Editorial Headache Research Methodology: Introduction to the Special Series Donald B. Penzien, PhD A well-designed study often requires no greater effort or resources to execute than a poorly de- signed study but promises substantially greater scien- tific yield. Research addressing the pathophysiology, assessment, and management of primary headaches is on the rise in both quantity and quality. Despite publication of many hundreds of studies, there re- mains a tremendous need for more and better studies of primary headache disorders. As the methodology and reporting of trials often are found lacking by to- day’s standards, an important goal of this special se- ries of articles addressing headache research method- ology is to assist in maximizing value of new research initiatives. This special series is in fact the unanticipated offspring of The Behavioral Clinical Trials Work- group. It was conceptualized during production of new guidelines for conducting clinical trials of behav- ioral headache therapies. 1 Emerging from discussions and debates, the thesis of each article in this series was judged to be a key methodological issue merit- ing further articulation and development expressly for headache investigators. The behavioral clinical trials guidelines referenced here 1 were developed to facilitate production of qual- ity research evaluating behavioral treatments for pri- mary headache disorders, and they are published in From the Department of Psychiatry and Human Behavior, and Director, Head Pain Center, University of Mississippi Medical Center, Jackson, MS. Address all correspondence to Donald B. Penzien, PhD, Profes- sor and Director, Head Pain Center, Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA. a supplemental issue of Headache released in tandem with this issue. They were produced under the auspices of the American Headache Society (AHS), and they are complementary to and modeled after guidelines published by the International Headache Society to address research methodology a propos to drug tri- als for migraine, 2 tension-type headache, 3 and cluster headache. 4 Explicit guidelines for evaluating behav- ioral headache therapies are needed as the optimal methodology for behavioral (and other nonpharma- cologic) trials necessarily differs from the preferred methodology for drug trials. In addition, trials com- paring and integrating drug and behavioral therapies present methodological challenges not addressed by guidelines for pharmacologic research. THE SPECIAL SERIES The series is subdivided into two sections with the first section examining headache research issues of more general relevance and a subsequent section addressing issues with specific relevance to behavioral factors and headache. The first three articles in the general series address key concerns for the design of clinical trials including sample size estimation (statisti- cal power), 5 methods for allocating patients to condi- tions (randomization, stratification, matching), 6 and outcomes assessment. 7 The subsequent two articles address the role for and value of powerful time-series analytic techniques that can elucidate potentially im- portant relationships among symptoms and behaviors over time, but that to date have been underutilized for the study of headache. 8,9 The final article among the general contributions addresses obstacles con- fronting literature reviewers and provides solutions for 408