Ketek Hearing Winners and Losers

By Steve Zisson

After listening to the Feb. 12th hearing by the House Energy and Commerce’s Subcommittee on Oversight and Investigations probing study fraud and the antibiotic Ketek, one thing is clear: PPD, which monitored the study in question sponsored by Aventis (now Sanofi-Aventis), took the least hits from Congress. And it is also quite clear that many in Congress, including committee staff, don’t seem to understand much about the research process.

Outside of the FDA—which the committee would like to hold in contempt of Congress for failing to respond to a subpoena— taking the toughest criticism from the committee was Sharon Hill Price, founder and chief executive officer of Copernicus Group, the institutional review board (IRB) which oversaw the study.

Price, who admitted to being a bit nervous, was hammered by Michigan Democratic Rep. Bart Stupak, chairman of the oversight and investigations subcommittee, and House Energy and Commerce Committee Chairman John Dingell.

Stupak was upset that Copernicus didn’t provide in a timely fashion a call log of a phone call from Ann Marie Cisnernos, the former PPD study monitor and whistleblower, who reported the fraud that led to the conviction of Anne Kirkman-Campbell, a clinical investigator on Study 3014. Price told committee members she doesn’t recall talking to Cisneros.

Visibly frustrated with Price’s answers, Stupak at one point asked Price, “Why do you exist?” Presumably Stupak was referring to the IRB and not Price herself. Many of Stupak’s and Dingell’s questions showed a clear lack of understanding of clinical research. At one point Stupak was baffled at what “GCP” stood for. He was told Good Clinical Practices, the research standard. Ouch.  Dingell seemed lost when trying to figure out where in the research process an IRB figured in.

Besides Copernicus, it was evident from the hearing title “Ketek Clinical Study Fraud: What Did Aventis Know?” that Sanofi-Aventis would come under prolonged fire. And the company did.  FDA investigator Douglas Loveland called Aventis’ handling of the study a “catastrophic failure” and later “willful blindness on steroids.”

“The decision making process Aventis used to investigate these (fraud) problems was illogical and ineffective and it could have led them to come to the wrong conclusion,” Loveland said.

However, Loveland said it couldn’t be proven “beyond a reasonable doubt" that Aventis was aware of the fraud when the company submitted the study data on Ketek to the FDA. He added that believed the statute of limitations had expired on bringing charges against the company.

Still, Dr. Paul Herbert Chew, president of U.S. research and development for Sanofi-Aventis Pharmaceuticals, held up well under the committee’s glare. He was well versed on the study’s problems and what the company was doing to prevent similar frauds in the future. With all those charges flying, in an encouraging sign for contract research organizations, PPD came away pretty much unscathed.

Cisnernos didn’t really go after PPD. And, in a telling exchange, Stupak asked Chew how well PPD did monitoring the study.  Chew responded: “PPD did a good job.”

Fred Eshelman, chief executive officer of PPD, did take some revealing questions concerning how PPD selects investigators and whether it relies on FDA’s debarment list during that process. Committee members were incensed with the FDA that Kirkman-Campbell was not on the list and prevented from doing clinical research even though she was convicted of fraud. Eshelmann said the company does check the FDA list.

“If the debarment process is flawed, it could present serious issues,” Eshelman told members. The committee released a report critical of the debarment process Feb. 12. Read it here.

While CROs can be buoyed a bit from the hearing, they and their lobbying group, ACRO, still have a big job ahead of them keeping Congress informed about how research actually works. We are sure they will be asked more questions about the debarment list and investigator selection. Keeping Congress informed on these issues is a very big job.

Steve Zisson, managing editor of  CenterWatch.

Comments

[Sherry Reuter]

Comments from Sherry Reuter, BSN, MSHS:

Steve Zisson’s statement: “one thing is clear: PPD, which monitored the study in question sponsored by Aventis (now Sanofi-Aventis), took the least hits from Congress.

And it is also quite clear that many in Congress, including committee staff, don’t seem to understand much about the research process” is actually not such a clear conclusion."

I attended the same hearing and came to very different conclusions.

After working on this case for over a year, the committee members know much more than they let on, as they used a frequently utilized strategy of leading the witnesses to show how much the witnesses did not know.

Frustrated with the lack of forthcoming information from the witnesses, their comments were sarcastic, rhetorical and crafted to illicit statement from the tight-lipped executives from the sponsor, CRO and IRB.

For example, House Energy and Commerce Committee Chairman John Dingell, a very experience politician, engaged Sharon Hill Price in a long discussion in which he asked her many questions about the purpose of IRBs – not because he did not know the purpose of IRBs, but because he wanted to illicit statements from her showing the incompetence with which her IRB conducted business. Zisson’s statement that “Dingell seemed lost when trying to figure out where in the research process an IRB figured in” reveals a naiveté and lack of understanding of the context of the committee members’ statements. Dingell was not “lost” at all – he knew exactly what he was doing, as dumb as a fox.

And when Representative Bart Stupak, Chairman of the Oversight and Investigations Subcommittee, asked in an extremely frustrated and sarcastic tone ‘what “GCP” stood for’ it was not because he did not know or was “baffled” as Zisson wrote- he was indignantly asking the witness a rhetorical question because they had ignored the many cases of non-compliance with GCP.

Zisson’s impression that “Dr. Paul Herbert Chew, president of U.S. research and development for Sanofi-Aventis Pharmaceuticals, held up well under the committee’s glare. He was well versed on the study’s problems and what the company was doing to prevent similar frauds in the future” are dramatically different from my observation, as well as that of others attending and watching the testimony. Chew consistently dodged the questions and did not give a compelling account of his company’s actions.

After his extremely weak testimony, the committee stated that they were frustrated with what they had heard and that they would be pursuing the case further. After Chew’s subpar responses to the Committee’s questions, he and Aventis are not home free.

So it is not the case that “many of Stupak’s and Dingell’s questions showed a clear lack of understanding of clinical research.” They knew more about clinical research than demonstrated by executives who were the witnesses at that hearing, and the committee responded in ways to address their lack of forthcoming information.

[Josephine Schloesser]

Mr. Zisson:

I read your recent editorial and it always amazes me that two people listening to the same discussion at the same time, could come away from it hearing two different things.

I also read Ms. Reuter’s rebuttal and I must say that I agree with her completely. While watching the questionings of Mr. Dingell and Mr. Stupak, it was plainly clear that they do know what GCP is all about, and they should, it does come under the Code of Federal Regulations. It was clear to me that the questioning was not for their education, but to lead the witnesses in declaring if they themselves knew the answer to what GCP stands for when it comes to protecting the research participants rights, welfare and safety.

During Ms. Price’s testimony, it was obvious that she was nervous, and I wondered why she did not elicit the aid of her lawyers, who were sitting directly behind her. However, when asked questions regarding GCP, as head of an IRB, that information should have flowed from her mouth like honey. There should have been no hesitation about the conduct of the research at Dr. Kirkman-Campbell’s office. When she received the call from Ms. Cisneros regarding this site and their conduct, all of Ms. Price’s weight should have been thrown behind Ms. Cisneros immediately and appropriate action taken.

I do agree that the debarment process is flawed and that Dr. Kirman-Cambell should have been debarred as soon as she was convicted. However, and correct me if I’m wrong, I believe it can take up to 8 years to be officially debarred from research. Which means, even in jail, Dr. Kirman-Campbell could still legally conduct research. Now that is a situation that congress and the FDA should deal with in a more timely manner.

Thank you.