A pair of researchers who have been calling for the retraction of two papers by cardiology researcher Don Poldermans say the New England Journal of Medicine is
“not justified” “disappointing” in its refusal to pull the articles.
A little background: Poldermans resigned from Erasmus University in 2011 after having been accused of misconduct. Last week, we reported that the European Heart Journal had issued an expression of concern for a 2001 article on which he was first author.
Readers of the Dutch report [on the Poldermans case] may wonder about the editors’ decision. As I reported this summer, although the Dutch investigators did not find hard evidence of falsified data, they found a number of troubling discrepancies between the trial conduct and the written protocol found in the archive of the Medical Ethics Committee. Poldermans told the investigators that there was an updated version of the protocol but this document has not been found.
In one important discrepancy, the NEJM article states that adverse events were evaluated by an adverse events committee consisting of 2 cardiologists, but both cardiologists told the investigators that they had no awareness that their names were listed in the publication. One said he remembered that Poldermans had asked him to judge some ECGs and the other had no recollection of being involved in the study in any way. Poldermans told the committee that the cardiologists had seen the data for all patients in the study.
Even more troubling are the discrepancies involving the trial’s safety committee. The role of this committee is especially important because the trial was stopped early after the first interim analysis. The NEJM paper states that the decision to stop the trial was made by the safety committee. But the 2 members of this committee told the investigation that they had no recollection of being on the safety committee or of analyzing the study data. One member said that he had given some advice to Poldermans by telephone about “stopping rules.” Poldermans told the investigators that, contrary to the published report, the decision to stop the trial had been made by “the steering committee.”
Two outspoken critics of Poldermans’ work, Darrel Francis and Graham Cole, of the United Kingdom, have been urging the NEJM to retract — without success. They provided us with excerpts from their communications with the journal.
From an August 29, 2014 letter from Francis/Cole to NEJM:
We write to request retraction of the above two articles in the interests of patient safety. We recognize that you may already be considering such action, in which case we hope our attached documents, published today, will be of assistance.
DECREASE I drives meta-analyses which in turn drive even 2014 guidelines. Meta-analysts, senior guideline leaders, political figures, and senior medical journal editors have used non-retraction of the articles as evidence of validity. Since it appears there is no mechanism to answer the questions over DECREASE I, it sits as an RCT roadblock holding back the American and European guideline authorities from grading initiation of perioperative beta blockade as Class III (“Not recommended”), in view of the aggregate of other RCT evidence indicating an increase in mortality.
After the 2011 and 2012 Erasmus reports, the ESC press office, European Heart Journal leadership, and 2014 ESC guideline continue to rely on DECREASE I as the only trial to reverse the aggregate result of other trials, which is that initiation of perioperative beta blockade increases mortality. DECREASE I reports an improbably powerful 91% reduction in death and myocardial infarction.
Information missing—When Erasmus University investigated DECREASE I, the patient identities could not be traced for verification of baseline data and outcomes against clinical records.
All members of the committee that assessed events and the committee that stopped the trial, named in the NEJM paper, now deny having had these roles. The say they did not know they had been named in the NEJM. Erasmus could not carry out its planned forensic statistical analysis with the limited information provided by the authors. We suggest that the published papers contain enough meaningful data to decide on the reliability of the reports.
An unusually narrow distribution of heart rate—The range of heart rate of patients at all eight measurement points is so narrow that it is biologically implausible. Each of the eight probabilities is of the order of one in a quadrillion.
Variation between published DECREASE I values and those provided for meta-analysis—Though the values published in NEJM and the values given to meta-analysts might be individually possible, they cannot both be true.
Mathematical uncertainty about the primary endpoint—The odds ratio of the primary endpoint, death and myocardial infarction, is presented with a confidence interval that is mathematically incompatible. Looking more deeply, both seem to be incorrect.
Confusion about which β blocker was used intravenously—The NEJM paper makes contradictory statements regarding whether the intravenous agent was metoprolol or bisoprolol.
Several inconsistencies in the tables—These include apparently fractional patients and a patient with minus 1 myocardial infarctions. The inconsistencies cannot be satisfactorily resolved without the raw data.
But that analysis didn’t sway the NEJM editors, who replied on September 22 with the following:
On receiving your inquiry about the DECREASE I publications, we recognized that the analysis you had performed differed fundamentally from the evaluation carried out by the Erasmus committee. While the Erasmus committee based its evaluation on process assessment – that is, access to data files, review of trial procedures, etc. – you based your evaluation on an assessment of the internal consistency of the trial report. Despite our original decision to base our actions, as is standard practice, on the conclusions of the Erasmus committee, we believed that your evaluation deserved a separate review by the editors.
After careful consideration of the additional evaluation you have carried out, we continue to believe that the available information does not provide clear evidence of scientific misconduct. As a result, it remains our judgment that retraction of the DECREASE I paper published in the New England Journal of Medicine is not justified. Our actions allow people who wish to use the data from this report to make their own judgment as to its veracity.
Thank you very much for bringing your concerns to the attention of the Journal. Following our review of the circumstances, we consider this question closed.