Bonertz Andreas, Tripathi Anubha, Zimmer Julia, Reeb Christina, Kaul Susanne, Bridgewater Jennifer, Rabin Ronald L, Slater Jay E, Vieths Stefan
Paul-Ehrlich-Institut, Langen, Germany.
US Food and Drug Administration, Silver Spring, Md.
J Allergy Clin Immunol. 2022 Mar;149(3):812-818. doi: 10.1016/j.jaci.2022.01.004.
Clinical studies demonstrate that efficacy and safety in allergen immunotherapy (AIT) are linked to a multiplicity of factors decisively influencing success or failure. In recent years, numerous trials were performed with correspondent study results published. Yet, the number of AIT products successfully obtaining licensure in the analogous time frame is comparably limited. Essential for licensure is that the AIT product investigated remains comparable in its qualitative and quantitative composition throughout the clinical development. Verification of efficacy is not solely demonstrated by a statistically significant difference between the test and control populations; it must also be shown to be clinically relevant. Choice of meaningful inclusion and end-point criteria is critical. Post hoc or subgroup analysis can be supportive but needs verification as predefined criteria in additional studies. Data analysis may be presented on varying analysis populations, while it should be based on the intention-to-treat population for regulatory review to allow objective assessment of the treatment effect on the overall study population. Apparently conflicting interpretations of clinical data between publications and regulatory review are frequently based on their inherently different objectives, with regulatory review taking into considerations the full data sets of all relevant clinical studies for the concerned AIT product to allow an informed decision on licensure.
临床研究表明，变应原免疫疗法（AIT）的疗效和安全性与多种决定性影响成败的因素相关。近年来，进行了大量试验并发表了相应的研究结果。然而，在同一时间框架内成功获得许可的AIT产品数量相对有限。获得许可的关键在于，所研究的AIT产品在整个临床开发过程中的定性和定量组成保持可比。疗效验证不仅要通过试验组和对照组之间具有统计学意义的差异来证明；还必须证明其具有临床相关性。选择有意义的纳入标准和终点标准至关重要。事后分析或亚组分析可能有帮助，但需要在额外研究中作为预定义标准进行验证。数据分析可以在不同的分析人群中呈现，而在监管审查时应基于意向性治疗人群，以便对整个研究人群的治疗效果进行客观评估。出版物和监管审查之间对临床数据明显相互矛盾的解释往往基于它们本质上不同的目标，监管审查会考虑相关AIT产品所有相关临床研究的完整数据集，以便就是否许可做出明智的决定。
