Horn Andreas, Bachert Claus, Brehmer Detlef
HNO-Praxis am Neckar, Heidelberg, Deutschland.
HNO-Universitätsklinik, Gent, Belgien.
Z Evid Fortbild Qual Gesundhwes. 2021 Feb;160:11-20. doi: 10.1016/j.zefq.2020.11.010. Epub 2021 Jan 15.
With the introduction of the Therapy Allergens Ordinance (TAV) the previously unapproved therapeutic allergens on the existing market need to be checked for their risk-benefit ratio as a basic prerequisite for approval under pharmaceutical law. This process is criticized because it can lead to long transition periods so that patients will probably be treated for two decades with preparations whose effectiveness has not yet been proven and may never be proven. The aim of this work is to list the critical preparations for which no publicly accessible study activity has been recorded since the beginning of the TAV in 2008. For this purpose, the European Clinical Trials Register (clinicaltrialsregister.eu) and the American study register (ClinicalTrials.gov) are systematically searched. The following hypothesis, consistent with the TAV, will be checked: "In the past years, study programs were carried out for the preparations in the process of the TAV - the majority of these preparations are about to be approved by PEI". The hypothesis is refuted with the findings of this work. In fact, no preparation can currently be identified that is about to be TAV approved. 61 preparations are currently in the TAV process; only two preparations have already passed this successfully. If the total of 63 (61+2) preparations are combined in the homologous groups - trees, grasses, mites and mixtures -, there are 33 preparations that can be classified as follows: For the 33 preparations in the TAV process, 36 studies (phase II and III) that may potentially be relevant for TAV were found as part of the screening. For 15 of these studies the results have duly been entered in the European study register. The results of another 13 studies have not been stored in the study register although they are marked as completed. No information has been stored in the European study register for four studies so that the status of these studies remains unclear. Four studies have not yet been completed. Responsible doctors can make recommendations for the prescription of a certain SIT preparation only if there is adequate evidence of its effectiveness. For preparations that have not yet started studies more than ten years after the introduction of the TAV, it is very doubtful whether approval can still be obtained or whether it is even being sought. For the three main inhaled allergens (grasses, trees and mites) there is already a selection of approved, evidence-based and effective alternatives for both subcutaneous (SCIT) and sublingual (SLIT) application from various manufacturers on the market. The use of therapies that have been approved and proven effective is essential in terms of guideline-compliant, sensible care for patients.
随着《治疗性变应原条例》（TAV）的出台，现有市场上先前未经批准的治疗性变应原需要根据其风险效益比进行检查，这是根据药品法批准的基本前提条件。这一过程受到批评，因为它可能导致漫长的过渡期，以至于患者可能会使用有效性尚未得到证实且可能永远无法得到证实的制剂接受二十年的治疗。这项工作的目的是列出自2008年TAV开始以来没有公开可查研究活动记录的关键制剂。为此，系统搜索了欧洲临床试验注册库（clinicaltrialsregister.eu）和美国研究注册库（ClinicalTrials.gov）。将检验以下与TAV一致的假设：“在过去几年中，针对TAV过程中的制剂开展了研究项目——这些制剂中的大多数即将获得PEI的批准”。这项工作的结果驳斥了该假设。事实上，目前无法确定有任何制剂即将获得TAV批准。目前有61种制剂处于TAV审批过程中；只有两种制剂已成功通过该过程。如果将这63种（61 + 2）制剂按照同源组——树木、草、螨及混合物——进行合并，有33种制剂可作如下分类：对于处于TAV审批过程中的这33种制剂，在筛选过程中发现了36项可能与TAV相关的研究（II期和III期）。其中15项研究的结果已正式录入欧洲研究注册库。另外13项研究虽标记为已完成，但其结果尚未存储在研究注册库中。有4项研究在欧洲研究注册库中没有存储任何信息，因此这些研究的状态不明。有4项研究尚未完成。只有在某种特异性免疫治疗（SIT）制剂有效性的充分证据存在时，负责的医生才能对其处方开具提出建议。对于在TAV出台十多年后仍未开始研究的制剂，能否仍获得批准或是否正在寻求批准都非常值得怀疑。对于三种主要的吸入性变应原（草、树和螨），市场上已有来自不同制造商的多种皮下（SCIT）和舌下（SLIT）应用的已批准、有循证依据且有效的替代产品可供选择。就符合指南、合理地照顾患者而言，使用已批准并经证实有效的疗法至关重要。
