The fading of reported effectiveness. A meta-analysis of randomised controlled trials.
The fading of reported effectiveness. A meta-analysis of randomised controlled trials.
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DOI：
10.1186/1471-2288-6-25
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发表时间：
2006-05-11
影响因子：
4
通讯作者：
Porzsolt, Franz
中科院分区：
文献类型：
--
作者：
Gehr, Bernhard T;Weiss, Christel;Porzsolt, Franz
背景：药物治疗的“真实”效果大小随着时间的推移是恒定的。相反，随机对照试验（RCT）中报告的效应大小可能会随着时间的推移而变化，因为影响报告有效性的各种偏倚的总和不一定是恒定的。由于这会影响荟萃分析的有效性，我们测试了报告的效应大小随着时间的推移而减小的假设。此外，我们测试了三个可以解释可能的变化的假设。 方法：由于已建立完善的结果测量，因此本研究选择降脂药物普伐他汀和阿托伐他汀（血清低密度脂蛋白胆固醇，LDL-C）以及抗青光眼药物噻吗洛尔和拉坦前列素（眼内压，IOP）。研究是通过标准化 MEDLINE 搜索确定的。随机对照试验研究了上述确定的以单一疗法和规定剂量给药的药物。提取每项研究的发表年份、基线（=感兴趣的治疗组的治疗前值）和干预后平均值、患者数量以及实验组或对照组的分配。 结果：总共筛选了 625 条引用； 206 人符合纳入标准。普伐他汀的报告效应大小（五年内报告效应大小的变化：-3.22% LDL-C，P < .0001）、噻吗洛尔（-0.56 mmHg，P < .0001）和拉坦前列素（-1.78 mmHg，P = .0074）随着时间的推移而下降，而阿托伐他汀没有显着变化（+0.31% LDL-C，P = .8618）。多元回归分析显示基线值是最重要的影响因素；研究规模或治疗组没有发挥显着作用。结论：随机对照试验中报告的药物治疗的有效性在四种研究药物中的三种中随着时间的推移而降低，这主要是由于基线差异造成的。我们将这种现象称为“报告有效性衰退”。在这种情况下，荟萃分析的有效性可能会受到损害。因此，我们建议在未来的荟萃分析中观察这种现象，以保证最大的透明度。
BACKGROUND: The "real" effect size of a medical therapy is constant over time. In contrast, the effect size reported in randomised controlled trials (RCTs) may change over time because the sum of all kinds of bias influencing the reported effectiveness is not necessarily constant. As this would affect the validity of meta-analyses, we tested the hypothesis that the reported effect size decreases over time. Furthermore, we tested three hypotheses that would explain a possible change.METHODS: Because of well established outcome measures, the lipid-lowering drugs Pravastatin and Atorvastatin (serum low-density lipoprotein cholesterol, LDL-C) and the anti-glaucoma drugs Timolol and Latanoprost (intraocular pressure, IOP) were chosen for this investigation. Studies were identified by a standardized MEDLINE search. RCTs investigating the above identified medications administered as monotherapy, and in defined dosages, were included. Publication year, baseline (= pre-treatment value in the treatment group of interest) and post intervention means, number of patients and the assignment to experimental or control group were extracted for each study.RESULTS: A total of 625 citations were screened; 206 met the inclusion criteria. The reported effect size of Pravastatin (change of reported effect size in five years: -3.22% LDL-C, P < .0001), Timolol (-0.56 mmHg, P < .0001) and Latanoprost (-1.78 mmHg, P = .0074) decreased over time, while there was no significant change for Atorvastatin (+0.31% LDL-C, P = .8618). Multiple regression analysis showed that baseline values were the most important influencing factor; study size or treatment group did not play a significant role.CONCLUSION: The effectiveness of medical therapies reported in RCTs decreases over time in three of the four investigated pharmaceuticals, caused mainly by baseline differences. We call this phenomenon "fading of reported effectiveness". Under this condition the validity of a meta-analysis may be impaired. Therefore we propose to observe this phenomenon in future meta-analyses in order to guarantee a maximum of transparency.