Commentary: Heading for a therapeutic stalemateBMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d3774 (Published 22 June 2011) Cite this as: BMJ 2011;342:d3774
In late May I went with an open mind to the sixth Invest in ME conference in London to listen to research presentations and take part, on behalf of the BMJ, in a concluding panel discussion. Although I was aware of Invest in ME’s stance against the recent PACE trial1 and other research on non-biological approaches, I was heartened by the conference theme: “The Way Forward for ME—A Case for Clinical Trials.” I knew that laboratory science had not yet yielded biological evidence that would lead to large scale clinical trials, so I hoped to hear about trials of health services and supportive interventions to improve patients’ experiences and lives.
I heard about just one clinical trial at the conference, however. Oncologists Oystein Fluge and Olav Mella, from the University of Bergen, talked about their recent placebo controlled trial of the monoclonal antibody rituximab in 30 patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). They had found positive results for some secondary outcomes, but not for the primary outcome (self reported symptoms and quality of life at three months2), so it was impossible to draw any firm conclusions about the efficacy of this costly and often toxic drug. (The trial has not been published yet, and we were asked not to report any detailed results.) Most of the other speakers reported, in highly technical language and with densely packed slides, exploratory studies on associations between CFS/ME and numerous biomarkers. Nobody discussed how this disparate collection of small scale laboratory studies might fit together with each other or the wider evidence base. By the end of the day the case for clinical trials had not been made.
I was particularly puzzled that Judy Mikovits of the Whittemore Peterson Institute reported her laboratory’s continuing work on xenotropic murine leukaemia virus-related virus (XMRV) as a possible infectious cause, without mentioning the increasing number of studies refuting that hypothesis. And although other speakers, such as microbiologist Andreas Kogelnik, reported disconfirming work, this was done almost in passing with no discussion. Why was there no scientific discourse about the conflict between these two sets of high profile results? One possible answer for this reticence came a couple of weeks after the conference, when Dr Kogelnik and colleagues published a study in Science firmly refuting the XMRV theory and suggesting contamination by virus samples from mice.3 This paper was accompanied by another disconfirming study4 and an expression of concern from the editor in chief 5 about Mikovits and colleagues’ 2009 Science paper that first proposed the theory.6
As the concluding panel discussion over-ran and it was almost time to run for my train, “the lady from the BMJ” was asked to comment on the day’s research. I said I’d hoped to hear about more patient centred research and admitted that I hadn’t understood many of the presentations. When I defended the PACE trial’s design and findings—albeit for a clearly defined, large subgroup of patients—and disclosed that I had a background in psychiatry, several people in the audience started shouting aggressively. It ended more constructively, with my offer accepted (I think) to speak at next year’s conference about the kind of research questions and study designs that might attract national research grants and be publishable in mainstream medical journals.
Personal abuse and threats from a vociferous minority to doctors and scientists researching CFS/ME are indefensible.7 But how much of this awful behaviour is at least partly fuelled by angry responses from a wider group of campaigners to any suggestion that the condition might be helped, at least in some patients, by interventions such as cognitive behavioural therapy? How much by campaigners’ insistence that the definition of CFS/ME must include a criterion that exercise causes a dangerous deterioration in symptoms and hence cannot be treated with even gradually increasing activity and exercise? And how much by doctors’ dislike of patients who won’t at least try something that research has shown to be effective and safe in well conducted trials?
There could soon be a therapeutic stalemate, with most patients and campaigners believing that only drug treatments based on biological causation will help, and most doctors believing that patients who won’t try graded exercise or cognitive therapy are untreatable. Campaigners may have a point when they complain that focusing only on the trials and systematic reviews (mostly of exercise and cognitive behavioural therapy) might skew research agendas, peer reviewers’ and editors’ priorities, clinical guidelines, healthcare purchasing decisions, assessments for incapacity benefit, and media interest so much that people with chronic and severe fatigue and debilitation (whatever the cause) who are unable to try such interventions (for whatever reason) may be unfairly underserved.
Why can’t CFS/ME be like other common chronic conditions where patients, carers, doctors, and researchers work together to pose research questions, gain understanding, and—in the absence of clear explanations and cures—at least find ways to respond to patients’ needs, help them live with and manage symptoms, and get more out of life?
Cite this as: BMJ 2011;342:d3774
Competing interests: The author has completed the unified competing interest form at www.icmje.org/coi_disclosure.pdf (available on request from her) and declares no support from any organisation for the submitted work; no financial relationships with any organisation that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned; not externally peer reviewed.
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