INTEGRITTY Aims to Shine a Light on Research Bias, Including in LM Disease

Even without new data, the contentious, back-and-forth debate between cardiac surgeons and interventional cardiologists continues unabated.

The latest volley across the net is the creation of a group calling itself the International Evidence Grading Research Initiative Targeting Transparency and Data Quality (INTEGRITTY), a consortium of surgeons and general cardiologists critical of how certain clinical trials, including those comparing surgery versus PCI for left main CAD, are carried out.

Rui M.S. Almeida, MD, PhD (Centro Universitário Fundação Assis Gurgacz, Cascavel, Brazil), one of the INTEGRITTY members, said the group was created in an effort to raise the bar when it comes to conducting studies and interpreting data not only for controversial areas like the treatment of left main disease, but also for research cited in the latest coronary revascularization and valvular heart disease guidelines.   

“We’ve been meeting to discuss papers because, as we all know, there is a conflict of interest in most clinical guidelines and in most randomized trials,” Almeida told TCTMD. “All of these papers are important, because they’ll be read by the clinician who will take steps to treat their patients based on the guidelines.”

As we all know, there is a conflict of interest in most clinical guidelines and in most randomized trials. Rui Almeida

The group recently published a rebuttal in the European Heart Journal that takes issue with an opinion piece, covered by TCTMD, which attempted to bridge the divide between surgeons and interventional cardiologists as to the best revascularization strategy for patients with left main CAD.

That earlier viewpoint, entitled an “evidence-based reconciliation,” is not evidence-based at all, according to the INTEGRITTY group, but rather just the opinion of the three clinicians, including Gregg Stone, MD (Icahn School of Medicine at Mount Sinai, New York, NY), lead researcher of the Abbott-sponsored EXCEL trial. In fact, they say, the viewpoint doesn’t even meet the lowest grade of evidence because the opinions expressed in it don’t reflect the sum of expert opinion or a consensus.  

Almeida, past president of the Brazilian Society of Cardiovascular Surgery and president-elect of the Latin American Association of Cardiac and Endovascular Surgery (LACES), said INTEGRITTY members don’t have any involvement with industry and aren’t officially affiliated with the various professional organizations. Their work, he said, is intended to push for higher levels of evidence and to draw attention to flaws in research or gaps in knowledge in different areas of cardiovascular medicine.

“We need industry, but the problem is that most of the people involved in these different [trials] have a whole lot of conflict of interest,” he said.

Many hospitals, universities, physicians, scientists, and research foundations depend on the financial support of industry for their continued work. Even unfunded research might not be up to par, Almeida added, noting that researchers depend on publishing to raise their profiles and to secure further grant support. Moreover, statistical analyses can be slanted towards different outcomes, some more favorable than others.

While INTEGRITTY physicians appreciated the efforts of Stone and his co-authors Mario Gaudino, MD (Weill Cornell Medicine, New York, NY), and Michael Farkouh, MD (University Health Network/University of Toronto, Canada), to provide a roundup of the evidence, the group still has significant concerns about “data integrity, endpoints, and comparative outcomes,” specifically with studies comparing revascularization strategies for left main CAD, they write in the rebuttal.

A Rebuttal to the Rebuttal

In response to INTEGRITTY’s criticisms, Gaudino, Farkouh, and Stone published another commentary in the European Heart Journal—a rebuttal to the rebuttal—in which they agree with many points raised by the INTEGRITTY group. However, they say their opinions on left main revascularization expressed in the original viewpoint were based on “robust evidence,” including data from a recent meta-analysis and prior quality-of-life studies. The viewpoint was intended to stimulate discussion around this controversial issue and to break through the “noise from non-evidenced-based prejudiced opinion,” its authors say.

The trio agree that clinical practice recommendations should be based on the evidence and that guidelines and consensus documents should be drafted by experts with “minimal financial and other biases.”

Even in the absence of industry, though, it’s still possible to be biased. “In this regard, it is essential to acknowledge that specialty organizations consisting entirely of proceduralists and their members have the greatest potential for partiality as their entire livelihoods depend on patient referrals and the performance of these procedures,” write Gaudino, Farkouh, and Stone.  

EXCEL Turned Volume Up to 11

This seemingly polite, but long-standing and vocal disagreement between surgeons and interventionalists intensified in 2019 with the 5-year results of the EXCEL trial and the European Association for Cardio-Thoracic Surgery (EACTS)’s decision to withdraw their support from the European Society of Cardiology (ESC) revascularization guidelines for left main CAD. The EACTS also called for an independent review, results of which are expected soon.

With respect to left main revascularization, the INTEGRITTY group wants a “new, comprehensive, objective, and fully transparent” consensus document, one that is “rigorously and ethically configured by a meticulous and thorough revision of current guidelines on this topic.” INTEGRITTY would also like to see that consensus document free from conflicts of interest and endorsed by multiple societies, including surgical societies.

It’s troubling to see that we’re developing this polarization, which is mostly not helpful for patients. William Boden

The group is also weighing in on controversies surrounding the recently published American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) guidelines for coronary revascularization. As reported by TCTMD, the American Association for Thoracic Surgery (AATS) and Society of Thoracic Surgeons (STS) refused to endorse the clinical guidelines for a number of reasons, including the downgrading of CABG surgery in patients with multivessel CAD.

SCAI, asked by TCTMD about the recent to-and-fro between the different camps, including the allegations of bias in the guidelines, declined to comment. 

William Boden, MD (Boston University School of Medicine/VA New England Healthcare System, MA), another member of INTEGRITTY, joined the group after meeting several cardiac surgeons at the recent STS annual meeting. INTEGRITTY “is a grassroots movement to see if we could put together a task force or group who is, perhaps, more devoid of conflicts of interest, a lot of that industry-related,” Boden told TCTMD.

He noted that surgeons have been pushing back more lately when it comes to how some of these coronary and structural heart trials are led, carried out, and analyzed. Unfortunately, the chasm between the surgical and interventional community when it comes to certain treatments is not unlike the divide between Democrats and Republicans in the United States, said Boden.

“It’s become recently polarized,” he said. “It’s not a good development. It’s troubling to see that we’re developing this polarization, which is mostly not helpful for patients.”

In their latest paper, Gaudino, Farkouh, and Stone point out that when it comes to the controversy surrounding PCI versus surgery for left main CAD, the principal investigators of the trials turned over their data to the Thrombolysis in Myocardial Infarction (TIMI) group so that the data could be analyzed independently. This meta-analysis, which showed no difference in mortality between PCI and surgery, was facilitated by the ESC to inform their review of the evidence behind the revascularization guidelines. 

The trio state that surgeons and interventionalists should be able to set aside their biases so that the best treatment is offered to the patient (emphasis theirs), but also add that societal recommendations should largely come from general cardiologists who’ve reviewed the data and not from surgeons or interventionalists with a vested interest in one procedure over the other.

Right Now, a Focus on Surgical Areas

For now, INTEGRITTY has no plans to publish independent research, but is instead focused on keeping tabs on studies where there is surgical involvement, such as revascularization or valvular heart disease, among others. They don’t, however, plan to limit their focus solely to interventional cardiology and cardiac surgery, said Almeida, noting the group took an active interest in the ISCHEMIA trial, a study comparing optimal medical therapy to revascularization.

In addition to the surgeons, cardiologists Raffaele de Caterina, MD, PhD (University of Pisa, Italy), Sanjay Kaul, MD (Cedars-Sinai Medical Center, Los Angeles, CA), and John Mandrola, MD (Baptist Health, Louisville, KY), along with Boden, are members of INTEGRITTY.