Posts Tagged 'government'

#Millions Missing

Millions of people are missing from everyday life because of Millions Missing from research and Millions Missing of appropriately educated healthcare professionals to care for patients

The #Millions Missing demonstration will take place on 25 May 2016 in select locations across the globe.

#MillionsMissing ME/CFS Protest Demands

  1. Increased Funding and Program Investments

Funding and program investments commensurate with the disease burden

  1. Clinical Trials

Clinical trials to secure medical treatments for ME/CFS

  1. Accurate Medical Education

Replacement of misinformation with accurate medical education and clinical guidelines

  1. A Serious Commitment

HHS leadership, oversight and a serious commitment to urgently address ME/CFS

#MEAction has posted the rationale for the demands.

NOTE –

There is an open community meeting hosted by MEAction on

Wed. May 11th, 2-3:30 pm EDT

to discuss the demands and

hear any questions or concerns you have about them.

More info and call sign-up here:

 https://my.meaction.net/events/millionsmissing-national-call

MEAction says “We are thinking of these demands as a living document. We plan that after the protests (May 25) it will evolve as we get input from the community. MEAction.net will set up a mechanism for receiving that community input. This task, and the evolution of the demands document, will happen after the protests, simply because we lack the capacity to do it while we are organizing the protests.”

MillionsMissing graphic 1

 

 

 

 

 

Talk is Cheap

For decades, stakeholders have advocated for funding commensurate with the severity of ME/CFS. The government’s response has been to hold an occasional meeting, commission a report from time to time, and little if anything has changed. More words are spoken, with clinicians and researchers saying things that have been said before. But officials haven’t followed through with the necessary funding increases or with the sustained attention required to address this severely disabling disease whose economic impact wildly exceeds the paltry dollars allotted to research.

For example, NIH hosted a State of the Knowledge Workshop in April 2011. The report from that meeting bears a great deal of resemblance to the NIH’s Pathways to Prevention (P2P) Workshop report published in June 2015. Four years have passed, but the situation remains the same.

Both reports acknowledged patients’ suffering.

2011: Individuals with ME/CFS, their families, and their caregivers have gone through untold suffering and difficulties from a disease that is poorly understood and for which there is relatively little to offer in the way of specific treatments. (p.5)

2015: Unfortunately, ME/CFS is an area where the research and health care community has frustrated its constituents, by failing to appropriately assess and treat the disease and by allowing patients to be stigmatized. (p.2)

Both reports recommended research on biomarkers and epidemiology.

2011: Continued research on biomarkers for ME/CFS, including biomarkers that are mediators of the illness, has the potential to aid in diagnosis, and treatment and prevention. (p.15)

2011: There is a lack of longitudinal, natural history, early detection, pediatric-versus-adult-onset, and animal model studies. . . . In addition, few studies look at comorbid conditions, biomarkers, or genetics.  (p.18)

2015: Research priorities should be shifted to include basic science and mechanistic work that will contribute to the development of tools and measures such as biomarker or therapeutics discovery. (p.8)

2015: Epidemiological studies of ME/CFS, including incidence and prevalence, who is at high risk, risk factors, geographical distribution, and the identification of potential health care disparities are critical.   (p.11)

Both reports recommended a network of collaborative centers.

2011: Creating coordinated and collaborative systems for sharing research was an important topic that included creating standard operating procedures for the field, within and across labs, as well as common data elements. (p.18)

2015: Create a network of collaborative centers working across institutions and disciplines, including clinical, biological, and social sciences. These centers will be charged with determining the biomarkers associated with diagnosis and prognosis, epidemiology (e.g., health care utilization), functional status and disability, patient-centered QOL outcomes, cost-effectiveness of treatment studies, the role of comorbidities in clinical and real-life settings, and providing a complete characterization of control populations, as well as those who recover from ME/CFS. (p.15)

Both reports recommended central repositories.

2011: To capture the extensive information from such studies, a centralized interactive database, using common data elements and accessible to everyone, is sorely needed to collect, aggregate, store, and analyze results.   (p.18)

2015: Biologic samples (e.g., serum and saliva, RNA, DNA, whole blood or peripheral blood mononuclear cells, and tissues) and de-identified survey data should be linked in a registry/repository to understand pathogenesis and prognosis, and facilitate biomarker discovery. (p.11)

Both reports highlighted the urgent need for consensus on case definition.

2011: Throughout the Workshop, participants identified opportunities for advancement in the current research paradigm for ME/CFS, beginning with a need to define and standardize the terminology and case definitions.   (p.6)

2015: Define disease parameters. Assemble a team of stakeholders (e.g., patients, clinicians, researchers, federal agencies) to reach consensus on the definition and parameters of ME/CFS.   (p.9)

2015: Thus for progress to occur, we recommend (1) that the Oxford definition be retired, (2) that the ME/CFS community agree on a single case definition (even if it is not perfect), and (3) that patients, clinicians, and researchers agree on a definition for meaningful recovery.   (p.16)

Both reports highlighted the need for collaboration and new scientists.

2011: The study of ME/CFS can benefit from an interdisciplinary collaborative approach using well-connected clinical and research networks. . . . Moreover, additional highly qualified investigators must be attracted to study ME/CFS.   (p.18)

2015: [T]here is a need for partnerships across institutions to advance the research and develop new scientists.   (p.14)

Both reports noted the need for educated clinicians.

2011: However, the biggest barrier to treating patients, according to Workshop participants, is lack of informed clinicians… (2011, p.6)

2015: Thus, a properly trained workforce is critical…   (p.14)

***************

If I just listed the quotes without telling you which report they came from, I bet you would not be able to tell which were from 2011 and which were from 2015. That the same points are repeated without substantive differences illustrates how little has changed, other than the year the report was issued.

Perhaps time moves at a different pace for those in charge of allocation of funds and they don’t feel the urgency we feel. However, for more than thirty years patients have grown up, lived and died, all the while being subjected to disdain and neglect. Failed policies mean there are no treatments, and this horrid disease is so disabling that patients usually live isolated, impoverished lives.

We NEED better and we DESERVE far better than occasional federal lip-service and occasional meetings.

  • We (patients/caregivers, healthcare professionals, policy makers, HHS) need to be very clear about the disease being addressed.
  • We need a total overhaul of federal policy regarding this disease with stakeholders as active participants.
  • We need a sustained and meaningful increase in biomedical research funding and we need it now!
  • We need an awareness campaign like the one outlined here.
  • We need to be meaningfully involved at every step of the way in all of this.
  • We want and deserve to have our productive lives back! NOW!
  • We need to work together in a sustained manner to push for these changes.

And HHS ABSOLUTELY must do its part. The IOM report has been out for months and the P2P report is out now, yet there is no indication from HHS as to what they are going to do with these reports. So HHS – tell us – what you are going to do and when you are going to do it?

Talk is cheap. It’s relatively easy and cheap to hold a meeting and write a report. Investing the requisite resources in research and building the infrastructure needed to sustain progress is hard work. It’s expensive. But this is what is needed. Not more meetings. Not more spin.

Talk is cheap. It’s time to show ME the money.

They Know What They’re Doing (Not)

by Mary Dimmock (please re-post freely with attribution to Mary Dimmock)

Last week, Jennie Spotila and Erica Verillo posted summaries of just some of the issues with AHRQ’s Draft Systematic Evidence Review, conducted for P2P.

Jennie and Erica highlighted serious and sometimes insurmountable flaws with this Review, including:

  • The failure to be clear and specific about what disease was being studied.
  • The acceptance of 8 disparate ME or CFS definitions as equivalent in spite of dramatic differences in inclusion and exclusion criteria.
  • The bad science reflected in citing Oxford’s flaws and then using Oxford studies anyway.
  • The well-known problems with the PACE trial.
  • The flawed process that used non-experts on such a controversial and conflicted area.
  • Flawed search methods that focused on fatigue.
  • Outright errors in some of the basic information in the report and apparent inconsistencies in how inclusion criteria were applied.
  • Poorly designed and imprecise review questions.
  • Misinterpretation of cited literature.

In this post, I will describe several additional key problems with the AHRQ Evidence Review.

Keep in mind that comments must be submitted by October 20, 2014. Directions for doing so are at the end of this post.

We Don’t Need No Stinking Diagnostic Gold Standard

Best practices for diagnostic method reviews state that a diagnostic gold standard is required as the benchmark. But there is no agreed upon diagnostic gold standard for this disease, and the Review acknowledges this. So what did the Evidence Review do? The Review allowed any of 8 disparate CFS or ME definitions to be used as the gold standard and then evaluated diagnostic methods against and across the 8 definitions. But when a definition does not accurately reflect the disease being studied, that definition cannot be used as the standard. And when the 8 disparate definitions do not describe the same disease, you cannot draw conclusions about diagnostic methods across them.

What makes this worse is that the reviewers recognized the importance of PEM but failed to consider the implications of Fukuda’s and Oxford’s failure to require it. The reviewers also excluded, ignored or downplayed substantial evidence demonstrating that some of these definitions could not be applied consistently, as CDC’s Dr. Reeves demonstrated about Fukuda.

Beyond this, some diagnostic studies were excluded because they did not use the “right” statistics or because the reviewer judged the studies to be “etiological” studies, not diagnostic methods studies. Was NK-Cell function eliminated because it was an etiological study? Was Dr. Snell’s study on the discriminative value of CPET excluded because it used the wrong statistics? And all studies before 1988 were excluded. These inclusion/exclusion choices shaped what evidence was considered and what conclusions were drawn.

Erica pointed out that the Review misinterpreted some of the papers expressing harms associated with a diagnosis. The Review failed to acknowledge the relief and value of finally getting a diagnosis, particularly from a supportive doctor. The harm is not from receiving the diagnostic label, but rather from the subsequent reactions of most healthcare providers. At the same time, the Review did not consider other harms like Dr. Newton’s study of patients with other diseases being diagnosed with “CFS” or another study finding some MS patients were first misdiagnosed with CFS. The Review also failed to acknowledge the harm that patients face if they are given harmful treatments out of a belief that CFS is really a psychological or behavioral problem.

The Review is rife with problems: Failing to ask whether all definitions represent the same disease. Using any definition as the diagnostic gold standard against which to assess any diagnostic method. Excluding some of the most important ME studies. It is no surprise, then, that the Review concluded that no definition had proven superior and that there are no accepted diagnostic methods.

But remarkably, reviewers felt that there was sufficient evidence to state that those patients who meet CCC and ME-ICC criteria were not a separate group but rather a subgroup with more severe symptoms and functional limitations. By starting with the assumption that all 8 definitions encompass the same disease, this characterization of CCC and ICC patients was a foregone conclusion.

But Don’t Worry, These Treatment Trials Look Fine

You would think that at this point in the process, someone would stand up and ask about the scientific validity of comparing treatments across these definitions. After all, the Review acknowledged that Oxford can include patients with other causes of the symptom of chronic fatigue. But no, the Evidence Review continued on to compare treatments across definitions regardless of the patient population selected. Would we ever evaluate treatments for cancer patients by first throwing in studies with fatigued patients? The assessment of treatments was flawed from the start.

But the problems were then compounded by how the Review was conducted. The Review focused on subjective measures like general function, quality of life and fatigue, not objective measures like physical performance or activity levels. In addition, the Review explicitly decided to focus on changes in the symptom of fatigue, not PEM, pain or any other symptom. Quality issues with individual studies were either not considered or ignored. Counseling and CBT studies were all lumped into one treatment group, without consideration of the dramatic difference in therapeutic intent of the two. Some important studies like Rituxan were not considered because the treatment duration was considered too short, regardless of whether it was therapeutically appropriate.

And finally, the Review never questioned whether the disease theories underlying these treatments were applicable across all definitions. Is it really reasonable to expect that a disease that responds to Rituxan or Ampligen is going to also respond to therapies that reverse the patient’s “false illness beliefs” and deconditioning? Of course not.

If their own conclusions on the diagnostic methods and the problems with the Oxford definition were not enough to make them stop, the vast differences in disease theories and therapeutic mechanism of action should have made the reviewers step back and raise red flags.

At the Root of It All

This Review brings into sharp relief the widespread confusion on the nature of ME and the inappropriateness of having non-experts attempt to unravel a controversial and conflicting evidence base about which they know nothing.

But just as importantly, this Review speaks volumes about the paltry funding and institutional neglect of ME reflected in the fact that the study could find only 28 diagnostic studies and 9 medication studies to consider from the last 26 years. This Review speaks volumes about the institutional mishandling that fostered the proliferation of disparate and sometimes overly broad definitions, all branded with the same “CFS” label. The Review speaks volumes about the institutional bias that resulted in the biggest, most expensive and greatest number of treatment trials being those that studied behavioral and psychological pathology for a disease long proven to be the result of organic pathology.

This institutional neglect, mishandling and bias have brought us to where we are today. That the Evidence Review failed to recognize and acknowledge those issues is stunning.

Shout Out Your Protest!

This Evidence Review is due to be published in final format before the P2P workshop and it will affect our lives for years to come. Make your concerns known now.

  1. Submit public comments on the Evidence Review to the AHRQ website by October 20.
  2. Contact HHS and Congressional leaders with your concerns about the Evidence Review, the P2P Workshop and HHS’ overall handling of this disease. Erica Verillo’s recent post provides ideas and links for how to do this.

The following information provides additional background to prepare your comments:

However you choose to protest, make your concerns known!

Bits and pieces

Many thanks to all those who have written to Tell Dr. Collins to Stop P2P

If you have not already done so, fax or email Dr. Francis Collins today and request that he cancel the P2P Workshop.

Details here http://www.occupycfs.com/2014/06/02/tell-dr-collins-to-stop-p2p/

Additional information about P2P:

http://www.occupycfs.com/?s=P2P

A parallel action to contact Congressional officials about P2P will be released shortly.

WEGO Health Twitter chat about advocating for oneself while living with a stigmatized chronic disease. Hosted by Jennie Spotila

Date: Tuesday, June 10th

Time 3-4pm (Eastern time).

Details http://www.occupycfs.com/2014/06/08/twitter-chat/

The next meeting of the Chronic Fatigue Syndrome Advisory Committee (CFSAC)

Monday afternoon (12-5pm Eastern time) June 16th and Tuesday June17th (9am-5pm Eastern time).

The meeting will be live-video streamed at http://www.hhs.gov/live . (Registration to attend in person ends June 12th. Details https://www.federalregister.gov/articles/2014/05/29/2014-12371/meeting-of-the-chronic-fatigue-syndrome-advisory-committee )

Info on Accessing the CFSAC webinar Dec 10 and 11 2013

There has been a great deal of confusion about the CFSAC webinar meeting and how to access it.

(Contrary to what was previously said by HHS) Registration IS NOT required for viewing it.

HHS’ most recent information on viewing the webinar is:

Webinar Information

The Chronic Fatigue Syndrome Advisory Committee (CFSAC) Webinar will be a “virtual meeting” using Adobe Connect Pro, a web conferencing product that allows users to conduct live meetings and presentations over the internet. In order to view and listen to the proceedings during the CFSAC webinar participants will need to access the webinar using the information below:

Webinar Access:
Adobe Connect URL: http://hhs.adobeconnect.com/owhcfsac/

Access to the Audio Portion of the Webinar:
Conference Call Number: 877-918-6627 | Passcode: 4429527

Using Adobe Connect requires that you have an Internet connection, a Web browser, the latest version of the Adobe Connect Add-in to attend a Web conference. Adobe Connect Pro is supported by many operating systems, including Windows, Macintosh, Linux, and Solaris as well as the most widely used browsers, including Internet Explorer, Firefox, and Safari.

It is recommended that you test your computer prior to attending a meeting. You can do this by going to http://admin.adobeconnect.com/common/help/en/support/meeting_test.htm.

This diagnostic test will ensure your computer and network connections are properly configured to provide you with the best possible Adobe Connect meeting experience. The diagnostic test checks for the following:

  1. Clear connection to Adobe Connect

  2. Bandwidth availability

  3. Latest Adobe Connect Add-in

If the diagnostic check finds that you do not have the latest Adobe Connect Add-in installed on your computer (as seen below) please click on the “Install Add-in” link on your computer as circled in the picture below. Please note that you will not be able to view the webinar if the latest Adobe Connect Add-in is not installed.

Adobe Connect

Once the Add-in is installed, click on the link http://hhs.adobeconnect.com/owhcfsac/ to join the webinar. You should see the screen below.

Adobe Connect Login

Click the button to “Enter as a Guest” and type your name (if you choose to be identified) and click the “Enter Room” button. You will be directed to the CFSAC webinar.

If you have technical difficulty during the webinar, please contact Seamon Corporation at 301-658-3442 or CFSACDec2013@seamoncorporation.com.

The webinar will be archived on the HHS CFSAC Web site at http://www.hhs.gov/advocomcfs.

Additional “How to use” resources for Adobe Connect

If you have never used Adobe Connect, please click on the following link to get a quick overview: http://www.adobe.com/go/connectpro_overview.

The Visual Quick Start Guide provides basic information for participating in an Adobe Connect Webinar. Please click the following link to view the Visual Quick Start Guide: http://www.adobe.com/content/dam/Adobe/en/products/adobeconnect/pdfs/VQS_Guide_for_Participants.pdf

http://blsmeetings.net/CFSACdec2013/webinarinformation.cfm

Mary Dimmock has questions —–

(Mary has given permission for this to be shared widely and reposted)

Mary Dimmock asked IOM and HHS some questions about the IOM study. Find out if she got answers…

HHS recently issued an FAQ about the IOM contract. As Jennie Spotila, Erica Verillo, Lois Ventura and Jeannette Burmeister pointed out, the FAQ falls far short of providing useful answers, is misleading and leaves critical questions unanswered.

Like the fundamental question: “What disease is HHS developing definitions for – ME or the diverse conditions that meet the overly broad “CFS” criteria?

I recently asked that question of both IOM’s Kate Meck and HHS’ Dr. Nancy Lee. From their answers, which I summarized below, the only possible conclusion is that the IOM study is intended to establish diagnostic criteria for the diverse conditions that meet the overly broad “CFS” criteria and that ME will be treated as a subgroup.

All of us, patients, advocates and experts alike, must reject this as completely unacceptable. We must call on HHS to acknowledge that ME is not part of the overly broad CFS. We must continue to call on HHS to adopt the Canadian Consensus Criteria.

We all know the problem. ME, the neurological disease characterized by post-exertional malaise, cognitive issues and immunological dysfunction has been buried inside of “CFS”, a diverse collection of medically unexplained fatiguing conditions. Numerous authors, especially Dr. Jason of DePaul, have reported extensively on the serious research and clinical problems caused by these overly broad CFS definitions, definitions that lump biologically unrelated conditions together. Dr. Bruce Carruthers summed it up simply, “There is a poignant need to untangle the web of confusion caused by mixing diverse and often overly inclusive patient populations in one heterogeneous, multi-rubric pot called ‘chronic fatigue syndrome.”

Having rejected the Canadian Consensus Criteria as unacceptable, HHS is conducting three separate initiatives to develop its own criteria. But what does HHS intend to do about the “web of confusion” that ha been created by “CFS”? What disease will these new criteria describe?

The ME/CFS IOM Statement of Work is ambiguous on this point as it uses the same jumbled, non-specific disease labels that have gotten us into this mess to begin with. The SOW states:

the Committee will consider the various existing definitions and recommend consensus clinical diagnostic criteria for this disorder [ME/CFS]. . .
The Committee will also distinguish between disease subgroups . . .
For the purposes of this document, ME/CFS shall be used to refer to Myalgic Encephalomyelitis (ME), Chronic Fatigue Syndrome (CFS), Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS), Neuroendocrine Immune Disorder, and other terminologies in use for this illness.

I asked both Kate Meck at the IOM and Dr. Lee, the designated federal official for the CFS Advisory Committee (CFSAC) to clarify what “scope of disease” had been specified in the IOM contract. Has the IOM been contracted to develop clinical criteria specifically for ME? Or has IOM been contracted to develop clinical criteria for the range of unrelated fatiguing conditions that meet the “CFS” criteria? I asked Dr. Maier of NIH and Dr. Beth Collins-Sharp of AHRQ a similar question on the NIH Evidence Based Methodology Workshop process and am waiting on a promised response.

Here’s a summary of the responses I received from Dr. Lee of HHS and Kate Meck of the IOM:

Both Dr. Lee and Ms. Meck said that the scope of disease to be covered by the new clinical criteria has not been specifically defined at this point and that this will need to be defined as the process goes forward.

Dr. Lee indicated that the panel itself would need to resolve this issue and that possible outcomes could be ME as a subgroup of the broader CFS, ME as part of a spectrum that includes these other conditions, or ME as a separately defined disease. Ms. Meck indicated that HHS would be asked to clarify what scope of disease was intended at the first meeting. I raised the concern with Ms. Meck that the scope of disease directly affects panel selection and evidence base selection but she felt that the panel and process would be able to adjust as needed.

In a follow-up email, Dr. Lee confirmed the above statements but also reiterated an earlier point she had made that the IOM task list specifies that the “committee will also distinguish between disease subgroups”. She also said that in order for the target audience – defined as the primary care physicians – to effectively use the resultant guidance, “it is important to start a bit broad and then have criteria which distinguishes between subgroups.”

These answers are profoundly disturbing.

First, the statement that the scope of disease has not yet been defined is frankly hard to believe. This is a million dollar contract and panel selection is due to be announced soon. How can such a critical issue as the scope of disease to be covered by the new criteria be undecided at this point? If it really is undecided, who will decide and how? What criteria have been used to select the panel? And will that panel still be the appropriate one once a decision is reached on what disease or diseases the new criteria will cover?

But the statements about subgroups and spectrum of illnesses are much more disturbing.

Yes, ME is a complex disease that needs to be broken down into legitimate subgroups in order to better understand the disease and the treatment options. Perhaps those subgroups are based on whether onset is sudden or not, the level of severity of the disease or the nature of the immune profile and viral load. But let’s be realistic. What is the likelihood that the panel selected for the IOM study is going to be able to identify proper subgroups of ME itself when our experts are still working through that? Or when the evidence base lacks the ME specific studies – studies done with proper ME definitions – that would be needed to substantiate ME subgroups?

At the same time, we have an agency with a long-term commitment to studying medically unexplained chronic fatigue as the single clinical entity, “CFS”. We have an agency that has taken the position that Oxford, Fukuda and the Canadian criteria all describe the same set of patients for whom one set of clinical guidance is appropriate. We have an agency that questions the scientific evidence surrounding even post-exertional malaise and its measurement while simultaneously rejecting the Canadian Consensus Criteria because it does “not account for scientific evidence developed since 2003.” We have the CDC’s Dr. Unger, rhetorically asking at the May 2013 CFSAC “If a patient doesn’t have [PEM], wouldn’t you still manage them as a “CFS” patient?” And we have the IOM adopting the same overly broad view of CFS as HHS in recent IOM publications on Gulf War Illness.

Now we have Dr. Lee stating that the target audience of the new criteria is the primary care physicians and that they need criteria that start broader and then distinguish between subgroups. What about the patients who desperately need criteria that accurately reflect their disease?

What are we to conclude from all this? HHS has not committed to criteria specific to ME. HHS is not talking about the proper subgroups of ME that we all envision. HHS intends the IOM study to define criteria for the broader set of CFS conditions, with ME characterized as a subgroup. Or worse, ME becomes a subgroup of the even broader chronic multisymptom illness (CMI).

Either way, this will be a disaster that will degrade ME research and worsen the abysmal clinical care and stigma that ME patients receive today. This is the nightmare scenario that we all fear.

If HHS truly wants to reverse the chaos and the grievous harm to patients caused by years of sloppy definitions, it will first and foremost declare that ME, the disease described by the Canadian Consensus Criteria, is not the same disease as the overly broad “CFS” and should not be considered as either a subgroup of CFS or part of a spectrum of CFS diseases.

And if HHS cares not only about primary care physicians but also about the ME patients that they treat, it will acknowledge the harm done to patients by its clinical guidelines as reported at a recent Mount Sinai conference. CDC will immediately highlight PEM as a hallmark symptom of ME, will provide “black box warnings” about the adverse effects of exercise on ME patients and will point clinicians to the Canadian Consensus Criteria and the IACFS/ME primer.

Beyond that, HHS needs to immediately require that the Canadian Consensus Criteria be used in every study funded by NIH, even if it is used in parallel with Fukuda as an interim step.

Patients, advocates and experts alike must demand and accept no less, especially in the context of the IOM study and the NIH Evidence Based Methodology process.

 

 

 

More experts have signed the letter!

Remember back on the 23rd of September when the letter signed by 35 ME(cfs) experts was released?

(https://speakupaboutme.wordpress.com/2013/09/24/our-mecfs-experts-have-spoken-on-the-case-definition/)

 

Additional experts have signed the letter bringing the total (as of 26 October 2013) to 50!

Check it out!

https://dl.dropboxusercontent.com/u/89158245/Case%20Definition%20Letter%20final%2010-25-13.pdf