Special Coverage: AAHRPP conference 2006

Stanford’s COI policy covers gray areas

Fictitious vaccine scenario illustrates complexity

Stanford University (Stanford, CA) has an extensive human subjects research conflict of interest (COI) policy that covers details that sometimes are overlooked at research institutions. Despite having strong COI policies and procedures, the institution’s research programs have remained strong.

"We have an amazingly entrepreneurial faculty," says Harry B. Greenberg, MD, a Joseph D. Grant professor in the Stanford University School of Medicine. Greenberg was scheduled speaker about conflict of interest and research at the Association for the Accreditation of Human Research Protection Programs (AAHRPP) 2006 conference on Quality Human Research Protection Programs, held Feb. 26-28 in Phoenix.

"Though we’re trying to exercise rigor in following our COI principles, we haven’t stopped any good science from getting translated into the commercial realm," Greenberg says. "Stanford prides itself on being a great translating university."

Managing conflicts of interest is very important in human subjects research because of the great concern that problems can lead to direct problems with research subjects, Greenberg notes.

Greenberg illustrates the complexity of ironing out conflicts of interests with this fictitious scenario: "Supervax is a company involved in a late-stage, phase III, multi-site study of a vaccine, and a two-month-old child develops hives and wheezing right after getting the vaccine," Greenberg says.

The child is brought to the emergency department and is treated and gets better. Assistant professor Dr. Brill is the principal investigator of the study. Dr. Brill needs publications in order to receive a promotion, and 10 percent of her salary is paid through the vaccine study, he adds.

Dr. Brill wants to classify the baby’s reaction as a serious adverse event (SAE), and she asks her department chair Dr. Roberts about the case. Dr. Roberts correctly points out that the event must be life-threatening and not potentially life-threatening in order to be a serious adverse event. Dr. Roberts has stock options in the company conducting the study, and he had agreed prior to the study’s initiation to not be involved in subject recruitment or treatment. But Dr. Roberts was involved in lab analyses for the study, Greenberg says.

The question Greenberg asks research audiences is whether Dr. Brill and/or Dr. Roberts have conflicts of interest.

The answer is that Dr. Brill does have a conflict of interest, although it’s not a traditional COI from a financial perspective, he says. "Dr. Brill has no direct personal financial relationship with the company, but since part of her salary is being paid by the company and through the university to her, she has some form of conflict of interest. Nobody addresses that issue, but it’s still a conflict of interest."

Also, and probably, more importantly, Dr. Brill needs publications in order to be promoted, so she also has a non-financial conflict of interest that almost all academic faculty have, and this is another area of conflict of interest that is sometimes overlooked, Greenberg says.

Dr. Roberts, on the other hand, has a direct financial conflict of interest, and he should not have been involved at all with the clinical part of the study, and he certainly should not have given advice to Dr. Brill, he says.

"Dr. Roberts gave accurate advice about SAEs, but that involvement pollutes the study," Greenberg says. "We would not have permitted him to make a response to Dr. Brill at Stanford."

"Would you allow this study to occur at Stanford Medical School?" Greenberg says. "Probably not; we might allow a human study where there’s a significant financial involvement by a principal investigator when there’s a compelling reason to justify the PI’s involvement." For instance, if a study was unique and it might not happen elsewhere, and there was a chance it could help people, then the institution might find a way to enable the study to occur, Greenberg says.

But in the case of a multi-site, phase III study, there is nothing unique about it, and so it could have easily been done at another clinical trial site where there was no financial COI, he says.

Stanford University sets an example in its COI policies pertaining to the institution itself with its policy of relinquishing all equity that the university has in start-up companies when there’s any likelihood that a human subjects clinical trial, sponsored by the start-up company, might occur at Stanford, Greenberg says.

"In the first couple of cases after initiating this policy we had to simply give away the equity," Greenberg notes. "Now we build it into our licensing agreements with buy-back clauses that say the company will buy back the equity at whatever price is fair if there’s a desire to do the clinical trial of that product at Stanford."

For staff, Stanford’s COI policy prohibits Stanford faculty from holding titles that are managerial titles in outside companies while the faculty members are Stanford employees, Greenberg says.

"This policy even pertains to start-up companies that the employee has initiated as well as for any other for-profit entity," Greenberg adds.

"And we have a zero dollar reporting requirement," he says. "We ask people to report conflicts of interest at the zero dollar level."

Although the university generally will permit conflicts of interest to occur at a higher dollar threshold, the faculty and staff are required to report all COIs under the threshold, as well, Greenberg explains.

"Another area where Stanford is different from other institutions is we have a very strong disinclination to permitting students to be involved in start-ups initiated by their faculty mentor," Greenberg says.

"This policy came after some issues that have been reported in the press in the past where there was concern by students about their involvement in start-up companies," he says. "Involvement of students seems so inherently full of potential conflict that we strongly discourage it."

The university’s philosophy is that the student’s primary role at Stanford is to get an education, and it would be difficult to decipher what a faculty mentor’s motivation is when the students are working for a mentor in a start-up, Greenberg adds.

"The other thing we have done that many other universities have not done as frequently is we basically disallowed, in almost all cases, the funding of research in the laboratories of people who are the sponsoring company’s founder," he says. "So say I founded a company, and the company says We want to give Harry Greenberg’s lab a gift or a grant to do research.’"

This type of relationship is very difficult to manage because of the inherent conflict of interest, Greenberg says.

"When you give that grant are you using Stanford labs and university to advance your company for personal gain, or is this work directed at your academic mission?" Greenberg says. "It’s better not to let it happen."