Could A Lack Of Extensive And Unbiased ME/CFS Education And Research Place Limitations On The Ability Of Ethical Reviewers To Raise Appropriate Concerns?
For many ME/CFS patients, advocates and medical professionals alike, the latest Graded Exercise Therapy trial will project a feeling of deja vu onto them. According to a ProHealth.com summary, the trial which takes place at St Bart's Hospital led by Professor Peter White intends to study:
• How beneficial for CFS/ME patients is graded exercise therapy (GET, recommended by the NICE guideline as being “one of only two therapies for which there is research evidence of benefit”)?
• And can GET be harmful (as “most ME charities,” which “do not recommend it,” believe)?
With a reasonable understanding of the current state of Science on ME/CFS and taking a wide view that considers the opinions of Doctors and Researchers working out of many prestigious institutions (from Stanford, to Harvard to name just a couple), it is hard to believe that such a trial can commence without serious and potentially insurmountable ethical hurdles.Many researchers describe ME/CFS as a heterogeneous condition. There are some who would like to split ME from CFS creating two separate illnesses (often with the intent to split the neurological from the psychological) and there are those who would like to move to a single term, which tends to reflect their beliefs about the aetiological mechanisms of the disease. Adjoined to this issue of nomenclature is the very issue of disease definition. There are several criteria for the diagnosis of ME/CFS which include: London, Oxford, Reeves, Fukuda, Canadian Consensus Criteria and the International Consensus Criteria.
There are no operational and ubiquitously accepted objective tests for ME/CFS and there is no irrefutable evidence that defines single or multiple aetiological mechanisms for the onset of the disease. There are compelling correlations but for the time being causation remains elusive. A combination of poor funding and insufficient epidemiological research leads to this dearth of evidence and understanding. However, despite this lack of research, comparatively, there does not appear to be a dearth of passionate and sometimes obstinate belief about ME/CFS.
In a joint statement by Dr Esther Crawley, Dr Alistair Miller and Professor Peter White himself, on the subject of the Canadian Consensus Criteria, it is noted that: “There is no evidence that different diagnostic criteria diagnose a different condition.”. Similarly, by inference of the lack of an irrefutable aetiological mechanism whilst also considering the differing illness experience from patient to patient (I.E sudden onset vs gradual decline), it can be hard to state that there is any evidence that any of these criteria diagnose the same condition. In both cases the overriding issue is again most likely a lack of both research and funding for it.
The trial itself talks about a belief held by ME charities that GET is causing harm. A large patient survey on ME/CFS treatments including GET conducted by the ME Association  revealed thousands of reports of exacerbated symptoms as a result of the application of this treatment. White himself might want to explore the possibility that poor delivery or poor participation could be the cause of this harm, and some are likely to believe it is the act of a true agnostic to consider this possibility. What we can say pretty reliably, given the thousands of patients reporting harm from a relatively small sample is that GET has ended in harm for many patients and the possibility that the treatment itself is the cause of this harm is an extremely significant consideration moving forward.
When Professor White refers to GET as “one of only two therapies for which there is research evidence of benefit” , I take the view that this actually an unreliable statement to make at this juncture. The results of the PACE trial showed that GET had a positive (yet not curative) effect on a small percentage of patients. Initial media reports seemed to suggest the trial had proven GET a successful treatment, but investigations about strength of the figures and the meaning behind them by several professionals and advocates  has revealed that the PACE trial, in the view of many, fails as a convincing argument for the application of CBT&GET that is currently recommended by the NICE for ME/CFS patients.
Given the mixed research on the efficacy of GET, I would find it difficult to agree a reliable evidence base exists which supports GET as a beneficial treatment. While it may have a beneficial effect on a small percentage of patients, when you combine the significant levels of harm reported by ME/CFS patients, the lack of a confirmed aetiological mechanism and the inability to state that current operational criteria have any ability to define a uniform group of patients, this surely raises serious ethical concerns when considering yet another Graded Exercise Therapy trial.
It is not necessarily for Professor White himself however to raise this objection, and a level of cognitive bias when pursuing a particular area of research is even excusable as a method of avoiding an impractical level of distraction or when collecting the data itself answers the question far more expeditiously. Trials of medical treatments do not come without risk to patients' health and as a researcher, Professor White's research proposals will be subjected to ethical reviews. This safety net should then serve to help him refine any planned research to present as little danger to patients as possible, and if the risk is too significant, deny permission for that research to go ahead.
So I raise the question to every would be ethical reviewer of ME/CFS research, have you yet considered how little certainty there remains in the fields of ME/CFS diagnostics and definition? Is it truly safe to be piloting potentially harmful treatments on a group of patients which compared to those of other more well researched illnesses, so little is understood? Or, could it be that the safest option is to preclude further GET treatment trials until more research is carried out on the causes and symptoms of ME/CFS?
Perhaps the most haunting thing of all is the ostensible lack of objective efficacy measurements, once again plaguing a Graded Exercise Therapy trial. If the agnostic assumes that the patient could be unreliable as a participant in GET, and that this is a possible explanation for the reported failures of this treatment, it surely holds that this fallibility also applies to positive results and that human vanity or the desire to get better at all costs makes the patient a source of bias. Again I must ask, is it ethical to put patients through such a trial without quality objective measurements? Not only because harm itself can escape the perception of the patient, but because a lack of quality data could be seen by many as a lack of respect for the brave and pioneering patients who subject themselves to potentially harmful trials.
 http://www.prohealth.com/library/showarticle.cfm?libid=17710 (accessed 22/11/2012) - “Controlled Trial of Graded Exercise Therapy for CFS/ME Recruiting in London Now” – Prohealth.com
 http://www.meassociation.org.uk/?p=7156 (accessed 22/11/2012) Use of the Canadian criteria to diagnose CFS, British Medical Journal, 18 July 2011 - MEAssociation news.
 http://www.meassociation.org.uk/?page_id=1345 (accessed 22/11/2012) ‘Managing my ME.’ ME Association publish results of huge survey report
 http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=12053 (accessed 22/11/2012) UK Clinical Research Network
 www.youtube.com/watch?v=Sa3LyYxu49s ,
www.youtube.com/watch?v=b3_mjQe-t1M (accessed 22/11/2012) MEAnalysis video series on the PACE trial
On The Latest GET Trial
Blog entry posted by Stukindawski, Nov 21, 2012.