ME Research UK — Energising ME Research

Biomedical research in ME/CFS: issues and challenges

Author

Dr Vance Spence, Chairman of ME Research UK

Presentation

A presentation given on 2nd March 2005 at a reception for MSPs, members and scientists hosted by the Cross Party Group on ME (XPG) at the Scottish Parliament.

Part 2

The core cause of this confusion is probably the fact that CFS is a diagnosis of exclusion, consisting of (in one reseacher’s words) a “ragbag of common non-specific symptoms with many causes, mistakenly labelled as a syndrome”. Nevertheless, for the patient on the ground who needs somehow to get out of this ‘diagnostic dustbin’ into the specific clinic where he or she belongs, the end result can be a Kafkaesque nightmare involving physical illness compounded by the scepticism of healthcare professionals and the disbelief of family and friends. And life at the bottom can be a long, cruel journey — two separate recent reviews have concluded that, “…patients exhibit severe, long-term functional impairment. Substantial improvement is uncommon and is less than 6%” (1), and “Full recovery…is rare” (2). Crucially, this confusion about the diagnosis (though not about the personal suffering, which is not in doubt) also complicates biomedical research.

Let me give an example. In the ideal experiment using a theoretical outcome measure, what we wish to see at the end are two distinct groups — with the patients (whatever their illness) clearly distinct from age and sex-matched control subjects (graph below).

Figure 3. What we would like to see
Figure 3. What we would like to see

In ME/CFS, what we see over and over again is the graph below (which shows real data points from a real biochemical experiment on ME/CFS patients) — with the controls nicely tightly packed, and the ‘CFS’ patient measurements much more widely scattered. There is clearly something going on since the patients have higher values than the controls on average, yet the scatter is problematic, and researchers scratch their heads when they see it. Why is this happening? Well, if the broad diagnostic net ‘CFS’ really catches all different kinds of fish, this is what we would see, isn't it?

Figure 4. What we actually see
Figure 4. What we actually see

The slide below attempts to show this problem graphically. While the greatest portion of the circle represents the ‘set’ of patients with chronic fatigue (CF); i.e., with at least some of the non-specific symptoms including the F-word ‘fatigue’ (and this set may represent between 1 and 4% of the population), you can see that the set of patients with CFS (i.e., those with ‘fatigue’ plus four symptoms) is much smaller (estimated to be 0.2 to 0.4% of the population in the CMO report of 2002), while those with ME as described in the older scientific literature might represent a subset of CFS itself, since post-exercise ‘fatigue’ is a key element in their illness (population estimates are unavailable for this subset since healthcare professionals no longer diagnose ME per se). The important point is that each slice melds into the next, and that — in the absence of a full clinical assessment — the popular press, healthcare professionals and medical researchers may easily be deceived about the placing of a particular patient (i.e., experimental subject) in a particular diagnostic category.

Figure 5. ME/CFS Research: Core Problem?
Figure 5. ME/CFS Research: Core Problem?

It is also important to recognise that this is only a scheme, a way of seeing, and that the problem may be more or less complex in reality. However, Dr Charles Shepherd of the ME Association put the situation very well in a recent letter (3):

The medical profession has only itself to blame for the awful mess that currently surrounds ME/CFS. It has created an illness that covers a wide variety of fatigue state clinical presentations, with or without psychiatric co-morbidity, and almost certainly an equally diverse range of possible pathological and physiological explanations. Doctors who deal with patients suffering from unexplained abdominal pain, arthralgia or headaches do not work on the basis that they all have the same patho-aetiology and will therefore respond to the same form of treatment. So why apply this form of flawed logic to ME/CFS?

References

  1. Andersen MM, Permin H, Albrecht F. Illness and disability in Danish CFS patients at diagnosis and 5-year follow-up. J Psychosomatic Research 2004; 56: 217–29.
  2. Cairns R, Hotopf M. A systematic review describing the prognosis of chronic fatigue syndrome. Occupational Medicine 2005; 55: 20–31.
  3. Shepherd C. Patients with chronic fatigue syndrome are being ignored. BMJ 2004; 329: 1405.