Germany: IQWIG Report to government on ME/CFS - report out now May 2023

Michiel Tack said:
It might be good to ask for patient representatives to be involved in the making of this guideline. You could refer to NICE or the Dutch guideline as examples of this.

Patient representatives can point out flaws or potential problems more rapidly when the report is still being written, which is likely a more effective method than only allowing comments on a draft version.

There are several influential publications that recommend involving patients in the creation of medical guidelines such as the Appraisal of Guidelines for Research and Evaluation (AGREE) and The Guideline International Network (GIN) documents. The following citations might be usefu
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Good ideas -- thanks @Michiel Tack.

Just to clarify:

The IQWiG invited German patient organizations to a meeting at the begining of the project and there will be more meetings on some occasions.

See here:

https://translate.google.com/translate?sl=auto&tl=en&u=https://www.iqwig.de/faq-zum-mecfs-projekt/

"When and how are those being affected involved?"

Discussion with those affected: In May 2021, a conversation with 6 patients or relatives took place. Such discussions serve to find out how patients experience the disease, what problems and challenges are associated with the disease, what experiences have been made with the diagnosis and treatment, what wishes and expectations exist in terms of treatment, such as everyday life with the disease It is experienced which content those concerned consider to be particularly important on this topic and where they see gaps in the current information landscape. The number of participants is always strictly limited so that everyone can have their say. The conversation is confidential.
  • Hearings: In the further course of the project, two public hearings are planned in which those affected will have the opportunity to comment (see above).
  • User testing: The drafts of the health information are subjected to at least one user testing by those affected.
General information can be found on our website under the point " Bringing the view of the affected person ".
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And:

"When and how are external experts involved?"

The IQWiG working during the preparation of the report and health information with medical experts with special expertise in ME / CFS together. The award notice was published under "Current commenting procedures and tenders" .

Other professionals will have the opportunity to comment during the public hearings on the report plan and preliminary report .

General information can be found on our website under the point “ Contributing expertise ”.
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https://translate.google.com/transl...www.iqwig.de/sich-einbringen/stellung-nehmen/

"The (optional) scientific discussion"

If aspects of the written comments remain unclear, the institute can also invite you to a scientific discussion.

Such a discussion

is limited to: respondents whose personal appearance is necessary to clarify questions, institute employees, external experts and external reviewers. The number of representatives per opinion can be limited by the institute. This will be communicated accordingly with the invitation to the discussion.
  • takes place in the form of a discussion.
  • is not public.
  • is recorded: A sound recording and verbal transcript are made by IQWiG . The verbatim transcript is published together with the statements on the institute's website in the “Documentation of the to the [// provisional / Method paper] ”published. A sound recording by the participants is not permitted.
  • is carried out in German. Simultaneous translation into other languages is not possible.
If a discussion is held, the date will be posted on the project website when the released. In the case of the method paper, information is provided on the date of a planned discussion after reviewing the comments. After the deadline for submitting comments has expired, the required participants will usually be invited explicitly in writing 10 working days before the date set by the institute. If the discussion takes place on a cost-benefit assessment according to §35b SGB V , the participants will be invited no later than 5 working days before the appointment.

Travel expenses are usually not reimbursed.

In exceptional cases, representation by a person previously named to the institute is possible.

The discussion is recorded verbatim by a note-taker from the North Rhine-Westphalian state parliament on behalf of IQWiG . The verbatim transcript is contained in a separate document “Documentation of the"Or" Documentation and appreciation of the "Published on the project or method paper website. If we consider it necessary, previously unpublished documents will also be published in full text, which have been attached to a statement as evidence or which have been mentioned during the discussion and subsequently requested and made available by IQWiG upon request .
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So there is some form of participation but not cooperation -- as you pointed out, not comparable e.g. to NICE where patient representatives are on the committee.
 
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Got a reply from the DG. They won't publish their comment prior to the publication by the IQWiG but sent me some hints on their main points. That's very helpful and much appreciated.

I will need to focus now on putting a comment together. So apologies if I won't provide further information about the DG's comment.

Details on the process and how people can get involved can be found here:

https://translate.google.com/translate?sl=auto&tl=en&u=https://www.iqwig.de/faq-zum-mecfs-projekt/

orginal page: https://www.iqwig.de/projekte/n21-01.html
 
The plan doesn't mention an assessment or consideration of the quality of outcome measures for ME/CFS (like for example SF-36 or the Chalder fatigue scale). So if someone submits a comment they can mention that, if they want.

The cochrane handbook chapter on patient reported outcomes could be cited:

Johnston BC, Patrick DL, Devji T, Maxwell LJ, Bingham III CO, Beaton D, Boers M, Briel M, Busse JW, Carrasco-Labra A, Christensen R, da Costa BR, El Dib R, Lyddiatt A, Ostelo RW, Shea B, Singh J, Terwee CB, Williamson PR, Gagnier JJ, Tugwell P, Guyatt GH. Chapter 18: Patient-reported outcomes. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.2 (updated February 2021). Cochrane, 2021. Available from www.training.cochrane.org/handbook.
 
It’s quite a challenge that the comment has to be in German and the discussion here has to be in English – but I’ll try. Text in English has been automatically translated by deepl (reduced structure) or google translate (table of contents).

The report plan is about the scope (topics) of the knowledge that will be reviewed and how that will be done.

Here’s the reduced structure of the main part to which I’ll add some of my thoughts and references I plan to use in the following posts.

More specific comments and questions will follow after that.

The detailed structure is attached as a PDF document.


4. Methods

4.1 Current state of knowledge .

First, the current state of knowledge on ME/CFS is systematically reviewed. This includes a presentation of results on the following topics:

a) Complaints / symptoms (including description of relevant symptoms, severity and burden of the disease, description of the course of the disease, consequences of the disease, etc.).


b) Etiology / causes (including description of underlying pathophysiology)


c) Epidemiological and care-related aspects (including information on the number of individuals belonging to the target population, including information on incidence of the target disease, density of care, etc.)


d) Diagnostics (presentation of current diagnostic criteria, e.g., according to published
guidelines)


4.2 Evidence mapping of treatment options relevant to care.

Second, the report includes an evidence mapping (i.e., an overview of the data) of treatment options relevant to the care of patients with ME/CFS with respect to selected patient-relevant outcomes.


4.3 Benefit assessment

Third, based on the evidence mapping, an additional benefit assessment will be conducted for 2 specific therapy options for patients with ME/CFS with regard to selected patient-relevant outcomes.


4.4. Health information

Fourth, a health information document will be prepared that conveys the relevant knowledge in an understandable way. The health information will be tested in user trials and will be published in the report as well as on the website www.gesundheitsinformation.de.


Translated with www.DeepL.com/Translator (free version)
 

Attachments

4. Methods

4.1 Current state of knowledge .

First, the current state of knowledge on ME/CFS is systematically reviewed. This includes a presentation of results on the following topics:

a) Complaints / symptoms (including description of relevant symptoms, severity and burden of the disease, description of the course of the disease, consequences of the disease, etc.).

b) Etiology / causes (including description of underlying pathophysiology)

c) Epidemiological and care-related aspects (including information on the number of individuals belonging to the target population, including information on incidence of the target disease, density of care, etc.)

d) Diagnostics (presentation of current diagnostic criteria, e.g., according to published
guidelines)

I haven’t understood yet in which way this section on the current state of knowledge will also include clinical trials and systematic reviews of interventions. Treatments will be dealt with in the following two sections.

But it seems the evidence on the etiology, population, symptoms etc generated in clinical trials and other studies primarily investigating treatments will also be included in the review of evidence for this section:


4.1.1.3 Study types

Systematic reviews of randomised controlled trials (RCTs) and diagnostic quality
studies, evidence-based guidelines, health technology assessment (HTA)
reports and overviews of reviews are included as the authoritative basis for the systematic
review of the current state of knowledge (see Section 9.2 of General Methods 6.0 [11]).

In justified individual cases, if necessary, further documents such as
Primary studies or systematic reviews of observational studies included (see section 4.1.2.2).


And that’s how the studies will be evaluated:

4.1.3 Information evaluation and synthesis

Each included source is subjected to a quality assessment according to the study type. For example, in the case of systematic reviews, HTA reports, overviews of reviews, and evidence-based guidelines, this is done using selected items of the Oxman and Guyatt index. Among other things, the quality of information procurement and study selection are assessed.

Any opinion on this section would be highly appreciated: I won’t be able to check if the Oxman and Guyatt Index is fit for the purpose.


Points for 4.1 that I will address:

– Symptoms: Fatigue isn’t specified; difficulty to define PEM isn’t mentioned.
References:
  • Wilshire, C.E., McPhee, G., and the Science for ME CFQ working group (2018), Submission to the public review on common data elements for ME/CFS: Problems with the Chalder Fatigue Questionnaire, https://www.s4me.info/docs/CFQ-Critique-S4me.pdf
  • Submission to the public review on Common Data Elements for ME/CFS: Concerns with the proposed measure of post-exertional malaise (citation)
– Diagnostic criteria of patient population that will be included are vague: “The patient must have a history of ME/CFS, as defined by the Canadian Consensus Criteria” [12], or other information that suggests the presence of a condition that can be classified as ME/CFS.

Edit: Language in paragraph 4.13.
 
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4.2 Evidence mapping of treatment options relevant to care.

Second, the report includes an evidence mapping (i.e., an overview of the data) of treatment options relevant to the care of patients with ME/CFS with respect to selected patient-relevant outcomes.

– Patient population: ME/CFS diagnosis required for at least 80% of the population. Is that sufficient?

If I understood correctly what they mean by evidence mapping is to include only clinical trials, studies and reviews that fulfill some basic quality criteria. Only treatments that have been investigated according to these criteria will be assessed in detail.

So a detailed assessment of the evidence will be done in a second step.

What’s strange here is that they limited the number of treatments eligible for that next step to two.

What might be good is that they say the next step will be only done if there is sufficient quality of evidence for any treatment.

References:
  • Michiel Tack, David M. Tuller & Caroline Struthers (2020) Bias caused by reliance on patient-reported outcome measures in non-blinded randomized trials: an in-depth look at exercise therapy for chronic fatigue syndrome, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2020.1848262
 
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Joh said:
They are back now! Apparently a glitch. I was worried because of the comments for the IQWiG report.
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OK, I deleted my post on the NICE thread.

A pragmatic question: In the comment form it says that for all references we use that aren't already included in the report plan, we need to provide the full texts.

  1. Die Volltexte der in der Stellungnahme zitierten Literatur, die von direkter Relevanz für die Bewertung sind und nicht bereits im zur Anhörung gestellten Dokument zitiert wurden, müssen eingereicht werden.
That's quite a hurdle. Do they really mean that we need to include the PDFs of all references or will the URL to the full texts be OK if they are free access?

And as that's quite an extra hurdle for paywalled papers: Will they accept authors' original manuscripts from Research gate instead? Or / and downloads from sci-hub? :cool:
 
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MSEsperanza said:
OK, I deleted my post on the NICE thread.

A pragmatic question: In the comment form it says that for all references we use that aren't already included in the report plan, we need to provide the full texts.

  1. Die Volltexte der in der Stellungnahme zitierten Literatur, die von direkter Relevanz für die Bewertung sind und nicht bereits im zur Anhörung gestellten Dokument zitiert wurden, müssen eingereicht werden.
That's quite a hurdle. Do they really mean that we need to include the PDFs of all references or will the URL to the full texts be OK if they are free access?

And as that's quite an extra hurdle for paywalled papers: Will they accept authors' original manuscripts from Research gate instead? Or / and downloads from sci-hub? :cool:
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I'm not sure what they mean by that, but if you download a pdf from sci-hub it's the same as the pdf you would've gotten from the journal website, so they can't tell you got it from sci-hub
 
"A preliminary report for the German guideline on #MECFS recommends graded exercise, despite the fact that @NICEComms found these therapies to be ineffective and that thousands of patients have reported being harmed. A one month consultation period is now open."

"The report can be read here (in German): iqwig.de/download/n21-0…"

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Link to Google translated version of the IQWIG announcement, https://www-iqwig-de.translate.goog...=de&_x_tr_tl=en&_x_tr_hl=en-US&_x_tr_pto=wapp

Myalgic encephalomyelitis/chronic fatigue syndrome: preliminary report published

IQWiG is asking for comments by November 11 - and in view of its interim results on the possible benefit of two therapies, it expects a lively response.

......

Indications of the benefit of two therapies - for some of those affected

The evidence mapping of the therapy options showed that there are only a few studies in which the current diagnostic criteria were used and which are suitable for a benefit assessment: The Institute only considered it sensible to carry out a more detailed benefit assessment for two interventions and used three studies for this purpose . Due to the shortcomings of these studies, such as vague descriptions of the intervention or incorrectly recorded endpoints, all conclusions on this basis are uncertain. On the one hand, cognitive behavioral therapy and, on the other hand, what is known as Graded Exercise Therapy ( GET ) were compared with standard care. Under Graded Exercise Therapy or activation therapy is a gradual increase in physical activity, starting from an individual starting value.

From the studies, IQWiG derived a hint of a short- to medium-term benefit for cognitive behavioral therapy , which is expressed, for example, in the endpoints fatigue, social participation or feeling ill after exertion. In the longer term, neither an advantage nor a disadvantage can be identified.

There are statistically significant but very small advantages for Graded Exercise Therapy compared to standard therapy in several patient-relevant endpoints. The advantages are clearer in the two endpoints general symptoms and feeling sick after exertion. Overall, there is a hint of a benefit of GET compared to standard treatment in both the short and medium term. In the longer term, neither an advantage nor a disadvantage can be identified.

“We are aware that GET in particular has a miserable reputation in large parts of the self-help scene. There are reports of a significant deterioration in the patient's condition in the course of activation therapy carried out according to schedule, for example as part of rehabilitation," says Jürgen Windeler, director of the institute. “Therefore, I would like to further classify this result here. First, only mildly to moderately ill people took part in the studies. The extent to which their results can be transferred to seriously ill patients is questionable. Second, the bad reputation of the GET may also have been fueled by inappropriate implementation, for example where individual baseline levels were not well assessed.”
 
Thanks for posting @Andy.

Currently too unwell and too much other existential stuff on my agenda so not sure when I will be able to post some translated snippets of the pre-report.

Also too unwell to word a succinct summary of the good things and bad things.

So just leave this here:

For the assessment of treatment recommendations, they only included three 'RCT's:

1) PACE

2) Janse 2018 = Janse A, Worm-Smeitink M, Bleijenberg G, Donders R, Knoop H. Efficacy of web-based cognitive-behavioural therapy for chronic fatigue syndrome: randomised controlled trial. Br J Psychiatry. 2018 Feb;212(2):112-118. doi: 10.1192/bjp.2017.22. PMID: 29436329.

3) GETSET

They say that only these studies fulfilled their criteria, among other reasons because at least 80% of the participants in each of these trials had PEM.


Edited to remove muddled part.
 
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The IQWIG draft for the "Gesundheitsinformationen" (advice for patients), they repeatedly quote the current NICE guidelines especially for support of severely affected; they name the use of mobility aids, application for disability assesment/ disability payments etc.

So that's a good thing.

There are some not-so-good-things, especially it's pretty clear from their response to the comments, that they're not too impressed by S4ME peoples' critique of the only-subjective-primary-outcomes-in-unblinded-trials thing.
 
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