FDA, Comments from FDA presented at IOM Open Meeting 1/27/2014 by Sara Eggers

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Transcript of comments by FDA representative Sara Eggers to IOM Open Meeting on 1/27/2014 (transcript by Patricia Carter)

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So it’s my pleasure to reconvene this session this afternoon to…to hear from…uh…from…gosh…patients and advocates about …um…about our task and about this disorder. I want to begin today by…uh…inviting Sara Eggers from the Office of Program and Strategic Analysis of the FDA…um…to talk about the voice of the patient. And do be aware that we are timing these things. We did that this morning and earlier this afternoon too, but we will be, so thank you.


Thank you very much. I’m Sara Eggers from FDA in the Office of Strategic Programs. And we’re the office that is coordinating the Patient Focused Drug Development Initiative that FDA is running. A personal disclaimer is that I am not a clinical expert in any way. I learned a tremendous amount, myself personally, from this experience, and I want to thank everyone in advance who helped in that effort. I am here reporting on behalf of the patients who attended our meeting.

I’m going to start out by saying that FDA recognizes that CFS and ME is a serious disease, or set of diseases, for which there are no currently approved FDA therapies. I’m going to be using the term “CFS and ME” throughout my presentation, again, making no judgment on the cause or causes of the condition.

We share in the commitment to facilitate the development of safe and effective drug therapies for CFS and ME, and that’s why we did this initiative; and that’s why, I believe, we are here today is to share that perspective.

In April of 2013, we held a public meeting to hear perspectives from patients with CFS an ME and patient representatives, those who care for people with CFS and ME or advocate on behalf of those patients.

This was the first meeting conducted as part of our Patient Focused Drug Development Program, and if you will oblige me, I’m going to say “PFDD” from now on. It’s a mouthful.

This program has provided us and others, I believe, an opportunity to hear directly from patients.

The meeting that we conducted on April 25 was part of a larger workshop to explore important issues related to CFS and ME drug development.

I’m going to give a little bit of background on the PFDD initiative, and then I’ll give an overview of the specific meeting for CFS and ME. And then I’m going to give just the highlights of patient input, particularly as it relates to disease symptoms and impact on daily life. That’s my understanding, what would be likely most relevant to you here today. I do encourage you, though, to not take my word for it, to read the report that we have posted. I have a link at the back. I brought a few copies if anyone wants a hard copy, and can get to me first.

To understand why we’re doing Patient Focused Drug Development, a little bit about FDA’s benefit risk assessment: when the agency is reviewing drugs for pre-market approval in particular, there is an assessment that has to be done that takes into account a number of factors in weighing the benefits and risks.

This is a framework that we have developed, and we are beginning to implement it. I have another resource at the back that can give you more information on this, but I wanted to highlight what those key decision factors are. These five things on the…uh…left. Left of the grid here.

The analysis of the condition

The current treatment options

And then the benefit, risk, and risk management.

What the first two do is provide the regulator with the therapeutic context for weighing the benefits and risks. Because that weighing of benefits and risks really depends on how bad the condition is, how serious the condition is, what’s available for patients, and how well those current therapies are meeting patients’ needs.

With that context then, the weighing of the benefits and risks that thorough expert judgment of what those benefits and risks are and what can be done in terms of risk management to better understand or manage those risks.

With that context in mind, those weighings happen.

Patients are uniquely positioned to inform those first two rows that their therapeutic context, but the current mechanisms of all the different ways that FDA can engage patients. We typically focus on obtaining patient input in a context of a specific application under review, for example, under a committee advisory meeting.

So PFDD offers a more systematic way of providing patient input on their conditions and treatment options for their conditions in the broader context, without thinking of specific …you know, thinking of specific applications.

So we have committed to conducting 20 meetings on specific disease areas in 2013 through 2017, and we hope that these meetings can advance a systematic approach toward gathering input.

A little bit on how we choose CFS and ME:

In 2012 we started the process by nominating some disease areas. We got public input through a meeting, through a federal docket, a federal register notice, We received over 4500 comments addressing 90 different diseases—over 90 different diseases—and from that 16 were selected for our first three years of the program. These were published and, in 2015, we’ll start another process for the final two years.

We saw a diversity along the ranges of diseases, focusing on diseases that are chronic, symptomatic in the activities of daily living, have few or no therapies, or those that exist do not directly affect how a patients feels, functions or survives, has important aspects that are not formally captured in clinical trials, etc. And CFS and ME fits the bid in many of these categories.

And I’ll just say that I was delighted that we worked with CFs and ME as our first one. It was such a learning experience, and such a great lead-in to…to really serve as a…as a model. It really kind of raised the bar for the rest of these that follow.

And, as someone who facilitates many of these meetings, it makes my brow sweat a little bit more, I have to go into the next ones. So just to show you the meetings that we’ve done, we’ve done CFS and ME, HIV, lung cancer and narcolepsy.

Next, in two weeks we’re doing fibromyalgia and sickle cell disease. Fibromyalgia—we were supposed to do it in December, but it was that one day of the government closure, so that will be happening in March. And then a number of other diseases.

The meetings all follow a very similar design that is tailored to the context—to the disease context—such as the state of drug development, specific interests of the review division at FDA and taking into account the patient population, for example, why there is a diverse patient population, etc. The input is generated in numerous ways and the astute observer will notice that not all of these ways were used in the CFS and ME meeting, but we are continuing to explore more ways that we can get patient input. So at the meeting for CFS and ME, we had a patient panel for different discussion topics to provide some comments. We followed that with facilitated discussion with the patients in the audience. We tried to engage web participants, and we have a federal docket that allows people to submit more or detailed comments or comments that they weren’t able to attend.

Each meeting results in a report that captures that patient input from the multiple streams, and this input supports FDA staff as we are reviewing drugs and those benefit-risk perceptions that I just talked about, or perhaps when advising drug sponsors in their development program. We believe that the input might support drug development more broadly; for example, helping identify specific areas of unmet need in the patient population, or helping to identify potential outcome measures.

So, as I mentioned, the CFS and ME meeting on April 25 was part of that 2-day workshop. The Day 2 was a much more technical discussion with regulatory and clinical experts as well as patients on that day too. And we have a separate report on Day 2 that’s underway too. So that’s worth coming. I mean, what I’m talking about, focused on two primary topics:

What are the most significant symptoms that you you have, and How do those…what impact do they have on daily life?

And what were patients’ perspectives on current approaches to treating CFS and ME? As I mentioned, the patient advocate community was so engaged, we had about 70 patient, patient representatives at the meeting, many on the web. We received 228 docket comments, very…many of them were in such detail, so informative, and the advocates and the patient community did a lot of preparation in advance of the meeting to help make sure that the patient representatives and all of the panelists were as prepared as they could be. It was great.

So our report posted in September of 2013, and we hope it provides a narrative of the patients’ experiences and perspectives in a way that’s accessible to FDA staff. It is a snapshot in time of the story that patients collectively told us. We believe it reflects the content of the meeting and the docket submission, so it’s not meant to be reflective of the entire patient population. We know that…that it’s a very self-selected group who could come to the meeting and submit to the dockets, and we’re aware of that, but we got a snapshot in time of the patients’ perspectives in their own words as much as possible.

I’m going to get into some key themes and then I’ll get into some specific things. So the key themes is that, you know, many participants said they knew the specific time in their lives when their symptoms began, whether it was after a specific illness or just waking up one day and not feeling good. They stress that CFs and ME is much more than simply feeling fatigued. In both the meeting and the docket comments, more than 50 symptoms were reported, both cognitive and physical manifestations. Post-exertional malaise or, I’m going to call it now—a crash, because that’s the word that the patients used, is an exacerbation of symptoms, and I’m going to be separating it out from a symptom, because they did stress it—really, it’s hitting us with all symptoms, making them worse. So I’m going to talk about that a little bit later.

The meeting reiterated the devastating toll that the disease can take on patients and families. Some who call themselves the “working ill,” reported still being able to function in society, go to work, but that’s about all they could do, in many cases. While others reported that they were virtually housebound or bedbound. Many described themselves as being successful professionals or students before, but now struggle with many aspects of day to day living.

Patients use a complex regimen of drug and non-drug therapies to treat their disease or manage their symptoms, and over a hundred therapies were mentioned in the meeting or on the docket comments.

They also mentioned a range of diagnostic tools and biomarkers that their clinicians use to help treat their condition. They talked about the varying degree of effectiveness of their treatments, and how their treatments are often associated with bothersome side effects which can exacerbate other aspects of their disease, making treatment a very complex endeavor.

They are desperate for research and development of CFS and ME treatments, at a minimum to relieve their most significant symptoms, but ideally to address the underlying cause or causes of their disease.

I’m going to get into a little bit of specifics…some specific things. I’m going to start with the cognitive impairment because that’s what they started with. They wanted to talk about the most, as some mention, it was the most debilitating—that sort of set of symptoms is the most debilitating they feel.

They use general terms, the “brain fog,” the impaired executive functioning. And then they talk about specific manifestations such as disorientation, inability to process information, slowed reaction times, word-finding difficulties, etc.

They gave very concrete examples of the impact on day to day life, how they have to limit their concentration—15-20 minutea a day or every other day in some cases. They reported having difficulty interacting with people or being in social situations, and having decision making be very stressful .

Then there was, of course, fatigue. They used many words to describe fatigue, and ranging in severity. Fatigue, lack of energy, weakness, exhaustion, feeling drained or difficulty recovering their strength, feeling tired but wired, and then, in some cases, feeling that extreme and bone-crushing fatigue. They describe the specific impacts that limit their ability to walk, to climb stairs, to stand, to take care of their personal…their personal hygiene needs, and they commented that the inability to be active further exacerbates their weakness, pain and fatigue.

Many talked about sleep dysfunction, both as having an impact on its own, but how it exacerbates the other effects that they feel in their day to day life. They talked about suffering from insomnia, sleep disruptions, having difficulty staying asleep or waking up feeling unrefreshed or not rested. They describe how sleep quality can exacerbate their other symptoms, and they mention that it doesn’t matter how much sleep they get. They can get 10,12, more hours of sleep and still wake up feeling unrefreshed. Then if they sleep less than that, then the day is going to be even worse. They commented on the challenge of finding treatments that can help them sleep without exacerbating their fatigue.

Chronic pain was another symptom talked about in great detail, in varying degrees and varying types. Muscle, muscle burning, muscle spasms, joint pain, pain in the eyes, pain behind the eyes, neck pain, nerve pain, neuropathy. They talked about headaches and migraines. And then they talked about this whole body pain as well.

They expressed concern about the lack of knowledge about the fundamental causes of their pain, and a few commented that they have fibromyalgia, but they didn’t attribute all of their pain to that.

They commented again on the challenge of finding the right treatments for their pain. A number of other symptoms—the sore throat which … as one indicated, it’s not the normal type of sore throat, it’s more an inflammatory response. Other flu-like symptoms, orthostatic intolerance, other issues related to blood pressure drops, susceptibility to viral and other infections.

Sensitivity to light, sound, and temperature an other stimuli. For some, this is their most debilitating set of symptoms, and it’s all different types of stimuli that limits their ability to engage in social interactions or go outsie. GI issues and vision problems.

The crash—I’m not going to get into much detail because I see my little timer slide going up, but the crash is the incapacitating exacerbation of all symptoms that can occur with even minimal exertion and without warning.

If you read the report, you’ll get the details they talked about. We probed into this in some detail. For example, the difference between a physical crash and a cognitive crash. The physical is your body feeling like you can’t move. And the cognitive crash where your mind feels like you can’t think and get different exacerbations of that. They described the best days and worse days in great detail, and I have an excerpt from one of the surveys that was submitted to our docket where on the best days of the survey respondents, 67 percent could do light housework or could work part-time on some houseold tasks, versus 6 percent who could not, and it gets flipped during the worse days where 61% reported being bedbound on those days.

The overall impact—you can get that in the report. It’s…as one summarized…we’re operation at 25 percent of normal—that’s how one summarized it. But they talked in great detail about the impact that it has on their ability to work, on their ability to engage in social activities, to do the things they love, to … They commented on their isolation, financial difficulties, and their feeings of hopelessness and despair.

So in conclusion, this meeting really reiterate that CFS and ME is a debilitating disease that can have a devastating impact on patients’ lives. The patient input strengthens understanding of the specific symptoms that matter most to patients, the burden that this disease has on patients and their families, the range of treatments that are currently being used, how well those treatments are currently meeting their needs.

We have received positive feedback on the report and its value, both internally from FDA, from federal partners, and externally from the stakeholders themselves. Again, the key to success was the meaningful engagement and valuable input by the patients and the patient community.

And with that, I will stop. I didn’t get the one minute warning, so … Okay, I think I made it.

CLAYTON: Thank you so much for that really helpful summary…of the document which the committee already has, thank goodness.

Does anyone on the committee have any questions that they would like to ask Ms. Eggers before we…about this?

I do have one question. I mean, if you have…this is a summary, do you have the primary data that the committee can have access to as well?


The primary data is in the form of a transcript, which is available, and public docket comments.

One challenge is that not all of the public docket comments were actually put on the website. So I would have to look into seeing how…if and how we can make those accessible. That’s the raw data.




I just have a comment. Dr. Eggers gave some of the results of this survey up there regarding best and worse days. And if the committee wants that data, Dr. Jason and I conducted that survey, and we can share it with the committee.


Yeah, if I can make one…I didn’t mention it in the slides, but two of the submissions to the docket comments were surveys that were conducted by the … by patient stakeholders and submitted to us through the docket, and we treated them as a…as a…as a piece of input like the docket comments.


Thank you. I noticed that you were involved in that. So, thank you very much.


Uh, Nancy…


Another comment that came up at the FDA meeting is the PatientsLikeMe site also has a huge data set on symptoms and the…even outcomes. So there’s more than seven thousand patients, I think, right now.


Thank you.

So thank you very much. That was really very…



I’m sorry. I just have one quick question. You mentioned at the beginning of your presentation that there was a second report more technical that was going… that was in process…when will that be done and will it be publicly available?


That one, when it is done, will be publicly available, and that will be a summary report of the second day of our workshop, so it’s not a more detailed, technical report of this meeting; it’s of those more technical discussions, and that should be posted as soon as it’s available and it’ll be on…I’ve lost my slides…it’ll be on that last … in the second bullet of the relevant links on that last page of my slide deck. It can be found there.


Any other questions?


Thank you so much. We really appreciate it.

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