Tag: Matthees

Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT

Abstract:

Background: The PACE trial was a well-powered randomised trial designed to examine the efficacy of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for chronic fatigue syndrome. Reports concluded that both treatments were moderately effective, each leading to recovery in over a fifth of patients. However, the reported analyses did not consistently follow the procedures set out in the published protocol, and it is unclear whether the conclusions are fully justified by the evidence.

Methods: Here, we present results based on the original protocol-specified procedures. Data from a recent Freedom of Information request enabled us to closely approximate these procedures. We also evaluate the conclusions from the trial as a whole.

Results: On the original protocol-specified primary outcome measure – overall improvement rates – there was a significant effect of treatment group. However, the groups receiving CBT or GET did not significantly outperform the Control group after correcting for the number of comparisons specified in the trial protocol. Also, rates of recovery were consistently low and not significantly different across treatment groups. Finally, on secondary measures, significant effects were almost entirely confined to self-report measures. These effects did not endure beyond two years.

Conclusions: These findings raise serious concerns about the robustness of the claims made about the efficacy of CBT and GET. The modest treatment effects obtained on self-report measures in the PACE trial do not exceed what could be reasonably accounted for by participant reporting biases.

Source: Carolyn E. Wilshire, Tom Kindlon, Robert Courtney, Alem Matthees, David Tuller, Keith Geraghty and Bruce Levin. Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC PsychologyBMC series. Received: 29 May 2017; Accepted: 22 February 2018; Published: 22 March 2018.  https://doi.org/10.1186/s40359-018-0218-3 (Full article) © The Author(s) 2018.

Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial

Abstract:

BACKGROUND: Publications from the PACE trial reported that 22% of chronic fatigue syndrome patients recovered following graded exercise therapy (GET), and 22% following a specialised form of CBT. Only 7% recovered in a control, no-therapy group. These figures were based on a definition of recovery that differed markedly from that specified in the trial protocol.

PURPOSE: To evaluate whether these recovery claims are justified by the evidence.

METHODS: Drawing on relevant normative data and other research, we critically examine the researchers’ definition of recovery, and whether the late changes they made to this definition were justified. Finally, we calculate recovery rates based on the original protocol-specified definition.

RESULTS: None of the changes made to PACE recovery criteria were adequately justified. Further, the final definition was so lax that on some criteria, it was possible to score below the level required for trial entry, yet still be counted as ‘recovered’. When recovery was defined according to the original protocol, recovery rates in the GET and CBT groups were low and not significantly higher than in the control group (4%, 7% and 3%, respectively).

CONCLUSIONS: The claim that patients can recover as a result of CBT and GET is not justified by the data, and is highly misleading to clinicians and patients considering these treatments.

 

Source: Carolyn Wilshire, Tom Kindlon, Alem Matthees & Simon McGrath. Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial. Fatigue: Biomedicine, Health & Behavior Volume 5, 2017 – Issue 1. http://www.tandfonline.com/doi/full/10.1080/21641846.2017.1259724 (Full article)

 

Assessment of recovery status in chronic fatigue syndrome using normative data

Abstract:

INTRODUCTION: Adamowicz et al. have reviewed criteria previously employed to define recovery in chronic fatigue syndrome (CFS). They suggested such criteria have generally lacked stringency and consistency between studies and recommended future research should require “normalization of symptoms and functioning”.

METHODS: Options regarding how “normalization of symptoms and functioning” might be operationalized for CFS cohorts are explored.

RESULTS: A diagnosis of CFS excludes many chronic disabling illnesses present in the general population, and CFS cohorts can almost exclusively consist of people of working age; therefore, it is suggested that thresholds for recovery should not be based on population samples which include a significant proportion of sick, disabled or elderly individuals. It is highlighted how a widely used measure in CFS research, the SF-36 physical function subscale, is not normally distributed. This is discussed in relation to how recovery was defined for a large intervention trial, the PACE trial, using a method that assumes a normal distribution. Summary data on population samples are also given, and alternative methods to assess recovery are proposed.

CONCLUSIONS: The “normalization of symptoms and function” holds promise as a means of defining recovery from CFS at the current time. However, care is required regarding how such requirements are operationalized, otherwise recovery rates may be overstated, and perpetuate the confusion and controversy noted by Adamowicz et al.

Comment on

 

Source: Matthees A. Assessment of recovery status in chronic fatigue syndrome using normative data. Qual Life Res. 2015 Apr;24(4):905-7. doi: 10.1007/s11136-014-0819-0. Epub 2014 Oct 11. https://www.ncbi.nlm.nih.gov/pubmed/25304959 (Full article)

Comment:

Alem Matthees 2015 Aug 16 11:22 p.m.

In response to post-publication feedback, I wish to clarify some aspects of the abstract, so there are no further misunderstandings about the scope and content in the full text of this article:

a) Classification and naming issues aside, ME/CFS occurs at all ages, including young children and adolescents. [1] I never intended to suggest otherwise. The statement about patients being almost exclusively of working age was in context of research cohorts, particularly intervention trials which typically exclude patients under 18 years of age and rarely recruit those over 65 years. It is argued that studies consisting of such cohorts should not use normative data from general populations which include the elderly.

b) The physical function subscale of the Short Form 36 health survey (PF SF-36) is discussed because it is a commonly used measure in research and was used in the PACE trial. This article is not a defence of the PACE trial, but uses it to exemplify how the issues described earlier in the article can cause normative data to be misinterpreted or misapplied. Selected details on this issue can be found in an BMJ Rapid Response (open-access) which does not require subscription to view. [2]

c) This article is not meant to be a comprehensive analysis of recovery or case definitions, it is simply a commentary which focuses on using normative data from other comparison groups, one of the issues raised in the review by Adamowicz et al. [3] It explores the appropriate control groups or comparison populations, highlights a problem with using the mean ±1 SD as a threshold if the data does not follow a normal distribution, includes some summary statistics, mentions statistical testing at the group level, and encourages researchers to publish enough information so that others can accurately estimate the functional status of participants. Subjective self-reported measures are important but have potential biases (particularly in nonblinded trials lacking placebo control). Objective measures are also important, particularly when assertions that the intervention is effective at increasing function and activity are contradicted by a range of objective measures. See commentaries by Twisk [4] and others. [5-7]

References

1: Bakken IJ, Tveito K, Gunnes N, Ghaderi S, Stoltenberg C, Trogstad L, Håberg SE, Magnus P. Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008-2012. BMC Med. 2014 Oct 1;12:167. doi: 10.1186/s12916-014-0167-5. PMID 25274261. http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25274261

2: Matthees A. Re: Tackling fears about exercise is important for ME treatment, analysis indicates. BMJ Rapid Response, 21 January 2015. http://www.bmj.com/content/350/bmj.h227/rr-16

3: Adamowicz JL, Caikauskaite I, Friedberg F. Defining recovery in chronic fatigue syndrome: a critical review. Qual Life Res. 2014 Nov;23(9):2407-16. doi: 10.1007/s11136-014-0705-9. Epub 2014 May 3. PMID: 24791749. http://link.springer.com/article/10.1007/s11136-014-0705-9

4: Twisk FN. A definition of recovery in myalgic encephalomyelitis and chronic fatigue syndrome should be based upon objective measures. Qual Life Res. 2014 Nov;23(9):2417-8. doi: 10.1007/s11136-014-0737-1. Epub 2014 Jun 17. PMID: 24935018. http://link.springer.com/article/10.1007/s11136-014-0737-1

5: Kindlon TP. Objective measures found a lack of improvement for CBT & GET in the PACE Trial: subjective improvements may simply represent response biases or placebo effects in this non-blinded trial. BMJ Rapid Response, 18 January 2015. http://www.bmj.com/content/350/bmj.h227/rr-10

6: Wilshire CE. Re: Tackling fears about exercise is important for ME treatment, analysis indicates. BMJ Rapid Response, 19 January 2015. http://www.bmj.com/content/350/bmj.h227/rr-7

7: Faulkner G. In non-blinded trials, self-report measures could mislead. Lancet Psychiatry. Volume 2, No. 4, e7, April 2015. doi: 10.1016/S2215-0366(15)00089-9 http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00089-9/fulltext