AUST SENATOR QUESTIONS GOVERNMENT ON LACK OF ACTION ON ME

Senator Ludlam on ME: “I am struggling to think of a cohort of people in our community that large for whom there is so little”. This is the first story in the series, more news was published in February 2016.

West Australian Senator and deputy leader of the Greens party, Scott Ludlam, asked the Australian Government what they are doing for people with myalgic encephalomyelitis. The answer is ‘not much’.

When asked about funding for ME, the government admitted it was small. “The NHMRC (National Health and Medical Research Council) has provided a little over $2 million in funding between 2000 and 2013. So you are correct of course that the amount of money over all that has come from NHMRC is quite small into this area”, said Prof Anne Kelso, CEO of the NHMRC. Australian $2 million dollars is equivalent to around US$1.43m or UK 935,800 pounds.

Senator Ludlam raised questions relating to diagnosis, cure, management plans and treatment of myalgic encephalomyelitis, which is he said may be more commonly known as ME or chronic fatigue syndrome.

“They put modern estimates at 0.4 to 2.6 per cent of the population. In an Australian context that would be between 92,000 and 598,000 people. They [Emerge Australia] also say on their website that there is no collective diagnosis, there is no cure and there is no management plan. I am struggling to think of a cohort of people in our community that large for whom there is so little. That is why I fronted up tonight, to see if you can help out.”

Senator Ludlam’s figures on the number of people affected came from Emerge Australia*.

Is ME of national significance to Australia and who decides? Prof Kelso said “areas of substantial and national significance will get special funding from time to time. Up to this point ME has not been one of those. It [national significance status] is a discussion; it can be suggestions that come from outside, maybe from the public,” Prof Kelso replied. 

If you’d like to let the NHMRC know that ME is an issue of national significance, you can write to them or write to your federal representative and ask them to tell the Health Minister and the NHMRC.

The questions were asked at the triannual Budget Estimates hearings at Parliament House, Canberra. The hearings provide an opportunity for non-government senators to ask questions of public servants about the running of government and government spending. The Senate is the upper house of Australia’s Parliament. Here is the transcript.

The Department of Health took two ‘questions on notice’: what is the type of research the NHMRC is funding and what funding is available to ME advocacy groups. Questions on notice are questions which couldn’t be immediately answered by the department, so the department has to provide the answers in writing to the Senator by mid-December.

According the NHMRC website, funding in 2000 to 2014 was given to the University of NSW for ‘Depression, anxiety and somatic distress: syndromal structure and relationship to onset of clinical disorder’ ($224,000); ‘A prospective study of the psychiatric & medical characteristics of post-infective fatigue & chronic fatigue syndrome’ ($500,000); ‘Determinants of the outcomes from infectious diseases’ ($550,000, funding allocated from 2013 through to 2017); and just over $1m for two five-year fellowships.  Monash University received $58,000 for the study ‘Respiratory and neurological health, symptoms and chronic fatigue syndrome in Australian Gulf War veterans’.

Senator Ludlam posted “14 things we learned at Senate Estimates” and at number five:

Between 0.4 and 2.6 per cent of the population suffer Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) but so little is known. Anywhere from 92,000 to 598,000 Australians suffer from this extraordinarily complex and debilitating condition. There is no collective diagnosis, there is no known cure and there is no consistent management plan. The NHMRC has provided a little over $2 million in funding between 2000 and 2013, which matches the slow pace of research worldwide. It is time to step up our efforts to fund basic research and advocacy and provide real hope for people with this ‘invisible disease’.

*Australia has no national advocacy group, however Emerge Australia represents Victoria, the Northern Territory, Tasmania & other people in Australia can join.  There is also the ME/CFS Society of Western Australia, in South Australia the ME/CFS Australia (SA) Inc, the ME/CFS Society of NSW, the ME/CFS/FM Support Association Queensland and the ACT ME/CFS Society (who provide support but not advocacy and may close in 2016).

Read more in the second story and third story in this series and follow @sashanimmo on Twitter for updates.

AUST SENATOR QUESTIONS GOVERNMENT ON LACK OF ACTION ON ME

PACE TRIAL’S ‘SISTER’ STUDY OVERLOOKED

In his Virology blog post, David Tuller examines results of ‘sister’ to the PACE trial

In 2003, when the United Kingdom (UK) Medical Research Council announced the PACE trial, they also announced the Fatigue Intervention by Nurses Evaluation (FINE) trial. Why haven’t we heard more about it?  David Tuller examined the study, the results and how the results were shared in “Why has the PACE Study’s “Sister Trial” been “Disappeared” and Forgotten”. Below is a summary of David’s fascinating findings.

Announcing the trial

The FINE trial tested two treatments: pragmatic rehabilitation and supportive listening (alongside a control group). The trial used the Oxford criteria, the same as PACE. The Medical Research Council announced it at the same time as the PACE trial and committed 1.3 million pounds. It included 296 participants.

The theory behind the FINE trial was similar to PACE’s. Physical symptoms were presumed to be the result of “deconditioning” or “dysregulation” caused by sedentary behavior, disrupted sleep cycles and stress. The sedentary behavior was presumed to be due to patients’ “unhelpful” conviction that they suffered from a progressive medical illness.
While the trial was underway

The treatment manual for pragmatic rehabilitation told participants the therapy could help them get better—even though the trial itself was designed to test the effectiveness of the therapy.

“This booklet has been written with the help of patients who have made a full recovery from Chronic Fatigue Syndrome,” stated the FINE pragmatic rehabilitation manual on its second page.

A qualitative study about the FINE research process showed the frustration of nurses and the anger of trial participants:

Their [the nurses’ ] frustration has reached the point where they sort of boiled over. There is sort of feeling that the patient should be grateful and follow your advice, and in actual fact, what happens is the patient is quite resistant and there is this thing like you know,“The bastards don’t want to get better.”

Results of the FINE trial

BMJ published the FINE results in 2010. The FINE investigators found no statistically significant benefits to either pragmatic rehabilitation or supportive listening at 70 weeks.

Patients were evaluated at 20 weeks as well, but 70 weeks was the ‘primary outcome point’.
There was a small improvement at 20 weeks, so this is what the authors chose to report on first in the paper’s abstract.

The FINE paper cited no oversight committee approval for this expanded interpretation of the trial’s primary outcome points to include the 20-week assessment, nor did it mention the protocol’s caveat about the “misleading” nature of short-term assessments in chronic health conditions.

When the first PACE results were published in The Lancet the following year, the investigators did not mention the FINE trial.

Post-publication fiddling

A month after publishing the study, the investigators analyzed it using a different scoring method. They now reported a “clinically modest, but statistically significant effect” of pragmatic rehabilitation at 70 weeks.
Tom Kindlon, a patient and advocate, responded to the FINE investigators’ decision:

 “I’m sure many pharmacological and non-pharmacological studies could look
 different if investigators decided to use a different scoring method or
scale at the end, if the results weren’t as impressive as they’d hoped,” he wrote. “But that is not normally how medicine works. So, while it is interesting that the researchers have shared this data, I think the data in the main
paper should be seen as the main data.”

Coverage
The Science Media Centre in London doesn’t appear to have publicized the 2010 release of the FINE trial, despite its interest in the topic.
Other researchers paid scant attention to the FINE trial, especially compared to the PACE study. According to Google Scholar, the 2011 PACE paper in The Lancet has been cited 355 times. In contrast, the 2010 FINE paper in BMJ has only been cited 39 times.

Read Tuller’s analysis in full.

PACE TRIAL’S ‘SISTER’ STUDY OVERLOOKED

MUSCLE DEFECT STUDIED IN UK

UK’s National Health Service collaboration between university and hospitals will hopefully trial drugs for muscle abnormality

Patients in the United Kingdom’s north east could benefit from research put into action.

Professor Julia Newton, Clinical Professor of Ageing and Medicine at Newcastle University, who also works within Newcastle upon Tyne Hospitals National Health Service (NHS) Foundation Trust, led a team who found an abnormality of a protein which could lead to the development of new drugs and treatments.

Researchers have found for the first time that patients with the condition have a defect in a molecule associated with the production of a protein known as AMP kinase (AMPK).

“Our study focused on whether there were any biochemical changes so that we can start to understand what happens in the muscle with fatigue,” Professor Newton said.  The study looked at 20 Fukuda-definition patients and 20 controls.

“What we have been able to identify is that production of AMPK is impaired in patients with CFS compared to those without. This is an important finding because there are drugs that are currently already available that we know will modify this abnormality. The next step is to carry out experiments to see whether or not we can reverse changes in AMPK with drugs that might ultimately form the basis of clinical trials…this is an exciting step towards that holy grail of trialling medicinal products,” Professor Newton said.

The new partnership brings together Newcastle Hospitals and Northumberland, Tyne and Wear NHS Foundation Trusts with Newcastle University, the newly-formed ‘Newcastle Academic Health Partners’  will deliver healthcare through collaborative scientific research, education and patient care.

“A real strength in the North East is that the University and hospital trusts work closely together, pulling on each other’s academic and clinical strengths so that we can be sure our work is of the very highest quality to help patients,” added Professor Newton.

Click here for more information on the partnership.

MUSCLE DEFECT STUDIED IN UK

GIVE YOUR PATIENT OPINION (UK, IR & AUS)

Giving voice to opinions on health services via online forum

Many people diagnosed with ME or with chronic fatigue syndrome run into difficulties with the healthcare system, while some have great care which has improved their health. What could change for the better? Who can we tell? How do we know we have been heard?

In Australia, Ireland and the United Kingdom, consumer health groups are encouraging patients to write about their experiences – positive or negative – on Patient Opinion Australia,  Patient Opinion UK and Patient Opinion Ireland.  It is a feedback platform to help healthcare providers improve, change or know about the things you are happy with. They are independent, not-for-profit, charitable organisations. Health services pay a small subscription fee to Patient Opinion and this is how the service is funded.

“Patient Opinion was founded by Paul Hodgkin a GP in Sheffield, UK who wanted to make the wisdom of patients available to the NHS. The old ways of doing this – inviting a patient to sit on a working party or carrying out a survey – did not work very well so he devised Patient Opinion as a way for thousands of patients to share their experience, and help busy health service staff to improve.”

Honest conversations can happen here and you can read other peoples’ experiences and the health services’ response. You can search by hospital or clinic, by diagnosis or by postcode.

Patient Opinion say “we exist to help improve dialogue between patient and health service providers and to improve health services” so let’s tell them what we need!

GIVE YOUR PATIENT OPINION (UK, IR & AUS)

TREADMILL TEST SHOWS WHO AMPLIGEN MAY HELP

Drug company research team identifies which CFS patients may respond best to Ampligen

Hemispherx Biopharma has identified new criteria to see which CFS patients may get significant clinical benefit from Ampligen (rintatolimod). Patients who are able to complete more than 9 minutes of exercise (modified Bruce protocol exercise tolerance test) are likely to benefit from Ampligen.

Data from a previous Phase III clinical trial of Ampligen were analysed to determine whether baseline exercise tolerance could be used to predict responses to Ampligen  vs. placebo in CFS patients. A modified treadmill test was used because of the severe physical exercise intolerance of CFS patients. The paper uses both 1988 Holmes criteria and 1994 Fukuda criteria to define CFS patients.

For patients with baseline exercise tolerance of more than 9 minutes, 33% of patients on Ampligen improved exercise tolerance duration by 25% or more (vs. 12% of patients on placebo), while 23% of Ampligen-treated patients improved by 50% or more (compared to 4.5% placebo patients).

There was also a group of patients identified who, although termed ‘non responders’, had their deterioration slowed by taking Ampligen.

What prompted this research?

This study was prompted by the Phase III clinical trial, where patients were given Ampligen twice weekly for 40 weeks compared to placebo. Some patients dramatically responded while others did not. Their hypothesis was that baseline exercise tolerance could be used to predict responses to rintatolimod. This report identifies three classes of patients. The first is defined by marked improvement in exercise tolerance and quality of life. The second class was not significantly responsive. The third class, although deteriorating on rintatolimod, do so at a reduced rate compared to controls.

Full paper: Published in the Journal of Drug Research and Development, the paper is Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME): Characteristics of Responders to Rintatolimod.

 

TREADMILL TEST SHOWS WHO AMPLIGEN MAY HELP

CHRONIC FATIGUE SYNDROME ADVISORY COMMITTEE (USA) RECOMMENDATIONS

USA’s Advisory Committee wants bigger research aimed at finding diagnostic tests, using Canadian Consensus Criteria and private-public partnerships to find drug treatments. 

In August 2015, the Chronic Fatigue Syndrome Advisory Committee (CFSAC) made recommendations to the United States government in its role advising the Secretary of Health and Human Services.  It met to summarise the recommendations of the Institute Of Medicine report Beyond ME/CFS: Redefining an Illness and the National Institutes Of Health’s Pathways to Prevention report.

The bottom line is funding. Low funding has impacted research but rapid scientific discovery is within reach. CFSAC uses strong language for a government report: “research funding for this disease has been woefully inadequate”.  Based on disease prevalence, CFSAC says equitable funding is $250 million annually. CFSAC estimates ME/CFS costs US society $17 to $24 billion annually, to put this in perspective.

CFSAC recommends the government:

  • Prioritise finding biomarkers and diagnostic tests, which will encourage drug development.
  • Encourage research which compares patients to each other, rather than healthy controls, to distinguish “important subsets (which) can be identified in terms of disease symptomatology, responses to physical and cognitive stressors, brain imaging, the microbiome, virology, immune function, and gene expression.”
  • Encourage public-private partnership to fast-track drug trials. NIH Clinical Center and others should look at drugs approved for other autoimmune, neurodegenerative, viral and other diseases, such as Valganciclovir and Rituxan.
  • Use consistent criteria. Federally-funded research should specify use of the 2003 Canadian Consensus Criteria as a research case definition for patient selection so there can be reproducible research. Also develop clinical guidelines to assess post-exertional malaise (PEM).
  • Assign the disease to the National Institute of Neurological Disorders and Stroke who has “the expertise, authority and resources needed to fund, facilitate, coordinate, and monitor the considerable work that is needed and to ensure that the disease is a part of the NIH-Wide Strategic Plan.”
  • Educate medical professionals, include in the United States Medical Licensing Examination and use consistent language across all websites and materials.
  • In the International Classification of Diseases, the USA  should follow international convention and use G93.3 for this disease until such time that robust research justifies reclassification and creation of a new code.

Here are the full recommendations.

About CFSAC 
CFSAC advises the USA’s Secretary of Health and Human Services on myalgic encephalomyelitis/chronic fatigue syndrome. The issues include  access and care for persons with ME/CFS; the science and definition of ME/CFS; and broader public health, clinical, research and educational issues related to ME/CFS.  CFSAC meets twice a year. It comprises 11 members, seven biomedical research scientists with expertise in ME/CFS; four with expertise in health care delivery, private health care services or insurers, or voluntary ME/CFS organisations.

CHRONIC FATIGUE SYNDROME ADVISORY COMMITTEE (USA) RECOMMENDATIONS

STUDY SHOWS IMMUNE DIFFERENCES IN MODERATE AND SEVERE CFS/ME

Australian university’s longitudinal study into immune changes in patients with CFS/ME may lead to diagnostic test

Griffith University researchers have looked at the immune systems of patients with moderate and severe CFS/ME (1994 Fukuda criteria) once, then again six months later. The study has just been published in the Journal of Translational Medicine.

They found severe CFS/ME patients had significant NK (Natural Killer) cell receptor differences over time, compared to controls and moderate CFS/ME, along with other alterations suggesting severe patients have an enhanced immune activation. In moderate CFS/ME patients,  iNKT* CD62L expression significantly increased over time.

The study shows it is important to look at potential immune biomarkers over time in both moderate and severe patients and it may lead to a test based on immunological markers.

This is the first study investigating immune cells over six months while also examining CFS/ME patients of varying symptom severity.  It included 18 healthy controls, 12 moderate and 12 severe CFS/ME patients. The severity of the patients’ illness was identified using a questionnaire.

Griffith University point out research has established immunological abnormalities, which you can see in their other studies at the National Centre for Neuroimmunology and Emerging Diseases.  Reduced Natural Killer (NK) cell cytotoxic activity is the most predominant and consistent outcome of immunological studies in CFS/ME.

 

*According to NatureiNKT or Invariant natural killer T cells exist in a ‘poised effector’ state, which enables them to rapidly produce cytokines following activation. Using a nearly monospecific T cell receptor, they recognize self and foreign lipid antigens presented by CD1d in a conserved manner, but their activation can catalyse a spectrum of polarized immune responses.

STUDY SHOWS IMMUNE DIFFERENCES IN MODERATE AND SEVERE CFS/ME