The last draft post I wrote about the MEGA petition was superseded by events before I finished it, so I’ll try and crack on with this one before the same thing happens again. Of course ‘cracking on’ in ME terms is still kind of slow but I’ll see if I can break the tortoise barrier.
So, what’s happened recently?
Well, we’ve been told that Peter White is retiring from research and will only be an ‘advisor’ to MEGA from now on. This perspective appears to be endorsed by the latest list of MEGA personnel, which no longer includes him. I can only give a muted ‘hurrah’ to this one. Advice is dangerous stuff and you can still do a lot of damage with it. His PACE Trial is swiftly becoming a watchword for bad science (see here, here, and here). Is he really the sort of ME ‘expert’ that either we patients or the MEGA team want around to guide this latest project?
It really is astonishing that MEGA apparently do still want him around after all he has done, and that they clearly expect patients to put up with it. It seems to me that if a passing Martian was given a brief course in English and the full facts, then even he (or she) would swiftly understand why we don’t want Prof White anywhere near this project. Why do the MEGA team not get this?
People with ME have been left on the scrapheap for decades. I myself have been ill for over thirty years. That’s over half my life. I have no children because of it. I lost my job. My life is very limited. Yet I am one of the relatively lucky ones. I can sit and tap at this keyboard – as long as I take plenty of rests to fend off the shoulder and eye pain and overall exhaustion. There are plenty of others who have to spend all their lives in bed, who can’t stand the light, who can’t even talk to their loved ones. We’ve all heard about Whitney Defoe whose birthday it recently was. He is not alone in his suffering. The vast majority of the severely ill are left to fend for themselves as best they can. Rarely do doctors come near them and they wouldn’t know what to do if they did.
And all this time, all these decades, so little research has been done, in large part because of the fairy story dreamed up by the PACE researchers and their associates: the fairy story that all we have to do is cast away our fear and we can get better again. In their attempts to give credence to this pipe dream, they have sucked up the majority of what little research funding there has been for ME in the UK and channeled it into their largely inconclusive projects, testing on populations with fatigue conditions other than ME and even then achieving unconvincing results – foremost among them PACE itself, which has now been exposed as a sham, even the modest results it claimed revealed to be dodgy statistics and sleights of hand.
Why is it so hard for those in MEGA to understand why we feel so strongly about Peter White and his friends? Now at last we are getting some biomedical research and they want him in on it. Why? How can they expect us to trust him?
This graphic (produced by Action for ME) illustrates precisely to whom the UK research money has gone in recent years (2006 to 2015), and those getting the most funding have not been doing biomedical research:
Two names predominate: Peter White and Esther Crawley, and the latter seems to me to be just as much of a liability for MEGA as is White.
Earlier this year, you may remember, Esther Crawley published a study suggesting that the prevalence of (as she described it on BBC Radio 4) CFS/ME at age 16 was higher then previously considered. For this analysis, she relied on children and their parents filling in questionnaires about whether they felt tired or not. There was no input from a doctor and no attempt to screen out patients with other fatigue-related conditions (other than depression, which was once again assessed from questionnaire results). The paper reads: ‘it is important that the uncertainties regarding the population prevalence of pediatric CFS are resolved’ yet it seems unlikely that a study involving such haphazard self-assessed inclusion criteria could have done anything other than add to the confusion. It would seem to me to be very unfortunate for a researcher who seems to have such a poor grasp of the need for carefully defined criteria to be involved with patient selection for MEGA.
A few days ago, at the CMRC conference, she was seeking to justify her trial of GET for children by saying there was ‘good evidence’ for its use in adults. I presume she meant the PACE trial. She does not seem to have kept abreast of recent developments.
But enough of the personnel. We have made it very clear why we don’t want Profs White and Crawley involved with the project but I think there other issues with it which are just as important.
The latest MEGA update, which appeared a few days ago, made it clear that patients for the study would come from the English NHS clinics, which diagnose using the NICE criteria. I have to admit to a sinking feeling when I heard this, one which has stayed with me ever since.
To put it baldly, this will not produce a representative sample of people with ME/CFS. There are a number of reasons why:
- Most severely affected people are unable to access the NHS clinics. A few are reached by home visits or telephone/Skype consultations but most do not have this opportunity. Is it really intended that they should not be included in this massive project? The material accompanying the MEGA petition reads: “We want to investigate not just the causes and underlying biology of M.E./CFS, but also its different types (sub-phenotypes) which may be caused by different underlying mechanisms. This may eventually enable development of new diagnostic tests and new treatments for each sub-phenotype.” Is it not likely that the severely ill have important data to provide towards this end? Prof Ron Davis has said that severely affected patients provide the most useful data “because their biology would show the greatest differences compared with healthy controls”. Is this opportunity to be lost to MEGA – and are the severely affected to be ignored yet again, even as £5m or more is invested?
- The plan to use other diagnoses subsequent to NICE is unsound. The same sort of error was made in the PACE trial. The patients will have been initially diagnosed using the NICE criteria and subsequently will be filtered with others. But any patients who didn’t fit NICE but might have fitted one or more of the other criteria will be lost to the project. It is wrong to assume you have everyone covered just because NICE is a broad criteria.
- Now we get to the tricky bit. It is controversial but there’s no way to ignore it. The clinics select their patients with the treatments they have to offer in mind. This will inevitably entail a bias in selection. They will be more likely to diagnose patients with CFS/ME if the clinician feels they will respond well to GET or GAT. We need to remember that they have one eye on their outcome figures and are under pressure to perform well in comparison with other clinics. The bias may not be a conscious one but it is a bias nevertheless and it is surely appropriate to take this sort of bias into consideration in research (in the same way as the desirability of double blinding for instance). Steps will need to be taken to correct the effect of the bias.
- There is also a problem, which I suspect is widespread, that patients who do not respond well to the therapies (or refuse them in the first place) and therefore drop out are not necessarily followed up by the clinics. These are likely to be genuine ME patients rather those who might have CFS. Unless they can be chased up and brought into the study, this will be another factor skewing the sample of patients.
If the will is there, it should be possible to correct these various ‘skewing factors’ (I expect there’s a proper word for that but I’m not a statistician!) by reaching out to other patients in addition to those provided by the clinics. Prof Julia Newton, with the assistance of Victoria Strassheim (who also spoke at the CMRC conference the other day) placed adverts in ME support group magazines and social media etc to find patients for their own severely affected study. Similar measures (perhaps after consultation with Newton and/or Strassheim) could be taken by MEGA to find not only severely affected patients but also additional patients to make up for those who did not fit the NICE criteria and those who were lost by the inevitable bias mentioned earlier.
I feel it is also important that MEGA reaches out to children in the same way so that not all them come from the Bristol clinic. Once again, it is a question of balance and diversity to build up a representative cohort. Perhaps they could come from Scotland and Wales, and perhaps Jane Colby would be willing to help to ensure that severely affected children are represented.
An additional issue is that there are numerous references throughout the latest MEGA update to having to limit the amount of data collection if finances don’t allow or the patient advisory group objects. The issue seems to me to be overstated and I’m concerned it might serve as an all too useful excuse for not developing a Canadian Criteria cohort, which I feel is vital to the success of the study. My fears in this respect are amplified by the knowledge that Profs White and Crawley have already made it clear that they consider the Canadian criteria to be ‘not practicable’.
It’s also worth pointing out that diagnoses in the NHS clinics are usually made by triage involving OTs, nurses etc rather than by doctors. Many of these may be good clinicians but others will inevitably be inexperienced and may only have picked up what they know about ME/CFS from reading the clinic’s own leaflets. Some of them will have a background in mental health. It seems likely therefore that they will concentrate on what they believe to be the principal symptoms of ME rather than taking a full medical history as the MEGA update suggests..
Finally I’d like to make it clear that, unlike some patients, I’m not against the clinics per se. The ones which teach graded activity (as opposed to exercise) seem to me to be helping people to pace. They may also employ CBT to assist people in coming to terms with having the illness rather than (as in PACE) trying to brainwash patients into thinking they’re not ill. Many people find these clinics helpful. Other clinics unfortunately use graded exercise but I’m fortunate enough not to have direct experience of any of those.
However, I don’t think, as I’ve explained, that the clinics will automatically provide a representative sample of patients for MEGA. Steps will have to be taken to redress the balance and there will need to be a will to take those steps. To judge from the latest update, objections will be made on the grounds of cost, to which, I think, our rejoinder must be: if you can’t afford it, do something cheaper. Whatever is done, it needs doing properly. If the patients are taken only from the NHS clinics, the sample will be skewed towards CFS rather than genuine ME, and MEGA will be another PACE around our necks.
I intend to write along these lines to whoever seems appropriate. My wife has already sent such a letter to Dr Charles Shepherd of the ME Association who has promised to bring all patient concerns to the appropriate people on the MEGA team.He has also suggested that people send feedback to Prof Stephen Holgate, Chair of the CMRC. I will also write to Sonya Chowdhury of AfME (who represents the patient charities on the MEGA team) and ME Research UK.
The above are just my ideas. I’m sure there are many other issues I haven’t even thought of. Over to you! I must say that working through them all seemed a bit like working through the faults in PACE, which is not an encouraging thought..