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Clinical Relevance of Efficacy Endpoints in OTC Headache Trials
Author(s) -
Pageler Lutz,
Diener HansChristoph,
Pfaffenrath Volker,
Peil Hubertus,
Aicher Bernhard
Publication year - 2009
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/j.1526-4610.2008.01242.x
Subject(s) - medicine , tolerability , visual analogue scale , placebo , clinical endpoint , surrogate endpoint , clinical significance , clinical trial , logistic regression , rating scale , anesthesia , physical therapy , adverse effect , psychology , alternative medicine , developmental psychology , pathology
Objective.— This analysis evaluates and ranks efficacy endpoints often used in headache trials concerning their clinical relevance in relation to the patient‐related criterion “global assessment of overall efficacy” based on data gained in a large trial investigating different over‐the‐counter drugs in the treatment of headache. Background.— The original study showed a significant superiority of the fixed combination of acetylsalicylic acid+ paracetamol+caffeine over the combination without caffeine, the single preparations, and placebo in the treatment of headache. Methods.— For 1734 patients included in the efficacy analysis we investigated the correlation of patient's global efficacy assessment with the endpoints “time to 50% pain relief” (primary endpoint), “time to be pain‐free,” pain intensity difference, sum of pain intensity difference, and extent of impairment of daily activities. Patients recorded pain intensity on a visual analog scale. Efficacy, tolerability, and extent of impairment of daily activity were assessed on verbal rating scales. A logistic regression, proportional odds model was adapted to the time to event data. Results.— The highest correlation with patient's global efficacy assessment was demonstrated for the primary endpoint time to 50% pain relief ( r = 0.6727) and the sum of pain intensity difference ( r = 0.7037). The frequency distribution of patient's global efficacy assessment depended primarily on the time to 50% pain relief and similarly, but to a somewhat lesser extent, on the reduction of pain intensity to 10 mm as assessed on the visual analog scale. More than 86% of the patients assessed efficacy as very good or good when their pain was reduced by 50% at least within 1 hour after drug intake. The patients accept a longer time span than 2 hours for reaching no pain to give a positive global evaluation of efficacy. Conclusions.— The time to 50% pain relief proved to be the best predictor for the global assessment of efficacy by the patient and is a useful endpoint for a univariate analysis.