Japanese National Diet Adopts JMEA’s 2018 Petition for ME/CFS Research

We are pleased to announce that the Japanese National Diet has adopted Japan ME Association’s 2018 petition to the national government,  “Petition Seeking Research Advancement for the Neurological Disease ME/CFS,” as a result of voting on the petition by the House of Representatives and the House of Councillors, respectively. The adoption of our most recent petition follows the successful adoption of our formal petitions to the Japanese national legislature in 2014 and 2015, and again in 2016.

The petition was introduced to the 2018 Diet session by 99 Diet members across multiple political parties and submitted with more than 13,500 signatures. We are deeply grateful to all of the individuals (which included not only patients but those who first learned about ME/CFS through the petition effort) and Diet members who generously contributed to this significant result.

The petition will now be delivered to the Cabinet, and the Cabinet will produce approximately two reports annually to the House of Representatives on progress on the petition items.

ME/CFS has been classified in the World Health Organization’s International Classification of Diseases as a neurological disorder since 1969, and the disease has again been classified as a neurological disorder in the revised ICD-11 announced on June 18, 2018. This past April, AMED (the Japan Agency for Medical Research and Development) adopted the neurologist Dr. Takashi Yamamura’s research team for ME/CFS. ME/CFS was also featured in the scientific publication Nature this year, indicating that the disease is now recognized at a global level.

Japan ME Association greatly appreciates your continued support as we advocate for ME/CFS to be designated as Intractable/Rare Disease in Japan and for research advancements that will bring much-needed effective treatments to ME/CFS patients.

JMEA signs Letter to WHO Director-General Dr. Tedros Adhanom Ghebreyesus

As part of our collaborative actions with international ME advocacy organizations along with our participation in the global day for health equality for ME/CFS #MillionsMissing, Japan ME Association has co-signed an open letter to the WHO Director-General Dr. Tedros Adhanom Ghebreyesus from the International Alliance for ME requesting a meeting to highlight the serious and significant impact of ME and to “explain why we are seeking urgent national and international action to increase research on [ME] and ease the suffering of patients around the world.”

We support this letter along with ME advocacy organizations from the UK, the United States, Australia, South Africa, Spain, and other countries in our sincere hope that the Director-General will accept the International Alliance’s invitation to speak with him to address the urgent situation facing ME patients worldwide at the WHO level. The full text of the letter can be found here.

JMEA to participate in #MillionsMissing at Geneva Event

On Saturday, May 12, 2018, Japan ME Association will participate in the global #MillionsMissing protest as part of the International Alliance for ME’s Visibility Event at Place Des Nations in Geneva, Switzerland, the location of the World Health Organization (WHO).

#MillionsMissing is a global day of public action that calls for health equality for patients with ME. This year, Japan ME Association joins for the first time through its participation in the event in Geneva, where messages from Japanese ME patients will be displayed among those from many other countries. The International Alliance for ME is a joint international advocacy movement which aims to raise the profile and awareness of ME at the WHO level. The goal of the Alliance is to collaborate with organizations and individuals at the national and international levels to advocate for the adoption of a resolution by the WHO and its Member States recognizing ME as a “serious, chronic, complex and multisystem disease that frequently and dramatically limits the activities of affected patients (Institute of Medicine, 2015)” and to adopt measures to provide a global and coordinated public health response to ME.

JMEA believes that it is critically important to combine our efforts with ME advocacy organizations internationally to more effectively convey to the Japanese government the urgent need to improve the current public health response to ME. We firmly believe that advances at the WHO level and in other countries will positively influence the situation of ME patients in Japan and vice versa.  

Public Comments on the Proposed Treatment Guidelines

In December 2017, in addition to requesting an external review from Japan ME Association among other groups on its “ME/CFS Treatment Guidelines for Japan,” the Research Committee on the Development of Treatments and Treatment Guidelines for ME/CFS also solicited comments from the public.

Several organizations and individuals within Japan have shared with us the public comments they submitted to the guidelines research committee. We highlight three of them (translated from the original Japanese) here.

  • “According to a 2012 to a survey conducted with the ME/CFS association, 47% of patients visited more than six medical institutions before they obtained a diagnosis. Patients struggled from misunderstanding and prejudice even after receiving an ME/CFS diagnosis, with a lack of understanding from family and friends. They are often viewed as being malingerers. The proposed guidelines include many problems as the patient association has indicated, and will result in further deepening misunderstanding about the disease among medical professionals who do are not familiar with ME/CFS. I hope these guidelines can be reconsidered using reliable factors such as diagnostic criteria and clinical treatment information.” – Dr. Miwako Hosoda, Vice President, Seisa University 
  • “What patients seek regardless of where they live is discovery of the pathology of ME/CFS and the development of effective treatments. It is unacceptable to have situations that may result in harm to patients even outside the context of clinical treatment. This is because the suffering that accompanies illness onset, diagnosis, and visiting doctors in search of treatment is endured by patients and their families, and more precisely, by patients. Of course, risks accompanying research such as clinical treatment trials may be unavoidable. But such risks must be minimized as much as possible, not just limited to clinical trial research… At the very least, I am uncomfortable with the release of the current proposed guidelines, which have been created without convening a panel consisting of stakeholders such as patients, members of the public, and specialist researchers.” – Natsuko NojimaResearcher, Japan Society for the Promotion of Science
  • “In treating illnesses like ME/CFS where the pathology is not yet known, it is only with the passage of time when the actual situation becomes known that medical treatment and medical policies may be truly evaluated. For example, there could be a treatment that may be applied with the best of intentions, but which could constitute a human rights issue. There is a need to be cautious. If there is no treatment with an A-grade recommendation, I believe the guidelines should make clear that there are currently no effective treatments. Since there is no such statement, many clinicians may overlook this important fact and may select graded exercise therapy, which is recommended as a B-grade treatment but has the potential to make patients worse. It could spread the promotion of exercise for illnesses with fatigue even if they make patients worse, as these incidences often remain unreported and patients may end up paying for treatment only to find themselves suffering more.” – Keiji Nakazawa, President, Non-Profit Organization Healthcare Innovation in Japan

Our Opposition to Proposed National Treatment Guidelines for ME/CFS

Japan ME Association held a press conference at the Ministry of Health, Labour and Welfare’s press club on December 14, 2017 to announce our opposition to the public draft of proposed “Treatment Guidelines for ME/CFS for Japan,” issued by the Research Committee for the Development of Treatments and Treatment Guidelines for ME/CFS for public comment. The  proposed clinical treatment guidelines for ME/CFS are scheduled to be published in spring 2018 in Nihon Iji Shimpou, one of the most widely read medical journals in Japan.  JMEA received a request to submit an external review in November 2017, and we announced our opposition to the proposed guidelines at the press conference. NHK, The Asahi Shimbun, The Sankei Shimbun, Kyodo News, and several regional media outlets attended.

JMEA believes that the proposed treatment guidelines do not provide an adequate, reliable, or safe basis for clinicians in Japan to make treatment decisions for ME/CFS patients in real-life clinical settings. The research committee evaluated various treatments to create the proposed treatment guidelines solely on the basis of a literature review (using an “Evidence-Based Medicine” analysis), with each treatment given an effectiveness grade of an ‘A’ to ‘I’ grade-rating (with an A-grade being the most effective).

The result is a document that merely discusses the results of the committee’s literature review, with no A-grade treatments and with a single B-grade treatment recommendation for Graded Exercise Therapy (GET) (all other treatments mentioned in the guideline document — CBT, antidepressants and other drug treatments, Chinese herbal medicines, and yoga — were rated C-grade or lower), with no discussion or guidance on how to distinguish among the appropriateness of the various treatments for actual ME/CFS patients, each with varying symptoms and severity of illness.

Further, the proposed treatment guidelines pose a risk to worsening the symptoms and overall health of ME/CFS patients in recommending Graded Exercise Therapy (GET) as the single treatment with the highest B-grade rating. In particular, gradually increasing aerobic exercise until the patient can return to their normal lives is recommended. (The guidelines recommend GET under the guidance of an appropriate instructor. However, as the document acknowledges apart from its recommendation, primary care doctors, rehabilitation specialists, and physical therapists in Japan do not have knowledge or training about ME/CFS or its symptoms.)

We believe that there is a serious problem where GET is set be established in the national treatment guidelines for Japan as the most highly-rated treatment where GET has been under harsh scrutiny and is being re-evaluated or rejected in the rest of the world. The document acknowledges in footnotes, for example, that the United States Centers for Disease Control (CDC) recently removed GET from its ME/CFS website. Nevertheless, GET is still presented in the proposed guidelines as a highly effective ME/CFS treatment based on the result of the committee’s “evidence-based medicine” literature analysis of research studies mostly from the United States and Europe. The guidelines cite to old studies where the diagnostic criteria used to screen patients are opaque, as well as to studies published in psychology journals and to the highly criticized PACE trial in its list of references in support of its treatment recommendations.

Recent research studies have shown that increasing exercise after a certain (low) threshold leads to a worsening of symptoms, with more medical institutions finally acknowledging this reality in the West. Japan and Japanese ME/CFS patients should not remain in the dark ages on this critical development.

In addition to posing a risk of worsening symptoms – especially where there is a complete lack of knowledge among Japanese physicians, physical therapists, and exercise specialists about ME/CFS and its symptoms, including the post-exertion exacerbation of symptoms – the recommendation of GET in the treatment guidelines will inevitably (and unnecessarily) deepen prevalent and mistaken beliefs about ME/CFS that are currently held among the vast majority of Japanese medical professionals (for example, that ME/CFS is a psychological illness that can be improved by gradually increasing exercise).

JMEA opposes the proposed treatment guidelines for the simple reason that they pose a serious risk to ME/CFS patients. With only a very small handful of doctors in Japan who have experience diagnosing and treating ME/CFS, the individuals who stand to suffer most from this document are ME/CFS patients in Japan of all severities of illness, including and especially severely ill patients.

We outlined the following seven reasons for our opposition to the proposed ME/CFS treatment guidelines in our written external review submitted to the research committee:

1. With no A-grade treatment recommendation and one single B-grade recommendation, the proposed ME/CFS treatment guidelines do not provide an adequate and reliable basis for physicians to determine safe and appropriate treatments for ME/CFS patients of varying illness severity in real-life clinical settings.

2. We are seriously concerned that the mostly highly recommended treatment in the proposed treatment guidelines for Japan will be for Graded Exercise Therapy (GET), a treatment being rejected around the world, and which poses a risk of worsening, and not improving, patients’ symptoms.

3. We question whether the research committee took into account the diagnostic criteria employed in the research studies that were evaluated for the “evidence-based medicine” literature review analysis on which the development of the proposed guidelines was based.

4. We question the paper’s analysis regarding the effectiveness of antidepressants to treat ME/CFS. If the selected literature included studies where there were a mix of ME/CFS patients and patients with major depression (which can easily result from the use of old diagnostic criteria such as the Oxford criteria), there is a question about the effectiveness of antidepressants to treat ME/CFS, distinguished from its effectiveness for treating depression, including secondary depression symptoms that some ME/CFS patients experience as a result of the social, financial, and personal consequences of living with a serious disabling physical illness. Because this distinction is not explained in the document, the proposed treatment guidelines gives a misleading impression about the effectiveness of antidepressants to treat ME/CFS itself.

5. In its explanation of ME/CFS, the draft treatment guidelines omit the fact that the ME is classified as a neurological disorder in the World Health Organization’s International Classification of Diseases.

6. In its explanation of ME/CFS, the proposed treatment guidelines state that the estimated the number of ME/CFS patients in Japan is 300,000, while the most recent (2012) AMED research committee concluded that the number is 0.1% of the population (a number closer to 100,000).

7. The proposed treatment guidelines were created solely using a literature review, without considering clinical information or data.

Patients already suffer from being told that the illness is “all in their heads,” that they can be cured with a change in thinking, antidepressants, or exercise, with even close family members and friends not grasping the seriousness of the illness. Patients often do not look sick and are often viewed as being malingerers. As a patient association, we cannot permit a foreseeable situation to come about that harms patients by perpetuating and exacerbating the existing problems about how the illness is viewed, understood, and treated by medical professionals in Japan.

Questions from the press included: “Did the Ministry of Health commission the drafting of these guidelines?” “Why do you believe guidelines were drafted which would be opposed by patient groups?” “If the treatment guidelines are published, will they actually be implemented?” “What kind of treatments are patients currently receiving?” and “What position is the Japanese Neurology Society taking?”

We welcome your comments in English or Japanese on the serious issues raised by the proposed national treatment guidelines for ME/CFS. Please send them to the following email address for Japan ME Association: cfsnon@gmail.com

Democratic Party Hosts Study Group on ME/CFS

The Democratic Party’s Disability/Intractable Disease Policy Promotion group held a study group on ME/CFS at a conference room in the House of Representatives Building on May 11, 2017. The objective of the study group was to discuss ways to help bring relief to patients. 14 Democratic Party Diet members as well as the Secretaries to 23 additional Diet members attended.

With Representative Yasuko Komiyama serving as moderator, group chairman Representative Kazuhiro Haraguchi said in his opening remarks that when he disclosed [his] intractable disease osteogenesis five months ago, what surprised him was how many people are suffering, and that the study group would “give a voice to those who do not have a voice.” Japan ME Association president Mieko Shinohara then gave brief remarks, reading our request letter, and delivering the letter to Mr. Haraguchi. 

House of Councillors member Ryuhei Kawada said, “When I met Ms. Shinohara six years ago, we discussed the name “chronic fatigue syndrome” made it difficult to understand the disease. The disease is now being researched as a neurological disease, and it is classified as a neurological disorder by the WHO. A therapy called rituximab may be emerging. We’d like study this disease as myalgic encephaloymelitis so that we can create a system where research advances may be made.”

Next, National Center for Neurology and Psychiatry (NCNP) Director of Immunology Dr. Takashi Yamamura provided an informational brief to the group as a medical specialist. Dr. Yamamura is a neurology specialist who has treated and researched multiple sclerosis (MS). He explained how, having received a request from the patient association to use the technology and learning at NCNP to treat this disease, “[we] began research and seeing patients with the belief that we have to do this. One problem of this disease is that patients may not be properly diagnosed at a hospital because abnormalities do not show up on current standard medical tests. Hospitals handle this by telling the patients that there are no abnormalities or that they should visit another hospital because they may be suffering from a psychiatric illness. It is a miserable situation, which is why I believe we must develop an objective diagnostic method.” 

Dr. Yamamura explained the state of ME research, indicating that there is increased focus on abnormalities in the brain, including a PET image study indicating inflammation in the brain. Various diseases of inflammation should be treatable using drugs to effectively suppress inflammation. US patients advocated for research and the US National Institutes of Health (NIH) is investigating the disease with the US government increasing the amount of funding. Oncologists in Norway have published two papers in which the cancer drug rituximab had a significant benefit for about 60% of patients. The issue is how to move forward in this research context. Rituximab is a drug that kills tumors of lymphocytes called B cells and is thought to be a drug that modifies the immune system, and the possibility of using immune modulators for ME is something that is discussed by many scientists overseas.

Dr. Yamamura explained his experience with treating the disease optic nerve myelitis, a disease where severe fatigue is a symptom. Inflammation occurs in the eyes and the spinal cord and fatigue is severe. He explained that in optic nerve myelitis, where the inflammatory substance IL6 is elevated in patients, drugs used for rheumatoid arthritis led to dramatic improvement of fatigue symptoms in these patients. Fatigue is closely related to the immune system and it is important to focus on the immune system.

Many of the ME patients examined demonstrated immune abnormalities. Detailed analysis of patients’ lymphocytes using state-of-the-art flow cytometry technology has shown some of the B cells with clear abnormalities. Since the drug rituximab targets B cells, it is consistent with rituximab being effective. There is a need to shift gears from conventional fatigue research to research for treatments that target the immune system, and there is momentum in this direction globally.

On June 14 there will be a meeting of the Federation of Clinical Immunology Societies in the United States, and the NIH has organized a special four-hour symposium. There will be a session to study information with other researchers on immune abnormalities in myalgic encephalomyelitis and Dr. Yamamura would participate; there was momentum, and he appealed to the study group that he wanted to bring relief to patients as soon as possible.

Japan ME Association president Mieko Shinohara gave brief remarks. She recounted that “I had an onset of ME while studying abroad in the United States in 1990, by 1992 I already knew that I had brain abnormalities by MRI, an immune modulating drug called Ampligen was being tested since 1988. The disease has been treated as the neuro immune disease in Western countries. The NIH study used the Canadian Consensus Criteria as the basis for its research, a document that points to the WHO’s classification of the disease as a neurological disorder, as with the clinical guidelines issued by the IACFS/ME in 2012. It is common knowledge in the West that the disease is a neuro (immune) disease.”

She also mentioned that the phase III trial study of rituximab being conducted in Norway would conclude in October, with patients all over the world awaiting the results. There are many patients who have been ill for 20-30 years. The Ministry of Health survey made clear that 30% of patients in Japan are severely ill patients who are bedridden or close. The patients want more than anything to get better and to have clinical trials proceed. We ask that politicians and Ministry of Health officals understand the situation that patients are in and to act in a way that brings relief to their suffering.

After showing the trailer for the documentary that the Association is filming, Mr. Hiraiwa from the Ministry of Health explained the current intractable disease law and reported on ME/CFS research so far.

A lively question and answer session followed. Among the questions asked were whether Japan would be ready to test rituximab if the Norwegian study published positive results; whether there was evidence of infectious disease in light of historical outbreaks; whether there were neurologists prepared to conduct clinical drug trials; whether a specialized outpatient practice at NCNP could be established; whether the disease could be designated as an intractable; and why ME and CFS were described together. Dr. Yamamura explained that if there is a positive study result for rituximab in Norway and it is approved for clinical use, information would need to be submitted by the drug maker to the Japanese review agency PMDA before it could be used in Japan; that while in many cases a virus has been involved in triggering the onset of ME, the abnormality of the immune system continues but there is no increase in the triggering virus in the patient’s body; and that the name ME/CFS is being used for official purposes. The Ministry of Health Disease Control Division expressed that the ministry would continue to consult with Dr. Yamamura and work together with the patient association.

Representative Yasuhiro Nakane gave closing remarks. “We would like to firmly understand the wishes of the patient association. The budget has been an obstacle in medicine and administration generally, but it is the role of politicians to do something. Please accept our best wishes as we work under the leadership of Mr. Haraguchi.”

JMEA Meets Parliamentary Vice-Minister Fusae Ota

Ota meeting1JMEA held an in-person talks with Parliamentary Vice-Minister of Health, Labour and Welfare Fusae Ota at the Ministry offices on January 29, 2015. JMEA was represented by eight members, including three ME patients and one family member, each who braved the cold weather to attend.

Since this was JMEA’s first meeting with Vice-Minister Ota, we briefed Ms. Ota on the disease’s main characteristics as well as the serious situation of ME patients in Japan revealed by the Ministry’s 2014 patient survey.

We discussed last fall’s decision by NIH to move the leadership for ME/CFS research in the United States to the National Institute of Neurological Disorders and Stroke (NINDS), and the January signing of a Memorandum of Cooperation between NIH and the Japan Agency for Medical Research and Development (AMED), in which the agencies agreed to strengthen cooperative research efforts including in areas such as rare diseases and infectious disease treatments. JMEA requested that Japan take similar steps to advance research on ME as a neurological disease.

We told the Vice-Minister of the rising interest among Japanese neurologists to pursue serious research on the treatment of ME. As medical research on effective treatments is the government action that patients seek most, we requested that the Ministry support research on ME/CFS treatments. (We also mentioned the widespread effort by scientists and patients to challenge the PACE study and its conclusions.)

Our patient members also appealed to the Vice-Minister with specific comments about their personal experiences and desire for effective treatments as soon as possible:

“There are so few doctors who can even diagnose the disease that it took me years to receive a diagnosis. I would like research on treatment to proceed as soon as possible.”

“I have been mostly surviving on IV infusions five times a week for the last six to seven years. I would like treatment research to proceed while I am still living.”

“Most ME patients are forced to quit school and work. There are many patients who aren’t able to come to meetings like this are who are pressed by extreme financial hardship because they are unable to obtain any public disability assistance.”

The Vice-Minister shared that she had traveled to the U.S. to attend the signing ceremony for the NIH-AMED Memorandum of Cooperation. She also explained to us that while there have been shifts towards funding disability and welfare in the U.S., Japan remains a vertically-oriented, compartmentalized bureaucracy in which the moving around of government resources is not a simple matter.

At the same time, Ms. Ota understood the need for research on treatments, and commented that more “decisive politics” is being sought within government. She believed that learning the situation of ME patients from meetings like ours (from patients themselves) was the most effective, and that she would work diligently to understand the situation. She would convey the details of our meeting to the Health Minister.