Felson D T, Anderson J J, Boers M, Bombardier C, Furst D, Goldsmith C, Katz L M, Lightfoot R, Paulus H, Strand V
Boston University Arthritis Center, Massachusetts, USA.
Arthritis Rheum. 1995 Jun;38(6):727-35. doi: 10.1002/art.1780380602.
Trials of rheumatoid arthritis (RA) treatments report the average response in multiple outcome measures for treated patients. It is more clinically relevant to test whether individual patients improve with treatment, and this identifies a single primary efficacy measure. Multiple definitions of improvement are currently in use in different trials. The goal of this study was to promulgate a single definition for use in RA trials.
Using the American College of Rheumatology (ACR) core set of outcome measures for RA trials, we tested 40 different definitions of improvement, using a 3-step process. First, we performed a survey of rheumatologists, using actual patient cases from trials, to evaluate which definitions corresponded best to rheumatologists' impressions of improvement, eliminating most candidate definitions of improvement. Second, we tested 20 remaining definitions to determine which maximally discriminated effective treatment from placebo treatment and also minimized placebo response rates. With 8 candidate definitions of improvement remaining, we tested to see which were easiest to use and were best in accord with rheumatologists' impressions of improvement.
The following definition of improvement was selected: 20% improvement in tender and swollen joint counts and 20% improvement in 3 of the 5 remaining ACR core set measures: patient and physician global assessments, pain, disability, and an acute-phase reactant. Additional validation of this definition was carried out in a comparative trial, and the results suggest that the definition is statistically powerful and does not identify a large percentage of placebo-treated patients as being improved.
We present a definition of improvement which we hope will be used widely in RA trials.
类风湿关节炎（RA）治疗试验报告了接受治疗患者在多种结局指标上的平均反应。测试个体患者是否因治疗而改善在临床上更具相关性，这确定了单一的主要疗效指标。目前不同试验中使用了多种改善的定义。本研究的目的是推广一种用于RA试验的单一定义。
使用美国风湿病学会（ACR）RA试验结局指标核心集，我们采用三步法测试了40种不同的改善定义。首先，我们利用试验中的实际患者病例对风湿病学家进行了一项调查，以评估哪些定义与风湿病学家对改善的印象最相符，从而淘汰了大多数改善的候选定义。其次，我们测试了剩余的20种定义，以确定哪些能最大程度地区分有效治疗与安慰剂治疗，同时也使安慰剂反应率最小化。在剩下8种改善的候选定义后，我们测试哪些最易于使用且最符合风湿病学家对改善的印象。
选择了以下改善定义：压痛和肿胀关节计数改善20%，以及美国风湿病学会核心集其余5项指标中的3项（患者和医生整体评估、疼痛、残疾和急性期反应物）改善20%。在一项比较试验中对该定义进行了进一步验证，结果表明该定义具有统计学效力，且不会将很大比例的接受安慰剂治疗的患者判定为病情改善。
我们提出了一种改善定义，希望能在RA试验中广泛使用。
