Amendment 6.0 Cover letter — 13/12/2007 Substantial amendment form — 13/12/2007 REC opinion letter — 26/02/2008PACE Trial Coordinating Centre, 3° Floor Dominion House, St. Bartholomew's Hospital, London, EC1A 7BE, Telephone: 020 7601 8160, Facsimile: 020 7601 8176 Email: pace@amul.ac.uk ‘Nicola Murphy Committee Coordinator, West Midiancs Mult-centre Research Ethics Committee 27 Highfield Road, Edgbaston, Birmingham, 815 3DP 13" December 2007 —— @% SENOWE zo REPLACE LesT Dear Ms Murphy, TEA Dt] ar(eooy. Full title of study: 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 fatique syndrome / myaigic encephalomyeitis or encephalopathy MREC reference number 02/7/89 Re: Substantial Amendment 6.0 Please find attached Substantial Amendment 6.0 for the PACE trial to inform the committee of an increase to funding to allow extension of the tial recruitmentirandomisation period ‘Substantial amendment (non-iMP) for GET self help guide Version 1.0, 2007 Two and a half year PACE trial follow up protocol Version‘.0, 26.11.2007 ‘Two and a halt year PACE trial follow up booklet Version 1.0, 26.11.2007 Please do not hesilaie to contact me should you require any further information relating to this or any other PACE trial matter. Yours sincerely, ‘DeCesare - Tnal manager fA behalf of Professors Peter D White, Michzel Sharpe and Trudie Chalder (Principal Investigators and the PACE Trial Management Group, apie DWP RisinES National Patient Safety Agency National Research Ethics Service NOTICE OF SUBSTANTIAL AMENDMENT For use in the case of all research other than clinical tials of investigational medicinal products (CTIMPs). For substantial amendments io CTIMPs, please use the EU-approved notice of amendment form (Annex 2 to ENTRICT1) at http.//eudract emea eu jnt/édocument, htmM¥quidance. To be complated n typescript by the Chief Investigator in language comprehensible to a lay porson and submited to the Research Ethics Committee that gave @ favourable opinion of the research (‘the main REC’). In the case of multi-site studies, there is no need to send copies to other RECs unless specifically required by the main REC. Further guidance is available at htip:/waw.nres. nose.nhs.ul/epplicants/review/afteriamendments. hrm, Details of Chief Investigator: Name: Professor Peter D White Address” clo Julia DeCesare PACE Trial Manager Barts and the London Queen Mary's School of Medicine and Dentistry Department of Psychiatry institute of Community Health Sciences Room 3 112 3rd Floor, Dominion House St Bartholomew's Hospital London EC1A 7BE Telephone. 020 7601 8160 Email pace@mul.ac.uk Fax: 020 7601 7188, Short title of trial: Full file of study: Pacing, craded Activity, and Cognitive behaviour therapy; a randomised Evaluation Long title of 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Name of main REC: West Midlands REC REC reference number: MREC/02/7/89 Date study commenced: First approval 31% March 2003 inal approval 11" February 2005 Further verbal approval 25" February 2005 (verbal by phone to confirm submitted minor amendments were indeed minor), First participant randomised 18" March 2005 ; ISRCTN number: ISRCTN54285094 Protocol reference (if applicable), | MRC code number: G0200434 current version and date: Final protocol Protocol version number 5.3 Protocol date: 06 April 2006 Amendment number and date: 60 Type of amendment (indicate all that apply in bold) a) Amendment to inforinetion previously given on the NRES Application Form Yes tyes, please refer to relevant sections of the REC applicetion in the “summary of changoe” boiow [b) Amendment to the protoco! Yor tyes, please submit ether the revised protocol with ¢ new version number and date, highlighting changes in bold, or 2 document listing the changes ana giving both’ the previous and revised text (c) Amenament to the information sheet(s) and consent form(s) for participants, or to any other ‘supporting documentation for the study Yos tyes, please submit al revised documents with new version numbers ard detes, highlighting new fext in bold. Is this a modified version of an amendment previously notified to the REC and given an unfavourable opinion? No Notice of amencment (non-CTIMP). version 3.1, November 2008Summary of changes Briefly summanse the man changes proposed in this amendment using language comprehensible to a lay person, Explain the purpose of tne changes and their significance for ihe study. In the cese of ‘2 modified amendment, highlight the modifications that have been made. Ifthe amendment significantly alters the research design er methodology, 0° could etherwise affect the scientific value of the study, supporting scientific information should be given (or enclosed separately). Indicate whether or not addtional sceentiic cntique nas been obtained. ‘The PACE Trial Management Group with the support of the PACE Trial Steering Committee and Data Monitoring Committee would like permission to implement the following items: Graded Exercise Therapy (GET) self help guide Participants that are randomised to receive Standardised Specialist Medical Care (SSMC) alone are encouraged to try self manegement approaches to CFS/ME with the support of their treating doctor. As part of this self management approach, participants are either supplied with a reading list (see substantial amendment 5.8 for a copy of the present reading list), or f the centre prefers, participants are offered publications to borrow, the availability of which depends upon the local clinic resources. Ithas long been felt by the PACE trial team that there is a lack of equipoise in the self help approach as whilst there are publications available that discuss Cognitive Behavioural Therapy (CBT) and pacing, no suitable publication exists that explain the graded exercise approach as a self-help management approach As a consequence, the PACE trial GET therapists have written a self help guide that we would like to make available to trial participants, receiving SSMC alone, that would like to read it. A copy of the guide is attached for MREC approval. This guide has been revised many times, incorporating comments from patient representatives ac well as CFS/ME patients who have finished their time in the PACE trial Website updates ‘We would like to notify the REC that we will be updating the website for newsletters previously passed by the REC and the most recent version of the participant information sheet ‘Two and a half year follow up for the PACE trial In the onginal consent forms for the PACE trial, we have sought permission from all participants to contact them again after their time on the trial has completed, to gather information about their long term CFS/ME status. The research teams inform us that participants frequently enquire about long term follow up and are keen to provide information even afier their time in PACE has finished. The PACE trial teem are now seeking permission from the MREC to begin carrying out this study and gathering data two end a half years post-randomisation. A greatly reduced set of questionnaires has been selected to gather data on the primary outcomes, and Notice of amendment (non-CTIMF), verson 9.1, November 2005other key variables, which will be gathered pimarily by post. These data wil allow us to report long-term consequences of PACE trial treatment, while taking into account other treatments received since finishing the trial. Please find attached a protocol and questionnaire booklet for review by the MREC. Applicants may indloate any specific ethical issues relating to the amendment, on which the opinion of the REC is sought. List of enclosed documents Document Version Date. GET solf help guide Two and a half year PACE tial follow up protocol “Two and a helf year PACE tral follow up bocklet Declaration ‘© | confirm that the information in this form 1s accurate to the best of my knowedge and | take full responsibilty fort. ‘= | consider that it would be reasoneble for the proposed amendment to be impiementeé. Sonature of Chef investigate: Print name: ROL WEN! Kee Date of submission: Ordgtrale Rel Hea (2[12boF Jas requis Pan tary Roa Hea meV ees [Notice of amendment (non-CTIMP), version 3.1, November 2005GE National Research Ethics Service West Midlands Research Ethics Committee Osprey House ‘Alben Sireet Reediich Worcestershire, BO7 20E ‘Acting Chauman tr Paul Hemiten Co-ranator Ws Anne McCullough Tek 01527 587573, Fax 01827 507501 26 February 2008 Dr Peter D White Senior Lecturer in Psychological Medicine Barts and The london William Harvey House West Smithfield London ECIA 7BE Dear Dr White Study title: A randomised, controlled trial of adding cognitive behaviour therapy, graded exercise, or adaptive pacing to usual medical care, compared to usual medical care alone for the chronic fatigue syndrome [ME] PACE TRIAL REC reference: 02/7/1089 Amendment numt Amendment date: 13 December 2007 The above amendment was reviewed at the meeting of the Sub-Committee of the REC held on 26 February 2008, Ethical opinion ‘The members of the Committee present gave a favourable ethical opinion of the amendment on the basis described in the notice of amendment form and supporting documentation. Approved documents ‘The documents reviewed and approved at the meeting were: Document [Version [Date Two anda half PACE tial folow up booklet 0 [25 Novernber 2007 [Two and o half year PAGE trial follow up prolocol 0 [26 Novertber 2007 [GET self help auice Version 1.0 | Notice of Substantial Amendment (non-CTIMPS) [13 December 2007 This Research Ethics Committee is an adwsory committee to West Midlands Strategic Heath Authority The Hetional Research Ethics Service (NRCS) sepresents the NRES Drectorate within the Neaional Pstient Safety Agency ana Research Ethics Committees in EnglsndMembership of the Committee The members of the Committee who were present at the meeting are listed on the attached sheet, R&D approval All nvestigators ard research eollaboraters in the NHS should nly the R&D office for the ‘elevant NHS care organisation of this amendment and check whether it affects RED approval of the research, Statement of compliance The Commitiee is constituted in accordance with the Governance Arrangements for Research Ethics Committees (July 2001) and complies fully with the Standard Operating Procedures for Research Ethics Committees in the UK. o2r7/089: Please quote this number on all correspondence Yours sipgerely Miss Nikki Murphy Assistant Committee Co-ordinator Enclosures List of names end professions of members who were present al the meeting and those who submitted written comments,West Midlands Research Ethics Committee Attendance at Sub-Committee of the REC meeting on 26 February 2008 [fame Profession Capacity [DeRonald witb Consultant Rhoumatologiat Vise Chaw Exper | irs Pat Meseley Retred Teacher lay Member