RPM Report- FDA and Cancer Drug Development: An Advocate’s View | Friends of Cancer Research

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RPM Report- FDA and Cancer Drug Development: An Advocate’s View

By Ramsey Baghdadi, Friends of Cancer Research (www.focr.org) has been among the most vocal supporters of a robust FDA review process for oncology drugs.

 Chair & Founder Dr. Ellen Sigal has taken the advocacy group from a one-person shop to an organization with strong ties to the agency and the lawmakers on Capitol Hill who matter most to the future of cancer treatment.

The RPM Report: How do you work with the other cancer advocacy groups?

Ellen Sigal: We have broad cross section of the cancer community as members of our board, including several advocacy groups, which allows for routine communication about science and policy issues that are important for the entire cancer and biomedical community. Examples of advocacy groups on our board include the Leukemia & Lymphoma Society, Research!America, the American Cancer Society, and the National Patient Advocate Foundation. We also work on specific projects with advocacy organizations that are not on our board, and may not even be focused on challenges in oncology. We are a bit of a hybrid so it depends on what we’re working on.

When we identified that the reauthorization of PDUFA in 2007 was a significant opportunity to improve drug safety, we worked with advocacy groups within cancer and outside of cancer—we worked with 40 groups on that. When we published a report on comparative effectiveness, we worked with the academic sectors and we worked with advocates as well. When we finished the report, we had the endorsement of over 26 advocacy groups on it. So it depends what we’re working on and how it defines the issue.

It is extremely important for the cancer community, and really the broad advocacy community, to work in tandem and identify key opportunities, develop consensus, and provide scientifically based policy recommendations that can help advance biomedical research. Consensus is a powerful tool, and by working through the tough problems together we can generate better solutions.

More Science in FDA’s Oncology Group

RPM: How did you get involved in the elevation of the cancer drug review group at FDA from a division within the Center for Drug Evaluation & Research to an office-level entity?

Sigal: Early on FDA wasn’t on our radar screen. Initially, the entire mission of Friends was appropriations for the National Cancer Institute and town halls. But about six years ago, we facilitated a public-private partnership on clinical trial accrual for Phase I trials and it was a partnership between the NCI and five pharmaceutical companies. The goal was to examine ways to increase clinical trial participation in minority communities, disadvantaged communities and the elderly, specifically in early development, or Phase I. At that time, a lot of people talked about the problems with the oncology division and they said the problem wasn’t so much the accrual, it was just the structure of oncology at FDA.

FDA was a black box to us. So we spent about a year and internally studied the structure at FDA. We felt that before we started to criticize it or even make comments, we needed to understand it. At that time there was little consistency to the review of oncology products. In fact, they were being reviewed in several different divisions within the agency that didn’t always work together or even require trained oncologists to review.

We started meeting with [CDER director] Janet Woodcock and [division director] Richard Pazdur. We worked with ASCO, AACR, the American Cancer Society and all the cancer centers and we developed a white paper on the structure that was very much a consensus document from the community. We had about 25 groups involved in it.

There was clear consensus that the status of cancer in FDA needed to be elevated—we were looking at a cancer center at that point—there needed to be coordination, there was no cancer program. We went to speak to [then Acting FDA Commissioner] Lester Crawford and Janet Woodcock and as a result of that there was the ability to elevate cancer from a division to an office. There was the beginning of a cancer program; and we began to understand the complexity, the hierarchy, and the funding issues at FDA. Although it wasn’t everything we wanted, it was the beginning of a rational program. We were even able to be involved in the search committee for a new director.

RPM: How do you think the Office of Oncology Products has fared so far since its elevation within FDA? Is the agency approving as many drugs as you would like?

Sigal: Those are separate issues. I think the cancer program exists in name and the organization and resources haven’t been there. The elevation of the office happened, but it’s still a work in progress. Part of the problem is because FDA has been so chronically underfunded. It has been so difficult the last few years that it’s hard for FDA to begin to ramp up their program and recruit the additional people they need to compliment the experts that are already working at the agency to make this program a real program. The dots are connected on paper but in reality there isn’t a robust program.

Elevating the office of oncology was one positive step, but we feel that this is just part of a larger FDA oncology program. With the direction science is moving it will be important for the agency to outline processes in which different divisions and center at FDA communicate about areas of different jurisdiction. For example diagnostics and therapeutics fall in different centers but are being used in combination with more and more frequency.

We’re very hopeful now that with some more resources into the program they’re going to bring in more people internally and working with the external community, that situation will change but it is certainly a work in progress.

I don’t think the raw number of approvals by the Office of Oncology is the right metric. In reality, the reason that most cancer drugs don’t reach approval is due to the fact that they don’t work well. This means that we all must do better if we are going to get better products for patients.

RPM: What recommendations have you been making to Congress in attempting to improve the cancer program at FDA?

Sigal: The biggest issue is the integration of science into that program. Right now, as our understanding of the underlying biology of diseases like cancer advances at such a rapid rate, it’s just crucial that the agency and the cancer program keep up with the science and have the tools necessary to best evaluate. It’s very hard for them to do that because they’ve been so busy approving drugs or working on safety and so many other issues that they haven’t had the resources or input into bringing the science to the next level.

Whether it’s through external advisory boards, partnerships, or through personnel and coordination, we think it’s important to better the science. How can a diagnostic and a therapeutic be developed together? How can cancer vaccines best be evaluated in patients? How do you develop new methods and trial designs to evaluate targeted therapies that may only work in a specific subpopulation? It’s all very connected and generating the evidence that meets the criteria for approval may have to be done very differently.

It’s not really Congress, though they clearly play an important role in positioning the agency in the right direction. Our attention is really toward the agency and how to facilitate these very important changes that are really going to get us to personalized medicine and targeted therapeutics where we think there are major opportunities in cancer.

FDA’s Advisory Options

RPM: If there was a specific cutting edge drug being reviewed, would you like to see a formalized process where FDA consults with external experts outside of the advisory committees?

Sigal: I think there are huge challenges but I do think one major opportunity is FDA’s sister agencies, the NCI and NIH. I think there are already robust relationships in oncology, there’s the interagency task force that exists, and I think there is a lot of science at NIH, and through the appropriate mechanisms, could be a very important resource for FDA.

We’ve also been pressing for Oncology Drugs Advisory Committee (ODAC) meetings that are not drug specific but rather provide topic specific expertise and advice to the agencies to deal with complex issues such as biomarker qualification and advanced trial design. We think exchange and fellowship programs—bringing in people from Georgetown University, Johns Hopkins University, and George Washington University to work at the agency would be very helpful. I think there are lots of opportunities but ultimately there has to be some way to accelerate the science.

RPM: What are your thoughts on ODAC?

Sigal: I think it’s a complicated process. We need to remain focused on the goal of these committees and that is to provide access to the best possible expertise on issues that are very timely to the agency. What I would like to see more of are a lot more ODACs on trial design, pathways for biomarker validation, methodologies for evaluating the safety and efficacy of chemopreventitive agents, the use of circulating tumor cells as a measure of response—all of the things that we think are important. Or for FDA centers to develop their own advisory—not conflicted—board of scientific advisors that can help identify the scientific priorities of the agency and develop a plan forward. This is done at other agencies quite often.

Comparative Effectiveness and Cancer

RPM: How do you expect comparative effectiveness to play out in the cancer field? What do you want to study?

I think it’s a major opportunity for cancer and if used properly, funded properly, we’re going to get to more personalized treatment, targeted treatment, and better identify populations we know can benefit from the drug so we don’t put patients through these toxic regimes that don’t have a prayer of working for them.

There is a great deal of focus on advancing the health IT infrastructure. That in many ways can help inform the future of comparative effectiveness research to be sure that we are indeed asking the right questions and designing the right trials. There are rich database at FDA, NIH and the academic and private sector and I think connecting those databases is crucial. Then conducting the trials that are necessary, you’ll get better information. Right now, there is a tremendous amount of information that is missing. Comparative effectiveness is about better treatment and knowledge and we’re enthusiastic about it.

RPM: Do you worry about it being linked to Medicare coverage decisions?

Sigal: I think that’s a little bit of a red herring. People have made it clear that it will not be, nor should it be. On the other hand, people are making decisions every single day in Medicare and at insurance companies on treatments for which there is incomplete evidence as is. Generating more evidence has rarely been a bad thing.

The Future of Reagan-Udall

RPM: You’re vice-charwoman of the Regan-Udall Foundation. How did you get involved?

Sigal: The process was very clear. A majority of members had to be recommended by the National Academies. The legislation was very prescriptive. I was one of the people recommended. Then there was a group, the heads of FDA, NIH, CDC, and AHRQ that had to make a final recommendation.

When we formed the board, Mark McClellan was the chair, there was an election for me to be vice-chair. It’s been slow-going but we’re finally getting there. We have some projects that we are looking at finalizing that are relatively imminent in the next two or three months. We are talking to the Bill & Melinda Gates Foundation about a very important project. I think we’re optimistic now. We’re getting our bylaws and conflict-of-interest policies done.

RPM: How often do you meet?

Sigal: We have quarterly meetings. It’s happening and we exist—it’s slow but it’s happening.

RPM: Have you received funding yet?

Sigal: Not yet, but we’re optimistic that will happen. I think people want to understand what we’re doing, what our mission is, and the type of projects we’re doing. [Editors’ Note: The FDA Amendments Act of 2007 called for funding from the agency to help start the Reagan-Udall Foundation. Appropirations for those expenditures were blocked in early 2008. (See “Undermining the Foundation” The RPM Report, April 2008.)]

RPM: What is the vision for Reagan-Udall?

Sigal: The vision is to support the mission of FDA. We can do anything like the fellows programs, public-private partnerships that couldn’t be done otherwise within the agency because there are no real mechanisms to do that. We are not there to regulate. We are not there to be advisors for regulation but we are there to support the science mission of the agency and that can go beyond drugs. We’re conveners. It is very similar to the NIH Foundation.

RPM: Where did the creation of the Reagan-Udall provision come from in Congress?

Sigal: It was developed from the beginning within the reauthorization of the FDA with great support from Senators Kennedy and Enzi.