Calzetta Luigino, Rogliani Paola, Ora Josuel, Puxeddu Ermanno, Cazzola Mario, Matera Maria Gabriella
Dept of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
Division of Respiratory Medicine, University Hospital Tor Vergata, Rome, Italy.
Eur Respir Rev. 2017 Jan 17;26(143). doi: 10.1183/16000617.0043-2016. Print 2017 Jan.
When there are no randomised clinical trials directly comparing all relevant treatment options, an indirect treatment comparison via meta-analysis of the available clinical evidence is an acceptable alternative. However, meta-analyses may be very misleading if not adequately performed. Here, we propose and validate a simple and effective approach to meta-analysis for exploring the effectiveness of long-acting β-agonist (LABA)/long-acting muscarinic antagonist (LAMA) fixed-dose combinations in chronic obstructive pulmonary disease.14 articles with 20 329 patients (combinations n=9292; monocomponents n=11 037) were included in this study. LABA/LAMA combinations were always more effective than the monocomponents in terms of the improvement in trough forced expiratory volume in 1 s, transition dyspnoea index and St George's Respiratory Questionnaire scores after 3, 6 and 12 months of treatment. No significant publication bias was identified. Significant discrepancies with previous network meta-analyses have been found, with overall differences ranging from 26.7% to 43.3%.Results from previous network meta-analyses were misleading because no adequate attention was given to formulating the review question, specifying eligibility criteria, correctly identifying studies, collecting appropriate information and deciding what it would be pharmacologically relevant to analyse. The real gradient of effectiveness of LABA/LAMA fixed-dose combinations remains an unmet medical need; however, it can be investigated indirectly using a high-quality meta-analytic approach.
当没有直接比较所有相关治疗方案的随机临床试验时，通过对现有临床证据进行荟萃分析来进行间接治疗比较是一种可接受的替代方法。然而，如果荟萃分析执行不当，可能会产生很大的误导性。在此，我们提出并验证了一种简单有效的荟萃分析方法，以探讨长效β受体激动剂（LABA）/长效毒蕈碱拮抗剂（LAMA）固定剂量组合在慢性阻塞性肺疾病中的有效性。本研究纳入了14篇文章，共20329例患者（联合用药组n = 9292；单一组分治疗组n = 11037）。在治疗3、6和12个月后，就1秒用力呼气容积谷值、过渡性呼吸困难指数和圣乔治呼吸问卷评分的改善情况而言，LABA/LAMA联合用药组始终比单一组分治疗组更有效。未发现明显的发表偏倚。发现与之前的网状荟萃分析存在显著差异，总体差异范围为26.7%至43.3%。之前网状荟萃分析的结果具有误导性，因为在制定综述问题、明确纳入标准、正确识别研究、收集适当信息以及决定分析哪些药理学相关内容方面没有给予充分关注。LABA/LAMA固定剂量组合的实际有效性梯度仍然是未满足的医疗需求；然而，可以使用高质量的荟萃分析方法进行间接研究。
