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Too many questions still unanswered by this trial.....

Posted by JoanCrawford on 07 Aug 2012 at 13:25 GMT

The PACE trial at best showed modest effect for the interventions and only for a small minority of the patients who took part – around 1/3rd. Ideally, this would warrant a more thorough and critical discussion of its relative success, cost effectiveness and limitations, such as:

Patients were selected for inclusion in the PACE trial using the Oxford criteria (Sharpe et al., 1991). The main symptom here is fatigue. This is a symptom of numerous medical and psychiatric conditions so there is a problem with specificity and sensitivity, and hence it is hard to generalise the results with such a heterogeneous group of participants. Assumptions that research on chronically fatigued participants can be generalised to patients with ME or CFS remain just that: assumptions.

Adaptive Pacing Therapy (APT) as described in the PACE trial literature is not necessarily the pacing as used and understood by patients and charity/support groups. Pacing is not a “treatment” and is used widely in the management of many chronic medical conditions. Symptom contingent pacing is unlikely to result in patient improvement by its very nature unless the underlying condition improved simultaneously. As the underlying condition(s) is ill-defined at this time it cannot be claimed that this trial has meaning for subgroups of patients who have demonstratable, ongoing immune dysfunction, neurological and infectious components to their condition.

If the condition is maintained, as claimed by the authors of the PACE trail, by deconditioning then the modest improvements attained suggest a more complex picture. The lead author of the PACE trial’s own work objectively demonstrates that patients are not necessarily deconditioned (Fulcher & White, 2000), thus contradicting themselves. Peak oxygen uptake (VO2), heart recovery rate after exercise challenge and maximum lung ventilation were not found to be different between patients and healthy sedentary controls (Fulcher & White, 2000) making deconditioning as a major reason for persistence of symptoms too simplistic at best.

There is no objective evidence demonstrating that patients actually adhered to the PACE trial protocol and complied with increases in activity during the trial itself. It is quite possible that patients adapted to their condition by challenging themselves through increased activity in the CBT/GET groups and learned more about their limitations and by improving well-being by adapting and staying within their limits by the end of the trial, e.g. energy modulation (Jason et al., 2009) thus raising the possibility of confounding in the CBT/GET groups.

Baseline objective measures of activity (actimeters) were made in the PACE trial but were not followed up at the end so we have no objective measures that the trial succeeded in what it intended to do – objectively increasing patient activity and simultaneously reducing symptoms and improving well-being. See my above comment regarding adaptation.

One trial provides some overall information as to the benefit or otherwise of interventions, however, it does not provide the whole context. Meta-analysis is needed. It is worth noting that the sister trial to this one (FINE, Wearden et al., 2010) promoting increased activity in this patient group did not find support for improved well-being and outcome post-therapy at one year follow up. A Spanish trail (Nunez et al., 2011) using group CBT/GET intervention found that post intervention patients had worse physical functioning and increased pain at outcome. Other CBT/GET trials have had mixed results too. Also, no trial to date has demonstrated that objectively measured increases in activity confer to improved well-being, recovery, return to work and participation fully in society.

Having demonstrated that some patients subjectively feel somewhat better after the PACE trial’s CBT/GET interventions, although nothing close to the expected outcomes if these disorders were being maintained by faulty information biases, deconditioning and fear avoidance (operant conditioning), it doesn’t necessarily follow that it is cost effective to invest in these therapies especially as return to work decreased and medications remained roughly constant at the end of the trial. Also, more patients appeared to use inpatient hospital services post participation. Suggesting that these types of interventions will result in objective cost reductions as reported in the press running to millions is perhaps therefore an exaggeration.

Others have commented on the definitions of recovery used in the PACE trial and other criticisms of the PACE trail were published in the Lancet in May 2011 (Kindlon, 2011; Feehan, 2011; Giakoumakis, 2011; Mitchell, 2011; Kewley, 2011; Stouten, Goudsmit, & Riley, 2011).

While debate continues surrounding aetiology it is important that patients are supported and appropriate medical and psycho-social care is provided that respects the patient’s condition and experiences. Over exaggeration of the benefits at outcome of research, such as the PACE trail, is unlikely to bolster patient confidence and buy in to these type of interventions.

Fulcher, K, & White, PD. (2000). Strength and physiological response to exercise in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 69, 302-307.

Jason, L., Benton, M., Torres-Harding, S., & Muldowney, K. (2009). The impact of energy modulation on physical functioning and fatigue severity among patients with ME/CFS. Patient Education and Counselling. 77, 237–241.

Sharpe et al., (1991). A report--chronic fatigue syndrome: guidelines for research. J R Soc Med 84(2): 118–121.

Wearden, A., et al., (2010). Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ. 340, 959.

Competing interests declared: Volunteer (unpaid) chair of a patient support group – Chester MESH

RE: Too many questions still unanswered by this trial.....

ZigZag replied to JoanCrawford on 09 Aug 2012 at 11:06 GMT

Only approx 13% of patients responded to treatment with GET or CBT in the PACE Trial, as measured by the primary outcome measures, as per Table 3 in the original PACE Trial paper. (Approx 87% did not respond to treatment with CBT or GET.)

The "30%" figure, that has been misreported as a 'recovery', only relates to a 'reference range' known as the 'normal range', and does not indicate 'normal health', as the term is usually understood. Indeed, to fall within the 'normal range' a patient could have deteriorated after treatment, and not experienced any improvement at all. Also, the "30%" figure includes improvements seen in the control group.

Another point of interest is that CBT failed to achieve a clinically useful outcome for one of the two primary outcome measures, SF-36 physical function.

No competing interests declared.