18th
May 2011
On 17th May 2011
Zoe Mullan, Senior Editor at The Lancet, sent an email to Professor Hooper
in response to the complaint he submitted about the PACE Trial article
published online by The Lancet on 18th February 2011 and
subsequently in the journal on 5th March 2011. In her email, Zoe
Mullan wrote: “We asked the authors of the PACE trial to respond to your
concerns, which they have duly done. Your complaint and their response were
discussed at the highest management level and this group of executive
editors was fully satisfied that there were no grounds whatsoever on which
to take further action. We attach the response provided to us here. From
an editorial perspective, the case is now closed”.
The undated response to
Professor Hooper’s complaint by Professors White, Sharpe and Chalder that
was sent to Dr Richard Horton (Editor-in-Chief of The Lancet) on behalf of
all the co-authors will, in the interests of openness and transparency, be
placed in the public domain and will be fully addressed in due course, as
will Professor Hooper’s concerns over what he believes is the failure of The
Lancet’s editorial process in this instance, but there is one point in
Professor White’s letter that is of particular importance, so it is
addressed in this initial response.
In their letter, Peter White
et al state: “The PACE trial paper refers to chronic fatigue syndrome
(CFS) which is operationally defined; it does not purport to be studying
CFS/ME”.
The sentence continues by
stating that the PACE Trial studied: “CFS defined simply as a
principal complaint of fatigue that is disabling, having lasted six months,
with no alternative medical explanation (Oxford criteria)”.
This is exactly what the ME/CFS community has been
saying from the outset, namely that the PACE Trial was not studying those
with ME.
Soon after the Oxford
criteria were published in 1991, one of the co-authors, psychiatrist Anthony
David, wrote in the British Medical Bulletin: ““British investigators
have put forward an alternative, less strict, operational definition which
is essentially chronic…fatigue in the absence of neurological signs,
(with) psychiatric symptoms…as common associated features” (AS
David; BMB 1991:47:4:966-988).
Given that ME is a
classified neurological disorder (ICD-10 G93.3), there thus ought to have
been no dispute that the PACE Trial Investigators were not studying those
with ME, but the Investigators have persistently confirmed that they were
studying those with ME, for example:
1.
The PACE Trial Identifier is clear: “Myalgic encephalomyelitis
is thought by most to be synonymous with CFS” (PACE
Trial Identifier; 2.1). The cited references for this statement are given as
(i) Fukuda K et al. The chronic fatigue syndrome: a comprehensive approach
to its definition and study. Ann Intern Med 1994; 121: 953-959; (ii) Sharpe
MC et al. A report – chronic fatigue syndrome. JR Soc Med 1991; 84: 118-121;
(iii) Wessely SC et al. Chronic fatigue and its syndromes. Oxford, Oxford
University Press, 1998; (iv) Working group report to the Chief Medical
Officer,
www.doh.gov.uk/cmo/cfsmereport
2002 and (v) NHS Centre for Reviews and Dissemination. Interventions for the
management of CFS/ME. Effective Health Care 2002; 7(4): 1-12.
2.
The two versions of the PACE Trial Protocol (both the Full Protocol and
short version that was published in BMC Neurology 2007:7:6) are equally
clear; the PACE Trial was: “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”.
3.
In the Glossary to the Full Protocol, Professor White et al specifically
state that CFS/ME is the official term for the illness described
in the “Working Group Report to the Chief Medical Officer (2002) and the
MRC RAG Report (2003)”.
4.
In the PACE Trial Patient Clinic Leaflet, Professor White et al state:
“This illness is also known as
post-viral fatigue syndrome, myalgic encephalomyelitis (ME) and myalgic
encephalopathy (ME). Medical authorities are not certain that CFS is
exactly the same illness as ME…but we will be calling this illness
CFS/ME”.
In The Lancet article
itself, Peter White et al use the term myalgic encephalomyelitis throughout
the text and actually state: “Myalgic encephalomyelitis is thought
by some researchers to be the same disorder….Several
diagnostic criteria exist for chronic fatigue syndrome and myalgic
encephalomyelitis”, thus implying that they had indeed studied those
with ME.
Moreover, in the authors’
reply published in the Lancet on 17th May 2011 (The PACE trial in
chronic fatigue syndrome – Authors’ reply), Peter White is unambiguous: “…however
we defined CFS and myalgic encephalomyelitis, we found that cognitive
behaviour therapy and graded exercise therapy provided a significant and
clinically useful advantage….”.
Here, though, Professors
White, Sharpe and Chalder have categorically stated that the PACE Trial
“does not purport to be studying CFS/ME”.
This may explain why so many
recruits were not accepted into the PACE Trial on the stated grounds they
did not fulfil the Oxford criteria for “CFS” (which according to the
Principal Investigators themselves, is not the same as “CFS/ME”).
If the PACE Trial was not
studying CFS/ME (as now asserted by Professor White et al), then the results
cannot be used by NICE to support its Clinical Guideline 53 for CFS/ME.
NICE, however, announced on 14th March
2011 that there will be no review of CG53 until 2013: “…interventions
recommended in the original guideline, such as CBT and GET, were described
as the interventions for which there is the clearest evidence-base of
benefit. This is supported by the recently published PACE trial….The
results of the study are in line with current NICE guideline recommendations
on the management of CFS/ME….There are no factors…which would
invalidate or change the direction of the current guideline
recommendations. The CFS/ME guideline should not be updated at this
time”.
Most certainly, this
statement by the Principal Investigators that the PACE Trial did not purport
to be studying those with CFS/ME raises important issues about the alleged
generalisability of the PACE Trial results, given that The Lancet article
unambiguously states: “The PACE findings can be generalised to
patients who also meet alternative diagnostic criteria for chronic fatigue
syndrome and myalgic encephalomyelitis but only if fatigue is their
main symptom”.
That The Lancet supports the
Principal Investigators’ inconsistent and indefensible position and refuses
to engage with clearly articulated complaints must be of concern to anyone
interested in the integrity of the scientific process.
