ME/CFS Research a partnership with primary care Improving health worldwide Caroline Kingdon CURE-ME International Centre for Evidence in Disability Clinical Research Department Faculty of Infectious and Tropical Diseases LSHTM July 2015

Presentation overview Background Why research on ME/CFS? The UK ME/CFS Biobank Recruitment strategy & procedures Sample processing & resources available Importance of recruitment in primary care

The LSHTM Mission To improve health and health equity in the UK and worldwide; working in partnership to achieve excellence in public and global health research, education and translation of knowledge into policy and practice

The CURE-ME research team Creating clinical and biomedical Understanding through Research Evidence – For the ethical study of ME/CFS 2011 – 2014: A private donor 2013: 3-yr grant from US NIH allows expansion of recruitment “A longitudinal immunological and virological study for ME/CFS biomarker discovery”

Disease definition FATIGUE… New or had a specific onset (that is, it is not lifelong) Persistent and/or recurrent Unexplained by other conditions Substantial reduction in activity level Further requirements vary according to definition

SF-36v2™ scores in men and women with ME/CFS, other health conditions or healthy. RA - Rheumatoid arthritis; PF - Physical Functioning, RP - Role-Physical, BP - Bodily pain, GH - General Health, VT - Vitality, SF - Social Functioning, RE - Role-Emotional, MH - Mental health. Source: Nacul et all, The functional status and well being of people with myalgic encephalomyelitis/chronic fatigue syndrome and their carers. BMC Public Health, 11:402

The importance of clinical assessment Source: IOM, 2015.

Research Priorities Epidemiological method Biomarkers discovery Intervention studies Case stratification

UK ME/CFS Biobank target population Cases: Confirmed ME/CFS (Canadian or CDC-94 criteria) years old Informed consent Includes severely affected (mostly bed- or house-bound) Controls: “Healthy” and with multiple sclerosis (MS) Matched by age group and gender (area of residence) Informed consent

London area East of England Recruitment strategy Aim: ~ 500 participants

Recruitment strategy NHS Research Network Norfolk and Suffolk ME/CFS Specialist Service East of England PCRN NCH&C NNUH London UCL hospitals o Department of Clinical Immunology of the Royal Free Hospital o The Royal London Hospital for Integrated medicine o Hammersmith and Charing Cross hospitals – MS service Support groups for PWME - severely affected ME/CFS Disease Register

Recruitment strategy Ethics IRAS - Integrated Research Application System – NHS NRES/Research Ethics Committee (REC) London-Bloomsbury (11/LO/1760) – NHS / R&D offices (CSP 77765) East Coast Community Health Care CIC NHS Norfolk NHS Great Yarmouth & Waveney NHS Suffolk Joint Research Office (Royal Free site) LSHTM Ethics Committee approval HTA license Informed consent & free withdrawal All samples anonymous

Outline of recruitment procedures Probable case or control UCL/Royal Free Biobank Cases: NHS primary & secondary services; severely-affected through DR & support groups Controls: NHS primary & secondary services; invited by consenting PWME Collection of samples blood (& urine) Processing and storage of blood samples 1. Invitation of participants 2. Recruitment of consenting subjects Clinical assessment Exclusion 3. Sample collection 4. Confirmation of diagnosis, sample processing and storage Lab tests results(NHS) Confirmed ME/CFS cases Non- ME/CFS chronic fatigued group Consent given & criteria met Controls MS cases

Recruitment in East of England Phase 1Phase 2

Current recruitment

UK ME/CFS Biobank target population  Over 500 participants planned so far, including:  Cases: Confirmed ME/CFS (Canadian or CDC-94 criteria) years Fully informed consent provided NIH: 1/3 severely-affected (mostly bed- or house-bound)  Controls: Both “healthy” and those with multiple sclerosis (MS) Frequency matched by age, gender, and area of residence Fully informed consent provided

UK ME/CFS Biobank

Resources available: Data Clinical data blood pressure (seated and standing) hand grip strength test waist circumference standing height weight and bioimpedance spirometry pulse oximetry Questionnaire data Medical Outcomes Survey Short Form (SF-36v2) Pain analogue scale Fatigue scales (assessing severity and disability) General Health Questionnaire (GHQ-28) Epworth sleepiness score

Resources available: B aseline tests Laboratory test results full blood count blood chemistry liver function tests ESR CRP rheumatoid screening thyroid function tests tissue transglutaminase antibodies serum vitamin B12 red cell folate

Resources available: Aliquots Blood products stored /participant / timepoint Whole blood Serum Plasma Red Blood Cells (RBCs) Peripheral Blood Mononuclear Cells (PBMCs) Blood for RNA 17,000 aliquots stored as of March 2015

Conclusions Research evidence on ME/CFS still weak Evidence should be based on studies with robust methodology – Carefully designed study protocols – Large sample sizes – Combined case definitions – Higher specificity and validity Understanding pathophysiology and development of biomarkers are essential for definition of cases, stratification and specific treatments Partnership with the East of England primary has been proven successful for recruitment or research participants

Thank you from the CURE-ME Team! Learn more: Contact us: Erinna Bowman, Luis Nacul, and Eliana Lacerda Caroline Kingdon