RETRACTED: Vitamin D levels do not predict cardiovascular events in statin-treated patients with stable coronary disease [Am Heart J 2012;164:387-393]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).This article has been retracted at the request of the author.The main findings of the TNT Trial were published in 2005.1 Since that time, members of the Steering Committee and other investigators have published 32 papers based upon additional analyses of TNT. The data for these papers were derived from analyses of the TNT clinical database, managed by Pfizer. The clinical database has been crosschecked many times and the data in it is valid.During the trial, blood samples were drawn from the patients at regular intervals for subsequent analysis. We performed a nested case-control study that included 1509 patients (497 patients who experienced a CV event and 1,012 control patients) to determine the relationship between vitamin D serum levels and cardiovascular outcomes in the TNT population. The biomarker database was separate from the clinical database. An anonymization code had been run in 2007 to link patients from one database to the other.In late 2012, the TNT frozen blood samples were integrated into a large automated biobank that includes samples from other Pfizer trials. At that time discrepancies were noted among the samples, indicating that an error had occurred when the samples were anonymized in 2007. Further investigation revealed that the code created to manually anonymize the data was accidentally run twice. During the first run, anonymized subject identifiers were successfully assigned to both biosamples and clinical data. However, after this first run had passed quality control checks, the anonymization code was re-run inadvertently, replacing the first correct set of identifiers with a random and incorrect set. We do not understand how or why the code was re-run. The study team, who were blinded as to patient identity, thus reported on mismatched clinical and biomarker data.The analysis for the biomarker and PCSK9 data preceded the analysis of the vitamin D data. The investigators of the biomarkers study were puzzled that none of the 18 biomarkers were predictive of cardiovascular events. However they were reassured because on-treatment LDL-cholesterol, HDL-cholesterol and triglyceride levels were all strongly predictive of events, and reported this in the JACC paper. These lipid levels were part of the clinical database, however, and thus were not subject to the error that occurred with the biomarkers.In the PCSK9 analysis, PCSK9 levels were predictive of events in the atorvastatin 10 mg group (p=0.039) but not in the 80 mg group. This finding, which we now know is totally spurious, was not unexpected and raised no red flags.Similarly, the failure of vitamin D levels to predict events as reported in our 2012 AHJ paper was not surprising and provided no reason to question the integrity of the biomarker database.Since the error was discovered, we have created a new anonymized clinical and biomarker database by restoring the original set of anonymized identifiers. We are currently reanalyzing the data according to our original study plans. However, the nested case-control feature of the original study design has been lost because the patient selection for biomarker sampling was random. Only approximately one tenth of participants in the re-analysis now had an event, compared to one third in the original study design. Thus the power to detect a difference in the level of Vitamin D or the other biomarkers between patients with and without events has been attenuated.All of the authors of this manuscript are anguished to have made this mistake and published incorrect information.Reference[1] LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease N Engl J Med. 2005;352:1425-35.