FDA Meeting Materials

The FDA Drug Development Workshop for ME and CFS is finally here!!! I will be speaking on a panel at the meeting on Friday, and am in frantic preparation mode. I’ve gathered the pertinent materials together in one post to help you prepare as well. This is an historic meeting, and I hope you will watch and participate.

WATCH THE MEETINGI will add the link as soon as it becomes available Watch it here
Meeting Materials

FDA’s meeting materials page

Final Agenda (pdf link)

FAQs about the meeting (pdf link)

 

Preparing to Participate

Finding Your Strongest Voice for Public Testimony webinar by the CFIDS Association on April 4th

Training for the Drug Development Workshop webinar by PANDORA on April 16th

 

Understanding FDA

FDA 101 webinar offered by FDA on April 18th

Overview of the Drug Development Landscape webinar offered by the CFIDS Association on March 28th

How FDA Defines “Safe and Effective Treatment” webinar offered by the CFIDS Association on April 11th

FDA’s Drug Approval Process

Drug Approval Process Infographic (pdf link)

 

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Vincent Departs

Eagle-eyed Tom Kindlon posted on Twitter last night that Dr. Ann Vincent’s name has been removed from the CFS Advisory Committee roster. It appears that Dr. Vincent has resigned, although I have no information on when or why she may have done so. I’ve emailed Dr. Nancy Lee for more information and will share what I learn. (see update below) For now, I can try to put this change in context for you.

Dr. Vincent was nominated to the CFSAC by the CDC in October 2010 and appointed to the Committee in April 2011. She was midway through her four year term on the CFSAC. The focus of Dr. Vincent’s clinical practice and research is fibromyalgia and fatigue. Many advocates were critical of her appointment to the Committee because some of her publications suggest she ascribes to the psychosocial view of fibromyalgia and CFS. On the other hand, Dr. Casillas told me last year that he was forming a collaboration with Dr. Vincent and Dr. Jordan Dimitrikoff to look at a potential biomarker.

Last year, Dr. Vincent published a CFS prevalence study conducted in Olmsted County, Minnesota. The study was a retrospective medical records review that identified people who might meet criteria for CFS. Patients meeting the Fukuda criteria, and who had no exclusionary conditions, were considered to have CFS based on the information in the records. The study found a CFS prevalence of 71.34 per 100,000 persons, or 0.071%. This is much lower than other studies that have estimated the prevalence as 0.29% to 2.6%. Study design likely contributes to this wide variance, in part due to the strict exclusionary criteria applied. If Vincent’s study is correct, then the number of people with CFS in the United States is closer to 225,000. This is quite a contrast from one of the most quoted prevalence studies which estimated that approximately 1,000,000 people in the US have CFS. Also notable in Vincent’s study is that only 36% of patients had documented post-exertional malaise. However, this could be a result of doctors not knowing how (or whether) to assess for PEM.

You may recall that Dr. Jacqueline Rose resigned from the CFSAC shortly after her appointment in 2012. The CFSAC bylaws requires that a vacancy be filled within 90 days, and Dr. Koh said that the 2011 nominations were being reviewed for a replacement. Ten months have passed and the vacancy remains, although my understanding is that a replacement for Dr. Rose has been selected and will attend the May CFSAC meeting.

Now there will be another vacancy to fill. I’ve asked Dr. Lee if a new call for nominations will be made, or if previous nominations will be reexamined. I have no additional information about why Dr. Vincent resigned or what timeline we can expect for a replacement, but I will keep you posted as I learn more. 

 Updated April 22, 2013: Dr. Lee’s office said by email: “Dr Vincent has resigned; the reason for her resignation is private information.  We will be following the FACA rules to select her replacement.  The new member replacing the member who resigned last year will be introduced at the May meeting.  We will post the name on the CFSAC website soon. Thanks for your continued interest in CFSAC.”

Updated April 23, 2013: The new member of the CFSAC, replacing Dr. Jacqueline Rose, is Rebecca Patterson Collier, RN.

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I Heard the News Today, Oh Boy

What is there to say about something like the Boston Marathon bombing? There is no sane way to reconcile the gruesome images, the suffering and destruction with our need to believe that we are safe. We are privileged enough in this country to think that this sort of thing does not happen here. Once I confirmed that everyone I love in Boston was ok, my real-world connection to the event faded. But this morning, my mind and heart are still bound up in the news.

Being housebound makes me vulnerable in an odd way. On the one hand, I am remarkably safe in my home and neighborhood. I rarely go in to the city or to places with large crowds. But on the other hand, I am an automatic audience for big news events.  I don’t have a meeting to go to, or kids to pick up from school, or any other demands on my attention. Most of the time, it’s just me, the tv, Facebook and Twitter. If I choose to tune in, I end up vicariously experiencing these events.

I watched the Columbine shootings unfold. For a week after 9/11, I only turned off the tv to sleep. Six years ago today, I followed the Virginia Tech shootings on CNN, and I held my breath between the phone calls from my brother who was there. It has gotten to the point where I start to cry as soon as I learn about an incident like these. Sometimes I have the self-discipline to avoid the media if I think the news will be too upsetting. I stayed off Twitter and Facebook for days after the Newtown shootings, and I still have not seen any footage from that day. I long ago decided that tv news is shallow, and frequently borderline moronic, so it’s easy to avoid that. But if I pay attention – and Twitter makes that incredibly easy – I get sucked in to following every update and rumor.

Emotional shock and distress quickly induces a cascade of physical exhaustion, pain, and brain fog. The more I watch, the worse I feel. Compounding the simple stress is an overwhelming feeling of powerlessness. I am trapped in my home, alone with the images of people who need help. There is nothing I can do. I remember the despair I felt after 9/11 because I couldn’t simply drive to New York and pitch in. After the Virginia Tech shootings, my brother started volunteering for an emergency services provider. I am limited to donating to the Red Cross or knitting afghan squares. This is not a substitute for directly helping people face to face. Watching people suffer, and being unable to do anything about it, feels like sandpaper against my heart.

This morning, I’m thinking about the people who will now join the ranks of the disabled. There are reports of people who lost legs or feet. Sure, they’ll get prosthetic limbs and rehab and lots of attention. But their lives will never be the same. Perhaps there will be people disfigured by the blasts, or people who develop post-traumatic stress disorder. Some of them may have great family support and health insurance, but others may not. In the moment of the explosions, everything changed for these people. They have to run a different marathon now. This is the marathon of doctors and procedures and medication and paperwork and learning to live with a changed body. This is the marathon of people helping in the immediate aftermath and then fading away and going back to their lives. This is the marathon of answering the “how are you?” and “it could have been worse” comments. This is the marathon of the sick and injured.

I don’t know what it’s like to be the victim of any crime, let alone a crime like this. But I do know about suffering and endurance and navigating a changed life. The real crisis is not the moment of explosion. It’s everything that comes after. I know a little bit about that marathon, and I wish I could help other people on that path. But my own marathon keeps me imprisoned, acutely aware that others are suffering and completely unable to help them.

 

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Ring Theory

We’ve all had the experience of someone saying the wrong thing to us about our disease.

“I hate that you always cancel at the last minute.”

“You rest all day. Can’t you make dinner once in awhile?”

“Work is killing me. I am so exhausted!”

If you have ever been on the receiving end of a comment like that (or have made a comment like that to someone else), let me introduce you to the Ring Theory.

Write your name on a piece of paper and draw a small circle around it. Draw a larger circle around the first and write in the name of the person who is closest to you – your spouse or partner, a sibling, etc. Repeat this process, drawing increasingly larger circles and filling in the names of people based on how emotionally close they are to you. So after your spouse, maybe a best friend or parent is next closest. Trusted friends should be closer than work colleagues; your favorite aunt might be closer than your brothers.

Now apply a simple rule: people can only complain to those who are in larger circles. Ring Theory says that complaints, moaning, despair, criticism, and negativity should flow only from smaller circles towards larger circles. There’s nothing wrong with expressing negative or difficult feelings, as long as you direct that at someone in a larger ring. You, as the sick person in the center, can whine to anyone you want in the other circles. Your best friend can complain to your work buddy. But negativity should never flow towards the smaller circles. Your old roommate should not give unsolicited advice about your medical care to your spouse. Only comfort and support should flow from larger circles to smaller ones. Offers of help, sympathetic listening, and understanding should be offered to those closer to the center of the circle, and especially to the person at the very center.

The one problem I see with Ring Theory is that it seems to be designed for acute crises – whether illness or trauma or other acute events. For those of us with chronic illnesses or permanent disability, I’m not sure that the “comfort in, dump out” should always apply. For example, I want and need my husband to share with me how hard my illness is for him. I can’t be the center of attention all the time. Sometimes, my husband needs my support to deal with the impact of ME/CFS on our lives. The same is true for my closest friends and family. Part of what motivates me to cope with ME/CFS the best I can is to make things easier for the people I love.

Overall, the Ring Theory is great advice for all of us. No matter what the crisis may be – illness, death, unemployment, trauma – remember to keep comfort flowing towards the center of the circle, and keep negativity flowing away from the center. It may be one of the best ways you can help, and be helped in return.

 

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Learning About FDA

FDA’s decision making process is complex, to say the least. But the more we can learn about the process and how FDA fulfills its mission, the better equipped we will be to participate meaningfully in the upcoming Drug Development Workshop for ME/CFS. Fortunately, there are a variety of resources to help us out.

FDA is hosting a webinar entitled “FDA 101” to help educate the ME/CFS community about FDA’s basic functions and regulatory framework. The webinar is scheduled for April 18th at 3pm Eastern, and you need to register in advance.

The CFIDS Association recently hosted two webinars about FDA. The first was an overview of the drug development landscape, and explained the pipeline from lab discovery through clinical trials and into commercial use. The second explained the intricacies of the phrase “safe and effective treatment for ME/CFS,” and its relevance in the context of the upcoming FDA Workshop (recording should be available soon). Recording is now available.

I’ve gathered other materials relevant to the Workshop in a single post. I’ve also written about FDA’s goals for the meeting, and why the meeting is so important. There are also other resources for consumers available on the FDA’s website.

Whether you are attending the Workshop or watching online, take some time to watch one of these webinars or read more about FDA’s approval process. The more we know about how treatments are created and approved, the more effectively we can advocate for the swift development of such treatments for ME/CFS.

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Down to the Wire

Tomorrow is the big deadline to register for the FDA meeting on Drug Development for ME/CFS. I’m recapping the deadlines and also providing a little more information on how participation will work:

If you want to attend the meeting in person, you MUST REGISTER by 5pm Eastern on Monday, April 8th. This deadline applies even if you do not wish to provide public comment.

If you want to participate in one of the panels on Day One of the meeting, you must indicate your interest when you register. You must ALSO send a brief summary of your answers to the Federal Register questions (pdf link) by 5pm Eastern on Monday April 8th in order to be considered for one of the panels. Your summary should be emailed to ME-CFS-Meeting@fda.hhs.gov

If you want to offer comment on a topic not covered by the Day One panels, you must indicate your interest when you register. You must ALSO send a brief summary of your comments to ME-CFS-Meeting@fda.hhs.gov by 5pm Eastern on Monday April 8th in order to be considered for the open comment period.

If you want to watch the webcast of the meeting, FDA is asking people to REGISTER by 5pm Eastern on Monday, April 8th. However, FDA has told advocates that anyone who has the sign in access to the webcast will be able to see it, and the webcast access information will be posted on the FDA website about a week before the meeting.

If you want to submit written comments, you have until August 2nd to post comments through the meeting docket. The docket page currently says it will close on April 8th, but FDA has said in the Federal Register and in communication to advocates that the docket will be open until August 2nd.

How will these panels and public comment work? I’m seeing a lot of confusion among advocates about how this comment process will work. We are all accustomed to the CFSAC comment process, but this is very different. Based on FDA’s descriptions of the day in the Federal Register notice, the meeting FAQs (pdf link), and follow up emails to advocates, here is my understanding of how this will work:

  • Most of the Day One meeting will be devoted to discussion of the questions posed in the Federal Register notice. FDA will select panelists for each topic from those who indicated interest in their meeting registrations. Those panelists will be selected and notified some time after registration closes on April 8th.
  • For each panel topic on Day One, a brief panel discussion will start the dialogue. Two FDA moderators will then facilitate discussion by inviting comments from other patients. If you are at the meeting and want to comment, the moderators will recognize people from the floor and you do not have to register in advance for that. This is something we have NEVER had – a chance for interactive discussion at a public meeting.
  • The configuration of the panels, time allocation and other aspects of the discussion will not be finalized until after the registration deadline. So we don’t know who will be on the panels, how much time will be spent on each topic, and so on. These details will come out about a week before the meeting.
  • There is approximately 30 minutes allocated for public comment on other topics at the end of Day One. This time may change based on the final panel and discussion configuration. FDA has said that there have been significant numbers of requests to comment, and so it will be a challenge to give everyone a chance to speak. Comment by proxy will not be permitted, and the time allotted to each commenter has not been determined yet. In any case, this section of the day will be more similar to what we do at CFSAC meetings in terms of time-limited statements with no discussion or interaction.

This is an important opportunity for all of us in the ME/CFS community. Make sure you can participate by registering on time and providing comment in whatever way is possible for you.

 

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In Which I Rant at NPR

Two weeks ago, NPR published a story about the rise in Social Security disability claims. The bottom line of the story is that unemployed people are choosing to go on SSDI because they have conditions that prevent them from doing physical labor and are not educated or qualified enough for desk jobs. According to this story, Social Security “has also become a de facto welfare program for people without a lot of education or job skills.” This is a legitimate issue, but there was plenty to object to in the story and I fired off an email to NPR. Since then, criticism of the story has skyrocketed, and NPR’s minor revisions of the story have not stemmed the tide. Others have done great analyses of the story and its many errors, and a coalition of disability rights advocates sent a terrific letter to NPR (pdf link).  Personally, I’m focused on a few comments by reporter Chana Joffe-Walt and the stereotypes those comments reinforce.

Joffe-Walt says that disability with Medicare could be a better deal than a minimum wage job with no healthcare. In the original version of the story, she said “it’s a deal 14 million Americans have chosen for themselves.” NPR has since revised the online text to read, “it’s a deal 14 million Americans have signed up for.” This is a distinction without a difference. Whether you use the verb “choose” or “sign up,” this is a statement that everyone on SSDI is there voluntarily. It’s the stereotype that disabled people are lazy slackers happy to live on the government dime.

I have a problem with that. I was forced to apply for, and now collect, Social Security disability. This was not anything that I chose. I got sick, I could not work, I applied for disability. And I hate collecting disability benefits. I would much rather be working, even if I couldn’t go back to the career I originally trained for and pursued. Furthermore, Joffe-Walt makes it sound like it’s easy to get SSDI. I don’t know if she actually investigated application and approval rates, but SSDI is not easy to obtain. I was denied twice, and finally succeeded after an ALJ hearing. The process took three years to complete. I know people who have spent even longer in the disability application process, and many have no other source of income during the long fight.

Joffe-Walt also points out, “Once people go onto disability, they almost never go back to work.” Gee, I don’t know, maybe because they’re disabled? Social Security requires that an applicant be disabled for at least a year, and unlikely to return to work, in order to qualify. Furthermore, the rigorous application and review process, and the years-long process of denial and appeal, would weed out all those able to return to work within a year or two of the illness or injury. Those of us who end up collecting benefits likely suffer from permanent or near-permanent disability, meaning that we will never return to work no matter how much we desire to do so.

The economics of disability is a worthwhile and complex subject. But of all the issues NPR could have covered – the cost of lost productivity, the plight of disabled people who cannot get benefits, the people who continue to work while being disabled, employment discrimination, the challenges of having invisible disabilities – of all these issues, NPR chose to focus on the slacker angle. The they’re-technically-disabled-but-have-chosen-to-exploit-the-system angle. Really, NPR? It’s like covering the economic impact of Hurricane Sandy by reporting on people who pad their losses in order to collect more insurance. Yes, it happens, but the most significant issues are more complex than the tired stereotype of people trying to collect money they do not deserve.

 

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FDA Deadlines

Deadlines are coming fast and furious as we enter the home stretch before the FDA meeting on Drug Development for ME/CFS. Here are the key dates:

APRIL 8TH:

APRIL 17TH:

APRIL 18TH:

Meeting materials should be posted to the FDA website about a week before the meeting.

APRIL 25TH AND 26TH:

Watch the meeting! You have to register to see the webcast version.

AUGUST 2ND:

You have until August 2nd to submit written comments to the meeting docket.

 

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What FDA Wants

I think it’s clear what ME/CFS patients want to come out of the FDA’s Drug Development Workshop for CFS and ME. We want short, straight lines through the drug development landscape to FDA-approved treatments for our disease. But what does FDA want to come out of the meeting? To understand that, we need to understand the Patient Focused Drug Development (PFDD) Initiative.

The PFDD is part of the latest set of commitments between pharmaceutical manufacturers and FDA over the next five years (you’ll hear this described as “PDUFA Five”).  The FDA has committed to holding a minimum of 20 public meetings, and each meeting will focus on a specific disease area. Day One of the ME/CFS Drug Development Workshop is the inaugural disease specific meeting of the PFDD Initiative.

For the most part, patient perspectives inform FDA’s review of specific products. Just as we saw at the December advisory committee on Ampligen, patients offer public comment on a product and, perhaps, the need for approved treatments. FDA recognized the value in having a more broad and systematic way to collect patient points of view on their diseases, not limited to a specific product.

FDA reviewers need to evaluate a specific product within the broader context of the disease the product treats. The only way to adequately assess whether a product is safe and effective enough for people with a particular disease is to understand the impact of that disease. FDA needs to understand the severity of a condition, the most significant impacts on patients, and the range and effectiveness of current treatment options. The idea behind PFDD is to develop that contextual understanding with the direct input of the patients themselves. In addition, the patient input has to be collected in a way that will be useful to reviewers in the future. FDA’s goal for the PFDD is to explore and develop the process for collecting this patient input.

Patient perspectives on these issues will not only inform FDA’s internal review process, but can also help inform the drug development process for industry. It’s easy to see how this could happen in ME/CFS. If we asked a pharmaceutical company what symptom mattered most to ME/CFS patients, what would that company say? Probably that fatigue was the worst symptom, and that a successful treatment would reduce that feeling of fatigue. But I suspect that at the April meeting we will hear that post-exertional relapse is one of the most troubling symptoms, and a successful treatment should improve exercise testing results. Another likely symptom target is cognitive dysfunction, including impairment in focus, concentration, processing speed, and word-finding. If we are successful in communicating our input at the meeting, perhaps we will see a shift in the way treatments are developed for our disease, as well as how FDA reviews those treatments.

Through the PFDD, patients have the opportunity to educate FDA and industry about their diseases. The questions FDA has posed to the ME/CFS patient community (pdf link) are designed to elicit the input that FDA believes will be helpful. What are the most significant symptoms and how has the disease impacted your life? What treatments have you tried and what impact have the treatments had on you? This is the kind of input FDA believes it needs to create that contextual understanding of the severity of the disease and the available treatments.

After each PFDD meeting, FDA will produce a report of the meeting, which will be available to the public (including researchers and industry). The input patients provide in person at the meeting and through comments submitted to the meeting docket will form the backbone of that report. Hopefully, drug development companies will rely upon that report in targeting new compounds and designing clinical trials. Our input could help shape the drug targets and the ways trials measure the impact of the drugs on those targets.

Everyone – patients, FDA, drug developers – want to identify treatments that will successfully target the worst aspects of ME/CFS and that will move quickly through the FDA review process. Patients want treatments that are more than palliative. FDA wants to improve its assessment of product safety and efficacy by understanding the context of our disease. And drug developers want to make money by creating FDA approved products. PFDD meetings are an attempt by FDA to make progress toward those goals. The April meeting will be the first test of whether FDA has designed a process of collecting patient input that will accomplish it.

 

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AAFP Follow Up

After the American Academy of Family Practitioners published an article on CFS in October 2012, Dr. Lucinda Bateman and I submitted a Letter to the Editor. Today, that letter was published and the full version is free online. There is also a reply from Dr. Yancey, one of the authors of the original article.

My original analysis of the article covers the methodology and the overemphasis, in my opinion, of psychological factors in CFS. In his reply, Dr. Yancey cites the PACE trial as providing evidence that CBT and GET provide “moderate benefit” to people with CFS. But since the PACE trial was published in 2011, numerous authors have documented a multitude of problems with the study design and data analysis, including this one from the CFIDS Association (pdf link).

I fear that the PACE trial will continue to dog our steps until better data are published. This is why the FDA meeting is so important, and why you should participate to the fullest extent of your ability.

 

Edited to add: Links to some other analyses of the PACE trial can be found here.

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