Study supports use of independent committee to mitigate adverse event bias

Issue: December 2012

A study on an industry-sponsored spine surgery trial showed that an independent clinical events committee of orthopedic surgeons reclassified, and in many cases upgraded, the severity of reported adverse events and their relation to the device and surgery.

Perspective from David M. Glaser, JD

As part of a prospective, investigational device exemption trial comparing the Coflex device (Paradigm Spine, LLC) to laminectomy and posterolateral fusion for stenosis with up to grade 1 spondylolisthesis, Joshua D. Auerbach, MD, and colleagues studied whether an independent clinical events committee (CEC) would mitigate potential bias in adverse event reporting.

“The clinical events committee reclassified the level of severity, relation to surgery and/or relation to device in 37.3% of site-reported adverse events, most of which were upgraded,” Auerbach,of Bronx-Lebanon Hospital Center and The Albert Einstein College of Medicine in the Bronx, N.Y., said during his presentation. “The status of the investigator’s financial interest in the company has little effect on the clinical events committee reclassification of adverse events, and investors tended to underemphasize adverse events with equal frequency from the Coflex group and from fusion. We submit that an independent clinical events committee can mitigate potential investigative bias in adverse event reporting and facilitate a more accurate assessment of device safety profile, and should be considered an essential component in future clinical studies.”

The study included 384 patients, with 270 patients in the Coflex group and 114 controls who underwent laminectomy and posterolateral fusion. Study investigators for the Coflex trial rated adverse events based on level of severity (mild, moderate or severe) and relatedness to the device and/or surgery as unrelated, unlikely, possibly, probably or definitely. Three independent, board-certified orthopedic surgeons who formed the CEC then upgraded, downgraded or rated adverse events as no change.

The committee reclassified 37.3% of all adverse events in both the Coflex and fusion groups, according to Auerbach, with most upgraded in severity or given greater relatedness to device or surgery. The investigators found the committee was 5.3 times more likely to upgrade severity, 7.3 times more likely to upgrade the relation to surgery and 11.6 times more likely to upgrade for relatedness to device. When study investigators were also company investors, Auerbach discovered that the status of the investigator as an investor had little effect on CEC reclassification of adverse event severity, relatedness to device or relation to surgery in both fusion and Coflex cohorts. When CEC reclassifications took place, however, upgrades (compared to downgrades) were 8.9 times more common for investor-reported adverse events, irrespective of the device.

“Clearly, there is a need to increase transparency in the reporting of adverse events in industry-sponsored research,” Auerbach said. – by Renee Blisard Buddle

Reference:

Auerbach JD. Mitigating the potential for adverse event reporting bias: Utilization of an independent clinical events committee. Presented at: SpineWeek; May 28-June 1, 2012; Amsterdam.

For more information:

Joshua D. Auerbach, MD, can be reached at the Department of Orthopedics, Bronx-Lebanon Hospital Center, Albert Einstein College of Medicine, 1650 Grand Concourse, 7th Floor, Bronx, NY 10457; email: auerspine@gmail.com.
Disclosure: Auerbach received study support and is a consultant to Paradigm Spine LLC.

Perspective

David M. Glaser, JD

Since physicians are professionals, it is not surprising that many will act in a way some might perceive to be contrary to their "investment interest." First, many physicians place patient care above any economic interest. Moreover, many physicians will recognize that improving the quality of a product is essential to preserve the company’s value, and may willingly accept the risk of short-term harm for a long-term benefit. While I find this study reassuring, I will note that I am predisposed to trust physicians. Perhaps the most important lesson from the study is that we all have our biases, and being aware of them may lower the risk they result in poor decisions.

David M. Glaser, JD

Orthopedics Today Editorial Board member

Fredrikson & Byron, P.A.

Minneapolis

Disclosures: Glaser has no relevant financial disclosures.