Tag: research

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.”