[Federal Register Volume 88, Number 11 (Wednesday, January 18, 2023)]
[Notices]
[Pages 2924-2926]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2023-00813]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Centers for Disease Control and Prevention

[Docket No. CDC-2021-0053]


The Systematic Review Report for Diagnosis and Treatment of 
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS); Notice of 
Availability

AGENCY: Centers for Disease Control and Prevention (CDC), Department of 
Health and Human Services (HHS).

ACTION: Notice.

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SUMMARY: The Centers for Disease Control and Prevention (CDC), located 
within the Department of Health and Human Services (HHS), announces the 
availability of the final systematic review report titled ``Diagnosis 
and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome 
(ME/CFS).'' The report is accompanied by a summary of public comments.

DATES: The final document is available January 18, 2023.

[[Page 2925]]


ADDRESSES: The document may be found in the docket at 
www.regulations.gov, Docket No. CDC-2021-0053 in the Supporting 
Materials tab and at https://www.cdc.gov/me-cfs/programs/evidence-review.html.

FOR FURTHER INFORMATION CONTACT: Anindita Issa, MD, National Center for 
Emerging and Zoonotic Infectious Diseases, Centers for Disease Control 
and Prevention, 1600 Clifton Road NE, Mailstop H24-12, Atlanta, Georgia 
30329; Telephone: 404-718-3959; Email: [email protected].

SUPPLEMENTARY INFORMATION: In 2022, the systematic review titled 
``Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue 
Syndrome (ME/CFS)'' conducted by the Pacific Northwest Evidence-Based 
Practice Center at Oregon Health and Science University, concluded that 
there is limited evidence on effective treatments for ME/CFS. The 
review updates a 2014 Agency for Healthcare Research and Quality 
(AHRQ)-funded review and its 2016 addendum. It also expands upon the 
prior AHRQ review by including children as well as adults, evaluating 
harms as well as benefits of diagnosis, and evaluating effects of 
treatment on depression, anxiety, sleep quality, pain, and other 
symptoms associated with ME/CFS in addition to fatigue, function, and 
quality of life. The report evaluates the quality of the scientific 
literature and does not make recommendations or guidelines. While 
improving clinical care remains a critical issue, the lack of 
sufficient evidence from the review resulted in the decision for CDC 
not to proceed with developing clinical management guidelines.
    On May 17, 2021, CDC published a notice in the Federal Register (87 
FR 26733) requesting public comment on the draft report of the 
systematic review for ME/CFS. One hundred and thirty-five commenters 
provided feedback including those from academia, professional 
organizations, advocacy groups, and the public. Some of the comments 
received were from organizations that represented patient advocacy 
groups. CDC highly values insights gained from these public comments 
and especially thanks patients living with ME/CFS, who shared their 
personal experiences in this public forum.
    Comments were centered around several themes. All comments were 
carefully reviewed and considered by CDC. Themes from the comments 
included (1) concerns with cognitive behavioral therapy and graded 
exercise therapy; (2) personal testimonials; (3) inclusion of studies 
with high risk of bias; (4) exclusion of certain studies on harms 
evidence; (5) concerns with case definitions and impact on the 
systematic review; (6) interpretation of results; (7) CDC programmatic 
concerns and recommendations; and (8) recommended references.
    Comments: Concerns with cognitive behavioral therapy (CBT) and 
graded exercise therapy (GET): Commenters expressed concern with 
inclusion of the CBT and GET in the systematic review, including 
personal testimony of harms experienced after attempting treatment with 
CBT or GET, and critiques of the proposed mechanism (or lack of) of CBT 
or GET.
    Response: CDC acknowledges the concerns that commenters have about 
the inclusion of CBT and GET in this systematic review. The authors of 
this systematic review report were aware of the criticisms of CBT and 
GET as treatments for ME/CFS. The studies for CBT and GET were included 
in the report because they met the inclusion and exclusion criteria of 
this systematic review protocol, and the limitations of the evidence on 
these therapies were described in the report as well. The purpose of 
this systematic review was to provide a summary of available published 
literature, including limitations. This systematic review does not make 
treatment recommendations, and therefore, does not recommend GET or 
CBT.
    Comments: Personal testimonials: These testimonials spoke to the 
sincere frustration and desperation experienced by many patients with 
ME/CFS, including difficulty finding providers familiar with ME/CFS, 
struggles during and after attempted treatment with GET or CBT, and the 
impact of ME/CFS on their daily lives.
    Response: CDC appreciates the patients living with ME/CFS to share 
their stories and acknowledges the struggles that they face on a daily 
basis. CDC highly values insights gained from these public comments. 
Some patients felt that this systematic review was recommending 
treatment with GET or CBT. However, the purpose of this systematic 
review was to provide a summary of available published literature, 
including limitations. This systematic review does not make treatment 
recommendations, and therefore, does not recommend GET or CBT.
    Comments: Inclusion of studies with high risk of bias: Commenters 
expressing concern that unblinded trials and studies reporting 
participant-reported outcomes should have been rated high risk of bias 
or should be downgraded unless there were other methodological 
limitations.
    Response: CDC recognizes commenters' concerns about such studies. 
For interventions where blinding is not possible, we followed the 
standard approach used in many other systematic evidence reviews and 
downgraded for open-label design, but did not necessarily downgrade to 
high risk of bias unless there were other methodological limitations.
    Comments: Exclusion of certain studies on harms evidence: 
Commenters suggest that the review missed potentially relevant evidence 
on harms by excluding observational studies and patient surveys.
    Response: CDC understands commenters' concern about exclusion of 
these studies. We will take them into consideration for future 
systematic reviews. This review focused on randomized controlled trials 
(RCT) for evaluation of benefits and harms of treatments because 
observational studies and non-RCTs are susceptible to bias and 
confounding, particularly for more subjective outcomes like those 
evaluated in this report.
    Comments: Concerns with case definitions and impact on the 
systematic review: Some commenters suggested the removal of studies 
that used older case definitions for the inclusion of this review.
    Response: CDC respects the reasons for commenters' concerns with 
the case definitions used in the report, as many case definitions have 
emerged over the past several decades. To address the issue of the 
multitude of case definitions, regrouped analyses were performed for 
various case definitions.
    Comments: Interpretation of results: Commenters questioned the use 
and interpretation of meta-analysis in the systematic review, due to 
high heterogeneity, low strength of evidence, and high risk of bias 
studies.
    Response: CDC appreciates commenters' concerns with meta-analysis 
methodology. In the revision we incorporated some of these comments and 
added more details to address these concerns. Essentially, the meta-
analysis results were restructured for visualization and to facilitate 
the interpretation of results, thus overcoming this challenge and 
allowing for useful information to be reviewed.
    Comments: CDC programmatic concerns and recommendations: Commenters 
included requests or recommendations to the CDC ME/CFS program 
regarding future research and/or guidelines.
    Response: CDC appreciates the comments for improving the CDC ME/

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CFS program and will address them with leadership during program 
planning activities.
    Comments: Recommended references: Commenters suggested additional 
information available on websites and in scientific publications.
    Response: CDC recognizes the importance of reviewing these 
suggested references. Each suggested reference was assessed for this 
current review with pre-established inclusion/exclusion criteria. For 
future systematic reviews CDC may consider different criteria, which 
may allow for taking the suggested references into further 
consideration.
    Based on public comments, CDC revised the final report to include 
(1) information about the decision not to proceed with developing 
clinical management guidelines; (2) regrouping of plots for the meta-
analysis by case definition to facilitate the interpretation of results 
by various case definitions; (3) regrouping limitations into two major 
categories (study and clinical trial limitations and limitation in 
methods used to conduct the review); and (4) adding a description about 
the importance of collecting common data elements via standardized 
instruments or other assessment tools. The final report and a thematic 
summary of responses to public comments can be found in the Supporting 
Materials tab of the docket and at https://www.cdc.gov/me-cfs/programs/evidence-review.html. Although ultimately, at this time, CDC did not 
find sufficient evidence from the review to proceed with the 
development of clinical management guidelines for ME/CFS, the review 
was instrumental in spotlighting the research gaps in the currently 
available literature, and consequently, possible improvements for 
future clinical trial design and ways to leverage funding resources for 
clinical trials.

    Dated: January 11, 2023.
Tiffany Brown,
Acting Executive Secretary, Centers for Disease Control and Prevention.
[FR Doc. 2023-00813 Filed 1-17-23; 8:45 am]
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