Wednesday, 6 December 2017

ME/CFS Collaborative Research Center at Stanford University, funded by OMF

https://www.omf.ngo/collaborative-research-center-stanford/

The ME/CFS Collaborative Research Center at Stanford will be led by Dr. Ron Davis, Professor of Biochemistry and Genetics at Stanford University, and Director of our Scientific Advisory Board. Dr. Davis has assembled a truly world-class team of researchers, many of whom have never before focused their expertise on ME/CFS, and has planned several innovative projects that will help us to understand the molecular basis of ME/CFS, develop better diagnostics, and discover new treatments. Given the number and quality of investigators that this grant would bring into the field, and the likelihood of groundbreaking discoveries coming from this research, OMF has decided to fund this highly promising proposal. Although the National Institutes of Health decided against funding this plan as one of their Collaborative Research Centers, we believe this work is too important and too promising not to pursue. We are not willing to miss the opportunity to actively involve a scientific team of this caliber in the field of ME/CFS research. OMF will, therefore, be supporting the first year of this groundbreaking research with $1.2 million, and we are actively and enthusiastically raising the funds needed to support the remaining 4+ years it will take to complete it.

Scientific Plan

The Center will pursue three distinct projects, all related to understanding and treating ME/CFS by developing and using cutting-edge technologies. This work will build on previous projects that OMF has supported. For more information about these projects from the scientists involved, please see the YouTube videos from our recent Community Symposium on the Molecular Basis of ME/CFS.

1. T cells and the molecular immunology of ME/CFS

Sequencing single T cells and discovering their targets

Many studies have shown that the immune system is affected in ME/CFS patients, e.g., low activity of NK cells, altered levels of cytokines (signaling molecules of the immune system), and the likelihood of a microbial infection preceding the illness. Now, scientists on this team have implicated T cells – the immune cells responsible for identifying and killing infected cells – in ME/CFS. Specifically, their discovery of T cell clonal expansion indicates that patient T cells are reacting to a foreign invasion (e.g., virus) and/or to the ‘self’ (autoimmunity). HLA genes play a part in this reaction, and personal variations in these genes may also be playing a role in the risk of developing the disease. Discovering what is triggering this T cell clonal expansion will help to determine immunological causes of ME/CFS, may explain the elevated cytokine levels, and could lead to new treatments.

The Collaborative Research Center at Stanford will investigate the immunological basis of ME/CFS using several approaches. Dr. Mark Davis’ team will investigate the clonal expansion of T cells in ME/CFS, including what they might be targeting – viruses, bacteria, or self (autoimmune). Dr. Ron Davis’ team has invented a highly accurate, cost-effective method for HLA gene sequencing and a very sensitive method for detecting viral DNA as a sign of viral infections, which he will use in this project. Dr. Lars Steinmetz’ team has developed effective methods for sequencing RNA from single T cells, which they will use to understand how T cell behavior may be different in ME/CFS. Overall, these methods will help to determine if ME/CFS is an autoimmune disease, and what immune factors may be triggering ME/CFS or sustaining it as a chronic disease. By helping to understand the immunology of ME/CFS, it may be possible to identify treatments that modulate the immune response.

2. Extended big data study in families

Genome sequencing, gene expression, metabolomics, cytokines, clinical features, and more

OMF has funded a big data study of 20 severely ill ME/CFS patients, encompassing a huge variety of molecular and clinical tests, the largest of its kind in this disease. Among many things, this study is helping to look for genetic factors and potential molecular biomarkers, and is allowing us to generate many hypotheses. The analysis of this dataset, led by Dr. Wenzhong Xiao, has yielded many interesting observations, but it is clear that more patients must be profiled in this way to validate and extend these observations to a less severe population. The Collaborative Research Center at Stanford will expand this big data study to patients of varying severities and their families.

It has been clear for some time that there are families with multiple members affected. This might be caused by a genetic predisposition to the disease. Studying these families is likely to yield a better understanding of the factors that make someone susceptible to ME/CFS. Fereshteh Jahanbani, PhD, a Research Associate with Mike Snyder, PhD, hypothesizes that using unaffected members of these families as controls will reduce the variance in the data between controls and affected, because of the similarities in their genetics, environment, and diet. The team anticipates that this study will help define meaningful subgroups of patients, biomarkers that could be useful in diagnosis and monitoring of disease progression, and molecular defects that could be targeted with new treatments.

3. Developing blood-based diagnostic and drug screening technology

Enabling fast, inexpensive diagnosis of ME/CFS and discovery of new treatments

One of the greatest obstacles in ME/CFS research and patient care is the lack of a biological diagnostic. Dr. Davis’ engineering team has promising preliminary technologies that can distinguish ME/CFS blood samples from healthy samples, and is currently refining these technologies and investigating what the results tell us about ME/CFS biology. The technologies include the nanoneedle biosensor, developed by Rahim Esfandyarpour, PhD, the magnetic levitation platform developed by Gozde Durmus, PhD, and more. The Collaborative Center will continue this work to engineer a blood-based diagnostic device that would also be useful as a reporter for drug screening. Dr. Davis’ team has already tested chemicals in two of our platforms, some of which have made the patient samples behave more like healthy samples. To validate these findings and test large numbers of samples and candidate drugs, they will further develop and optimize the technology. Eventually, the developed technology will be shared across the ME/CFS research community to accelerate its evaluation and adoption as a clinical diagnostic assay. The Stanford Genome Technology Center has developed a number of diagnostic assays that have been commercially exported and are now in clinical use. Dr. Davis’ team has experience in the complex process of developing and implementing an assay that becomes approved for clinical use, in the USA, as well as in Europe and other countries.

Scientific Team

To carry out this ambitious work, Dr. Davis has assembled a team of extraordinary scientists with expertise in a variety of areas directly relevant to ME/CFS research. Most of these scientists are new to ME/CFS, bringing with them extensive knowledge and perspective from other fields and diseases.

ME/CFS Collaborative Research Center at Stanford Team:

Ron Davis, PhD, Professor of Biochemistry and Genetics, Stanford University School of Medicine; Director, Stanford Genome Technology Center; Director, Chronic Fatigue Syndrome Collaborative Research Center at Stanford University; Director, Open Medicine Foundation ME/CFS Scientific Advisory Board.

Mark M. Davis, PhD, Director, Stanford Institute for Immunology, Transplantation and Infection (ITI); Professor of Microbiology and Immunology; Howard Hughes Medical Institute Investigator.

Mike Snyder, PhD, Chair, Stanford Department of Genetics; Director, Stanford Center for Genomics and Personalized Medicine

Wenzhong Xiao, PhD, Director, Immuno‐Metabolic Computational Center, Massachusetts General Hospital, Harvard Medical School.

Craig Heller, PhD, Professor of Biology, Stanford University, exercise physiologist.

Robert Phair, PhD, Chief Science Officer, Integrative Bioinformatics, Inc..

Lars Steinmetz, PhD, Co-Director, Stanford Genome Technology Center; Professor of Genetics, Stanford University; Senior Scientist, Genome Biology Unit, European Molecular Biology Laboratory.

Raeka Aiyar, PhD, Director of Communications and Development, Stanford Genome Technology Center.

Laurel Crosby, PhD, Engineering Research Associate, Stanford Genome Technology Center – multi-system integration

Rahim Esfandyarpour, PhD, Engineering Research Associate, Stanford Genome Technology Center – electrical engineering, device fabrication

Fereshteh Jahaniani, PhD, Research Associate, Stanford Center for Genomics and Personalized Medicine – multi-omics

Mohsen Nemat-Gorgani, PhD, Life Science Research Scientist, Stanford Genome Technology Center – protein biochemistry, enzymology

Peidong Shen, PhD, Research Associate, Stanford Genome Technology Center – biochemistry, cell-free DNA detection methods

Gozde Durmus, PhD, Postdoctoral Fellow, Stanford Genome Technology Center – magnetic levitation platform, bioengineering

Julie Wilhelmy, Life Science Research Professional, Stanford Genome Technology Center – experimental genomics, immunology

Robert Naviaux, MD, PhD, Professor of Medicine, Pediatrics, and Pathology, University of California, San Diego; Co-Director of Mitochondrial and Metabolic Disease Center

William Robinson, MD, Associate Professor of Medicine (Immunology and Rheumatology), Stanford University

Curt Scharfe, MD, Associate Professor of Genetics, Yale University

Lucinda Bateman, MD, founder and Medical Director of the Bateman-Horne Center for ME/CFS and Fibromyalgia

David Kaufman, MD, ME/CFS Physician

Working Group

We are fortunate that many members of the scientific, medical, and biotechnology communities have offered their expertise and resources to this Center.

Paul Berg, PhD, Professor of Biochemistry, Emeritus, Stanford University; Nobel Laureate

Mario Capecchi, PhD, Professor of Human Genetics and Biology, University of Utah; Nobel Laureate

Baldomero Olivera, PhD, Professor of Biology, University of Utah

Alain Moreau, PhD, Professor of Biochemistry and Molecular Medicine, University of Montreal

Øystein Fluge, MD, Department of Oncology and Medical Physics, University of Bergen, Haukeland University Hospital, Bergen, Norway

Olav Mella, MD, Department of Oncology and Medical Physics, University of Bergen, Haukeland University Hospital, Bergen, Norway

Jonas Bergquist, MD, PhD, Professor of Analytical Chemistry and Neurochemistry, Uppsala University, Sweden

Jonas Blomberg, MD, PhD, Professor of Clinical Virology, Emeritus, Uppsala University, Sweden

Maureen Hanson, PhD, Professor of Molecular Biology and Genetics, Cornell University

Chris Armstrong, PhD, Department of Biochemistry and Molecular Biology; Bio21 Molecular Science & Biotechnology Institute researcher at the University of Melbourne, Melbourne, Australia

Neil McGregor, BDS, MDSc, PhD, senior researcher, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia; Adjunct Professor, Victoria University, Melbourne, Australia

Ronald Tompkins, MD, ScD, Professor of Surgery, Harvard Medical School; Founding Director of Center for Surgery, Science & Bioengineering at Massachusetts General Hospital

Catherine Blish, MD, PhD, Assistant Professor of Medicine and of Immunology, Stanford University

Christopher Garcia, PhD, Professor of Molecular and Cellular Physiology, Stanford University

Roger Howe, PhD, Professor of Engineering, Stanford University; Director, Stanford Nanofabrication Facility

Tom Soh, PhD, Professor of Electrical Engineering, Radiology, and by courtesy, Chemical Engineering, Stanford University

Robert Tibshirani, PhD, Professor of Biomedical Data Sciences and Statistics, Stanford University

Alan Light, PhD, Professor of Anesthesiology, University of Utah

Emmanuel Mignot, MD, PhD, Professor of Sleep Medicine and of Psychiatry and Behavioral Sciences, Stanford University; Director of Stanford Center for Sleep Sciences and Medicine

Gerald Shadel, PhD, Professor of Pathology and Genetics, Yale University; Director of Yale Center for Research on Aging

Jarred Younger, PhD, Associate Professor of Anesthesiology and Rheumatology and of Psychology, University of Alabama at Birmingham; Director, Neuroinflammation, Pain, and Fatigue Laboratory

John Ryals, PhD, President and CEO, Metabolon

Chunlin Wang, PhD, Chief Technology Officer, iRepertoire, Inc.

Michael Mindrinos, PhD, President of Sirona Genomics, an Immucor company

David Bell, MD, ME/CFS Physician

Kevin Tracey, MD, Professor of Neurosurgery and Molecular Medicine, Hofstra Northwell School of Medicine

Jennifer Frankovich, MD, Clinical Associate Professor of Pediatric Rheumatology, Stanford University

Jose Montoya, MD, Professor of Medicine, Stanford University; ME/CFS Physician

Susan Levine, MD, ME/CFS Physician

Harry Greenberg, MD, Senior Associate Dean of Research, Professor of Medicine, Stanford University

Bela Chheda, MD, ME/CFS Physician

Patient partners

We are very grateful for the support and contributions of the ME/CFS patient community, which has and will continue to play an integral role in moving research forward. We are committed to continuing to involve patients as participants and consultants throughout these projects, and maintaining open communication about our findings through a variety of venues. We are especially grateful to all the patients who selflessly volunteer to be subjects in our research, who generously donate to make our research possible and who send Dr. Davis their ideas, scientific analyses, and links to publications. Our patient partners are a significant and essential part of our team.

Friday, 1 December 2017

Professor Malcolm Hooper – Off the PACE

Professor Malcolm Hooper – Off the PACE

At a conference in November run by the Academy of Nutritional Medicine (http://aonm.org/) entitled “Waking to a New Dawn: The Emergence of 21st Century Acquired Immune Deficiences & Innovative Solutions”, the keynote speaker was Professor Malcolm Hooper, who is well known to people with ME, and who gave a talk called “OFF THE PACE: CMIs, BPS, PACE, GUIDELINES and CONSEQUENCES”. 

To view the PowerPoint presentation of Professor Hooper’s talk -


To read his notes –


Well worth looking at by anyone interested in the background of all that has happened in the ME world over the last 30 years or so, and in finding out how things have ended up as they are now.

Monday, 27 November 2017

ME Association Statement: Negative phase III clinical trial result from Norway for Rituximab in ME/CFS


ME Association Statement: Negative phase III clinical trial result from Norway for Rituximab in ME/CFS | 27 November 2017

By Dr Charles Shepherd, Hon. Medical Adviser, ME Association.

“I was disappointed to learn – while at the Royal Society screening of the documentary, Unrest, in London last Thursday – of the preliminary (but unpublished) results from the phase III clinical trial of Rituximab, that has been carried out in Norway.

“This large, multicentre, ‘gold standard’ clinical trial, involved 152 people with ME/CFS receiving either Rituximab or a placebo, with initial treatment followed by maintenance treatments at 3, 6, 9 and 12 months, and a two year follow up.

“The ME Association has consistently taken the position that Rituximab could be one of the most promising developments in the search for a safe and effective drug treatment that is targeted at the underlying disease process in ME/CFS.

“We also know that the physicians involved in this research – Drs Oystein Fluge and Olav Mella from the Haukeland University Hospital in Norway – have taken great care in the way that they have devised the protocols for the clinical trials that have been carried out and reported.

“Despite the headline negative finding, we believe that this trial will still provide useful insights and contribute to a better understanding of M.E., and we also have the results from the Cyclophosphamide clinical trial to look forward to. We are very pleased that this knowledgeable, and valued, research team will continue with their work, trying to find answers to the M.E. puzzle.

“The ME Association Ramsay Research Fund had set aside around £60,000 to help support this research, or to help fund a clinical trial of Rituximab here in the UK, if such funding was required, and applied for by a reputable research or clinical trials group. No research grant applications have been received.

“It is difficult to comment further on these very basic preliminary results, and my understanding is that no further comment will be made by those involved until the study is published early next year. However, we do believe that it is correct and helpful for the patient community to be notified about the disappointing key conclusions prior to publication.

“Any decision – including if it is going to be sensible for the charity sector to be raising or spending further large sums of money on research involving the theoretical basis to this treatment (i.e. immune system dysfunction, involving the B-cell component of the body’s immune system), or further clinical trials to assess the safety and efficacy of Rituximab – will have to wait until more detailed information becomes available about the outcome of this phase III clinical trial, and the scientists involved have expressed their opinion as to whether further such research is justified.

“Based on the results from the clinical trials that have been published so far – along with the rather mixed evidence from people with M.E. who have been prescribed Rituximab outside formal clinical trials – it does appear that this type of immunotherapy could still be relevant to at least a sub-group.

“If it is agreed by experts in this area of immunotherapeutics (and we will be seeking expert advice), that we should continue to explore the role of Rituximab as a possible treatment for ME/CFS – and try to find immune system biomarkers that could help to identify the sub-group of people with M.E. who are most likely to respond to such treatment – the ME Association will continue to invite applications for research grants to the Ramsay Research Fund.

“Medical journals are less enthusiastic about publishing negative research findings or negative results from clinical trials. However, given the enormous amount of interest in Rituximab, from both people with M.E. and the medical community, I am confident that these results from Norway will be accepted for publication in due course.

“The ME Association is currently considering a number of other research applications – some of them quite large – and trustees will discuss the latest news about the Rituximab clinical trial at their Board meeting in December. A decision will then be made as to whether the £60,000 currently set aside, should remain as a ring-fenced sum for funding Rituximab research, or used for other biomedical research applications.”

Dr Charles Shepherd,
Hon Medical Adviser, ME Association.

Wednesday, 22 November 2017

Invest in ME Research Initial Statement on Norwegian Phase III Rtiuximab Clinical Trial

http://www.investinme.org/IIMER-Newslet-1711-03.shtml

Rituximab Trial Status   November 2017

Norwegian Statement on Phase III Trial

Professor Olav Mella recently publicly released early details from the Phase III multi-centre double-blinded placebo-controlled Rituximab Clinical Trial which has been ongoing in Norway for the past year.

Invest in ME Research have been informed by Dr Oystein Fluge of this.

Invest in ME Research have issued this preliminary statement (below).

The Haukeland team will be presenting at the IIMEC13 13th International ME Conference in London on 1st June 2018


Invest in ME Research Initial Statement on Norwegian Phase III Rtiuximab Clinical Trial

November 21, 2017

The statement from Haukeland University, Bergen from Professor Mella is a major disappointment for people with ME and their families.

What had looked to be a promising line of research that could lead to an effective treatment for a subgroup of patients defined by the Canadian Criteria and major understanding of the pathology of this disease has proven to be inconclusive.

Naturally, at the charity, everyone is disappointed. We are disappointed for all the ME patients and carers and families and friends.

We are especially disappointed for all of our supporters and all who have made such generous and tireless efforts to raise funds and awareness of our campaign.

We are very disappointed also for the Haukeland research team - a wonderful team who have brought hope to all patients - and, importantly, brought new insight into this disease and new interest from other areas. 

However, we have found, throughout 12 years of trying to change the way that ME is perceived, researched and treated that it is never easy.

It would be easy to give up, to resign oneself to nothing changing, to accept the status quo.

But we think differently.

At the 2017 Colloquium/Conference we invited Karolinska Institutet in Stockholm to present negative results. Because it is important to use negative results for positive effects. Negative results are data and the Norwegian rituximab trial has generated a lot of data that needs to be looked at very carefully. 

When we first engaged Professor Jonathan Edwards into research into ME one of the earliest comments he made was that he was pleased to note that our conference did contain negative results.

We see the positives in this research which has been performed by researchers of the utmost integrity who have not made headlines for the sake of it but have thoroughly conducted outstanding research, and still retained a humility that is to their credit and that of their colleagues and team.

We have an excellent research team in Norway which has served the ME patient community and their families with honesty, integrity, professionalism, detemination and an empathy which had never been seen before in this field.

We have established good working relationships between the Norwegian researchers and the UK Centre with input from UCL and UEA/Quadram Institute.

We have data now – more than before.

We have research which IiMER has established and a foundation for the Centre of Excellence for ME.

We have international collaboration in research into ME that will continue.

And we have new plans – already in the making.

The researchers from Haukeland will give more detail on their results and publish a paper or two which will benefit all studying ME. 

For us, we have invited the Haukeland team to Norwich to discuss the way forward.

We remain positive. Another setback, another day.

We have already been in discussion with our advisors and with the Norwegian team and we will meet to clarify the best way forward in the near future with our major funder and researchers.

We still have much good research being funded and being planned and feel our stategy is, and will pay off and lead to the most rapid route to finding cause(s) of ME and effective treatments.

In another age, and in another struggle which has some parallels to that which is forced upon people with ME, these words strike a chord -

“We must accept finite disappointment, but never lose infinite hope. ” 

- Dr Martin Luther King

Friday, 10 November 2017

The eternal God is thy refuge


C H Spurgeon's Morning Devotional for 10th November 

"The eternal God is thy refuge."

Deuteronomy 33:27

The word refuge may be translated "mansion," or "abiding-place," which gives the thought that God is our abode, our home. There is a fulness and sweetness in the metaphor, for dear to our hearts is our home, although it be the humblest cottage, or the scantiest garret; and dearer far is our blessed God, in whom we live, and move, and have our being. It is at home that we feel safe: we shut the world out and dwell in quiet security. So when we are with our God we "fear no evil." He is our shelter and retreat, our abiding refuge. At home, we take our rest; it is there we find repose after the fatigue and toil of the day. And so our hearts find rest in God, when, wearied with life's conflict, we turn to Him, and our soul dwells at ease. At home, also, we let our hearts loose; we are not afraid of being misunderstood, nor of our words being misconstrued. So when we are with God we can commune freely with Him, laying open all our hidden desires; for if the "secret of the Lord is with them that fear Him," the secrets of them that fear Him ought to be, and must be, with their Lord. Home, too, is the place of our truest and purest happiness: and it is in God that our hearts find their deepest delight. We have joy in Him which far surpasses all other joy. It is also for home that we work and labour. The thought of it gives strength to bear the daily burden, and quickens the fingers to perform the task; and in this sense we may also say that God is our home. Love to Him strengthens us. We think of Him in the person of His dear Son; and a glimpse of the suffering face of the Redeemer constrains us to labour in His cause. We feel that we must work, for we have brethren yet to be saved, and we have our Father's heart to make glad by bringing home His wandering sons; we would fill with holy mirth the sacred family among whom we dwell. Happy are those who have thus the God of Jacob for their refuge!

Friday, 3 November 2017

Will The UK Establishment Finally Stop Denying The Reality Of ME?


By Dr Simon Duffy, Director of the Centre for Welfare Reform

Jennifer Brea's powerful film Unrest exposes the reality of Myalgic Encephalopathy or ME. This condition leaves people utterly exhausted, or as Brea puts it, like a broken battery, unable to charge beyond 10%.

ME is poorly understood and receives minimal research. Brea was repeatedly misdiagnosed and, on one occasion, even told that it was all in the mind - the result of some long-forgotten trauma.

Eventually Brea discovered that there was not only a name for her condition but that there are millions of other people suffering with ME. With the correct diagnosis she has managed to reduce the impact of ME on her life, but she also came to understand how this real disease creates double-barrelled suffering: first, it devastates your life by robbing you of energy; second, the failure of society to respect the reality of your illness makes you invisible and defenceless.

So, why has ME been so badly misunderstood?

Dr Charles Shepherd explains that in the UK two psychiatrists played a particularly damaging role, by treating an outbreak of ME (within a hospital) in 1955 as an example of hysteria. This dangerous desire to solve a problem by evading the problem, has been made all the easier by the emergence of something called the biopsychosocial (BPS) model: this is an all encompassing framework for rethinking illness - making it part biological, part mental, part social. This may seem reasonable, but it easily becomes a way of blaming the victim and claiming it's all in the mind.

The PACE Scandal also demonstrates the powerful forces at work. PACE was a research programme to test two 'therapies' for people with ME - Cognitive Behaviour Therapy (CBT) and Graded Exercise Therapy (GET). Although these therapies did not prove effective, researchers amended the rules of the evaluation so that people who had got worse were counted as having benefited from these therapies.

Outside the UK the PACE research has been severely criticised; but the Countess of Mar believes that the UK media has been frightened into silence by the Science Media Centre whose board members include Sir Simon Wessely, one of the psychiatrists connected to the PACE scandal. Even more disturbing is that Mrs May has now asked Wessely to lead an Independent Review of the Mental Health Act 1983 - a decision heavily criticised by independent advocates.

The UK Government also seems to have a stake in maintaining the belief that ME is all in the mind. Mo Stewart, in her book Cash Not Care, has shown how the US Insurance Company Unum has promoted the BPS model within the DWP, encouraging the UK Government to reduce disability benefits in order to grow the market for their own disability insurance products. Lord Freud cited the PACE research as important evidence to justify the use of BPS in their welfare 'reforms' and medical diagnoses have now been replaced with dubious catch-all assessments of 'readiness for work' or 'level of help.' The film I, Daniel Blake accurately captures many of the horrors of these mindless and inhuman processes.

Fortunately, in the USA, researchers are now taking ME seriously, and making important progress. CBT and GET are no longer recommended as helpful therapies and instead there is increasing recognition that excessive exercise can be extremely dangerous. The level of research is still inadequate, but no one doubts the reality of the illness and important and revealing tests have been developed.

Brea's film, which is winning awards and being widely seen, may help undermine the resistance of the UK establishment, but there is still a long way to go. Even if there are research breakthroughs people will still be living with the disabling consequences of ME. It is for this reason that the Centre for Welfare Reform is supporting the Chronic Illness Inclusion Project. Our aim is to help the community of people suffering from chronic illnesses (including, but going beyond, ME) to find their own voice, to build alliances with other disabled people and to ensure that they are no longer invisible before the eyes of the powerful.

Wednesday, 1 November 2017

ME sufferers being shamefully let down by professionals


LINDA BURNIP and DENISE McKENNA from Disabled People Against Cuts spotlight how people with ME are having their health and welfare harmed by poor research and misuse of statistics

LAST week, over 65 deaf and disabled people’s organisations, campaigns and mental health professionals wrote to the Prime Minister asking her to urgently rethink her decision to appoint Professor Sir Simon Wessely to lead the much-anticipated independent review of the Mental Health Act as announced in her speech at the Conservative Party conference on October 4.

Wessely’s body of work on myalgic encephalomyelitis (also known as chronic fatigue syndrome), and his conduct in relation to people with ME, make him resoundingly unfit to lead an inquiry into the Mental Health Act.

ME is a poorly understood illness, believed by most researchers in the field to have a physical cause. But the “psychiatrisation” of ME through a cognitive-behavioural approach to the illness led by Wessely since the late 1980s has resulted in treatment (particularly graded exercise therapy, or GET) which can be harmful and even coerced, in the stigmatisation of patients and let to the frequent denial of their entitlement to social security and support.

Wessely has consistently promoted the unsubstantiated suggestion that ME is caused or maintained by patients’ false illness beliefs and abnormal behaviour.

As a result, the integrity of patients’ experience of this devastating illness been destroyed as their testimony is deemed unreliable.

This form of “epistemic injustice” (according to medical ethics scholars Blease et al) has seen people with ME derided within the medical profession and wider society for misperceiving, exaggerating, even creating their own illness.

Wessely’s approach to ME involves treatment with GET, aimed at reversing the physical consequences of what he sees as their dysfunctional behaviour.

Nearly 50 per cent of people with ME surveyed reported that treatment with GET made their condition worse.

Yet Wessely and his colleagues are silent on the subject or dismiss patient experience as unreliable evidence or poor treatment compliance.

As a result, thousands of people with ME have received NHS treatment informed by his model that has further damaged their health.

Wessely continues to defend the notorious Pace trial, a study into CBT and GET treatment for ME/CFS part-funded by the Department for Work and Pensions and widely condemned by academics for misuse of statistical methods in order to produce positive-looking results.

Wessely’s involvement in media discussions about ME has further suppressed patients’ voices. Following the publication of results from the Pace trial, Wessely and his colleagues responded to concerns about their work by taking part in media campaign which promoted prejudice and led to those patients who had identified serious methodological and statistical problems being dismissed as irrational extremists motivated by anti-psychiatry.

The Science Media Centre, for which Wessely is a trustee, has played a key role in promoting misleading information about the Pace trial, and smearing critics.

During the 1990s Wessely advised the DWP (then DSS) that classifying ME as a neurological illness, as the World Health Organisation does, would perpetuate patients’ false beliefs, prolong their illness and result in a deluge of disability claims.

The influence of Wessely and his colleagues on DWP training manuals on CFS/ME has undoubtedly resulted in a disability assessment system biased against people with ME and caused them great additional difficulty in accessing support with the extra costs of their disability.

The work of Jonathan Rutherford reveals how Wessely was among a group of medical and insurance industry professionals whose work on “malingering and illness deception” influenced the DWP’s understanding of ill-health and disability.

Wessely and his colleagues shaped the ideology underpinning the disastrous work capability assessment (WCA) known as the “biopsychosocial model.” According to Professor Tom Shakespeare and colleagues who have exposed the poor science underpinning the biopsychosocial model, this approach to disability effectively blames disabled people seeking social security support for their own misfortune.

The WCA has had a devastating impact on the lives of disabled people as part of a package of welfare reforms leading, in the words of the UN disability committee, to “human catastrophe.”

All of these activities amount to an abuse of power by Wessely against people with ME. His thoughts and actions have led to stigma, iatrogenesis and a denial of their rights to support, all of which have compounded the burden of this illness immeasurably.

Monday, 23 October 2017

ME Association petition has been sent to Sir Andrew Dillon at NICE: M.E. is not a functional disorder


The most recent ME Association petition called on NICE to amend its proposed guideline on suspected neurological conditions, and remove all reference to ME/CFS being a functional disorder.

We wrote to Sir Andrew Dillon last Friday, with a covering letter (below) and enclosed the final petition – supported by 13,593 people – along with 199 pages of comments; such was the strength of feeling shown.


Dear Sir Andrew,

Firstly, thank you for the recent decision to fully review and update the NICE guideline for ME/CFS. It was a very welcome development and, as registered stakeholders, The ME Association and Forward ME Group (a collaboration of ME/CFS charities of which we are a member) are very much looking forward to representing the patient community at future meetings.

I am writing to you today in support of the Forward ME Group submission as stakeholders in the development of a new guideline for suspected neurological conditions. The draft guideline currently includes reference to ME/CFS being an example of a ‘functional disorder’ which the guideline  defines as a condition that is ‘emotionally generated’ and ‘which may mimic physical disease’. This ‘functional disorder’ classification is then used as a basis for advising health professionals to not refer patients with specific ME/CFS symptoms such as deteriorating cognitive dysfunction for a neurological opinion.

The submission sets out the reasons why this description of ME/CFS is inaccurate and rather alarming – especially as it is not reflected in CG53, the guideline for ME/CFS, and as this disease is recognised by the World Health Organisation (in ICD10) and Department of Health, as being neurological.

In support of this submission, The ME Association launched a public petition for a period of two weeks, that enabled people who are affected by ME/CFS to demonstrate their support that this erroneous description and implied causation be removed.

The petition closed on 11th October and was supported by 13,593 people – all of whom want to see all references to ME/CFS being a ‘functional disorder’ removed from the new guideline and/or ME/CFS removed in its entirety.

As well as enclosing the petition for your reference, I have also enclosed 199 pages of comments – such was the strength of feeling about this error – from patients, carers, family members of the severely affected and health professionals working in this field, for example:

“Having been a specialist therapist for 20 years working with CFS/ME patients I can assure you that this is not a functional illness.”
“This devastating disease has destroyed my life and that of others I’ve met. Adding to that destruction by denying the revealing international medical research highlighting the physical dysfunctional processes and pretending it is psychological in origin is heartlessly cruel.”

Neurology should be welcoming people with ME/CFS and not trying to pass them off onto other specialisms, especially when neurology can play such a key role in diagnosis and management.

We would very much like the guideline development members, who are meeting to consider stakeholder submissions and finalise the suspected neurological conditions guideline, to consider the content and strength of feeling demonstrated by this petition and in the comments, it attracted.

If NICE can again show that it has listened to feedback from stakeholders, patients and their representatives – as well as professionals working in the field – and correct the error in this new guideline, we believe the decision will be as warmly welcomed by the ME/CFS patient community as your decision to review the guideline for ME/CFS.

We would welcome an explanation as to how this error arose and why, when NICE prides itself on consideration of the evidence-base, no evidence was considered before ME/CFS was deemed to be a ‘functional disorder’ and referral of patients to neurology was decided to be unnecessary.

Please show you have listened and take on board this significant feedback.

I look forward to hearing from you in due course.

With kind regards

Yours sincerely

Dr Charles Shepherd.
Hon Medical Adviser

Enclosures:



Wednesday, 18 October 2017

Trial By Error: Another Letter to NICE’s Sir Andrew Dillon


17 October 2017

By David Tuller, DrPH

First, for those who might have missed it, here’s a conversation from This Week in Virology (TWiV), posted a few days ago. Dr. Racaniello and I discuss the CDC, NICE, Esther Crawley’s ethically challenged behavior, the CMRC, and other stuff.

Second, earlier today, I sent the following e-mail to Sir Andrew Dillon, the NICE chief executive:

Dear Sir Andrew:

I would like to congratulate NICE on its decision to pursue a full update of CG53, the CFS/ME guidance, rather than accept the surveillance report’s recommendation to leave it as is. The Guidance Executive made the right call, based on the current science—and given the international controversy over PACE trial and other CBT/GET trials. In NICE’s announcement, the list of concerns about the 2007 guidance was a fair accounting of what has troubled people for years and led to the outpouring of stakeholder comments opposed to the initial recommendation.

The decision to pursue a full update leaves some unanswered questions. Given that the new guidance might not be available until 2020, I am hoping you or someone else at NICE can shed light on these issues. The first involves the official status of the current guidance. The second involves references to CFS/ME elsewhere within NICE that do not appear to be aligned with the decision to fully update the guidance.

1) What is the official status now of CG53? Is it considered “provisional” or on stand-by in some way? Or does it remain fully in force? In other words, if National Health Service clinics and doctors claim to be following the “NICE guidance” for CFS/ME, do they also have an obligation to inform patients that the current version has been deemed no longer fit for purpose and is undergoing a “full update”? If these clinics and doctors prescribe CBT and/or GET, citing NICE as evidence and support, do they now have an obligation to explain that the effectiveness of these two treatments is under serious question?

2) The decision to pursue a “full update” suggests that NICE has joined the international scientific community in questioning whether psychological and behavioral approaches are appropriate for this illness—especially given the extensive evidence of physiological dysfunction. Does that mean NICE will reconsider other references to CFS/ME in agency documents? So far, patients and advocates have noted two sets of references to CFS/ME that do not appear to reflect the updated NICE position on CG53 and the illness itself.

One involves a NICE initiative called Improving Access to Psychological Therapies. According to the IAPT site, NICE is working with NHS England on the program. IAPT is designed to “assess digitally enabled therapies for anxiety, depression and medically unexplained symptoms which offer the potential to expand these services further.”

Chronic fatigue syndrome is included in the list of thirteen conditions identified by “the NICE expert IAPT panel” as appropriate targets for interventions developed through this program. The IAPT site indicates that these interventions need to be consistent with NICE guidance. The site then refers readers to CG53 but makes no mention that this guidance is undergoing a full update.

Why is chronic fatigue syndrome still listed under the IAPT program? Does the Guidance Executive agree that it should be removed, since it is not a psychological or psychiatric disorder and the use of CBT and GET is very much under question? If it is not removed from under the auspices of IAPT, does that mean NICE intends to encourage the development of digital methods of delivering CBT and GET to people with CFS/ME, even as the guidance itself undergoes a full update?

Is the Guidance Executive aware that inclusion of CFS/ME in the IAPT program creates enormous concern among patients and advocates specifically because it suggests NICE might adopt or endorse some version of FITNET-NHS? That is the trial in which Professor Esther Crawley is examining the delivery of online CBT to children, based on the purported success of earlier Dutch research. Is the Guidance Executive aware that, as with the PACE trial, critics (including me) have documented serious methodological flaws in both the Dutch FITNET study and Professor Crawley’s own work in this field?

A second set of references to chronic fatigue syndrome is in a recent draft guideline on “suspected neurological conditions”—essentially, a primer on the symptoms and signs that might indicate a neurological condition and trigger a referral to specialist care. NICE published the draft in August and sought stakeholder comments. In its stakeholder submission, Forward ME noted that the draft guideline includes several unfortunate references to chronic fatigue syndrome as being a “functional” symptom or disorder.

As the draft guideline itself explains: “Functional symptoms are complaints that are not primarily explained based on physical or physiological abnormalities. They are likely to have an emotional basis. They may mimic neurological disorders.” The draft guideline suggests, for example, that “concentration difficulties” do not warrant referral to a neurologist if these difficulties are “associated with chronic fatigue syndrome or fibromyalgia.”

Psychiatrists and other adherents of the biopsychosocial field have long classified chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, and other conditions involving so-called “medically unexplained symptoms” as functional somatic syndromes or disorders. Given the current effort to revamp the CFS/ME guidance and the significant evidence of actual physiological dysfunctions, does NICE feel comfortable at this point describing the illness elsewhere as a “functional” symptom that is “not primarily” organic in nature but is “likely to have an emotional basis”?

Thank you, Sir Andrew. I look forward to your response. –

Best–David


Tuesday, 17 October 2017

He shall gather the lambs with His arm


C H Spurgeon's Evening Devotional for 17th October 

“He shall gather the lambs with His arm."

Isaiah 40:11

Our good Shepherd has in His flock a variety of experiences, some are strong in the Lord, and others are weak in faith, but He is impartial in His care for all His sheep, and the weakest lamb is as dear to Him as the most advanced of the flock. Lambs are wont to lag behind, prone to wander, and apt to grow weary, but from all the danger of these infirmities the Shepherd protects them with His arm of power. He finds new-born souls, like young lambs, ready to perish-He nourishes them till life becomes vigorous; He finds weak minds ready to faint and die-He consoles them and renews their strength. All the little ones He gathers, for it is not the will of our heavenly Father that one of them should perish. What a quick eye He must have to see them all! What a tender heart to care for them all! What a far- reaching and potent arm, to gather them all! In His lifetime on earth He was a great gatherer of the weaker sort, and now that He dwells in heaven, His loving heart yearns towards the meek and contrite, the timid and feeble, the fearful and fainting here below. How gently did He gather me to Himself, to His truth, to His blood, to His love, to His church! With what effectual grace did He compel me to come to Himself! Since my first conversion, how frequently has He restored me from my wanderings, and once again folded me within the circle of His everlasting arm! The best of all is, that He does it all Himself personally, not delegating the task of love, but condescending Himself to rescue and preserve His most unworthy servant. How shall I love Him enough or serve Him worthily? I would fain make His name great unto the ends of the earth, but what can my feebleness do for Him? Great Shepherd, add to Thy mercies this one other, a heart to love Thee more truly as I ought.


Tuesday, 3 October 2017

UK ME/CFS Biobank team receives largest ever grant to continue biomedical research project


Breaking News! UK ME/CFS Biobank team receives largest ever grant to continue biomedical research project

By Russell Fleming, Content Manager, ME Association.

ME Association trustees and staff were over the moon when we heard that the CureME team at the London School of Hygiene and Tropical Medicine had received a new grant of $2.1 million from the National Institutes of Health (NIH) in America.

The funding represents the biggest ever single investment in biomedical research to happen in the UK and it will enable a current project, that is searching for disease biomarkers, to be extended for another 4 years – until 2021.

The project is a longitudinal study that is measuring changes in the immune system and genetic profile of individuals in a disease whose symptoms are known to fluctuate over time. The initial £1 million project, which began in 2013, was over 3 years and had also been made possible by funding from NIH.

Dr Luis Nacul, who leads the CureME team, is also responsible for overseeing the UK ME/CFS Biobank, which has been built and maintained by charity support and the funding from America.

The new grant will enable the Biobank to increase in size as even more blood samples and clinical data will be collected from people with ME/CFS, multiple sclerosis, and healthy controls, and then made available to research applicants.

“The new grant from the NIH (US) will enable, for the first time, comprehensive prospective assessments of cases of ME/CFS at regular intervals.
“This greatly enhances the chances of a breakthrough in the understanding of the pathophysiology of this complex disease and the identification of much-needed biomarkers for the diagnosis of different sub-groups of patients.
“We very much look forward to continuing our partnership with the patient community, which has been key to the success of our research so far.” 
Dr Luis Nacul, Principle Investigator, CureME team, LSHTM.

The Biobank is the only resource in the world able to include samples from those most severely affected – the house- or bed-bound – and is the premier resource outside the United States for the study of the disease. All participants are examined by a clinician and must conform to the Biobank’s rigorous protocols.

The ME Association has been a long-time supporter of the Biobank and provides funding to support its development. This longitudinal project, that in total will amount to some £2.56 million, represents one of the most exciting opportunities to learn more about this devastating disease.

Dr Charles Shepherd, Hon. Medical Adviser to the ME Association, and Chair of the UK ME/CFS Biobank Steering Group, commented:

“This is a significant and vital sum of money that will help scientists unravel the mysteries of this devastating illness. 
“The irony is that the funding comes once again from America.
“What this seems to suggest is that the USA is far more serious about finding the underlying causes of M.E., while the UK seems most willing to invest in inappropriate studies using cognitive behavioural therapy and graded exercise.
“The fact that the NIH has decided to provide another major grant is an important endorsement of the ME/CFS Biobank, and we would like to congratulate all the staff who have been involved in setting up and developing what has become a vital new part of biomedical research infrastructure here in the UK.
“We hope that other research groups will also now start to make use of this unique resource to achieve desperately-needed breakthroughs into the cause and treatment of ME/CFS.” 
Dr Charles Shepherd, Hon. Medical Adviser, ME Association,Chair of the UK ME/CFS Biobank Steering Committee.

Research: A longitudinal immunological study for ME/CFS biomarker discovery

What are the UK ME/CFS Biobank team proposing to do with this funding?

  • They will be studying 110 ME/CFS cases (half severe, half mild-moderate) meeting all of the CDC, Canadian Consensus, and Institute of Medicine, criteria.
  • They will focus on detailed immunological and clinical phenotypes (subgrouping patients by immune differences, such as the number of different immune cells and cytokines, and clinical differences, such as severity).
  • Analyse inter-relationships (the relationship between the immune differences and differences in severity/symptoms and changes over time).
  • Cases will be assessed every 6-12 months, over 5 time points, to record changes in biomarker expression and link these to clinical parameters (whether their condition has gotten better, worse or remained stable) in order to analyse biomarkers at different stages of disease progression and try to identify subgroups.
  • Cases will be grouped according to trends in symptom severity using scores relating to pain, fatigue and functional status.
  • In-depth Immunological Profiling (to try and identify biomarkers) will involve:
* Phenotyping Lymphocytes (T cells, B cells and NK cells) and monocytes from the blood samples.
* Measuring the functional response of NK (natural killer) and T cells after stimulation (by a virus, for example).
* Analysing secreted cytokines from the stimulated NK and T cells.
* Genotyping the donors for MHC class 1 (molecules that trigger an immune response to a specific toxin or foreign substance) and KIR (recognise MHC class 1 cells and activates the killing response of NK cells).

  • They then want to determine whether changes in immune parameters come before, after or predict the changes observed in clinical presentation (changes in symptoms and severity over time).
  • This will be done by quantifying correlations between immunological biomarkers and by identifying biomarkers associated with changes in ME/CFS clinical status.
 Significance of the study

“This study is unique for its strict inclusion criteria and detailed clinical phenotyping, adding specificity and validity to our analysis.”

“This is, to our knowledge, the first long-term prospective study of ME/CFS to incorporate both ambulatory and severe cases and to include comprehensive clinical data and in-depth immunological profiling.”

“This research will contribute to the development of better diagnostic tools and treatments.”

“The inclusion of severe cases through home visits will allow for research on a subset of patients often neglected in ME/CFS studies.”

“Because 1- 2.5 million Americans have ME/CFS, this study has the potential to improve the lives of a large patient population in the U.S. as well as advance the state of the field in the U.S. and internationally.”

“Patients and stakeholders are involved in all aspects of the research.”

More study information, here.

More Reaction

“This is great news for quality research into ME/CFS. The Biobank team has always put the needs of the patient first and it’s fantastic that their good work can now continue”

Cecilia Finnerty, Patient Representative.

“Such wonderful news for people with ME.  It is a privilege to serve on the Steering Committee alongside a committed professional team who have such a heart for people with this illness.”

Hannah Clifton, Director, The ME Trust. 

“ME Research UK is delighted that the team has been awarded a new grant from the NIH worth $2.1m. The funding will enable further research on those affected by ME/CFS over the next 4 years and will ensure that the UK’s first biobank of human blood samples continues to be a valuable resource for all researchers in the UK and beyond.”

Sue Waddle, Vice-Chair, ME Research UK.

“Congratulations to the London School of Hygiene & Tropical Medicine team for their grant award from the NIH. This is the most important development in UK research into ME this year and all the more so because it shows the international standing of the group. Very well deserved.”

Professor Jonathan Edwards, Emeritus Professor of Connective Tissue Medicine, University College London