Johannessen T, Petersen H, Kristensen P, Fosstvedt D, Kleveland P M, Dybdahl J, Løge I
Dept. of Community Medicine and General Practice, University of Trondheim, Norway.
Scand J Gastroenterol. 1992;27(3):189-95. doi: 10.3109/00365529208999947.
Double-blind randomized controlled trials in single subjects (N of 1 RCTs) have demonstrated a beneficial symptomatic effect of cimetidine in reflux- or ulcer-like non-ulcer dyspepsia (NUD). However, spontaneous fluctuations in symptoms reduce the validity of such trials when performed as continuous trials with fixed dosages. This study was carried out to identify individual responders to cimetidine in NUD, peptic ulcer disease, and oesophagitis and to confirm the beneficial average effect of cimetidine in these clinical entities. We evaluated N of 1 multi-crossover trial designs, which compare the effects of single doses of cimetidine and placebo taken on-demand for symptomatic relief. Each trial consisted of six cimetidine (400 mg or 800 mg) and six placebo tablets randomized in successive pairs. The symptomatic effect of each tablet was measured 1/2-6 h after the intake. Outcomes were assessed by individual p values and confidence intervals. A minimal clinically important difference was defined, to assess the clinical significance as demonstrated by the confidence intervals. Thirteen of 25 patients (52%) with reflux- and ulcer-like NUD obtained individual p values below 0.20. Similarly, 7 of 9 patients (78%) with oesophagitis and 6 of 12 patients (50%) with peptic ulcer obtained such p values. On the basis of the 80% confidence intervals the corresponding numbers of subjects with clinically significant effect were six (NUD), three, and three. The combined data showed a significantly better effect of cimetidine than of placebo (p less than 0.0001) in each of the three diagnostic groups studied. Cimetidine taken on-demand may have a rapid symptom-relieving effect in dyspepsia.(ABSTRACT TRUNCATED AT 250 WORDS)
针对单一个体的双盲随机对照试验（单例随机对照试验，N-of-1 RCTs）已证明西咪替丁对反流样或溃疡样非溃疡性消化不良（NUD）有有益的症状改善作用。然而，当以固定剂量进行连续试验时，症状的自发波动会降低此类试验的有效性。本研究旨在确定NUD、消化性溃疡疾病和食管炎患者中对西咪替丁有反应的个体，并证实西咪替丁在这些临床病症中的有益平均效应。我们评估了N-of-1多交叉试验设计，该设计比较按需服用单剂量西咪替丁和安慰剂以缓解症状的效果。每个试验包括六片西咪替丁（400毫克或800毫克）和六片安慰剂，依次成对随机排列。每片药服用后1/2至6小时测量其症状改善效果。通过个体p值和置信区间评估结果。定义了最小临床重要差异，以评估置信区间所显示的临床意义。25例反流样和溃疡样NUD患者中有13例（52%）个体p值低于0.20。同样，9例食管炎患者中有7例（78%）和12例消化性溃疡患者中有6例（50%）获得了这样的p值。根据80%置信区间，具有临床显著效果的相应受试者数量分别为6例（NUD）、3例和3例。合并数据显示，在所研究的三个诊断组中，西咪替丁的效果均显著优于安慰剂（p<0.0001）。按需服用西咪替丁可能对消化不良有快速缓解症状的作用。（摘要截取自250字）
