In mijn beleving gaat dit onderzoeksprogramma van ZonMw niet om de patiënten.
In mijn beleving heeft ZonMw er alles aan gedaan om patiëntvertegenwoordigers de mond te snoeren.
In mijn beleving is ZonMw er alles aan gelegen om niet de inhoudelijke discussie te voeren over het gegeven dat de aanvragen van ME/CFS Lines en de bijbehorende deelonderzoeken niet aan de programmatekst en de subsidieoproep voldoen.
In mijn beleving haalt ZonMw alles uit de kast om klachten en bezwaren van patiënten en patiëntvertegenwoordigers niet te behandelen.
Voorbeeld 1. Hoe gaat ZonMw om met mijn klacht?
Op 4 oktober 2022 diende ik een klacht in over het gegeven dat ME/CFS Lines niet voldoet aan de eisen die zijn gesteld in de programmatekst en dat ZonMw deze aanvragen onterecht heeft voorgelegd aan de referenten en aan de programmacommissie.
Op 4 november kreeg ik een informeel e-mail bericht van ZonMw “om onnodige juridisering te voorkomen” dat mijn klacht niet-ontvankelijk was. Ik heb een brief gestuurd dat ik wilde dat mijn klacht formeel zou worden behandeld.
Op 12 december, de molens draaien niet zo snel bij ZonMw, stuurde mevrouw Timmerhuis de formele reactie. Mijn klacht was geen klacht zoals bedoeld of passend in de klachtenregeling. Hoofdargument is dat ik geen primair belanghebbende ben en “omdat er in de visie van ZonMw nog steeds geen sprake is van een bejegeningsklacht”.
De Nationale Ombudsman die ik inschakelde, was het niet eens met de zienswijze van ZonMw:
“Het hoofdargument van ZonMw dat u geen primair belanghebbende bent bij de aangelegenheid waarop uw klacht ziet volgen wij niet, omdat een ieder op grond van de Awb een klacht mag indienen. Dat geldt ook voor het argument van ZonMw dat geen sprake zou zijn van een onbehoorlijke gedraging jegens u. Een klacht kan namelijk ook betrekking hebben op een gedraging jegens een ander. Ik zal ZonMw, gelet op dit advies, vragen het ingenomen standpunt ten aanzien van uw klacht beter te motiveren of uw klacht alsnog te behandelen.”
Op 3 mei heeft de ombudsman contact gehad met ZonMw. Zij zouden het oppakken volgens de ombudsman. Intussen is het 22 mei en heb ik nog steeds niets hierover vernomen van ZonMw.
Voorbeeld 2. Hoe gaat ZonMw om met mijn bezwaar?
Op 10 maart 2023 diende ik bezwaar in tegen het besluit om ME/CFS Lines en de bijbehorende deelprojecten te subsidiëren. Belangrijkste reden voor het bezwaar is dat ME/CFS Lines niet voldoet aan de eisen die zijn gesteld in de programmatekst die een voorwaarde vormen voor subsidietoekenning. Daarnaast zijn er nog andere argumenten die ik hier niet verder zal uitwerken.
Eerst ontving ik op 21 april een bericht dat de beslissing op het bezwaar met maximaal 6 weken wegens vakantie werd verdaagd voor ten hoogste 6 weken. Met een telefoontje op vrijdag 12 mei om 17.38 uur “gezien mijn speciale relatie met ZonMw leek hem dat op zijn plaats” kondigde het clusterhoofd van ZonMw aan dat ook mijn bezwaar niet-ontvankelijk zou worden verklaard omdat ik geen direct belanghebbende ben volgens ZonMw. Op 17 mei ontving ik de brief per e-mail.
“Uw bezwaarschrift wordt niet in behandeling genomen, aangezien u naar mijn oordeel geen belanghebbende bent bij de besluiten waartegen uw bezwaar zich richt. Het bezwaar verklaar ik daarmee (kennelijk) niet-ontvankelijk.”
De brief is als bijlage toegevoegd onderaan deze pagina.
Voorbeeld 3. Hoe gaat ZonMw om met andere bezwaren?
Er zijn naar verluidt nogal wat patiënten die zelf een bezwaar hebben ingediend tegen de onterechte subsidietoekenning door ZonMw aan ME/CFS Lines.
Een aantal van hen heeft intussen bericht van ZonMw ontvangen dat ze hun bezwaar te laat zouden hebben ingediend omdat ZonMw reeds op 22 februari j.l. de subsidie aan ME/CFS Lines heeft toegekend en de deadline voor bezwaar daarop volgens ZonMw dus op 5 april 2023 was verlopen.
“De termijn voor het indienen van een bezwaarschrift bedraagt – op grond van artikel 6:7 van de Algemene wet bestuursrecht – zes weken. Deze termijn vangt aan met ingang van de dag na de datum waarop bovengenoemde besluiten zijn verzonden. Dat betekent in dit geval dat de bezwaartermijn duurde tot 6 weken na 23 februari 2023, waardoor uw bezwaarschrift buiten de wettelijk voorgeschreven bezwaartermijn is ingediend. Wij kunnen uw bezwaarschrift daarom alleen in behandeling nemen indien redelijkerwijs niet kan worden geoordeeld dat u in verzuim bent geweest.
Van een dergelijk geval is sprake indien zich ernstige omstandigheden hebben voorgedaan. In uw bezwaarschrift maakt u van dergelijke omstandigheden geen melding.”
De toekenning werd echter pas op 24 april 2023 openbaar gemaakt, waardoor ZonMw zelf het onmogelijk maakte om voor 5 april bezwaar in te dienen. Bezwaarmakers moeten dus argumenten aanleveren op basis waarvan “redelijkerwijs niet kan worden geoordeeld dat u in verzuim bent geweest”.
Op 9 maart 2023 stuurde ik een Woo-verzoek naar ZonMw. Ik vroeg daarin om een afschrift van de schriftelijke besluiten van het bestuur aangaande de volgende aanvragen:
ME/CFS Lines – A multidisciplinary consortium and biobank for unravelling ME/CFS aetiology in Lifelines ingediend door professor dr. J. Rosmalen.
Post-exertional malaise: a starting point to investigate and understand ME/CFS ingediend door dr. C. Zuidewind.
Antibody repertoires against microbiota as biomarkers for ME/CFS (CFSmicroAbs) Ingediend door professor dr. S. Zhernakova.
A role of microbiome in the pathogenesis of ME/CFS: a population-based study ingediend door A. Kurilshchikov.
Identifying causal biological mechanisms in ME/CFS by a functional genetic approach ingediend door dr. C. Boer
De zesde aanvraag zal ik hier niet noemen omdat die niet is toegekend.
Op 4 mei ontving ik de reactie van ZonMw. Is dat niet erg laat? Jazeker! Ik ben intussen gewend dat ZonMw tussentijds de termijn oprekt en pas op de allerlaatste dag het antwoord stuurt.
De informatie die ik ontving omvat heel veel pagina’s en is totaal nietszeggend. U vindt het document onderaan deze tekst. Alle relevante informatie is door ZonMw zwart gemaakt, waarbij mevrouw Timmerhuis, de algemeen directeur van ZonMw, zich beroept op de uitzonderingsbepalingen in de WOO.
De Woo is in 2022 ingevoerd als opvolger van de Wet openbaarheid van bestuur (Wob) en regelt het recht van burgers op informatie van de overheid. Zo krijgt iedereen meer inzicht in het handelen van de overheid. Het doel van de Wet is dus dat de overheid transparanter is.
Dat lijkt ZonMw niet helemaal goed begrepen te hebben.
Toen we ongeveer twee jaar geleden een verzoek indienden om openbaarmaking van de gegevens van het ReCOVer onderzoek van professor Knoop ontvingen we wel detailinformatie over kwaliteit en relevantie en andere zaken. https://me-cvsvereniging.nl/wp-content/uploads/2022/01/Ontvangen-stukken-obv-WOB-verzoek.pdf. Waarom nu ineens veel meer informatie mag worden achtergehouden dan ten tijde van de Wob is mij niet duidelijk.
Hoe zorgvuldig is ZonMw met mijn verzoek omgegaan?
Mijn indruk is dat het niet erg zorgvuldig is gebeurd. Het is onthutsend om te zien wat er nu allemaal zwartgelakt is in de stukken die ZonMw stuurde. In feite heeft ZonMw niets anders gestuurd dan lege formats met een heleboel tekst eromheen Zelfs het oordeel over relevantie en kwaliteit is onzichtbaar gemaakt en dat terwijl dat oordeel open en bloot vermeld staat op de website van ZonMw bij de beantwoording van vragen over de toekenningen: Het ME/CFS Lines consortium voldoet aan de eisen uit het onderzoeksprogramma. Het consortium richt zich op biomedisch onderzoek en de programmacommissie geeft in haar oordeel aan dat het voorstel van hoge kwaliteit en relevant is.
Het maakt in alles de indruk dat iemand bij ZonMw de rigoureuze opdracht heeft gekregen alle inhoud te verbergen en dat er geen zorgvuldige afweging heeft plaatsgevonden.
Wat opvalt bij ME/CFS Lines is dat de programmacommissie 10 verzoeken heeft bij de uitvoering van het project. Dat is niet weinig voor een project dat aan alle eisen voldoet, van hoge kwaliteit en relevant is. Wat mogen wij niet zien? ZonMw maakt het onmogelijk om te controleren of het wel klopt dat ME/CFS Lines aan alle eisen voldoet. Dat doet een forse aanslag op het vertrouwen, maar dat had ik al verloren zoals ik op 13 april meldde.
Het is dan ook de vraag in hoeverre de juristen van ZonMw correct hebben geadviseerd over het verbergen van informatie. Bij het niet-ontvankelijk verklaren van mijn klacht in oktober 2022 die ook betrekking had op deze onderzoeksaanvragen heeft ZonMw volgens de Nationale Ombudsman onvoldoende en ondeugdelijke argumenten aangevoerd. Die klacht moet nog steeds afgehandeld worden. Ook weer lange termijn werk dus.
Op 10 maart 2023 heb ik een bezwaarschrift ingediend tegen deze subsidietoekenningen. Kunt u al met mij voorspellen wat daarvan te verwachten is?
Ik ben Céline Corsius, 31 jaar, 21 jaar ziek, laatste 6 jaar in bed.
Ik heb ME en ME-patiënten worden schandelijk behandeld. Een aantal wetenschappers heeft ervoor gezorgd dat hun nooit bewezen theorie, dat patiënten zelf hun ziekte in stand houden, kritiekloos wordt aangenomen. De patiënten zijn volgens hen te veel bezig met fysieke klachten en ze bewegen te weinig. Ze zouden ‘bewegingsangst’ hebben.
Patiënten laten volgens deze wetenschappers geen “adequaat herstelgedrag’ zien en moeten daarom de speciale cognitieve gedragstherapie met opbouwende fysieke training doen. In werkelijkheid is dat helemaal niet goed voor ze. Bij ME is juist sprake van inspanningsintolerantie en achteruitgang door te veel inspanning.
Dit weet ik allemaal pas recent. Jarenlang heb ik aangehoord en aangenomen dat ik gewoon net iets beter mijn best moet doen. Ik ben opgenomen geweest in een revalidatiecentrum. Terwijl ik bezig was om mijn targets te halen, ging het juist steeds slechter met mij. Ik vertrouwde de signalen van mijn eigen lijf niet meer en ik raakte psychisch steeds verder in de knel. Jarenlang kreeg ik psychologische behandelingen die uiteindelijk allemaal hetzelfde uitgangspunt hadden: het ligt aan jezelf. Kom eens in beweging!
Ik was bang om met de behandelingen te stoppen. Ik dacht dat ik het niet alleen kon. Maar ik kon het wel. Toen ik eenmaal stopte met de behandelingen ging ik me beetje bij beetje mentaal beter voelen. Nu heb ik zoveel geestkracht dat het me zelf soms verbaast. Al die jaren dat ik gebukt ging onder het BPS[1] regime waren vreselijk. Dat overkomt me niet meer.
Maar het heeft me dus wel kapot gemaakt.
Daar ben ik BOOS over.
En ik ben BOOS dat er nog steeds niks veranderd is.
Ik ben BOOS omdat de bedriegers die dit verkeerde beeld van de ziekte hebben gecreëerd nog steeds hun tentakels overal hebben: in de zorg, bij zorgverzekeringen, in de academische wereld, bij de uitkeringsinstanties, bij de overheid en door de overheid opgerichte instanties. Daardoor is er voor mijn ziekte nog steeds geen passende behandeling.
Céline Corsius
[1] BPS = biopsychosociaal waarbij bio terzijde wordt geschoven.
Op donderdag 12 mei wordt het brugklasgebouw van de Katholieke Scholengemeenschap Etten-Leur weer in de blauwe spotlights gezet. Dat is ter gelegenheid van wereld ME dag. Al tientallen jaren wordt op deze dag wereldwijd aandacht gevraagd voor de ziekte ME. Over de hele wereld worden opvallende gebouwen blauw verlicht. Sinds 2019 doet ook de KSE daaraan mee.
ME (Myalgische Encephalomyelitis) is een chronische lichamelijke ziekte met een complex klachtenpatroon. Patiënten worden ernstig beperkt in hun functioneren. De Gezondheidsraad heeft in 2018 een advies over de ziekte uitgebracht onder de noemer ME/cvs. De ziekte wordt ook wel chronisch vermoeidheidssyndroom genoemd (cvs). Dat is een misleidende term die geen recht doet aan de ernst van de ziekte en de aard van de klachten. Het is het onvermogen om een inspanning te leveren en rust brengt geen verbetering. Er zijn bijkomende symptomen, bijvoorbeeld problemen met de spijsvertering, pijnlijke klieren, een verhoogde gevoeligheid voor prikkels zoals licht, geluid en geur, orthostatische intolerantie (je voelt je naar als je staat of rechtop zit)
Een belangrijk kenmerk is dat de symptomen toenemen na een geringe inspanning. Dat kan na een lichamelijke activiteit zijn, maar ook een cognitieve, emotionele of sociale activiteit kan leiden tot een toename. Dat verschijnsel heet PEM (post-exertionele malaise).
De ziekte treedt vaak op na het doormaken van een virusinfectie. Naar schatting zijn er in Nederland ongeveer 37.000 patiënten die lijden aan ME.
Tot voor kort werd in Nederland en in het Verenigd Koninkrijk cognitieve gedragstherapie voor cvs in combinatie met graduele opbouw van fysieke activiteit (GET, graded exercise therapy) als behandeling aanbevolen. Intussen is gebleken dat die behandeling, waarbij je niet luistert naar de signalen van je lichaam, in veel gevallen tot verergering van de ziekte leidt.
Eind 2021 is in het Verenigd Koninkrijk een vernieuwde NICE richtlijn uitgebracht die deze behandeling niet langer adviseert en iedere vorm van fysieke opbouw volgens een vast schema zelfs afraadt.
In december 2021 heeft ZonMw een onderzoeksprogramma opgestart naar de biomedische verschijnselen van de ziekte.
Sinds de coronapandemie zijn er veel mensen die na een besmetting met het coronavirus langdurige klachten houden die sterk lijken op de symptomen van ME. De verwachting is dat ook het onderzoek naar langdurige COVID-klachten zal bijdragen aan meer kennis over ME.
In July 2020, ZonMw awarded a grant of €308,000 to Professor Knoop of the Dutch Knowledge Center for Chronic Fatigue (NKCV) for research into the efficacy of iCBT (cognitive behavioral therapy via the Internet) in patients with longCOVID (ReCOVer). This research proposal has been qualified as “very relevant” and “of very good quality”. As representatives of the Group ME Den Haag, the Steungroep ME en Arbeidsongeschiktheid and the ME/cvs Vereniging participating in the ZonMW ME/CFS biomedical research agenda steering committee, we had serious questions about this decision.
After discussions with ME/CFS program managers and the program managers of ZonMw’s Covid-19 program, we submitted a request based on the Dutch legislation (Wet Openbaarheid Bestuur), similar to an FOI request, to obtain more clarity about the process that led to awarding a €308.000 grant to the ReCOVer study). At the same time, our goal was to prevent that in the future grants will be awarded to a treatment that is not based on scientific knowledge about the nature and cause of the disease, but on the assumption that the patient maintains his own fatigue through unhelpful thoughts and wrong behaviour. The treatment in the ReCover study has the same principles as ‘CBT for CFS’. The British NICE has determined that the quality of the scientific evidence for this treatment is low to very low. It is also clear from Dutch and foreign patient surveys that this form of CBT does not help the majority of patients and leads to deterioration in a considerable number of patients. We aim to prevent this for longCOVID patients too.
In retrospect we provide an overview of the steps taken. A number of questions have remained unclear, such as:
Who were the 3 reviewers,
What is their background and
How did the program committee ultimately come to the judgement “very good quality” and “very relevant”.
Looking back
The ReCOVer study started in October 2020, led by professor J.A. Knoop of the Knowledge Center for Chronic Fatigue in The Netherlands (NKCV). The research protocol can be found here . This study investigates whether early treatment of longCOVID patients using cognitive behavioral therapy via the Internet (or possibly live) can lead to a significantly lower fatigue score. As the registration of the study describes: “This intervention is based on the cognitive-behavioural model of fatigue, stating that disease and/or its treatment initially triggers fatigue while cognitive-behavioural variables perpetuate fatigue”.
The research is subsidized by ZonMw. The processing of the subsidy application took place in the period May-July of the year 2020
We were surprised that ZonMw is subsidizing this research. After all, we know that cognitive behavioral therapy (CBT), based on the assumption that the complaints are maintained by thoughts and behaviour, usually does not help in ME patients and can even lead to damage. This has recently been reaffirmed in the new UK NICE guideline for ME/CFS. The recommendation to offer cognitive behavioral therapy as a curative treatment was abandoned because the evidence for the effectiveness of that treatment is low to mostly very low. Part of this specific type of CBT that is based on the cognitive-behavioral model of fatigue is a time-contingent build-up of activities. Time contingent means building up activity without taking into account any increase in complaints. This is called Graded Activity or Graded Exercise Therapy (GET). The NICE guidelines state that GET should not be used in ME/CFS and warn against any form of treatment that includes this time-contingent activity build-up. In addition to a lack of evidence, the experience that this treatment can lead to health damage is also an important consideration.
On behalf of the Groep ME Den Haag, de Steungroep ME en Arbeidsongeschiktheid en de ME/cvs Vereniging, we warn against the possible consequences of such treatment in patients with a post-viral syndrome after a COVID-19 infection. We are referring to the CBT/GET treatment that can potentially lead to serious worsening of complaints. Some of those patients have to deal with a disease that resembles ME.
Our questions to the program managers
We asked the program managers for biomedical research ME/CFS and Covid-19 at ZonMw how it could have been possible that the study proposal has been judged to be highly relevant and of very good quality, while it is known that an open trial like this, in which the researchers and those studied know which treatment is used, with only subjective outcome measures is known for a very high riskof bias and that therefore objective outcomes must also be measured. Knowing what treatment is being given to a patient can influence their response to treatment. A patient who knows that he is receiving a new drug that will be evaluated may have an a priori positive attitude towards this treatment and thus will report a better therapeutic response, especially when it comes to more subjective outcome measures. Patients tend to be nice to their therapist and therefore describe the results of the treatment more positively (‘pleasing the doctor’). And if patients are taught during treatment that they should not focus on their fatigue and should not think and talk about it, they will probably give their fatigue a lower score in a questionnaire, without anything actually having improved. Patients entering the control group may feel disadvantaged, which can affect their scores.
We also asked whether the study design took into account the risk of damage as a result of the treatment and, if so, how this will be investigated. We have been in contact with ZonMw about this subject by telephone and e-mail. Our letter of 3 September 2020 to the ZonMw program manager below reflects the core of the discussion.
Letter to ZonMw programm manager
Dear Mrs (…)
Thank you for the explanation in response to our questions about the grant awarded to Professor Knoop for ReCOVer, Can cognitive behavioral therapy via the internet prevent fatigue symptoms of COVID-19 patients from becoming chronic? A controlled and randomized study
project number: 10430012010025.
First of all, a response to what you wrote:
“We know and respect your views on Cognitive Behavioral Therapy (CBT) as an intervention in the treatment of chronic fatigue in ME/CFS. ZonMw has consistently shown this.”
It is not about ‘opinions about CBT’, it is about scientifically proven facts and systematically inventoried experiences of many patients at home and abroad. It is to ZonMw’s credit that it shows respect for the factual scientific findings; it’s not about accommodating us or doing us a favor. The ZonMw project of the ME/CFS research agenda arises from the recommendations from the GR (Dutch Health Council) report of March 2018 and the order of parliament and the minister, not from what we would like to see.
‘But that does not mean that ZonMw must reject all research questions relating to CBT from now on’.
That is a rather short-sighted view of what we stand for. It is a widespread misconception that ME patients are basically dismissive of CBT (and GET) as an intervention. ME patients are opposed to any intervention that has been shown to worsen symptoms and complaints, and ZonMw should do the same. It seems to us that would be a moral obligation. ME patients also reject the specific CBT treatment for CFS according to the protocol of Prof. Knoop and the NKCV. This is based on an incorrect, refuted hypothesis about the nature of the disease. The treament contains a structured build-up of activities in which the increase in complaints must be ignored. In addition, ‘CBT for CFS’ is recommended as a curative treatment, while the majority of patients do not improve or even worsen (we have included an appendix reviewing the methodological quality of the studies on CBT for CFS and its bias).
ME patients are aware of the fact that CBT in general (i.e. not according to the procotol ‘CBT for CFS’) can be supportive to some in coping with a chronic illness. At the same time, your sentence implies that ZonMw does indeed have the authority to reject an application on medical-scientific grounds. Without being sufficiently aware of the scientific controversy surrounding the research into ‘CBT in CFS’ and the patient experiences with this treatment, Prof. Knoop’s proposal cannot be properly assessed. As far as we know, it is ZonMW’s responsibility and authority to engage the appropriate reviewers.
More and more publications show the analogy between a post-viral syndrome after COVID-19 and ME. No research has yet been conducted into PEM/PENE in a post-viral syndrome after COVID-19. We would like to warn against the consequences of experiments in patients who suffer from a post-viral syndrome after COVID-19 and who may suffer from aggravation of complaints to such an extent that a very serious disease can develop. Thus, experiments are underway with possible harmful consequences known in advance. The question is whether this has been taken into account in the research design and, if so, how this will be followed up.
We would like to receive the text of the relevant grant application and the research protocol, how was it handled procedurally.
Which committee handled the application?
How was the committee formed?
How is it determined that the committee members do not have a COI?
Who performed the peer review?
What is the committee’s positive opinion based on?
What is the subsidy amount?
We assume that all this has been done in an open and transparent manner.
Thanks in advance,
On behalf of Groep ME Den Haag, Rob Wijbenga
On behalf of the Steungroep ME en Arbeidsongeschiktheid, Ynske Jansen
On behalf of the ME/cvs Vereniging, Lou Corsius
End of letter
WOB request
According to the Dutch legislation (WOB), we then requested data regarding the processing of the subsidy application. Our aim was to draw attention to the problems with this kind of treatment in the future and to prevent patients from undergoing an ineffective and potentially harmful treatment.
We have received data in response to the WOB request. These data are public and have been added as Appendix 1. However, a number of questions we asked were not clarified, not on paper and not during the discussion we had with 3 program managers of the MEC/CFS research program and the COVID-19 program, the department head and a lawyer, all from ZonMw. This concerns in particular the question how it has been possible that the program committee has given this positive assessment, who were the reviewers and what is their background? Were they aware of the developments regarding CBT/GET in ME/CFS and QFS?
ZonMw does not disclose a part of the information, and that includes the names of the reviewers. Because we consider this information to be of great importance, we have submitted an objection (see appendix 2.). The hearing of the objections committee took place in June 2021, in which Professor Knoop also participated.
We wanted to avoid turning our request and our objection into a legal matter because we are concerned about the scientific content. That is why we agreed during that session that we would have another meeting with the program managers at ZonMw ànd that we would have a meeting with Professor Knoop. The conversation with Professor Knoop was to aim at the possible damage to some of the patients as a result of the treatment and the way in which he monitors the possible deterioration in his research.
Follow-up to the hearing
On 20 September 2021, as a follow-up to the hearing, we had a meeting with three program managers at ZonMw. As a result of that meeting, we received the following email sent by them on September 24:
“Dear Arthur, Lou and Ynske
First of all, thank you very much for the meeting we had last week (Monday 20 September). Your concern about the possible consequences of applying CBT and especially GET is clear to us. Although we cannot and will not exclude applications with this subject from handling within ZonMw, we have promised that we will inform colleagues from adjacent programs such as COVID-19, Lyme and Q fever and infectious disease control about your concerns and the underlying reasons. You have indicated that you will let us know within two weeks whether you will withdraw the objection.
Thanks again for the pleasant conversation.
Yours faithfully
(name and position)
ZonMw”
We withdrew our objection by letter dated 12 October 2021. In the letter we once again emphasized the substantive arguments.
Withdrawal and explanation
Dear members of the Objections Committee,
Following the digital hearing on 3 June 2021, a meeting has taken place between ZonMw, represented by the ladies … and mr … and on behalf of the objectors A. de Groot and L. Corsius.
We also recently informed Mr Knoop that we accepted his invitation to talk about the ReCOVer study.
Based on the hearing and the meeting with ZonMw, we have decided to withdraw the objection.
The reason for withdrawal lies in the fact that the substantive aspects of the subject matter to us are paramount. We consider it important that ZonMw pays attention to this subject, especially during the handling and weighing of research proposals and during the evaluation of research that has been carried out.
We want to emphasize the following points:
The “CBT for CFS treatment” is based on the assumption that the disease is perpetuated by the perception of the disease. An earlier response from ZonMw that biomedical research into ME/CFS does not mean that ZonMw will never again subsidize a CBT study shows a lack of understanding of the difference between CBT and ‘CBT for CFS’. Employees of ZonMw and assessors of research proposals should be aware of the fact that Cognitive Behavioral Therapy (CBT) for CFS (and for Q fever and longCOVID) is not ordinary CBT. It focuses on a time-contingent building up of activities and pretends to be curative, while that is explicitly not the case for other forms of CBT. ZonMw’s representatives have pledged that they will “inform and notify those involved in the assessments about this subject”.
In our view, the public interest is served by openness. Not only being able to find committee members and assessors (the argument for not disclosing data) is important, but also the quality and objectivity of the assessment is important. It is in the public interest that assessors take responsibility for their judgment. We regret the fact that ZonMw does not provide this openness in this case, and as we understand, it does not in any case.
In addition to the fact that we will also talk to Mr. Knoop, ZonMw will, in accordance to their promises, check during the interim evaluation of the study whether and how the harmful effects of the treatment are reported. We are curious how this will be implemented. We have reported that the way in which adverse effects have been examined in previous studies in ME/CFS provides insufficient insight. This concerns, among other things, the definition of adverse effects, the lack of follow-up of dropouts and the omission of the results of the objective measurements. The measurement in the ReCOVer study using the actometer at T3, the main objective measurement, is not guaranteed. We talked about the importance of objective outcome parameters. This is an essential point given the increased chance of bias in purely subjective measurements in such an open trial. It is important to be able to measure the negative effects. We have agreed with Mr (ZonMw program manager name removed) that we may approach him if we have any questions about the (interim) evaluation of the ReCOVer study.
Finally, we expressed our concern that on the one hand, biomedical research in ME/CFS is being worked on and, on the other hand, a group is being subsidized for a treatment that is again based on the premise that patients no are longer ill as a result of biomedical factors, but because of perpetuating thoughts and behavior.
During the meeting with ZonMw, we once again explained our substantive objections and we appreciate ZonMw’s commitment that the relevant assessors will be informed.
As stated above, this promise has led us to withdraw our objection.
Yours faithfully,
drs. Y. Jansen (drs. Is the title equal to Msc)
mr. A. de Groot (mr. is the title for a lawyer)
drs. L. Corsius
Copy to: ZonMw
Meeting with Professor Knoop
On November 18, 2021 we had a meeting with Professor Knoop. Afterwards we sent him the report below on November 26, in order to correct any factual inaccuracies. We received the following response:
“I don’t have the time for this, would you like to explicitly state that it is your reproduction of the conversation.
gr,
Hans knoop”
On December 2, we presented the draft to Professor Knoop again with a response period of more than six weeks. He rejected this request too.
“I’m sorry, I can’t manage that.
Greeting,
Hans knoop”
Note: We have carefully prepared the report below and we are convinced it is an accurate representation of the discussion.
Report of the conversation with professor Dr. H. Knoop about the risk of deterioration as a result of CBT treatment for longcovid patients.
Date: November 18, 2021
Participants: Prof. dr. H. Knoop, responsible for the ReCOVer research, Clinical psychologist, Professor, Department of Medical Psychology AMC – Academic Medical Center
Drs. Y. Jansen, Support Group ME and Disability
Mr. A. de Groot, lawyer, Group ME The Hague
Drs. L. Corsius, ME/CFS Association
Introduction
This meeting takes place in response to the WOB (“FOI”) procedure in which the three patient organizations have requested information about the assessment and award by ZonMw of the subsidy application for the ReCOVer study. This conversation was planned as a spin off from that procedure.
The patient organizations warn against the possible consequences of the treatment for patients who suffer with a post-viral syndrome after COVID-19 which may lead to a worsening of complaints to such an extent that a very serious healthsituation can develop. The question is whether this has been taken into account in the research design and, if so, how will this be followed up.
Professor. Knoop indicates that there is a clear difference compared to CFS patients; the longcovid patients undergo treatment at a very early stage in contrast to CFS patients who are only treated after 5-6 years. The ReCOVer study is based on the hypothesis that early treatment by means of cognitive behavioral therapy (CBT) according to a specific protocol can prevent chronicity of the complaints.
Questions to Professor Knoop
Professor Knoop’s answers are in italics and begin with (K).
1. The underlying idea for this particular CBT treatment is that thoughts and behavior perpetuate the disease. Part of the treatment protocol is that patients should not focus on their complaints, but should continue with a time-contingent increase of activities regardless of the complaints. This could mean that patients may not report worsening.
(K) That is not worded correctly. We ask patients to shift their focus.
The risk of this treatment is small. Studies into the use of this treatment in other diseases largely demonstrate the efficacy of the treatment and show that there is no increased risk. The Medical Ethics Review Committee (METC) has also established this.
2. Is the treatment protocol available?
(K) The treatment protocol is not available. This has to do with two reasons: 1. The university has Intellectual Property (IP) on the protocol and only the university can and may determine what happens to it and 2. The treatment must first be tested in research. Otherwise, there is a risk that others will adopt the treatment that has not yet been studied because there are so few treatment options available for this patient group. (Mr Knoop does share the view that the results of the protocol and the protocol should be made available through eventual publications, even if research shows that the protocol has shortcomings or turns out to be unusable).
3. What is seen as a deterioration in the study? In what terms are these adverse events described? Are dropouts followed up? Are the results of the actometer also taken into account?
(K) As adverse events, we register hospitalization and visits to a doctor and we have a questionnaire to inventory Postexertional malaise (PEM). The actometer plays no role in this.
4. The study design shows that actometry is not considered a primary or secondary outcome measure. Actometry does take place. What is done with the results of the actometer?
(K) The actometer is only used to divide the patients into an active group and a less active group prior to treatment.
We are seriously concerned about the possibility that you will not recognize deterioration, partly as a result of the fact that you do not use an objective outcome measure such as the actometer or objective data on labor participation.
5. It is known that measuring only subjective outcome parameters in such an open trial has a high risk for bias. Therefore, objective outcome parameters must be used also. How do you handle that?
(K) Why are patient organizations so obsessed with objective measures? Objective measures are subjective too. They depend on how you interpret them.
It is well known that the outcomes on subjective measures such as fatigue are directly influenced by the treatment (we have used the term ‘manipulated’ in the conversation).
(K) So you’re basically saying you don’t trust the outcomes reported by the patients themselves? How does that relate to the fact that you as a patient organization represent these patients while you do not take their answers seriously?
We take patients very seriously. But with regard to your research, we indicate that the treatment is aimed directly at influencing the patient’s thoughts about fatigue, the main outcome measure. That leads to bias.
(K) We have only subjective primary and secondary outcome parameters. In medical research, more and more researchers are moving away from objective outcomes and they are looking at what is relevant for the patient and how he feels. The outcome measurements we perform are in accordance with ZonMw’s decision.
In previous research, we have shown that there is no correlation between the objective and subjective outcome parameters.
Isn’t that a strong indication that there is bias in the subjective measurements?
6. What is the cut-off point for the primary outcome measure, the CIS-F, which represents fatigue? in other words when is the treatment considered effective?
(K) Treatment is considered effective if the post-treatment CIS-F score is less than 35 (correction april 2022) combined with at least 6 points change from the first measurement. A score equal to 35 or higher prior to treatment is the inclusion criterion. This is considered severely fatigued.
7. What are the results in the interim report to ZonMw? (i.e. the way of monitoring of deterioration and the results of that monitoring)
This is not mentioned in the interim report on the ZonMw website.
(K) We did include that in our report to ZonMw. They determine what is published on the website.
The patient representatives will contact the relevant ZonMw program manager about this.
Closing
We thank Mr Knoop for the conversation. We find that there is a big difference between his view and ours about the possible risks associated with the treatment and about the need to measure objective outcome measures too. We note that we are unable to reach an agreement and that we remain deeply concerned about the possibility that the ReCOVer study may fail to recognize a possible deterioration in patients as a result of treatment.
(End of report)
Postscript
There is a big difference between Professor Knoop’s and our opinion about the possible beneficial effects and especially about the possible risks associated with treatment with this particular version of CBT and about the need to measure objective outcomes too. We note that we are unable to reach an agreement and that we continue to have serious concerns about the possibility that the ReCOVer study will fail to recognize possible deterioration of patients as a result of treatment. We expect that false positive results will be claimed.
We asked ZonMw about the interim report on ReCOVer and whether Professor Knoop has described the way in which any damage as a result of the treatment is measured and whether there has been any damage.
This led to the following response by ZonMw: “The ReCOVer research project group has indeed answered and justified the relevant questions sufficiently. There are no indications for a decline in functioning in the intervention group.”
Prof. dr. H. Knoop, responsible for the ReCOVer research, Clinical psychologist, Professor, Department of Medical Psychology AMC – Academic Medical Center
Drs. Y. Jansen, Support Group ME and Disability
Mr. A. de Groot, lawyer, Group ME The Hague
Drs. L. Corsius, ME/CFS Association
Introduction
This meeting takes place in response to the WOB (“FOI”) procedure in which the three patient organizations have requested information about the assessment and award by ZonMw of the subsidy application for the ReCOVer study. This conversation was planned as a spin off from that procedure.
The patient organizations warn against the possible consequences of the treatment for patients who suffer from a post-viral syndrome after COVID-19 which may lead to a worsening of complaints to such an extent that a very serious healthsituation can develop. The question is whether this has been taken into account in the research design and, if so, how will this be followed up.
Professor. Knoop indicates that there is a clear difference compared to CFS patients; the longcovid patients undergo treatment at a very early stage in contrast to CFS patients who are only treated after 5-6 years. The ReCOVer study is based on the hypothesis that early treatment by means of cognitive behavioral therapy (CBT) according to a specific protocol can prevent chronicity of the complaints.
Questions to Professor Knoop
Professor. Knoop’s answers are in italics and begin with (K).
1. The underlying idea for this particular CBT treatment is that thoughts and behavior perpetuate the disease. Part of the treatment protocol is that patients should not focus on their complaints, but should continue with a time-contingent increase of activities regardless of the complaints. This could mean that patients may not report worsening.
(K) That is not worded correctly. We ask patients to shift their focus.The risk of this treatment is small. Studies into the use of this treatment in other diseases largely demonstrate the efficacy of the treatment and show that there is no increased risk. The Medical Ethics Review Committee (METC) has also established this.
2. Is the treatment protocol available?
(K) The treatment protocol is not available. This has to do with two reasons: 1. The university has Intellectual Property (IP) on the protocol and only the university can and may determine what happens to it and 2. The treatment must first be tested in research. Otherwise, there is a risk that others will adopt the treatment that has not yet been studied because there are so few treatment options available for this patient group. (Mr Knoop does share the view that the results of the protocol and the protocol should be made available through eventual publications, even if research shows that the protocol has shortcomings or turns out to be unusable).
3. What is seen as deterioration in the study? In what terms are these adverse events described? Are dropouts followed up? Are the results of the actometer also taken into account?
(K) As adverse events, we register hospitalization and visits to a doctor and we have a questionnaire to inventory Postexertional malaise (PEM). The actometer plays no role in this.
4. The study design shows that actometry is not considered a primary or secondary outcome measure. Actometry does take place. What is done with the results of the actometer?
(K) The actometer is only used to divide the patients into an active group and a less active group prior to treatment.
We are seriously concerned about the possibility that you will not recognize deterioration, partly as a result of the fact that you do not use an objective outcome measure such as the actometer or objective data on labor participation.
5. It is known that measuring only subjective outcome parameters in such an open trial has a high risk for bias. Therefore, objective outcome parameters must be used also. How do you handle that?
(K) Why are patient organizations so obsessed with objective measures? Objective measures are subjective too. They depend on how you interpret them.
It is well known that the outcomes on subjective measures such as fatigue are directly influenced by the treatment (we have used the term ‘manipulated’ in the conversation).
(K) So you’re basically saying you don’t trust the outcomes reported by the patients themselves? How does that relate to the fact that you as a patient organization represent these patients while you do not take their answers seriously?
We take patients very seriously. But with regard to your research, we indicate that the treatment is aimed directly at influencing the patient’s thoughts about fatigue, the main outcome measure. That leads to bias.
(K) We have only subjective primary and secondary outcome parameters. In medical research, more and more researchers are moving away from objective outcomes and they are looking at what is relevant for the patient and how he feels. The outcome measurements we perform are in accordance with ZonMw’s decision.
In previous research, we have shown that there is no correlation between the objective and subjective outcome parameters.
Isn’t that a strong indication that there is bias in the subjective measurements?
6. What is the cut-off point for the primary outcome measure, the CIS-F, which represents fatigue? in other words when is the treatment considered effective?
(K) Treatment is considered effective if the post-treatment CIS-F score is less than 35 (correction april 2022) combined with at least 6 points change from the first measurement. A score equal to 35 or higher prior to treatment is the inclusion criterion. This is considered severely fatigued.
7. What are the results in the interim report to ZonMw? (i.e. the way of monitoring of deterioration and the results of that monitoring)
This is not mentioned in the interim report on the ZonMw website.
(K) We did include that in our report to ZonMw. They determine what is published on the website.
The patient representatives will contact the relevant ZonMw program manager about this.
Closing
We thank Mr Knoop for the conversation. We find that there is a big difference between his view and ours about the possible risks associated with the treatment and about the need to measure objective outcome measures too. We note that we are unable to reach an agreement and that we remain deeply concerned about the possibility that the ReCOVer study may fail to recognize a possible deterioration in patients as a result of treatment.
(End of report)
Postscript
There is a big difference between Professor Knoop’s and our opinion about the possible beneficial effects and especially about the possible risks associated with treatment with this particular version of CBT and about the need to also measure objective outcomes. We note that we are unable to reach an agreement and that we continue to have serious concerns about the possibility that the ReCOVer study will fail to recognize possible deterioration of patients as a result of treatment. We expect that false positive results will be claimed.
We asked ZonMw about the interim report on ReCOVer and whether Professor Knoop has described the way in which any damage as a result of the treatment is measured and whether there has been any damage. This led to the following response by ZonMw: “The ReCOVer research project group has indeed answered and justified the relevant questions sufficiently. There are no indications for a decline in functioning in the intervention group.”
Yesterday, October 5th, I received an answer from a senior communications manager to the questions I sent to NICE and specifically the chairman of the board on September 14th. Well actually, it’s a rather evasive response but on some points it offers a remarkable insight if I understand it correctly. My original questions are in Bold, the answers from NICE in Italic and my reactions are underneath those answers.
Thank you for your following up email to myself and our chairman Sharmila Nebhrajani. Ms Nebhrajani has asked me to respond on her behalf and I address each question in turn:
Can you tell me by whom and how Professor Black was appointed as chair for the round table session? How was her independent position evaluated and on which grounds?
NICE’s chief executive, Professor Gillian Leng approached Dame Carol and she kindly agreed to chair the round table. We asked Dame Carol as she is an experienced chairperson, is independent of NICE and our guideline development processes.
This answer has been given before and it means that Dame Carol is independent of NICE but it doesn’t mention that she is linked to other important parties with vested interests, as others have written before, and they are certainly not the patients. So the meaning of the word independent is seriously subject to erosion.
The round table is for discussion of the issues raised that led to the pause in publication, it is not a decision-making forum. Any subsequent decisions will be made by NICE’s guidance executive.
So the round table is not decision-making, but anyone can imagine that there will be lots of influence on the already approved text of the final guideline. According to this answer the NICE guidance executive (who exactly?) will be deciding. How does this compare to the guideline processes and regulations that NICE have described themselves? What are the rules for this kind of decision making? Will the guideline committee be totally ignored now?
Why is the round table session postponed?
In order for the meeting to be as effective as possible it is important to fully understand the issues and concerns that all groups attending the meeting wish to raise. We also recognise the difficulty that holding the meeting at short notice created for some attendees who would have been unable to make the original date.
This is an evasive answer. It doesn’t give any clarity.
How can you explain a round table session at all after a guideline process that took almost 4 years and that had been closed?
The roundtable will be an opportunity for all parties to discuss key issues raised prior to publication. The decision on next steps will be taken by NICE, taking into account comments made at the roundtable. The meeting will take place on 18 October 2021 and we will release the agenda ahead of the meeting and minutes will be published afterwards.
Key issues have been discussed prior to publication. The almost 4 years lasting guideline process was meant to discuss key issues. In fact the guideline had already been approved and only minor textual changes could have been made in this phase. The answer given is not an answer to my question.
Can you explain why the publication has been postponed just hours before publishing?
Changing clinical practice and clinical attitudes is one of the most challenging parts of our role. We want to ensure that the guideline makes a difference for patients and to make a real difference, guidelines need to be supported by all relevant stakeholders. In this case, we took the difficult decision to pause publication in the light of feedback from some key groups. Taking some extra time now to bring everyone together at the roundtable event is an important step.
This nonsensical and extremely evasive answer has been given on and on. It is in no way an answer to the question. How is it possible that these “key groups” can uphold a guideline publication just hours before publication when all steps have already been taken? What will happen if the patients “key group” does not support the irreglementary altered guideline?
How does that fit into the NICE guideline processes?
Decisions to publish final guidance are taken by NICE’s guidance executive. In this case, because of issues raised during the pre-publication period with the final guideline, guidance executive took the decision to pause publication.
This reaction describes a fact, but it is not an answer to my question. How does this fit into the guideline processes? Does it fit into the guideline processes at all? Please answer the question.
At what exact moment did professor Gillian Leng send her letter of resignation?
Professor Leng discussed her plan to retire from NICE with the chairman and other colleagues and stakeholders. NICE confirmed Professor Leng’s intention to retire in a statement on 09 September 2021.
This again is an evasive answer, but perhaps it gives more information than intended. Apparently there was no letter of resignation and may we conclude that professor Leng had no intention to leave before postponing the publication and all that happened then?
According to the NICE message dated August 17, 2021, you have decided to pause the publication of the guideline ME/cfs that was scheduled for today after a period of three years.
‘NICE has used its usual rigorous methodology and process in developing this guideline but despite the best efforts of the committee, that followed these to the letter to bring together the available evidence and the real, lived experience and testimony of people with ME/CFS, we have not been able to produce a guideline that is supported by all.’
Your decision has far reaching consequences for patients, for science and for your own institute.
Patients have been confronted with a very poor and damaging NICE-guideline since 2007. That guideline is based on hardly any scientific underpinning at all. Despite that, it recommends the detrimental treatments CBT/GET and GET. As you have found according to the draft guideline, the scientific base for these treatments is actually non-existent. As stated by NICE the quality of the evidence for these treatments is low to mainly very low.
As a result of your decision this obsolete and damaging guideline will be followed even longer. Patients will still be confronted with these treatments. For your information: our daughter has deteriorated after undergoing CBT in combination with GET and is bedbound for six years now.
According to your message NICE has used its usual rigorous methodology and process. The question is what will be accomplished by talking to professionals who don’t agree on the outcomes of that process. Will you consider compromises? That would be inevitably contradictionary to the evidence you rigorously evaluated. By not adhering to the scientific considerations towards the low to very low quality of the evidence you will degrade the importance of science as a result of your decision. Apparantly eminence prevails over evidence.
The mere fact that you decided to pause the publication (again) based on the very feable argumentation that a number of professionals will not accept the guideline and the fact that you are going to negotiate despite your rigorous methodology and process, undermines the position of NICE.
Once a guideline has been established along your rigorous process and methodology, professionals have an obligation to follow those guidelines. You don’t have to negotiate about that. That is what guidelines are for.
The credibility, trustworthiness and independent position of NICE have been damaged severely. That is not only the case in the United Kingdom. You can be assured that the whole world is following this process.
Based on the above I ask you to reconsider your decision and publish the guideline this week.
Yours sincerely
Lou Corsius, Msc Health Sciences
The Netherlands
Copy to the Board: Mrs Sharmila Nebhrajani MA, OBE, chairman
In CBT/GET research regarding ME/cfs we find a considerable number of studies and outcomes that have been disappeared or reasoned away because they show the opposite of what the researchers want us to believe.
It appears that the academic world has no adequately functioning mechanism for self correction. These articles have been published in scientific journals one would think to be respectable. Despite the severe and well-elaborated criticism these journals have refused to withdraw the publication.
In this short inventarisation some of these researches are presented.
You will find studies or outcomes that have been buried underneath loads of silence or that have been delayed. You will also find studies the researchers bragged about that they were proof their therapy works and in the meantime they chose not to mention the outcomes that prove the opposite. The third kind is mentioning an outcome was opposite to what was expected and then go on polishing that inconvenience away in the discussion and conclusion section. The fourth approach is treating data on and on to obtain a satisfying outcome.
British and Dutch CBT/GET researchers have a longstanding tradition in this kind of scientific juggling.
In November 2017 Frank Twisk and I published an analysis of five Dutch hallmark studies into the efficacy of cognitive behaviour therapy with a graded activity protocol for chronic fatigue syndrome and Myalgic Encephalomyelitis.
These studies show severe shortcomings including inconvenient results that have been hidden.
1. Prins JB, Bleijenberg G, Bazelmans E (2001) Cognitive behaviour therapy for chronic fatigue syndrome: a multicentre randomised controlled trial. Lancet 357: 841-847. [Crossref]
Apart from the fact that this study incorrectly claimed having selected patients who fulfilled the Fukuda criteria, the objective outcome (actometer) was not published until 9 years later and did not support the efficacy the authors claimed. Prof. dr. James Coyne writes about it on his blog.
2. Bazelmans E, Prins JB, Lulofs R (2005) Cognitive behaviour group therapy for chronic fatigue syndrome: a non-randomised waiting list controlled study. Psychother Psychosom 74: 218-224. [Crossref]
Curiously non-intervention had a positive effect on functional impairment but CBT+ had a small negative effect on the mean SIP 8 score. As the authors phrased it: “For functional impairment, the effect was opposite to what was expected”. The authors polished this incovenient outcome away by stating the therapists (they themselves chose and trained them) were inexperienced. That was the explanation for this effect. The option that their therapy didn’t work in itself and that the underlying hypothesis could have been incorrect, was not considered.
3. Stulemeijer M, de Jong LWAM, Fiselier TJW (2005) Cognitive behaviour therapy for adolescents with chronic fatigue syndrome: randomised controlled trial. BMJ 330: 14. [Crossref]
The negligible effects of CBT+ on activity levels using an actometer, with great delay published in a secondary outcome study five years later, are at odds with less school absence after CBT+.
4. Knoop H, Bleijenberg G, Gielissen MF (2007) Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? Psychother Psychosom76: 171-176. [Crossref]
Knoop ‘forgot’ to include the most important treshold in his most comprehensive definition of recovery. So, ‘the most comprehensive definition of recovery’ isn’t based on stringent criteria. Curiously, the SIP 8 score, used as a criterion to select patients (caseness) in this study and other trials, isn’t included in these two definitions of recovery. The study doesn’t report how many CFS patients reached ‘normal levels’ (≤203), but considering the size of the effect of CBT+ on SIP 8 in this study and other trials, few patients, if any, would reach ‘normal levels’. In stead of aknowledging this, they shouted in the press that 70% of the patients did no longer fulfill the criteria for cfs.
5. Nijhof SL, Bleijenberg G, Uiterwaal CS (2012) Effectiveness of internet-based cognitive behavioural treatment for adolescents with chronic fatigue syndrome (FITNET): a randomised controlled trial. Lancet 379: 1412-1418. [Crossref]
In our article we discuss many flaws in this study. Vink, MD and Ghatineh, PhD wrote an extensive article on the serious flaws in this study. In the light of this inventarisation it is important to state that data with regard to objective measures were not reported. The actometer result were not published. They were very important because they can show that the alledgedly positive results were actually based on substitution of activities and not on increasing physical activity in total.
On top of that the follow up study demonstrated that there was no difference between the intervention group and the control group. In all publicity about FITNET this important fact has not been mentioned. In spite of the fact the follow up study proved CBT did not work, the FITNET study has been presented as proof for the efficacy of CBT/GET in the recent Dutch guideline MUS for children (2019). The authors included cfs in this guideline knowingly ignoring the Dutch Health Council advice on ME/CFS (2018). The chair of the guideline committee was prof. dr. Elise van de Putte. She was one of the FITNET authors.
In general these CBT/GET studies are characterised by the fact that the dropout numbers in the intervention group are considerable. Nevertheless the authors claim that the intervention is safe. The argumentation to support this claim is largely insufficient. It is clear that these researchers have the intention to prove their therapy works. Facts that might contradict this proof have been hidden, severely delayed or reasoned away.
PACE-trial
The ultimate example of ‘How not to conduct a randomized clinical trial’ is the British Pace-trial published in The Lancet in 2011 and hailed by two Dutch colleagues.
Anything you can think of has been used to hide the fact that the outcome was NILL. A complete special issue of the Journal of Health Psychology was dedicated to this failing study.
Wilshire et al. analysed the study using the original protocol and came to the conclusion that the result was negligible to nill.
Just a couple of these extravagancies:
– Halfway outcome switching with serious impact on the outcomes.
– Changing the inclusion criteria so 13% of participants were sick enough to enter the trial and good enough to be considered recovered at the same time.
– Telling the intervention group (during the intervention) that this was the best therapy and that is was approved by government.
– Refusing to present data for a critical review, claiming that asking for the data was vexatious. (two courts judged they had to present the data)
– Etc.
– Etc.
– Etc.
As the minutes of the steering committee show, the authors were warned during the research period by their Dutch colleagues that the actometer results did not show any improvement. So they deciced to skip this outcome measure.
The negative outcomes of the sister study (FINE) were buried underneath the earlier described loads of silence. As Dr. David Tuller wrote: ‘The FINE results were published in BMJ in April, 2010. Yet when the first PACE results were published in The Lancet the following year, the investigators did not mention the FINE trial in the text. The trial has also been virtually ignored in the subsequent public debate over the results of the PACE trial and the effectiveness, or lack thereof, of the PACE approach.’ See the weblog Trial By Error, Continued: Why has the PACE Study’s “Sister Trial” been “Disappeared” and Forgotten?
In more recent times we have the Dutch Q-fever Qure study and the follow-up study by mainly the same Dutch group of authors, now assisted by new PhD candidates. And again these studies fit in perfectly in the earlier mentioned longstanding tradition. On my weblog I discuss the shortcoming of these two studies.
In this case also, unwelcome (ojective) outcomes such as actometer results were measured but not presented. The (subjective)outcomes that were published, initially seemed to show some improvement, but they were largely insufficient to reach normal values. The follow-up study showed the intervention group did worse than the control group. As in other CBT studies, the dropout rates in the CBT intervention group were considerable compared to the control group.
Despite these facts, CBT for cfs (wich includes activity extending tasks) was added to the guideline for
Q-fever fatigue syndrome. When asked why since there is no proof of efficacy and possible detrimental effects, one of the guideline committee members, a GP, told me it was important he could offer something to his colleagues. That was the important argument. Not the wellbeing of patients.
The research group has performed several statitistic reanalyses of the data to underpin their claim booster sessions would be the answer to the fact that their therapy does not work.
De ME/CVS stichting vraagt op haar website aandacht voor een onderzoek onder ME/cvs-patiënten naar het coronavirus.
“Vermoeidheidkliniek en ME/CVS Stichting Nederland hebben daarom samen het initiatief genomen om de mogelijke impact van deze ziekte op ME/cvs patiënten te onderzoeken. Dat doen ze in nauwe samenwerking met Erasmus Universiteit.”
De vraag is echter wat zij gaan onderzoeken en bij wie? Op basis van de onderzoeksopzet kom ik tot de volgende bevindingen:
Bij Context en Doel:
Er wordt hier geen doel aangegeven. Het is belangrijk om te weten wat de opbrengst uiteindelijk moet zijn en wat je met dat resultaat vervolgens kan.
Bij Het Onderzoek:
Bij het aandachtspunt staat: het nieuwe coronavirus moet ons vooral verenigen in alles wat bij de bestrijding daarvan kan helpen. Uit de onderzoeksopzet blijkt niet hoe dit onderzoek daarbij gaat helpen.
Bij Vraagstelling Onderzoek:
Hebben mensen met ME/CVS vaker COVID-19 dan mensen zonder ME/cvs?
De vraag is hoe je dat op basis van dit onderzoek gaat beantwoorden. Zie ook populatie en controlegroep.
Hebben mensen met ME/cvs meer/andere klachten dan mensen zonder ME/cvs?
Wat moet dit inzicht opleveren? Geven de vragen over de klachten en de antwoordmogelijkheden voldoende houvast om daar gegronde conclusies uit te kunnen afleiden?
Bij Populatie:
Patienten met ME/cvs, al dan niet met een COVID-19 diagnose.
Controlegroep uit de omgeving van de participerende patiënt.
Wie is de ME/cvs groep in deze? Er is geen nadere uitvraag naar de ME/cvs klachten en de belastbaarheid. Het is dus de vergaarbak waar wij steeds voor waarschuwen. Op basis daarvan kan je geen specifieke conclusies trekken.
Door de manier van uitzetten is geen enkele controle op de respondenten mogelijk. Iedereen kan wat invullen ook mensen die niet ziek zijn.
De controlegroep bestaat uit mensen uit de naaste omgeving van de patiënt. De kans dat daarmee onderlinge besmetting met COVID-19 plaatsvindt, is dus hoog. Dat maakt een antwoord op vraag 1 onmogelijk.
De wijze waarop navraag gedaan wordt naar de diagnose COVID-19 is sterk afhankelijk van wat men zelf rapporteert. Er is geen controle op. Hebben we dus werkelijk met COVID-19 te maken? Ook de aanname van instanties doordat een huisgenoot positief is getest en er ook klachten bij u zijn Er is in Nederland vooralsnog weinig coronatesten uitgevoerd. Het is dus een aanname. Deze manier van vaststellen leidt dus ook tot problemen bij de beantwoording van de vraag of het meer voorkomt bij ME/cvs patiënten dan bij anderen.
Bij Vragenlijst:
Er is discussie geweest over de optie de klachten via een schaalverdeling te laten scoren. Daar is van afgezien.
Dit is een beperking in het onderzoek.
De uitkomst blijft bovendien gebaseerd op zelfevaluatie. We weten dat zelfevaluatie leidt tot onzuivere antwoorden. Objectieve en controleerbare maatstaven zijn dus noodzakelijk, maar die ontbreken.
Er wordt gevraagd naar de datum vaststelling van COVID-19. Vervolgens wordt gevraagd aan de hand van een aantal vragen naar de toestand op dit moment (meer of minder dan vorige week). Dat kan dus enorm verschillen ten opzichte van de situatie op de datum vaststelling, bovendien geeft het geen beeld van de beginsituatie voordat men besmet werd met het virus.
Kortom: dit onderzoek wordt m.i. gekenmerkt door zodanige zwakten dat het niet tot onderbouwde conclusies kan leiden.
Aan een van de onderzoekers is op 28 maart een reactie gevraagd op de bovenstaande punten. Op het moment van deze publicatie (13-4-2020) heb ik nog geen inhoudelijke reactie op deze punten mogen ontvangen.
Inmiddels heeft de heer Louwen gereageerd. Zijn conclusie leest u in de reacties.
it's about ME 