The PACE trial missteps on pacing and patient selection

[RogerBlack]

Abstract
As others have pointed out a variety of complicating factors with the PACE trial (e.g. changing outcome criteria), I will limit my remarks to issues that involve the composition of adaptive pacing therapy and issues involving patient selection. My key points are that the PACE trial investigators were not successful in designing and implementing a valid pacing intervention and patient selection ambiguity further compromised the study’s outcomes.

http://journals.sagepub.com/doi/10.1177/1359105317695801

Various criticisms, to sum up:
APT: The patients were instructed to do 70% of their percieved energy limit, and this could have lead to the patients regressing because they were doing too little, as well as the extra time resting eating into vital tasks.
Contrasts with energy envelope theory, 'staying within the envelope of percieved energy', and reasons this may be better, citing trials of functioning and severity.
it's likely that SMC contained elements of pacing.
'Discouraging patients from pacing could cause harm'.
Case definitions matter - CBT might work on some in a loose case definition.
'Any major chronic health condition, such as ME, can cause depressive disorder. Some investigators do not understand or appreciate this important diagnostic issue'
'CFSness' of sample - 'only 77% had poor memory/concentration and only 84% had PEM'


In short - there are some criticisms that I don't think have been directly published before.

A welcome addition to the literature, from someone that's been doing interesting work for a while.

The author is an author of https://www.ncbi.nlm.nih.gov/pubmed/10205371 back in 1999 - "Managing chronic fatigue syndrome: overview and case study."

1. The basic principles of envelope theory are explained. By not overexerting themselves, people with CFS can avoid the setbacks and relapses that commonly occur in response to overexertion while increasing their tolerance to activity. 2. By collecting time series data on fluctuations in energy levels, important clinical observations can be made in respect to a client's unique condition and experience with CFS.

 

[Dr Speedy]

Thx; I'm bedridden and I've got many serious problems including cognitive dysfunction but I do not suffer from poor memory/concentration ...

 

[Grigor]

The more the merrier. Been quiet around PACE. It's needs to be taken down. Always good to have fellow top psychologist criticise PACE

 

[Esther12]

I thought this paper broadened criticisms of PACE in some good ways, being able to leave what I think are some of the stronger criticisms to others. I wonder how PACE will respond? I suspect that them having lost credibility in other areas will make it harder for them to respond to Jason's concerns in the way that they would have five years ago (I can't believe it's been so long since PACE came out!).

More
specifically, the APT intervention used by the
investigators instructed patients to not go
beyond 70 percent of their perceived energy
limit. However, if expended energy is consistently
lower than available energy, patients can
become too inactive. In other words, the APT
pacing intervention instructed patients to do less
than there available energy might have allowed.
By doing less than what patients have the energy
to do, and the resulting pre-emptive rest, this
intervention could even have the unwitting
effects of increasing social isolation (Goudsmit
et al., 2009).

Good to have the 70% restriction being challenged.

Finally, by the authors widely disseminating
through the often-quoted Lancet publication
that pacing was not effective, some health care
providers, family members, and friends were
discouraged from supporting what patients feel
are their most effective coping strategy. These
are iatrogenic effects that could have major
consequences for further stigmatizing a vulnerable
population.

I've got a half memory of a DWP document that was critical of pacing post-PACE too. A number of patients have reported being quizzed by tribunal doctors on their approaches to their illness during benefits appeal, and getting a disapproving respose if they expressed a preference for pacing over CBT/GET approaches.

The possibility that the PACE trial included
individuals without the illness is also supported
by data regarding many within their sample
who lacked core symptoms of CFS. For example,
at baseline, only 72–77 percent had poor
memory/concentration and only 82–87 percent
had post-exertional malaise. These levels of key
symptoms are low, suggesting the inclusion of a
proportion of cases without CFS. A variety of
factors, in addition to psychiatric issues, can
result in CFS-like symptoms. These include
poor sleep hygiene, poor diet, and deconditioning.
It is critical to exclude people whose CFSlike
symptoms and fatigue are due to these
lifestyle factors as well as excessive exertion
such as being over-committed. Given the PACE
trial’s position of adopting a broad case definition,
such as the Oxford criteria, it is unclear if
they excluded those whose fatigue and symptoms
were due to these lifestyle factors.

This is the conclusion:

Conclusion
When studies using broad criteria like Oxford
were eliminated, the Agency for Healthcare
Research and Quality (2016) downgraded their
evaluation of CBT stating that given the inconsistent
results and mixed quality of the studies
made it impossible for them to determine if
CBT was effective for those meeting the Fukuda
et al. (1994) criteria. Individuals who meet very
broad criteria, as well as those with solely affective
disorders, would react much better to CBT
and GET, thus complicating any interpretation
of the treatment outcomes. This suggests that
developing a consensus for a narrower case
definition remains a critical task for investigators,
as without a research case definition of
ME, it continues to be unclear whether samples
in different studies are comparable and have
core symptoms of this illness.

There are many questions that remain unanswered,
and it is possible that with encouragement
of positive expectations and greater
frequency and intensity in the cognitive therapy
and graded exercise arms, nonspecific factors
were influential in these treatments, and it is
unclear if such factors were left out of the adaptive
pacing arm. Other major problems for this
study included using an APT intervention that
had multiple components as well as recommendations
that might have inappropriately limited
activity. The problems with patient selection
due to the use of broad case definitions that
might not have excluded those not having this
illness, along with the problematic implementation
of the pacing arm, remain significant obstacles
in interpreting the outcomes of this trial.

I wonder if, tactically, a wise retreat for the PACE researchers would be to say 'well, CBT and GET seem to be effective for our CFS patients, if you want to define CFS differently then...'

I wouldn't really like to see them get away with that, and it would still be humiliating enough for them that I expect they'd want to avoid it if they feel they have a chance of doing so.

Thanks a lot to Jason for another piece chipping away at the PACE ediface!

 

[alex3619]

Thx; I'm bedridden and I've got many serious problems including cognitive dysfunction but I do not suffer from poor memory/concentration ...

After almost two months of bedrest in hospital I had much less severe memory and concentration problems. Supine might mean improved blood flow to the brain, especially in patients with orthostatic intolerance. The question is what happens when a bedridden patient can mobilize and be up and about longer. Does this increase cognitive symptoms?

 

[user9876]

Good to have the 70% restriction being challenged.





I wonder if, tactically, a wise retreat for the PACE researchers would be to say 'well, CBT and GET seem to be effective for our CFS patients, if you want to define CFS differently then...'

I wouldn't really like to see them get away with that, and it would still be humiliating enough for them that I expect they'd want to avoid it if they feel they have a chance of doing so.

Thanks a lot to Jason for another piece chipping away at the PACE ediface!

Given what we have seen of the data I don't think they could claim that it works for 'our cfs patients'. I don't see the issues around patient selection as particularly damning in terms as the results when compared to the different expectations covered by the different treatment arms along with the subjective measurements.

The thing about the 70% is that is reduces peoples abilities and hence a drop in the sf36 measures would be expected (if it were an interval scale and APT was neutral we would expect a 30% drop).

 

[alex3619]

The thing about the 70% is that is reduces peoples abilities and hence a drop in the sf36 measures would be expected

I am not sure this is always the case. Yes, it has the potential to do so. Yet this will only apply to patients who are at or over their 100% safe limit before intervention. The idea of a lower limit is to give a buffer, and allow for occasional increased demand as necessities arise, which is quite often. Now given how many of us are pushing our 100% constantly, this might be an issue for some.

 

[Dr Speedy]

I thought this paper broadened criticisms of PACE in some good ways, being able to leave what I think are some of the stronger criticisms to others. I wonder how PACE will respond? I suspect that them having lost credibility in other areas will make it harder for them to respond to Jason's concerns in the way that they would have five years ago (I can't believe it's been so long since PACE came out!).



Good to have the 70% restriction being challenged.


I've got a half memory of a DWP document that was critical of pacing post-PACE too. A number of patients have reported being quizzed by tribunal doctors on their approaches to their illness during benefits appeal, and getting a disapproving respose if they expressed a preference for pacing over CBT/GET approaches.



This is the conclusion:



I wonder if, tactically, a wise retreat for the PACE researchers would be to say 'well, CBT and GET seem to be effective for our CFS patients, if you want to define CFS differently then...'

I wouldn't really like to see them get away with that, and it would still be humiliating enough for them that I expect they'd want to avoid it if they feel they have a chance of doing so.

Thanks a lot to Jason for another piece chipping away at the PACE ediface!

PACE came out in February 2011 so 6 years ago ;-)