The PACE Trial:

An Expression Of Concern -

A Summary
 

Extracted from "The PACE Trial: An Expression of Concern"

by Douglas T Fraser

28th June 2011


 

 

In February 2011 the Lancet published "PACE: a randomised trial" (ISRCTN54285094). Ethics approval had been given in March 2003 and the trial was registered with Current Controlled Trials (a WHO Key Register) in May 2003. The Trial funders included both UK Member Organisations of Current Controlled Trials i.e. the Department of Health and the Medical Research Council  [6,7,8].

There is grave concern that correct procedures were not followed in the PACE trial registration or in the way the trial was conducted. The PACE Trial has been invalidated and should be removed from any association with research into myalgic encephalomyelitis (ME – also referred to as ME/CFS or CFS/ME).

Our concerns are summarised below with references. Please also refer to “The PACE Trial: An Expression Of Concern” by Douglas T Fraser [A]

 

The points of concern are - 

1.   PACE Trial does not confirm to the Ottawa Statement on Trial Registration

 

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 Trial registration has become a universal prerequisite to publishing in reputable journal

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 Essentially an unblinded trial, the PACE Trial appears to be falsely registered as a RCT [1a], an example of “strawman design” [2], and published in breach of the Lancet's own requirements [3].

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 In publishing the article, the Lancet appears to have breached its own conditions requiring formal Trial Registration without “missing fields or fields that contain uninformative terminology”, among other obligations [24].

 

2.   The PACE Trial was not fully transparent

 

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The PACE Trial registration was neither transparent nor correctly performed or administered

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In "Trial registers: protecting patients, advancing trust", Lancet Editor Dr Richard Horton commented that WHO Director General J W Lee "needs the continuing support of patients' groups and clinical researchers to convert sound principles into real practice". In a companion article Dr Ida Sim and colleagues cautioned that to "help restore public trust, however, trial registration must itself be fully transparent". It is stated "that CCT does not remove information from a record, or overwrite previous information, but will instead add any updated information, along with a date stamp to show when the changes were made to the trial record" [9].

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Previously logged information has been removed from the trial record, fields are missing, and fields contain uninformative terminology.

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The PACE Trial has not recorded data correctly and the record for ISRCTN54285094 (PACE) is incomplete [11].

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Changes to sponsors have not been recorded. The changes to sponsors recorded earlier, from: 1) the “MRC Clinical Trials Unit” to: 2) the “Medical Research Council” to: 3) the “Queen Mary University of London (UK)” have not been recorded [12].

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Changes in the previously recorded parameters have not been recorded.

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The deletion of previously recorded: “Eligibility criteria exclusion - meet criteria for chronic somatisation disorder”, has not been recorded [13].

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The removal from the record of previous “Endpoints/primary outcome(s)” measurements.

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Although data on endpoints/primary outcomes and their measurement were partly recorded at a point in 2005 (now viewable only through externally archived public record), complete outcome measures and their mode of measurement, and changes in these are not recorded as required.

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Primary and secondary endpoints and the detailed means of measuring, and their descriptions, are missing [11].

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Precise details of endpoints and their measurement, entry and exclusion criteria, and other data required by the WHO 20-item minimum dataset [29], and any changes to any field, should be recorded.

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It was recorded that “the GDG does not state that ME/CFS is a behavioural disorder, a psychiatric illness, a somatic/functional disorder, an illness belief, depression or anxiety disorder” and “have recognised that CFS/ME is a physical illness”.  A “recommendation that CFS/ME should be recognised as a physical illness had been made” [16]. The “recommendation” was subsequently removed from the Guideline [15].

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Change in previously recorded eligibility inclusion criteria i.e. from: “Chalder fatigue score of 4 or more and an SF36 physical function score of less than 75”, to: “6 or more” (Chalder) and “65 or less changed from 60 or less” (SF-36), have not been recorded [13].

 

3.   Testing for harm (safety) is not recorded in the trial registration

 

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Medical Journals Editors agreed to publish trials that have completed all 20 fields in the WHO minimal data set.

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One of two main aims of the trial was to search for harms ("designed to test safety"), an enterprise described as being without "sound scientific basis". That aim of the trial is not recorded in the requisite fields. Register users with an interest in harms or trial dissemination, who otherwise may have investigated the logic behind PACE safety testing and unusual media attention around that aspect of the trial, may be disadvantaged as a consequence of this register omission [10,11,12].

 

4.   Informed consent documents not published

 

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A former Chair of a Multi-Centre Research Ethics Committee clarified that the role of Ethics Committees included protecting trial patients against "misleading information". It has been argued that "researchers should do more than just disclose information about conflicts of interest to subjects; they should also help subjects to understand and interpret this information". It has also been proposed that "all clinical trial investigators be required to post the informed consent documents in public clinical trial registries", the documents having been described as "the translation of what the protocol dictates to the patient level" [13,14,15].

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A lack of salient information may cause as much harm as “misleading information”, and it has been suggested that “the public’s informed consent to what we do in a clinical trial will not be complete unless the patients’ informed consent document becomes public”. However, absent rudimentary information and deleted and imprecise entries on a public trial register are also a potential source of harm requiring remedy, particularly with regard to trials which may severely lack generalisability* and where it may be "difficult to distinguish a true effect from biased reporting (response bias), as polite patients may tend to report what they think socially most acceptable"[13,15,18*,19].

 

5.   Eligibility Inclusion Criteria Not recorded

 

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Changes in entry (inclusion criteria) are not fully detailed, nor are two changes in the trial's sponsor.

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Changes in previously recorded eligibility inclusion criteria have not been recorded [13].

  

6.   Conflicts of Interest

 

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Dr. Sim, of WHO Trials Registry, confirmed in 2005 that Key Registers "Must not have conflicts of interest over which trials or trial information to register" [3,4,5].

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The extent to which possible unnecessary suffering, hardship and distress may have resulted from the principal investigators secretive involvements with insurance and government over many years, is unknown, but such unusually serious conflicts of interest may in the end leave the PACE Trial and it's publishers without any moral credibility.

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Partly funded by the UK Medical Research Council, under the “Role of the funding source” it is reported in the Lancet that “The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report”.

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It is not reported that during the life of the PACE trial, Sharpe M and Chalder T (including interested colleagues at the Department of Psychological Medicine at the Institute of Psychiatry London and elsewhere), were members of the MRC Advisory Board, and that White PD and Chalder T served on the MRC Neurosciences and Mental Health Board [23] (http://tinyurl.com/6ld6m3q ).

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Authors of the trial have undertaken paid work for insurance industry.

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All three of the trial principal investigators (White PD, Chalder T, Sharpe M) declared conflicts of interest involving insurance companies. Two principal investigators declared being in conflict over both “voluntary” and paid work for government and insurance.

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The main principal investigator (White PD) declared conflicts of unknown specification working for one of the trial funders, the UK Department and Work and Pensions, a Department that partly funded the trial anticipating that it would show: “that work is good for physical and mental well-being and that being out of work can lead to poor health and other negative outcomes” [21]. White PD also declared being conflicted in some manner over his interest in working for the reinsurance company “Swiss Re” - billed as a “Leading Global Reinsurer” [22].

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The full PACE proposal was approved by the MRC in 2001. An insight into the nature of "PACE" Conflicts of Interest, "inadequately" reported in the Lancet, was provided in 2002. While promoting "psychologically informed rehabilitative treatments" UnumProvident were advised by a PI that "symptoms and disability are shaped by psychological factors..some persons appear to exaggerate symptoms but this is often hard to prove..both State and private insurers pay people to remain ill..[they] have even been threatening towards individuals and organisations who question the validity and permanence of the illness they champion. Again the ME lobby is the best example" [16, 17].

  

7.   Basis of Trial was Falsified

 

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The “disease/condition/study domain” for ISRCTN59388875 (“family focused CBT” ; Prof Trudie Chalder) is given as: “Chronic Fatigue Syndrome (CFS) otherwise known as Myalgic Encephalomyelitis (ME)” [26], and the “disease/condition/study domain” for ISRCTN74156610 (FINE; Dr Alison Wearden)  is given as: “Chronic fatigue syndrome (CFS)” [25].

Professor Malcolm Hooper was informed by email shortly before the IIMEC6 conference in May 2011 that the PACE Trial was not meant to address ME -

The PACE trial paper refers to chronic fatigue syndrome (CFS) which is operationally defined; it does not purport to be studying CFS/ME” [8].

 

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 In the Lancet PACE article the claim is made that CBT and GET “moderately improve” what is referred to as “outcomes” for chronic fatigue syndrome.

The trialists advised potential participants:

"You must be diagnosed by us as having CFS/ME. Fatigue or lack of energy must be your main problem, and it must be sufficiently severe and disabling". ” …you will be helping others who get the same condition you have now” [5].

The letter from White et al to Horton [8] directly contradicts the Lancet PACE article [5].The PACE Trial is therefore again shown to be flawed in its description, and therefore its outcome. 

 

 

References

 

A]       “The PACE Trial: An Expression Of Concern” - http://tinyurl.com/3vwztz8
 

1)       http://ottawagroup.ohri.ca/

"The Ottawa Statement is a consensus document that aims to guide the implementation of global trial registration. Endorsed by individuals and organisations throughout the international research community, the Statement recognises that public availability of information about all trials in healthcare is essential to ensuring ethical and scientific integrity in medical research". 

1a)     “For controlled trials, the identity of the control arm should be clear. The control intervention(s) is/are the interventions against which the study intervention is evaluated (e.g. placebo, no treatment, active control). If an active control is used, be sure to enter in the name(s) of that intervention, or enter "placebo" or "no treatment" as applicable. For each intervention, describe other intervention details as applicable (dose, duration, mode of administration, etc)”.

http://www.who.int/ictrp/network/trds/en/index.html

2)       http://www.icmje.org/update_may05.html

Update on Trials Registration: Is This Clinical Trial Fully Registered?: A Statement from the International Committee of Medical Journal Editors (May 2005) Catherine De Angelis, Richard Horton et al.

3)       http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2806%2968709-6/fulltext

Trial registers: protecting patients, advancing trust

Richard Horton: Co-chair, with Kay Dickersin, the Scientific Advisory Group that advises WHO on aspects of trial registration

4)       http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2806%2968708-4/fulltext

The Lancet, Volume 367, Issue 9523, Pages 1631 - 1633, 20 May 2006

Clinical trial registration: transparency is the watchword

Ida Sim , An-Wen Chan, A Metin Gülmezoglu, Tim Evans,Tikki Pang

5)       www.who.int/ictrp/news/ICTRP_ACHR.pdf      
WHO International Clinical Trials Registry Platform Ida Sim, MD, PhD Project Coordinator Department of Research Policy and Cooperation World Health Organization Geneva, Switzerland November 7, 2005

6)       http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2811%2960096-2/fulltext
The Lancet, Volume 377, Issue 9768, Pages 823 - 836, 5 March 2011
Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial
Prof PD White MD, KA Goldsmith , AL Johnson PhD, L Potts MSc , R Walwyn MSc , JC DeCesare BSc , HL Baber BSc , M Burgess PhD, LV Clark PhD, DL Cox PhD, J Bavinton BSc, BJ Angus MD, G Murphy MSc, M Murphy FRCP, H O'Dowd PhD, D Wilks FRCP, Prof P McCrone PhD, Prof T Chalder PhD, Prof M Sharpe MD, on behalf of the PACE trial management group

"We aimed to assess effectiveness and safety of all four treatments".

"We sought evidence  of benefit and harm".

" Observers—Sir Mansel Aylward (Department for Work and Pensions, London, UK) ..."

"The PACE trial was funded by .. the UK Department for Work and Pensions ..". http://www.publications.parliament.uk/pa/cm200506/cmselect/cmworpen/616/616we37.htm

Select Committee on Work and Pensions Written Evidence Supplementary memorandum submitted by UnumProvident following the publication of the Welfare Reform Green Paper

"In 2004 Professor Mansel Aylward was appointed to be the first director of the UnumProvident Centre for Psychosocial and Disability Research at Cardiff University"

"It is known paradox that despite the vast advances in medical treatments in the later half of the 20th century that there is a huge increase in people who are considered too ill to work. This rise in incapacity has taken place from the 1980s onwards and is seen in all developed countries. It cannot be easily explained in medical terms. Clearly the increase in illness is a complex social and psychological problem and definitely not imaginary. The biopsychosocial model of disability not only explains this part of this phenomenon, but also suggest how best to manage it"

"At UnumProvident we have a non-medical, enabling model of rehabilitation and we are working with our partners at the UnumProvident Centre for Psychosocial and Disability Research at Cardiff University to better understand what places people at risk of long-term or chronic illness"

7)       http://tinyurl.com/5tnpndl
          http://tinyurl.com/6etn39n
RCT of CBT, graded exercise, and pacing versus usual medical care for the chronic fatigue syndrome ISRCTN54285094

Sequential outpatients attending six chronic fatigue clinics in secondary care, who meet the Oxford criteria for chronic fatigue syndrome (CFS). We will operationalise CFS in terms of fatigue severity and disability as follows: a Chalder fatigue score of 4 or more and an SF36 physical function score of less than 75. Sponsor MRC Clinical Trials Unit

http://tinyurl.com/67vpmnp
Sequential outpatients attending six chronic fatigue clinics in secondary care, who meet the Oxford criteria for chronic fatigue syndrome (CFS). We will operationalise CFS in terms of fatigue severity and disability as follows: a Chalder fatigue score of 4 or more and an SF36 physical function score of less than 75.
Eligibility criteria - exclusion Patients who (a) are at significant risk of self-harm (b) meet criteria for chronic somatisation disorder (c) are unable to either speak or read English adequately (d) are unable to either attend hospital reliably or to do the therapies (e) are less than 18 years old
Endpoints/primary outcome(s)  1. The 11 item Chalder fatigue questionnaire, using categorical item scores to allow a categorical threshold measure of “abnormal” fatigue with a score of 4 having been previously shown to indicate abnormal fatigue. 2. The SF-36 physical function sub-scale, counting a score of 75 (out of a maximum of 100) or more as indicating normal function. 20 May 2005

8)       http://www.controlled-trials.com/isrctn/governing_board

ISRCTN is a not-for-profit organisation with the following Directors, Members and Member Organisations. Directors Frank Davidoff, Emeritus Editor, Annals of Internal Medicine Kate Law, Cancer Research UK Laura Leviton, Robert Wood Johnson Foundation, USA Marc Taylor on behalf of Department of Health, UK Chris Watkins on behalf of Medical Research Council, UK
Members John Simes on behalf of NHMRC Clinical Trials Centre, Australia
Member Organisations Canadian Institutes of Health Research Department of Health, UK Istituto di Ricerche Farmacologiche 'Mario Negri' Medical Research Council, UK Netherlands Organisation for Health Research & Development

9)       http://www.controlled-trials.com/isrctn/updating_record/
Updating an ISRCTN record

10)     http://issuu.com/lisakass/docs/centre_for_psychiatry_newsletter_-_issue_2
CENTRE_FOR_PSYCHIATRY May 22, 2011
Showing the way to treating Chronic Fatigue Syndrome by Peter White
"The PACE trial was therefore designed to test safety and effectiveness of these four interventions".

11)     http://www.nyuhjdbulletin.org/Permalink.aspx?permalinkId=9fdac2d6-2252-4339-8574-e86e69aedec0
Bulletin of the NYU Hospital for Joint Diseases 2007;65(2):132-4
Use and Abuse of the Controlled Clinical Trial Hasan Yazici, M.D.

12)     http://www.sciencemediacentre.org/pages/press_releases/11-02-17_cfsme_trial.htm
Science Media Centre 17 February 2011
Expert reaction to Lancet study looking at treatments for Chronic Fatigue Syndrome/ME
"GET and CBT are safe and effective"
"it confirms the effectiveness of two treatments, and their safety"
"cognitive behavioural therapy and graded exercise therapy as safe and effective"
"The study also allays fears that CBT or GET may be harmful".
"there is no need to worry about harm from the treatment"
"The study has definitively shown that there is no harm associated with GET"

https://www.kcl.ac.uk/research/rae/uoa9.pdf

"Wessely: Founder Member, Science & Media Centre, Royal Institution"

http://www.kcl.ac.uk/newsevents/news/newsrecords/2011/02Feb/SafeandeffectivetreatmentsforCFSME.aspx
King’s College London
Safe and effective treatments for CFS/ME
(photo caption) Sad and tired woman

13)     http://www.controlled-trials.com/news/bma_04oct99.asp
Registering information about randomised controlled trials
Meeting organised by the BMJ Publishing Group, The Lancet, and The Association of the British Pharmaceutical Industry, and held at the British Medical Association, London Monday, October 4, 1999

14)     http://www.ncbi.nlm.nih.gov/pubmed/15675055
Accountability in  Research. 2004 Apr-Jun;11(2):141-59.
Disclosing conflicts of interest to research subjects: an ethical and legal analysis.
Resnik DB. National Institute of Environmental Sciences, National Institute of Health, Box 12233, MD NH06, Research Triangle Park, NC 27709, USA. resnik@niehs.nih.gov

15)     http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911861/
Arthritis Res Ther. 2010; 12(3): 121.
Informed consent: time for more transparency
Yusuf Yazici and Hasan Yazici "What is not understandable is why the informed consent forms, basically  the translation of what the protocol dictates to the patient  level, is not part of these registries"

16)     http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020124
Why Most Published Research Findings Are False John P. A. Ioannidis
"Corollary 5: The greater the financial and other interests and prejudices in a scientific field, the less likely the research findings are to be true. Conflicts of interest and prejudice may increase bias, u. Conflicts of interest are very common in biomedical research, and typically they are inadequately and sparsely reported. Prejudice may not necessarily have financial roots. Scientists in a given field may be prejudiced purely because of their belief in a scientific theory or commitment to their own findings".

17)     http://tinyurl.com/69obogh

http://tinyurl.com/6ccvnnx (PDF version with missing text)

UnumProvident
Trends in Health and Disability 2002
Chief Medical Officer’s Report 2002 –
Functional Symptoms and Syndromes – Dr M Sharpe
Health and Welfare – Prof M Aylward
18) http://www.pacetrial.org/docs/ssmc-doctor-manual.pdf MANUAL FOR DOCTORS

STANDARDISED SPECIALIST MEDICAL CARE (SSMC) Gabrielle Murphy, David Wilks, Michael Sharpe, Mary Burgess & Trudie Chalder on behalf of the PACE Trial Management Group:

"You must be diagnosed by us as having CFS/ME. Fatigue or lack of energy must be your main problem, and it must be sufficiently severe and disabling".

19)     http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003974.pub3/full
The Cochrane Collaboration. Placebo interventions for all clinical conditions Asbjørn Hróbjartsson, Peter C Gøtzsche 20 JAN 2010 Assessed as up-to-date: 10 NOV 2009

20)     Initial response by Professor Malcolm Hooper to an undated letter sent by Professor Peter White to Dr Richard Horton, Editor-in-Chief of The Lancet - http://tinyurl.com/64jumec

 

21)     Part funding of the PACE trial by the DWP Freedom of Information request to Department for Work and Pensions http://www.whatdotheyknow.com/request/part_funding_of_the_pace_trial_b

 

22)     www.swissre.com/

 

23)     http://web.archive.org/web/20040117025403/http://www.mrc.ac.uk/

http://web.archive.org/web/20020804013216/www.mrc.ac.uk/index/about/about-organisation/about-bodies_and_members/about-mrc_advisory_board_(mab)/about-mab_e-k.htm

Professor M Knapp  HSPHRB Representative  Centre for Analysis of Social Exclusion  London School of Economics  London

http://web.archive.org/web/20030423052737/www.mrc.ac.uk/index/about/about-organisation/about-bodies_and_members/about-mrc_advisory_board_(mab)/about-mab_a-d.htm

Dr D Bhugra  HSPHRB Representative  Department of Psychiatry  Institute of Psychiatry  London 

Dr T Chalder  HSPHRB Representative  Department of Psychological Medicine  Institute of Psychiatry  London 

Dr A Cleare  NMHB Representative  Department of Psychological Medicine  Institute of Psychiatry  London 

Professor A David  NMHB Representative  Department of Psychological Medicine  Institute of Psychiatry  London 

Professor C F Dowrick  NMHB Representative  Department of Primary Care  University of Liverpool  Liverpool 

http://web.archive.org/web/20030423051347/www.mrc.ac.uk/index/about/about-organisation/about-bodies_and_members/about-mrc_advisory_board_(mab)/about-mab_e-k.htm

Professor A E Farmer  Ordinary Member  Social, Genetic & Developmental Psychiat  Institute of Psychiatry  London 

Dr J R Geddes  NMHB Representative  Department of Psychiatry  University of Oxford  Oxford 

Professor GM Goodwin  MCMB Representative  Department of Psychiatry  University of Oxford  Oxford 

Professor A Haines  Ordinary Member  Public Health & Primary Care  London School of Hygiene & Tropical Medicine  London 

Professor P W Halligan  NMHB Representative  Department of Psychology  University of Wales College of Cardiff  Cardiff 

Dr M H Hotopf  NMHB Representative  Department of Psychological Medicine  Institute of Psychiatry  London 

Professor A House  Ordinary Member  Academic Unit of Psychiatry & Behavioural Sciences  University of Leeds School of Medicine  Leeds 

http://web.archive.org/web/20030423053029/www.mrc.ac.uk/index/about/about-organisation/about-bodies_and_members/about-mrc_advisory_board_(mab)/about-mab_l-r.htm

Dr S M Lawrie  NMHB Representative  Department of Psychiatry  University of Edinburgh  Edinburgh 

Professor R M Murray  NMHB Representative  Department of Psychological Medicine  Institute of Psychiatry  London 

http://web.archive.org/web/20030728111049/www.mrc.ac.uk/index/about/about-organisation/about-bodies_and_members/about-mrc_advisory_board_(mab)/about-mab_s-z.htm

Dr M C Sharpe  Ordinary Member  Department of Psychological Medicine  University of Edinburgh  Edinburgh 

http://web.archive.org/web/20030423053029/www.mrc.ac.uk/index/about/about-organisation/about-bodies_and_members/about-mrc_advisory_board_(mab)/about-mab_l-r.htm

Dr S M Lawrie  NMHB Representative  Department of Psychiatry  University of Edinburgh  Edinburgh 

Professor R M Murray  NMHB Representative  Department of Psychological Medicine  Institute of Psychiatry  London 

http://web.archive.org/web/20030728111049/www.mrc.ac.uk/index/about/about-organisation/about-bodies_and_members/about-mrc_advisory_board_(mab)/about-mab_s-z.htm

Dr M C Sharpe  Ordinary Member  Department of Psychological Medicine  University of Edinburgh  Edinburgh 

Professor A Thapar  Ordinary Member  Department of Psychological Medicine  University of Wales College of Medicine  Cardiff   

www.mrc.ac.uk/consumption/groups/public/documents/content/mrc003093.pdf

http://classic-web.archive.org/web/*/http://www.mrc.ac.uk/consumption/groups/public/documents/content/mrc003093.pdf

Members of the College of Experts affiliated to the

Neurosciences and Mental Health Board

Professor R P Bentall School of Psychological Sciences The University of Manchester Manchester

Professor T Chalder Department of Psychological Medicine Institute of Psychiatry London

Professor P Cowen Psychopharmacology Research Unit Warneford Hospital Oxford

Professor A E Farmer Social, Genetic & Developmental Psychiatry Institute of Psychiatry London

Professor J R Geddes Department of Psychiatry University of Oxford Oxford

Dr S M Lawrie Department of Psychiatry University of Edinburgh Edinburgh

Professor P D White Department of Psychological Medicine Medical College of St

Bartholomew's London

 

24)     Update on Trials Registration: Is This Clinical Trial Fully Registered?: A Statement from the International Committee of Medical Journal Editors( May 2005) Richard Horton, FRCP
Editor,
The Lancet  et al.   http://www.icmje.org/update_may05.html

 

25)     A randomised controlled trial of nurse facilitated self-help treatment for patients in primary care with chronic fatigue syndrome. The FINE trial (Fatigue Intervention by Nurses Evaluation).

http://www.controlled-trials.com/ISRCTN74156610/fine+chronic+fatigue

26)   Family focused cognitive behaviour therapy versus behaviourally oriented psycho-education for chronic fatigue  syndrome in 11 to 18 year olds: a randomised controlled treatment trial
http://www.controlled-trials.com/ISRCTN59388875/chalder

 

 

 


Further information

Click here for more references to the PACE Trials on this site.

 

 

Last Updated: 18/02/2013


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