ME Research UK supports calls for creation of an internationally recognised and operationalised research criteria for ME. In doing so, it joins leading researchers, clinicians, fellow charities, patients, advocates, and supporters from across the globe.
As pointed out by the proposal an international effort to create consensus on the criteria and methods for selecting cases in ME research would create a modern, specific research criteria to aid research efforts.
Research Case Definition Consensus Statement
Internationally, clinical definitions for Myalgic Encephalomyelitis (ME), sometimes called ME/CFS, have been adopted in many countries, but there is still no consensus around research criteria. In 2015, the Institute of Medicine in the US developed a clinical case definition for ME/CFS, but this was never meant to be used for research. For decades, research into ME has been hampered by heterogeneous diagnostic criteria and the inclusion of participants who may not actually have ME.
This has impacted the validity of many studies and created a risk of harm for patients. There is still not an international consensus on a research case definition or case definitions.
The core problem is that many case definitions do not require key symptoms such as post-exertional malaise and do not take the severity of the symptoms into account. Further, methods for evaluating cases have been inconsistent. The time has come to improve cross-study comparability and ensure study participants have ME. We the undersigned believe the time has come to sponsor an international effort to create a consensus on the criteria and methods for selecting cases in research. Such a consensus will need to address multiple issues, including those below.
● A consistent set of required inclusion criteria. One example is the requirement for substantial impairment in functioning and post-exertional malaise1 lasting six months or more in all research criteria for people with ME, with cognitive impairment and unrefreshing sleep considered key features.2,3,4*
● A consistent approach to exclusionary conditions. This includes any previously diagnosed medical condition whose resolution has not been documented beyond reasonable clinical doubt and whose continued activity may explain the symptoms of ME.5**
● A consistent approach for evaluation of key criteria. This is done with structured questionnaires that evaluate both symptom severity and frequency as well as level of functional impairment. An example of a widely used method is the DePaul Symptom Questionnaire.6,7,8 Research publications should outline how criteria have been operationalized.
● A consistent approach to characterizing and labeling overall disease severity of cases .9,10,11,12,13***
* There are many secondary symptoms that may be experienced by people with ME including orthostatic intolerance, pain, immune, and gastro-intestinal complaints.
** While clinically a patient can have both ME and other diagnoses, in research, it’s important to have a consistent approach to exclusions to improve cross-study comparability.
The Canadian Consensus Criteria, ME-International Consensus Criteria, and NICE 2021 criteria meet many of these standards. The IOM criteria meet these standards when using the proposed exclusionary criteria and when cognitive impairment is required. The Fukuda criteria do not meet these standards.
Footnotes
1 Recently, the World ME Alliance, with 24 member organizations across 17 countries, supported the inclusion of PEM as a core symptom. Standing Strong: Global ME Community unified in support of NICE 2021 ME/CFS Guideline. 2023.Available at: https://worldmealliance.org/2023/08/standing-strong-global-me-community-unified-in-support-of-nice-2021-me-cfs-guideline/
2 Kingdon, C, Abken, E, Lacerda, E & Nacul, L. A proposal for consensus diagnostic criteria for ME/CFS research. Poster presented at the meeting of the International Association of ME/CFS, Stonybrook University, N.Y. 2023
3 Jason, L. A. & Ravichandran, S. An effort to develop a consensus on critical ME/CFS definitional issues. Poster presented at the meeting of the International Association of ME/CFS, Stonybrook University, N.Y. 2023
4 Nacul L, Authier FJ, Scheibenbogen C, Lorusso L, Helland IB, Martin JA, Sirbu CA, Mengshoel AM, Polo O, Behrends U, Nielsen H, Grabowski P, Sekulic S, Sepulveda N, Estévez-López F, Zalewski P, Pheby DFH, Castro-Marrero J, Sakkas GK, Capelli E, Brundsdlund I, Cullinan J, Krumina A, Bergquist J, Murovska M, Vermuelen RCW, Lacerda EM. European Network on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME/CFS in Europe. Medicina (Kaunas). 2021 May 19;57(5):510. doi: 10.3390/medicina57050510.
5 See Table 2 in Jason, L.A., Ravichandran, S., Katz, B.Z., Natelson, B.H., & Bonilla, H.F. Establishing a consensus on ME/CFS exclusionary illnesses. Fatigue: Biomedicine, Health & Behavior, 2023; 11(1), 1-13. https://doi.org/10.1080/21641846.2022.2150487
6 Nacul L, Kingdon CC, Bowman EW, Curran H, Lacerda EM. Differing case definitions point to the need for an accurate diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome. Fatigue: Biomedicine, Health & Behavior, 2017;5(1):1-4. doi: 10.1080/21641846.2017.1273863. PMID: 29250461; PMCID: PMC5730342.
7 Sunnquist, M., Lazarus, S., & Jason, L.A. The development of a short form of the DePaul Symptom Questionnaire. Rehabilitation Psychology, 2019, 64(4), 453–462. PMCID: PMC6697554 https://doi.org/10.1037/rep0000285
8 Cotler, J., Holtzman, C., Dudun, C., & Jason, L.A. A brief questionnaire to assess post-exertional malaise. Diagnostics, 2018, 8, 66. doi:10.3390/diagnostics8030066
9 Carruthers BM, van de Sande MI, De Meirleir KL, et al. Myalgic encephalomyelitis: International Consensus Criteria. J Intern Med. 2011; 270: 327-338.
10 Bateman L, Bested AC, Bonilla HF, et al. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: essentials of diagnosis and management. Mayo Clinic Proc. 2021;96(11):2861–2878. Available from: https://www.mayoclinicproceedings.org/action/showPdf?pii=S0025-6196%2821%2900513-9#page=10.
11 Cox, D. L., & Findley, L.J. The Management of Chronic Fatigue Syndrome in an Inpatient Setting: Presentation of an Approach and Perceived Outcome. British Journal of Occupational Therapy, 1998, 61(9), 405–09. https://journals.sagepub.com/doi/10.1177/030802269806100907
12 Conroy, K., Bhatia, S., Islam, M., & Jason, L.A. Homebound versus bedridden status among patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Healthcare, 2021, 9(2), 106. https://doi.org/10.3390/healthcare9020106
13 Wiedbusch, E., & Jason, L.A. Comparing operationalized approaches for substantial reduction of functioning in Chronic Fatigue Syndrome and Myalgic Encephalomyelitis. Archives of Community Medicine, 2022, 4(1), 59-63. PMCID: PMC9168545 https://doi.org/10.36959/547/653
