作者: Carole A. Federico , Taiji Wang , Adélaïde Doussau , Jeffrey S. Mogil , Dean Fergusson
DOI: 10.1001/JAMAINTERNMED.2018.5705
关键词:
摘要: Importance After a drug receives regulatory approval, researchers often pursue small, underpowered trials, called exploratory aimed at testing additional indications. If favorable early findings from trials are not promptly followed by confirmatory then physicians, patients, and payers can be left uncertain about drug’s clinical value (clinical agnosticism). Such may encourage the off-label use of ineffective drugs. Objective To characterize relationship between postapproval for blockbuster drug, pregabalin (Lyrica). Evidence Review Ovid MEDLINE Embase databases were used to identify published prior January 2018 that tested efficacy nonapproved Indications, trial outcomes, publication dates, design elements recorded. Time elapsed was calculated generation agnosticism (ie, publications reporting positive or inconclusive evidence on primary endpoint) it being addressed (publication least 1 in same indication, regardless outcome). Findings There 238 identified 33 indications; 5 indications eventually received European Medicines Agency and/or US Food Drug Administration marketing approval. Sixty-seven percent (22 33) first new have generated agnosticism. Of those with years follow-up, 63% (17 27) within years. As development expanded approval other indications, linkage diminished. Conclusions Relevance initial suggesting went unconfirmed extended periods time. Poor coordination represent an important vehicle through which prescription is recommended practice guidelines encouraged absence evidence.