Anderson J J, Baron G, van der Heijde D, Felson D T, Dougados M
Veterans Administration Medical Center, Bedford, Massachusetts, USA.
Arthritis Rheum. 2001 Aug;44(8):1876-86. doi: 10.1002/1529-0131(200108)44:8<1876::AID-ART326>3.0.CO;2-F.
To develop criteria for symptomatic improvement in patients with ankylosing spondylitis (AS), using outcome domain data from placebo-controlled clinical trials of nonsteroidal antiinflammatory drugs (NSAIDs).
Patient data from 5 short-term, randomized, controlled trials were used to assess equivalence, reliability, and responsiveness of multiple items in the 5 outcome domains for AS treatment: physical function, pain, spinal mobility, patient global assessment, and inflammation. At least one measure per domain was responsive (standardized response mean of > 0.5), except for the spinal mobility domain, which was omitted from the criteria. We developed and tested candidate improvement criteria in a random two-thirds subset from the 3 largest trials and used the remaining one-third for validation. These 3 largest trials included 923 patients (631 receiving NSAIDs, 292 in placebo groups). We selected the multiple domain definition that best distinguished NSAID treatment from placebo by chi-square test and that had a placebo response rate of < or = 25%.
Candidate definitions were changes in single domains and in multiple measure indices, as well as combinations of improvements in multiple domains. Worsening in a domain was defined as a change for the worse of > or = 20% and a net change for the worse of > or = 10 units on a scale of 0-100. Partial remission (for comparison purposes) was defined as an end-of-trial value of < 20/100 in each of the 4 domains. Among 20 candidate criteria, change of > or = 20% and > or = 10 units in each of 3 domains and absence of worsening in the fourth discriminated best in the development subset (51% of patients improved with NSAIDs, 25% with placebo; chi2 = 36.4, P < 0.001). Results were confirmed in the validation subset. Almost all patients satisfying the definition of partial disease remission at the end of the trial had also improved by this criterion. Among all 923 patients, improvement rates using this criterion were 49% for NSAID-treated patients and 24% for placebo-treated patients.
Although further validation using data from new trials is still needed, we conclude that we have developed a clinically valid, easy-to-use measure of short-term improvement in AS.
利用非甾体抗炎药（NSAIDs）安慰剂对照临床试验的结局域数据，制定强直性脊柱炎（AS）患者症状改善的标准。
来自5项短期随机对照试验的患者数据用于评估AS治疗的5个结局域中多个项目的等效性、可靠性和反应性：身体功能、疼痛、脊柱活动度、患者整体评估和炎症。除脊柱活动度域外，每个域至少有一项指标具有反应性（标准化反应均值>0.5），该域未纳入标准。我们在3项最大试验中随机抽取的三分之二子集里制定并测试了候选改善标准，并用其余三分之一进行验证。这3项最大试验纳入了923例患者（631例接受NSAIDs治疗,292例在安慰剂组）。我们通过卡方检验选择了能最好地区分NSAIDs治疗与安慰剂且安慰剂反应率≤25%的多域定义。
候选定义包括单域变化、多指标指数变化以及多域改善的组合。一个域的恶化定义为在0至100分的量表上变差≥20%且净变差≥10分。部分缓解（用于比较）定义为试验结束时4个域中每个域的值<20/100。在20个候选标准中，3个域中每个域变化≥20%且≥10分且第4个域无恶化在开发子集中区分度最佳（NSAIDs治疗组51%的患者改善，安慰剂组25%；χ2 = 36.4，P < 0.001）。结果在验证子集中得到证实。几乎所有在试验结束时满足部分疾病缓解定义的患者也符合该标准的改善情况。在所有923例患者中，使用该标准的改善率在NSAIDs治疗患者中为49%，在安慰剂治疗患者中为24%。
尽管仍需要使用新试验数据进行进一步验证，但我们得出结论，我们已经制定了一种临床上有效的、易于使用的AS短期改善测量方法。
