Posts Tagged 'development initiative'

updated post

 

Please note that OccupyCFS has some clarifying info about public comment http://www.occupycfs.com/2013/03/28/clarity-on-comment/ for the FDA April 25/26th meeting as well as lots of background info about the meeting.

 

The following has been slightly revised to reflect information FDA provided as answers to some questions.

On April 25-26, 2013, the FDA is holding a workshop to discuss how best to facilitate and expedite the development of safe and effective drug therapies to treat signs and symptoms related to CFS and ME. This meeting is expected to attract not only patients and ME/CFS expert clinicians, but also other groups including pharmaceutical companies and the FDA. This is an unprecedented opportunity for us to get the attention and interest of the pharmaceutical industry and to bring a patient perspective to the development and review of drugs for ME/CFS.

 

Day 1 of the workshop will give patients the opportunity to share the symptoms and signs that they experience, their experience with treatments and how this disease affects their quality of life. This is being conducted as part of the Patient-Focused Drug Development Initiative, an FDA effort to incorporate the patient experience into the drug approval process by better understanding the patients’ perspective on the severity of their disease and the effectiveness of available treatments. ME/CFS has been chosen as one of the 20 diseases for which such a workshop will be conducted and will be the first of the 20 to go! For a disease like ME/CFS whose impact is poorly understood by those outside the community, this first day will provide the critical insights needed for discussions on the second day of the FDA workshop but just as importantly will also ensure that the drug approval process better incorporates the patient perspective going forward.

 

Day 2 of the workshop will include a scientific workshop on how to best facilitate and expedite the development of safe and effective drug therapies for the signs and symptoms related to ME/CFS. Presentations will include:

  • Lessons learned from previous studies
  • The role of drug repurposing
  • Pathways to expediting drug therapies
  • Appropriate clinical trial design in CFS and ME
  • Outcome measures to assess efficacy
  • Potential valid endpoint measurements of symptom improvement.

 

The Importance of both Symptoms and Biological Abnormalities

Obviously, it is critical that FDA and the pharmaceutical companies understand the symptoms you experience and the impact of those symptoms on your quality of life. But it is just as essential that they also understand the biological abnormalities that are associated with ME/CFS – biological abnormalities that are already being measured through lab tests and other testing. Some examples include:

  • Neurological impairment seen in symptoms like sleep dysfunction, headaches and sensory disturbances and that can be measured in lab tests like SPECT scans or MRI.
  • Cognitive dysfunction seen in symptoms like impaired memory and processing speed and that can be measured through various cognitive performance tests.
  • Immunological dysfunction seen in cytokines abnormalities, high viral titers, RNASE-L abnormality and low natural killer cells.
  • Autonomic dysfunction and orthostatic intolerance causes symptoms like dizziness, racing heart and feeling sick when stand for long periods and that can be measured by tests like tilt table tests, heart rate and blood pressure monitoring and blood volume.
  • Post exertional malaise and low anaerobic threshold that cause a relapse after mental or physical exertion and documented by cardiopulmonary exercise testing.

By understanding both the symptoms and the related biological pathologies and associated abnormalities, pharmaceutical companies will be in a better position to identify opportunities to subgroup patients and potentially repurpose existing drugs that might treat ME/CFS. This is especially critical in a disease like ME/CFS which is too often described simply in terms of “fatigue not improved by rest”, is assumed to be due to depression, deconditioning or is thought to be simply another name for chronic fatigue.

 

To ensure that the pharmaceutical companies understand this biology, a group of ME/CFS organizations and advocates submitted a joint letter to the FDA to ask for assurance that a brief overview of the biology and abnormalities of ME/CFS will be summarized right at the beginning of the meeting. The letter that was sent can be found athttps://dl.dropbox.com/u/89158245/LetterFDAWorkshopMar18.pdf

 

Take Action

So what can you do to make sure the FDA and the pharmaceutical companies understand how ME/CFS has affected you and what you have experienced with treatments? There are a number of opportunities for you to participate and to provide comments.

 

  1. Register to attend the meeting and optionally provide comments

Here’s what you need to do:

  • To attend in person, register first-come, first-serve at http://mecfsmeeting.eventbrite.comby April 8. You will be asked to provide your name and business, organization, or personal affiliation as applies (e.g., industry, government, patient). When you register, you will need to indicate that you wish to provide comments as outlined next.

 

  • There are three opportunities to present comments at the meeting:
    • You can request to be part of an initial panel discussion on the topics listed below.

If you wish to be considered to present comments part of initial panel discussions, you will need to indicate the topic that you wish to address when you register. Then, you will need to send a brief summary of your response to the topic(s) you selected to ME-CFS-Meeting@fda.hhs.gov. The deadline to send the summary of your comments is April 8.  You will be notified before the meeting if you will be on a panel.

 

    • You can participate in open moderated discussion following the panel discussions on the topics listed below.

You do not need to register to provide comments or have prepared testimony for this part of the discussion. A moderator will recognize participants to comment when they raise their hands.

 

    • You can request to provide comments on other topics as part of the open comment period at the end of the day

If you want to do this, you will need to register as above. In addition, you will need to send a brief summary of your comments for the open public comment session to ME-CFS-Meeting@fda.hhs.gov. The deadline to submit the summary of your comments is April 8.

 

  • Suggestions for those providing comments: For those who wish to provide comments, either as part of the panel or as part of the ‘open discussion’, the following information will be useful:
    • The suggested topics include:
      • Topic 1: Disease Symptoms and Daily Impacts That Matter Most to Patients
      • Topic 2: Patients’ Perspectives on Current Approaches To Treating CFS and M

The questions that the FDA is asking on each of these topics are listed below. You are also given the option to suggest a topic when you register.

    • In addition to the questions that the FDA asked, please provide comments about your lab/test abnormalities – linked to symptoms and dysfunction where possible – and indicate how those abnormalities changed as a result of treatment if known. Examples include:
      • Abnormal VO2Max as a result of PENE/PEM
      • Abnormal tilt test as indicative of orthostatic intolerance
      • High inflammatory cytokines indicative of immunological issues
      • Cognitive issues seen in impaired working memory and slow processing speed tested by cognitive performance testing
    • Other suggestions:
      • Comments should be concise and to the point. Avoid jargon. Speak about your personal experience and how this disease has affected you.
      • For some people, the term biomarker may imply that the biomarker has been “validated”. It is better to use the term abnormalities or test abnormalities to avoid this confusion.
      • Given that the time for comments may need to be shortened, it would be good for you to have both a 1-2 minute version and a 3-4 minute version.
  • Provide comments by proxy: If you cannot attend but wish to provide comments, you can have a proxy provide them for you. You will need to register to do this.

 

  1. Participate in the FDA meeting remotely
  1. Respond to two different surveys that are collecting information for the meeting.
  • Both surveys are collecting information a) disease symptoms and daily impacts that matter most to patients and b) patient perspectives on current approaches to treating ME/CFS.
  • Dr. Leonard Jason and his team and Dr. Lily Chu have created an online survey that uses checkboxes to collect information on symptoms, impact on daily life, treatments being used and the effect of treatments. For those who live outside the U.S., ignore questions about the U.S. region. The link to Dr. Jason’s and Dr. Chu’s survey is here.
  • The CFIDS Association of America (CAA) has taken the questions from the FDA workshop agenda and turned them into an online questionnaire where you can type answers into text boxes. The link to the survey is here.
  • Both surveys are open to everyone no matter where you live. Your responses will be anonymous and confidential.
  • Please try to answer both questionnaires.
  • Although the surveys may not ask for it specifically, don’t forget to also include comments as above about your lab abnormalities – linked to symptoms and disease dysfunction where possible – and indicate how those abnormalities changed as a result of treatment if known. Examples are given above in #1.

 

  1. Provide comments directly to the FDA now
  • Go here and submit comments now by clicking on the ‘Comment Now!” box in the upper right corner of the page.
  • You can also submit written comments to Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Include the docket number, which is FDA-2012-N-0962-0004”.
  • The Docket is open until August 2, 2013.
  • The FDA is encouraging patients to provide answers to the questions asked in the Federal Register. But again, don’t forget to also include information about the biological abnormalities – linked to symptoms where possible – and indicate how those abnormalities changed as a result of treatment if known. Examples are given in above.

 

Get more information

You can get additional information from the following sources:

  • The FDA maintains this webpage that lists information on its efforts regarding ME/CFS.
  • The Federal Register Notice for the April 25-26 FDA workshop can be found here.
  • The FDA has also provided a set of FAQs here about the meeting, which provide additional information.
  • A description of the Patient-Focused Drug Development Initiative can be found here.

 

 

 

Details on the questions that the FDA would like asked on the two topics.

Remember to also provide information on the biological abnormalities associated with these symptoms and the known neurological, immunological and energy production dysfunction and how treatments have affected these biological abnormalities. Examples are given above in #1.

 

Topic 1: Disease Symptoms and Daily Impacts That Matter Most to Patients

  1. What are the most significant symptoms that you experience resulting from your condition? (Examples may include prolonged exhaustion, confusion, muscle pain, heat or cold intolerance.)
  2. What are the most negative impacts on your daily life that result from your condition and its symptoms? (Examples may include difficulty with specific activities, such as sleeping through the night.)
    1. How does the condition affect your daily life on the best days and worst days?
    2. What changes have you had to make in your life because of your condition?

 

Topic 2: Patients’ Perspectives on Current Approaches To Treating CFS and ME

  1. What treatments are you currently using to help treat your condition or its symptoms? (Examples may include FDA-approved medicines, over-the- counter products, and other therapies, including non-drug therapies such as activity limitations.)
    1. What specific symptoms do your treatments address?
    2. How has your treatment regimen changed over time and why?
  2. How well does your current treatment regimen treat the most significant symptoms of your disease?
    1. Have these treatments improved your daily life (for example, improving your ability to do specific activities)? Please explain.
    2. How well have these treatments worked for you as your condition has changed over time?
    3. What are the most significant downsides of these treatments (for example, specific side effects)?

 

Comments due November 1st!

REMINDER – The Patient Focused Drug Development Initiative is an excellent opportunity to help the FDA better understand how ME/CFS affects the patients.

Send your comments in by November 1 to ensure that the FDA understands why ME/CFS should be selected as one of the 20 diseases. A sample letter has been provided in case you want to pull from it to develop your own. As you write your own letter, make points that reflect how ME/CFS meets the criteria above.

Comments should be submitted electronically at

http://www.regulations.gov/

FDA-2012-N-0967

http://www.regulations.gov/#!docketDetail;D=FDA-2012-N-0967

Written comments can be submitted to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Make sure you include the docket number (FDA-2012-N-0967).

Further information on the patient focused drug development initiative and the list of 39 diseases initially nominated can be found here: https://www.federalregister.gov/articles/2012/09/24/2012-23454/prescription-drug-user-fee-act-patient-focused-drug-development-public-meeting-and-request-for

1. Sample Letter

  • Note that the letters are limited to 2000 characters so you may need to remove some of the sample text provided to allow additional space for your personal story.
  • If you are sending in comments by regular mail, include the’To’, the ‘From’ and the ‘Docket number’. These are not necessary if sending in electronically.
  • If you are sending in electronically, select ‘Individual Consumer’ for the ‘Category’ and ‘None’ for ‘Organization’ if no other choice is appropriate

To: FDA Patient Focused Drug Development Initiative

From: <include your name here>

Docket Number: FDA-2012-N-0967

I am writing to request that chronic fatigue syndrome (also called myalgic encephalomyelitis or ME/CFS in the U.S.) be included as one of the 20 diseases in the patient focused drug development initiative.

ME/CFS is a complex, neuroimmune disease that affects one million Americans of all ages, races and income levels. According to the CDC, ME/CFS can be as debilitating as Multiple Sclerosis (MS), end-stage renal disease, chronic obstructive pulmonary disease (COPD) and similar chronic conditions. Patients can be sick for decades, with 25% house, bed or wheelchair bound. While some patients work part time or rest all weekend to keep going in their jobs, others struggle to take care of themselves, let alone take care of their families or work. One study suggests patients can die prematurely from cancer, heart disease and suicide.

And yet, tragically, in the almost thirty years since the outbreaks that brought ME/CFS to national attention, there are NO approved drugs, NO agreement on biomarkers or outcome measures and there have been almost no clinical trials for drugs to treat the disease course of ME/CFS. Patients have been abandoned with no relief from the devastation of ME/CFS.

<Include personal story here – make points that speak to one of the criteria – e.g. how this has affected you functionally, symptomatically (e.g. cognitive impact, pain), or how it has affected your daily activities, how this has affected your child with ME/CFS, the lack of therapy or your inability to access cause they are not approved for ME/CFS.

By ensuring a thorough understanding of the severity of ME/CFS from a patient perspective, especially given the lack of any treatments to change the course of the disease, the patient focused drug development initiative could make a tremendous difference in the lives of one million Americans.

2. Additional information

FDA Disease Area Selection Criteria and How ME/CFS Meets These Criteria

This table is intended to help you as you are writing your letter by providing additional information about how ME/CFS meets the FDA criteria for selection of disease areas. Try to include points in your letter that hit on these key criteria.

FDA Criteria How ME/CFS meets that criteria – examples as food for thought
Disease areas that are chronic, symptomatic, or affect functioning and activities of daily living;
  • Chronic, sick for decades, low percentage of patients improve
  • 25% bedbound or homebound, unable to work. Patients who do work may work part time and/or are underemployed. Relapsing course means little predictability. Impact of disease on patient’s life is so great that suicide risk increased
Disease areas that reflect a range of severity;
  • Wide range of severity – some patients work a 40 hour week and compensate by sleeping weekends but many patients can not work at all. The most serious patients are unable to do little more than the most basic activities of personal care
Disease areas for which aspects of the disease are not formally captured in clinical trials;
  • There is only one drug in clinical trials and its been there since 1997
  • There are a few INDs but most are focused on nutriceuticals. There have been studies into psychological treatments
Disease areas that have a severe impact on identifiable subpopulations (such as children or the elderly);
  • Severe impact on children because they are unable to attend school or graduate. Even if they get better, they have missed on significant life lessons
Disease areas that represent a broad range in terms of size of the affected population
  • Estimated that 1 million are affects – women and men, all economic levels, all ethnic groups
Disease areas for which there are currently no therapies or very few therapies, or the available therapies do not directly affect how a patient feels, functions, or survives.
  • No approved therapies, only limited symptom relief

Letters can be from patients, family members, friends….. and from any country as well!

Please help make sure that ME/CFS is one of the 20 diseases selected.

(During the FDA meeting on Oct 25th 2012, FDA officials said that it will take them a couple of months to determine which diseases will be selected.)

 

 

 

CALL TO ACTION

Summary of the Patient Focused Drug Development Initiative

What is it: As part of its commitment under the recently approved Prescription Drug User Fee Act (PDUFA V), the FDA will be conducting an initiative, called the patient-focused drug development initiative, to provide for a more systematic approach to obtain the patient’s perspective on the disease severity and the currently available treatments. The intent is to ensure a thorough understanding of the severity of the treated condition and the adequacy of the existing treatment options.

This initiative will be conducted for each of 20 different disease areas over a period of 5 years. The FDA has nominated an initial list of 39 diseases, including ME/CFS, using the following criteria:

  • Disease areas that are chronic, symptomatic, or affect functioning and activities of daily living;
  • Disease areas that reflect a range of severity;
  • Disease areas for which aspects of the disease are not formally captured in clinical trials;
  • Disease areas that have a severe impact on identifiable subpopulations (such as children or the elderly);
  • Disease areas that represent a broad range in terms of size of the affected population
  • Disease areas for which there are currently no therapies or very few therapies, or the available therapies do not directly affect how a patient feels, functions, or survives.

The next step in the process is for the FDA to gather public input between now and November 1st on which of disease areas should be selected for inclusion in this initiative. Additional disease areas may also be nominated during this time.

Note that initiative is in addition to the ME/CFS FDA stakeholder meeting that Dr. Woodcock, Director of the Center for Drug Evaluation and Research at the FDA, has already committed to.

How can you help: For ME/CFS, this is an excellent opportunity to help the FDA better understand how ME/CFS affects the patients. Your support is essential to ensure that ME/CFS is one of the 20 selected diseases.

Please send your comments in by November 1 to ensure that the FDA understands why ME/CFS should be selected as one of the 20 diseases. A sample letter has been provided in case you want to pull from it to develop your own. As you write your own letter, make points that reflect how ME/CFS meets the criteria above.

Comments should be submitted electronically at

http://www.regulations.gov/

FDA-2012-N-0967

http://www.regulations.gov/#!docketDetail;D=FDA-2012-N-0967

Written comments can be submitted to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. Make sure you include the docket number (FDA-2012-N-0967).

Further information on the patient focused drug development initiative and the list of 39 diseases initially nominated can be found here: https://www.federalregister.gov/articles/2012/09/24/2012-23454/prescription-drug-user-fee-act-patient-focused-drug-development-public-meeting-and-request-for

1. Sample Letter

  • Note that the letters are limited to 2000 characters so you may need to remove some of the sample text provided to allow additional space for your personal story.
  • If you are sending in comments by regular mail, include the’To’, the ‘From’ and the ‘Docket number’. These are not necessary if sending in electronically.
  • If you are sending in electronically, select ‘Individual Consumer’ for the ‘Category’ and ‘None’ for ‘Organization’ if no other choice is appropriate

To: FDA Patient Focused Drug Development Initiative

From: <include your name here>

Docket Number: FDA-2012-N-0967

I am writing to request that chronic fatigue syndrome (also called myalgic encephalomyelitis or ME/CFS in the U.S.) be included as one of the 20 diseases in the patient focused drug development initiative.

ME/CFS is a complex, neuroimmune disease that affects one million Americans of all ages, races and income levels. According to the CDC, ME/CFS can be as debilitating as Multiple Sclerosis (MS), end-stage renal disease, chronic obstructive pulmonary disease (COPD) and similar chronic conditions. Patients can be sick for decades, with 25% house, bed or wheelchair bound. While some patients work part time or rest all weekend to keep going in their jobs, others struggle to take care of themselves, let alone take care of their families or work. One study suggests patients can die prematurely from cancer, heart disease and suicide.

And yet, tragically, in the almost thirty years since the outbreaks that brought ME/CFS to national attention, there are NO approved drugs, NO agreement on biomarkers or outcome measures and there have been almost no clinical trials for drugs to treat the disease course of ME/CFS. Patients have been abandoned with no relief from the devastation of ME/CFS.

<Include personal story here – make points that speak to one of the criteria – e.g. how this has affected you functionally, symptomatically (e.g. cognitive impact, pain), or how it has affected your daily activities, how this has affected your child with ME/CFS, the lack of therapy or your inability to access cause they are not approved for ME/CFS.

By ensuring a thorough understanding of the severity of ME/CFS from a patient perspective, especially given the lack of any treatments to change the course of the disease, the patient focused drug development initiative could make a tremendous difference in the lives of one million Americans.

2. Additional information

FDA Disease Area Selection Criteria and How ME/CFS Meets These Criteria

This table is intended to help you as you are writing your letter by providing additional information about how ME/CFS meets the FDA criteria for selection of disease areas. Try to include points in your letter that hit on these key criteria.

FDA Criteria How ME/CFS meets that criteria – examples as food for thought
Disease areas that are chronic, symptomatic, or affect functioning and activities of daily living;
  • Chronic, sick for decades, low percentage of patients improve
  • 25% bedbound or homebound, unable to work. Patients who do work may work part time and/or are underemployed. Relapsing course means little predictability. Impact of disease on patient’s life is so great that suicide risk increased
Disease areas that reflect a range of severity;
  • Wide range of severity – some patients work a 40 hour week and compensate by sleeping weekends but many patients can not work at all. The most serious patients are unable to do little more than the most basic activities of personal care
Disease areas for which aspects of the disease are not formally captured in clinical trials;
  • There is only one drug in clinical trials and its been there since 1997
  • There are a few INDs but most are focused on nutriceuticals. There have been studies into psychological treatments
Disease areas that have a severe impact on identifiable subpopulations (such as children or the elderly);
  • Severe impact on children because they are unable to attend school or graduate. Even if they get better, they have missed on significant life lessons
Disease areas that represent a broad range in terms of size of the affected population
  • Estimated that 1 million are affects – women and men, all economic levels, all ethnic groups
Disease areas for which there are currently no therapies or very few therapies, or the available therapies do not directly affect how a patient feels, functions, or survives.
  • No approved therapies, only limited symptom relief

Letters can be from patients, family members, friends….. and from any country as well!

Please help us make sure that ME/CFS is one of the 20 diseases selected.