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Rehabilitative treatments for chronic fatigue syndrome: long-term follow-up from the PACE trial, 2015, Sharpe,White,Chalder

Discussion in 'PsychoSocial ME/CFS Research' started by Sly Saint, Apr 24, 2021.

  1. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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    obviously not new.

    "
    Summary
    Background
    The PACE trial found that, when added to specialist medical care (SMC), cognitive behavioural therapy (CBT), or graded exercise therapy (GET) were superior to adaptive pacing therapy (APT) or SMC alone in improving fatigue and physical functioning in people with chronic fatigue syndrome 1 year after randomisation. In this pre-specified follow-up study, we aimed to assess additional treatments received after the trial and investigate long-term outcomes (at least 2 years after randomisation) within and between original treatment groups in those originally included in the PACE trial.
    Methods
    The PACE trial was a parallel-group randomised controlled trial of patients meeting Oxford criteria for chronic fatigue syndrome who were recruited from six secondary care clinics in the UK between March 18, 2005, and Nov 28, 2008. Participants were randomly allocated to receive SMC alone or plus APT, CBT, or GET. Primary outcomes (were fatigue measured with Chalder fatigue questionnaire score and physical functioning with short form-36 subscale score, assessed 1 year after randomisation. In this long-term follow-up, we sent postal questionnaires to assess treatment received after the trial and outcomes a minimum of 2 years after randomisation. We assessed long-term differences in outcomes within and between originally randomised groups. The PACE trial is registered at http://isrctn.org, number ISRCTN54285094.
    Findings
    Between May 8, 2008, and April 26, 2011, 481 (75%) participants from the PACE trial returned questionnaires. Median time from randomisation to return of long-term follow-up assessment was 31 months (IQR 30–32; range 24–53). 210 (44%) participants received additional treatment (mostly CBT or GET) after the trial; with participants originally assigned to SMC alone (73 [63%] of 115) or APT (60 [50%] of 119) more likely to seek treatment than those originally assigned to GET (41 [32%] of 127) or CBT (36 [31%] of 118; p<0·0001). Improvements in fatigue and physical functioning reported by participants originally assigned to CBT and GET were maintained (within-group comparison of fatigue and physical functioning, respectively, at long-term follow-up as compared with 1 year: CBT −2·2 [95% CI −3·7 to −0·6], 3·3 [0·02 to 6·7]; GET −1·3 [–2·7 to 0·1], 0·5 [–2·7 to 3·6]). Participants allocated to APT and to SMC alone in the trial improved over the follow-up period compared with 1 year (fatigue and physical functioning, respectively: APT −3·0 [–4·4 to −1·6], 8·5 [4·5 to 12·5]; SMC −3·9 [–5·3 to −2·6], 7·1 [4·0 to 10·3]). There was little evidence of differences in outcomes between the randomised treatment groups at long-term follow-up.
    Interpretation
    The beneficial effects of CBT and GET seen at 1 year were maintained at long-term follow-up a median of 2·5 years after randomisation. Outcomes with SMC alone or APT improved from the 1 year outcome and were similar to CBT and GET at long-term follow-up, but these data should be interpreted in the context of additional therapies having being given according to physician choice and patient preference after the 1 year trial final assessment. Future research should identify predictors of response to CBT and GET and also develop better treatments for those who respond to neither.
    Funding
    UK Medical Research Council, Department of Health for England, Scottish Chief Scientist Office, Department for Work and Pensions, National Institute for Health Research (NIHR), NIHR Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust, King's College London."
    https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00317-X/fulltext
     
    Barry, Peter Trewhitt and Trish like this.
  2. Sly Saint

    Sly Saint Senior Member (Voting Rights)

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  3. cassava7

    cassava7 Senior Member (Voting Rights)

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    Of note, this is what the reanalysis of the PACE trial by @Carolyn Wilshire, @Tom Kindlon, @dave30th and Alem found:

    Background

    Long-term follow-up
    A mail survey was conducted at least two years after randomisation (median 31 months [7]). Survey response rates were 72%, 74% and 79% for the Control, CBT and GET groups respectively. Participants were again asked to complete the trial’s primary fatigue and physical rating scales, and several other questionnaires. A 2015 paper reported the results for the fatigue and physical function measures, again treating them as separate, continuous variables [7]. Analyses of these measures, based on an available case approach, failed to yield any significant effects of treatment group. However, the investigators did not view this negative result as a cause for concern at all. They argued that many patients in the Control and Adaptive therapy trial arms had received some CBT or GET after the conclusion of the main trial, and this could explain why they had since improved to the level of the other patients.

    Methods

    Finally, to explore the PACE investigators’ hypothesis that long-term treatment effects may have been obscured by patients’ post-trial treatment choices, we isolated the long-term self-rated fatigue and physical function scores for those patients who did not receive any post-trial CBT or GET. The relevant individual patient data are not available in the FOIA dataset, so a systematic reanalysis could not be performed. However, since the relevant summary data are reported in [7], see Supplementary materials, Table C], we were able to perform a simple one-way analysis of variance examining the effect of original treatment allocation on long-term outcomes in this subgroup.

    Results

    Long-term outcomes

    Out of those who responded to the long-term follow-up, 43% of the Control participants had received no further CBT or GET after the completion of the trial. This was also the case for 74% and 75% of the respondents from the CBT and GET arms respectively. Considered together, this subset of participants was perhaps slightly less severely affected than the remaining patients: they scored slightly better on the primary physical function and fatigue scales at 52 weeks than those who opted for further treatment (physical function: 61.3 vs. 48.1; fatigue: 23.9 vs. 25.9). However, at 52 weeks, the pattern of scores across treatment arms was the same as for the sample as a whole: the CBT and GET participants in our subset rated their fatigue as slightly lower and their physical function slightly higher at 52 weeks than the Control participants. In this respect, our subsample may be considered reasonably representative of the sample as a whole.

    Table 2 provides arithmetic means for the two major self-report outcome measures for this subset of patients (i.e., those who received no further treatment). The pattern of results presented here mirrors that obtained for the entire cohort: the small group differences apparent on these measures at 52 weeks are no longer evident at long-term follow-up. A one-way analysis of variance revealed that there were no statistically reliable effects of treatment group on either outcome measure (Physical function: F(3,291) = 0.70, ns; Fatigue F(3,291) = 0.17, ns). If we repeat the analyses, adding in those cases who received some additional therapy sessions, but less than the minimum 10 considered by the investigators to be an “adequate” dose ([7], p.1071), the outcome does not change (Physical function: F(3,384) = 1.85, ns; Fatigue F(3,384) = 0.86, ns). Consequently, the disappearance of group differences at long-term follow-up cannot be attributed to the effects of additional post-trial therapy.

    Discussion

    Turning now to long-term follow-up, the original publication of the long-term follow-up data reported no significant differences amongst treatment groups at this time point [7]. However, the authors dismissed their own finding, arguing that many participants received additional post-trial therapy which might have operated to obscure group differences. Instead, they based their main conclusion on comparisons between time points. For example, the first line of the Discussion reads: “The main finding of this long-term follow-up study of the PACE trial participants is that the beneficial effects of the rehabilitative CBT and GET therapies on fatigue and physical functioning observed at the final 1 year outcome of the trial were maintained at long-term follow-up 2·5 years from randomisation.” ([7] p. 1072, Italics added). This conclusion is repeated in the Abstract. The decision to lead with this conclusion again operated to show the findings in a more positive light than would have been possible based on their own primary between-groups analysis. The informal analyses we presented here provide no support for the investigators’ claim that post-trial therapy contaminated the long-term outcome data. Of course, our analyses did not include important potentially confounding variables that might differ amongst trial arms, and such a comprehensive analysis might possibly produce a different result. However, until there is positive evidence to suggest that this is the case, the conclusion we must draw is that PACE’s treatment effects are not sustained over the long term, not even on self-report measures. CBT and GET have no long-term benefits at all. Patients do just as well with some good basic medical care.
     

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