IOM solicited as external review body

A representative for the Institute of Medicine confirmed Monday that the organization has been approached about conducting an external scientific review of cancer researcher Dr. Anil Potti’s work.

Although Duke Medicine officials said Aug. 16 that an agreement with an external review organization was near finalization, at the time Dr. Victor Dzau declined to name the organization being hired, citing a confidentiality agreement between Duke and the agency.

A representative for the Institute of Medicine confirmed Monday that the organization has been approached about conducting an external scientific review of cancer researcher Dr. Anil Potti’s work.

“All studies conducted by branches of the National Academy of Sciences, including the IOM, have to be approved by [NAS’s] governing board, and the request for this [review] is going through that process and hasn’t yet been finalized,” Christine Stencel, media relations officer for the IOM, wrote in an e-mail Monday. “But what this would entail if it’s approved is an examination of the scientific validity of the Potti predictive models and suggestions of criteria for determining when predictive tests based on genomic expression profiles have sufficient validity to provide a basis for clinical trials.”

Stencel added, however, that the manner in which the charge is addressed will be determined by the IOM’s appointed review committee.

The IOM, the “health arm” of the National Academy of Sciences, is an independent, non-profit organization of scientists and researchers who provide advice on issues of health to policy and decision makers, according to the IOM website. The organization works outside of the government and takes on projects mandated by Congress as well as those requested by federal agencies and independent organizations such as Duke.

Duke commissioned an outside review of Potti’s work in late 2009 in response to questions about the safety of clinical trials based on Potti’s research. Although the clinical trials were reinstated on the completion of the first investigation, recent concerns raised by scientists and allegations regarding falsifications and embellishments in Potti’s resume have led to the second external review. According to a Duke News release Friday, an internal investigation of Potti’s resume did, in fact, find “issues of substantial concern.”

“That puts everything in a whole new light for me and for [Vice Dean for Research] Dr. [Sally] Kornbluth and for Duke University,” said Dr. Michael Cuffe, vice president for medical affairs. Cuffe and Kornbluth signed the statement reinstating the clinical trials after the 2009 investigation.

The situation changed in 2009, however, when Baggerly and fellow biostatistician Kevin Coombes published another article in the fourth issue of the 2009 volume of Annals of Applied Statistics, which raised additional concerns suggesting that Duke was putting the patients taking part in Potti’s clinical trials at risk, Cuffe added. Potti and his collaborator Joseph Nevins, director for the Center for Applied Genomics and Technology, claimed to be able to use genomic technology to predict responses to chemotherapy for cancer patients.

“[Duke then] collaborated with the National Cancer Institute and with others to try and figure out how to best address this issue of patient safety, so we identified, together with the NCI, a set of outside reviewers who could independently look at this work,” Cuffe said.

Cuffe declined to identify the outside reviewers, but according to The Cancer Letter, Duke’s Institutional Review Board for this matter turned to three directors of other cancer centers and an independent panel of biostatisticians.

In addition to temporarily suspending the three cancer clinical trials under Potti and Nevins, the reviewers were assigned two specific tasks—to make sure that Potti and Nevins had addressed all of the published concerns by Baggerly and Coombes and to evaluate the issue of patient safety and validity of their research, Cuffe said. The reviewers, who Cuffe said could communicate freely with Potti and Nevins and had complete access to their lab, concluded that although Potti and Nevins could have been more forthcoming and descriptive in the public literature about their methods, they had adequately addressed all concerns that Baggerly and Coombes had brought forward. Moreover, the reviewers concluded that it was “very likely” that Potti and Nevins’s work would be a productive line of research, Cuffe added.

“In doing so, [Duke’s] Institutional Review Board reviewed [the findings] and [in January 2010] endorsed restarting the trials,” Cuffe said.

However, since then, additional issues have been brought forward, including more concerns raised by Baggerly and Coombes expressed through The Cancer Letter, as well as a July 19 letter of concern signed by 33 other statisticians. The statisticians expressed their concern for the cancer patients taking part in the three reinstated clinical trials that were being funded by the Department of Defense and Duke University. According to the letter, because of “the inability of independent experts to substantiate [claims made by Potti and Nevins] using the researchers’ own data,” it was “absolutely premature to use [their] prediction models to influence the therapeutic options open to cancer patients.”