Tfelt-Hansen P, Olesen J
Neuroepidemiology. 1985;4(4):204-26. doi: 10.1159/000110232.
Treatment of migraine attacks and prophylactic treatment of migraine are each discussed under the four headings: patient selection, trial design, evaluation of results and statistics. Checklist of problems encountered in these trials are given in the tables. The unsuitability of currently used migraine definitions for scientific investigations is stressed. Operational diagnostic criteria for common and classic migraine are given. No clear separation of common migraine attacks and interval headaches is possible, but the problem can be reduced by setting an upper limit (4-6/month) on migraine attack frequency. For the treatment of migraine attacks, the crossover design should always be used. We suggest dose-response studies to solve the problem of equipotency of doses, when 2 drugs are compared. A prophylactic drug should be studied both with the crossover design and with the less powerful group comparison design. Evaluation of results should be based on patients' attack report forms and, in prophylactic studies, a headache diary. We suggest global rating of attack severity. A rather simple headache index (sum of severity scores for each day with migraine) and perhaps a sum of global scores should be used in prophylactic trials. Confidence limits and power should be given, particularly when statistically insignificant results are reported. Migraine frequency often decreases with time regardless of treatment, and this 'time effect' should be separated from the therapeutic effect by appropriate statistical methods.
患者选择、试验设计、结果评估和统计学。这些试验中遇到的问题清单列于表格中。强调了目前使用的偏头痛定义不适用于科学研究。给出了普通型和典型偏头痛的操作性诊断标准。普通偏头痛发作和发作间期头痛无法明确区分，但通过设定偏头痛发作频率的上限（每月4 - 6次）可以减少该问题。对于偏头痛发作的治疗，应始终采用交叉设计。当比较两种药物时，我们建议进行剂量反应研究以解决剂量等效性问题。预防性药物应采用交叉设计和效力较弱的组间比较设计进行研究。结果评估应基于患者的发作报告表，在预防性研究中，应基于头痛日记。我们建议对发作严重程度进行整体评分。在预防性试验中，应使用相当简单的头痛指数（偏头痛发作每一天的严重程度评分总和），或许还应使用整体评分总和。应给出置信区间和检验效能，尤其是在报告统计学无显著意义的结果时。无论治疗如何，偏头痛发作频率通常会随时间降低，应通过适当的统计方法将这种“时间效应”与治疗效果区分开来。
