can lead to more enlightened approaches to prescribing and policy decisions in this increasingly contentious area. Many physicians prescribe drugs for non-FDA-approved reasons ("off-label uses"), but when this practice occurs without sufficient evidence basis, it raises important health policy concerns about patient safety and cost-effectiveness. We propose to study the characteristics of off-label drug use in three select classes-cancer drugs, neuropsychiatry drugs, and drugs for other rare diseases. Using expert interviews and pharmaceutical claims data from a variety of large databases, we will identify the predictors and frequency of off- label use and determine how the practice is affected by certain external scientific, market, and regulatory events.

描述（由申请人提供）：超说明书处方药物是医生的常规做法。美国食品和药物管理局 (FDA) 根据新药对特定适应症的有效性来批准新药，但一旦药物进入市场，医生就可以为他们认为合适的其他适应症开药。有时，此类处方是基于严格的随机试验数据，但尚未获得 FDA 对特定适应症的正式批准；其他超说明书使用是基于不太确定的证据。由于对护理成本和/或质量的担忧，私营和公共部门的付款人都试图禁止超说明书使用、限制其覆盖范围和/或要求患者承担越来越多的费用。因此，标签外药物使用涉及的处方可能是或可能不是合理的治疗，可能会给患者带来不必要的风险，可能具有成本效益或成本无效​​，或三者兼而有之。尽管据估计超说明书使用占某些药物使用量的近四分之三，但人们对这种做法仍然知之甚少。很少有研究详细说明新批准的药物用于超说明书用途的程度，或支持这种用途的证据。此外，关于患者、医生或药物特征的数据很少，无法预测何时更有可能发生超说明书使用。尽管药品说明书外用途的推广受到严格监管，但最近发生了几起引人注目的违反这些规定的事件。尚无研究系统评估营销或其他法律、监管或财务力量对超说明书用药实践的影响。我们建议制定一个研究超说明书用药的综合方案，对不同类型的超说明书用药及其临床、经济和政策影响进行分类。我们将应用这种类型学来评估三个重要类别的超说明书用药的频率和模式：肿瘤药物、神经精神药物和其他罕见疾病药物。我们将确定目标药物并审查有关每种产品具体用途的医学文献和专家意见，以确定支持每种标签外用途的证据质量。然后，我们将在处方和诊断的大型人群数据库中评估超说明书用药的特征，包括医疗补助患者、医疗保险患者以及大型健康保险公司承保的患者。使用这些数据集，我们将使用多变量回归来确定为特定目的使用特定标签外药物的预测因素，并确定与标签外使用相关的患者、医生和药物的特征。最后，我们将使用时间趋势分析来确定影响标签外使用的法律、监管或财务因素变化的影响。更好地了解标签外使用的特性和预测因素可以为这些产品的循证处方提供信息。研究与此类用途相关的效益-风险-成本关系可以在这个日益有争议的领域带来更开明的处方和政策决策方法。许多医生出于非 FDA 批准的原因（“标签外用途”）开药，但当这种做法在没有足够证据基础的情况下发生时，就会引起对患者安全和成本效益的重要卫生政策担忧。我们建议研究三个选定类别（癌症药物、神经精神药物和其他罕见疾病药物）的超说明书用药特征。利用专家访谈和来自各种大型数据库的药品声称数据，我们将确定标签外使用的预测因素和频率，并确定某些外部科学、市场和监管事件对实践的影响。