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Scientific Studies Showing Serious Adverse Effects from GET?

Discussion in 'Latest ME/CFS Research' started by joshualevy, Jan 24, 2015.

  1. joshualevy

    joshualevy Senior Member

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    Can someone post a list of randomized scientific studies showing serious adverse effects from GET, as compared to a control group? By "scientific study", I mean something peer reviewed and published in the scientific literature. By "randomized" I mean a study where one group got GET and other group(s) got other treatments or even no specific treatment, and then numbers of SAEs were compared for the different groups.

    If there is nothing for serious adverse effects, but something for adverse effects, then I'd be interested in the studies showing adverse effects.

    I'm not interested in marketing style surveys, unless they were done on comparative groups that got GET and didn't get it. I'm also not interested in letters to the editor, or other reports which are not published (in the scientific sense) or not peer reviewed.

    I thought there would be a list somewhere, but I haven't found it.

    Joshua Levy
     
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  2. A.B.

    A.B. Senior Member

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    Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up.

    http://www.ncbi.nlm.nih.gov/pubmed/21234629

    Patients in the CBT and GET group had lower physical functioning and higher pain scores at the end.

    As for proper adverse events, I doubt this exists. If I'm not mistaken the above is the only study which reported negative effects for CBT and GET. Why are you interested anyway?
     
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  3. Bob

    Bob

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  4. Esther12

    Esther12 Senior Member

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    PACE is really the only RCT on GET reporting adverse outcomes, and GET didn't do significantly worse than SMC there.

    Maybe they were worse on one harms measure, but the therapists had judged these harms were not related to GET? Sorry - I can't remember the details on this, but remember thinking it didn't look that important either way.

    Generally, reporting on harms has been poor for GET, and with PACE, we don't have evidence that patients were really increasing exercise levels (fitness did not improve), so there's more of a danger that the results from PACE will be used to promote a more active form of GET than that tested, and this will cause more harms in the 'real' non-RCT world.
     
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  5. joshualevy

    joshualevy Senior Member

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    A.B: Your study is very close to what I want (and reporting lower physical functioning and higher pain scores rather than SAEs or AEs is fine with me: it means the same thing). It's not perfect only because the study group got GET and CBT and drugs (compared to the other group which got none of that). So there's no way to compare just GET or just CBT. But it's close.

    Bob: that paper is not useful to me for several reasons: not peer reviewed, not published in the scientific literature, and based on survey data. I am looking through it to see if any of it's footnotes will help me. But footnotes 76-85 are all survey data, so it's not looking to good.

    Ester12: I agree that PACE did not find any SAEs (or AEs) when comparing GET to SMC, which is why I'm asking for other studies.

    Joshua Levy
     
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  6. Esther12

    Esther12 Senior Member

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    That journal did require peer review, but I think it has since closed.
     
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  7. biophile

    biophile Places I'd rather be.

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    Actually: "There were more serious adverse events in the GET group than there were in the SMC group (p=0·0433)."

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065633

    An effect size for this statistically significant difference is not given, but when looking at Table 4, it appears that SAEs were roughly 2.4 times more common for +GET than for SMC-alone, although confidence intervals seem somewhat high for SAEs per 100 person-years. They may not have been particularly common, but they occurred nevertheless.

    But were these events related to GET or just a (statistically significant) coincidence? Serious adverse reactions (SARs) are SAEs which were later judged to be related to therapy. Coincidently, as Esther12 said, once "independent assessors" were unblinded to participant allocation in order to judge whether SAEs were the result of therapy or not, this significant difference between +GET and SMC-alone disappeared. Should patients risk their health based on this?

    PACE have given their definition for serious adverse events:

    "(a) Death; b) Life-threatening event; c) Hospitalisation (hospitalisation for elective treatment of a pre-existing condition is not included), d) Increased severe and persistent disability, defined as a significant deterioration in the participant’s ability to carry out their important activities of daily living of at least four weeks continuous duration; e) Any other important medical condition which may require medical or surgical intervention to prevent one of the other categories listed; f) Any episode of deliberate self-harm."

    PACE have given their definition for serious deterioration:

    "… defined as any of the following outcomes: a short form-36 physical function score decrease of 20 or more between baseline and any two consecutive assessment interviews; scores of much or very much worse on the participant-rated clinical global impression change in overall health scale at two consecutive assessment interviews; withdrawal from treatment after 8 weeks because of a participant feeling worse; or a serious adverse reaction."

    All other adverse events which did not meet this criteria were apparently regarded as safe and insignificant. Some of these measures required sustained severe worsening over a long period of time. What about "non-serious" adverse events, which patients themselves may still deem important to them even if researchers do not when researching their pet therapies? PACE reported that these were very common but not significantly different between groups. However, the collected data on these particular events had also been graded for severity (so it was possible to have a severe non-serious adverse event), but in the published paper all these types were lumped together without any consideration for severity, and so far there has been no data published on the number of these events judged to be a result of therapy.

    The key points for understanding safety in the PACE Trial:

    • The threshold for major harm is greater than what most patients would consider relevant. During the trial, the threshold for harm was raised further while the threshold for improvement was lowered. Not all the relevant harms data was published.

    • All the objective evidence from the trial points towards no sustained increases in exercise anyway, so it can be said that that merely encouraging exercise was relatively "safe", but it cannot be said that actual increases in exercise are safe, since the trial did not show that participants were actually exercising more.

    • PEM was not required from participants and the trial excluded anyone with contraindications or aversions to exercise.

    Very few CBT/GET studies have actually recorded adverse effects at the individual level.
     
    Last edited: Jan 24, 2015
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  8. joshualevy

    joshualevy Senior Member

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    Thank you biophile. I think I got confused by their use of "serious adverse events", "serious deterioration", and "serious adverse reactions" as separate data points in their paper. And that's not even going into the assessors's role in this.

    Joshua Levy
     
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  9. Bob

    Bob

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    The paper was properly published in a (now closed) journal, but the journal wasn't indexed on ncbi. Yes, Kindlon looks at surveys, but he also discusses the issue of under-reporting of harms in CBT/GET research, which I've found very helpful when presenting arguments re CBT/GET.
     
    Last edited: Jan 25, 2015
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  10. Sea

    Sea Senior Member

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    Didn't the FINE trial show deterioration in patients given GET?
     
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  11. Ecoclimber

    Ecoclimber Senior Member

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    With your research background, I'm curious why you are asking this community for such studies since you have supported the Pace Trial study and knocked down every biomedical cause for this illness in every one of your postings?
     
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  12. Bob

    Bob

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    @biophile @joshualevy

    I'd forgotten, and I've just looked it up... The separately-published PACE trial deterioration paper shows deterioration rates in Table 5... As far as I can tell, these are straightforward deterioration rates, using the same measures as the published improvement rates, and they show that CBT/GET were no worse than SMC.

    Dougall D, Johnson A, Goldsmith K, Sharpe M, Angus B, Chalder T, White P. (2014) Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome. J Psychosom Res. 77:20-6.
    http://dx.doi.org/10.1016/j.jpsychores.2014.04.002
     
    Last edited: Jan 24, 2015
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  13. Bob

    Bob

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    Good point. Their intervention was "pragmatic rehabilitation" (PR) which was based on CBT/GET. I haven't studied the FINE trial closely but I think PR caused significant deterioration in fatigue scores when compared to treatment-as-usual (edit: this seems to be at 20 weeks but no significant difference at 70 weeks.) For physical function scores the outcome for PR was slightly worse than the treatment-as-usual control group, but it doesn't look like a significant difference. See treatment effects here and here. (Caveat: I might be wrong - I haven't studies the FINE trial in close detail.)
     
    Last edited: Jan 24, 2015
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  14. Esther12

    Esther12 Senior Member

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    I think you're wrong.

    No significant difference to TAU for their primary outcome, but if they used Likert instead of bimodal scoring PR ended up with a statistically but not clinically significant improvement in fatigue.
     
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  15. biophile

    biophile Places I'd rather be.

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    That quote from 2011 was for the total number of SAEs, but in the 2014 paper Bob mentions, they use the number of participants with SAEs. When comparing the number of participants with SAEs (not the total number of SAEs), there was no statistically significant difference. It may have been statistically underpowered though?

    Participants with serious adverse events: APT 15 (9%), CBT 7 (4%), GET 13 (8%), SMC 7 (4%).
     
    Last edited: Jan 24, 2015
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  16. Bob

    Bob

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    Ah, yes, thanks. But it seems to be a mixed picture. For fatigue at 20 weeks there seems to be a statistically significant difference between PR and TAU, but no significant difference at 70 weeks, according to figure 2. Unless I've misinterpreted it.
     
    Last edited: Jan 25, 2015
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  17. WillowJ

    WillowJ คภภเє ɠรค๓թєl

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    The authors who are interested in adverse effects of non-pharmacological therapies like GET or CBT and the ones who are interested in using CBT/GET do not tend to be the same authors, so there is not much published data.

    Tom's paper discusses this limitation of the literature.

    This sort of short-sightedness in the advocates of these therapies extends beyond the world of ME and CFS. If you look for it, you will find arguments over whether CBT is effective for psychiatric diseases (the mainstream application of this therapy), such as on James Coyne's blog (he argues the evidence base is not able to show an effect).
     
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  18. Woolie

    Woolie Senior Member

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    This isn't a prmary empirical study, but its at least a published source that discusses the reports of risk, and considers the possible basis of the effect:

    Twisk, F. N., & Maes, M. (2008). A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuro endocrinology letters, 30(3), 284-299.

    Abstract:
    Benign Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) is a debilitating disease which, despite numerous biological abnormalities has remained highly controversial. Notwithstanding the medical pathogenesis of ME/CFS, the (bio)psychosocial model is adopted by many governmental organizations and medical professionals to legitimize the combination of Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET) for ME/CFS. Justified by this model CBT and GET aim at eliminating presumed psychogenic and socially induced maintaining factors and reversing deconditioning, respectively. In this review we invalidate the (bio)psychosocial model for ME/CFS and demonstrate that the success claim for CBT/GET to treat ME/CFS is unjust. CBT/ GET is not only hardly more effective than non-interventions or standard medical care, but many patients report that the therapy had affected them adversely, the majority of them even reporting substantial deterioration. Moreover, this review shows that exertion and thus GET most likely have a negative impact on many ME/CFS patients. Exertion induces post-exertional malaise with a decreased physical performance/ aerobic capacity, increased muscoskeletal pain, neurocognitive impairment, "fatigue", and weakness, and a long lasting "recovery" time. This can be explained by findings that exertion may amplify pre-existing pathophysiological abnormalities underpinning ME/CFS, such as inflammation, immune dysfunction, oxidative and nitrosative stress, channelopathy, defective stress response mechanisms and a hypoactive hypothalamic-pituitary-adrenal axis. We conclude that it is unethical to treat patients with ME/CFS with ineffective, non-evidence-based and potentially harmful "rehabilitation therapies", such as CBT/GET.
     
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  19. alex3619

    alex3619 Senior Member

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    There is also an ethical and research question issue here. Those who think its harmful may have ethical obligations to not pursue this kind of study. Those who think its not harmful may not design a study rigorous enough to detect the problem. Patient experience and published pathophysiology does show harm, but the long term effect on a large group is unknown. Given the poor cohort selections its also very difficult to infer from these groups to anyone else.

    This problem is pervasive throughout the psychiatric literature, and I presume the psychological literature as well. There are a small number of papers looking at harm from psycho-psychiatric interventions, and I am currently looking into that and might have something to say by the end of the year.

    Let me make one thing clear. While a lot of psychology and neurology is sound science, and neuroscience tends to be sound, its not clear that much of psychiatry is sound science. Psychiatry seems to have a universal pass that allows it to produce research that is vague, bias-laden, poorly tested, primarily verificationist, and all around nonscience. As an academic area this would be not very important except that, clinically at least, its usualy treated as scientific. Nonscience treated as science is by definition pseudoscience.

    In particular there is not one category in the DSM that has been proved to be valid as a discrete mental illness. The diagnostic categories are malleable, and its a lot like what is happening with the Oxford definition. When you have a highly heterogeneous and overlapping cohort of mixed etiologies how are you going to find a single biiomarker? How are you going to identify causal mechanisms and focus on those to develop treatments?

    Psychiatry is a mess.
     
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  20. Gijs

    Gijs Senior Member

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    Don't forget the high rates (drop outs) patiënts who stop with the therapy because it is to heavy. Anyone know how much this rate in the PACE study? In the Netherlands the study from Blijenberg et al. lancet 2001had a dropout rate of more then 50 %.
     
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