风险偏差和品牌解释了在氨基葡萄糖治疗骨关节炎症状缓解的安慰剂对照试验中观察到的不一致性：一项荟萃分析。

Risk of bias and brand explain the observed inconsistency in trials on glucosamine for symptomatic relief of osteoarthritis: a meta-analysis of placebo-controlled trials.

机构信息

The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Copenhagen, Denmark.

出版信息

Arthritis Care Res (Hoboken). 2014 Dec;66(12):1844-55. doi: 10.1002/acr.22376.

DOI:10.1002/acr.22376

PMID:24905534

Abstract

OBJECTIVE

To determine whether study sponsor, chemical formulation, brand of glucosamine, and/or risk of bias explain observed inconsistencies in trials of glucosamine's efficacy for treating pain in osteoarthritis (OA).

METHODS

A systematic review and stratified meta-analysis of randomized placebo-controlled trials was performed, and random-effects models were applied with inconsistency (I(2) ) and heterogeneity (tau(2) ) estimated using Review Manager and SAS, respectively. The major outcome was reduction of pain; the standardized mean difference (SMD [95% confidence interval (95% CI)]) served as effect size.

RESULTS

The inclusion criteria yielded 25 trials (3,458 patients). Glucosamine moderately reduced pain (SMD -0.51 [95% CI -0.72, -0.30]), although a high level of between-trial inconsistency was observed (I(2) = 88%). The single most important explanation (i.e., covariate) was brand, reducing heterogeneity by 41% (P = 0.00032). Twelve trials (1,437 patients) using the Rottapharm/Madaus product resulted in significant pain reduction (SMD -1.07 [95% CI -1.47, -0.67]), although a sensitivity analysis of 3 low risk of bias trials using the Rottapharm/Madaus product showed less promising results (SMD -0.27 [95% CI -0.43, -0.12]), which is only a small effect size. Thirteen trials (1,963 patients) using non-Rottapharm/Madaus products consistently failed to show a reduction in pain (SMD -0.11 [95% CI -0.46, 0.24]). The second most important explanation was overall risk of bias (reducing heterogeneity by 32%).

CONCLUSION

Most of the observed heterogeneity in glucosamine trials is explained by brand. Trials using the Rottapharm/Madaus glucosamine product had a superior outcome on pain in OA compared to other preparations of glucosamine. Large inconsistency was found, however. Low risk of bias trials, using the Rottapharm/Madaus product, revealed a small effect size.

摘要

目的

确定研究赞助商、化学配方、氨基葡萄糖品牌和/或偏倚风险是否可以解释氨基葡萄糖治疗骨关节炎（OA）疼痛疗效试验中的观察到的不一致性。

方法

对随机安慰剂对照试验进行系统评价和分层荟萃分析，并使用 Review Manager 和 SAS 分别估计不一致性（I²）和异质性（tau²），应用随机效应模型。主要结局是疼痛减轻；标准化均数差（SMD [95%置信区间（95%CI）]）作为效应大小。

结果

纳入标准产生了 25 项试验（3458 例患者）。氨基葡萄糖可适度减轻疼痛（SMD -0.51 [95%CI -0.72，-0.30]），但观察到试验间存在高度不一致性（I² = 88%）。最重要的单一解释因素（即协变量）是品牌，可降低 41%的异质性（P = 0.00032）。使用 Rottapharm/Madaus 产品的 12 项试验（1437 例患者）可显著减轻疼痛（SMD -1.07 [95%CI -1.47，-0.67]），但对使用 Rottapharm/Madaus 产品的 3 项低偏倚风险试验进行敏感性分析的结果不太理想（SMD -0.27 [95%CI -0.43，-0.12]），这只是一个较小的效应大小。使用非 Rottapharm/Madaus 产品的 13 项试验（1963 例患者）始终未能显示疼痛减轻（SMD -0.11 [95%CI -0.46，0.24]）。第二重要的解释因素是整体偏倚风险（降低 32%的异质性）。