Pfaar Oliver, Agache Ioana, Bergmann Karl-Christian, Bindslev-Jensen Carsten, Bousquet Jean, Creticos Peter S, Devillier Philippe, Durham Stephen R, Hellings Peter, Kaul Susanne, Kleine-Tebbe Jörg, Klimek Ludger, Jacobsen Lars, Jutel Marek, Muraro Antonella, Papadopoulos Nikolaos G, Rief Winfried, Scadding Glenis K, Schedlowski Manfred, Shamji Mohamed H, Sturm Gunter, van Ree Ronald, Vidal Carmen, Vieths Stefan, Wedi Bettina, Gerth van Wijk Roy, Frew Anthony J
Department of Otorhinolaryngology, Head and Neck Surgery, Section of Rhinology and Allergy, University Hospital Marburg, Philipps-Universität Marburg, Marburg, Germany.
Transylvania University, Brasov, Romania.
Allergy. 2021 Mar;76(3):629-647. doi: 10.1111/all.14331.
The placebo (Latin "I will please") effect commonly occurs in clinical trials. The psychological and physiological factors associated with patients' expectations about a treatment's positive and negative effects have yet to be well characterized, although a functional prefrontal cortex and intense bidirectional communication between the central nervous system and the immune system appear to be prerequisites for a placebo effect. The use of placebo raises certain ethical issues, especially if patients in a placebo group are denied an effective treatment for a long period of time. The placebo effect appears to be relatively large (up to 77%, relative to pretreatment scores) in controlled clinical trials of allergen immunotherapy (AIT), such as the pivotal, double-blind, placebo-controlled (DBPC) randomized clinical trials currently required by regulatory authorities worldwide. The European Academy of Allergy and Clinical Immunology (EAACI) therefore initiated a Task Force, in order to better understand the placebo effect in AIT and its specific role in comorbidities, blinding issues, adherence, measurement time points, variability and the natural course of the disease. In this Position Paper, the EAACI Task Force highlights several important topics regarding the placebo effect in AIT such as a) regulatory aspects, b) neuroimmunological and psychological mechanisms, c) placebo effect sizes in AIT trials, d) methodological limitations in AIT trial design and e) potential solutions in future AIT trial design. In conclusion, this Position Paper aims to examine the methodological problem of placebo in AIT from different aspects and also to highlight unmet needs and possible solutions for future trials.
安慰剂（拉丁语为“我将取悦”）效应在临床试验中普遍存在。与患者对治疗的正面和负面影响的期望相关的心理和生理因素尚未得到充分表征，尽管功能性前额叶皮层以及中枢神经系统与免疫系统之间强烈的双向通信似乎是安慰剂效应的先决条件。安慰剂的使用引发了某些伦理问题，尤其是如果安慰剂组的患者长时间无法获得有效治疗。在变应原免疫疗法（AIT）的对照临床试验中，安慰剂效应似乎相对较大（相对于治疗前评分高达77%），例如全球监管机构目前要求的关键、双盲、安慰剂对照（DBPC）随机临床试验。因此，欧洲变态反应和临床免疫学会（EAACI）发起了一个特别工作组，以便更好地了解AIT中的安慰剂效应及其在合并症、盲法问题、依从性、测量时间点、变异性和疾病自然病程中的具体作用。在本立场文件中，EAACI特别工作组强调了关于AIT中安慰剂效应的几个重要主题，例如a）监管方面，b）神经免疫学和心理机制，c）AIT试验中的安慰剂效应大小，d）AIT试验设计中的方法学局限性，以及e）未来AIT试验设计中的潜在解决方案。总之，本立场文件旨在从不同方面审视AIT中安慰剂的方法学问题，并突出未来试验中未满足的需求和可能的解决方案。
