Adverse events & deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome, 2014, Sharpe,White,Chalder et al

[Sly Saint]

Highlights
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This study shows the distribution of adverse events in a trial of treatments for CFS.

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Non-serious adverse events were common, but no different between treatments.

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Non-serious adverse events were more related to ill health than treatments.

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Deterioration in physical function was more likely after adaptive pacing therapy.

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Differences between centres may be related to different ascertainment methods.

Abstract
Objective
Adverse events (AEs) are health related events, reported by participants in clinical trials. We describe AEs in the PACE trial of treatments for chronic fatigue syndrome (CFS) and baseline characteristics associated with them.

Methods
AEs were recorded on three occasions over one year in 641 participants. We compared the numbers and nature of AEs between treatment arms of specialist medical care (SMC) alone, or SMC supplemented by adaptive pacing therapy (APT), cognitive behaviour therapy (CBT) or graded exercise therapy (GET). We examined associations with baseline measures by binary logistic regression analyses, and compared the proportions of participants who deteriorated by clinically important amounts.

Results
Serious adverse events and reactions were infrequent. Non-serious adverse events were common; the median (quartiles) number was 4 (2, 8) per participant, with no significant differences between treatments (P = .47). A greater number of NSAEs were associated with recruitment centre, and baseline physical symptom count, body mass index, and depressive disorder. Physical function deteriorated in 39 (25%) participants after APT, 15 (9%) after CBT, 18 (11%) after GET, and 28 (18%) after SMC (P < .001), with no significant differences in worsening fatigue.

Conclusions
The numbers of adverse events did not differ significantly between trial treatments, but physical deterioration occurred most often after APT. The reporting of non-serious adverse events may reflect the nature of the illness rather than the effect of treatments. Differences between centres suggest that both standardisation of ascertainment methods and training are important when collecting adverse event data.

https://www.sciencedirect.com/science/article/pii/S0022399914001883?via=ihub

(was this data ever released?)

 

[cassava7]

From the discussion of the reanalysis of the PACE trial, which cited this paper (spacing mine):

Turning now to safety issues, there were few group differences in the incidence of adverse events, and the researchers concluded that both CBT and GET were safe for people with CFS. This finding – particularly that relating to GET - contrasts markedly with findings from informal surveys conducted by patient organisations [38, 39].

In these surveys, between 33% and 79% of respondents report worsened health as a result of having participated in some form of graded exercise programme (weighted average across 11 different surveys: 54% [39]). Of course, in such surveys, participant self-selection may operate to enhance the reporting rates for adverse outcomes. However, this finding is so consistent, and the number of participants surveyed is so large (upwards of 10,000 cases), that it cannot be entirely dismissed.

One likely reason for the discrepancy between PACE’s findings and those of patient surveys is the conservative approach used in PACE’s GET programme. Patients were encouraged to increase activity only if it provoked no more than mild symptoms [40]. Unfortunately, compliance with the activity recommendations was not directly assessed: actigraphy data were collected only at trial commencement [1] and never reported. This is a significant omission, since there is evidence that graded exercise therapies are not always successful in actually increasing CFS patients’ activity levels [41]. Even those who comply with exercise goals may reduce other activities to compensate [42]. The lack of improvement in fitness levels in PACE’s GET group does suggest that participants may not have substantially increased their activity levels, even over the course of an entire year.

Also, even though the majority of GET participants chose walking as their primary activity [2], this group demonstrated an average increase in walking speed of only 10% after an entire year (increases of 50% or more have been observed in other patient populations [35]). Given these features, it is inappropriate to generalise the safety findings from PACE to graded activity programmes more widely, especially as they are currently implemented in clinical settings.​