Full disclosure: not just of conflict, but also of data.

THE events of the past 2 yr since the initial controversial publication by Mangano et al. regarding the effect of aprotinin on renal failure and mortality have been of great interest to the anesthesiology community. In this issue of ANESTHESIOLOGY, Dietrich et al. test the hypothesis that any potential nephrotoxic effect of aprotinin (Bayer Healthcare Inc., Toronto, Ontario, Canada) is dose dependent. This hypothesis is rooted in the original article by Mangano et al., where they reported an increase in risk of the composite renal outcome from 7% to 18% (P 0.001) comparing lowand high-dose aprotinin. Dietrich et al. were unable to replicate this finding in either univariate or multivariate analysis (odds ratio, 0.98; 95% confidence interval, 0.90–1.07) in an adequately powered and statistically robust study, for identical renal outcome measures to those used by Mangano et al. Importantly, three reality checks of the results are reassuring: the overall incidence of the composite outcome in aprotinin-treated patients (8.2%) is similar to that reported by Mangano et al. (8%); the multivariable model reported by Dietrich et al. contains clinically sensible variables that are in overall concordance with those reported by Mangano et al.; and finally, analysis of each of the effects of aprotinin dose on each of the individual components of the composite renal outcome variable shows a lack of effect of aprotinin. No matter which side of the debate one takes, there is little doubt that much of the discussion has been fed by lack of information. The report by Mangano et al. was questioned for its lack of detail and conflict with prior publications from the Multicenter Study of Perioperative Ischemia group. The furor was further fueled by a notable lapse in judgment by Bayer, when at the US Food and Drug Administration (FDA) public meeting on aprotinin on September 21, 2006, Bayer officials failed to disclose preliminary findings of a large observational cohort being examined by faculty of the Harvard School of Public Health (Boston, Massachusetts), at Bayer’s request, that supported the findings of Mangano et al.* These preliminary findings were later repudiated.†‡ So, we are left with a conundrum. Why do two studies, performed by respected and statistically savvy researchers using similar surgical populations, show diametrically opposing results? Subtle but important differences in study design and definitions may contribute to this discrepancy. Alternatively, access to the raw data in both data sets could allow a more complete analysis and perhaps allow one to resolve the discrepancy. One merely has to look at the Web site of the National Center for Biotechnology Information§ to grasp the ready availability and power of such information. The penultimate example of the disbursement of information is seen at the National Institutes of Health Database of Genotype and Phenotype, where the complete genotyping of more than 32,000 individuals is available to accredited researchers. Secure methods for data deposition and distribution that “demonstrate a new commitment to shared scientific knowledge that should facilitate rapid advances” are logistically feasible and imperative. Quite simply, it is time that journals encourage the public availability of source data as a prerequisite for publishing human drug studies. It is also time that this obligation be extended to the drug approval process and the data provided by pharmaceutical companies to the FDA. The FDA does not require full disclosure of all information that comprises a New Drug Application. It is time that data from every patient reported to the FDA for a New Drug Application should be made available to the research community. Arguments against such action that invoke proprietary information and patient confidentiality can be countered by review of which data should be released and by the benefit of such release to the public. In the heyday of support of faster drug approval seen in the early 1990s, Congress passed the Prescription Drug User Fee Act to This Editorial View accompanies the following article: Dietrich W, Busley R, Boulesteix A-L: Effects of aprotinin dosage on renal function: An analysis of 8,548 cardiac surgical patients treated with different dosages of aprotinin. ANESTHESIOLOGY 2008; 108:189–98.