As noted in the accompanying article, OT tried to speak with various SPORE directors about their thoughts about the recent and proposed changes to the SPORE program, but only a few were available or willing to comment. What loomed as a major point of confusion for those interviewed, though, was the origin of the SPORE PI executive committee.
After various attempts to reach John D. Minna, MD, the executive committee's chair, and the lung cancer SPORE PI from the University of Texas Southwestern Medical Center, he said via his assistant that he didn't want “to obligate” himself with a specific time or day and would call back when it was convenient. As of the time this issue went to press about a month later, though, we had still not heard from him.
I did speak with Stephen B. Baylin, MD, head of Johns Hopkins' Lung Cancer SPORE and one of the four members of the PI executive committee, along with Dr. Minna; Jennifer R. Grandis, MD, PI of the University of Pittsburgh's Head and Neck Cancer SPORE; and Joe W. Gray, PhD, head of the University of California at San Francisco's Breast Cancer SPORE.
Dr. Baylin said that his SPORE was originally secured during the first round in 1992, but “we don't know whether the last competitive renewal we put in will be renewed. There's a good possibility it won't be renewed this round and we may have to put it back in again… it will officially end sometime in July.”
OT also learned that renewal was also uncertain for the SPOREs directed by Drs. Minna and Gray.
Time of Evolution
Dr. Baylin said that the executive committee has understood from its conversations with Drs. Niederhuber and Doroshow that “a lot of things are in evolution, and they are working on the plans.”
The executive committee was not appointed by Dr. Niederhuber, Dr. Baylin said. “The four of us were elected by the SPORE PIs at the last national SPORE meeting. Dr. Niederhuber agreed to the concept of having those leaders, but the leaders came from the SPORE PIs.
“It's a two-way flow—we listen and work with the leadership of the NCI to understand what's going on so we can transmit to them and we try to be a voice for the SPORE PIs to the leadership as well.
“Grant people who receive grants from NIH and NCI in the program can only be in an advisory capacity,” he continued. “We don't make the rules. Dr. Niederhuber gives us every voice to suggest things, and to transmit suggestions from the spore PIs, but that is our only role.
“It's important to understand that we are a communications forum bilaterally—we have the ability to suggest, we listen, and we try to transmit. This is a time of transition, and we are all listening.”
Dr. Baylin added “we have been very transparent with our peers, so we are not going to communicate false information to them.”
He said that there will be a meeting at the American Association for Cancer Research Annual Meeting this month in San Diego between NCI leadership and the SPORE principal investigators.
“I do think that we've been given every indication by the [NCI] leadership that there is no attempt to devalue the SPOREs or to remove them from the scene. Now they are working under that broader translational mandate they are trying to institute, and we'll see how exactly that all plays out.”
He said he still remains optimistic and thinks NCI is trying to communicate to the SPORE PIs and the rest of the community how this will work.
This explanation seems to be at odds, though, with what OT learned from the SPORE PIs who were interviewed. Not one of them could recall having voted for an executive committee or its chair, although a few said they did vaguely remember hearing something about an election.
Some speculated there may have been some confusion regarding what had happened at a specially convened, non-NCI-sanctioned SPORE directors retreat hosted in Dallas by Dr. Minna in March 2006 (OT, 4/10/06; 6/25/06) when Dr. Minna had been informally designated as their spokesperson at subsequent meetings held with Dr. Niederhuber and other NCI officials about the program's future at that time.
All of them said that since its inception they had received no communications from the executive committee.
Gabriel N. Hortobagyi, MD, Breast Cancer SPORE PI at M. D. Anderson, said that over the last few months very little information had filtered down to the SPORE directors from NCI or the executive committee.
He said the March 2006 Dallas meeting had been called by John Minna in reaction to the budgetary cutbacks then, and remembered Dr. Minna taking on a role as spokesperson, but couldn't recall any formal election or vote taken.
Dr. Hortobagyi knew that Dr. Gomez was leaving the program, and added that the only other communication he had received was a Feb. 14 e-mail from Dr. Niederhuber referring to “my monthly teleconference with your executive committee,” and said that he was aware of the April 13 meeting at AACR.
William G. Nelson, MD, PhD, who co-chaired NCI's Translational Research Working Group (TRWG) with Lynn Matrisian, PhD, is Prostate Cancer SPORE PI at Johns Hopkins.
He said his group had a competitive renewal pending but he hadn't received notification from NCI regarding funding.
He said that the only official word he had received about changes in the SPORE program was Dr. Gomez's letter, and that he was aware of the cancellation of the annual SPORE directors meeting, which would become part of a larger NCI translational research meeting.
He also had no recollection of voting for members of a SPORE PI leadership team.
‘Marked Change in Enthusiasm in SPOREs’
David Carbone, MD, PhD, Director of Vanderbilt-Ingram's Lung Cancer SPORE, which was renewed six months ago, said there has been a marked change in enthusiasm in the SPORE program over the last five to eight years.
“There's much less positive thinking. Now discussions deal more with how to cut budgets and the number of SPOREs and how to prevent programs from getting eliminated. This has been a distraction from science and collaborations, especially in lung cancer, which only has three funded programs now when there had been seven.
“Collaborations have been dropping and these grants seem more like RO1s [NIH Research Project Grants]. The original vision of SPOREs fitting in between the laboratory and clinic is dissipating, and the concept is in risk of disappearing.
“This has been a program that meets particular research needs, and its role is becoming very unclear from a programmatic point of view, but the need is still there from the points of views of patients and progress.”
Dr. Carbone said he believed the executive committee was self-selected: “Some say there was an election, but I don't remember seeing ballots or voting. And I think that members should be replaced annually, but that's not happening.”
He also said he'd rather see teleconferences between NCI and all the SPORE PIs. “We weren't asked about the cancellation of the summer SPORE meeting, and I don't see any evidence that there is any bilateral communication.”
Dr. Carbone said the plan for the potential phase-out of Phase II clinical trials run by SPOREs was something he had heard others talking about, but had not been mandated.
He said it was consistent with a very simplified notion that SPOREs take a drug from the lab and move it into Phase I and then hand it off to cooperative groups. “If I have one gripe about the emerging sentiment reflected by the opinion of the TRWG to this problem, that's it. It's a very linear simplified drug-development kind of perspective on cancer therapeutics as if all the science we will ever learn is learned before the first drug gets into the first person.
“That's absolutely not true,” he said. “We have hypotheses that need to be tested and confirmed at a molecular level in a Phase II level requiring intensive biopsying or laboratory analysis that's just not suitable for cooperative group settings. We are doing two Phase II trials now in my SPORE, and these are things that would never work in a cooperative group setting.”
Interactions with cooperative groups have been very poor in the past, he said, noting that he sits on the Eastern Cooperative Oncology Group's thoracic core committee and has been trying to work with the cooperative groups.
“I've had three proposals to CTEP [NCI's Cancer Therapy Evaluation Program] for trials based on SPORE research that were rapidly and efficiently approved by ECOG, but disapproved by CTEP. And that process took two years, whereas if I was able to do those trials myself through a SPORE or interSPORE collaboration they could have been done by now.
“I think part of the lack of cooperation with the SPOREs has been the historical problem of CTEP micromanaging what the SPOREs try to do through cooperative groups, and killing a lot of good proposals that have come through the cooperative group mechanism.”