Yesterday, the FDA hosted a webinar for the ME/CFS community on “Working Together for Change.” Their stated goal was to show what has been successful for patient groups in the past in working with FDA and other entities. The slides and recording of the meeting will be available on the FDA website, and I will update this post with that link when it becomes available.
Dr. Sandra Kweder, Deputy Director of the Office of New Drugs (Center for Drug Evaluation and Research, FDA) opened the meeting with a presentation similar to the one she gave at the CFS Advisory Committee meeting on October 3, 2012. She reviewed the history of the FDA and the role of CDER in ensuring that only safe and effective drugs are marketed to the public. Dr. Kweder explained the review process and the unique challenges of evaluating drugs for conditions that do not have objective measures of disease state or signs. She suggested that ME/CFS advocates could learn from the process other disease groups have followed in addressing those challenges, such as irritable bowel syndrome, functional dyspepsia, depression, and fibromyalgia. Dr. Kweder’s advice included: partnering with organizations and centers equipped to conduct trials; recognize that a research definition is for research; filling in the gaps and remember that the science matters; and to be creative in learning from other groups.
I saw a lot of chatter during and after the meeting expressing frustration that this presentation was so similar to the CFSAC presentation. Neither slide deck is available, but the presentations did seem very similar to me. However, there were almost certainly participants in yesterday’s webinar who did not see the CFSAC meeting. Dr. Kweder provided essential background on what FDA does and does not do, and it is crucial for all advocates to understand this. I think it is reasonable to spend some time at these meetings making sure everyone has some shared basic knowledge.
Richard Klein from FDA’s Office of Special Health Issues provided an overview of the ways FDA seeks inputs from patients. He reviewed the history of how this process has evolved, particularly since the HIV/AIDS crisis of the 1980s. FDA uses several mechanisms in this process, including the Patient Representative Program which places patient representatives on advisory committees reviewing drug applications. Mr. Klein emphasized several things advocates should understand about FDA:
- FDA works within a tight regulatory framework that restricts what the agency can and cannot do
- FDA can guide sponsors of drug development but cannot direct drug research and development
- FDA provides assistance but has no direct control over drug development
- FDA must follow strict confidentiality rules
- FDA is only one piece of a larger puzzle that includes researchers, industry, and Congress
- FDA has a strict oversight role and that is its only role
Mary Dwight, Vice President of Government Affairs with the Cystic Fibrosis Foundation gave a presentation on the path that the Foundation pioneered in working with FDA. Cystic fibrosis is a rare genetic disease affecting approximately 30,000 patients. In 1955, the life expectancy for a child with cystic fibrosis was 5 years; today the life expectancy is to the 40s and beyond. This drastic change is the result of a successful drug development process, and the Foundation has played a critical role in that process. Ms. Dwight explained how the Foundation achieved this remarkable success:
- Good science about the disease was essential, including the discovery of the cystic fibrosis gene by Dr. Francis Collins (now Director of NIH) in 1989.
- Drug developers were reluctant to invest, so the Foundation provided venture philanthropy to spur investment. Drug developers also needed data and expertise, so the Foundation stepped up there as well.
- They created a patient registry and Foundation-accredited care centers. This enabled them to connect the drug developers with the patients for clinical trials.
- They created a national therapeutic network, coordinated from one central location, to provide best practices in study design, standardized research procedures and expert advice on correct outcome measures. They also assemble scientific consortia to foster communication and collaboration among researchers.
- The Foundation sees FDA as a partner to talk about patient data, but that it is the patients’ job to bring the data to the table. FDA only evaluates data, it does not collect the data.
Ms. Dwight also said that as science and treatments have evolved, their approach has evolved too. She recommended that if the ME/CFS community does nothing else, it should collect natural history and group data for the patient population.
Pat Furlong of the Parent Project Muscular Dystrophy started her presentation by saying that ten years ago the Duchenne community was where the CFS community is now. Duchenne is a progressive and fatal genetic disorder affecting boys, with approximately 20,000 new cases per year. She said that stakeholders (patients, researchers, regulators, etc) interact with non-living parts of the system (regulations, etc) in an ecosystem of drug development. Ms. Furlong said that they modeled their process on the work of the Cystic Fibrosis Foundation, and started with a patient registry. While there is still no treatment for Duchenne, there are now drugs in the pipeline. She categorized the elements of a successful program:
- Clinical infrastructure – patient registry; identify endpoints; research networks
- Advocacy – increased money from NIH, DOD and CDC; direct engagement of regulators
- Education – patients; drug developers; clinical trials; management of expectations (because this is a lengthy process)
Ms. Furlong said that her organization’s Board created a policy statement on its goals for FDA advocacy. They’ve held two meetings with CDER to discuss the policy and what data FDA needs. They are working with a consulting firm to develop and publish a risk-benefit framework for rare diseases, and are developing a parent survey on risk tolerance.
Participants had an opportunity to ask questions of the panel. Patricia Carter, myself, Marly Silverman, Courtney Miller, and Hillary Johnson made statements or asked questions. Steve Morin of the Office of Special Health Issues also invited people to submit questions since we ran out of time.
Overall, I found this webinar to be very informative, and not a little daunting. The CFS community is a long way from accomplishing what the Cystic Fibrosis and Duchenne communities have done. However, there are steps being made in the right direction. FDA will hold a meeting next year to address the issues of endpoints and outcome measures in CFS. The CFIDS Association is competing for prize money to fund patient registry projects. Several organizations, including the Chronic Fatigue Initiative and the CFIDS Association have established biobanks. CFI’s Bank will house 200 patient and 200 control samples; the Association’s Biobank has enrolled more than 500 patients and controls. One of the Association’s grants this year was to a pharmaceutical company to screen approved drugs for applicability in CFS. Finally, on December 20th, the FDA will hold an advisory committee meeting on Ampligen, the only new drug currently in the pipeline for CFS.
The main takeaway from the webinar was this: patients, advocacy groups, researchers, industry, NIH, CDC, FDA, legislators and policymakers must all cooperate to help make treatment for CFS a reality. As Mary Dwight said, forced collaboration among the players is essential but the patient is the only player who participates in every step of the process and is the only one with a holistic view of the disease. We must be at the table at each stage in the process.
Good summary. Interesting, but even as a patient community we are nowhere near where the cystic fibrosis and duchenne community were when they started.
Not only are there at least a dozen different definitions for ME and CFS, but cystic fibrosis and duchenne seem to be well-defined diseases, while ME and CFS are syndromes and probably hide several unknown and undiagnosed known diseases. I don’t find the “I am ME” hype where CFS patients and people who HAVE Lupus, Lyme, Addison, whiplash, … self-diagnose and claim that they ARE ME-patients helpful in this respect either.
Where I live patient organizations are quarrelsome, secretive, ranging from science-illiterate (not knowing how to spot difference between SBM/EBM, CAM, experiments and quackery) to anti-science attitude …
I’m looking at you guys & girls in the USA (CFIDS) and UK (ME A) to take the lead to get us out of this mess.
Good points, Johan. A question I was not able to ask and that I submitted today was, “Cystic fibrosis and Duchenne are both genetic disorders for which the mechanism of illness has been identified. This is is stark contrast to ME/CFS. My experience has been that ME/CFS advocacy involves a great deal of education, answering those who believe the illness is psychological, and sorting out who does and does not have the illness. Given that difference, can anyone on the panel comment on how that might affect the advocacy process?”
Also Johan, how big a problem are those who self-diagnose with ME vs are misdiagnosed by doctors? Why would anyone who knows anything about this illness WANT to carry this label instead of lupus, etc?
@Jennie Spotila
I have no idea how many ME patients there are. I have seen numbers for the prevalence for Fukuda CFS, Oxford CFS, Reeves CFS and CCC ME/CFS, but not for ME. Numbers for ME mentioned by patients are usually those of Fukuda CFS. According to recent article on MERUK 40-50% of CFS patients are misdiagnosed (sleeping disorder, depression, obesity, MS, diabetes, …) and that is just for patients who didn’t fit the criteria on closer inspection.
About the self-diagnose when you have a disease that in some cases excludes a diagnosis of CFS and/or ME, I have been wondering about that myself. I would be relieved to have a different diagnosis, get treatment and maybe get (part of) my life back. In some cases it is almost like a status symbol (I am ME patient vs I am ME patient and I have Lupus vs I am ME patient and I have Lyme with at least 4 co-infections vs …). In some cases I believe it is to not face up to real problems (depression, anxiety, eating disorder). Been in some discussions (too many) about this (and other topics), but it is a very touchy subject.
PS: the moment I realized that the online community represents less than 1% of the total number of patients, I decided to no longer participate in those spoon-wasting yes/no discussions again. Left most patient groups on Facebook for that reason,.
Good points Jennie. Getting the CDC on board with this seems well neigh impossible. Don’t know if we could bypass them & get the little clusters of good doctors to support us. CDC toolkit is describing a different illness.
@Jean Harrison
Does the CDC toolkit describe a different illness? Or is it as vague or even more vague than the Fukuda definition? I usually visualize the different definitions as concentric circles, meaning ME and ME/CFS as subsets of Fukuda, as subset of Oxford, as subset of empiric, but that’s just me.
The moment you decide to give up trying to convince organizations like the CDC and rely on clusters of “good” doctors, is the moment you give up trying to go mainstream. Whether or not this disease gets accepted as biomedical with biomarkers or different definition depends on organizations like the CDC and FDA, not just in the USA but world-wide, so you’ve got to keep an open line. How do you define a “good” doctor? IMO some of them (don’t ask me names) are really hurting our cause promoting/using unproven, experimental and even quack treatments. Hang out on some skeptic, SBM/EBM forums and you will start realizing that demanding this disease gets accepted as a physical disease and needs biomedical treatment and at the same time promoting “fringe” scientists and doctors is not really helping.
@Johan
hi Johann,
I agree with you that it’s a good idea to win over agencies and professional organizations, but I think CDC is going to require a personnel change. FDA implied that this was what it took there. I think it would be a good idea to focus on Congress and some professional organizations like the American College of Rheumatology and the American Academy of Family Physicians. And similar bodies in Australia. We are working on lobbying in UK but it is difficult to make headway there, of course. Work is ongoing elsewhere as well.
Also, @Jennie Spotila , thanks for that good question. I was wondering that as well.
Another big difference is that these groups’ advocacy efforts are done primarily by healthy mothers of patients (who, granted, may have a lot to do already, caring for a very ill child), while ours are done primarily by the patients themselves.
bye,
Janelle
The webinar had some good information, mostly from Mary Dwight and Pat Furlong, but it left me wondering what to do or say on December 20th. I have no metrics endpoints to present, so should I say anything at all? Does the FDA want my input? Their message left me in doubt.
One way I believe patients can maximize these opportunities is to remember that a Q&A is for questions that can be answered and that have not been answered during the presentation.
Anything else is less productive in such a format. In this particular webinar only four people were able to speak before time ran out. Thanks to Ms. Spotila for adhering to the format.
Written statements of opinion can be submitted either ahead of time or after the webcast. And to be fair, in this case, the FDA was remiss in not enforcing this. On radio you hear them do this all the time. If someone doesn’t have a question, the moderator simply moves on to someone that does.
I agree, Kelly. So few people have the opportunity to speak. I was shocked to be second. We need to make that time count! Let’s follow the format (questions or comments), time limits, etc.
Was it on ME/CFS or is this just the ME/CFSers substituting and switching terms. Because it is not what we believe or visualize, but about science and taxonomic principles. ME patients are not ME/CFS advocates or partnering with ME/CFS groups. Because science and treatments have not evolved with these undifferentiated mixed groups which the ME/CFS crowd is creating and promoting.
@Johan
Johan and Jennie, I just want to comment on the MERUK commentary on misdiagnosis of ME/CFS. While there are likely cases of misdiagnosis, if you actually read the papers cited, subjects were classified as “misdiagnosis” based on having an alternative diagnosis (depression, thyroid disease, sleep apnea, etc.) that MIGHT explain their symptoms. However the TRUE test of misdiagnosis would have been if they had pointed out to these subjects doctors possible alternate diagnoses and followed up with these subjects after they had been adequately treated for these alternate diagnoses. If their CFS symptoms resolved, that is a true misdiagnosis. Otherwise, these could merely be other illnesses the CFS patients happen to have at the same time. In fact, Dr. Klimas believes up to 50% of the CFS patients she has have sleep apnea but treatment of this does NOT resolve most of their CFS symptoms. Having CFS does not protect one from having any other disease as far as we know.
Good point about follow up and TRUE exclusion of disease.