Research priorities for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): the results of a James Lind alliance priority setting exercise

Figures & data

Table 1. Characteristics of respondents to the first and second survey.

	First Survey (n/%) n = 1565	Second Survey (n/%) n = 1752
How severe is your ME/CFS or the person you care for, at the moment? Mild Moderate Severe Very Severe In remission	n = 1498 184 (12%) 691 (46%) 520 (35%) 74 (5%) 29 (2%)	n = 1679 194 (12%) 821 (49%) 579 (34%) 58 (3%) 27 (2%)
Approximately how long ago did you, or the person you care for, first become ill with ME/CFS? <1year 1–5 years 5–20 years More than 20 years	n = 1496 20 (1%) 320 (21%) 681 (46%) 475 (32%)	n = 1684 32 (2%) 313 (19%) 789 (47%) 550 (33%)
Age of the person with ME/CFS* (years) Less than 25 25–44 45–64 65 + Prefer not to say	n = 1506 168(11%) 482 (32%) 654 (43%) 198 (13%) 4	n = 1693 157 (9%) 631 (37%) 706 (41%) 192 (11%) 7
Health Care professionals (n) Doctors Occupational therapists Psychologist/ counsellor Nurse NHS manager (including of ME/CFS services) Social worker Physiotherapist Alternative health practitioner Support worker Other	n = 89 26 13 10 10 1 5 5 5 2 12	n = 86 27 7 20 6 2 0 5 2 7 10

*NB. Carers of people with ME/CFS responded with the age of the person they cared for.

Table 2. Summary questions in Survey Two.

CAUSE
C1	Is there a genetic link to ME/CFS? If yes, how does it affect the risk of ME/CFS in families? Could this lead to new treatments?
C2	Why do some people develop ME/CFS following an infection? Is it linked to long-covid?
C3	Is ME/CFS caused by a faulty immune system? Is ME/CFS an autoimmune condition?
C4	Are there factors that increase the risk of developing ME/CFS (such as stress, trauma or exposure to toxic chemicals)?
C5	Do hormonal imbalances (such as thyroid hormone or cortisol imbalances) cause ME/CFS and/or affect symptoms? Could this lead to new treatments?
C6	Can ME/CFS be prevented?
C7	Is ME/CFS infectious? Can it be transmitted to others?
C8	What causes ME/CFS to become severe?
C9	What can be learnt about the cause of ME/CFS from clusters of cases?
DIAGNOSIS
D1	How can an accurate and reliable diagnostic test be developed for ME/CFS?
D2	How can the current approach to diagnosing ME/CFS be improved, to reduce delays and include other conditions commonly linked to ME/CFS (such as POTS, EDS and MCAS)?
PROGNOSIS
P1	What is the typical course of ME/CFS over a lifetime, for children and adults? What influences this?
P2	Why do symptoms vary between people with ME/CFS? Why are there short term and long term changes in ME/CFS symptoms?
P3	Why are women at greater risk of ME/CFS than men?
P4	Are there different types of ME/CFS linked to different causes and/or how severe it becomes? Do different types of ME/CFS need different treatments and/or have different chances of recovery?
P5	How do some people recover from ME/CFS? How might this understanding help others?
P6	Do hormonal changes (such as during the menstrual cycle, pregnancy and menopause) affect ME/CFS symptoms in women? Does ME/CFS affect menstrual cycles, risks during pregnancy or menopause?
P7	Which conditions are commonly linked with ME/CFS (such as EDS, POTS, gut disorders and MCAS)? Do they have the same root cause or does one cause the other?
P8	What causes people with ME/CFS to relapse and their symptoms to get worse? Are there ways to prevent or minimise relapses?
P9	Does ME/CFS affect life-expectancy?
P10	Are people from ethnic minorities at greater risk of developing ME/CFS? What barriers do they face to getting a diagnosis and treatment?
P11	Are there long-term effects of repeated post-exertional malaise (symptoms caused by physical, mental or emotional effort, often with a delay)?
TREATMENT & CARE
T1	Based on people’s experiences, what needs to be included in a long-term monitoring and follow-up care plan for people with ME/CFS?
T2	What causes sleep problems and sleep pattern changes in people with ME/CFS? How are these best managed and treated?
T5	Can prompt treatment and advice when diagnosed prevent ME/CFS from getting worse over time? What does this mean for people whose illness starts gradually?
T6	Does the immune system continue to over-function or under-function in some people with ME/CFS to cause symptoms? What does this mean for treatment and risks from infections and vaccinations, including with COVID-19?
T7	Which existing drugs used to treat other conditions might be useful for treating ME/CFS (such as low dose Naltrexone, or drugs used to treat POTS)?
T8	Do complementary and alternative therapies benefit people with ME/CFS?
BASIC BIOLOGY
B1	What causes ongoing fatigue (tiredness or exhaustion) in people with ME/CFS? How is this best treated and managed?
B2	What is the biological mechanism that causes post-exertional malaise (symptoms caused by physical, mental or emotional effort often with a delay) in people with ME/CFS? How is this best treated and managed?
B3	Are there changes in the central nervous system (brain and spinal cord) that cause ME/CFS symptoms?
B4	How are mitochondria, responsible for the body’s energy production, affected in ME/CFS? Could this understanding lead to new treatments?
B5	What causes gut problems and difficulties with swallowing and eating in people with ME/CFS? How are these best managed, for example with tube feeding for people who are very severely affected?
B6	Do heart problems, changes to blood cells or blood/lymph circulation cause ME/CFS symptoms? If so, how is this best treated?
B7	What causes brain fog in people with ME/CFS? How is this best treated and managed?
B8	What happens to muscle function in people with ME/CFS?
B9	Do postural or structural problems in the head, neck and spine cause symptoms of ME/CFS? If so, how is this best treated?
B10	What causes pain in people with ME/CFS? How is this best treated and managed?
B11	What causes some people with ME/CFS to become intolerant to alcohol, chemicals and/ or medicines?
B12	What are the links between nervous, digestive and immune systems that could cause ME/CFS symptoms?
B13	What causes transport in and out of cells to be affected in people with ME/CFS? Could this understanding lead to new treatments?
HEALTH SERVICES
N1	What would be the make-up of a high-quality specialist service for people with ME/CFS? Would this improve the treatment and care of people with ME/CFS?
N2	Why don’t some health professionals accept ME/CFS is a serious illness? What would help them to recognise and respond appropriately to people’s symptoms?
N3	How can the needs of people with ME/CFS best be met when accessing and using health and social care services (for example while in hospital)?
MANAGEMENT
S1	How does ME/CFS impact on people’s physical health, and does their physical health impact on their ME/CFS? What can people with ME/CFS safely do to maintain their physical health?
S2	Does changing diet or taking supplements help people with ME/CFS?
S3	Is there a way for people with ME/CFS to monitor and manage their activities (such as using a heart rate monitor) to avoid triggering post-exertional malaise?
S4	What causes sensory problems in people with ME/CFS (such as sensitivity to light, noise, smell and touch)? How are these best managed and treated?
S7	What causes nerve damage in the body in people with ME/CFS? How does this affect the autonomic nervous system causing symptoms such as orthostatic intolerance (e.g. feeling dizzy or unwell on standing or sitting up) or problems controlling body temperature? How is this best managed and treated?
S9	Are there ways to objectively measure how severely someone is affected by ME/CFS and whether their symptom levels are changing over time?
S10	Does poor delivery or use of oxygen within the body cause ME/CFS symptoms? If so, how is this best treated?
S11	Does continuing viral or bacterial infection cause ME/CFS symptoms? If so, are antivirals or antibiotics effective treatments?
S12	What causes headaches and migraines in ME/CFS? How are they best treated and managed?
S13	What causes skin problems in ME/CFS? How are they best treated and managed?
PSYCHOLGICAL AND SOCIAL IMPACT
Y1	What are the impacts of ME/CFS on people’s quality of life, including work, finances and family and social life? What practical support would be most effective, particularly in terms of social care and welfare benefits?
Y2	What are the psychological impacts of ME/CFS? How are these best treated and managed?
Y3	What harms do people with ME/CFS experience as a result of the lack of professional recognition and stigma from the condition? How can these best be addressed?
Y4	What practical and emotional support do carers/ parents of people with ME/CFS need and how can these needs be met?
Y5	What support do pupils and students with ME/CFS need to help them in their education?