BackgroundRegistration of clinical trials has been introduced largely to reduce bias toward statistically significant results in the trial literature. Doubts remain about whether advance registration alone is an adequate measure to reduce selective publication, selective outcome reporting, and biased design. One of the first areas of medicine in which registration was widely adopted was oncology, although the bulk of registered oncology trials remain unpublished. The net influence of registration on the literature remains untested. This study compares the prevalence of favorable results and conclusions among published reports of registered and unregistered randomized controlled trials of new oncology drugs.MethodsWe conducted a cross-sectional study of published original research articles reporting clinical trials evaluating the efficacy of drugs newly approved for antimalignancy indications by the United States Food and Drug Administration (FDA) from 2000 through 2005. Drugs receiving first-time approval for indications in oncology were identified using the FDA web site and Thomson Centerwatch. Relevant trial reports were identified using PubMed and the Cochrane Library. Evidence of advance trial registration was obtained by a search of clinicaltrials.gov, WHO, ISRCTN, NCI-PDQ trial databases and corporate trial registries, as well as articles themselves. Data on blinding, results for primary outcomes, and author conclusions were extracted independently by two coders. Univariate and multivariate logistic regression identified associations between favorable results and conclusions and independent variables including advance registration, study design characteristics, and industry sponsorship.ResultsOf 137 original research reports from 115 distinct randomized trials assessing 25 newly approved drugs for treating cancer, the 54 publications describing data from trials registered prior to publication were as likely to report statistically significant efficacy results and reach conclusions favoring the test drug (for results, OR = 1.77; 95% CI = 0.87 to 3.61) as reports of trials not registered in advance. In multivariate analysis, reports of prior registered trials were again as likely to favor the test drug (OR = 1.29; 95% CI = 0.54 to 3.08); large sample sizes and surrogate outcome measures were statistically significant predictors of favorable efficacy results at p < 0.05. Subgroup analysis of the main reports from each trial (n = 115) similarly indicated that registered trials were as likely to report results favoring the test drug as trials not registered in advance (OR = 1.11; 95% CI = 0.44 to 2.80), and also that large trials and trials with nonstringent blinding were significantly more likely to report results favoring the test drug.ConclusionsTrial registration alone, without a requirement for full reporting of research results, does not appear to reduce a bias toward results and conclusions favoring new drugs in the clinical trials literature. Our findings support the inclusion of full results reporting i...

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Using historical research that draws on new primary sources, I review the causes and course of the first, mainly iatrogenic amphetamine epidemic in the United States from the 1940s through the 1960s. Retrospective epidemiology indicates that the absolute prevalence of both nonmedical stimulant use and stimulant dependence or abuse have reached nearly the same levels today as at the epidemic’s peak around 1969. Further parallels between epidemics past and present, including evidence that consumption of prescribed amphetamines has also reached the same absolute levels today as at the original epidemic’s peak, suggest that stricter limits on pharmaceutical stimulants must be considered in any efforts to reduce amphetamine abuse today.

This paper explores the exchange relationships underlying collaborations between pharmaceutical companies and preclinical (laboratory-based) researchers, in universities and similar contexts, during the interwar period. It also examines the arguments advanced to justify such collaborations in particular contexts as a way of investigating the perceived costs and benefits, especially among the academic parties in these collaborations, and the way these collaborations were regarded in the US biomedical research community.

Although amphetamine was thoroughly tested by leading scientists for its effects in boosting or maintaining physical and mental performance in fatigued subjects, the results never provided solid grounds for approving the drug's use, and, in any case, came too late to be decisive. The grounds on which amphetamine was actually adopted by both British and American militaries had less to do with the science of fatigue than with the drug's mood-altering effects, as judged by military men. It increased confidence and aggression, and elevated "morale."