The primary results of the pace trial



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  1. Aus:
    http://forums.phoenixrising.me/index.php?threads/the-pace-trial-–-the-results.18950/


  2. This post is intended to explain the actual primary results of the PACE Trial (as opposed to the spun results.)

    The figure to remember is an average 'response rate' (the proportion of participants who responded to treatment) of 13% for CBT and GET. (So 87% of CFS/ME patients did not respond to treatment with CBT and GET.)

    Also, CBT was shown to be clinically ineffective at reducing disability (as per the primary and secondary outcome results).

    CBT and GET failed to reduce welfare benefit claims or private insurance claims, or to significantly increase employment.

    Let's make sure that everyone in our community knows these results.


    The primary results of the PACE Trial

    Improvement Rates

    These are the primary results of the PACE Trial, taken from Table 3. (1)

    The proportion of patients who responded to treatment (achieved a clinically useful outcome) after treatment with CBT and GET.

    Overall, the average improvement rates for CBT/GET was 13% (NNT = 1 in 8)

    So, to be clear, only an average of approximately 13% of participants in the PACE Trial responded to treatment with CBT or GET.



    Details:

    CBT physical function 13% (NNT = 1 in 8)
    CBT fatigue 11% (NNT = 1 in 9)

    GET physical function 12% (NNT = 1 in 8)

    GET fatigue 15% (NNT = 1 in 7)

    The average for all these primary results for CBT/GET was 13% (NNT = 1 in 8)

    (NNT = number needed to treat)

    Various other sets of unhelpful and/or misleading ‘post-hoc’ results have been promoted by the authors (see subheading: “Misinformation and The 'Normal Range'”, below), but these are the main primary results of the PACE Trial which demonstrate the effectiveness of the therapies.


    Clinical Effectiveness / Therapeutic Effect Size

    CBT physical function = Did not meet the threshold for a clinically useful therapy (7.1 points improvement on a scale of 0 to 100.)
    (CBT was found to be clinically ineffective at reducing physical disability using the primary outcome measure: SF-36 Physical Function.)
    (CBT did not achieve a clinically useful difference from SMC, and had a small effect size, using the methodology of the PACE Trial paper.)

    CBT fatigue = moderately effective (3.4 points improvement on a scale of 0 to 33)

    GET physical function = moderately effective (9.4 points improvement on a scale of 0 to 100)

    GET fatigue = moderately effective (3.2 points improvement on a scale of 0 to 33)

    The threshold for a CUD was 8 points for SF-36 physical function and 2 points for Chalder fatigue, so the therapeutic effects did not go far beyond a CUD where treatments were 'moderately effective', and did not reach the threshold of a CUD in the case of CBT and physical function.


    _______________________________________________________________________
    _______________________________________________________________________


    The PACE Trial - Background and Explanation of Results

    Introduction

    The PACE Trial, published in the Lancet in February 2011, was a multi-million pound UK government-funded research study, researching the effects of four potential treatments for CFS/ME, involving 641 patients. The treatments investigated were Cognitive Behavioural Therapy (CBT), Graded Exercise Therapy (GET), Adaptive Pacing Therapy (APT), and Specialist Medical Care (SMC).

    The PACE Trial recruited secondary care patients, and excluded housebound patients, so the results do not apply to severely affected patients. (1)(16)

    The study was divided into four therapy groups: SMC only; CBT with SMC; GET with SMC; and APT with SMC. The SMC group was designed to be used as a control group, against which the other therapies were compared.

    The average response rate (the proportion of patients who experienced a clinically useful therapeutic effect) for the primary outcomes was approximately 13% for CBT and GET. (See the detailed results above, and Table 3 of the published paper.) (1)(18)

    CBT failed to demonstrate clinical effectiveness at improving physical disability for the primary and secondary outcomes.

    I've seen many patients incorrectly stating that the primary result of the PACE Trial was a 30% improvement rate for CBT and GET. This is incorrect. The actual result was approximately 13% for CBT and GET.

    The misunderstanding isn't surprising considering the misleading information promoted by: the Lancet (2); at least one of the PACE Trial authors (3); the media (4)(5); and now the MRC (6). The media and the Lancet have misreported a "30% recovery rate" (2)(4)(5) (but no recovery data has yet been released), and the MRC has now reported a 60% rate of improvement which they have misattributed to CBT and GET. (6)

    I hope this will set the record straight.


    Measures of a Positive Outcome

    First of all, it is essential to focus on the primary outcomes. The primary outcomes were the main results of the PACE Trial, and the main measures of therapeutic effect of each of the therapies.

    The two primary outcome measures were the SF-36 Physical Function questionnaire (which measured self-reported physical disability) and the Chalder Fatigue questionnaire (which measured self-reported subjective levels of fatigue.)

    The measure of a 'positive outcome', and the definition of a 'clinically important difference', that were proposed in the Trial protocol (7), were subsequently abandoned in favour of a 'post-hoc' definition of a 'clinically useful difference' (CUD), which had a substantially lower threshold for the therapies to be considered successful. The ‘post-hoc’ measure of a ‘CUD’ placed CBT and GET in a more favourable light than the protocol measures would have done.

    In the published PACE Trial paper, the (post-host) definition of the 'clinically useful' outcome (represented in the paper as the 'clinically useful difference' or 'CUD'), for the two primary outcome measures, was defined as 2 points on the Chalder Fatigue scale of 0 to 33, and 8 points on the SF-36 physical function scale of 0 to 100. Questions have been raised about whether the post-hoc definition of the CUD was statistically appropriate. (17)

    Every patient who improved by at least an amount defined by the CUD was considered to have clinically responded to treatment. If changes in health outcomes failed to meet the threshold of the CUD, then the therapy was not considered to be clinically useful (i.e. was considered to be clinically ineffective.)

    Despite the authors changing the measure of a 'positive outcome' and a 'clinically important outcome', set out in the Trial protocol, to a lower threshold in the 'post-hoc' definition of a CUD, the primary results for CBT and GET were still far from impressive.



    The primary results of the PACE Trial


    Response Rates

    The proportion of patients who responded to treatment (achieved a clinically useful outcome) after treatment with CBT and GET.



    CBT physical function 13% (NNT = 1 in 8)
    CBT fatigue 11% (NNT = 1 in 9)

    GET physical function 12% (NNT = 1 in 8)
    GET fatigue 15% (NNT = 1 in 7)

    The average for all these primary results for CBT/GET was 13% (NNT = 1 in 8)

    (NNT = number needed to treat)

    These results are taken from Table 3 in the PACE Trial, and are the primary results of the study. (Number improved from baseline: Difference from SMC.)




    So, the PACE Trial demonstrated that an average of only about 13% of CFS/ME patients respond to treatment with CBT or GET.

    This means that approximately 87% of patients did not benefit from CBT or GET, the only treatments recommended for ME by NICE.

    By contrast, 58% (physical function) and 65% (fatigue) of the SMC group achieved a clinically useful outcome.

    Note that SMC group was a 'control' group, so it is not legitimate to compare the results of CBT/GET with SMC, as if SMC was a normal therapy group. The SMC control group was designed for the PACE Trial to take account of natural fluctuations over time, and so any improvements seen in the SMC group might have taken place with no treatment.

    The improvements attributable to CBT and GET were improvements over and above (i.e. in addition to) those seen in the SMC control group, as CBT and GET were always used as supplements to SMC. Subtracting the results of the SMC-alone group from the results of the CBT+SMC and GET+SMC groups, gives us the results attributable to CBT and GET.

    To reiterate, only about 13% of patients responded to treatment with CBT or GET, as per the primary results. This left 87% of patients without any benefit from CBT or GET.




    The primary results of the PACE Trial


    Clinical Effectiveness / Therapeutic Effect Size

    The published PACE Trial paper declares that CBT and GET are 'moderately effective' therapies. However, when the data tables are studied closely, it becomes apparent that CBT failed to meet the threshold for a 'moderately effective' therapy, for physical function (SF-36 physical function), one of the two primary outcome measures.

    This means that CBT failed to demonstrate clinical usefulness, or clinical effectiveness, in terms of reducing physical disability. So CBT is clinically ineffective at reducing physical disability.

    This primary outcome result for CBT was supported by the only other measure used in the PACE Trial to assess physical disability: The 'six minute walking distance test' was an objectively measured secondary outcome measure (the only objective measure used in the PACE Trial, after the planned actometers were dropped from the Trial) which measured physical capacity, or physical disability. CBT failed to improve walking distances beyond the improvements seen for SMC.

    CBT was therefore found to be clinically ineffective at reducing physical disability, in all the outcome measures used.

    For the primary outcomes, CBT was found to be moderately effective only at reducing subjective symptoms of fatigue.

    So, CBT moderately improved subjective feelings of fatigue, but made no difference to physical disability.

    GET was found to be 'moderately effective' for both primary outcome measures.

    It should be noted that the term 'moderate' in relation to a clinical 'effect size' (e.g. 'moderately effective'), is a strictly defined scientific term, and does not necessarily reflect the use of the word 'moderate' as a lay person might use it.

    The average improvements for CBT were as follows:

    CBT physical function = 7.1 on a scale of 0 to 100 (not a clinically useful outcome)

    (CBT did not achieve a clinically useful difference from SMC, and had a small effect size, using the methodology of the PACE Trial paper.)

    CBT fatigue = 3.4 points on a scale of 0 to 33. (moderately effective)

    GET physical function = 9.4 points on a scale of 0 to 100 (moderately effective)

    GET fatigue = 3.2 points on a scale of 0 to 33. (moderately effective)

    The threshold for a CUD was 8 points for SF-36 physical function and 2 points for Chalder fatigue, so the therapeutic effects for each measure did not go far beyond a CUD, where they were moderately effective, and did not reach the threshold of a CUD in the case of CBT and physical function.

    (These figures are taken from Table 3: Mean difference from SMC.)


    The overall results were not impressive.

    The median average SF-36 physical function score, for all adults in England, is 95 points (8). (This is on a scale of 0 to 100, where a score of 100 is the healthiest score.)

    At the end of the PACE Trial, the average SF-36 physical function score for CFS/ME patients (after treatment with CBT+SMC and GET+SMC) was ‘58’ points for both groups, well below the median average score for all adults in England. An SF-36 physical function score of ‘58’ is possibly (this needs to be confirmed) within the poorest functioning 10 percent of the adult population. (20)

    This post-treatment average score of 58 points, for the CBT and GET groups, is worse than average patient scores for 'Class I' chronic congestive heart failure patients, with a score of 79.2 (9); Hepatitis C patients, with a score of 79.3 (9); Osteoarthritis of the Hip patients, with a score of 62.4 (10); and rheumatoid arthritis patients, with a score of 62.3 (10).

    The entry criteria for the PACE Trial was an SF-36 physical function score of 65, for which the PACE Trial literature described fatigue being 'severe'. (19)

    So although there were some 'clinically useful', as defined by the PACE Trial, average improvements in some measures, the end results in all groups were not impressive at all.

    The PACE Trial paper, itself, even concludes:
    "Our finding that studied treatments were only moderately effective also suggests research into more effective treatments is needed."


    Misinformation, and The 'Normal Range'

    All the reports of a "30% recovery rate" (2), or of 30% “getting back to normal" (3), or even a "60% improvement rate" (6), as a result of treatment with CBT or GET, are simply incorrect.

    The 'recovery' data has not yet been released, so there are no 'recovery rates', despite a glowing Lancet commentary making that mistake (as yet, still uncorrected).

    The misreporting of a 'recovery rate' seems to have been based on a misunderstanding of the meaning of the post-hoc 'normal range' analysis.

    The so called 'normal range' analysis is purely a statistical tool, more appropriately known as a 'reference range', that can be used by researchers to help them understand their results, and in this case it does not indicate a 'normal' level of health as a lay person would understand the term 'normal', and it does not indicate a 'good' level of health, or even an ‘improvement’ in health.

    The 'normal range' post-hoc analysis used in the PACE Trial seems to be quite meaningless, for a number of reasons.

    To be within the 'normal range' a patient had to have an SF-36 physical function score of at least 60, which was a worse score than the upper threshold of the entry criteria for the PACE Trial of 65 points. So a patient could be recruited into the PACE Trial with a score of 65, and then could have deteriorated after treatment with CBT or GET to a score of 60, to then be declared as being within the 'normal range', and subsequently misreported in the media and the Lancet as having 'recovered'.

    A person within the 'normal range' could also be ill enough to be recruited into the Trial, so clearly not in good health.

    Also, a score of 60 clearly does not indicate ‘good health’, as the average scores for other illnesses demonstrate, listed above. According to the normative data, an SF-36 physical function score of ‘60’ is possibly (this needs to be confirmed) within the poorest functioning 10 percent of the adult population (20). 25% of the population have an SF-36 physical function score of 75 or lower (23).

    It didn't help to clarify the situation when one of the authors of the PACE Trial inappropriately talked of patients "getting back to normal" in a press conference (3). Clearly, without studying the paper in depth, anyone being told that patients were "getting back to normal", or were within the 'normal range', could easily misinterpret this as meaning a "recovery", as indeed it was misinterpreted by the media and the Lancet itself.

    Any reports of "30%" being within the normal range, or "60%" improvement rates, as a result of CBT and GET, are misleading also because the changes in the control group have to be taken account before the effects attributable to CBT and GET can be calculated. Once the effects seen in the control group are taken into account, then we see the primary results listed above. The authors know this, but we are still seeing these misleading figures being promoted all over the place, allegedly attributable to CBT and GET, including from the MRC and the Lancet, who should both know better. It is dangerous to promote inaccurate or misleading medical trial results.

    As an example, the “60%” improvement rate (incorrectly and misleadingly attributed to CBT and GET) that has recently been promoted by the MRC (6) is based on a ‘secondary’ ‘post-hoc’ analysis, and is not the main or primary result. It is based on the results for the proportion of participants who achieved a CUD in both of the primary outcome measurements. However, (approximately) “60%” applies to improvements seen for CBT plus SMC, and it does not indicate improvements attributable to CBT. Once the improvements in the SMC control group (45%) are taken into account, then the improvements in this secondary post-hoc analysis are 14% for CBT and 16% for GET.

    And, for the 'normal range' analysis, the proportion of participants within the 'normal range' in the SMC group was 15%, so if this analysis had any usefulness, then the figures that apply to CBT and GET would be 15% (CBT) and 13% (GET). As explained above, the 'normal range' does not indicate an improvement in health, or 'good health', but this is yet another example of how the "30%" 'normal range' figure has been promoted unhelpfully.



    A note regarding misinformation about SMC (Specialist Medical Care).

    Specialist Medical Care (SMC) included advice about avoiding extremes of activity, and prescribed medication such as antidepressants, sleeping medication and pain medication where appropriate. (7)

    The authors of the PACE Trial have talked a lot about CBT and GET being more successful than SMC (11). But this is incorrect, based on the results of the PACE Trial.

    The SMC control group was not designed to test the effectiveness of SMC, as it was intended to be used as a control against which to test APT, CBT and GET.

    CBT and GET were used always as a supplement to SMC, and then the effects of CBT+SMC and GET+SMC were tested against an SMC-alone group.

    The incremental effects of CBT and GET could then be determined, by subtracting the results of the SMC-alone group from the CBT+SMC and GET+SMC groups.

    This shows us the effectiveness of CBT and GET.

    The effects of SMC-alone exceeded the incremental effects of CBT and GET, so it is not correct to say that CBT and GET were more successful therapies than SMC, as the authors have done since publication.

    What can be said, for example, is that CBT and GET had therapeutic value (where they did) when used as a supplement to SMC. Or that when CBT was used as a supplement to SMC, the combined effects of CBT and SMC were more effective (where they were) than SMC alone.

    To demonstrate this further, 58% (physical function) and 65% (fatigue) of the SMC group achieved a clinically useful outcome, compared with an average of 13% for CBT and GET.



    Unpublished Data

    The 'recovery rates', and the ‘deterioration rates’ (as determined by an equivalent measure as the improvement rates) have not yet been published.

    Clearly the 'recovery rates' will be less than 13% in relation to CBT and GET, as only 13% of the participant responded to treatment with CBT and GET.

    The 'deterioration rates' are essential information for such an important clinical trial, because clinicians need to know what proportion of their patients will be harmed by the therapies, as well as how many might benefit.




    A quick note about the diagnostic criteria used in the PACE Trial

    All participants were recruited using the Oxford Criteria (13). The effects of the therapies were further analysed by sub-grouping the recruited Oxford Criteria participants, using a set of criteria by Reeves et al., published in 2003 (14), and a modified version of the London Criteria. (15) (It should be noted that the London criteria have never been published in a peer reviewed journal.)

    The PACE Trial paper acknowledges that the Oxford criteria are not an internationally recognised set of criteria, so the use of them to recruit patients to the PACE Trial raises questions about the quality and relevance of the results.

    The Oxford Criteria (used to recruit patients) only requires unexplained chronic fatigue of definite onset, and no other symptoms are necessary, for a diagnosis. Therefore, the Oxford Criteria may select idiopathic chronic fatigue patients, or “Fatigue syndrome” patients (WHO ICD-10: ‘Neurotic, stress-related and somatoform disorders’: ‘Other neurotic disorders’: F48.0), who may respond differently to psychological interventions than CFS/ME patients (WHO ICD-10: ‘Other disorders of the nervous system’: ‘Other disorders of brain’: G93.3) selected using international criteria, such as CFS Fukuda. (21)

    CFS Fukuda, and other international CFS/ME criteria (22), require other symptoms to be present, and are therefore more exclusive than the Oxford Criteria. The Oxford criteria are thus likely to define a more heterogeneous cohort, than internationally recognised criteria, and it is questionable whether the results of the PACE Trial can be extrapolated to a population of CFS/ME patients using internationally defined criteria.

    The authors say that by sub-grouping patients using the London criteria and the Reeves et al. criteria, they have demonstrated that CBT and GET work equally well with patients diagnosed using different criteria. However, best practise is to recruit patients using the sets of criteria intended to be investigated, so that distinct cohorts are investigated. Selecting patients using one set of criteria and then sub-grouping using other criteria can lead to unexpectedly skewed results, or a set of results that does not represent a clear picture of events.

    ____________________________________________________________________




    References:

    (1) Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial.


    Prof PD White et al.
    The Lancet, Volume 377, Issue 9768, Pages 823 - 836, 5 March 2011
    doi:10.1016/S0140-6736(11)60096-2
    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60096-2/abstract

    (2) The Lancet commentary


    Chronic fatigue syndrome: where to PACE from here?
    Gijs Bleijenberg and Hans Knoop
    doi:10.1016/S0140-6736(11)60172-4
    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60172-4/fulltext
    "In accordance with this criterion, the recovery rate of cognitive behaviour therapy and graded exercise therapy was about 30%—although not very high, the rate is significantly higher than that with both other interventions."

    (3) PACE Trial press conference podcast


    http://www.meactionuk.org.uk/PACEpressconf.mp3
    Conference was held at the Science Media Centre on the 17th February 2011
    Professor Trudie Chalder stated:
    "...if you think about the number of people who get back to normal levels of functioning and fatigue then you see twice as many people in the graded exercise therapy and cognitive behavioural therapy group improving and getting back to normal compared the other two groups."

    (4) The Times


    18 February 2011

    http://www.thetimes.co.uk/tto/health/news/article2917876.ece

    "About 30 per cent of patients given cognitive behavioural therapy (CBT) or graded exercise made a full recovery to normal levels of activity, the study found..."

    (5) The Independent


    18 February 2011
    http://www.independent.co.uk/life-s...-out-and-exercise-say-scientists-2218377.html
    "Overall, 60 per cent of patients who received CBT or GET made progress and 30 per cent recovered sufficiently to resume normal lives.”

    (6) MRC Press Release


    1st August 2012
    http://www.meassociation.org.uk/?p=12343
    “In 2011, the first findings from the PACE trial showed that CBT and GET benefit around 60 per cent of patients with CFS/ME...”

    (7) PACE Trial - Full Protocol:


    PACE. Pacing, graded Activity, and Cognitive behaviour therapy; a randomised Evaluation
    Full Protocol
    Final Protocol Version 5.0
    01 February 2006
    ISRCTN54285094
    http://www.meactionuk.org.uk/FULL-Protocol-SEARCHABLE-version.pdf

    (8) Normative Data


    Health Survey for England (HSE) 1996 (All adults, ages 16+)

    (9) Health related quality of life in patients with congestive heart failure: comparison with other chronic diseases and relation to functional variables


    J Juenger et al. Heart 2002;87:235–241

    http://heart.bmj.com/content/87/3/235.full.pdf

    (10) Health related quality of life in multiple musculoskeletal diseases: SF-36 and EQ-5D in the DMC3 study

    H S J Picavet, N Hoeymans 26 July 2003
    Ann Rheum Dis 2004;63:723–729. doi: 10.1136/ard.2003.010769
    http://ard.bmj.com/content/63/6/723.full.pdf

    (11) The EACLPP / European Association for Consultation Liaison Psychiatry and Psychosomatics


    Abstracts, oral presentations (appearing in session order)
    Conference takes place 27 - 30 June 2012 at the Aarhus University Campus, Aarhus - Denmark
    http://www.eaclpp-ecpr2012.dk/Home/DownloadOral
    "We found that CBT and GET were more effective than APT and SMC"

    (12) Adaptive Pacing, Cognitive Behaviour Therapy, Graded Exercise, and Specialist Medical Care for Chronic Fatigue Syndrome: A Cost-Effectiveness Analysis


    Paul McCrone, Michael Sharpe, Trudie Chalder, Martin Knapp, Anthony L. Johnson, Kimberley A. Goldsmith, Peter D. White.
    August 1, 2012
    PLoS ONE 7(8): e40808. doi:10.1371/journal.pone.0040808
    http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040808

    (13) Oxford Criteria


    A report - chronic fatigue syndrome: guidelines for research
    Journal of the Royal Society of Medicine Volume 84 February 1991
    Dr M C Sharpe et al.
    Report of a consensus meeting held at Green College, Oxford 23 March 1990

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1293107/pdf/jrsocmed00127-0072.pdf

    (14) Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution

    William C Reeves, Andrew Lloyd, Suzanne D Vernon, Nancy Klimas, Leonard A Jason, Gijs Bleijenberg, Birgitta Evengard, Peter D White, Rosane Nisenbaum, Elizabeth R Unger and the International Chronic Fatigue Syndrome Study Group
    BMC Health Services Research 2003, 3:25
    doi:10.1186/1472-6963-3-25
    http://www.biomedcentral.com/1472-6963/3/25/

    (15) The London criteria. Report on chronic fatigue syndrome (CFS), post viral fatigue syndrome (PVFS) and myalgic encephalomyelitis (ME).


    Westcare, Bristol: The National Task Force, 1994.
    Info:
    http://www.mecfsforums.com/wiki/London_definition
    http://www.meactionuk.org.uk/Ellen_and_the_London_criteria.htm
    http://www.meassociation.org.uk/?p=4702

    (16) PACE Trial FAQs


    http://www.pacetrial.org/faq/faq2.html
    “13. Are the results applicable to those worst affected? We do not know as we did not study housebound participants. Results cannot be therefore be extrapolated to those who are severely affected.”

    (17) The PACE trial in chronic fatigue syndrome


    Jane Giakoumakis
    The Lancet doi:10.1016/S0140-6736(11)60689-2
    http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60689-2/fulltext

    (18) Michael Sharpe on ABC National Radio, The Health Report.

    Comparison of treatments for chronic fatigue syndrome - the PACE trial.

    http://www.abc.net.au/rn/healthreport/stories/2011/3192571.htm#transcript
    “We have a number needed to treat; I think it's about seven to get a clinically important treatment benefit with CBT and GET. What this trial isn't able to answer is how much better are these treatments than really not having very much treatment at all.”

    (19) Pacing, graded Activity, and Cognitive behaviour therapy; a randomised Evaluation


    Final Protocol Version 5.0
    01 February 2006
    ISRCTN54285094
    http://www.meactionuk.org.uk/FULL-Protocol-SEARCHABLE-version.pdf
    "How do I qualify for your study?
    You must be diagnosed by us as having CFS/ME. Fatigue or lack of energy must be your main problem, and it must be sufficiently severe and disabling."

    (20) Short Form 36 (SF-36) Health Survey questionnaire: which normative data should be used? Comparisons between the norms provided by the Omnibus Survey in Britain, The Health Survey for England and the Oxford Healthy Life Survey.


    Ann Bowling, Matthew Bond, Crispin Jenkinson and Donna L. Lamping.
    J Public Health (1999) 21 (3): 255-270. doi: 10.1093/pubmed/21.3.255
    Normative Data for SF-36
    Figure 1. Histograms of SF-36 dimensions with normal plot.
    Histogram of Physical Functioning with normal plot

    (21) The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study


    Keiji Fukuda et al
    Ann Intern Med. 1994;121:953-95 1994

    http://www.ncf-net.org/patents/pdf/Fukuda_Definition.pdf

    (22) Myalgic encephalomyelitis: International Consensus Criteria

    Carruthers et al
    doi: 10.1111/j.1365-2796.2011.02428.x
    http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02428.x/pdf

    (23) Health Survey for England (HSE) 1996 (ages 16+)


    http://www.archive.official-documents.co.uk/document/doh/survey96/tab5-18.htm

    ________________________________________________________________________




The Cost Effectiveness Paper

The cost effectiveness paper has recently been published (1), and it showed that CBT and GET resulted in no significant difference to the number of patients receiving welfare benefits or private financial payments (insurance and pensions), compared with the control group. (The number and proportion of participants claiming benefits increased in every benefit category, for every therapy group, across the board.)

There was also no significant change in the number of days of lost employment after treatment with CBT and GET, compared to the control group.

So, some useful info to take from the cost effectiveness paper is that CBT and GET resulted in no significant difference to:


1. The number of patients receiving welfare benefits (income-related and illness/disability-related welfare benefits) and private financial payments (income protection insurance and private pensions).
2. The number of days of lost employment.


References:

(1) Adaptive Pacing, Cognitive Behaviour Therapy, Graded Exercise, and Specialist Medical Care for Chronic Fatigue Syndrome: A Cost-Effectiveness Analysis

Paul McCrone, Michael Sharpe, Trudie Chalder, Martin Knapp, Anthony L. Johnson, Kimberley A. Goldsmith, Peter D. White.
August 1, 2012
PLoS ONE 7(8): e40808. doi:10.1371/journal.pone.0040808
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0040808

Flawed hypothetical cognitive behavioural model of illness

The PACE Trial, published in the Lancet in February 2011, was a multi-million pound UK government-funded research study, researching the effects of four potential treatments for CFS/ME, involving 641 patients. The treatments investigated were Cognitive Behavioural Therapy (CBT), Graded Exercise Therapy (GET), Adaptive Pacing Therapy (APT), and Specialist Medical Care (SMC).

CFS/ME is categorised by the WHO, and the UK government, as a neurological disorder. However, the versions of CBT and GET, which were investigated in the PACE Trial, were based on a controversial cognitive behavioural model of CFS/ME which hypothesises that the illness is a ‘reversible’ psychosomatic condition, perpetuated by a (maladaptive) 'fear of exercise' and a (maladaptive) ‘avoidance of exercise' leading to 'deconditioning'.(1) (2)

The results of the PACE Trial confirmed what many patients already know: That CBT and GET cannot be used to successfully treat or cure CFS/ME. Only approximately 13% of participants responded (achieved a clinically useful outcome) to treatment with CBT or GET. This demonstrated that the hypothesis that CFS/ME is a psychological or psychosomatic condition, perpetuated by a fear of exercise etc., is unfounded.

The fact that the main UK government scientific research funding body, the MRC, and the DWP (Dept of Work and Pensions), chose to fund such an expensive investigation into psychological therapies that are designed to treat and reverse a psychologically 'perpetuated', or psychosomatic, illness when CFS/ME is categorised as a neurological disease by both the UK government and WHO, suggests a misappropriation of funds. If only patients had been listened to, then the authorities would already have known that CBT and GET are of limited value. (3)

It is not surprising that CBT and GET, as treatments for CFS/ME, remain controversial with patients while they are promoted as successful treatments that reverse illness, or reverse disease progression. Such a model of illness is not supported by the evidence of the PACE Trial, in which 87% of participants did not respond to treatment, and it is not supported by the anecdotal experiences of many patients, some of whom report being harmed by CBT and GET in clinical settings (3).

Interestingly, based on information in the protocol, the authors of the PACE Trial, many of whom have a background in psychiatry, and in promoting CBT and GET as treatments for CFS/ME, seem to have expected the results to show a 60% benefit for CBT and GET, and only a 10% benefit for specialised medical care (the SMC control group), but in fact, it was the opposite: Roughly 60% improved in the control group, and only approximately 13% improved as a result of CBT or GET.

I believe that the psychiatrists had mistakenly believed that their therapies were highly successful, when in fact, the improvements were due to natural improvements seen in some CFS/ME patients over time, as demonstrated by SMC control group in the PACE trial (58% and 65% improvement rates for SMC). The psychiatrists say that CFS/ME patients have 'maladaptive' cognition and behaviour which perpetuates the illness, but the PACE Trial gave us evidence that patients and the WHO were always correct about the nature of ME, and that the psychiatrists, were in fact, mistaken about the treatments they offer and the nature of the illness.

It should be noted that the PACE Trial’s deterioration rates for CBT and GET, determined by an equivalent measure as the improvement rates, have not yet been released. Once the deterioration rates are released, the results for CBT and GET might confirm CFS/ME patients’ anecdotal reports of harm from CBT and GET. (3)

Harm from exposure to CBT and GET (3)(6) may be a result of ‘post exertional malaise’ or ‘postexertional neuroimmune exhaustion’, widely recognised to be a primary symptom of CFS/ME (4)(5). CFS/ME is reactive to activity or exertion (4), which is why patients often use ‘pacing’, to self-manage symptoms. It should be noted that Adaptive Pacing Therapy (APT), was a failed novel therapy, devised specifically for the PACE Trial, and that it is not the same as ‘pacing’, as recognised by many CFS/ME patients.


References:

(1) Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial.


Prof PD White et al.
The Lancet, Volume 377, Issue 9768, Pages 823 - 836, 5 March 2011
doi:10.1016/S0140-6736(11)60096-2
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)60096-2/abstract

(2) CBT and GET treatment manuals


PACE Trial website
http://www.pacetrial.org/trialinfo/

(3) Action for ME patient survey 2010:


http://www.actionforme.org.uk/get-i...t-and-exercise-on-prescription-survey-results
Action for ME patient survey 2008:
http://www.actionforme.org.uk/get-informed/about-me/treatment/which-treatments-have-other-people-found-helpful

(4) Myalgic encephalomyelitis: International Consensus Criteria


Carruthers et al
doi: 10.1111/j.1365-2796.2011.02428.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02428.x/pdf

(5) The Chronic Fatigue Syndrome: A Comprehensive Approach to Its Definition and Study


Keiji Fukuda et al
Ann Intern Med. 1994;121:953-95 1994
http://www.ncf-net.org/patents/pdf/Fukuda_Definition.pdf

(6) Reporting of Harms Associated with Graded Exercise Therapy and Cognitive


Behavioural Therapy in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Tom Kindlon
Bulletin of the IACFS/ME. 2011;19(2): 59-111

http://www.iacfsme.org/LinkClick.aspx?fileticket=Rd2tIJ0oHqk=&tabid


  1. alex3619 said:

Hi Bob, I agree the PACE trial excluded the severe patients (mostly bedbound), but the definition of moderate used now is "mostly housebound". I suspect it had limited numbers of moderate patients, and was heavy on mild or misdiagnosed patients.

Very severe patients (fully dependent on others) are in a whole other category. Even light movement in bed would be problematic for them, so graded exercise would not be an even remote option.

Hi Alex,

Yes, the PACE Trial excluded 'completely' housebound and bedbound patients, and I suppose that a proportion of 'mostly' housebound patients would have felt that they could not participate.

So it could have excluded a proportion of 'moderately effected' patients, who were mostly housebound.
But some patients would have attended the clinic with assistance.

And, some 'mildly affected' patients might have been excluded because the recruitment criteria was a score of 65, or less, on the SF-36 physical function scale. I'm not sure what range of scores would cover 'mildly affected' patients, but maybe it would go above 65 for SF-36 physical function, in which case, some mildly affected patient might have been excluded.

Also, patients who knew that CBT and GET would have been no benefit to them, might also have declined to participate.

What we know for certain, is that the results cannot be extrapoloted to housebound or bedbound patients.

So my main point was that the results cannot be extrapolated to severely affected patients because they were excluded. On the PACE Trial website, the authors acknowledge that the results cannot be extrapolated to severely affected patients. I have included a reference for this.

The little-publicised (UK-government funded) 'FINE Trial', published in 2010, studied a CBT-based therapy with GET components, and included severly affected patients. The FINE Trial found that a CBT-based therapy, with GET components, was of no benefit to severely affected CFS/ME patients. I should have included this in my main text:


The Fine Trial.
Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial.
Wearden AJ, Dowrick C, Chew-Graham C, Bentall RP, Morriss RK, Peters S, Riste L, Richardson G, Lovell K, Dunn G; Fatigue Intervention by Nurses Evaluation (FINE) trial writing group and the FINE trial group.
BMJ. 2010 Apr 23;340:c1777.
doi: 10.1136/bmj.c1777.
http://www.bmj.com/content/340/bmj.c1777
http://www.ncbi.nlm.nih.gov/pubmed/20418251

Something that I forgot to include in my first post, was that at the same time as the PACE Trial was being carried out, another medical trial was being carried out in the UK, on 296 primary care patients, including housebound CFS/ME patients. (Housebound patients were excluded from the PACE Trial).

Originally known as the 'FINE Trial', (FINE = Fatigue Intervention by Nurses Evaluation), it tested a CBT-based therapy, with GET components, known as 'pragmatic rehabilitation'. I haven't studied the FINE Trial as closely as the PACE Trial, but the therapy seems to be at least partly based on reversing deconditioning.

Like the PACE Trial, the FINE Trial was also funded by the UK government's main research funding body, the MRC (Medical Research Council).



The results were that CFS/ME patients did not respond to CBT-based therapy or GET (when assessed at one year follow-up.)

Unlike the PACE Trial, there was very little fanfare or media attention when the paper was published. In fact, there was hardly a squeak about it. It's almost as if it never existed.



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