The Life Raft Group (LRG) is the world’s leading 501-C-3 non-profit organization providing information, support, and assistance to patients and families with a rare cancer called Gastrointestinal Stromal Tumor (GIST). In 2007 the LRG, with a generous start-up grant from Novartis, initiated a unique research program to find the answers to GIST treatment resistance and to embark upon a pathway to find a cure for GIST that will serve as a model for other cancers.
Starting with the creation of a realistic five-year strategic plan to identify the priority projects needed to overcome GIST treatment resistance, we brought together a core group of the world’s best GIST researchers and introduced cooperation, coordination and accountability as key building blocks of this historic effort. We created a grants structure designed to give maximum support to this research effort, including a 0% cap on the administrative overhead that could by charged by the researcher’s institutions.
We are approaching a critical intersection on the pathway to finding a cure for a cancer. We have the right scientific tools and the right researchers at the perfect time and place to demonstrate how to treat and cure cancer. We have achieved an historic understanding of the fundamental genetics driving GIST and the know how to identify and overcome the remaining downstream pathways of resistance. We have two approved targeted drugs, imatinib (Gleevec) and sunitinib (Sutent), and a number of other promising ones in the pipelines. We need to keep our core team in place, expand it ever so slightly to add a few additional priority research projects and commit the remaining three years of funding.
This opportunity to complete the pathway to a cure is unprecedented and well within our grasp.
Each year billions of dollars are contributed by government, charities and individuals to fund cancer research. Few causes touch so many families and create such passionate responses.
What has all this money accomplished? The 2005 Annual Report of the National Institutes of Health (NIH) proclaims that cancer death rates continue to decline and notes that death rates from all cancers dropped 1.1 percent per year from 1993 to 2002. A closer look shows that most of this progress has come from earlier diagnoses of cancer and lifestyle behavior changes like a decrease in smoking. Progress in finding effective cancer treatments has been relatively slow. And if one takes a longer historical view one finds that cancer death rates have not substantially improved.
The chart below provides a prospective from 1976 to 2000:
Finally, if we look at the success we have had in lowering death rates from cancer compared to that of other major diseases the disparity is quite striking. From 1950 to 2005 death rates from heart disease have dropped from over 586 per hundred thousand to under 245 per hundred thousand. In the same period, death rates from cancer have remained constant.
The term ”cancer” is comprised of many different diseases. The libraries of health statistics would likely provide data to support all sorts of opinions about the effectiveness of cancer research in providing treatments which lower cancer death rates but few would argue with the point that the death rates from cancers are too high and simply unacceptable.
GIST cancer research provides a perfect model for demonstrating how to cure other cancers. GIST, although quite deadly, is a relatively simple cancer and has an increasingly understood mechanism of cancer mutations. Further, there is a growing list of targeted drugs to address these mutations. Finally, we have created an innovative research strategy, including prioritized project areas and the means to achieve them.
The history of this disease is summarized below. It has brought us to the point where we have the right scientific tools and the right researchers at the perfect time and place to demonstrate how to treat and cure cancer.
What the experts say about GIST as a model
- “GISTs appear to serve as a model for molecule-based diagnosis and treatment of solid tumors.” Y. Kitamura; Cancer Sci 2003
- “GISTs are basically a model for what is coming." Christopher Corless; CAP TODAY 2004
- “It also serves as a model for other more common cancers. By studying GIST, we expect to learn new things about the big four killers - breast, colon, lung, and prostate cancers. Science and medicine often make the biggest leaps forward in unusual, rare diseases.” George Demetri, Harvard Gazette
- “Continued intense study of gastrointestinal stromal tumor may lead to new paradigms that could revolutionize all of oncology.” Jonathan Trent and Bob Benjamin, Dept. of Sarcoma Medical Oncology, MD Anderson Cancer Center
Rarer cancers, like GIST, attract smaller amounts of funding from all sources than do more common cancers like breast and prostate. With that as a reality it became particularly important for the Life Raft Group to understand how best to leverage its limited research dollars so that the maximum amount possible went into actual research rather than administrative overhead and so that we had the best possible chance of actually finding more effective treatments and ultimately a cure.
Upon investigating, the LRG found that there is an assumption by many that handing a check to a major cancer charity or cancer research institution results in that money actually being used for research for a particular cancer. Let’s follow that money to see what actually happens.
A sum of $10,000 has been raised by a group of individuals and donated to a cancer research center for breast cancer research. The center subtracts $7,400 for administrative overhead.
What happened to the remaining $2,600? As the donation was not directed to any particular project (only to “breast cancer research”) and as nobody asked for any accounting, nobody knows what the money was spent on and what it accomplished.
This scenario actually happened. The beauty of a community gathering for a common cause is that it raises spirits and solidifies bonds while working toward a noble cause. Feeling good about what you are accomplishing, however, is only half the battle. The money needs to be accounted for.
Rare cancer patients cannot afford trickle down funding
We do not suggest that there is anything necessarily wrong with prestigious research institutions charging a particular administrative overhead rate but we do feel that rare cancer organizations like the Life Raft Group simply cannot afford to pay a proportionate share of administrative overhead rates ranging from 50 percent to 75 percent. One reason for such rates is that top administrators of major medical centers are paid far more than leading researchers are. CEOs of these centers have been known to make salaries in the seven-figure range. If the total amount of money on the table is limited, as is the case with GIST, we could not rely upon this trickling down of funding to put enough in the hands of the actual researchers.
Picking up the money trail again, let’s follow how it gets to the investigator and what happens to it then:
The traditional way of distributing available money to cancer researchers is to issue a call for proposals by individual investigators and to have an expert board review them and make funding decisions (peer review). Although this process has some merit, it is time consuming and not at all guaranteed to fund those researchers with the best chances of success in finding effective cancer treatments. Finally it is not driven by any strategic plan and is almost guaranteed to foster competition rather than collaboration amongst the various researchers. Dr. Susan Love, President of the Susan Love Foundation, recently wrote in a New York Times article that “the problem with cancer is the way that it is researched.” She went on to say that peer review “works well at eliminating poor investments but it squelches innovation and fosters the old boy network…(and) end(s) up giving money to better ways of doing the same thing…that have a good chance of quickly leading to publications…”
This process lacks any deliberate sense of critical accountability for how this traditional allocation of research money was actually spent and particularly for what it has accomplished. Even when an individual research grant is followed by a publication it is rarely connected to any overall strategy or to any criteria of success related to significantly improved treatments and survival of cancer patients. Alas, the publication of the research is often the endpoint in and of itself. As to any sense of urgency in finding and sharing information about more effective cancer treatments, it simply is not consistent with the culture of the cancer research community.
Pathway to a cure:
Based on an analysis of this information the Life Raft Group decided not to follow more traditional rules and simply hand over money to cancer centers for the purpose of GIST cancer research. We also decided not to send out a call for research proposals from individual investigators. Instead:
- We identified a core group, with complementary expertise, of the world’s leading GIST cancer researchers whose combined personalities would permit them to work together synergistically.
- We challenged them to create a strategy which consisted of specific prioritized projects with the greatest chance of success to guide GIST cancer research and to commit to a collaborative rather than a competitive philosophy. In return, we committed to allocate our research funds to implement that strategy.
- We also asked each of our investigators to assume a cross cutting responsibility for coordinating and reporting on key priority areas assigned to them even though some of the grant funding went to investigators in other institutions.
- We created a supportive grants process which capped all administrative overhead at 0%, which conditioned each of a series of six month grant awards upon both a financial and research project accountability for the prior six month period and which provided mechanisms for correction that could redirect funding from less productive to more productive areas.
- We created tissue banks, both for adult and pediatric GIST, to support this research process
- We have begun receiving required progress reports to account for what the money was spent on and what it was accomplishing.
- Most significantly our plan is beginning to work.
An early third-party evaluation is found in the statement below:
April 18, 2006
In the Life Raft Group Research plan of action, one finds both true dedication and conviction that can only emerge from one’s heart as well as efficiency and professionalism… It seems to me that this combination is the best ground for successful research and I would like to express my sincere respect and admiration for your efforts and the efforts of your group. I have no doubt that you will succeed in making a significant contribution to GIST research …
Dan Vasella, M.D., CEO, Novartis
On a parallel track the Life Raft Group continues to expand both the scope and the content of its GIST Patient Registry with medical updates provided by patients.
We utilize the data from this registry to identify critical areas not being covered in a timely way by clinical trials or by the traditional cancer research community, including understanding the non-toxic but life-altering side effects of cancer drugs and the implications of changes in drug levels after a clinical trial has started.
What do others have to say about our GIST Patient Registry?
What are the implications of patient-generated data? This is powerful and compelling stuff! I remain incredibly impressed by the data-coordinating abilities of the Life Raft personnel. I see the major purpose of this sort of data as hypothethesis-generating. Unfortunately, it cannot be free of bias and thus cannot stand by itself, but it certainly can point investigators and the Company in the right direction and let us know what we need to be looking at more closely. Thus, its importance cannot be overstated.
July-August, 2001 LRG Newsletter
Charles Blanke, M.D., Director, GI Oncology Program, OHSU Oregon Cancer Institute
The Life Raft Group that Norman helped to start (and has since become the leader of) has provided various people, patients, doctors, investigators, with a unique kind of data bank that cannot be replicated anywhere else, not even in patient trials.
Magic Cancer Bullet, 2003
Daniel Vasella, M.D., CEO of Novartis
‘One of the great benefits of patient-initiated research is its speed,’ Scherzer says. ….professional research has a built-in lethal lag time-a period of delay between the time some people know about an important medical breakthrough and the time everyone knows. And, as a result, many patients who could have been saved by the latest treatments die unnecessarily. …Physicians are just as much a victim of this lethal lag time as their patients.
In October, 2001, the group published a review of Gleevec’s side effects. And in addition to collecting the usual data, the Life Raft Group’s study broke new ground in several areas:
- It provided data on the quality of the clinical care available to study participants at each of the centers conducting clinical trials.
- It attempted to evaluate the information sources patients relied upon.
- It developed a methodology by which patients could, in effect, serve as their own control group.
- It introduced a new scale for rating the severity of side effects from the patient’s point of view, as opposed to the toxicity standards established for clinical trials by the National Cancer Institute.
Tom Ferguson, M.D., Editor and Publisher of the Ferguson Report
from “Bypassing the ‘Lethal Lag Time’"
The future of medical research
Such patient-initiated medical research projects turn the traditional medical paradigm upside down. Before the Internet, researchers took the lead, research trials were structured to meet their needs and the delay between discovery and dissemination was considered an unavoidable part of the process.
The prospect of research-oriented online support groups offers a number of appealing scenarios. Patient groups could design and conduct their own studies, collecting their own data, analyzing their results, and publishing their results. They could provide researchers with access to perfectly targeted study populations at little or no cost. But whatever role they play, once they become active players in medical research, patient groups will demand a voice in deciding what should be studied and how that research will be conducted. While such e-patient initiatives may encounter some resistance, in the end it seems likely that the financially-strapped medical research establishment will come to consider such e-patient research an offer it can’t afford to refuse.
The new research model pioneered by the Life Raft Group is making it possible for patients and family members to contribute to clinical research for their diseases in unprecedented ways. I predict that we’ll be seeing a lot more of this sort of thing in the years to come.
George Demetri, M.D., Medical Director of the Center for Sarcoma and Bone Oncology at Boston’s Dana-Farber Center
Cyberspace has spawned a powerful breed of advocates. Consider the case of Gleevec. Members of an internet group spread the word about Gleevec, bringing scores of patients into new clinical trials. Then they went one step further, creating a group called Life Raft, where participants in one trial could share information about the drug’s efficacy, its side effects and their interactions with doctors. Conservative clinical oncologists cringed. Life Raft represented a major break with medical precedence.
Sara Solovitch, Wired Magazine, September 2001
As these examples show, patient-driven research will become more and more important, and will provide an example of the way things will go in the future. As other patient groups begin generating their own medical data, it will change the relationships between research professionals, clinicians, and patients quite dramatically. These groups have been phenomenally successful in recruiting new patients for badly needed clinical trials. And I can assure you that their potential role in medical research is not lost on the drug companies. Those patients taking Gleevec do not consider themselves guinea pigs. They are the recipients of experimental medicine.
Gilles Frydman, President of Association of Online Cancer Resources
You know, despite the terrible overuse of the term ‘paradigm shift,’ I believe that when patients came together the way the (Life Raft) group did, and accomplish what you have accomplished, even the father of the term … would agree it is the appropriate description. It is an honor to know a person who is part of the solution.
Bernard Glassman, University of North Carolina and Deputy Director for Population Sciences, Lindberger Cancer Center
Life Raft is unusually important to our communications research, and for many of the same reasons that it is important to the future of clinical research. We believe that Life Raft will turn out to be the first in what will become a wave of survivor-involved, self-researching virtual teams. As such, Life Raft offers both a model and an inspiration to other survivors and other researchers.
As genomics, proteomics and pharmacology progress, clinical trials will depend increasingly on smaller pools of participants who are genetically appropriate for a particular targeted therapy. This will not be possible in just a few geographical areas, and will require the kind of connectedness and cooperation Life Raft has been able to achieve. At the same time, we will need to identify the risks and benefits of new treatments more rapidly than ever, because the sheer numbers of patients will be smaller. Again, the Life Raft approach to self-monitoring offers enormous potential as well as proven results.
Barbara Rimer, University of North Carolina and Deputy Director for Population Sciences, Lindberger Cancer Center
Because we are dying too fast for the traditional cancer research process, the Life Raft Group has decided to carve out a seat for itself at the cancer research decision making table. Traditionally most cancer research decisions are made by three key players, those representing the Pharmaceutical Industry, the Clinical Researchers and the Government. Although the decisions are made about patients and although patient representatives are sometimes given token roles, particularly by the government, we submit that patients not only do not play a critical role in the cancer research decision making process but that they are generally totally excluded. What’s wrong with this process?
There is a general injustice in one group of adults making life altering decisions about another group without their knowledge or consent. On top of this, the current situation is generally not focused primarily upon finding the drug or the combination of drugs that the cancer patients in mind need.
The pharmaceutical representative understandably must focus upon finding drugs that can be brought to market and that can earn a profit. That makes trials with drugs made by multiple pharmaceutical companies very difficult to bring about. The clinical researcher must be cognizant of choosing a particular clinical trial that is different though not necessarily better than that which is being done by a colleague and must choose which trial to process first if he/she has more than one. Whether that decision is influenced by any financial benefit provided by the pharmaceutical company is always an open issue. Finally the government must judge the merits of the research in question based upon the narrow protocol it approved in the first place, not against any strategic plan to treat and cure the cancer in question. Only the patient has as their primary focus the issue of the likelihood that a particular research will contribute to the survival and well being of the patients and the sense of urgency to accomplish that.
The rationale for our approach is based upon the tremendous respect we have for our colleagues in the pharmaceutical, clinical research and government worlds. We believe that putting patients at the cancer research decision making table, if not at the head, will help free all three of these disciplines from the market place and cultural restrictions that limit their effectiveness in carrying out critical cancer research.