Controversies related to chronic fatigue syndrome

Historically, many professionals within the medical community were unfamiliar with CFS, or they did not recognize it as a real condition, and disagreed on its prevalence or seriousness.[1][2][8] A 2005 study in the UK surveyed 811 general practitioners' attitudes and knowledge of CFS. 72% accepted CFS as a recognizable clinical entity, but 48% did not feel confident diagnosing it, and 41% did not feel confident in treatment.[9] The CFS Advisory Committee (Part of the US Department of Health) in 2007 found that a survey of 1,500 US primary care providers showed that 90% believed CFS can impair quality of life, 20% strongly or somewhat agreed that CFS is only in the patient's head, and 70% said not enough information is available to diagnose CFS.[10] A 2008 Norwegian study that explored barriers to quality care faced by patients with chronic fatigue syndrome concluded, "Current medical scepticism and ignorance regarding CFS shapes the context of medical care and the illness experiences of CFS patients, who may feel they neither get a proper assessment nor management."[11]

Training may influence attitudes to CFS. One study conducted a relatively brief seminar presenting factual information on CFS to a cohort of fourth year medical students. The authors concluded the information provided was associated with a more favorable attitude toward CFS.[12] In the UK, the 2002 Chief Medical Officer's report stated that all doctors should consider CFS as a serious chronic illness and treat patients accordingly.[13] In 2006, the US Centers for Disease Control and Prevention (CDC) launched a national program to educate the American public and health care professionals about CFS.[14]

There has been much disagreement over proposed cause(s), diagnosis, and treatment of the illness.[15][16][4] Contrasting viewpoints have been expressed by different CFS researchers. One influential 1993 Lancet paper argued that CFS was a form of neurasthenia to be classified as a psychiatric condition, and a subsequent 1998 paper concluded that behavioral, cognitive, and affective factors all played a role in perpetuating fatigue.[17][18] More recently, a 2005 population-based study, which used a similar methodology to the earlier 1998 study, found important differences between CFS and psychiatrically explained chronic fatigue which could affect the development of therapy and explanatory models. They concluded that the 1998 model adequately represented chronic fatigue secondary to psychiatric conditions, but not CFS.[19]

Contested causation may have serious negative effects on healthcare for individuals, as it may erode patient-provider trust, test the provider's self-assurance and capacity to share power with the patient, and raise problematic issues of reparation, compensation and blame.[20]

In 2011, a major divide still existed as to whether funding should be directed towards biomedical or psychological research.[21]

In 2009, the journal Science[22] published a study that identified the XMRV retrovirus in blood samples of a population of people with CFS. After the Science publication, media attention generated interest in the XMRV virus worldwide. Doubts over the legitimacy of CFS had long caused patient frustration about the marginalization of the debilitating illness, and persons with CFS and their support organizations were optimistic the cause of their symptoms had been found.[23]

Many countries reacted quickly to protect the blood supply from the XMRV retrovirus by banning persons with CFS from donating blood. The United States funded a 1.3 million dollar study to try to validate the findings, and some people with the illness started taking antiviral drugs in hopes of symptomatic improvement.[23]

Many studies failed to reproduce this finding,[24][25][26] and recriminations of misconduct from the various stakeholders grew angry and bitter.[23]

In 2011, the editor of Science formally retracted its XMRV paper[27] while the Proceedings of the National Academy of Sciences similarly retracted a 2010 paper which had appeared to support the finding of a connection between XMRV and CFS.[28] Studies eventually concluded that neither people nor the blood supply had been infected with the XMRV virus, and the origin of the virus was likely a lab contaminant in the supplies used by the polymerase chain reaction (PCR) process of the studies that found virus in blood.[29]

PACE was a large trial investigating the efficacy and safety of three treatments adjunctive to specialist medical care (SMC): cognitive behavioural therapy (CBT), graded exercise therapy (GET), and adaptive pacing therapy (APT). The results were published in February 2011 and concluded that CBT and GET were each "moderately" effective compared to SMC alone, while APT was not found to be effective when added to SMC.[30]

The trial generated considerable adverse criticism. Letters to the editor critiqued the definitions of secondary outcomes, questioned post-hoc protocol changes, and expressed concern over generalisability of the results. Patient groups and the IACFS/ME (an organization of researchers and health care professionals interested in CFS)[31] criticized the trial for over-simplified and exaggerated conclusions, for using a flawed psychosocial illness model that ignores biological evidence, for testing a non-representative version of pacing, and because the results seriously conflict with their member surveys which show that pacing is effective and CBT or GET can cause deterioration in many patients who use the treatments.[32][33][34] One notable researcher submitted a 442-page letter to the Medical Research Council outlining his criticisms of the trial, and a shorter 43-page complaint to the Lancet. The MRC and the Lancet rejected the submissions. A Lancet editorial responded to the adverse criticism by suggesting that some critics could be part of "an active campaign to discredit the research."[35][21] In 2011, Lancet Editor Richard Horton defended the trial, calling the critics "a fairly small, but highly organized, very vocal and very damaging group of individuals who have, I would say, actually hijacked this agenda and distorted the debate so that it actually harms the overwhelming majority of patients."[36][37]

More recent criticisms of the trial have come from the scientific community. For example, biostatistician Bruce Levin of Columbia University described the study as "the height of clinical trial amateurism", and Ronald Davis of Stanford University wrote, "I’m shocked that the Lancet published it...The PACE study has so many flaws and there are so many questions you’d want to ask about it that I don’t understand how it got through any kind of peer review".[38] In an analysis of the study's design, the mathematician Professor Rebecca Goldin wrote that "There were problems with the study on almost all levels... the flaws in this design were enough to doom its results from the start."[39] Professor Jonathan Edwards of University College London (UCL) has written that the PACE trial "is an unblinded trial with subjective outcome measures. That makes it a non-starter in the eyes of any physician or clinical pharmacologist familiar with problems of systematic bias in trial execution."[40]

The full research data for the PACE trial was requested by both patients acting as citizen scientists, and by other researchers but was initially denied until a 2016 tribunal ordered the data be released.[41] Several researchers published a re-analysis of the PACE trial data, but drawing the conclusion that the CBT and GET treatments were not effective and possibly not safe.[42][43][44][45] The full PACE trial outcome data showed that the treatments did not result in patients being able to return to work or study,[46] and that they were not able to walk significantly further after treatment.[45] This new information was one of several factors that lead to the UK deciding to complete a full review and update to its diagnostic and treatment guidelines for CFS/ME.[41]