麻豆传媒

Leaders of ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) have rejected charges that they inappropriately "moved the goalposts" in the closely watched trial.

ISCHEMIA, which is still underway, was designed to test whether an early invasive strategy is better than medical therapy alone for patients with stable angina.

That the primary endpoint of the trial went from cardiovascular deaths and myocardial infarction (MI) to include the softer outcomes of hospitalization for unstable angina or heart failure went mostly unnoticed until Darrel Francis, MA, MD, of Imperial College London, and colleagues used it to accuse the investigators of "moving the goalposts into unblinded territory" in an article published online in .

Now Judith Hochman, MD, of NYU School of Medicine, and David Maron, MD, of Stanford University School of Medicine -- the ISCHEMIA study co-chair and principal investigator, respectively -- have responded in the of the original article.

"Of note, the grant application funded by the National Heart, Lung, and Blood Institute in 2011 was based on the current five-component primary endpoint," Hochman and Maron wrote. "However, we sought and received approval to implement the study protocol with a primary endpoint of cardiovascular death or MI and to specify that a change to include resuscitated cardiac arrest and hospitalization for unstable angina or heart failure would be made in the event it became necessary to preserve the power of the trial."

Additionally, Hochman and Maron identified what they characterized as several inaccuracies in the Francis group's critique: one being the allegation that the January 17, 2018, change to the on ClinicalTrials.gov occurred more than 99% of the way into the recruitment period. The investigators said the change was actually approved in June 2017 upon separate reviews by an independent advisory panel and the Data and Safety Monitoring Board.

Hochman and Maron also addressed the suggestion that "readers should retain their focus on the primary endpoint that was pre-specified and not one that was post-specified." They said that the original protocol in 2012 had specified that the primary endpoint could be changed during the trial, as long as 75% of the final primary endpoint events had not yet accrued.

"Although the final number of primary endpoint events is not yet known because the trial is ongoing, estimates performed at the time of the Independent Advisory Panel meeting suggested that the ratio of accrued endpoint events to final endpoint events was below 50%," according to Hochman and Maron.

Their final qualm was with the assertion that their trial would be reported within the next few months. In fact, it has been extended, such that the last patient visit is planned for June 2019 with results to come in early 2020.

"As study leads, if we had been given the opportunity to vet the information about the trial included in the manuscript prior to the article's publication, we might have prevented the dissemination of misinformation. We plan to follow up with a detailed article that addresses the rationale for the addition of hospitalization for unstable angina or heart failure and resuscitated cardiac arrest to cardiovascular death and MI in the primary endpoint, and the rigorous methods employed to maximize reporting of all events."

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