RESUMEN

STUDY OBJECTIVES: The primary objective was to evaluate the change in publication rate of noninferiority trials over a 20-year interval (1989-2009). Secondary objectives were to analyze the frequency of noninferiority trials by therapeutic category, the frequency of noninferiority trial publication by journal, the impact factors of the publishing journals, any potential special advantages of the study drug over the control, the funding sources of the trials, pharmaceutical industry affiliation of the authors, and the use of ghostwriters in the creation of manuscripts. DESIGN: Retrospective literature review of 583 articles. DATA SOURCES: PubMed (January 1989-December 2009) and EMBASE (first quarter 1989-fourth quarter 2009) databases. MEASUREMENTS AND MAIN RESULTS: A total of 583 articles of the results of randomized controlled clinical trials with a noninferiority study design that evaluated drug therapies, published in English, between 1989 and 2009, were included in the analysis. A consistent increase was noted in their yearly publication rates, with no trials published in 1989 versus 133 in 2009. One hundred twenty-six articles (21.6%) were in the therapeutic category of infectious diseases, followed by 78 (13.4%) in cardiology. Among the journals identified, The New England Journal of Medicine had the highest publication rate of trials with a noninferiority design, with 29 (5.0%) of the identified trials published in this journal. The median impact factor of the journals publishing noninferiority trials was 4.807 (interquartile range 3.064-7.5). The most common advantage of the study drug over the control was reduced duration of treatment or reduced pill burden (80 studies [22.9%]). A total of 425 trials (72.9%) listed the pharmaceutical industry as the only funding source. Among 369 trials with authors employed by the pharmaceutical industry, 101 (17.3%) disclosed an acknowledgment to an individual, other than those listed as authors, who contributed to writing the manuscript and who was affiliated with a medical information company and/or a pharmaceutical company (i.e., potential ghostwriters). CONCLUSION: The publication of noninferiority trials increased during the 20 years from 1989 until 2009, particularly in the therapeutic areas of infectious diseases and cardiology. Because of this growth, clinicians and researchers need to be familiar with the caveats of the noninferiority study design to appropriately interpret and design these clinical studies.

Asunto(s)

Publicaciones Periódicas como Asunto/tendencias , Ensayos Clínicos Controlados Aleatorios como Asunto/tendencias , Humanos , Factor de Impacto de la Revista , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/economía , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos

RESUMEN

Although epidemiologic evidence has not supported the hypothesis of a causal relationship between thimerosal-containing vaccines and autism, concerns continue about pediatric exposure to mercury through vaccine administration. A statement issued by the American Academy of Pediatrics and the US Public Health Service in 1999 prompted the removal of thimerosal from many vaccines. In 2004, the Immunization Safety Review Committee of the Institute of Medicine rejected the hypothesis of a causal relationship between thimerosal-containing vaccines and autism.In a search of MEDLINE and EMBASE, we identified articles that address the potential association between thimerosal and neurodevelopmental disorders, specifically autism. In this article, we review recent pharmacokinetic and epidemiologic studies published between 2003 and 2008 regarding the proposed link between thimerosal and autism.