Discussion in 'PsychoSocial ME/CFS Research' started by Andy, Dec 31, 2018.
Brandolini's law (2013): The amount of energy needed to refute bullshit is an order of magnitude bigger than to produce it.
Part 2 - CBT for CFS does not Qure patients suffering with QFS
CBT for CFS does not Qure patients suffering with QFS
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.
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.
The conclusion of the authors is incomprehensible. We will explain that in the following observations:
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)
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.
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.
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.
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 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.
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.
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?
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.
The CBT treatment eventually led to a higher fatigue level than the Placebo treatment did.
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..
The model of the sustaining factors is (again) invalidated by this research.
The conclusions regarding the safety of the CBT treatment lack a solid substantiation, especially now that 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.
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.
There is no reasonable underpinning to advise CBT as a possible treatment for QFS.
[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.
Thanks to Lou Corsius. I think he (and a fellow writer?) makes a lot of good points.
However, I disagree a little with some of the points in the first blog:
Treatments don't have to bring about such large improvements that scores are at normal for them to have some value. A treatment which brings about some improvements can still be useful.
Also within a mean score, there will be individuals with even better scores. It is a very high threshold to look for means scores to get down to mean normal values. So even if a mean score is not the same as a mean normal score, some individuals could still have reached to mean normal score.
Though it is possibly a bit fairer to look for results closer to mean normal scores when the model for CBT is that the participants should recover and no longer see themselves as patients.
If a drug got the same results as CBT in the initial study, I would be impressed. The biasing effect of the treatment on subjective measures is a big factor here.
Thank you Dolphin for your comment. There is no co-writer. I applied the pluralis modestiae.
Although I agree in general with your remarks about the mean scores that leave a possibility for individuals to score better, I do not agree in this case when looking at the follow-up results where the score intervals are also given. Especially when you combine the scores on CIS F and SIP 8 you will find that nobody in the CBT-group or Doxycycline-group fullfilled the criterium of a normal value (CIS F <35 and SIP8 < 450). Another important fact is that only two subjective outcomeparameters were used. Subjective outcomes do not necessarily give a correct impression of the factuality as measured by objective tools. In this study they did not publish the actometer results.
I could find no numbers mentioning this, but I did find the following:
A reader could easily miss that
Direct link to paper, "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", that is discussed above.
Open access at https://www.sciencedirect.com/science/article/pii/S0022399918308183
What a nonsensical conclusion.
Separate names with a comma.