Off-label prescriptions in dermatology: A prospective, multicentre and supraregional study of applications and decisions on the reimbursement of costs in Germany

“标签外使用”的定义是在批准的适应症之外开具药品处方或进行干预。罕见病通常缺乏“标签内”治疗选择。鉴于大量的疾病实体具有低患病率，如寻常天疱疮或系统性硬皮病，皮肤病学领域特别受到标签外使用引起的问题的影响。法定健康保险仅在特定情况下保证对标签外处方的费用覆盖。为了避免报销，德国的医生可以根据具体情况，在开具标签外治疗处方之前向医疗保险申请费用报销（标签外申请，OL-A）。由于处理时间和可能的拒绝，这可能很耗时，并导致罕见病患者的相关治疗延迟。计划的医疗保健研究项目的目的是评估和分析有关OL-A频率的数据，费用报销的决定，时间消耗和对患者护理的影响。OL-A和连续通信将从提供皮肤科门诊的德国大学医院连续收集。除了这些来自常规患者护理的数据之外，进一步的方面（例如，决定和开始适应症外治疗之间的持续时间）。该项目的结果将是超说明书使用的频率和相关性，生成针对特定适应症的经常批准的干预措施列表，以及量化患者治疗开始的延迟。此外，我们将研究批准率和决定和开始适应症外治疗之间的持续时间是否由以下任何因素决定：健康保险公司，地区，OL-A的质量，所要求的治疗费用，该研究旨在调查当前的法律的环境是否限制了最佳的患者护理，以及由于精心制作而花费的时间量的O-A。将揭示批准率的决定因素，并评估健康保险公司之间的区域差异或差异。生成针对特定适应症的经常批准的干预措施列表可以作为未来研究的基础，以建立批准OL-A的标准化标准。此外，频繁获批的超说明书处方清单可能会促使德国监管机构（Bundesinstitut für Arzneimittel und Medizinprodukte）的专家组将更多积极建议纳入德国获批的超说明书使用清单（“Arzneimittelrichtlinie”）。在医疗保健政策的背景下，研究结果可能会鼓励讨论罕见疾病患者的情况和改善医疗保健过程的可能性。

"Off-label use" is defined as the prescription of pharmaceutical products or interventions outside their approved indications. Rare diseases frequently lack "in-label" treatment options. Given the large amount of disease entities with a low prevalence such as pemphigus vulgaris or systemic scleroderma, the field of dermatology is particularly affected by problems arising with off-label use. Cost coverage of off-label prescriptions by the statutory health insurance is only warranted under specific circumstances. In order to avoid reimbursement claims, physicians in Germany can - on a case-by-case basis - file an application for cost coverage by the health insurance prior to the prescription of off-label therapies (off-label application, OL-A). Due to processing times and possible rejections, this may be time consuming and lead to a delay of the initiation of relevant treatments for patients who have rare diseases. Intention of the planned healthcare research project is to assess and analyze data concerning the frequency of OL-A, decisions on the reimbursement of costs, time consumption and implications for patient care. OL-A and the consecutive correspondence will be collected consecutively from German university hospitals offering a dermatology outpatient clinic. Apart from these data derived from routine patient care, further aspects (e.g., duration between decision for and initiation of an off-label treatment) will be assessed. Outcomes of the project will be the frequency and relevance of off-label use, the generation of a list of frequently approved interventions for specific indications and the quantification of the delay in the initiation of patient treatment. Furthermore, we will investigate whether approval rates and duration between the decision for and initiation of an off-label treatment are determined by any of the following factors: health insurer, region, quality of the OL-A, costs of the requested treatment, or patient age.The study aims at investigating whether the current legal circumstances restrict an optimal patient care and what amount of time expenditure is attributable to the elaboration of OL-A. Determinants of approval rates will be revealed and regional disparities or differences between health insurers assessed. The generation of a list of frequently approved interventions for specific indications may serve as a basis for future research to establish standardized criteria for approvals of OL-A. Moreover, the list of frequently approved off-label prescriptions may stimulate the expert groups of the German regulatory institution (Bundesinstitut für Arzneimittel und Medizinprodukte) to include further positive recommendations into the list of approved off-label use in Germany (“Arzneimittelrichtlinie”). In the context of health care policy, the study results may encourage a discussion of the situation of patients who have rare diseases and possibilities to improve medical care processes.