Deschamps M, Band P R, Hislop T G, Rusthoven J, Iscoe N, Warr D
J Pain Symptom Manage. 1992 Oct;7(7):384-92. doi: 10.1016/0885-3924(92)90017-c.
We compared the effects of controlled-release and immediate-release morphine preparations in adult patients with moderate-to-severe cancer pain and report methodologic approaches to pain evaluation. The study consisted of a two-phase randomized crossover trial preceded by a titration phase; all phases were conducted under double-blind conditions. To evaluate pain intensity, a visual analogue scale (VAS) and the Present Pain Intensity scale of the McGill Pain Questionnaire were used. Additional morphine solution for breakthrough pain was used as an outcome measure. Pain was evaluated nine times daily, which permitted correlation of pain scores with the pharmacokinetic patterns of the test drugs. Side effects were rated once daily, using a scale from 0 to 3. To assess the relative importance of side effects, a toxicity index was designed based on both the intensity and duration of each side effect. The overall VAS pain scores during treatment with controlled-release and immediate-release morphine were 1.3 (SD = 0.1) and 1.4 (SD = 0.2), respectively. Use of supplemental morphine solution for breakthrough pain expressed as the percentage of the daily dose of the test drug was 5.5% for the controlled-release drug and 10.9% for the immediate-release drug. Differences in pain scores, side effects, and supplemental morphine requirement between the two groups were not significant. We discuss methodologic issues in double-blind clinical trials of analgesics, in particular the validity of "Patient Preference" as an outcome measure and problems related to the titration phase.
我们比较了控释和即释吗啡制剂对中重度癌症疼痛成年患者的疗效，并报告了疼痛评估的方法学途径。该研究包括一个滴定阶段之前的两阶段随机交叉试验；所有阶段均在双盲条件下进行。为评估疼痛强度，使用了视觉模拟量表（VAS）和麦吉尔疼痛问卷的当前疼痛强度量表。将用于爆发性疼痛的额外吗啡溶液用作一项结局指标。每天对疼痛进行9次评估，这使得能够将疼痛评分与受试药物的药代动力学模式进行关联。每天使用0至3级量表对副作用进行一次评分。为评估副作用的相对重要性，根据每种副作用的强度和持续时间设计了一个毒性指数。控释和即释吗啡治疗期间的总体VAS疼痛评分分别为1.3（标准差=0.1）和1.4（标准差=0.2）。用于爆发性疼痛的补充吗啡溶液用量以受试药物日剂量的百分比表示，控释药物为5.5%，即释药物为10.9%。两组之间在疼痛评分、副作用和补充吗啡需求量方面的差异不显著。我们讨论了镇痛药双盲临床试验中的方法学问题，特别是“患者偏好”作为一项结局指标的有效性以及与滴定阶段相关的问题。
