A long-standing request to clarify data irregularities in a 2021 ISCHEMIA substudy resulted in the publication of one correction, with a second correction in the works.
Further, the lone cardiac surgeon on the ISCHEMIA trial steering committee, T. Bruce Ferguson, MD, has resigned from the committee, citing a series of factors, including an inability to reconcile data in the substudy and two additional ISCHEMIA papers currently under review.
As previously reported, cardiac surgeons Faisal Bakaeen, MD, and Joseph Sabik III, MD, notified the journal Circulation in March that the Dr. Reynolds et al. substudy had inconsistencies between data in the main paper and supplemental tables detailing patients’ coronary artery disease (CAD) and ischemia severity.
The substudy found that CAD severity, classified using the modified Duke Prognostic Index score, predicted 4-year mortality and myocardial infarction in the landmark trial.
Circulation published a correction for the substudy on May 20, explaining that a “formatting error” resulted in data being incorrectly presented in two supplemental tables. It does not mention the surgeons’ letter to the editor, which can be found by clicking the “Q” icon below the paper.
Dr. Bakaeen, from the Cleveland Clinic, and Dr. Sabik, from University Hospitals Cleveland Medical Center, told this news organization that they submitted a second letter to editor on May 23 stating that “significant discrepancies” persist.
For example, 7.2% of participants (179/2,475) had moderate stenosis in one coronary vessel in the corrected Reynolds paper (Supplemental Tables I and II) versus 23.3% (697/2,986) in the primary ISCHEMIA manuscript published in the New England Journal of Medicine (Table S5).
The number of patients with left main ≥ 50% stenosis is, surprisingly, identical in both manuscripts, at 40, they said, despite the denominator dropping from 3,845 participants in the primary study to 2,475 participants with an evaluable modified Duke Prognostic Index score in the substudy.
The number of participants with previous coronary artery bypass surgery (CABG) is also hard to reconcile between manuscripts and, importantly, the substudy doesn’t distinguish between lesions bypassed with patent grafts and unbypassed grafts or those with occluded grafts.
“The fact that the authors are working on a second correction is appreciated, but with such numerous inconsistencies, at some point you reach the conclusion that an independent review of the data is the right thing to do for such a high-profile study that received over $100 million of National Institutes of Health support,” Dr. Bakaeen said. “No one should be satisfied or happy if there is any shadow of doubt here regarding the accuracy of the data.”
Speaking to this news organization prior to the first correction, lead substudy author Harmony Reynolds, MD, NYU Langone Health, detailed in depth how the formatting glitch inadvertently upgraded the number of diseased vessels and lesion severity in two supplemental tables.
Dr. Harmony Reynolds
She noted, as does the correction, that the data were correctly reported in the main manuscript tables and figures and in the remainder of the supplement.
Dr. Reynolds also said they’re in the process of preparing the data for “public sharing soon,” including the Duke Prognostic score at all levels. Dr. Reynolds had not responded by the time of this publication to a request for further details or a timeline.
The surgeons’ first letter to the editor was rejected because it was submitted outside the journal’s 6-week window for letters and was posted as a public comment April 18 via the research platform, Remarq.
Dr. Bakaeen said they were told their second letter was rejected because of Circulation’s “long standing policy” not to publish letters to the editor regarding manuscript corrections but that a correction is being issued.
Circulation editor-in-chief Joseph A. Hill, MD, PhD, UT Southwestern Medical Center, Dallas, said via email that the journal will update its online policies to more clearly state its requirements for publication and that it has been fully transparent with Dr. Bakaeen and Dr. Sabik regarding where it is in the current process.
He confirmed the surgeons were told June 1 that “after additional review, the authors have determined that whereas there are no errors, an additional minor correction is warranted to clarify the description of the study population and sample size. This correction will be published soon.”
Dr. Hill thanked Dr. Bakaeen and Dr. Sabik for bringing the matter to their attention and said, “It is also important to note that both updates to the Dr. Reynolds et al. paper are published as corrections. However, the results and conclusions of the paper remain unchanged.”