NIH's National Heart, Lung, and Blood Institute (NHLBI) on Monday announced it has suspended a clinical trial testing a stem cell treatment in patients with heart failure, after Harvard Medical School and Brigham and Women's Hospital last month called for the retraction of research related to the trial's foundation.
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Background
Harvard and Brigham and Women's through an internal investigation determined that 31 papers published by cardiologist Piero Anversa in prominent scientific journals contain falsified and fabricated data, and have called for the research to be retracted.
Anversa, who previously worked at the medical school and hospital, has been recognized for his research suggesting stem cells in the heart, known as c-kit+ cells, could be used to regenerate damaged heart muscle. The research paved the way for new start-up companies and further studies into ways to stem cells could be used to repair the heart, including NHLBI's clinical trial.
Over the years, Anversa has collaborated with leaders in the field of cardiology and has co-authored more than 100 scientific papers in various journals. For instance, the New England Journal of Medicine (NEJM) in 2001 published a paper co-authored by Anversa that claimed the heart is capable of regeneration, and in 2001 published a paper reporting evidence of stem cells in the lungs.
However, subsequent studies have been unable to replicate the stem cell findings that came from Anversa's lab, prompting some experts to raise concerns over the research. Mounting concerns prompted Harvard and Brigham and Women's to launch an internal, multi-year investigation into Anversa's lab and research findings. In a joint statement issued in October, the hospital and medical school said, "Following a review of research conducted in the former lab of Piero Anversa, we determined that 31 publications included falsified and/or fabricated data, and we have notified all relevant journals." Harvard recommended the journals retract the 31 articles, though it did not publicly state which articles are being called into question.
NHLBI pauses cardiac stem cell study
In light of Harvard's Brigham and Women's call for the retractions, NHLBI said it is pausing its clinical trial testing cardiac stem cell treatments in patients with heart failure. "Recent calls for the retraction of journal articles in related fields of cell therapy research have raised concerns about the scientific foundations of this trial," NHLBI said.
The clinical trial is designed to evaluate whether c-kit+ cells alone, or in combination with stem cells derived from bone marrow, are safe and benefit patients with heart failure, STAT News reports.
David Goff, director of the Division of Cardiovascular Sciences at NHLBI, said the clinical trial had been approved in 2015 based on 11 reports from eight different labs—none of which were tied to Anversa's research lab—showing animals benefited from c-kit+ cells in experiments. Goff said researchers aimed to enroll a total of 141 patients with heart failure at seven different sites for the trial. According to Goff, researchers already had enrolled 125 patients, including 117 who already have had tissue collected from their bone marrow or heart muscle, and 90 who have received treatment.
NHLBI noted that none of the articles recommended for retraction were used as a basis for the clinical trial, called CONCERT-HF, but the agency decided to convene the trial's Data and Safety Monitoring Board (DSMB) "out of an abundance of caution to ensure the study continues to meet the highest standards for participant safety and scientific integrity." NHLBI then decided to pause the clinical trial based on the DSMB's recommendations. NHLBI said patients enrolled in the study are being notified of the trial's status.
NHLBI said, "While the DSMB did not have any participant safety concerns, this pause enables the DSMB to complete its review" of the trial. Goff said the agency asked DSMB to conduct an "expeditious review in keeping with appropriate rigor."
Lem Moye of the University of Texas, which is co-sponsoring the trial, said, "Although we do not follow the protocols of … Anversa … NHLBI would like to assure itself that our lab is in fact generating c-kit+ cells. We hope that this will not take long" (Cooney, STAT News, 10/29; Allar, Cardiovascular Business, 10/30; Stile, Medscape, 10/29; Kaiser, Science, 10/29).
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