I'd encourage readers interested in the background to the response paper by Michael Sharpe and colleagues  to have a look at a previous blogging occasion when the topic of the PACE trial, chronic fatigue syndrome (CFS) and 'recovery' were discussed (see here).
Suffice to say that this latest paper is a reply to one published by Carolyn Wilshire and colleagues  who concluded that: "The claim that patients [with CFS] can recover as a result of CBT [cognitive behaviour therapy] and GET [graded exercise therapy] is not justified by the data, and is highly misleading to clinicians and patients considering these treatments." Said discussions linking back to some quite extensive debates on how one should (and shouldn't) treat/manage conditions like CFS (see here).
I wanted to highlight the latest Sharpe paper because (a) I anticipated a reply from these authors following the Wilshire paper criticism of their recovery paper , and (b) although the debates in this area have been quite extensive already, the use of the scientific peer-reviewed medium to discuss and even argue is an important avenue. The authors have a right to scientific reply.
So how did Sharpe et al respond? Well the words 'recovery', 'threshold' and ''no generally agreed measure of recovery" when it comes to CFS form the crux of the response to the Wilshire paper. They address the issue of recovery thresholds that have been a real source of discussion in relation to the PACE trial secondary analysis concluding that: "No participant met our full criteria for recovery at baseline." They point out that whilst "13% of participants met the recovery criterion of being within the normal range... for physical functioning when entering the trial" physical functioning was but one measure they used to determine recovery.
They also approach the topic of 'changing thresholds' when it came to the definition of recovery in the PACE trial. To quote: "We changed these thresholds for our detailed analysis plan because after careful consideration and consultation, we concluded that they were simply too stringent to capture clinically meaningful recovery." They also report that elements of their assessment - the PACE walking test - are "not comparable with data collected in other studies" as a function of their reliance on personal motivation/ability over and above the use of encouragement as in other studies.
Finally, authors also talk about 'what other studies have found regarding recovery' when it comes to CFS. They note that their findings in relation to the use of standard medical care (SMC) for CFS in the PACE trial were similar to other reports . They also point to research suggesting that the use of CBT in independent study for CFS show similar rates of recovery  to theirs originally reported. In other words, they make a case for their findings fitting in with some of the other literature on this topic.
A quick trawl of PubMed with the terms 'chronic fatigue syndrome' and 'recovery' reveals that there is indeed quite a bit more to do in this area of science. To quote from one paper (a critical review) : "Estimates of recovery ranged from 0 to 66 % in intervention studies and 2.6 to 62 % in naturalistic studies." What this tells us is that (a) how recovery is reported in relation to CFS is still in need of some clarification  and perhaps more importantly, agreed uniformity is still required in its assessment; (b) some of the measures used to form judgements of recovery when it comes to CFS are not necessarily fit for purpose  (bearing in mind not everyone agrees with this); and (c) further efforts need to go into looking at many more aspects of CFS recovery outside of just a reliance on the fatigue parameter (see here and see here for examples). In short, science does not really know what recovery looks like in relation to CFS  despite it seemingly happening for all manner of reasons...
Where do we go from here? This is a difficult question to answer. It is doubtful that the response from Sharpe and colleagues is going to change too many opinions about PACE given the strength of feeling on the topic and the various goings-on that have occurred around debate in this area (see here). Still today, other comments on the PACE trial continue to emerge in the peer-reviewed domain  from notable CFS researchers and there are even calls to retract the original recovery paper (see here). Yes, there are lessons to be learned from the PACE trial (e.g. stick to your "original protocol thresholds", make your data 'open-access' and think about how to do this in the planning/recruitment stages of your trial, be mindful that short-term gains don't necessarily translate into long-term ones, work with the ME/CFS community (rather than labelling elements of them 'vexatious' or worse when they ask questions or request data) but I can't see how these factors will immediately and positively affect the lives of people living with CFS/ME here and now. That recommendations on the use of CBT for CFS have already altered in some parts of the world (see here) - "The strength of evidence on global improvement is downgraded from moderate to low when considering CBT separately from other counseling and behavioral interventions" - and are potentially likely to change here in Blighty perhaps signifies that science and medicine is moving on when it comes to this topic. Science should be doubling its efforts to expand its research boundaries when it comes to managing CFS outside of just a reliance on the [outdated?] psychosomatic model and indeed, it is...
And on the topic of other CFS research avenues, I've already talked about a few interesting avenues on this blog (see here and see here and see here) mindful that when we talk about CFS/ME, we're probably not talking about just one entity (see here). Also alongside, that there seems to be an awful lot of 'over-represented' comorbidity accompanying quite a lot of CFS/ME (see here for example) to also contend with...
Music: Lush Life (even if you don't know the song title, you might recognise the tune).
 Sharpe M. et al. Do more people recover from chronic fatigue syndrome with cognitive behaviour therapy or graded exercise therapy than with other treatments? Fatigue: Biomedicine, Health & Behavior. 2017. Feb 15.
 Wilshire C. et al. Can patients with chronic fatigue syndrome really recover after graded exercise or cognitive behavioural therapy? A critical commentary and preliminary re-analysis of the PACE trial. Fatigue: Biomedicine, Health & Behavior. 2016. Dec 14.
 White PD. et al. Recovery from chronic fatigue syndrome after treatments given in the PACE trial. Psychol Med. 2013 Oct;43(10):2227-35.
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 Flo E. & Chalder T. Prevalence and predictors of recovery from chronic fatigue syndrome in a routine clinical practice. Behav Res Ther. 2014 Dec;63:1-8.
 Twisk FN. A definition of recovery in myalgic encephalomyelitis and chronic fatigue syndrome should be based upon objective measures. Qual Life Res. 2014 Nov;23(9):2417-8.
 Matthees A. Assessment of recovery status in chronic fatigue syndrome using normative data. Qual Life Res. 2015 Apr;24(4):905-7.
 Brown B. et al. 'Betwixt and between'; liminality in recovery stories from people with myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS). Sociol Health Illn. 2017 Feb 27.
 Jason LA. The PACE trial missteps on pacing and patient selection. Journal of Health Psychology. 2017. Feb 1.
M Sharpe, T Chalder, AL Johnson, KA Goldsmith, & PD White (2017). Do more people recover from chronic fatigue syndrome with cognitive behaviour therapy or graded exercise therapy than with other treatments? Fatigue: Biomedicine, Health & Behavior, 1-5 : 10.1080/21641846.2017.1288629