This article is intended as a high-level summary of key issues in the conduct of reviews of the
ME evidence-base that have resulted in flawed conclusions and recommendations in clinical
guidance. This has misled medical providers on the nature of ME and its appropriate treatment
and put people with ME at risk of harm. Comments can be sent to
medimmock@gmail.com.
Summary
For many years, ME evidence-based reviews and clinical guidance globally, such as those from
Cochrane, UpToDate, Mayo, NICE, and various medical journals and societies around the world
have recommended cognitive behavioral therapy (CBT) and graded exercise therapy (GET) as
effective and safe treatments for ME. Further, these sources have sometimes claimed that
disease risk and poor prognosis is the result of behavioral and psychological factors such as
maladaptive coping, a history of abuse, perfectionism, and the patient’s belief that the disease is
organic. In spite of patient surveys and ancedotal reports that these treatments were not only
ineffective but harmful, these recommendations and statements have remained.
Since 2015, a growing chorus of international journalists and scientists, along with reports by
the U.S. Health and Human Sevices have documented serious deficiencies in the supporting
studies that call into question the validity of these recommendations. In parallel, the U.S.
Institute of Medicine (IOM, now called the National Academy of Medicine) published a report
that directly contradicts the disease theory underpinning these studies. These deficiencies and
contradictions include the following (Further details in Appendix II):
1. Lack of external validity:
According to the US Agency for Healthcare Research and
Quality (AHRQ), the use of an overly broad definition (the Oxford definition) in many of
these studies resulted in the inclusion of “patients who may have an alternate fatiguing
illness.” The 2016 AHRQ report also noted that studies using more specific definitions
requiring hallmark symptoms of ME such as an abnormal response to exertion were
“blatantly missing.” After excluding Oxford studies from its analysis, AHRQ found no
evidence of effectiveness for GET and barely any for CBT. This raises serious questions
about the validity of applying CBT and GET recommendations to people with ME.
2. Study design and conduct issues: The CBT and GET evidence base is biased by
unblinded studies that relied on subjective outcome measures, ignored or dismissed
objective findings that contradicted subjective reports, switched outcomes, inflated claims
of improvement and recovery, and contained other significant problems in the design and
conduct of studies. The issues in these studies, including the UK’s flagship £5 million
PACE trial, call into question the quality and reliability of claims of CBT and GET
effectiveness.
3. Inadequate reporting of harms: Conclusions that these therapies are safe are based on
studies that inadequately reported adverse effects and did not monitor treatment
