Patients with chronic fatigue syndrome can improve with graded exercise therapy: Response to Vink et al. 2022*

Evidence from gold-standard randomised controlled trials (RCTs) finds that graded exercise therapy (GET) is an efficacious treatment for chronic fatigue syndrome (CFS) [1,2]. We compared self-report clinical outcomes from patients who received GET in routine clinical practice with outcomes from RCTs and found that patients reported improvements in several outcomes [3]. We now respond to Vink et al. who raised a number of issues related to our evaluation [4].

We used a range of self-report measures to capture different aspects of the patient experience. We maintain that patients’ own perception of their symptoms is of utmost importance. We think it is important to assess self-report outcomes in routine clinical practice within the UK National Health Service, where the routine use of objective measures is precluded due to cost. In our evaluation, we acknowledged the drawbacks of self-report measures. While the therapists encouraged patients to use objective measures during therapy we did not collect objective audit data routinely. We are therefore not selectively reporting.

Vink et al. [4] state that our conclusion that GET is safe is unsupported. However, a recent review of randomised controlled trials (RCT) concluded there was no evidence of excess harm with graded exercise therapy by either self-rated deterioration or by withdrawing from GET, in comparison to control interventions [5]. This evidence is more robust than the survey conducted in Oxford Brookes which was subject to the many biases associated with non-randomised evaluations [6].

In our paper, we described GET as was used in our clinical service. We did not use fixed incremental increases in physical activity or exercise. Goals were not prescribed but individually negotiated with each patient. Patients were offered up to 12 sessions of GET and some people decided jointly with their therapist that they needed fewer than 12. 37/92 patients attended less than 12 sessions. This included those who completed GET early (n = 16) or dropped out (n = 21) for other reasons, such as their clinical need changed or there was a lack of funding described in the Appendix, in our original paper. More specifically, their clinical need changed or there was a lack of funding. Those who had less than 12 sessions, therefore, were not necessarily dropouts. Four patients indicated that they either got worse or did not engage with GET.

Vink et al. [4] suggest that the rate of adherence would not be acceptable in a research trial. Although this evaluation was not a randomised controlled trial but an evaluation of outcomes from a routine clinical setting, the dropout was not unusually high. There is much evidence to show that there is a general issue with adherence rates to psychological/behavioural treatment in healthcare services [7]. Additionally, adherence is generally poor in people with a condition that lasts for more than 6 months [8].

Vink et al. [4] state the problem of missing data is unacknowledged. They also state that using a mean score would inflate scores if a patient was deteriorating. In response, we clearly state the number of patients who completed follow-up data each time a result was reported. We also compared pre-treatment scores of those with data and those without. We used an accepted, standard multiple-imputation pro-rating procedure to minimise data misrepresentation and described this in our article. Mean scores of patients improving would be affected in a similar way to scores of patients deteriorating.

Vink et al. [4] assert our article used selective evidence to support our conclusions. They refer to the Oxford Brookes study [6], the new NICE guidelines [9] and the Larun Cochrane review [1] as well as the statement to update the review [10]. As previously stated the Oxford Brookes study was subject to biases associated with non-randomised evaluations. With regards to the NICE guidelines, our evaluation was carried out before the revised recommendations were available and were in line with the scientific evidence and the NICE guidelines at the time. The Cochrane review is in the process of being updated.

In our final summary, we state that effect sizes for improvement following treatment were not as high as those found in randomised controlled trials and as Vink et al. [4] stated some patients remained disabled. Although there were significant improvements in physical functioning and work and social adjustment, improvements were modest. Clearly, new treatments need to be developed and treatments such as GET with some evidence of efficacy, need to be improved.

Vink et al. [4] suggest that spontaneous recovery is likely as many patients had been ill for 2–3 years. However, evidence from a published review showed that prognosis is poor in people with CFS if left untreated [11]. Indeed, prolonged inactivity is harmful even in healthy people [12]. Furthermore, nocebo-related effects, the belief that a treatment will cause harm, is likely to be observed in CFS, as symptom worsening follows negative expectations in chronic pain [13].

Although our evaluation was uncontrolled, we used recommended bench-marking techniques to report findings. We stand by our conclusion that GET for patients is safe if delivered by trained health care professionals and can be an efficacious treatment for patients with CFS/ME in a clinical setting. Effect sizes were smaller in routine clinical practice than RCTs and we, therefore, need to improve treatments to bring about larger effect sizes.

Disclosure statement

TC received ad hoc payments for conducting workshops on evidence-based treatments for persistent physical symptoms. TC has received grants from NIHR programme grants, HTA, RfPB, Guy’s and St Thomas Charity. TC is the author of several self-help books on chronic fatigue and received royalties in the past. TC received expenses for BABCP Conferences (travel and accommodation). TC received ad hoc payments for conducting workshops on evidence-based treatments for persistent physical symptoms.

Additional information

Funding

TC acknowledges the financial support of the Department of Health via the National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health award to the South London and Maudsley NHS Foundation Trust (SLaM) and the Institute of Psychiatry at King’s College London. The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.