By David Tuller, DrPH
I have lately been focusing more time and posts on developments in the UK than in the US. I guess that’s not too surprising. After all, this whole project began as an investigation of the PACE trial, conducted by British experts in British health care centers and published in British journals. And there’s so much crap besides PACE to pursue, given the strength of the CBT/GET ideological brigades.
I’m glad that Mary Dimmock and others are keeping up the pressure here. Mary got involved in the issue after her son fell ill several years ago. She has been especially active in prodding US health agencies, and in particular the Centers for Disease Control and Prevention, to do their jobs. The article below, about the agency’s new systematic review of the evidence base for ME/CFS treatments, appeared in last month’s issue of the ME Global Chronicle. I am re-posting it in full here with Mary’s permission.
CDC Systematic Evidence Review of Treatments for ME/CFS
June 19, 2019
You may remember that in September 2018, the US Centers for Disease Control and Prevention (CDC) solicited bids to conduct a systematic evidence review of ME/CFS treatments as an update to the 2014-2016 systematic evidence review commissioned by the Agency for Healthcare Research and Quality (AHRQ). This new review, currently underway, could have a significant impact on treatment recommendations in clinical guidance for ME. I am a member of the key informants panel providing input on review questions and have agreed to hold those discussions and the names of the other members in confidence. In the meantime, the following summarizes what is known publicly about this important review, based on information provided by CDC and in the documentation for the bid solicitation.
The Key Takeaways:
• CDC is conducting this systematic evidence review as the first step in longer-term plans to develop treatment guidelines for ME/CFS
• The timeline for completion has not yet been stated publicly but is estimated to be the first half of 2020
• The handling of the disparate case definitions has not yet been specified. The 2016 Addendum to the 2014 AHRQ Evidence Review excluded Oxford studies from analysis
• This review may consider other peer-reviewed literature that provides context for treatment of symptoms seen in ME/CFS (e.g. orthostatic intolerance, pain, etc)
• The process for the review of the draft report has not yet been announced. During the 2014 evidence review, the public was given the opportunity to provide input
Details on the Project From CDC
At its March 2019 stakeholder call (1), CDC provided the following information on this project:
“CDC is committed to working with our partners to achieve the goal of improved healthcare access and quality for patients with ME/CFS. Treatment guidelines for ME/CFS could contribute to this goal, and the first step towards guidelines is an updated systematic review of the literature. We have contracted with the Pacific Northwest Evidence-based Practice Center at Oregon Health Sciences University to conduct this review. As you may be aware, systematic reviews start by framing the question(s) to be answered as well as the particular population, interventions, comparators, outcomes, settings, timings. These key questions are extremely important to assure the [usefulness] of the review. This week OHSU conducted interviews with key informants representing advocates and ME/CFS clinicians to refine questions. The discussion was very helpful and OHSU will finalize the key questions prior to initiating the evidence review.”
The Pacific Northwest Evidence-based Practice Center (EPC) contracted by CDC for this new review is the same group that conducted the 2014 diagnosis and treatment evidence review and the 2016 Addendum on behalf of the Agency for Healthcare Review and Quality (AHRQ) (2). The 2014 review concluded that CBT and GET were moderately effective based in large part on Oxford studies and rated PACE as a “good” trial. But it also noted evidence of harms from GET and called for the retirement of the Oxford definition because it included other fatiguing conditions. As a result of community requests to reassess the evidence, the EPC issued the 2016 Addendum, which concluded that there was insufficient evidence for GET and barely any for CBT once Oxford studies were excluded. The 2016 Addendum did not reassess the quality of studies, including PACE. The 2014 review was published in the peer-reviewed literature but the 2016 Addendum was only posted on the AHRQ website.
Information from the September 2018 Solicitation for Contractor Bids
While not the final contract, the September 2018 solicitation provides additional insight (3). The solicitation stated this new review would include studies of treatments in “ME/CFS” but did not specify what case definitions would be included or excluded or how Oxford studies would be handled. As noted above, in the 2016 Addendum, positive results for CBT and GET in Oxford case definition studies did not hold up when those studies were excluded. The 2016 Addendum also pointedly stated that studies of CBT and GET using case definitions requiring hallmark criteria of ME such as PEM were “blatantly missing” from the evidence base.
The 2018 solicitation also stated “any peer-reviewed literature that could provide context to inform treatment recommendations for symptoms associated with ME/CFS warrants review and consideration.” While not explicit, this suggests the review might consider evidence for treatment of symptoms such as orthostatic intolerance and sleep impairment from studies done in other conditions. However, the solicitation does not provide specifics on how this would be done.
Neither CDC nor the solicitation documentation has specified the process for the review of the draft evidence review or who will be involved. As noted above, the 2014 review provided a mechanism for public input on the draft review. Regarding the timeline for the review, the September 2018 project solicitation gives a 15-month timeline for the draft review and 18 months for the final report. Assuming the contract was awarded in October 2018 and these timelines were not changed, this suggests the draft review would be done by about January 2020 and the final review by about April 2020.
CDC staff told me that the Pacific Northwest Evidence-based Practice Center will publish the project description in PROSPERO when ready and CDC will then provide a link to that from its website. PROSPERO is an international database that prospectively registers information about the design and conduct of planned systematic evidence reviews (4). This includes information such as the body of literature to be searched, the population and interventions being studied, the outcomes evaluated and other aspects of how the assessment will be conducted. Prospective registration of the review description is intended to increase transparency and reduce reporting bias and duplication. Hopefully, the information provided in PROSPERO will answer some of the open questions.
1) Transcript of the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Stakeholder and Communication Conference Call. Centers for Disease Control and Prevention. March 11, 2019. https://www.cdc.gov/me-cfs/pdfs/orthostatic-intolerance-508.pdf
2) Diagnosis and Treatment Evidence Review. Agency for Healthcare Review and Quality. 2014, updated 2016. https://effectivehealthcare.ahrq.gov/topics/chronic-fatigue/research
3) Centers for Disease Control and Prevention. Evidence-based treatment guidelines for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Solicitation Number: 75D301-18-Q-69445 FedBizOps. September 8, 2018
• Summary: https://www.fbo.gov/?s=opportunity&mode=form&id=30dd6fa6af05215774b9d11d01f9f6c2&tab=core&_cview=0
• Details: https://www.fbo.gov/utils/view?id=051bae33d4ba7a1086c61e6d2f50b651
4) PROSPERO https://www.crd.york.ac.uk/prospero/#aboutpage