Abstract
AimsTo evaluate the crossover design in migraine preventive treatment trials by assessing dropout rate, and potential period and carryover effect in four placebo-controlled randomized controlled trials (RCTs).MethodsIn order to increase statistical power, the study combined data from four different RCTs performed from 1998 to 2015 at St. Olavs Hospital, Norway. Among 264 randomized patients, 120 received placebo treatment before and 144 after active treatment.ResultsOnly 26 (10%) dropped out during the follow-up period of 30–48 weeks, the majority (n = 19) in the first 12 weeks. No period effect was found, since the treatment sequence did not influence the responder rate after placebo treatment, being respectively for migraine 30.5% vs. 27.4% (p = 0.59) and for headache 25.0% vs. 24.8% (p = 0.97, Chi-square test) when placebo occurred early or late. Furthermore, no carryover effect was identified, since the treatment sequence did not influence the treatment effect (difference between placebo and active treatment). There was no significant difference between those who received active treatment first and those who received placebo first with respect to change in number of days per 4 week of headache (− 0.9 vs. -1.3, p = 0.46) and migraine (− 1.2 vs. -0.9, p = 0.35, Student’s t-test).ConclusionsSummary data from four crossover trials evaluating preventive treatment in adult migraine showed that few dropped out after the first period. No period or carryover effect was found. RCT studies with crossover design can be recommended as an efficient and cost-saving way to evaluate potential new preventive medicines for migraine in adults.
Highlights
Preventive medication is indicated for many migraine patients but used regularly by relatively few [1]
By using Student’s t-test we evaluated difference in number of days per 4 weeks of headache and migraine between active treatment and placebo according to sequence
In the two first studies, a total of 138 migraine patients entered the baseline period using placebo tablets, whereas in the two last studies 164 migraine patients entered the baseline period without using placebo tablets
Summary
Preventive medication is indicated for many migraine patients but used regularly by relatively few [1]. The randomized controlled trial (RCT) is the gold standard for evaluating the effect of preventive treatment in patients with migraine. According to the current guidelines for RCTs of preventive treatment in migraine published in 2012, either a parallel or crossover study design can be used, depending on the trial’s objectives [2]. The guidelines recommend that a placebo arm always should be included in trials [2], but this has been done in less than 10% of RCTs evaluating multiple preventive drugs [3]. Summaries of results of RCTs on oral medication for migraine prevention including placebo arms have shown that 21–22% of patients had at least 50% reduction of attacks during oral placebo treatment [4, 5]. Higher responder rates have been found in studies with parallel group design compared with crossover studies [4], possibly because of higher positive expectations in participants in parallel studies than in crossover studies [4]
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