Califf’s Confirmation Fall-Out: Should Sponsors Worry About Research Contracts?

With Sen. Warren reviewing Duke’s clinical research contracts with sponsors, any potential problems could embolden critics of industry-academia dealings.

Concerns with FDA commissioner nominee Robert Califf’s industry ties appear to be one of the few remaining speed bumps on the path to his confirmation.

Further vetting of Califf's research contracts from his time at Duke University may have a ripple effect on academic institutions’ relationships with sponsors for clinical trial work.

As part of the questioning during his Nov. 17 confirmation hearing in front of the Senate Health, Education, Labor and Pensions Committee, Califf was forced to defend his work as a clinical trialist and the ties to industry that it forged.

Sen. Elizabeth Warren, D-MA, was one of a few senators that broached the subject in-depth and promised more scrutiny in an effort to better understand how much influence industry has over academia when it comes to clinical trial planning, analysis and publishing.

Califf in the Spotlight

FDA commissioner nominee Robert Califf explained the mechanics of the contract Duke University required to conduct a clinical trial for a drug sponsor during his Nov. 17 confirmation hearing.

Photo by Derrick Gingery

Warren said she requested copies of the contract that Duke University required of any drug sponsor, which is intended to prevent sponsor interference, for further scrutiny.

Warren said that she looked forward to “reviewing them before this committee moves forward with [Califf’s] nomination.”

“These agreements typically spell out in detail the relationship between the researchers and the funders and so I think will help us better understand what’s happening here,” she said.

Califf’s industry ties were expected to come up during the question-and-answer session at the hearing. While at Duke, Califf received consulting and other fees from a number of pharma companies .

He also listed the pharma companies whose activities he would be recused from for a year along with a number of positions he was foregoing in a letter to HHS ethics officials (see sidebar).

Most senators appear satisfied with Califf's descriptions of his work with product sponsors.

Committee Ranking Member Patty Murray, D-WA, said in her opening statement that her review of Califf’s record “demonstrates a long-standing commitment to transparency in relationships with industry and to working to ensure academic integrity.”

Murray, along with Committee Chairman Lamar Alexander, R-TN, seemed more interested in allowing Califf to explain his industry ties than hammering him for his inability to be impartial.

Overall, the hearing was mostly collegial. Some committee members even joked with each other as well as teased Califf (Also see "Califf Supports Combo Products Pathway At Confirmation Hearing" - Pink Sheet, 17 Nov, 2015.).

Duke Walked Away From Some Studies

During the hearing, Warren asked Califf how much influence sponsors had over trials he and other Duke researchers conducted.

The Duke clinical trial contract mandates that its researchers have access to all of the study data and denies the sponsor any opportunity to prevent publishing of the results.

Califf said the data access requirement was a deal-breaker for many sponsors.

“I would say 70% of the studies I wanted to do we couldn’t do because companies were not willing to grant that right so we had to walk away,” he told Warren. “Publications are in the purview of the steering committee. … Industry has a right to make suggestions but no right to censor and no right to change.”

Warren persisted, apparently trying to push Califf into a corner.

“I hear you to be saying that there is no instance during your career or any instance involving Duke researchers at the Duke Clinical Research Institute during the time you were supervising it in which a pharmaceutical company provided any input into the analysis or the publication of the clinical trial that they paid to conduct. Is that right?” she asked.

Califf clarified again that with publishing “they can make suggestions. That’s perfectly allowable under our contract.”

“The way we can do our analysis, because the company has to submit the data to the FDA, is typically we’ll have an analysis done by the company and an analysis done by our statisticians, and then we compare the results to see if they match up and resolve any discrepancies,” Califf said.

“But in no case did we allow the company to do the analysis and we just were recipients of what they said the answer was.”

Califf side-stepped the question somewhat. But one of his goals for the hearing was to avoid backing into a corner on personal or policy issues (Also see "Robert Califf Wants You To Forget His Confirmation Hearing" - Pink Sheet, 16 Nov, 2015.).

Will Warren Find Issues With Duke Contract?

If Warren’s contract review turns up problems, not only could it affect the health of Califf’s confirmation, but it also might put pressure on academic research centers to alter their deals with pharma going forward.

Steve Nissen, chairman of the Cleveland Clinic Department of Cardiovascular Medicine, told “The Pink Sheet” that his and nearly all academic institutions now require contract language on data access and publication rights, which is intended to maintain academic independence.

If Warren finds holes in those deals, there may be renewed efforts to create a stronger firewall between academic medicine and industry.

While publication restrictions used to be written into investigator contracts, there has been a movement away from full publishing prohibitions for many years, Heather Pierce, senior director of science policy and regulatory counsel for the Association of American Medical Colleges told “The Pink Sheet.”

Of the exceptions seen now are potential delays, especially in the case of multi-site trials, to allow all sites to report before individual investigators begin publishing.

Pierce said restrictions on publishing confidential commercial information are common, but the movement has been toward more academic freedom.

Industry agreements with contract research organizations generally differ from those with academic institutions, even though CROs work with academic and non-academic investigators. CROs generally do not place as much importance on a publication rights requirement, according to the Association of Clinical Research Organizations.

Warren’s review also could provide more fodder for those critical of the industry-researcher relationship, especially as more attention is paid to rising drug prices.

Sen. Bernie Sanders, I-VT, who was by far the most combative of those questioning Califf during the hearing, said he opposed Califf’s nomination because he was not strong enough to stand up for consumers against industry.

He also grilled Califf about FDA’s ability to affect drug prices (Also see "FDA Can Help On Drug Prices – Except When It Can't, Califf Says" - Pink Sheet, 17 Nov, 2015.).