ME Biobank recruitment protocol:
Once eligibility was established, the research team booked appointments for participants for
clinical assessments and blood sample collection. Participants in the Greater London area
with severe disease and/or mobility restrictions were seen at their homes. Consenting
respondents ineligible according to the screening questionnaire were thanked by the
research team and told that their ineligibility was based on the exclusionary criteria.
Clinical assessments & phlebotomy
Clinical assessments included the following clinical measurements:
• blood pressure and pulse taken at rest in seated and standing positions (both taken
twice);
• hand grip strength test (three repeated 3-second measurements using the dominant
hand);
• waist circumference;
• standing height;
• weight and bioimpedance (a measurement of body composition estimating body fat
and lean body mass);
• spirometry; and
• pulse oximetry.
Recruitment took place in the East of England and within Greater London. Baseline blood
tests were carried out at the James Paget University Hospital in Great Yarmouth, the Royal
Free Hospital in London, and the Norfolk and Norwich University Hospital (NNUH). Samples
were transported to the UCL/RFH BioBank immediately after collection to ensure receipt by
the BioBank within six hours of collection for processing, aliquoting, and storage.
Baseline blood tests included a full blood count, blood chemistry, calcium, electrolytes,
creatinine, serum creatine kinase, liver function tests, erythrocyte sedimentation rate, Creactive
protein, rheumatoid factor, thyroid function tests, tissue transglutaminase
antibodies, serum vitamin B12, and serum folate. Additionally, participants were asked at the
time of the clinical assessment to produce a sample of urine to be screened for glucose,
blood, protein, and specific gravity.
The research team sent questionnaires to participants at the time of the blood collection
covering demographic, socio-economic, and other exposure variables as well as clinical
history, including information on illness onset and an extensive list of symptoms, family
health history, and symptoms currently being experienced (at the time of the blood
collection), which can all be linked to both the baseline laboratory tests and the de-identified
blood samples. Questions were chosen taking into account the team’s experience with
ME/CFS research (4, 9) and variables captured by the UK Biobank project (10).
The following instruments were used to further characterise participants:
1 Medical Outcomes Survey Short Form – SF-36v2 (11) for assessment of functional capacity;
2 the pain analogue scale (12), for assessment of pain severity;
3 a fatigue severity scale (13);
4 the energy fatigue scale (14);
5 a fatigue disability scale, based on the Karnofsky scale (15),
6 the General Health Questionnaire – GHQ-28 (16-24),
7 and the Epworth sleepiness score (25).
All participants meeting eligibility criteria were asked for blood samples (approximately
95ml), from which approximately 15ml was used for baseline laboratory tests to exclude
other diagnoses. The remainder was processed and stored at the UCL/RFH BioBank for
future ethically-approved studies, including those planned by the LSHTM research team, for
which participants have given “a priori” consent.
The UCL/RFH BioBank, a state-of-the-science facility licensed by the Human Tissue
Authority (Licence number 11016), which holds specific ethical approval for the processing
and storage of biological samples. No personally-identifiable information is stored in the
UCL/RFH BioBank database and so stored samples can be linked anonymously to a range
of clinical and other non-identifiable data from participants.
Figure 1 summarises the UK ME/CFS Biobank recruitment procedures. Further details on
the collection, transport, processing, and storage of blood samples follow:
• The LSHTM team prepared blood collection kits including the required number and
type of Vacutainer tubes and a needle. SOPs for blood collection and transport were
followed.
• Staff members at the UCL/RFH BioBank followed SOPs for receipt, logging,
processing, and storage of samples. The Vacutainer blood tubes received at the
BioBank yielded aliquots of serum, plasma (from both NaHep and EDTA tubes),
peripheral mononuclear blood cells, a red blood cell/granulocyte pellet, and whole
blood, in addition to the PAXgene tube for RNA. The separated cells, plasma and
serum samples can be used for a range of investigations and techniques, including
for RNA and DNA extraction.
• All samples can be stored at the UCL/RFH BioBank for up to five years in the first
instance. Inventories of samples in the BioBank are sent regularly to the research
team.
CS