OASIS Retraction Could Leave AF Rotor Ablation in Limbo

Patrice Wendling

September 13, 2016

WASHINGTON, DC — Retraction of its July 19, 2016 OASIS paper[1] by the Journal of the American College of Cardiology (JACC) is raising concerns over potential industry influence in scientific publication as well as broader implications when a study that may have lots to offer is yanked from the literature.

The report's conclusions had questioned the validity of focal impulse and rotor modulation (FIRM)–guided ablation in patients with atrial fibrillation and are reflected in heartwire from Medscape coverage of OASIS at the Heart Rhythm Society 2016 Scientific Sessions. JACC editors say it was retracted due to deviations in the trial's randomization that were not disclosed in the manuscript and patient enrollment that started before completion of OASIS registration with clinicaltrials.gov.

Asked whether these flaws met JACC's standard that retractions can occur only under "exceptional circumstances," Dr Paul Douglass, chair of the ACC publications and editorial content committee, told heartwire from Medscape, "After the review by the editors, I would say the unanimous decision by the editorial board was that this was a breach that did meet this standard."

JACC has issued just one other retraction in the last 2 years after an imposter penned a 2014 letter to the editor.

OASIS study author Dr Andrea Natale (Texas Cardiac Arrhythmia Institute, Austin), who raised concerns on Twitter last week that industry influenced the retraction process, told heartwire in an email that only nine patients were excluded from one site after the center enrolled them incorrectly.

He questioned why the investigators "were punished" for their oversights when "postrandomization exclusion and adaptive randomization are widely accepted analytic approaches that have been used by many published trials." He also cited a JAMA analysis showing that only 48% of studies were registered before patient enrollment[2].

Natale said the registration issue was not raised during the peer-review process and that the study start date and registration date were posted on the clinical-trial site and the NCT number was in the manuscript. Although they failed to provide details on the randomization errors in the manuscript, this information was given "at a later date" to the JACC editorial board.

"I believe this was an extreme action taken by JACC for some oversights that we could have easily explained by an addendum to the article at the most," Natale said.

Smackdown or Science?

Douglass confirmed that JACC received three letters, including one from industry, that raised several concerns about OASIS. When asked whether the industry letter was sent from Abbott, which purchased the rotor mapping system used in the trial in 2014 from Topera, he said the letters and the authors' identities are confidential.

Asked the same question, Abbott spokesperson Jonathon Hamilton said in an email to heartwire , "We are just referring questions to JACC at this time."

Natale, however, said that "some of the information mentioned in those letters such as procedure dates at different centers was known only to us and the company; it is therefore very obvious that these individuals were acting on behalf and in the best interest of the company."

He also observed that before OASIS, every publication reporting high efficacy of FIRM mapping came exclusively from groups that patented the concept, developed the technology, or had a financial relationship with the company marketing it.

Douglass strongly denied any commercial influence on the publication process.

"We certainly collaborate with our colleagues, and there is certainly a lot of discussion back and forth, but the science is the science, and the decisions that are made by the editorial board are completely dependent on the validity of the science," he said. "There's no place for any pressure from industry, regulators, government, or our own colleagues."

Douglass said he could not comment on whether JACC associate editor and Topera cofounder Dr Sanjiv Narayan (Stanford University, CA) participated in the review process, but Narayan said in an email to heartwire that he had recused himself from the entire process.

Baby With the Bathwater?

How a study that was reportedly so flawed was published in the first place could leave many clinicians questioning the peer-review process and exactly where rotor ablation fits into the treatment of afib.

Douglass said the fact that retractions are such rare events at JACC speaks to the validity of the peer-review process, but that "it's not a perfect process."

He added, "Patients who have atrial fibrillation certainly have scientific questions that need to be answered and whether this is the answer or not, I don't know. What I'm saying is this trial doesn't answer the question, so I think it's unfair for us to vilify this procedure based on a flawed trial."

Natale said, "The findings of the study are still valid; neither 'registering a study later than the first enrollment' nor 'nondisclosure of the randomization details' nullify or downgrade the reported data."

Dr Mintu Turakhia (Stanford University, CA), who was not involved with the study or JACC publication, told heartwire in an email that the potential harm of any full retraction is the risk for a type II error, "where some good data may be discarded with the bad."

For example, results of the TOPCAT study of spironolactone questioned whether patients enrolled at sites in Russia and Georgia even had heart failure, which was a major inclusion criterion. To address this, he noted that US sites were analyzed separately post hoc, "although this approach can also raise concerns, especially if there is a commercial interest."

Ultimately, a single trial cannot always provide a sufficiently high level of evidence to change guidelines and practice—especially for unblinded studies of procedures, Turakhia said. Hypothetically, if OASIS had shown that FIRM improved outcomes, the electrophysiology community may still have wanted additional studies to validate.

"Therefore, ongoing studies, randomized and observational, of rotor ablation were important before and will still be important," he said.

Two randomized trials of Abbott's rotor mapping system, the 350-patient REAFFIRM trial and 268-patient REDO-FIRM trial, are currently under way.

Douglass reported serving as a speaker for Novartis. Natale reported receiving speaker honoraria from Boston Scientific, Biosense Webster, St Jude Medical, Biotronik, and Medtronic and serving as a consultant for Biosense, St Jude, and Janssen Pharmaceuticals. Turakhia reported serving as a consultant for Medtronic, St Jude Medical, and Abbott.

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