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

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/

And:

https://translate.google.com/transl...www.iqwig.de/sich-einbringen/stellung-nehmen/

"The (optional) scientific discussion"

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.

 

It would be great but my personal opinion is that I can't see us having the capacity to take anything else on in the near future.

 

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)

 

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.

 

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

• Edwards, Jonathan CW (2020), The difficulties of conducting intervention trials for the treatment of myalgic encephalomyelitis/chronic fatigue syndrome: Expert testimony presented to the NICE guideline committee, 06.09.2019, https://www.nice.org.uk/guidance/GID-NG10091/documents/supporting-documentation-3

 

I just noticed that all of the NICE links are gone. Does anybody know more?

 

They are back now! Apparently a glitch. I was worried because of the comments for the IQWiG report.

 

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?

 

I find it strange that the IQWiG report plan only links to the old NICE guidelines not to the draft.

 

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

 

Thanks. Anyway, a lot of extra work and extra bytes.

 

As I don't feel comfortable to post all questions in the fully public area, I now will post specific asks for help and feedback on single draft paragraphs of my comment in the advocacy planning subforum (members only).

 

Hi MSEsperanza I haven't looked at your query but if you don't get an answer via Science 4 ME then I/Michiel can post here - #MEAction European Union (EU) - there are a lot of members from Germany.

@Michiel Tack

 

Thanks for your offer @FMMM1 .

Luckily, I got very helpful answers from S4ME members.

Many thanks to everyone.

 

"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…"

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.

 

"In the longer term, neither an advantage nor a disadvantage can be seen."

Then IQWiG schouldn't recommend CBT/GET. That makes no sense even if you don't take the potential side effects seriously.

 

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.