The Netherlands ME/CFS Cohort and Biobank (NMCB)

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a prolonged
debilitating disease, with unknown aetiology and unexplained pathophysiology,
resulting in a substantial reduction in previous activity levels and quality of
life. Diagnosis remains a challenge in the absence of biomarkers (e.g.
laboratory or imaging tests) and relies on the presence of characteristic
symptoms and the exclusion of disorders that may explain the symptoms, as well
as the patient*s clinical history. Patients often report an array of symptoms,
including extreme exhaustion with exercise intolerance and post-exertional
malaise, impaired sleep, cognitive dysfunction, musculoskeletal and/or
neuropathic pain, and orthostatic intolerance, and the inability to stand for
any length of time due to symptoms related to autonomic nervous system
dysfunction. However, the presence and severity of symptoms vary between
patients and can fluctuate over time. For healthcare professionals who
encounter ME/CFS*s characteristically heterogeneous symptom profiles and
illness course, management of these patients also remains a challenge.

The prevalence of myalgic encephalomyelitis or chronic fatigue syndrome
(ME/CFS) in the Netherlands is unknown but, based on international surveys,
estimated to be between 40,000 and 150,000 patients. Notwithstanding, the
Netherlands has invested little in biomedical research into ME/CFS; research is
scattered, with limited (inter)national collaboration, lacks an infrastructure
for patient data and sample collections, and provides poor funding prospects to
early career researchers creating a self-perpetuating situation. Meanwhile,
such research is urgently needed: patients experience debilitating physical
symptoms with little hope of spontaneous recovery. In the absence of a
biomarker the diagnosis relies on clinical judgment while treatment is
symptomatic. Further, ME/CFS is often stigmatized and linked with high
unemployment rates, causing substantial personal and societal costs.

It is important to acknowledge that ME/CFS research initiatives should be
informed by the experiences and desires of the patient community. ME/CFS
patients, along with their families and advocates, have consistently expressed
a strong desire for increased research efforts to understand the root causes,
improve diagnostic accuracy, and develop effective treatments. The patient
community has been vocal about the urgent need to validate the reality and
severity of this condition, combat stigma, and mitigate the substantial impact
it has on their daily lives.

To address this situation, ZonMw developed a *ME/CFS Research Agenda* (RA) to
initiate *substantive and long-term biomedical research into ME/CFS*. The
Netherlands ME/CFS Cohort and Biobank (NMCB) consortium was co-created with
Dutch patient organizations to implement the clear directives provided by this
RA. The NMCB mission is to establish a collaborative national research
infrastructure that collects and secures high-quality patient data, to test
hypotheses that will lead to a sound mechanistic understanding of ME/CFS, and
to see their translation into rational diagnosis and treatment. The NMCB will
actively disseminate its scientific output to improve the lives of patients and
their position in society. It builds on the principles of multidisciplinarity,
patient and stakeholder involvement, and (inter)national cooperation. Hence,
open science and FAIR data use are the core principles of the ME/CFS patient
registry and biobank.

ME/CFS patients have been and will continue to be involved throughout this
research process. Through the integration of patient perspectives, the NMCB
endeavours to bridge the gap between research and patient experiences,
ultimately leading to better understanding, improved healthcare practices, and
enhanced quality of life for people living with ME/CFS. By conducting this
research, not only will our scientific knowledge of ME/CFS be expanded but also
the ME/CFS community will be empowered and foster a sense of hope, solidarity,
and validation.

The primary objective is to characterise and understand the heterogeneity in
patients with ME/CFS (i.e. comorbidities, variability in symptoms and disease
progression, severity, and cognitive and autonomic impairment). Therefore, the
secondary objective is to develop a biobank with extensive and uniformly
collected clinical data and biological samples for the identification and
validation of biomarker panels and data-driven approaches. This biobank will
facilitate ME/CFS research as well as research into related post-infectious
fatigue syndromes (PIFS; e.g. long-COVID, Lyme*s disease, Q-fever). Such
studies will undergo a separate ethics review.

Cross-sectional collection of samples and data from cases and controls

All procedures have a moderate risk and moderate burden.

Questionnaires: Burden is limited through online data collection that allows
participants to self-pace. Patients can select to limit their involvement to
filling out a core questionnaire set whereby the remainder of questionnaires
are optional.

Physical assessments: All participants will be given the option to either come
into the clinic for these assessments or to be visited at home, limiting the
patient burden of having to travel.

Blood draws: A minor burden exists for blood draws, which may cause discomfort
and bruising at the injection site, and some participants may feel faint.

MRI: There are no major risks involved with MRI scanning. Well-trained
personnel will perform neuroimaging acquisitions from all participants.
Scanning may cause discomfort during scanning, and some participants may feel
claustrophobic. Individuals who have difficulties to lie still, or have
non-removable metal objects/materials (e.g. pacemakers) in their body will be
excluded.