How fatigue researchers reason away nil results and negative findings regarding CBT in CFS and QFS.

Studies that show treatment using cognitive behavioral therapy with activity-building program does not work, are now presented as if they were a success and an underpinning for the claimed favorable effect. A recent example is the Qure study and the corresponding follow-up study, showing that the treatment is not working. An earlier example is an investigation into group CGT. Both publications show how zero results and even negative findings are reasoned away.

Research 1. QFS  

At the end of 2017, the publication describing the Qure study[i] was presented, a study into the effects of CBT (Cognitive Behavioral Therapy) with a CFS approach and the effect of antibiotics on patients who are supposedly suffering with QFS.

QFS (Q Fever Fatigue Syndrome) occurs when symptoms persist and no active form of the bacterium Coxiella burnetii is found during lab tests. The original study found a very questionable outcome with regard to the effect of CBT. As I described earlier [ii], according to this study, there is indeed a statistically significant improvement in the CIS F score in the CBT group, but what is the relevance of this statistically significant improvement? The score of 31.6 still does not match the score <27 that is used as normal in other studies. (Knoop et al, 2007). What is the value of such a result if the level of activity is not increased when that is precisely the objective? It is striking that the only score (SIP 8) that indicates at least something about physical functioning does not lead to a substantial improvement. The score of 786.8 in the CBT group is so poor that in other studies patients are considered to be severely limited and it will lead to inclusion in research. The score is also completely inadequate compared to the normal value chosen in this study (450). As a normal value, a score of 203 is used in other studies [iii] (Knoop et al. 2007)

At the end of 2018, the follow-up study [iv] was published which clearly showed that CBT did not work. On the contrary, the CBT scores are significantly worse in the follow-up measurement, while the Placebo score on CIS-F even improves (although modestly). The outcome scores on SIP8 (physical functioning), which are completely inadequate for all three groups in the endpoint measurement, deteriorate at the follow-up for the CBT group but improve for the Doxycycline and Placebo group. The result at follow-up is that the Placebo group has better scores on CIS-F and on SIP8 (although still insufficient) than both treatment groups.

Quotes from the follow-up study:

  1. “Due to its initial positive effect and side effects of long-term doxycycline use, CBT is still advised as therapy of choice for QFS patients. At present, it is still the only well-investigated treatment modality for QFS patients with a positive effect.”
  2. “Throughout this study, all patients were functionally impaired. It is conceivable that persisting functional impairment leads to a constant confrontation with limitations caused by an impaired health status which could eventually lead to an increase in fatigue severity.” 
  3. “In addition, it can be noted that patients received a median of 9 CBT sessions in the original trial, which, although effective for fatigue severity, might be insufficient to address perceived functional impairment. As noted in the original trial, there was a trend towards a beneficial effect of CBT on functional impairment.”
  4. “An alternative explanation could be the recurrent negative media attention in the Netherlands for Q fever since the outbreak of 2007, frequently reminding patients of their complaints and possible unfavourable long-term outcome of QFS.”
  5. “Moreover, a large lawsuit, in which patients collectively sued the Dutch government for negligence during the Q fever outbreak, was still pending during the follow-up period. This encouraged patients to supply attorneys with proof of diagnosis and constantly reminded them of their often dire financial situation and perceived lack of social support.”
  6. “It is likely that not all relevant perpetuating factors for QFS have yet been identified and were therefore not addressed during CBT. It could be postulated that such inappropriately addressed perpetuating factors contributed to the relapse in fatigue severity at 1-year follow-up. The fact that there was a positive effect of CBT directly following CBT however speaks against this hypothesis. One could however also assume that the unknown and unaddressed perpetuatingfactors in QFS are responsible for the relapse.”

Notes to these statements:

point 1. There is no positive effect of CBT at all. The authors chose their words considerately. Although there seems to be some improvement on the CIS F score immediately after completion of the treatment, the effect disappears quickly and the CBT group scores during follow-up are even worse than the control group (although not statistically significant).

point 2. The reasoning that the patients experienced a limitation in physical functioning during the entire study shows that the treatment does not work.

point 3. The results with regard to physical functioning showed a tendency towards improvement. This too is cleverly described. One forgets to report that the outcomes were very poor. The authors acknowledge this in statement 2, because that is precisely what is being presented here as an explanation for the measured fatigue at follow-up. Moreover, there was a so-called “tendency towards improvement” in all groups and not just in the CBT group.

point 4. Returning negative news coverage in the media would cause the long-term effects to be worse. Well, and that was not the case during the endpoint assessment? Could it be that the known bias effects [v] that the patient has learned what are desirable answers and want to please his therapist, has faded out over time?

point 5. An ongoing lawsuit affects the scores. With this argument, the authors show that such subjective measures as the CIS F are very sensitive to the circumstances and that they therefore do not give a reliable picture of reality (see also my remark above at point v4). An objective outcome measure does not show this shortcoming or much less. This is an additional argument for the possibility that the “favorable score” on the CIS F is based on bias upon completion of the treatment. This is reinforced by the fact that the control group showed an improvement at follow-up. The logic in the authors’ arguments is therefore lacking; they contradict themselves.

point 6. The authors suggest that there may be a still unknown perpetuating factor. This is highly speculative, especially since they have dismissed another possible factor in the same statement. Moreover, in Keijmel’s research they have found that the underlying model of perpetuating factors is not applicable. The possible explanations why the treatment does not work are colorful and speculative. The consideration that cognitive behavioral therapy is neither an appropriate treatment nor will be, has apparently no place in their repertoire.

It is also questionable whether the patients were rightly diagnosed a QFS patient. In the Qure study, it is firmly stated that the QFS patients the active form of Coxiella burnetii cannot be found and therefore they do not suffer with chronic Q fever. There are three reasons though, why they cannot proclaim that with certainty:

  1. the research methods used are characterized by an above-average risk factor that the finding is not correct. See the article by Wielders et. al. [vi].
  2. The values found are only on border statistically significant in a small study population.
  3. Also the fact that the 1-year follow-up study shows that the CGT has deteriorated (as well as the fact that in the Qure study the SF36PF in the CGT group also still indicates underperforming physical functioning), is an indication that there is an incorrect diagnosis.

 

References

[i] Keijmel SP, Delsing CE, Bleijenber G et al (2017) Effectiveness of long-term doxycycline treatment and cognitive behavioral therapy on fatigue severity in patients with Q-fever fatigue syndrome Clinical Infectious Diseases, 64(8):998-1005

[ii] https://corsius.wordpress.com/2019/01/01/are-they-really-qured-reactie-op-de-resultaten-van-onderzoek-naar-een-cure-voor-qfs-q-fever-fatigue-syndrome/

[iii] Knoop H, Bleijenberg G, Gielissen MF (2007) Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? Psychother Psychosom 76: 171-176.

[iv] Raijmakers, PH, Keijmel, SP, Breukers, MC, Bleijenberg, G et al (2018) Long-term effect of cognitive behavioural therapy and doxycycline treatment for patients with Q fever fatigue syndrome: One-year follow-up of the Qure study Journal of Psychosomatic Research 116:62-67

[v] https://www.coyneoftherealm.com/blogs/mind-the-brain/when-psychotherapy-trials-have-multiple-flaws

[vi] Wielders CCH, Wijnbergen PCA, Renders NHM (2013) High Coxiella burnetii DNA Load in Serum during Acute Q Fever Is Associated with Progression to a Serologic Profile Indicative of Chronic Q Fever. Journal of Clinical Microbiology 51/10: p. 3192–3198

 

Research 2. CGT group program for CVS

In the study by Bazelmans et al., 2005 [i] on the effectiveness of group CBT with a graded activity program, CBT and no intervention had a very modest effect on CIS F scores after 6 months. The CIS F score in the CBT group changed from 51.0 at baseline,  to 45.6 at endpoint and that was a significant difference compared to the control group that received no treatment. The CIS F in the control group was at the start: 50.8, and after 6 months: 48.4. These outcomes for both groups  are absolutely inadequate and do not reach normal values ​​by far (<27).

Strangely enough, there was a positive effect on physical functioning in the control group, where no treatment was given. In the control group, the SIP 8 score at the start was 1.710, and after 6 months: 1.417. The CBT group showed a slight deterioration on the SIP 8 score. At the start it was 1.707, and after 6 months: 1.736.

The authors produced the following statements and recommendations (quote):

  1. “ In group therapy CFS patients may reinforce dysfunctional behaviour and resistance against psychological treatment. Furthermore, in Group therapy it is much harder to individualise CBT treatment to individual needs.”
  2. “In trials on individual CBT for CFS it was found that engagement in a claim for a disability related benefit (…) cognitive behaviour group therapy for chronic fatigue syndrome during CBT predicted less improvement after individual CBT for CFS. Our CBGT started beforecompletion of these studies.”
  3. “In the present study it was found that CFS patients with less severe complaints did profit most of CBGT. In future research on the effectiveness of CBGT for CFS these findings will have to be taken into account.”
  4. “Another explanation for the moderate effect of CBGT might be that the therapists had no prior experience with CB(G)T for CFS.(…) CFS patients are more difficult to treat than other patients with somatic complaints’. For our study this might count even more, since the therapists were inexperienced both in group therapy and in CBT for CFS.”  
  5. “Finally, based on this and former studies the treatment protocol CB(G)T for CFS has been improved. Rest and relaxation are less emphasised, and for passive CFS patients the treatment protocol has been adapted.”  
  6. “Recently, lack of social support has been identified as an important determinant of CFS and a new perpetuating factor. Dealing with a lack of social support may also have to become a more prominent aspect of CBT for CFS.”
Discussion:

point 1. In the text preceding this comment, the authors mention the benefits of group treatment, namely that they can be reinforced by the group effect to reach better results. So there is both an explanation in favor and against the group effects. The question remains why this is presented as an explanation that the therapy did not work.

point 2. The statement that the treatment is less effective in patients who are involved in a legal claim has been used more than once. The data do not show for how many patients in this study such a situation was at issue and whether it led to a deviation in the scores.

point 3. Patients with less severe complaints benefit more from the treatment. Do we have a heterogenious group of patients then? The recommendation to involve only less  what is at the bottom of the differences between the two groups.

point 4. The fact that the therapists had no experience is presented as an explanation. However, it concerns therapists who were specially selected for this research.

point 5. One refers to other research showing that the lack of social support is an important determinant for CFS and a new sustaining factor. Nothing shows that this has been of any influence in this research. There is no reporting about it. The comment is, again, speculative.

Despite all the negative findings, the authors conclude suggesting this research indicates a favorable effect of cognitive behavioral therapy, while there is no scientific underpinning for any such effect.

“In the current study we found a moderate effect of CBGT on fatigue, in an unselected group or CFS patients, and with newly-trained therapists.”

The fact that the CIS F outcomes point to severely affected patients is completely avoided in this text. The possibility that CBT could be an inadequate treatment is not considered.

References
[i] Bazelmans E, Prins JB, Lulofs R et al. (2005) Cognitive behaviour group therapy for chronic fatigue syndrome: a non-randomised waiting list controlled study. Psychother Psychosom 74: 218-224.
Advertenties

Hoe vermoeidheidsonderzoekers nulresultaten en negatieve resultaten van CGT bij CVS en QVS wegredeneren.

Onderzoeken die aantonen dat behandeling in de vorm van cognitieve gedragstherapie met activiteitenopbouwend programma niet werkt, worden nu juist voorgesteld als een succes en als onderbouwing van de gunstige werking. Een recent voorbeeld is de Qure studie en het bijbehorende follow-up onderzoek waaruit blijkt dat de behandeling niet werkt. Een ouder voorbeeld is een onderzoek naar groepsgewijze CGT. Beide publicaties laten zien hoe nulresultaten en zelfs negatieve bevindingen worden weggeredeneerd.

Onderzoek 1. QVS

Eind 2017 verscheen de publicatie over Qure[i], een onderzoek naar de werking van CGT (Cognitieve Gedrags Therapie ) met CVS-aanpak en de werking van antibiotica bij patiënten van wie wordt verondersteld dat zij QVS hebben.

Er is sprake van QVS (Q-koorts Vermoeidheids Syndroom) als klachten aanhouden en er geen actieve vorm van de bacterie Coxiella burnetii bij labonderzoek wordt aangetroffen.

Het oorspronkelijke onderzoek gaf een zeer twijfelachtige uitkomst met betrekking tot de werking van CGT. Zoals ik eerder beschreef[ii] is er volgens dit onderzoek weliswaar sprake van een statistisch significante verbetering in de CIS F score bij de CGT-groep, maar hoe relevant is deze statistisch significante verbetering? De score van 31,6 komt nog steeds niet overeen met de score < 27 die in andere onderzoeken als normaal wordt gehanteerd. (Knoop et al, 2007). Wat is de waarde van een dergelijke uitkomst als het activiteitenniveau niet wordt verhoogd terwijl dat nu juist de doelstelling is?

Het is opvallend dat de enige score (SIP 8) die tenminste iets zegt over het fysiek functioneren, niet leidt tot een wezenlijke verbetering. De score van 786.8 in de CGT-groep is zo slecht dat ze bij andere onderzoeken wordt beschouwd als ernstig beperkt en leidt tot inclusie in onderzoek. Ook ten opzichte van de norm in dit onderzoek (450) is de score volstrekt onvoldoende. Als normale waarde wordt in andere onderzoeken een score van 203 gehanteerd [iii](Knoop et al. 2007)

Eind 2018 verscheen het follow-up onderzoek[iv] waaruit duidelijk blijkt dat CGT niet heeft gewerkt. Integendeel, de CGT-scores zijn aanzienlijk slechter in de follow-up meting, terwijl de Placebo-score op CIS-F zelfs (bescheiden) verbetert. De uitkomstscores op SIP8 (fysiek functioneren) die volstrekt onvoldoende zijn voor alle drie de groepen bij de eindpuntmeting, verslechteren bij de follow-up voor de CGT-groep maar verbeteren voor de Doxycycline- en de Placebogroep. Het resultaat bij follow-up is dat de Placebogroep betere scores heeft op CIS-F en op SIP8 (hoewel nog steeds onvoldoende) dan beide behandelgroepen.

Citaten uit het follow-up onderzoek:

  1. “Due to its initial positive effect and side effects of long-term doxycycline use, CBT is still advised as therapy of choice for QFS patients. At present, it is still the only well-investigated treatment modality for QFS patients with a positive effect.”
  2. “Throughout this study, all patients were functionally impaired. It is conceivable that persisting functional impairment leads to a constant confrontation with limitations caused by an impaired health status which could eventually lead to an increase in fatigue severity.” 
  3. “In addition, it can be noted that patients received a median of 9 CBT sessions in the original trial, which, although effective for fatigue severity, might be insufficient to address perceived functional impairment. As noted in the original trial, there was a trend towards a beneficial effect of CBT on functional impairment.”
  4. “An alternative explanation could be the recurrent negative media attention in the Netherlands for Q fever since the outbreak of 2007, frequently reminding patients of their complaints and possible unfavourable long-term outcome of QFS.”
  5. “Moreover, a large lawsuit, in which patients collectively sued the Dutch government for negligence during the Q fever outbreak, was still pending during the follow-up period. This encouraged patients to supply attorneys with proof of diagnosis and constantly reminded them of their often dire financial situation and perceived lack of social support.”
  6. “It is likely that not all relevant perpetuating factors for QFS have yet been identified and were therefore not addressed during CBT. It could be postulated that such inappropriately addressed perpetuating factors contributed to the relapse in fatigue severity at 1-year follow-up. The fact that there was a positive effect of CBT directly following CBT however speaks against this hypothesis. One could however also assume that the unknown and unaddressed perpetuatingfactors in QFS are responsible for the relapse.”

Opmerkingen bij deze verklaringen:

Bij 1. Er is helemaal geen positief effect van CGT. De auteurs formuleren het slim. Er lijkt weliswaar enige verbetering te zijn op de CIS F score meteen bij afronding van de behandeling maar dat effect verdwijnt al snel en de scores bij de follow-up zijn (hoewel statistisch niet significant) zelfs slechter dan bij de controlegroep.

Bij 2. De redenatie dat de patiënten gedurende het gehele onderzoek een beperking ondervonden in het fysiek functioneren, toont nu juist aan dat de behandeling niet werkt.

Bij 3. De uitkomsten ten aanzien van het fysiek functioneren toonden een tendens tot verbetering. Ook dit is slim geformuleerd. Men vergeet te melden dat de uitkomsten gewoon slecht waren. Dat erkennen de auteurs bij verklaring b, want daar wordt dat nu juist opgevoerd als een verklaring voor de gemeten vermoeidheid bij follow-up. Bovendien was er bij alle groepen een zogenaamde “tendens tot verbetering” en niet alleen bij de CGT groep.

Bij 4. De regelmatig terugkerende negatieve berichtgeving in de media zou de oorzaak zijn dat de lange termijn effecten slechter waren. Tja, en dat speelde niet tijdens het onderzoek zelf? Zou het ook kunnen zijn dat de bekende bias effecten[v] dat de patiënt heeft geleerd wat wenselijke antwoorden zijn en zijn behandelaar wil plezieren, na verloop van tijd is uitgewerkt?

Bij 5. Een lopende rechtszaak heeft invloed op de scores. De auteurs tonen met dit argument aan dat dergelijke subjectieve maten als de CIS F zeer gevoelig zijn voor de omstandigheden en dat zij dus geen betrouwbaar beeld geven van de werkelijkheid (zie ook mijn bovenstaande opmerking bij 4.) . Een objectieve uitkomstmaat vertoont deze tekortkoming niet of veel minder. Dit is extra argument voor de mogelijkheid dat de “gunstige score” op de CIS F bij afronding van de behandeling berust op bias. Dit wordt nog eens versterkt door het gegeven dat de controlegroep bij follow-up juist een verbetering vertoonde. De logica in de argumentatie van de auteurs ontbreekt dus; zij spreken zichzelf tegen.

Bij 6. De auteurs suggereren dat er een nog onbekende ziekte in stand houdende factor kan zijn. Dat is hoogst speculatief temeer daar zij in dezelfde verklaring een andere mogelijke factor hebben afgevoerd. Bovendien hebben zij in onderzoek van Keijmel geconstateerd dat het onderliggende model van in stand houdende factoren niet van toepassing is.

De mogelijke verklaringen waarom de behandeling niet werkt, zijn kleurrijk en speculatief. De overweging dat cognitieve gedragstherapie geen passende behandeling is en ook niet zal zijn, komt in het verklaringenarsenaal niet voor.

Het is ook de vraag of de patiënten terecht werden gediagnosticeerd als QVS-patiënt. In het Qure onderzoek wordt met stelligheid aangegeven dat de QVS patiënten niet de actieve vorm van Coxiella burnetii hebben en dus geen chronische Q-koorts hebben.

Er zijn drie redenen waarom zij dat niet met die stelligheid kunnen verkondigen:

  1. de gebruikte onderzoeksmethoden worden gekenmerkt door een bovengemiddelde risicofactor dat de bevinding niet klopt. Zie hiervoor het artikel van Wielders et. al.[vi].
  2. De gevonden waarden zijn maar net statistisch significant bij een kleine onderzoekspopulatie.
  3. Ook het feit dat de 1-jaar follow-up studie laat zien dat de CGT is verslechterd (evenals trouwens het feit dat bij de Qure studie de SF36PF in de CGT-groep ook nog steeds duidt op een ondermaats fysiek functioneren), kan een aanwijzing zijn dat er sprake is van een onterechte diagnose.

Referenties

[i] Keijmel SP, Delsing CE, Bleijenber G et al (2017) Effectiveness of long-term doxycycline treatment and cognitive behavioral therapy on fatigue severity in patients with Q-fever fatigue syndrome Clinical Infectious Diseases, 64(8):998-1005

[ii] https://corsius.wordpress.com/2019/01/01/are-they-really-qured-reactie-op-de-resultaten-van-onderzoek-naar-een-cure-voor-qfs-q-fever-fatigue-syndrome/

[iii] Knoop H, Bleijenberg G, Gielissen MF (2007) Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? Psychother Psychosom 76: 171-176.

[iv] Raijmakers, PH, Keijmel, SP, Breukers, MC, Bleijenberg, G et al (2018) Long-term effect of cognitive behavioural therapy and doxycycline treatment for patients with Q fever fatigue syndrome: One-year follow-up of the Qure study Journal of Psychosomatic Research 116:62-67

[v] https://www.coyneoftherealm.com/blogs/mind-the-brain/when-psychotherapy-trials-have-multiple-flaws

[vi] Wielders CCH, Wijnbergen PCA, Renders NHM (2013) High Coxiella burnetii DNA Load in Serum during Acute Q Fever Is Associated with Progression to a Serologic Profile Indicative of Chronic Q Fever. Journal of Clinical Microbiology 51/10: p. 3192–3198

 

Onderzoek 2. CGT groepsprogramma voor CVS

In het onderzoek van Bazelmans et al., 2005[i] naar de effectiviteit van groeps-CGT met opbouwend programma, hadden GCT en geen interventie een zeer bescheiden effect op de CIS F scores na 6 maanden. De CIS F score in de CGT-groep was van 51.0, bij aanvang, gewijzigd naar 45.6 en dat was een significant verschil met de controlegroep die geen behandeling kreeg. De CIS F in de controlegroep was bij aanvang: 50.8, en na 6 maanden: 48.4. Dat zijn ook voor beide groepen uitkomsten die absoluut onvoldoende zijn en bij lange na de normale waarden niet bereiken (<27)

Vreemd genoeg was er in de controlegroep, bij wie geen behandeling plaatsvond, een positief effect ten aanzien van het fysiek functioneren. In de controlegroep was de SIP 8 score bij aanvang 1,710, en na 6 maanden: 1,417. De CGT-groep toonde een kleine verslechtering op de SIP 8 score. Bij aanvang was die 1,707, en na 6 maanden: 1,736.

De auteurs gaven de volgende verklaringen en aanbevelingen (citaat):

  1. “ In group therapy CFS patients may reinforce dysfunctional behaviour and resistance against psychological treatment. Furthermore, in Group therapy it is much harder to individualise CBT treatment to individual needs.”
  2. “In trials on individual CBT for CFS it was found that engagement in a claim for a disability related benefit (…) cognitive behaviour group therapy for chronic fatigue syndrome during CBT predicted less improvement after individual CBT for CFS. Our CBGT started beforecompletion of these studies.”
  3. “In the present study it was found that CFS patients with less severe complaints did profit most of CBGT. In future research on the effectiveness of CBGT for CFS these findings will have to be taken into account.”
  4. “Another explanation for the moderate effect of CBGT might be that the therapists had no prior experience with CB(G)T for CFS.(…) CFS patients are more difficult to treat than other patients with somatic complaints’. For our study this might count even more, since the therapists were inexperienced both in group therapy and in CBT for CFS.”  
  5. “Finally, based on this and former studies the treatment protocol CB(G)T for CFS has been improved. Rest and relaxation are less emphasised, and for passive CFS patients the treatment protocol has been adapted.”  
  6. “Recently, lack of social support has been identified as an important determinant of CFS and a new perpetuating factor. Dealing with a lack of social support may also have to become a more prominent aspect of CBT for CFS.”

 

Opmerkingen bij de verklaringen en aanbevelingen

Bij 1. In de tekst die voorafgaat aan deze opmerking noemen de auteurs het voordeel van groepsbehandeling, namelijk dat zij door het groepseffect tot betere resultaten kunnen worden aangezet. Er is dus zowel een argument voor als tegen. De vraag blijft waarom dit als een verklaring wordt opgevoerd.

Bij 2. De verklaring dat de behandeling minder aanslaat bij patiënten die in een juridische claim verwikkeld zijn, wordt te pas en te onpas opgevoerd. Uit de gegevens blijkt niet voor hoeveel patiënten in dit onderzoek een dergelijke situatie aan de orde was en of dit tot een afwijking in de scores heeft geleid.

Bij 3. Patiënten met minder ernstige klachten hebben meer baat bij de behandeling. Praten we dan wel over dezelfde patiëntengroep? De aanbeveling om alleen minder ernstige aangedane patiënten in onderzoek te betrekken is op zijn minst opmerkelijk. Het zou juist van belang zijn te onderzoeken wat het verschil maakt tussen beide groepen.

Bij 4. Het feit dat de therapeuten geen ervaring hadden wordt opgevoerd als verklaring. Het gaat echter om therapeuten die speciaal geselecteerd waren voor dit onderzoek.

Bij 5. Men verwijst naar ander onderzoek waaruit blijkt dat het gebrek aan sociale ondersteuning een belangrijke determinant is voor CVS en een nieuwe in stand houdende factor. Uit niets blijkt dat dit in dit onderzoek een rol heeft gespeeld. Er wordt niet over gerapporteerd. De opmerking is speculatief.

Ondanks alle negatieve bevindingen sluiten de auteurs toch af met de suggestie dat dit onderzoek duidt op een gunstig effect van cognitieve gedragstherapie, terwijl daar geen aanleiding toe is. 

“In the current study we found a moderate effect of CBGT on fatigue, in an unselected group of CFS patients, and with newly trained therapists.”

Het gegeven dat de CIS F uitkomsten wijzen op ernstig aangedane patiënten wordt in deze tekst geheel vermeden. De mogelijkheid dat CGT niet passend is, wordt niet overwogen.

 

Referenties

[i] Bazelmans E, Prins JB, Lulofs R et al. (2005) Cognitive behaviour group therapy for chronic fatigue syndrome: a non-randomised waiting list controlled study. Psychother Psychosom 74: 218-224.

CBT for CFS does not Qure patients suffering with QFS

This is part 2 of our comment on the Qure-study. This comment regards the outcomes of the Follow-up study. (Part 1 can be found here[i])

Nederlandse vertaling aan het eind van dit artikel.

Introduction The Qure study [ii] compared the efficacy of treatment with Doxycycline versus Placebo and Placebo versus Cognitive Behaviour Therapy for CFS in patients diagnosed with QFS, Q-fever Fatigue Syndrome. The conclusion of that study was that CBT for CFS had a positive effect on fatigue severity according to the outcomes of CIS-F (Checklist Individual Strength sublist Fatigue). In November 2018 the authors published the one-year follow-up study[iii] . Their conclusion is that the beneficial effect (as they call it) of CBT on fatigue severity at EOT was not maintained 1 year thereafter. Nevertheless they still recommend CBT as treatment for QFS. They suggest further investigation on tailoring CBT more to QFS, possibly followed by booster sessions. That however, is a controversial conclusion. A conclusion that we will dispute in this comment.

Comparison of outcomes

In the overview below, the outcomes at grouplevel are presented at the start of the treatment (Baseline) at the end of treatment (Endpoint) and at a moment 12 to 15 months after ending the treatment (Follow-up) . The outcomes of treatment with Doxycycline at Follow-up were compared to the outcomes in the Placebo Group at the same moment. The outcomes of the CBT treatment at Follow-up were equally compared to the Placebo outcomes. The initially statisticly significant better scores of the CBT –group for fatigue severity have disappeared. There is no longer a statistically difference between Placebo and Doxycycline, nor is there a statistically significant difference between CBT and Placebo.

The CBT scores got considerably worse at Follow-up, while the Placebo score on CIS-F even improved (although modestly). The outcome scores on SIP8 (Physical functioning) that were totally insufficient for all three groups at the endpoint, got worse for the CBT-group but improved for the Doxycycline- and the Placebo-group. The result at follow-up is that the Placebo-group has better scores on CIS-F and on SIP8 (although still insufficient) than both treatment groups.

qure follow up

Despite these findings the authors still suggest to advise CBT as a therapy of choice: Due to its initial positive effect and side effects of long-term doxycycline use, CBT is still advised as therapy of choice for QFS patients. At present, it is still the only well-investigated treatment modality for QFS patients with a positive effect.

Discussion The conclusion of the authors is incomprehensible. We will explain that in the following observations:

  1. Contrary to what the authors claim, there is no beneficial effect as a result from CBT. The initial fatigue severity score in the CBT-group on CIS F (31,6) was very poor in itself. As we have shown in part 1 of this comment, a score of 31.6 is still far above a score of <27 that is used in other fatigue researches.[iv] (a higher score is worse)
  2. The fact that the SIP 8 scores at Endpoint were still very high, indicates that patients did not function very well. The therapy has not been beneficial at all. These scores are still high enough for the patients to be included in research again.
  3. At follow-up the score on CIS F had got worse for the CBT-group. There is no longer a statistically significant difference between the CBT-group and the Placebo-group on CIS F. When we look closer we can conclude that the Placebo-group scored better than at Endpoint and now scores even better than CBT at Follow-up.
  4. We see the same effect on the SIP 8 scores: the scores of the CBT-group got worse, while the Placebo-group scores ameliorated. The SIP 8 scores in the Follow-up group are now better than those of the CBT-group.
  5. The better results in the Placebo group, although not yet statistically significant, confirm earlier findings from the scores of CFS patients. In the study by Bazelmans et al[v] the authors phrased it as follows: for functional impairment, the effect was opposite to what was expected. Looking at the improvement and the better scores on SIP 8 and CIS F in the non-intervention/Placebo group in the Qure study, this is once more an indication that CBT with a graded activity protocol is impeding the naturally-occurring recovery process.
  6. The findings in this follow-up study confirm the concerns of patients suffering with QFS as well as with CFS: the CBT treatment with a graded activity protocol will lead to deterioration because patient learn during this treatment not to trust on the signs of their body that they have overstretched their possibilities. In the long end this will lead to deterioration. Although authors in several studies contest this conclusion and claim CBT treatment with graded activity is safe, these findings seem to confirm the experiences of the patients.
  7. What would have been the cause of the initially “beneficial effect” on fatigue severity? As Professor James Coyne described [vi] multiple flaws in psychotherapy research that will influence the outcomes. The following flaws have been found in the Qure study:

Subjective self-report outcomes Note: subjective outcome measures do not necessarily reflect the actual or factual situation

Deliberate exclusion of relevant objective outcomes. Note:  As described in part one, no objective measures were reported, although an actometer has been used in this study.

Active treatment conditions carry a strong message how patients should respond to outcome assessment with improvement. Note: patients may have learned to give (socially) desirable answers that do not reflect the factuality.

Specifying a clinically significant improvement that required only that a primary outcome be less than needed for entry into the trial. Note: in this case the authors defined a clinically meaningful improvement as a reduction of 9 points plus a score <35 on CIS F. However, What is the value of such a result if the level of activity is not increased when that is precisely the objective?

 

Conclusions

In general: the QURE study and the follow-up study prove that Cognitive Behavioural Therapy with a gradual activity protocol is not effective in patients with QFS.

  1. The CBT treatment eventually led to a higher fatigue level than the Placebo treatment did.
  2. The physical functioning according to the SIP8 was far from normal at EOT and got worse in the CBT-group at follow-up while the Placebo group improved and scored better at follow-up than the CBT-groep did..
  3. The model of the sustaining factors is (again) invalidated by this research.
  4. The conclusions regarding the safety of the CBT treatment lack a solid substantiation, especially since the CBT-group had poorer scores at follow-up. Together with the considerable drop-out in the CBT-group this may be an indication of the adverse effect of the CBT-treatment with graded activity protocol.
  5. CBT with a graded activity protocol is neither efficacious nor safe in patient sufferings with QFS, as we also have seen before in CFS-patients.
  6. There is no reasonable underpinning to advise CBT as a possible treatment for QFS.

 

[i] https://corsius.wordpress.com/2018/12/30/are-they-really-qured/

[ii] Keijmel SP, Delsing CE, Bleijenber G et al (2017) Effectiveness of long-term doxycycline treatment and cognitive behavioral therapy on fatigue severity in patients with Q-fever fatigue syndrome Clinical Infectious Diseases, 64(8):998-1005

[iii] Raijmakers, PH, Keijmel, SP, Breukers, MC, Bleijenberg, G et al (2018) Long-term effect of cognitive behavioural therapy and doxycycline treatment for patients with Q fever fatigue syndrome: One-year follow-up of the Qure study Journal of Psychosomatic Research 116:62-67

[iv] Knoop H, Bleijenberg G, Gielissen MF (2007) Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? Psychother Psychosom 76: 171-176.

[v] 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.

[vi] https://www.coyneoftherealm.com/blogs/mind-the-brain/when-psychotherapy-trials-have-multiple-flaws

Nederlandse vertaling

Dit is deel 2 van onze reactie op de Qure-studie. Dit commentaar heeft betrekking op de uitkomsten van de Follow-up-studie. (Deel 1 is hier te vinden [i])

 

Introductie

 

In het Qure-onderzoek [ii] werd de werkzaamheid van behandeling met Doxycycline vergeleken met Placebo en Placebo met Cognitieve GedragsTherapie voor CVS bij patiënten met QFS, Q-fever-vermoeidheidssyndroom. De conclusie van dat onderzoek was dat CGT voor CVS een positief effect had op de mate van vermoeidheid volgens de uitkomsten van CIS-F (Checklist Individual Strength sublist Fatigue). In november 2018 publiceerden de auteurs de follow up studie na één jaar[iii].

 

Hun conclusie is dat het gunstige effect (zoals ze het noemen) van CGT op vermoeidheid zoals gemeten bij het eind van de behandeling niet werd gehandhaafd 1 jaar later. Niettemin bevelen ze toch CGT aan als behandeling voor QFS. Ze suggereren verder onderzoek naar het beter afstemmen van CGT op QFS, mogelijk gevolgd door boostersessies. Dat is echter een controversiële conclusie. Een conclusie die we in deze reactie zullen betwisten.

Vergelijking van uitkomsten

In het onderstaande overzicht worden de uitkomsten op groepsniveau weergegeven aan het begin van de behandeling (baseline), aan het einde van de behandeling (eindpunt) en op een moment 12 tot 15 maanden na het beëindigen van de behandeling (follow-up).
De uitkomsten van de behandeling met Doxycycline tijdens de follow-up werden vergeleken met de uitkomsten in de Placebogroep op hetzelfde moment. De uitkomsten van de CGT-behandeling tijdens de follow-up werden ook vergeleken met de Placebo-uitkomsten.
De aanvankelijk statistisch significant betere scores van de CGT-groep op vermoeidheid zijn verdwenen. Er is niet langer een statistisch verschil tussen Placebo en Doxycycline, noch is er een statistisch significant verschil tussen CGT en Placebo.De CGT-scores werden aanzienlijk slechter tijdens de follow-up, terwijl de Placebo-score op CIS-F zelfs (bescheiden) verbeterde. De uitkomstscores op SIP8 (fysiek functioneren) die volstrekt onvoldoende waren voor alle drie groepen bij de eindpuntmeting, verslechterden voor de CGT-groep maar verbeterden voor de Doxycycline- en de Placebogroep. Het resultaat bij follow-up is dat de Placebogroep betere scores heeft op CIS-F en op SIP8 (hoewel nog steeds onvoldoende) dan beide behandelgroepen.
.
qure follow up

Ondanks deze bevindingen suggereren de auteurs nog steeds om CBT te adviseren als een aanbevolen therapie : vanwege het initiële positieve effect en de bijwerkingen van langdurig doxycycline gebruik, wordt CBT nog steeds geadviseerd als therapie bij uitstek voor QFS-patiënten. Op dit moment is het nog steeds de enige goed onderzochte behandelingsmethode voor QFS-patiënten met een positief effect

Discussie

 

De conclusie van de auteurs is onbegrijpelijk. We zullen dat in de volgende opmerkingen uitleggen:

 

1. In tegenstelling tot wat de auteurs beweren, is er geen gunstig effect als gevolg van CGT. De initiële score voor de mate van vermoeidheid in de CGT-groep op CIS F (31,6) was op zich erg zwak. Zoals we in deel 1 van deze reactie hebben laten zien, ligt een score van 31.6 nog steeds ver boven een score van <27 die wordt gebruikt in andere onderzoeken naar vermoeidheid. [Iv] (een hogere score is erger)

2. Het feit dat de SIP 8-scores bij de eindpuntmeting nog steeds erg hoog waren, geeft aan dat patiënten niet goed functioneerden. De therapie was helemaal niet gunstig. Deze scores zijn nog steeds hoog genoeg om de patiënten opnieuw in onderzoek te in te sluiten.

3. Bij follow-up is de score op de CIS F verslechterd voor de CBT-groep. Er is niet langer een statistisch significant verschil tussen de CBT-groep en de Placebo-groep op CIS F. Als we dit nader beschouwen, kunnen we concluderen dat de Placebo-groep beter scoorde dan bij de Eindpuntmeting en nu zelfs nog beter scoort dan CGT bij de Follow-up .

 

4. We zien hetzelfde effect op de SIP 8-scores: de scores van de CGT-groep werden slechter, terwijl de Placebo-groep verbeterde. De SIP 8-scores in de follow-upgroep zijn nu zelfs beter dan die van de CGT-groep.

 

5. De betere resultaten in de Placebo-groep bevestigen, hoewel ze nog niet statistisch significant zijn, eerdere bevindingen op basis van de scores van CVS-patiënten. In het onderzoek van Bazelmans ea [v] hebben de auteurs het als volgt geformuleerd: voor functionele beperkingen was het effect tegengesteld aan wat werd verwacht. Als we kijken naar de verbetering en de betere scores op SIP 8 en CIS F in de niet-interventiegroep in het Qure-onderzoek, is dit nogmaals een indicatie dat CGT met een graded activityprotocol het natuurlijke herstelproces belemmert.

 

6. De bevindingen in dit vervolgonderzoek bevestigen de zorgen van patiënten die lijden aan QFS en CFS: de CGT-behandeling met een graded activityprotocol zal leiden tot verslechtering omdat de patiënten tijdens deze behandeling leren niet te vertrouwen op de tekenen van hun lichaam dat ze zich hebben overbelast. Uiteindelijk zal dit leiden tot verslechtering. Hoewel auteurs in verschillende onderzoeken deze conclusie betwisten en beweren dat CGT-behandeling met graded activityprotocol veilig is, lijken deze bevindingen de ervaringen van de patiënten te bevestigen.

 

7. Wat zou de oorzaak zijn geweest van het aanvankelijk “gunstige effect” op de mate van vermoeidheid? Zoals professor James Coyne heeft beschreven[vi] zullen meerdere tekortkomingen in onderzoek naar psychotherapie de uitkomsten beïnvloeden. De volgende tekortkomingen zijn gevonden in het Qure-onderzoek:

 

Subjectieve resultaten van zelfrapportage Opmerking: subjectieve uitkomstmaten geven niet noodzakelijk de feitelijke of feitelijke situatie weer.

 

Opzettelijke uitsluiting van relevante objectieve uitkomsten. Opmerking: Zoals beschreven in deel 1, werden er geen objectieve uitkomstmaten gerapporteerd, hoewel in dit onderzoek een actometer is gebruikt.

 

Actieve behandelingsomstandigheden dragen een krachtige boodschap over hoe patiënten op de uitkomstevaluatie moeten reageren met verbetering. Opmerking: patiënten hebben mogelijk geleerd om (sociaal) wenselijke antwoorden te geven die de feitelijkheid niet weerspiegelen.

 

• Het specificeren van een klinisch significante verbetering die alleen vereist dat een primaire uitkomst lager is dan nodig voor deelname aan de studie. Opmerking: in dit geval hebben de auteurs een klinisch betekenisvolle verbetering gedefinieerd als een verlaging van 9 punten plus een score <35 op CIS F.  Echter, wat is de waarde van een dergelijk resultaat als het activiteitsniveau niet wordt verhoogd terwijl dat precies het doel is?

 


Conclusies

In het algemeen: de QURE-studie en het follow-up onderzoek bewijzen dat Cognitieve gedragstherapie met een graded activityprotocol niet effectief is bij patiënten met QFS.

1. De CGT-behandeling leidde uiteindelijk tot een hoger vermoeidheidsniveau dan de Placebo-behandeling.

2. Het fysieke functioneren volgens de SIP8 was bij EOT lang niet normaal en werd bij de follow-up slechter in de CGT-groep, terwijl de Placebo-groep verbeterde en bij follow-up beter scoorde dan de CGT-groep deed.

3. Het model van de in standhoudende factoren wordt (wederom) weersproken door dit onderzoek.

4. De conclusies met betrekking tot de veiligheid van de CGT-behandeling missen een degelijke onderbouwing, temeer daar de CGT-groep slechtere scores had bij de follow-up. Samen met de aanzienlijke uitval in de CGT-groep kan dit een aanwijzing zijn voor het nadelige effect van de CBT-behandeling met graded activityprotocol.

5.CBT met een graded activityprotocol is niet effectief noch veilig voor patiënten lijdend aan QFS, zoals we ook eerder hebben gezien bij CVS-patiënten.

6. Er is geen redelijke onderbouwing om CGT te adviseren als mogelijke behandeling voor QFS.

Are they really QUREd? Reactie op de resultaten van onderzoek naar een ‘cure’ voor QFS (Q-fever Fatigue Syndrome

Dit commentaar heeft betrekking op het Qure-onderzoek [i]. Deze studie vergelijkt de werkzaamheid van behandeling met Doxycycline versus placebo en placebo versus cognitieve gedragstherapie voor CVS bij patiënten met QFS, Q-fever-vermoeidheidssyndroom. Volgens deze studie komt QFS voor in ongeveer 20% van de gevallen na een symptomatische acute Q-koortsinfectie. In tegenstelling tot chronische Q-koorts, die ook optreedt na asymptomatische C. burnetii-infectie, is er geen levensvatbare C. burnetii aanwezig.

qure a

qure b

Commentaar

    1. Het aantal participanten is relatief laag. Dat geldt zeker voor de CGT-groep, waar sprake is van een grote uitval. Ondanks alle statistische maatregelen, neemt de zeggingskracht van het onderzoek daardoor af.
    2. De diagnosecriteria voor QVS omvatten alleen vermoeidheid > 6 maanden en q-koorts doorgemaakt. Eventueel zijn er bijkomende verschijnselen, maar die zijn niet noodzaklijk voor de diagnose. Deze criteria zijn niet vergelijkbaar met de CDC-criteria voor CVS waar tenminste 4 additionele klachten uit 8 vereist zijn. De QVS eisen zijn vergelijkbaar met de te algemene Oxford-criteria voor chronische vermoeidheid. Overigens zijn inmiddels ook de Fukuda of CDC-criteria door de CDC als te aspecifiek uitgesloten. Onderzoeken naar de effectiviteit van CGT/GET op basis van deze Oxfordcriteria en de CDC of Fukudacriteria zijn door de AHRQ uitgesloten als bewijs voor de werking, omdat de criteria te algemeen zijn.
    3. De inzet van cognitieve gedragstherapie is uit de aard van de behandeling niet geblindeerd. Dat stelt bijzondere eisen aan de resultaatmeting. Een subjectieve meting moet dan tenminste vergezeld gaan van een objectieve meting. [ii] We know from medical trials that differences can be observed with subjective self-report measures that will not be found with objective measures.
    4. De CGT-behandeling omvat een sterke boodschap die bepaalt hoe de patiënt moet antwoorden op de subjectieve vragenlijsten. Active treatment condition carry strong message how patients should respond to outcome assessment with improvement.[iii]
    5. Een objectieve meting m.b.t. het activiteitenniveau ontbreekt bij de eindmeting terwijl bij aanvang wel een actometer werd gebruikt.
    6. Er is geen weergave van de mate waarin patiënten in de CGT-groep de geformuleerde doelen hebben bereikt, terwijl dat nu juist is waar de behandeling zich op richt.
    7. Subjectieve metingen geven slechts in beperkte mate een beeld van de feitelijkheid. iv.
    8. CBT for CFS is aimed at changing the beliefs and behaviors assumed to maintain fatigue. In het onderzoek(sprotocol) wordt beweerd dat het model van de in stand houdende factoren is aangetoond in onderzoeken bij CVS-patiënten. Dat is echter onjuist. Bij een verbetering van de vermoeidheidsscores neemt de fysieke activiteit van de patiënten niet toe[iv]. Het model van de instandhoudende factoren van Vercoulen et al 1998[v] wordt daarmee ontkracht. Ook Sunnquist en Jason (2017) geven aan dat de werking van het model bij CVS niet kan worden aangetoond.[vi]: This model may not accurately represent the experience of individuals with CFS, particularly those who fulfill more stringent case definitions.
    9. Er is een grote uitval in de CGT groep (15,7%). Ook bij andere CGT-onderzoeken blijkt er sprake te zijn van een verhoudingsgewijs grote uitval [vii]. Het feit dat er sprake is van een dergelijke grote uitval, zegt mogelijk iets over negatieve effecten van de behandeling en dient te worden onderzocht. In de publicatie is van een dergelijke analyse geen melding gedaan.
    10. Er is volgens dit onderzoek sprake van een statistisch significante verbetering in de CIS F score bij de CGT-groep. Hoe relevant is deze statistisch significante verbetering? De score van 31,6 komt nog steeds niet overeen met de score < 27 die in andere onderzoeken als normaal wordt gehanteerd. (Knoop et al, 2007). Wat is de waarde van een dergelijke uitkomst als het activiteitenniveau niet wordt verhoogd terwijl dat nu juist de doelstelling is?
    11. Het is opvallend dat de enige score (SIP 8) die tenminste iets zegt over het fysiek functioneren, niet leidt tot een wezenlijke verbetering. De score van 786.8 in de CGT-groep is zo slecht dat ze bij andere onderzoeken wordt beschouwd als severe impairment en leidt tot inclusie in onderzoek. Ook ten opzichte van de norm in dit onderzoek (450) is deze score volstrekt onvoldoende. Als normale waarde wordt in andere onderzoeken een score van 203 gehanteerd [viii](Knoop et al. 2007)
    12. Bij de SCL 90 wordt weliswaar gesproken over een significante verandering in de score bij de CGT groep, maar ook hier is de vraag hoe relevant de verschillen zijn in de praktijk zijn. We zien slechts gemiddelde totaalscores die zich bovendien alle in de lagere regionen van de scoremogelijkheden bevinden (total range is 90-450).
    13. De placebobehandeling (placebo geneesmiddel) vormt weliswaar een goede vergelijking met de doxycyclinebehandeling, maar is door zijn aard geen goede control voor de CGT-behandeling.
    14. De vergelijking van het aantal Adverse Events zegt weinig over de veiligheid. De beschikbare data in de publicatie zeggen niets over de aard van de events bij de CGT-groep. Zijn de AEs vergelijkbaar? De conclusie op basis van de verhouding in de aantallen of percentages AE dat CGT veilig zou zijn, is niet steekhoudend.
    15. De serologie en PCR in Tabel 1 laat zien dat er geen verschillen zijn tussen de verschillende groepen, dat ze allemaal q koorts hebben doorgemaakt (IgG en IgM). Op dit moment zou geen chronische infectie zijn gemeten o.b.v. de negatieve C burnetii PCR. In Tabel 2 is bijzonder dat men niet de uitkomst laat zien tussen DOX en CBT. De p-waarden zijn erg mager en de auteurs claimen dat de patiënten geen chronische q koorts hebben. Dat is zeer discutabel[ix]
    16. Er is geen follow-up meting voorhanden en er kan dus niet worden vastgesteld of de (volstrekt ontoereikende) wijzigingen die zich hebben voorgedaan ook op termijn worden vastgehouden. Op korte termijn worden de resultaten uit de follow-up gepubliceerd.

 

Conclusies

Algemeen: het QURE-onderzoek vormt geen bewijs voor de werkzaamheid van Cognitieve GedragsTherapie met graduele activiteitenopbouw bij patiënten met QFS.

  1. De CGT-behandeling leidt niet tot een aanvaardbaar (subjectief) vermoeidheidsniveau. De uitkomstwaarde van de CIS-F ligt nog steeds hoger dan in andere onderzoeken als normaal wordt beschouwd.
  2. Het fysieke functioneren volgens de SIP8 is verre van normaal en laat een score op groepsniveau zien die zou leiden tot inclusie in onderzoek.
  3. Het model van de in stand houdende factoren wordt met dit onderzoek (opnieuw) ontkracht.
  4. De conclusies met betrekking tot de veiligheid van de CGT-behandeling missen een degelijke onderbouwing.

 

References

[i] Keijmel SP, Delsing CE, Bleijenber G et al (2017) Effectiveness of long-term doxycycline treatment and cognitive behavioral therapy on fatigue severity in patients with Q-fever fatigue syndrome Clinical Infectious Diseases, 64(8):998-1005

[ii] https://www.coyneoftherealm.com/blogs/mind-the-brain/when-psychotherapy-trials-have-multiple-flaws

[iii] https://www.coyneoftherealm.com/blogs/mind-the-brain/when-psychotherapy-trials-have-multiple-flaws

[iv] Wiborg JF, Knoop H, Stulemeijer M (2010) How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity. Psychol Med 40: 1281-1287

[v] Vercoulen JH, Swanink CM, Galama J, et al. (1998) The persistence of fatigue in chronic fatigue syndrome and multiple sclerosis: development of a model. J Psychosom Res 45(6): p. 507 – 517.

[vi] Sunnquist M, Jason LA, A reexamination of the cognitive behavioral model of chronic fatigue syndrome Journal of clinical psychology 74 (7): 1234-1245

[vii] Prins JB, Bleijenberg G, Bazelmans E (2001) Cognitive behaviour therapy for chronic fatigue syndrome: a multicentre randomised controlled trial. Lancet 357: 841-847.

Knoop H, Bleijenberg G, Gielissen MF (2007) Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? Psychother Psychosom 76: 171-176.

[viii] Knoop H, Bleijenberg G, Gielissen MF (2007) Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? Psychother Psychosom 76: 171-176.

[ix] Wielders CCH, Wijnbergen PCA, Renders NHM, Schellekens JJA, Schneeberger PM, Wever PC, Hermans MHA (2013) High Coxiella burnetii DNA Load in Serum during Acute Q Fever Is Associated with Progression to a Serologic Profile Indicative of Chronic Q Fever, Journal of Clinical Microbiology 51: 3192–3198

 

 

 

 

 

 

 

 

 

 

 

 

Are they really QUREd?

The Qure[i] study compares the efficacy of treatment with Doxycycline versus placebo and placebo versus Cognitive Behaviour Therapy using CFS-protocol in patients diagnosed with QFS, Q-fever Fatigue Syndrome. According to this study QFS is occurring in approximately 20% of cases following a symptomatic acute Q fever infection. In contrast to chronic Q fever, which also occurs after asymptomatic C. burnetii infection, no viable C. burnetii is present.

qure a

qure b

Comment
1. The number of participants is relatively low. That certainly applies to the CBT Group as there is a major dropout. In spite of all statistical measures, the power of the research decreases as a result.
2. The diagnostic criteria for QFS include only fatigue> 6 months and q fever. Possibly there are additional symptoms, but they are not necessary for the diagnosis. These criteria are not comparable to the CDC criteria for CFS where at least 4 additional complaints from 8 are required. The QFS requirements are comparable to the too non-specific Oxford criteria for chronic fatigue. Incidentally, the Fukuda or CDC criteria have now been ruled out by the CDC as too non-specific. Investigations into the effectiveness of CBT / GET on the basis of these Oxford criteria and the CDC or Fukuda criteria have been excluded by the AHRQ as evidence for the effectiveness, because the criteria are too loose.
3. The study into cognitive behavioral therapy is not blinded as a result of the nature of the treatment. That requires special demands to the result measurement. A subjective measurement must then at least be accompanied by an objective measurement[ii].We know from medical trials that differences can be observed with subjective self-report measures that will not be found with objective measures.

4. The CBT treatment includes a strong message that determines how the patient must respond to the subjective questionnaires. Active treatment condition carry strong message about how patients should respond to outcome assessment with improvement.[iii]
5. An objective measurement of the activity level is missing in the final measurement, while an actometer was used at the start.
6. There is no indication of the extent to which patients in the CBT group have achieved the formulated goals, whereas this is precisely what the treatment focuses on.
7. Subjective measures only give a limited picture of the factuality. [iv]
8. CBT for CFS is aimed at changing the beliefs and behaviors of fatigue. The study (-protocol) claims that the model of sickness pepetuating beliefs has been demonstrated in studies in CFS patients. However, that is incorrect. Although the fatigue scores improved, the physical activity of the patients did not increase. The model of the pepetuating factors by Vercoulen et al 1998[v] has thus been invalidated.
Sunnquist and Jason (2017)[vi] also indicate that the model can not be demonstrated in CFS. : This model may not accurately represent the experience of individuals with CFS, especially those who fulfill more stringent case definitions.
9. There is a large dropout in the CGT group (15.7%). There is also a relatively large dropout in other CBT studies[vii]. The fact that there is such a large dropout may say something about negative effects of the treatment and should be investigated. No such analysis has been reported in the publication.
10. According to this study, there is a statistically significant improvement in the CIS F score in the CBT group. How relevant is this statistically significant improvement? The score of 31.6 still does not match the score <27 used in other studies as normal. (Knoop et al, 2007)[viii]. What is the value of such a result if the level of activity is not increased when that is precisely the objective?
11. It is striking that the only score (SIP 8) that indicates at least something about physical functioning does not show a substantial improvement. The score of 786.8 in the CBT group is so bad that in other studies it is considered severe impairment and leads to inclusion in research. This score is also completely inadequate compared to the normal value in this study (450). As normal value, a score of 203 is used in other studies (Knoop et al. 2007).
12. Although the SCL 90 is said to show a significant change in the score at the CBT group, here too the question is how relevant the differences are in practice. We only see average total scores that are all in the lower ranges of the scoring options (total range is 90-450).
13. Although the placebo treatment (= a placebo drug) is a good comparison to doxycycline treatment, it is by its nature not a good control for CBT treatment.
14. The comparison of the number of Adverse Events says little about safety. The available data in the publication say nothing about the nature of the events at the CGT group. Are the AEs comparable? The conclusion based on the ratio in the numbers or percentages AE that CGT would be safe is not sufficiantly substantiated.
15. The serology and PCR in Table 1 show that there are no differences between the different groups, that they all have experienced q fever (IgG and IgM). At this time, no chronic infection would have been measured, e.g. the negative C burnetii PCR. In Table 2 it is special that one does not show the outcome between DOX and CBT. The p-values ​​are very meager and the authors claim that the patients do not have chronic q fever. That is very debatable[ix]
16. There is no follow-up measurement available and it can therefore not be established whether the (inadequate) changes that have occurred are also retained in due course. The results of the follow-up are to be published in the short term.

Conclusions
In general: the QURE study does not provide evidence for the efficacy of Cognitive Behavioral Therapy with a gradual activity protocol in patients with QFS.
a. The CBT treatment does not lead to an acceptable (subjective) fatigue level. The outcome value of the CIS-F is still higher than in other studies is considered normal.
b. The physical functioning according to the SIP8 is far from normal and shows a score at group level that would lead to inclusion in research.
c. The model of the sustaining factors is (again) invalidated by this research.
d. The conclusions regarding the safety of the CBT treatment lack a solid substantiation.

References

[i] Keijmel SP, Delsing CE, Bleijenber G et al (2017) Effectiveness of long-term doxycycline treatment and cognitive behavioral therapy on fatigue severity in patients with Q-fever fatigue syndrome

Clinical Infectious Diseases, 64(8):998-1005

[ii] https://www.coyneoftherealm.com/blogs/mind-the-brain/when-psychotherapy-trials-have-multiple-flaws

[iii] https://www.coyneoftherealm.com/blogs/mind-the-brain/when-psychotherapy-trials-have-multiple-flaws

[iv] Wiborg JF, Knoop H, Stulemeijer M (2010) How does cognitive behaviour therapy

reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity.

Psychol Med 40: 1281-1287

[v] Vercoulen JH, Swanink CM, Galama J, et al. (1998) The persistence of fatigue in chronic fatigue syndrome and multiple sclerosis: development of a model. J Psychosom Res 45(6): p. 507 – 517.

[vi] Sunnquist M, Jason LA, A reexamination of the cognitive behavioral model of chronic fatigue syndrome Journal of clinical psychology 74 (7): 1234-1245

[vii] Prins JB, Bleijenberg G, Bazelmans E (2001) Cognitive behaviour therapy for chronic fatigue

syndrome: a multicentre randomised controlled trial. Lancet 357: 841-847.

[viii] Knoop H, Bleijenberg G, Gielissen MF (2007) Is a full recovery possible after

cognitive behavioural therapy for chronic fatigue syndrome? Psychother Psychosom

76: 171-176.

[ix]Wielders CCH, Wijnbergen PCA, Renders NHM, Schellekens JJA, Schneeberger PM, Wever PC, Hermans MHA (2013) High Coxiella burnetii DNA Load in Serum during Acute Q Fever Is Associated with Progression to a Serologic Profile Indicative of Chronic Q Fever, Journal of Clinical Microbiology 51: 3192–3198

 

How to react on criticism toward your seriously flawed research? A protocol.

Degrade the person who is criticizing your research

– A person who is criticizing the research is biased

– This person is not a scientist, let alone an expert, probably just a patient

– Suggest it is only a small but vocal group of patients that is criticizing your research

– There always is a Conflict of Interest because this person is a patient or has a relative who is a  patient or is funded by patients to attack science

Relabel this persons actions
– Criticizing research does not contribute to science

– Call it bullying and say nobody will enter this field anymore as a result of the bullying

– Submitting a formal complaint is bullying

– Say it is anti scientific

– call it activism

– Say it is libelous (or libellous)

– Say it is vexatious

– Say It is a campaign

– Say it is patients against scientists

Divert the attention from the real topic

– Create a non existing opposition and then accuse the other one of creating opposing positions

– Say It is unethical to prevent people from doing this therapy

– In case official institutions take infavourable measures, say it is the result of patients lobbying

– Say that is a disaster for science

What you have to forget

Forget that science means: taking your hypothesis to the test

What you have to keep in mind

Whatever you do: do not respond to the content of the criticism. Avoid any substantive discussion.

Last but not least

Apply all the above to this blog and its author

 

 

Journalisten van De Monitor geven geen juist beeld

English translation below

In het weerwoord op onze kritiek laten de journalisten van De Monitor  na één van de auteurs te vermelden (had dit een reden?), wordt geen link naar ons artikel voorzien en wordt nauwelijks op onze argumenten ingegaan. De Belgische studie die aantoonde dat de arbeidsparticipatie na CGT/GET daalt, of de financiële belangen van de PACE-auteurs bij verzekeringsinstellingen? Ondanks hun 20-delige artikelenreeks, valt hierover op de website van de Monitor niets te lezen.

De Monitor-journalisten blijven beweren dat de CDC de richtlijn aanpaste onder druk van de patiëntenlobby. Hun argument? Er werden niet één maar meerdere boze brieven geschreven. Ja, dan gaat een gigantische bureaucratie als de CDC natuurlijk meteen overstag… Feit is dat drie prestigieuze instituten kort voor de wijziging hun bevindingen publiceerden. Gedurende alle jaren die daaraan vooraf gingen was de CDC niet bereid gevolg te geven aan brieven van patiënten. Dat Elizabeth Unger met haar verklaring vooral een positieve connotatie wil verbinden aan de koerswijziging (luisteren naar de bezorgdheden van patiënten klinkt een stuk sympathieker dan door de wetenschap in het ongelijk gesteld worden) wordt door de Monitor-journalisten niet als een mogelijkheid aangegeven. Dat bedoelen wij met naïviteit.

Als het gaat om het wetenschappelijk bewijs dat CGT/GET schadelijk is, verschuilen De Monitor-journalisten zich achter de Cochrane review (Larun et al., 2017). Nochtans hebben patiënten hen er herhaaldelijk op gewezen dat dit literatuuroverzicht zowel onverklaarde chronische moeheid als ME/CVS omvat. Neem je daar een gemiddelde van, dan lijkt het inderdaad alsof CGT/GET nog zo slecht niet is. Dezelfde bemerking maakten wij bij de zeven studies die volgens Knoop aantonen dat CGT/GET veilig is; ook hier wordt chronische moeheid en ME/CVS met elkaar verward. Het feit dat de journalisten van De Monitor deze studies in hun verweer opnieuw aanhalen, roept de vraag op of zij dit argument wel voldoende begrijpen.

ME/CVS kent vele namen, maar ‘chronisch vermoeid’ hoort daar niet bij. Dat de term bij meer mensen een belletje doet rinkelen heeft  te maken met het onbegrip en stigma dat al jarenlang over deze ziekte heerst. De Monitor-journalisten hadden dit kunnen doorbreken, maar kozen ervoor dit niet te doen. Als verantwoording stellen zij dat er geen consensus is over de definitie van ME/CVS: onderzoekers kunnen die zelf kiezen. Ook dit klopt niet. Zowel het NIH als de AHRQ riepen op om de zogenaamde Oxford-definitie niet langer te gebruiken. De Gezondheidsraad zegt hierover:

‘Zij raadden onderzoekers af om in de toekomst nog gebruik te maken van de Oxford-definitie […], omdat deze van alle voorgestelde casusdefinities op verreweg de minste symptomen gebaseerd is en waarschijnlijk veel mensen met andere aandoeningen omvat.’

Toen de AHRQ alle onderzoeken die uitgaan van de Oxford-criteria wegliet in haar literatuuroverzicht, bleef de effectiviteit van CBT/GET niet overeind. Het maakt dus wel degelijk uit welke definitie gehanteerd wordt.

Ook De Monitor-journalisten verwijzen naar het rapport van de Gezondheidsraad waarna zij opmerken: “Wat opvalt is dat de rapporten het allemaal voorzichtig opschrijven. Hoe sommigen in dit debat alleen in stelligheden kunnen spreken, reflecteert niet de werkelijkheid.” Daar sluiten we ons bij aan. Het zijn echter de journalisten van  De Monitor die zich aan polariserende uitspraken bezondigen. In de uitzending wordt bijvoorbeeld het volgende beweerd (minuut 23:07):

“Ondanks alle klachten over de therapie, zijn schadelijke effecten nooit wetenschappelijk vastgesteld.”

Wij haalden verschillende wetenschappelijke studies aan waar wel schadelijke effecten van CGT/GET werden vastgesteld. Het zou de Monitor-journalisten sieren indien zij hier hun ongelijk toegaven.

Dat men bij CGT veronderstelt dat de ziekte psychisch is, is volgens de Monitor een hardnekkig misverstand. “Geen van de behandelaars die deze therapie toepast zegt hiervan uit te gaan. Sterker: de behandeling zegt helemaal niets over de oorzaak van de ziekte.” Nochtans gaf Gijs Bleijenberg, de voorganger van Knoop bij het NKCV, klaar en duidelijk aan dat het chronisch vermoeidheidssyndroom “niet het resultaat is van een organische ziekte”.

 

 

 

attribute symptoms

In een recent tv-interview met FOCUS gaf Bleijenberg aan dat de biologische component bij ME/CVS-patiënten volledig verdwenen is. Hij is niet de enige met dergelijke vooroordelen. De omstreden PACE-trial omschreef het doel van CGT als volgt:

“The aim of treatment was to change the behavioural and cognitive factors assumed to be responsible for perpetuation of the participant’s symptoms and disability.”

Ook Hans Knoop gaf in een recent artikel (Van der Schaaf et al., 2018) aan dat de vermoeidheid van ME/CVS-patiënten in stand gehouden wordt door ‘dysfunctional beliefs’. Dat wijst dus wel degelijk op een psychische reden. Waarom blijft De Monitor dan hardnekkig het tegendeel beweren? Omdat Hans Knoop hen dit zo toevertrouwde?

Het is opvallend hoe De Monitor de controversiële uitspraken van deze psycholoog blijft verdedigen:

“Knoop is overigens heel voorzichtig met deze cijfers, aangezien het er maar net van afhangt welke definities je gebruikt voor herstel, je beter voelen, etcetera.”

Laat dit duidelijk zijn: Knoop is helemaal niet voorzichtig met deze cijfers. Er is geen wetenschapper die zulke  succespercentages van CBT/GET claimt of het zou zijn voorganger Gijs Bleijenberg moeten zijn. Dit is een feit dat door iedere kritische journalist eenvoudigweg kan worden nagetrokken.

Verder werd een volledig artikel gewijd aan de visie van CBT-aanhanger Michael Sharpe, terwijl geen enkele buitenlandse expert aan het woord komt die zich kritisch uitlaat over deze behandeling. In de tv-uitzending wordt wel een patiënte geïnterviewd die dankzij CBT genas, maar geen patiënt die door CBT verslechterde. Dit is een eenzijdige benadering, die de heren  Van Loosdregt en Hetebrij weigeren te erkennen. In tegenstelling tot wat Knoop beweert (‘je eindigt niet in een rolstoel door gedragstherapie’) zijn er wel degelijk patiënten die door deze behandeling invalide werden. Dat De Monitor-journalisten deze uitspraak als titel voor hun stuk gebruiken, geeft aan hoe genuanceerd zij met dit onderwerp omgaan.

In plaats van in te gaan op onze kritiek, besloten De Monitor-journalisten om verder door te gaan op het ingeslagen pad. Hoe kan men nou beweren dat ME/CVS-patiënten de studies van Knoop niet serieus nemen als zij hierover een gedetailleerde analyse publiceerden? En waarom schrijft men dat patiëntenverenigingen enkel wetenschappers steunen die aan biomedisch onderzoek doen? In werkelijkheid ontwikkelden patiënten mee de ‘Energy Envelope Theory’ met psycholoog Leonard Jason van de DePaul Universiteit te Chicago. In het VK assisteerden ze gezondheidspsychologe Ellen Goudsmit om de principes van ‘pacing’ uit te werken. Beide benaderingen helpen patiënten om te gaan met hun ziekte door overbelasting tijdig te herkennen en te voorkomen. Geen biomedisch onderzoek dus, maar wel mede ontwikkeld door patiënten en ondertussen gepromoot door zowel de CDC als NICE als een essentieel onderdeel in de behandeling van ME/CVS.

Tot slot is er de fictieve zwart-wit stelling die De Monitor-journalisten in leven roepen om hun narratief te brengen. In tegenstelling tot wat deze journalisten beweren, ijveren patiëntenverenigingen er niet voor om CBT/GET “helemaal in de ban te doen”. Zij willen bovenal dat het niet langer als voorkeursbehandeling geldt, zoals de huidige richtlijn voorschrijft. Net als het advies van de Gezondheidsraad ijveren patiëntenverenigingen ervoor dat CBT en GET niet langer beschouwd worden als “naar algemeen medische maatstaven adequate behandelingen waartoe patiënten verplicht kunnen worden.”

De Monitor plaatst diegenen die kritiek hebben op CGT/GET-onderzoek stelselmatig in de beklaagdenbank. Patiënten die deze behandeling in vraag stellen worden voorgesteld als een probleem in plaats van een deel van de oplossing. Het beeld dat zij schetsen is  incorrect, onvolledig en misleidend. Die verantwoordelijkheid kan men niet blijven ontlopen.

Michiel Tack

Lou Corsius

Journalists of De Monitor do not give a correct impression

In their reply to our criticism, the journalists of De Monitor do not mention one of the authors (did this have a reason?), No link to our article is provided and hardly any reference is made to our arguments. The Belgian study showing that the working participation after CGT / GET falls, or the financial interests of the PACE authors at insurance institutions? Despite their 20-part series of articles, there is nothing to read about it on the Monitor’s website.

The Monitor journalists continue to claim that the CDC adjusted the guideline under pressure from the patients lobby. Their argument? Not one but several angry letters were written. Yes, a gigantic bureaucracy like the CDC will immediately give in… The fact is that three prestigious institutes published their findings shortly before the change. During all previous years, the CDC were not prepared to respond to letters from patients. That Elizabeth Unger, giving this explanation, mainly wants to connect a positive connotation to the change of course (listening to the concerns of patients sounds a lot more sympathetic than being corrected by science) is not indicated as a possibility by Monitor journalists. That is what we mean when we write about naivety.

When it comes to scientific evidence that CGT / GET is harmful, De Monitor journalists hide behind the Cochrane review (Larun et al., 2017). However, patients have repeatedly pointed out to them that this literature review includes both unexplained chronic fatigue and ME / CFS. If you take an average of that, it seems as if CGT / GET is not that bad. We made the same comment on seven studies that, according to Knoop, demonstrate that CBT / GET is safe; here too, chronic fatigue and ME / CFS are confused. The fact that De Monitor’s journalists reiterate these studies in their defense raises the question whether they understand this argument sufficiently.

ME / CFS has many names, but ‘chronic fatigue’ has no place in that chapter. The fact that the term rings a bell with more people has to do with the incomprehension and stigma that has been prevalent about this disease for years. The Monitor journalists could have changed that, but chose not to. As a justification they state that there is no consensus about the definition of ME / CFS: researchers can choose them themselves. This is also not true. Both NIH and AHRQ called for the so-called Oxford definition no longer to be used. The Health Council states:

‘They advised researchers not to use the Oxford definition in the future […], because it is based on the most limited number of symptoms of all proposed case definitions and probably involves many people with other disorders.’

 

When the AHRQ excluded all investigations based on the Oxford criteria in its literature review, the effectiveness of CBT / GET was not maintained. It does therefore matter which definition is used.

The Monitor journalists also refer to the report of the Health Council, and they remark: “What is striking is that the reports all write down carefully. How some can only speak in certainty in this debate does not reflect reality.” We agree. However, it is the journalists of De Monitor who are guilty of polarizing statements. For example, the following is claimed in the broadcast (minute 23:07):

“Despite all complaints about the therapy, harmful effects have never been scientifically established.”

We cited various scientific studies that observed harmful effects of CGT / GET. It would admit the Monitor journalists if they gave them their wrong.

That CGT assumes the illness is psychological is, according to the Monitor, a persistent misunderstanding. “None of the therapists who apply this therapy say that they are assuming that. In fact, the treatment says nothing about the cause of the disease.” Nonetheless, Gijs Bleijenberg, the predecessor of Knoop at the NKCV, clearly stated that chronic fatigue syndrome” is not the result of an organic disease “.


zon mw bleijenberg

attribute symptoms

In a recent TV interview on FOCUS, Bleijenberg indicated that the biological component in ME / CFS patients has completely disappeared. He is not the only one with such prejudices. The controversial PACE trial described the purpose of CGT as follows:

“The aim of treatment is to change the behavioral and cognitive factors to be responsible for perpetuation of the participant’s symptoms and disability.”

Hans Knoop also indicated in a recent article (Van der Schaaf et al., 2018) that the fatigue of ME / CFS patients is maintained by ‘dysfunctional beliefs’. That does indeed indicate a psychological reason. Why does De Monitor persistently claim the opposite? Because Hans Knoop entrusted them with that?

It is striking how De Monitor continues to defend the controversial statements of this psychologist:

“Knoop is also very careful with these figures, since it just depends on which definitions you use for recovery, feeling better, etcetera.”

Let this be clear: Kmoop is not careful at all presenting these numbers. There is no scientist who claims success rates of CBT / GET like these apart from his predecessor Gijs Bleijenberg. This is a fact that can be easily tracked by any critical journalist.

 

Furthermore, a full article was devoted to the vision of CBT supporter Michael Sharpe, while no foreign expert expresses criticism toward this treatment. In the TV broadcast a patient is interviewed who was cured by CBT, but not a patient who deteriorated as a result of CBT. This is a one-sided approach, which Van Loosdregt and Hetebrij refuse to acknowledge. Contrary to what Knoop claims (‘you do not end up in a wheelchair as a result of behavioral therapy’), there are certainly patients who became disabled as a result of this treatment. The fact that De Monitor journalists use this statement as a title for their article, shows how nuanced they deal with this subject.Instead of responding to our criticism, De Monitor journalists decided to continue on the chosen path. How can one claim that ME / CFS patients do not take Knoop’s studies seriously if they published a detailed analysis? And why is it written that patient associations only support scientists who are doing biomedical research? In reality, patients helped psychologist Leonard Jason from DePaul University in Chicago developing the ‘Energy Envelope Theory’. In the UK they assisted health psychologist Ellen Goudsmit to develop the principles of ‘pacing’. Both approaches help patients to cope with their illness by recognizing and preventing overload in a timely manner. No biomedical research, but also co-developed by patients and meanwhile promoted by both the CDC and NICE as an essential component in the treatment of ME / CFS.Finally, there is the fictional black and white position that De Monitor journalists base their narrative on. Contrary to what these journalists claim, patient associations do not seek to “banish” CBT / GET completely. Above all, they want it no longer to be a preferential treatment, as the current guideline prescribes. Just like the Health Council’s advice, patient associations are working to ensure that CBT and GET are no longer regarded as “adequate medical treatments that can be compulsory for patients.”The Monitor systematically places those who criticize CGT / GET research in the dock. Patients who question this treatment are presented as a problem rather than a part of the solution. The impression they give is incorrect, incomplete and misleading. That responsibility can not be denied.

 

https://demonitor.kro-ncrv.nl/artikelen/de-monitor-reageert-op-kritiek-uitzending-mecvs

The Monitor responds to criticism on broadcast ME / CFS

donderdag 13 september 2018 Leestijd: 12 min. Thursday, September 13, 2018 Reading time: 12 min.

Sietze van LoosdregtSietze van Loosdregt

Editor

Bastiaan Hetebrij

News reporter

Thursday, September 13, 2018 Reading time: 12 min.

Our broadcast on the ME / CFS disease could count on criticism from the angle of patient associations. For example, Lou Corsius , father of an ME / CFS patient and an active opponent of cognitive behavioral therapy, wrote a piece with the cooperation of patient Anil van der Zee. Here is a response to the criticism.

But first of all a response to the most frequently accused reproach: The Monitor finds ME / CFS a psychological illness. That is not right.  We do not claim that it is a mental illness. What is true is that we have not found sufficient reasons to ban the current preferential treatment according to the guideline (cognitive behavioral therapy, CBT), the same position as the Health Council earlier this year in a report on the disease.  CGT is usually given in combination with gradede exercise therapy (GET). As a program, we are not the opponents or opponents of this therapy, but we note that there are patients who are recovering from it. We are careful about the strength of the scientific evidence for the therapy and how many people it helps. But that nuance is lost in the debate with a number of critics. On social media, these types of questions are black and white for a number of people, and for a small group they are also right -wrong .

read also: CVS patient back to work after controversial behavioral therapy Thursday 30 August

Where does the accusation that we claim that the illness is psychological then come from? This stems from the statement that CBT assumes that the disease has a psychological cause.  If you have something positive to say about CBT, you deny that the disease has a biomedical or physical cause. That is also what practitioners who use the therapy often hear: They would assume that the disease is between the ears. That is a persistent misunderstanding.  None of the practitioners who apply this therapy say they assume this.  In fact, the treatment says nothing about the cause of the disease. What CGT does state is that behavioral factors play a role in the persistence of complaints, so that you can reduce your symptoms by influencing behavior .

Our broadcast was emphatically not about the cause of the disease, nor about all the biomedical research that is being done. The Health Council notes that these studies have not been reproduced for the time being – a condition for being able to consider a scientific finding as evidence. The Health Council states that ‘it is clear that a lot of work still needs to be done in the research into the development of ME / CFS before scientific results can be achieved that really help patients.’ That is why the Health Council states that more biomedical research must be done into ME / CFS.

Our TV broadcast was about whether it would be wise to remove the treatment from the guideline, as patient associations advocate. We show that the patient lobby is one-sided on this point, but that does not mean that the associations are also one-sided or poorly informed.  But, we do let patients who are helped with CBT. WWe believe that new patients who get lost on the internet and social media in a black and white debate should also be told about the shades of gray.

Let’s get on with the letter from Corsius and Van der Zee. Zij vatten de belangrijkste punten van kritiek samen. They summarize the main points of criticism. Below, on each point a reaction.

 

1. ‘Literature studies caused a change in the direction of CDC’

The debate about the ME / CFS disease is not just a scientific debate, it is also a campaign.  And so you are strong if you have an authoritative institute on your side. That explains why we are discussing the CDC, the authoritative American Centers for Disease Disease Control and Prevention. The CDC recently removed its recommendation for behavioral and remedial therapy from its website. The question is: is the CDC now anti-CGT , and is this due to scientific insights or lobbying of patients. Or is it perhaps a combination of both?

According to Corsius we wrongly suggest that the CDC has adapted the website because of assertive lobbying of patient associations. But according to Corsius it comes from literature studies of three prestigious institutes. To reinforce his argument, he quotes from an interview with Elizabeth Unger, responsible for the change of course of the CDC, on the website Medscape : “The update was prompted by the landmark evidence-based 2015 Institute of Medicine report”. by the landmark evidence-based 2015 Institute of Medicine report “.  This specific article only does not deal with the decision to remove CGT as recommended treatment from the website.

And exactly that is what we wanted to know from Unger : what are the motivations of the CDC to remove cognitive behavioral therapy (and exercise therapy) from the website? And does this also mean that the CDC now rejects these treatments? Unger ’s reply was : “Feedback from the ME / CFS patients and their loved ones showed that these terms can be confusing to the public and sometimes misinterpreted by doctors who are not familiar with ME / CFS. They were also sometimes misinterpreted as a healing treatment, which has not been shown to be for the majority of patients. ‘ Read more:

read also: US deletes recommended ME / CFS treatment after complaints patients Tuesday 28 August

Corsius speaks of a ‘shocking lack of background knowledge’ and ‘naivety’ when we think that ‘patient associations can simply record the CDC policy by writing an angry letter ‘. But the CDC received several letters over the years with the requirement to get the treatments from the website. And that is clearly one of the reasons for the adjustment. We have read some of them and from one of them we quote in the article in question.

 

2. ‘There is indeed scientific evidence that CBT / GET is harmful’

This is the main conflict in the debate on cognitive behavioral therapy. Logical: if CBT is indeed proven harmful, why is this treatment a recommended treatment in our medical guideline?We dive in one more time and detail. It is a difficult discussion because here personal testimonies from patients that the therapy is harmful stand against the opinion that it is not harmful.  The first group is in the majority according to patient surveys .  On the other hand, we found no scientific evidence for that damage. Hans Knoop, the representative of cognitive behavioral therapy in the Netherlands, explains the complaint from the fluctuating nature of the disease. In other words, a deterioration can also come with the course of the disease. Knoop speaks about seven studies that show that there is no damage caused by the therapy. The patient associations and their supporters on social media do not take him seriously by definition.

What did we do?We dive into the reports. In our search we found no scientific evidence for the harmful effects for cognitive behavioral therapy (and GET).

What about the statement of that AHRQ report ( Agency for Healthcare Research and Quality ), which Corsius refers to? According to Corsius, this clearly indicated the harmful effects of exercise therapy. The AHRQ report does indeed attract a number of studies that would demonstrate this. But in the same report we find several passages where it is said that no damage was found after undergoing such a therapy. The conclusions are cautious, because the reports on the damage are not well well reported ‘.

If we go to the conclusion, we first read that the AHRQ is not negative about CBT and GET, and also not wildly enthusiastic. They are again cautious about the potentially harmful consequences.  Here are two important phrases: “Although counseling approaches and GET have shown benefits in some measurements of fatigue, function and global improvement, they have not been well studied in subgroups of the population. (…) The reporting of adverse effects was poor, and although GET appears to be associated with worsening symptoms in some patients, the cause remains uncertain. ‘

If you take this report from the AHRQ as a starting point, you can not say that CGT and GET are harmful. However, it is clear that it needs to be better investigated.  We are in favor of that anyway.

Well, Corsius has more studies that report damage, such as the studies by Black and Nunez . We can not trace it from Black’s 2005 study, but Nunez’s study is simply included in the Cochrane Reviewfrom 2017.  That review is the scientific assessment and summary of the knowledge up until that moment. They conclude, again with due caution, for GET: no worsening of symptoms. ‘Patients with CFS can generally benefit from and experience less fatigue after exercise therapy, and there are no indications that exercise therapy could worsen the outcomes.’

Clicking further also provided this quote from the summary: “Exercise therapy did not exacerbate the symptoms for people with CFS. Serious side effects were rare in all groups, but limited information makes it difficult to draw firm conclusions about the safety of exercise therapy. ‘

Of course we also check the report of the Health Council. That is from the beginning of this year. This is what they write: “The damage that a part of them (the patients, ed.) Reports as a result of CBT, she understands (the GR, ed.) In a general sense as a consequence of the fact that CGT is unfortunately not always has a favorable effect, in combination with the often changing course of ME / CFS. It is quite understandable that some of the patients attribute a deterioration of their state of health during or after CBT to the CBT, while it is unclear whether there is a causal relationship. This does not alter the fact that there is a risk that patients may suffer from CGT in individual cases. The care provider must be alert to this possibility and, if this occurs, advise the patient to stop the further building of physical activity. ‘

The Health Council also finds no causal link between CGT and worsening. Of course, damage can occur in individual cases, but in general that is true of course.What is striking is that the reports all write it down carefully.  How some can only speak in certainty in this debate does not reflect reality.

 

3.  ‘Court declared intimidation accusations unfounded’

Corsius criticizes the fact that in an article we let one American psychologist speak who says he is not happy with the change of course of the CDC: ‘The sad thing is that the basic recommendation is now:’ Learn to live with it ‘.  That means that they now say there is NO approved treatment or cure for ME / CFS. ‘Corsius states that she wants to remain ‘strangely enough’ anonymous.  Why does  she want that, the psychologist also explains in the article.  She does not want to be named out of fear of becoming ‘a target’ of patients.   That may be strange to Corsius, he can not deny that everyone who expresses positive criticism about CGT / GET gets to suffer severe criticism. For example, everyone who comes to us on the website or in the broadcast will receive words of this nature from strong criticism.

Corsius states that American ME / CFS specialists recently joined the CDC step by step: ‘The summit panel voted unanimously to include a statement rejecting unanimously to include a statement rejecting those those modalities as inappropriate and potentially modalities as inappropriate and potentially harmful .’

What Corsius does not mention is that the conscious congress was organized by Lucinda Bateman , an avid opponent of behavioral therapy for CFS. Thirteen ME / CFS experts were present in the panel at this summit . Five of them signed a letter of lobbying to our own Minister Bruins of Medical Care and Sport.

No more than one American psychologist is representative of all American psychologists, we know whether the panel provides a representative picture of how ME / CFS expert America thinks about the best approach to the disease.

Corsius contradicts that there would be an atmosphere of intimidation towards scientists. “Meanwhile, Simon Wessely and Michael Sharpe are allowed to accuse patients of harassment unabashedly, although a court previously dismissed such accusations as unfounded.” Simon Wessely and Michael Sharpe worked on the so – called Pace research , which states that CGT and GET work. The research dates back to 2011 but they are still being tackled firmly by opponents to this day.

read more: Professor stops research into ME / CFS after intimidations Monday 03 September

A part of our broadcast was about the tone of the debate. We also wrote an article about it. You only have to watch Twitter to see someone like Sharpe being attacked. We quote some of them, but Sharpe Twitter timeline is full of them. The fact that a court would have swept away such an allegation as stated by Corsius does not change that. This clearly concerns a very select group of active patients, and we realize that this says nothing about the average patient or activist.

That Wessely and Sharpe specifically accuse ‘patients’ of intimidation at De Monitor, as Corsius writes, is not correct. They do that neither on our website nor in the broadcast.

 

4. Miraculous recovery rates

Hans Knoop, head of the Dutch Knowledge Center for Chronic Fatigue (NKCV), speaks extensively, both on the website and to a lesser extent in the broadcast. Logisch, hij is dé man in Nederland als het gaat over cognitieve gedragstherapie. Logically, he is the man in the Netherlands when it comes to cognitive behavioral therapy. Corsius is particularly disturbed by the success rates of treatment claimed by Knoop: ‘According to Knoop, half of the ME / CFS patients are no longer seriously tired after having followed behavior therapy, figures that are not supported by any research group in the world.’ Although it is a high percentage (50%), what do these people say?  That they are no longer seriously tired. But does that mean that they are all 100% better? No, that percentage is lower. Does that mean that they can do everything again? Not at all. Knoop is also very careful with these figures, since it just depends on which definitions you use for recovery, feeling better, etcetera .

read also: ‘You do not end up in a wheelchair through behavioral therapy’ Friday 31 August

Corsius continues: “Throughout the Netherlands, people now read that half of the ME / CFS patients get better if they start thinking or moving differently.  We consider the Monitor partly responsible for the incomprehension and psychological suffering that ensues from this. ‘  According to this reasoning of Corsius you can not allow advocates of CGT to speak because this can lead to misunderstanding and psychological suffering. We dissociate ourselves from that.

5. ‘ME / CFS is not a psychogenic disorder’

Here, Corsius addresses a relevant theme, namely that of incomprehension and stigmatization, because the disease became psychogenic and is labeled.  But why is a potentially psychogenic cause accompanied by misunderstanding and stigmatization? The Health Council makes the same observation as Corsius does: ‘Many doctors have prejudices about the ME / CFS disease and about the patients who suffer from it. They tend to interpret the illness psychologically. As a result, patients do not experience empathy from their doctor and do not feel taken seriously, which does not benefit their health and reinforces their social isolation. ‘ This is outrageous of course.  Are complaints less real, do we have to take them less seriously, if there is a psychogenic cause? WWe do not make any statement about the cause.

 

6. ‘Chronic fatigue is not equal to CFS, and certainly not to ME’

Our file is called chronically fatigued and our thought was that “chronically fatigued” would ring a bell in more people than, for example, ME / CFS. In our articles we speak consistently about ME / CFS.  It is noteworthy that differences of opinion exist among patient organizations as to who can now call ME, CFS or CFS patient . It just depends on the definition you use for the disease. There is no international standard for this – it is a choice.  About these definitions we spoke with Rob Wijbenga , publisher of the magazine The ME Global Chronicle :

read also: Widower ME patient : ‘ME has no psychic but a physical cause’ Wednesday, May 30

7. ‘Patients defend science’

It is true that Corsius states that patient associations and scientists are committed to biomedical research and that they work together. This mainly concerns scientists who are on the side of the patient associations and turn against CGT. Patient associations defend science as long as they do biomedical research, not when they state that behavioral or movement therapy works.

Corsius : ‘More than 100 scientists endorsed the letter to review the results of the infamous PACE trial , while 73 international ME experts warned Minister Bruins that CBT / GET might harm patients.’ Whether or not the criticism is ‘widely supported’, as Corsius states, we have not investigated this. That is very difficult. After all, for example, how many scientists still support the PACE trial ? Those who have little or no criticism of scientific research will not easily write a joint letter. We have not found it in any case. In short, we have no idea how representative these 100 and 73 scientists are for the science. In the summaries of scientific knowledge, such as the Cochrane review ,the image, as already outlined above, is a bit more nuanced.

 

read also: How do you as a journalist deal with a controversial scientific study? zondag 02 septemberSunday, September 2

Corsius also points to the fact that ME / CFS patients are hard at work ‘to enable scientific research into their disease’. For example, by raising funds ‘for the scientific research that the government is failing to finance.’ You may wonder whether patients are responsible for this themselves. The Health Council agrees with Corsius here , and states that it has indeed failed to investigate biomedical causes of the disease. In recent years there was ‘virtually no money for biomedical research into ME / CFS,’ the council writes. That is why we need more money here quickly: ‘This can contribute to a more balanced approach to the possible causes and consequences of the disease in the Netherlands, where until now the psychosomatic approach was the main focus.’

8. ‘Conflict of interest underexposed’

‘A complete article is devoted to the question of whether patients and their relatives are emotionally competent to question the treatment that causes them harm.’ He quotes De Monitor: “At a given point in time, we wondered to what extent you are so emotionally attached to a disease, that it makes sense to study the disease yourself, or to mix in debates about the quality of scientific research. “”

Also read: A remarkable amount of research into ME / CFS by relatives of patients Wednesday, August 29

It is undeniable that a remarkable number of researchers have a personal relationship to ME / CFS to the disease. The question we ask is therefore a logical one, and, both experts we asked for their opinion thought it was an interesting and relevant question. That the question arises because all the examples can be found on one side of the debate, works for a number of people like ared cloth on a bull. But in a polarized debate this is an obvious question. The conclusion of this article is that on all sides there is always bias, this is fine and as inspiration of research partly necessary, but then independent researchers need to take over.