Findings from the National Institutes of Health (NIH) intramural ME/CFS clinical study were published in Nature Communications last week to mixed reception by the patient advocate community. Co-written by 75 authors from 15 of the 27 NIH institutes, “Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome,” highlights results of the study that include brain activity differences, immune and other abnormalities in 17 people with ME/CFS compared with 21 healthy controls. Solve helped recruit for the study and encouraged our community to participate.
Begun in 2016, the eight-year study included cost more than $8 million. Researchers faced recruitment challenges, and only enrolled patients whose symptoms developed after a viral or bacterial illness, and had only been sick five years or less, while excluding anyone with other medical conditions that might confound the results.
In the NIH press release, National Institute of Neurological Disorders and Stroke (NINDS) director Walter Koroshetz stated, “People with ME/CFS have very real and disabling symptoms, but uncovering their biological basis has been extremely difficult. This in-depth study of a small group of people found a number of factors that likely contribute to their ME/CFS. Now researchers can test whether these findings apply to a larger patient group and move towards identifying treatments that target core drivers of the disease.”
Multiple major news outlets tapped members of Solve’s extensive network of experts, including multiple scientists from Solve’s Ramsay Research Grant Program, to share their big takeaways from the study.
Our response to the publication of this long-awaited and costly study is mixed.
The Good
On a positive note, the study underscores the commitment of the NIH to understanding ME/CFS, highlighting that patients are often neglected or ignored. Researchers discovered other biological differences between ME/CFS patients and healthy controls, including elevated heart rates and blood pressure normalization after exertion. The researchers also discovered that several patients were living with other undiagnosed health issues, making clear we need to see improvements in how patients get diagnosed, nationwide.
The study has also brought much-needed visibility to ME/CFS by garnering the attention of mainstream media. Millions of readers across the world will be educated and the publicity will be a vital tool to share with skeptical medical providers, political leaders, and family members.
In Science, Solve Research Advisory Council (RAC) member Dr. Nancy Klimas found it notable that, “This is a disease of the brain…The inability to sustain energy was coming from that organ.” Solve RAC member Dr. Anthony Komaroff echoed this in The New York Times, stating that NIH researchers “speculate that the chronic immune stimulation that they found and the changes in the gut microbiome that they found could lead to these brain changes, which then leads to symptoms.”
Dr. Jo Cambridge (Ramsay Class of 2016) told STAT News that the paper, “does bring together the complexity of the condition…It highlights all the things you’ve got to take into account when you’re investigating this disease.”
Dr. Katherine Seton (Ramsay Class of 2022) told the Science Media Centre, “Historically, studies investigating ME/CFS have often focussed on singular aspects of the disease, largely due to inadequate funding for this disease. These fragmented studies merely offer isolated pieces of a larger jigsaw puzzle. However, the current paper stands out with its extensive author list, featuring experts from diverse disciplines collaborating to assemble these pieces and reveal a more complete picture. This interdisciplinary approach is crucial for advancing our understanding of this disease.”
Perhaps most importantly, the study reveals the dire need for even more research on ME/CFS and other infection-associated conditions. Solve RAC member Dr. Maureen Hanson told STAT News, “We need to know at the molecular and biochemical level, how similar are pre-pandemic ME/CFS patients to people with long Covid? We don’t know that. There’s an assumption that they’re the same.”
The Complicated
We’re concerned that the study:
- Failed to adequately address post-exertional malaise (PEM)
- Claimed that an outsized portion of the participants recovered spontaneously
- Does not account for remission periods for people with ME/CFS
- Used highly problematic and controversial language regarding “effort preference”
The Bad
“For this kind of time, money, and expertise, I was expecting more,” shared Emily Taylor, Vice President of Advocacy and Engagement. “We’ve been watching and waiting for these results for eight years and when we finally got them, they didn’t address the needs of patients.
I can’t help but imagine what amazing advancements these resources could have yielded if the NIH had collaborated instead with researchers who were already familiar with this patient population, like our Solve Ramsay Research Grant scientists, instead. At the very least, the topic of post-exertional malaise would have been handled appropriately.
Perhaps most importantly, the glaring absence of patient voices at all stages of this project reflects a huge missed opportunity and contributed to the lackluster outcomes of the study.”
Dr. Carmen Scheibenbogen (Ramsay Class of 2016 ) noted in The New York Times, “They selected rather healthy patients. I think there are a lot of interesting findings, it’s just disappointing because that was such a major approach and they selected patients which are not very representative.”
The publication of the study has raised many questions, including:
- What was the patient engagement process in this study?
- What follow-up or long-term study is planned?
- What did this paper contribute to the field?
- Are the paper authors open to amending the paper to remove the confusing and misleading term of “effort preference”? If they do not, they risk future researchers following their lead and taking the field down the wrong path for years to come.
Solve Chief Scientific Officer Tim Hsiao, PhD, wrote of the study:
“I am also somewhat concerned about the use of the metric ‘effort preference’ and what this term might communicate to the lay, general audience. The authors didn’t say so in this report, but, just as a precaution, I want to make it super clear to the general audience that the concept of ‘effort preference’ does not and should not mean that people with ME/CFS simply do not want to apply effort or work on effortful tasks. On the contrary, many people with ME/CFS are hard-working and continually seeking higher levels of independence. Many people with ME/CFS, from time to time, actually risk applying too much effort and pushing themselves too hard, as they desire to support and/or relieve their family members and loved ones, and the result is a worsening of their symptoms, known as PEM.”
Read the NIH press release on the study here.
The NIH is currently seeking public comment on priorities for their ME/CFS Research Roadmap Working Group. The deadline for comment submission is March 8. Solve will be submitting comments, and we encourage you to take advantage of this opportunity to help the NIH shape ME/CFS research.
