Rethinking Headache Chronification

Authors


  • Financial Support: Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number R01NS065257.
  • Conflicts of Interest: Dana P. Turner: Ms. Turner receives research support from Merck; Todd A. Smitherman: Dr. Smitherman receives research support from Merck; Donald B. Penzien: Dr. Penzien receives research support from Merck; Richard B. Lipton: Dr. Richard B. Lipton receives research support from the NIH [PO1 AG03949 (Program Director), PO1AG027734 (Project Leader), RO1AG025119 (Investigator), RO1AG022374-06A2 (Investigator), RO1AG034119 (Investigator), RO1AG12101 (Investigator), K23AG030857 (Mentor), K23NS05140901A1 (Mentor), and K23NS47256 (Mentor), the National Headache Foundation, and the Migraine Research Fund; serves on the editorial boards of Neurology and Cephalalgia and as senior advisor to Headache, has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics (a company without commercial products); serves as consultant, advisory board member, or has received honoraria from: Allergan, American Headache Society, Autonomic Technologies, Boehringer-Ingelheim Pharmaceuticals, Boston Scientific, Bristol Myers Squibb, Cognimed, Colucid, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, MAP, Merck, Nautilus Neuroscience, Novartis, NuPathe, Vedanta, Zogenix. Timothy T. Houle: Dr. Houle receives research support from GlaxoSmithKline and Merck.
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Address all correspondence to T.T. Houle, Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA, email: thoule@wakehealth.edu

Abstract

The objective of this series is to examine several threats to the interpretation of headache chronification studies that arise from methodological issues. The study of headache chronification has extensively used longitudinal designs with 2 or more measurement occasions. Unfortunately, application of these designs, when combined with the common practice of extreme score selection as well as the extant challenges in measuring headache frequency rates (eg, unreliability, regression to the mean), induces substantive threats to accurate interpretation of findings. Partitioning the amount of observed variance in rates of chronification and remission attributable to regression artifacts is a critical yet previously overlooked step to learning more about headache as a potentially progressive disease. In this series on rethinking headache chronification, we provide an overview of methodological issues in this area (this paper), highlight the influence of rounding error on estimates of headache frequency (second paper), examine the influence of random error and regression artifacts on estimates of chronification and remission (third paper), and consider future directions for this line of research (fourth paper).

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