PACE Trial - letters that were not accepted by the Lancet

[oceanblue]

CBT/GET results suggest their underlying assumptions do not hold for most patients

another unpublished letter I've been asked to post:

White and colleagues sought to test graded exercise therapy (GET) and
cognitive behaviour therapy (CBT), two posited approaches for Chronic
Fatigue Syndrome (CFS).1

In both GET and CBT, "[p]articipants are encouraged to see symptoms as
temporary and reversible".2 This is re-iterated in the accompanying
editorial, "oth graded exercise therapy and cognitive behavioural therapy
assume that recovery from chronic fatigue syndrome is possible".3 The
secondary outcome measure "recovery" would have helped us assess if such an
assumption is valid;4 we are not given figures for this but it is apparent
from the other data that the numbers achieving "recovery" were small.1

The results for the only objective outcome measure, the 6 minute walking
distance (6MWD), were similarly unimpressive.1 At the end of therapy, CBT
had led to no improvement over the control group. GET participants did
perform slightly better than the controls (+35.3 metres), but a 6MWD mean
(SD) of 379 (100) metres in a group with a mean age of 40 is still well
below the 631 (83) metres obtained previously by elderly adults (mean age:
65).5

These results come from a trial lasting 12 months, allowing plenty of time
for recovery to occur if the model was accurate.

Scientific experiments are about testing out hypotheses; far from the
strengthening the evidence for the theory that the effects of CFS are
temporary and can be reversed with either CBT or GET, the trial suggests
this model does not hold for most patients.

References:
1. White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; on behalf of the
PACE trial group. Protocol for the PACE trial: a randomised controlled trial
of adaptive pacing, cognitive behaviour therapy, and graded exercise, as
supplements to standardised specialist medical care versus standardised
specialist medical care alone for patients with the chronic fatigue
syndrome/myalgic encephalomyelitis or encephalopathy. BioMed Cent Neurol
2007;7:6.

2. Bavinton J, Darbishire L, White PD - on behalf of the PACE trial
management group. Graded Exercise Therapy for CFS/ME (Therapist manual):
http://www.pacetrial.org/docs/get-therapist-manual.pdf (Last Accessed: 4th
March, 2011)

3. Bleijenberg G, Knoop H. Chronic fatigue syndrome: where to PACE from
here? Lancet. 2011;377:786-8

4. White PD, Goldsmith KA, Johnson AL, and the PACE trial management group.
Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded
exercise therapy, and specialist medical care for chronic fatigue syndrome
(PACE): a randomised trial. Lancet. 2011;377:823-36

5. Troosters T, Gosselink R, Decramer M. Six minute walking distance in
healthy elderly subjects. Eur Respir J. 1999 Aug;14(2):270-4. Eur Respir J.
1999;14:270-4.

 

[Uno]

If you are able please join this group on Facebook http://www.facebook.com/group.php?gid=116996221671476#!/event.php?eid=211803305514578, urging everyone to write to the editor of the Lancet requesting he attends the Invest in ME Conference. Real research for real patients.

Thanks very much

Uno

 

[Dolphin]

North Wales ME Research Forum letter

North Wales ME Research Forum letter

Dear Editor,

White and colleagues published how they would define "recovery" along with "positive outcomes and improvers, the latter two being the primary outcome measures.1 However such data, along with other pre-specified outcome measures, was not presented.2 Instead the data was analysed in other ways; surely the point of registering trials and publishing protocols is to avoid this sort of trial reporting.

The trial protocol involved a validated definition of fatigue caseness so why not use it?1,3 Instead, we are given information on those who are within one standard deviation (SD) of some (newly chosen) population norms, norms derived from heterogeneous cohorts where not every individual was healthy. One SD from the norms used does not represent any sort of normal functioning; indeed, participants could be classified in this group, with a SF-36 physical functioning score of 60 and a Fatigue scale score of 18 and still meet the eligibility requirements for entry to the trial! Even if one accepts the norms that are used, the null hypothesis here should be that a group with normal functioning should be no different from the population norm, which could be tested statistically; such a null hypothesis might be rejected with the current groups [i.e. those within 1 SDs of the norm] if they mainly had worse values than the means.

In the accompanying editorial, those with scores within one SD of the norms are described as being recovered, demonstrating the problems that can arise with how this trial has been reported.4

References:

1. White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; on behalf of the PACE trial group. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BioMed Cent Neurol 2007; 7: 6.

2. White PD, Goldsmith KA, Johnson AL, et al, on behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; published online Feb 18. DOI:10.1016/S0140-6736(11)60096-2.

3. Chalder T, Berelowitz G, Hirsch S, Pawlikowska T, Wallace P, Wessely S, Wright D: Development of a fatigue scale. J Psychosom Res 1993, 37:147-153

4. Bleijenberg G, Knoop H. Chronic fatigue syndrome: where to PACE from here? Lancet 2011; published online Feb 18. DOI:10.1016/S0140-6736(11)60172-4 1

Yours faithfully,

Karl S. Krysko BA (hons) BSc. Chair - North Wales ME Research Forum

Simon J. Retallick PhD Member - North Wales ME Research Forum

Carolyn J. Retallick MA Member - North Wales ME Research Forum

Dawn M. Naylor PhD Member - North Wales ME Research Forum

 

[Dolphin]

Anna K Sheridan's letter

Anna K Sheridan's letter:

The publication of the PACE trial results has been met by swift and categorical rejection by Myalgic Encephalomyelitis (ME) charities in the United Kingdom.1,2 This unprecedented response from patient organisations deserves serious consideration. No treatment can be successfully implemented without patient approval. In a recent patient survey, the largest to date, 56% of patients reported a reduction in health after Graded Exercise Therapy, and 19% reported a reduction after Cognitive Behavioural Therapy (CBT).3

A primary methodological issue lies in the selection criteria. The trial admitted only those whose primary symptom is fatigue. However, an ME Association survey of 3594 people found less than half those surveyed reported fatigue as their primary symptom.3 The PACE trial rejected one third of referrals for not meeting the Oxford criteria, which requires fatigue as the primary symptom.1 By doing so, the majority of those suffering from ME have been rejected or ignored.

In addition, the PACE trial did not include the severely affected, who make up approximately 15% of the patient population,3 and for whom these treatments have been shown to lack efficacy,4 and safety, with 8% of patients reporting serious adverse events after Graded Exercise Therapy (GET).1 The PACE trial therefore found a small therapeutic effect on a minority of the patient population, which only confirms what others have found,5 that CBT and GET are not the effective treatment sought by both patients and the charities who represent them.

Anna K Sheridan

Competing Interests:

Glasgow ME/CFS Support Group.


1 White PD, Goldsmith KA, Johnson AL, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; DOI:10.1016/S0140-6736(11)60096-2.

2 ME Association. ME Association press statement about the results of the PACE study.*http://www.meassociation.org.uk/?p=4607(accessed March 3, 2011)

3 ME Association. Managing my ME. What people with ME/CFS and their carers want from the UK's health and social services.http://www.meassociation.org.uk/?page_id=1345*(accessed March 3, 2011)

4 Wearden AJ, Dowrick C, Chew-Graham C, et al. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ 2010; 340:c1777

5 Maes M, Twisk FN. "Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways." BMC Med. 2010 Jun 15;8:35. Review. PMID: 20550693

 

[Dolphin]

Another person who wishes to remain anonymous. They sent two:

Dr. Peter White and colleagues claim that cognitive behavioral therapy (CBT) and graded exercise therapy (GET) can safely be added to specialist medical care for treatment of chronic fatigue syndrome (CFS).1

However, 89%-96% of trial participants experienced a non-serious adverse event but no details were reported. Importance of adverse events were determined by research staff without participant input although clinicians have been shown to regularly underestimate the severity of patient symptoms.2 Thus, what was determined to be a non-serious event by research staff may be perceived differently by participants.

Secondly, different standards were applied in assessing deterioration and improvement. Serious deterioration required an SF-36 physical function (PF) score drop of 20 points or more from the baseline score sustained across any two consecutive assessment periods, which were months apart, yet clinically useful improvement needed only an eight-point increase at one point in time, 52 weeks. No information was given about the number of participants who experienced an eight-point drop. This is also a change from the original protocol where an adverse outcome meant a decreased score from the prior measurement only.3

Finally, contrary to this study, a recent Spanish trial of CBT/GET for CFS showed a statistically significant eight-point decline in mean SF-36 PF score accompanied by increased pain and weakness at 52 weeks in the intervention arm compared to the control arm.4


1. White PD, Goldsmith KA, Johnson AL, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 823-836.

2. Basch, E. The missing voice of patients in drug-safety reporting. NEJM 2010; 362:865-869.

3. White PD, Sharpe MC, Chalder T, et al. Protocol for the PACE trial: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurology 2007; 7:6.

4. Nez M, Fernndez-Sol J, Nuez E, et al. Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up. Clin Rheum 2011. [Epub ahead of print January 15, 2011.]

--------------------------

The Consolidated Standards of Reporting Trials (CONSORT) Statement addressing non-pharmacologic treatments recommends that [d]etails of the experimental treatment and comparator as they were implemented be included in reports.1 Implementation of an intervention might vary from the planned intervention and treatment contamination might occur either through research staff inadvertently introducing components of one intervention to the non-corresponding arm or trial participants treating themselves with another intervention because they believe it to be superior.

Adequacy of treatment in the PACE trial was defined as attendance of ten or more therapy sessions without any reference to the content of those sessions.2 The PACE manual for cognitive behavioral therapy (CBT) asked participants to set and accomplish goals such as to go for two ten-minute walks daily while the graded exercise therapy (GET) version asked participants to record type/ minutes of exercise, heart rate, and, in some cases, steps taken recorded by a pedometer.3,4 Both CBT and GET encouraged subjects to maintain and gradually increase activity levels with minimal rest. Planned activity and not symptoms are used to determine what the participant does.4 However, there is no mention in the paper of whether participants achieved their target goals, exercised an increased amount, or maintained/ increased activity despite symptoms. Furthermore, only participant self-report, subject to response bias, is used and no objective measures such as actigraphy or observed exercise were employed.

Without details about what trial participants actually did, can accurate conclusions about the safety and efficacy of CBT and GET be made?


1. Boutron I, Mohair D, Altman DG, et al. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Ann Int Med 2008; 148: 295-309.

2. White PD, Goldsmith KA, Johnson AL, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet 2011; 377: 823-836.

3. Burgess M, Chalder T. PACE manual for participants. Cognitive behaviour therapy for CFS/ME. http://www.pacetrial.org/docs/cbt-participant-manual.pdf. Accessed March 11, 2011.

4. Bavinton J, Dyer N, White PD. PACE graded exercise therapy. Information for participants. http://www.pacetrial.org/docs/get-participant-manual.pdf. Accessed March 11, 2011.

 

[Dolphin]

From jace:

The PACE study1 criteria for primary outcome measures have been changed post randomisation2. The original criteria for a successful treatment in terms of lowering fatigue was a 50% improvement or a score of three. This was abandoned, and the minimum score in this study now equates to six on the Chalder Fatigue scale3.

'Secondary objective end point data....Recovery will be defined by meeting all four of the following criteria: (i) a Chalder Fatigue Questionnaire score of 3 or less [27], (ii) SF-36 physical Function score of 85 or above(iii) a CGI score of 1 , and (iv) the participant no longer meets Oxford criteria for CFS, CDC criteria for CFS or the London criteria for ME'2, p.12, item 4
This data remains unpublished as does the data appertaining to exertion and fitness levels1.

The information of the effect on treatment of the 8 other symptoms of CFS, the improvement in economic and quality of life data1 also remain to be published.

When a study first enters the public domain impressive p values usually dominate the headlines. when the quantum of benefit is examined more closely however a different picture can emerge. This appears to be the case here. The benefits although described as moderate appear to be miniscule. Without the data which has yet to be published a full evaluation of the treatment appears impossible.

references:

1 White, PD; Goldsmith, KA; Johnson, AL; et al; Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial; The Lancet, Early Online Publication, 18 February 2011doi:10.1016/S0140-6736(11)60096-2

2 White, PD; Sharpe, MC; Chalder T; et al; Protocol for the PACE trial: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy; BMC Neurology 2007, 7:6doi:10.1186/1471-2377-7-6

3 Chalder, T; Berelowitz, G; Pawlikowska T; et al: Development of a Fatigue Scale; J. Psychosom. Res. Vol.37, No.2, pp 147-153, 1993

 

[Dolphin]

Another letter:

White and colleagues tested graded exercise therapy (GET) and cognitive behaviour therapy (CBT) as treatments for Chronic Fatigue Syndrome (CFS)1 which are both based on the biopsychosocial model of CFS. CBT assumes that fear of engaging in activity and avoidance of activity are responsible for perpetuating the participants symptoms and disability. 1. GET is based on the theory that CFS is perpetuated by deconditioning and avoidance of activity. 1.

Peter White, along with the authors of the editorial, Gijs Bleijenberg and Hans Knoop, have argued previously that a full recovery from CFS is possible following CBT. 2,3

Participants receiving CBT and GET were encouraged to see symptoms as temporary and reversible, with GET, for example, aiming to return a patient to normal health and ability. 4

The minimal mean difference recorded for participants in the GET and CBT groups, in comparison with the SMC group, and the setting of the normal range to a level which overlaps the eligibility for entry into the trial, demonstrate that the both GET and CBT were minimally effective and that the biopsychosocial model of CFS is without foundation.

The number of participants who recovered following treatment was recorded but not reported. 1,5 This is a significant omission because without these data it is not possible to fully evaluate the reported effectiveness of the GET and CBT , and the biopsychosocial model that underpins them both cannot be validated. 4,5

References:

1. White PD, Goldsmith KA, Johnson AL, and the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011;377:823-36

2. Knoop H, Bleijenberg G, Gielissen MF, van der Meer JW, White PD. Is a full recovery possible after cognitive behavioural therapy for chronic fatigue syndrome? Psychother Psychosom. 2007;76(3):171-6.

3. Bleijenberg G, Knoop H. Chronic fatigue syndrome: where to PACE from here? Lancet. 2011;377:786-8

4. Bavinton J, Darbishire L, White PD - on behalf of the PACE trial management group. Graded Exercise Therapy for CFS/ME (Therapist manual): http://www.pacetrial.org/docs/get-therapist-manual.pdf (Last Accessed: 4th March, 2011)

5. White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; on behalf of the PACE trial group. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BioMed Cent Neurol 2007;7:6.

 

[Dolphin]

ME Research UK: Moving beyond psychosocial therapies

This one from ME Research UK didn't make it either unfortunately:

Moving beyond psychosocial therapies

Since 2005, the MRC has funded two large clinical trials of cognitivebehavioural approaches for ME/CFS, at a cost exceeding 3 million. The first of these (the FINE trial 1) reported that pragmatic rehabilitation for severely affected patients improved fatigue in the short term compared with GP treatment as usual, but had only a small, non-significant effect after one year. The second (the PACE trial 2) has now reported modest improvements in some ME/CFS patients after cognitive behavioural or graded exercise therapy; a clinically useful difference in the primary outcomes of fatigue and physical function after one year occurred in 45%, 59% and 61% of the standard medical care, cognitive behavioural and graded exercise groups, respectively.

Neither of these expensive trials has established cognitivebehavioural approaches as convincing, core treatments for most patients with ME/CFS. Indeed, when their results are placed side-by-side with the most recent Cochrane review 3 and the most comprehensive meta-analysis 4 to date (which reported a smallmoderate overall effect size from 13 diverse trials), it is clear that psychosocial interventions have only an adjunctive role. The situation is therefore akin to that in other chronic illnesses, such as multiple sclerosis 5, where these non-specific approaches help with managing symptoms and promoting coping, but form only a small part of the clinical and therapeutic armoury required to address the underlying disease processes.

We conclude therefore that academic interest (and funding) should now focus on biomedical investigation to arrive at specific therapies for this debilitating illness.

References
1. Wearden AJ, Dowrick C, Chew-Graham C, et al. Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial. BMJ 2010; 340: c1777
2. White PD, Goldsmith KA, Johnson AL, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial . Lancet Feb 18, 2011; Epub ahead of print
3. Price JR et al. Cognitive behaviour therapy for chronic fatigue syndrome in adults. Cochrane Database Syst Rev 2008 Jul 16;(3):CD001027
4. Malouff JM et al. Efficacy of cognitive behavioral therapy for chronic fatigue syndrome: a meta-analysis. Clin Psychol Rev 2008 Jun; 28(5): 736-45
5. Dennison L, Moss-Morris R. Cognitive-behavioral therapy: what benefits can it offer people with multiple sclerosis? Expert Rev Neurother 2010; 10(9): 1383-90.

Vance Spence PhD, Chairman; Neil Abbot, MSc PhD, Operations Director
ME Research UK,
The Gateway, North Methven St,
Perth PH1 5PP, UK.
meruk@pkavs.org.uk

 

[Dolphin]

CFIDS Association of America

CFIDS Association of America:
http://www.cfids.org/research/lancet-letter.pdf

To the Editors of Lancet:

In their recent paper on the PACE Trial, White et al conclude, Our finding that studied treatments were only moderately effective also suggests research into more effective treatments is needed. However, the public will likely only read headlines like this one, Talking and exercise could cure M.E. study. Such tidy conclusions are dangerous. They contribute to dismissive attitudes about chronic fatigue syndrome (CFS) and myalgic encephalomyelitis (M.E.) and undermine understanding of its severe and life-altering impact. They vastly oversimplify the individual patients ability to recover his or her health. As a result of reading quips like this, patients may attempt more aggressive regimens than their bodies can withstand and professionals may recommend and/or deliver services that are not tailored to the restrictions imposed by CFS, especially post-exertional relapse.

Post-exertional relapse is a distinguishing feature of the illness and its biological basis has been objectively demonstrated.1,2,3,4 Using exercise testing, researchers have identified physiological responses that persist for days or weeks. The PACE Trial was, at least in part, designed to show that the fear of physical activity was a barrier to improvement in patients. However, a casecontrol study showed that there was no evidence of exercise phobia among CFS patients.5

By now, a robust literature of biological abnormalities found in nearly every body system should put to rest the debate about whether CFS is real or imagined. Funding should be directed to studies that advance biologically based early detection, objective diagnosis and truly effective treatment.

K. Kimberly McCleary
President & CEO
The CFIDS Association of America
March 4, 2011

1 Whiteside A, Hansen S, Chaudhuri A (2004). Exercise lowers pain threshold in chronic fatigue syndrome. Pain, 109: 497?499.
2 Van Oosterwijck J, Nijs J, Meeus M, et al. Pain inhibition and post?exertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome. Journal of Internal Medicine, 2010 Mar. 3 (Epub ahead of print).
3 Paul L, Wood L, Behan W, et al. (1999). Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. European Journal of Neurology 6: 63?69.
4 Blackwood SK, MacHale S, Power M, et al. (1998) Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. Journal of Neurology, Neurosurgery & Psychiatry, 65: 541?546.
5 Gallagher AM, Coldrick AR, Hedge B, et al. (2005) Is the chronic fatigue syndrome an exercise phobia? A case control study. Journal of Psychosomatic Research 58: 367?373.

 

[Dolphin]

This person, who wishes to remain anonymous, only got a rejection letter yesterday - I'm guessing this may mean it nearly made the cut.

A troubling methodological issue with the PACE trial is that an earlier version of the trial protocol required the use of actigraphy (actometers) as an objective outcome measure, and baseline data was actually collected.1,2 But the final published version of the protocol did not require collection of actometer data at follow up,3 a serious and perplexing failure to obtain informative, easily available and high quality objective data, in a trial that is sorely deficient in reporting such data.

The authors' reason for this omission that actometers place an undue burden on patients seems weak.2 Actometers are a reliable, unobtrusive, and accepted measure of physical activity,4 and are particularly important in behaviour therapy trials for chronic fatigue syndrome as use in previous similar trials has shown no correlation between subjective and objective measures of therapeutic effect,5 a serious problem for the behaviour model being tested by PACE.

The only objective measure used at PACE follow up was the 6 minute walking test, which produced only very marginal gains, in contrast to the significantly better (but still quite modest) results from subjective measures.

This just emphasises the critical importance of gathering all relevant, reasonably available objective outcomes data, especially when baseline data exists. This is not an optional extra for rigourous clinical trials.

It is not too late. Actometer data still can, and should be promptly collected and added to existing PACE data.


References

1. White PD, Goldsmith KA, Johnson AL, et al, on behalf of the PACE trial management group. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet, 2011; published online Feb 18. DOI:10.1016/S0140-6736(11)60096-2.

2. Author's response in letters section at http://www.biomedcentral.com/1471-2377/7/6/comments/#306608

3. Protocol for the PACE trial: A randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy
White PD, et al. BMC Neurology 2007, 7:6 doi:10.1186/1471-2377-7-6

4. Scheeres K, Knoop H, Meer J, Bleijenberg G. Clinical assessment of the physical activity pattern of chronic fatigue syndrome patients: a validation of three methods. Health Qual. Life Outcomes, 2009; 1;7:29.

5. Psychol Med. 2010 Aug;40( 8 ):1281-7. Epub 2010 Jan 5. How does cognitive behaviour therapy reduce fatigue in patients with chronic fatigue syndrome? The role of physical activity.
Wiborg JF, Knoop H, Stulemeijer M, Prins JB, Bleijenberg G.

 

[Tom Kindlon]

People who had letters turned down by the Lancet could probably post them now here: http://www.bmj.com/content/347/bmj.f5963?tab=responses on the BMJs as an e-letter:

The BMJ says such e-letters can be considered published/similar and have their own unique link so can be quoted in the future.

Ideally, I'd like at least one other person to post as Sean Lynch (psychiatrist) has dismissed my concerns and I'd be in a stronger position to post again if somebody else posted.

You can read the White et al. letter when it was an e-letter here: http://www.bmj.com/content/347/bmj.f5731?tab=responses .

The BMJ posts most e-letters it reaches. Some don't even have any references.