Recently, the US National Institutes of Health (NIH) announced its protocol for a new intramural study examining post-infectious fatigue. The community has been eagerly awaiting the publication of the protocol since the October announcement that the NIH was finally making ME/CFS a priority.
Numerous patients and organizations have attempted to initiate a dialogue with the NIH in recent months. Many have particularly encouraged the NIH to involve patients in the planning of the protocol for the intramural study and of the organization’s ME/CFS plan as a whole. Unfortunately, the unilateral announcement of the protocol suggests that the NIH may not have any such intention.
From Vicky Whittemore at NIH: “We have received many questions about the study from individuals with ME/CFS, so we sent those off to the investigators at the NIH Clinical Center to provide responses. We will post the responses on the NIH website and I can send you a link when they are posted. ”
It appears that the protocol may have been unintentionally released.
— Julie Rehmeyer (@julierehmeyer) February 8, 2016
What criteria are being used to select patients?
A key point in this engagement has been trying to determine whether the NIH would be using the stricter Canadian Consensus Criteria to recruit patients or possibly the Institute of Medicine’s clinical definition for System Exertion Intolerance Disease. Instead, the study is using the 2005 Reeves Criteria (also known as the “empirical definition”), plus an added requirement of post-infectious onset.
The Reeves criteria is an unusual choice. It is based on the 1994 Fukuda criteria and does not require post-exertional malaise, a symptom the IOM committee deemed core to this disease. Absent post-infectious onset, it misdiagnoses depression as CFS 38% of the time and was rejected by the IOM for overinflating the disease’s actual prevalence. Although used by the Centers for Disease Control (CDC), which was the major author, it is not used by any extramural researchers.
What tests will be done?
Patients enrolled will provide samples of: blood, saliva, stool, cheek skin and cerebrospinal fluid. It is unclear what tests will be done on these samples. They will also undergo an MRI, neurocognitive testing, and heart monitoring, as well as exercise testing. It is unclear whether this is the 2-day CPET, a proposed biomarker for this disease, or another exercise test.
What other populations are being studied?
In addition to post-infectious fatigue patients, the NIH study is recruiting healthy controls, patients with Lyme disease without fatigue, and patients with functional movement disorders.
There is no explanation yet about why patients with functional movement disorders (which the NIH defines as a psychogenic disorder) and patients with Lyme disease are being used as comparison groups.
What are #MEAction’s concerns?
Our primary concern is that patients are being recruited to this study with a non-standard, insufficiently strict set of criteria. The NIH has a history of using strict criteria: its XMRV study, for example, required patients fulfill both the Fukuda and the CCC.
The NIH protocol also appears to require patients be very high-functioning to participate. We hope the following is a typo:
Functional impairment as determined using the Short-Form 36 (SF-36): score of greater than or equal to 70 physical function subscale, or greater than or equal to 50 on role physical subscale, or greater than or equal to 75 on social function subscale, or greater than or equal to 66 on emotional subscale.
#MEAction has repeatedly advised the NIH that their ME/CFS program needs to involve patients in critical decision-making, and that in particular, patient representatives should be including in committees that design study protocols and set research priorities. We believe strongly that this will save money and improve outcomes, and ultimately get us to what we all want – better diagnosis and treatment – much faster.
The NIH has signaled in numerous ways they want to turn over a new leaf with this disease and the community. The unilateral announcement of this protocol and the use of the Reeves definition endanger the credibility of that commitment.
How can you help?
The US Action Working Group is assembling a set of questions to send to the NIH about the study protocol. Please join the #MEAction NIH Working Group and add your questions and feedback to this thread.
Note: the views of #MEAction are not the views of the US Action Working Group.