This Talk Clinical Trials blog has been written by Sabrina Poirier, a patient advocate for Myalgic Encephalomyelitis (ME) and other complex chronic illnesses, and co-founder of the ICanCME Research Network. Drawing on her lived experience with ME, Sabrina shares her perspective on how the clinical trials community can better understand and engage with people living with ME.
Many of us living with Myalgic Encephalomyelitis (ME) see research as hope. We count on those in the clinical trials community to help bring safe and well-designed studies to reality – and ideally in collaboration with people like me who have lived experience.
This blog is intended to help you – no matter the role you play in the clinical trials space. Maybe you’re a trialist, on a research ethics board (REB), or a member of a research team. We hope that learning more about ME will help inform your critical work.
What is ME?
ME is formerly known as Chronic Fatigue Syndrome (CFS) and is often still referred to as ME/CFS. ME is a devastating, chronic, complex, multi-system illness that impacts all ages and backgrounds. There is a growing recognition that ME is a serious disabling disease rooted in dysfunctions that impair energy production, the immune system, the nervous system and more.1
The onset of ME can be sudden or ME can develop gradually, often following an infection. The SARS-CoV-2 virus is the most recent example, with as many as 30% of acute COVID cases developing into Long COVID and 50% or more of those developing into ME.2
Post-exertional malaise (PEM) is the cardinal symptom of ME.3 PEM is the delayed onset or worsening of ME symptoms, after physical or cognitive exertion, usually presenting about 24-72 hours after the exertion.4 PEM may take days, weeks or longer to recover from.4, 5 Unfortunately, some may never recover to their previous baseline.
Core symptoms of ME also include profound and debilitating fatigue, unrefreshing sleep, cognitive impairment, orthostatic intolerance, autonomic impairment, chronic and severe ‘flu-like’ symptoms such as tender or swollen lymph nodes, fever, headache, sore throat, as well as chronic pain, gastrointestinal symptoms and sensitivity to sound and light.1
ME severity can range from “mild” (which comes with a 50% reduction in function and debilitating symptoms, so it is not mild at all) to very severe (where individuals are completely bedridden, in a dark room, isolated from those they love, and left completely neglected by the healthcare system). Up to 25% of people with ME are bedbound or housebound at some point in their illness (many indefinitely), and 75% of us are unable to work. 6, 7
Those of us with ME find it difficult or impossible to function as we did before ME. ME affects all aspects of our lives. That includes activities of daily living (e.g., showering, eating), relationships, parenting tasks, work, etc.
While any illness can co-exist with ME, there are many common comorbidities such as Fibromyalgia, Postural Orthostatic Tachycardia Syndrome (POTS), Dysautonomia, Mast Cell Activation Syndrome (MCAS), Ehlers-Danlos Syndrome (EDS) or hypermobile Ehlers Danlos Syndrome (hEDS), Small-Fibre Neuropathy, Small Intestinal Bacterial Overgrowth (SIBO), Gastroparesis and Irritable Bowel Syndrome (IBS).
Research brings hope to people living with ME
There is currently no cure or approved treatments for ME. The few treatments that can be tried address only a few key symptoms or comorbidities.
Getting a diagnosis of ME can be extremely difficult. Generally, physicians and other healthcare providers lack awareness of ME. Often, people with ME are dismissed, gaslit and left neglected by our healthcare systems. Some people with ME are unable to access care at all due to healthcare systems (or specific clinicians) denying them virtual care options or disability accommodations. We constantly need to advocate for ourselves, but that’s incredibly hard to do with such limited energy. We want to be believed, listened to, and provided appropriate treatment for our condition so that we can improve our quality of life and preserve as much function as possible.
Given that we have so few treatment options, we likely have a different tolerance to risk and benefit than others. We are often willing to take risks that the general population would not, and even for less potential benefit. This underscores the importance of clear, transparent, and fully informed consent. An informed consent document that truly provides a full understanding of the risks, including PEM, allows each person to then decide their risk tolerance for themselves. Our higher tolerance to risk, without a fully informed decision, can lead us to participate in research that is not well-designed, or may even be harmful to us, without us realizing the risks we are taking.
Also, with our limited energy being a reality in this illness, we need researchers to understand that energy used to participate in research is energy that’s taken away from other parts of our lives, as we have much longer recovery times due to PEM.
Consequently, it’s important that research is designed appropriately for people with ME, and that it takes into account our perspectives, needs and priorities.
Why the lived experience of ME is a form of knowledge and evidence
ICanCME is the Canadian ME research network, funded by the Canadian Institutes of Health Research – Institute of Musculoskeletal Health and Arthritis (CIHR IMHA), which focuses on elevating the lived experiences of those with ME to be at the research table.8 ICanCME was co-founded by people with ME, and we are ‘threaded’ throughout the network as members of committees and working groups, and as partners on research teams.
ICanCME has adopted research priorities that will help drive research results to provide better outcomes for us. People with ME are contributing their lived expertise and their personal and professional knowledge, which complements that of the others on the research team. Our goal is to have a lasting impact on our research and create real change in the healthcare system for people with ME.
There are misconceptions about ME – even in the scientific community
Unfortunately, there continue to be misconceptions about ME – even within the scientific community.9 One of those misconceptions is that simply exercising will make things better. While this may be the case for many conditions and aspects of health, there is robust evidence about how this is not the case for ME.10 Unlike deconditioning states, ME is characterized by abnormal metabolic, autonomic, and immunologic responses to exertion that impair recovery.
Other misconceptions about ME are that it’s just ‘feeling tired’, that it only affects certain types of people, that it’s entirely different from Long COVID, that it’s psychological or psychosomatic in nature, or that there are no ways healthcare professionals can help people with ME.11 None of these are true.
To help you in your clinical research role
While many of you may not have interacted directly with ME to date, there may be opportunities in your role to do so in the future. To help you succeed in your role, while prioritizing the needs of people with ME, we have created a short list of requirements when designing and curating research:
- To ensure you have a cohort of individuals living with ME, please include the Canadian Consensus Criteria (CCC) 12 and the IOM Criteria 13 into your eligibility criteria (to confirm the presence of ME) and the DePaul PEM Questionnaire 14 (to screen for PEM).
Please note: The DePaul is not to be used as a pre and post measurement for interventions though. That is a common mistake in research. - Basic accessibility should be assessed for in-person research visits to ensure that elevators and automatic doors work from one end point to the other and that accessible and free parking is made available close to the front entrance. If there are any stairs to climb or expected delays, this information should be provided ahead of time to research participants so that they can prepare accordingly.
- Creating a research environment that is inclusive and respectful to those living with ME must be a priority. This would include:
- Choosing a time that is appropriate, as many people with ME struggle significantly in the mornings.
- Using a quiet and dimly lit room or providing eye protectors/an eye mask for participants to help with sensory sensitivities.
- Providing a space free of distractions (e.g., free of beeping or flashing machines, and research team cross-talk).
- Ensuring a quiet place to rest during and after the research visit.
- Selecting a space that is fully wheelchair accessible and preferably meeting research participants with a wheelchair at the front door of the research facility to help them navigate the building quickly and easily. This will help to conserve energy and steps and lower overall exertion.
- Masking with N95s and using air purifiers in the research setting to create a safer experience for participants.
- The research must take into account the cognitive challenges that people with ME face. This could include an informed consent form and questionnaires that break up text into smaller blocks or chunks, allowing for increased white space and fewer distractions. It could also include support and more time for participants to help them complete these components.
Understanding post-exertional malaise (PEM) as the cardinal symptom of ME means understanding that any and all exertion will contribute to the development of PEM (delayed onset and delayed recovery from worsening symptoms) for the research participants.
This means that every choice a researcher makes has the potential to add to or minimize PEM. Every measurement, test, tool or questionnaire adds to this. The anticipation and drive to and from the visit add to this. Every visit to our home or phone call can add to this. And that’s ok if the study is truly helping to illuminate an element of the illness and is needed, but researchers need to really ask themselves: “Is this necessary?” “How does this help us better understand ME?”
- Decentralized or hybrid components should be integrated in the research design whenever possible to increase participation and inclusion of more severe presentations of the illness. This could include samples being taken in a participant’s home or using wearables to collect data.
So, now knowing all of this, we ask that you please make thoughtful decisions and work collaboratively with patient partners from ICanCME. We ask that you do this to ensure your team understands the illness well, the impact of PEM, and how each design feature either adds to or minimizes PEM in research participants.
A final message
Research is our only way out of this illness. People with ME need more researchers to take an interest in this research topic. We also need you to collaborate to ensure research is relevant to the ME community’s needs and priorities, and is well designed, safe and inclusive. We need research ethics boards to better understand our needs and safety concerns as research ramps up. Our only way out is together.
Please consider sharing this post with your colleagues, so that they too can learn more about ME and about ME research.
Reference
- https://www.cdc.gov/me-cfs/about/index.html ↩︎
- Dehlia, A. and Guthridge, MA (2024), The persistence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis, Journal of Infection 89 (6), https://doi.org/10.1016/j.jinf.2024.106297 ↩︎
- Hartle, M., Bateman, L., & Vernon, S. D. (2021). Dissecting the nature of post-exertional malaise. Fatigue: Biomedicine, Health & Behavior, 9(1), 33–44. https://doi.org/10.1080/21641846.2021.1905415 ↩︎
- https://www.cdc.gov/me-cfs/hcp/clinical-care/treating-the-most-disruptive-symptoms-first-and-preventing-worsening-of-symptoms.html#:~:text=Post%2DExertional%20Malaise%20(PEM),by%20balancing%20rest%20and%20activity ↩︎
- https://www.cdc.gov/me-cfs/hcp/clinical-care/treating-the-most-disruptive-symptoms-first-and-preventing-worsening-of-symptoms.html ↩︎
- Pendergrast T, Brown A, Sunnquist M, Jantke R, Newton JL, Strand EB, Jason LA (2016). Housebound versus nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome. Chronic Illn. 12 (4): 292-307. ↩︎
- Unger ER, Lin JS, Tian H, Natelson BH, Lange G, Vu D, Blate M, Klimas NG, Balbin EG, Bateman L, Allen A, Lapp CW, Springs W, Kogelnik AM, Phan CC, Danver J, Podell RN, Fitzpatrick T, Peterson DL, Gottschalk CG, Rajeevan MS; MCAM Study Group (2017). Multi-Site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM): Design and Implementation of a Prospective/Retrospective Rolling Cohort Study. Am J Epidemiol. 185(8): 617-626. ↩︎
- https://icancme.ca/ ↩︎
- Thoma M, Froehlich L, Hattesohl DBR, Quante S, Jason LA, Scheibenbogen C. (2023). Why the Psychosomatic View on Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Is Inconsistent with Current Evidence and Harmful to Patients. Medicina (Kaunas). 31;60(1):83. doi: 10.3390/medicina60010083 ↩︎
- Vink M, Vink-Niese A. Graded exercise therapy for myalgic encephalomyelitis/chronic fatigue syndrome is not effective and unsafe (2018). Re-analysis of a Cochrane review. Health Psychology Open. 5(2). doi:10.1177/2055102918805187 ↩︎
- https://worldmealliance.org/2025/04/world-me-day-2025-six-myths-and-facts-everyone-should-know-about-myalgic-encephalomyelitis-me/ ↩︎
- Carruthers, BM and van de Sande, MI. Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome: An Overview of the Canadian Consensus Document. A Clinical Case Definition and Guidelines for Medical Practitioners. 2005. https://solvecfs.org/wp-content/uploads/2013/09/CanadianConsensusDoc.pdf ↩︎
- Institute of Medicine. Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness. Report for Clinicians. https://nap.nationalacademies.org/resource/19012/MECFScliniciansguide.pdf ↩︎
- DePaul College of Science and Health. Myalgic Encephalomyelitis & Chronic Fatigue Syndrome Projects. DePaul Questionnaires: https://csh.depaul.edu/academics/centers-and-institutes/ccr/myalgic-encephalomyelitis-cfs/measures ↩︎