Research bias in ME/CFS

Research in every field deals with bias. Research into myalgic encephalomyelitis/chronic fatigue syndrome faces specific kinds of bias issues as it navigates significant gaps in scientific knowledge and several opposing viewpoints.

Emphasis on randomized controlled trials and systematic reviews
Following an Evidence-Based Medicine (EBM) model gives greater weight to systematic reviews and randomized controlled trials. However, some systematic reviews and a number of randomized controlled trials have been shown to have significant flaws, including a failure to follow pre-defined procedures or standards, and altering the primary outcome(s) part way through unblinded trials either without adequate justification or without a referring to the change, and failure to comply with prespecified trial plans. The most influential examples of these are the Cochrane review of exercise therapy for CFS, which Cochrane initially planned to withdraw after admitting it did not meet the set standards, and the PACE trial, which is the largest treatment trial for CFS, and resulting in a legal battle for the release of the original primary outcome data including the results of the six-minute walk test.

PACE trial
Davenport et al. (2018) state the lack of randomized controlled trials in ME/CFS research mean that an evidence-based model can be unduly influenced by a very small number of studies, for example the PACE trial found that treating ME/CFS with graded exercise therapy or cognitive behavioral therapy did not result in clinically significant improvements - but this trial heavily influenced the clinical use of those treatments. The PACE trial was so problematic that it was used an the example for Prof. Bruce Levin's presentation How Not To Conduct A Randomized Clinical Trial, and The Lancet received open letters signed by over 100 people, including researchers and academics, calling for the trial to be retracted.

Cochrane systematic review
The highly influential Cochrane review of exercise therapy for chronic fatigue syndrome was also found to have significant flaws.

Editorials
A number of highly influential journals have published editorials either strongly in favor or controversial treatments, criticizing key publications which challenged the journals' previous ideas about ME/CFS, and harshly criticizing advocates or patients who raised genuine scientific queries or criticisms, and such criticism has continued for decades despite changes in editorship. Journals criticized for bias including the BMJ, the Lancet, and Archives of Disease in Childhood.

Bias recognition
Geraghty et al. (2019) looked at evidence behind the popular cognitive behavioral model of ME/CFS, and found that a number of research papers contained significant evidence that did not support the model combined with contradictory abstracts or conclusions at odds with the authors' results, and notable selective interpretation of evidence, such as ignoring any contradictory research.

Sonia Lee (PhD, University of Sydney) assessed research waste in ME/CFS by comparing the PACE trial with two cellular trials, finding that "selective reporting", an indicator of research waste, was greater in the PACE trial; however this paper (2017) was not peer-reviewed. Nacul et al. (2017) discussed the effects of selection bias, highlighting how psychosocial/biopsychosocial studies frequently used the broadest diagnostic criteria - the Oxford criteria - and did not break results down by subgroup. The use of the Oxford criteria lead to a 100-fold increase in disease prevalence compared to the Canadian Consensus Criteria (CCC); with 14 out of 15 patients meeting the Oxford criteria typically failing to meet the Canadian Consensus Criteria for ME/CFS.

Notable studies

 * 1982, Suffering and the Social Construction of Illness: The Delegitimation of Illness Experience in Chronic Fatigue Syndrome | (Abstract)


 * 2005, Chronic Fatigue Syndrome: Editorial Bias in The Lancet (Abstract) - Not peer-reviewed


 * 2011, Chronic Fatigue Syndrome: Editorial Bias in the British Medical Journal (Abstract)


 * 2017, Bias, misleading information and lack of respect for alternative views have distorted perceptions of myalgic encephalomyelitis/chronic fatigue syndrome and its treatment (Full Text)


 * 2017, How have selection bias and disease misclassification undermined the validity of myalgic encephalomyelitis/chronic fatigue syndrome studies? (Full text)


 * 2017, Research Waste in ME/CFS (Full text) - not peer reviewed
 * 2018, Checking our blind spots: current status of research evidence summaries in ME/CFS (Abstract) - Editorial
 * 2018, Are ME/CFS Patient Organizations "Militant"? : Patient Protest in a Medical Controversy. (Abstract)
 * 2019, The ‘cognitive behavioural model’ of chronic fatigue syndrome: Critique of a flawed model (Full text)

Articles and blogs

 * 2017, PACE team response shows a disregard for the principles of science - Jonathan Edwards


 * 2017, MEA Review: The SMILE trial - a lesson in how not to conduct clinical trials in people with ME/CFS (Full text) - by Dr Charles Shepherd, ME Association medical advisor