Tag: PACE trial

Patterns of Daytime Physical Activity in Patients With Chronic Fatigue Syndrome

Abstract:

Objectives: To classify patients with chronic fatigue syndrome (CFS) by pattern of physical activity and determine the clinical associations of each type.

Methods: 579 out of 641 participants with CFS from the PACE (Pacing, graded Activity, Cognitive behavioural therapy: a randomised Evaluation) trial wore an Actiwatch (accelerometer) for between 3 and 7 days before any trial treatments, which provided a measure of physical activity. Participants’ activity was categorised into one of four patterns (pervasively inactive, pervasively active, boom and bust, or indeterminate) primarily using a priori definitions of activity. Clinical associations were sought with each group using an exploratory logistic regression with the indeterminate activity group being the reference group.

Results: 124 (21%) of the participants were classified as pervasively inactive, 65 (11%) as pervasively active, 172 (30%) showed a ‘boom and bust’ pattern of activity, and 218 (38%) had an indeterminate pattern. Pervasively inactive patients were more physically disabled, those in the pervasively active group were more anxious, and those in the boom and bust group had more sleep disturbance.

Conclusion: We were able to classify patients with CFS into groups by their daytime activity pattern. The different patterns of activity were associated with important clinical variables, suggesting that they might be helpful in determining prognosis and targeting treatments. These associations need replication.

Response: Sharpe, Goldsmith and Chalder fail to restore confidence in the PACE trial findings

Abstract:

In a recent paper, we argued that the conclusions of the PACE trial of chronic fatigue syndrome are problematic because the pre-registered protocol was not adhered to. We showed that when the originally specific outcomes and analyses are used, the evidence for the effectiveness of CBT and graded exercise therapy is weak.

In a companion paper to this article, Sharpe, Goldsmith and Chalder dismiss the concerns we raised and maintain that the original conclusions are robust. In this rejoinder, we clarify one misconception in their commentary, and address seven additional arguments they raise in defence of their conclusions.

We conclude that none of these arguments is sufficient to justify digressing from the pre-registered trial protocol. Specifically, the PACE authors view the trial protocol as a preliminary plan, subject to honing and improvement as time progresses, whereas we view it as a contract that should not be broken except in extremely unusual circumstances. While the arguments presented by Sharpe and colleagues inspire some interesting reflections on the scientific process, they fail to restore confidence in the PACE trial’s conclusions.

Source: Carolyn E. Wilshire and Tom Kindlon. Response: Sharpe, Goldsmith and Chalder fail to restore confidence in the PACE trial findings. BMC Psychology20197:19
https://doi.org/10.1186/s40359-019-0296-x© The Author(s). 2019 https://bmcpsychology.biomedcentral.com/articles/10.1186/s40359-019-0296-x (Full article)

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.

The Young ME Sufferers Trust: No Reported Harassment at Bristol University (Information Obtained Under FOI)

There has been no reported harassment of staff at Bristol University. Yes, you read that correctly.

We have all become accustomed to the increasingly shrill ‘harassment’ accusations against ME patients
and ‘activists’, both via the media and in lectures. This campaign appears to have originated at that now
infamous meeting of the Science Media Centre, revealed by our original 2014 Freedom of Information
Report, now updated under the title Shining a Light on the CMRC Setup (http://www.tymestrust.org/pdfs/ shiningalight.pdf). Members of the UK Research Collaborative have continued to spread these allegations ever since its launch.

In Shining a Light we stated: In the records of the meeting where ‘harassment’ of researchers was discussed, no mention was made of personal threats such as have been reported in the media. Freedom of Information (FOI) requests were listed as the most damaging type of ‘harassment’. The 2016 tribunal appeal Judgement ordering QMUL to release the PACE trial data highlights that Professor Trudie Chalder accepts that “no threats have been made either to researchers or participants”.

And yet the accusations persist and have even escalated. Tymes Trust has found this constant narrative so abhorrent that we have sought some answers. We have, once again, sought evidence.

You can read the rest of this report here: http://www.tymestrust.org/pdfs/noharassmentbristol.pdf

How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies?

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome has been a controversial diagnosis, resulting in tensions between patients and professionals providing them with care. A major constraint limiting progress has been the lack of a ‘gold standard’ for diagnosis; with a number of imperfect clinical and research criteria used, each defining different, though overlapping, groups of people with myalgic encephalomyelitis or chronic fatigue syndrome. We review basic epidemiological concepts to illustrate how the use of more specific and restrictive case definitions could improve research validity and drive progress in the field by reducing selection bias caused by diagnostic misclassification.

Source: Nacul L, Lacerda EM, Kingdon CC, Curran H, Bowman EW. How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies? J Health Psychol. 2017 Mar 1:1359105317695803. doi: 10.1177/1359105317695803. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28810428

Cognitive behaviour therapy and objective assessments in chronic fatigue syndrome

Abstract:

Most evaluations of cognitive behavioural therapy to treat people with chronic fatigue syndrome/myalgic encephalomyelitis rely exclusively on subjective self-report outcomes to evaluate whether treatment is effective. Few studies have used measures appropriate to assessing whether cognitive behavioural therapy changes in more objective measures. A review of studies incorporating objective measures suggests that there is a lack of evidence that cognitive behavioural therapy produces any improvement in a patient’s physical capabilities or other objective measures such as return to work. Future studies of chronic fatigue syndrome/myalgic encephalomyelitis should include some objective assessments as primary outcomes. If this is to include activity monitors, we first need a sound baseline dataset.

Source: McPhee G. Cognitive behaviour therapy and objective assessments in chronic fatigue syndrome. J Health Psychol. 2017 Aug;22(9):1181-1186. doi: 10.1177/1359105317707215. Epub 2017 Jun 19. https://www.ncbi.nlm.nih.gov/pubmed/28805529

PACE investigators’ response is misleading regarding patient survey results

Abstract:

The PACE investigators’ citation of a patient survey might mislead readers into thinking that the experience of people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) supports PACE findings. In fact, patient survey evidence directly contradicts the results of the PACE trial. A review of survey data published between 2001 and 2015 reveals that for most patients, graded exercise therapy leads to worsening of symptoms, cognitive behavioural therapy leads to no change in symptoms, and pacing leads to improvement. The experience of people with ME/CFS as reflected in surveys is a rich source of information, made more compelling by the consistency of results. Consequently, patient survey evidence can be used to inform practice, research and guidelines. Misrepresentation of patient experience must be vigorously challenged, to ensure that patients and health professionals make decisions about therapies based on accurate information.

Source: Kirke KD. PACE investigators’ response is misleading regarding patient survey results. J Health Psychol. 2017 Aug;22(9):1168-1176. doi: 10.1177/1359105317703787. Epub 2017 May 11. https://www.ncbi.nlm.nih.gov/pubmed/28805528

Bias, misleading information and lack of respect for alternative views have distorted perceptions of myalgic encephalomyelitis/chronic fatigue syndrome and its treatment

Abstract:

The PACE trial is one of the most recent studies evaluating cognitive behavioural therapy and graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome. These interventions are based on a model which assumes that symptoms are perpetuated by factors such as misguided beliefs and a lack of activity. Our analysis indicates that the researchers have shown significant bias in their accounts of the literature and may also have overstated the effectiveness of the above treatments. We submit that their approach to criticisms undermines the scientific process and is inconsistent with best practice.

Source: Goudsmit E, Howes S. Bias, misleading information and lack of respect for alternative views have distorted perceptions of myalgic encephalomyelitis/chronic fatigue syndrome and its treatment. J Health Psychol. 2017 Aug;22(9):1159-1167. doi: 10.1177/1359105317707216. Epub 2017 May 29. https://www.ncbi.nlm.nih.gov/pubmed/28805527

The problem of bias in behavioural intervention studies: Lessons from the PACE trial

Abstract:

Geraghty’s recent editorial on the PACE trial for chronic fatigue syndrome has stimulated a lively discussion. Here, I consider whether the published claims are justified by the data. I also discuss wider issues concerning trial procedures, researcher allegiance and participant reporting bias. Cognitive behavioural therapy and graded exercise therapy had modest, time-limited effects on self-report measures, but little effect on more objective measures such as fitness and employment status. Given that the trial was non-blinded, and the favoured treatments were promoted to participants as ‘highly effective’, these effects may reflect participant response bias. In non-blinded trials, the issue of reporting biases deserves greater attention in future.

Source: Wilshire C. The problem of bias in behavioural intervention studies: Lessons from the PACE trial. J Health Psychol. 2017 Aug;22(9):1128-1133. doi: 10.1177/1359105317700885. Epub 2017 Mar 23. https://www.ncbi.nlm.nih.gov/pubmed/28805526

PACE-GATE: An alternative view on a study with a poor trial protocol

Abstract:

The controversies surrounding the effectiveness of cognitive behavioural therapy and graded exercise therapy for chronic fatigue syndrome are explained using Cohen’s d effect sizes rather than arbitrary thresholds for ‘success’. This article shows that the treatment effects vanish when switching to objective outcomes. The preference for subjective outcomes by the PACE trial team leads to false hope. This article provides a more realistic view, which will help patients and their doctors to evaluate the pros and cons.

Source: Stouten B. PACE-GATE: An alternative view on a study with a poor trial protocol. J Health Psychol. 2017 Aug;22(9):1192-1197. doi: 10.1177/1359105317707531. Epub 2017 May 12. https://www.ncbi.nlm.nih.gov/pubmed/28805525