By David Tuller, DrPH
David Tuller is academic coordinator of the concurrent masters degree program in public health and journalism at the University of California, Berkeley.
In 2010, the BMJ published the results of the Fatigue Intervention by Nurses Evaluation, or FINE. The investigators for this companion trial to PACE, also funded by the Medical Research Council, reported no benefits to ME/CFS patients from the interventions tested.
In medical research, null findings often get ignored in favor or more exciting “positive” results. In this vein, the FINE trial seems to have vanished from the public discussion over the controversial findings from the PACE study. I thought it was important to re-focus some attention on this related effort to prove that “deconditioning” is the cause of the devastating symptoms of ME/CFS. (This piece is also too long but hopefully not quite as dense.)
An update on something else: I want to thank the public relations manager from Queen Mary University of London for clarifying his previous assertion that I did not seek comment from the PACE investigators before Virology Blog posted my story. In an e-mail, he explained that he did not mean to suggest that I hadn’t contacted them for interviews. He only meant, he wrote, that I hadn’t sent them my draft posts for comment before publication. He apologized for the misunderstanding.
I accept his apology, so that’s the end of the matter. In my return e-mail, however, I did let him know I was surprised at the expectation that I might have shared the draft with the PACE investigators before publication. I would not have done that whether or not they had granted me interviews. This is journalism, not peer-review. Different rules.
In 2003, with much fanfare, the U.K. Medical Research Council announced that it would fund two major studies of non-pharmacological treatments for chronic fatigue syndrome. In addition to PACE, the agency decided to back a second, smaller study called “Fatigue Intervention by Nurses Evaluation,” or FINE. Because the PACE trial was targeting patients well enough to attend sessions at a medical clinic, the complementary FINE study was designed to test treatments for more severely ill patients.
(Chronic fatigue syndrome is also known as myalgic encephalomyelitis, CFS/ME, and ME/CFS, which has now been adopted by U.S. government agencies. The British investigators of FINE and PACE prefer to call it chronic fatigue syndrome, or sometimes CFS/ME.)
Alison Wearden, a psychologist at the University of Manchester, was the lead FINE investigator. She also sat on the PACE Trial Steering Committee and wrote an article about FINE for one of the PACE trial’s participant newsletters. The Medical Research Council and the PACE team referred to FINE as PACE’s “sister” trial. The two studies included the same two primary outcome measures, self-reported fatigue and physical function, and used the same scales to assess them.
The FINE results were published in BMJ in April, 2010. Yet when the first PACE results were published in The Lancet the following year, the investigators did not mention the FINE trial in the text. The trial has also been virtually ignored in the subsequent public debate over the results of the PACE trial and the effectiveness, or lack thereof, of the PACE approach.
What happened? Why has the FINE trial been “disappeared”?
The main goal of the FINE trial was to test a treatment for homebound patients that adapted and combined elements of cognitive behavior therapy and graded exercise therapy, the two rehabilitative therapies being tested in PACE. The approach, called “pragmatic rehabilitation,” had been successfully tested in a small previous study. In FINE, the investigators planned to compare “pragmatic rehabilitation” with another intervention and with standard care from a general practitioner.
Here’s what the Medical Research Council wrote about the main intervention in an article in its newsletter, MRC Network, in the summer of 2003: “Pragmatic rehabilitation…is delivered by specially trained nurses, who give patients a detailed physiological explanation of symptom patterns. This is followed by a treatment programme focussing on graded exercise, sleep and relaxation.”
The second intervention arm featured a treatment called “supportive listening,” a patient-centered and non-directive counseling approach. This treatment presumed that patients might improve if they felt that the therapist empathized with them, took their concerns seriously, and allowed them to find their own approach to addressing the illness.
The Medical Research Council committed 1.3 million pounds to the FINE trial. The study was conducted in northwest England, with 296 patients recruited from primary care. Each intervention took place over 18 weeks and consisted of ten sessions–five home visits lasting up to 90 minutes alternating with five telephone conversations of up to 30 minutes.
As in the PACE trial, patients were selected using the Oxford criteria for chronic fatigue syndrome, defined as the presence of six months of medically unexplained fatigue, with no other symptoms required. The Oxford criteria have been widely criticized for yielding heterogeneous samples, and a report commissioned by the National Institutes of Health this year recommended by the case definition be “retired” for that reason.
More specific case definitions for the illness require the presence of core symptoms like post-exertional malaise, cognitive problems and sleep disorders, rather than just fatigue per se. Because the symptom called post-exertional malaise means that patients can suffer severe relapses after minimal exertion, many patients and advocacy organizations consider increases in activity to be potentially dangerous.
To be eligible for the FINE trial, participants needed to score 70 or less out of 100 on the physical function scale, the Medical Outcomes Study 36-Item Short Form Health Survey, known as the SF-36. They also needed to score a 4 or more out of 11 on the 11-item Chalder Fatigue Scale, with each item scored as either 0 or 1. On the fatigue scale, a higher score indicated greater fatigue.
Among other measures, the trial also included a key objective outcome–the time to take 20 steps, (or number of steps taken, if this is not achieved) and maximum heart rate reached on a step-test.
Participants were to be assessed on these measures at 20 weeks, which was right after the end of the treatment period, and again at 70 weeks, which was one year after the end of treatment. According to the FINE trial protocol, published in the journal BMC Medicine in 2006, “short-term assessments of outcome in a chronic health condition such as CFS/ME can be misleading” and declared the 70-week assessment to be the “primary outcome point.”
The theoretical model behind the FINE trial and pragmatic rehabilitation paralleled the PACE concept. The physical symptoms were presumed to be the result not of a pathological disease process but of “deconditioning” or “dysregulation” caused by sedentary behavior, accompanied by disrupted sleep cycles and stress. The sedentary behavior was itself presumed to be triggered by patients’ “unhelpful” conviction that they suffered from a progressive medical illness. Counteracting the deconditioning involved re-establishing normal sleep cycles, reducing anxiety levels and gently increasing physical exertion, even if patients remained homebound.
“The treatment [pragmatic rehabilitation] is based on a model proposing that CFS/ME is best understood as a consequence of physiological dysregulation associated with inactivity and disturbance of sleep and circadian rhythms,” stated the FINE trial protocol. “We have argued that these conditions are often maintained by illness beliefs that lead to exercise-avoidance. The essential feature of the treatment is the provision of a detailed explanation for patients’ symptoms, couched in terms of the physiological dysregulation model, from which flows the rationale for a graded return to activity.”
On the FINE trial website, a 2004 presentation about pragmatic rehabilitation explained the illness in somewhat simpler terms, comparing it to “very severe jetlag.” After explaining how and why pragmatic rehabilitation led to physical improvement, the presentation offered this hopeful message, in boldface: “There is no disease–you have a right to full health. This is a good news diagnosis. Carefully built up exercise can reverse the condition. Go for 100% recovery.”
In contrast, patients, advocates and many leading scientists have completely rejected the PACE and FINE approach. They believe the evidence overwhelmingly points to an immunological and neurological disorder triggered by an initial infection or some other physiological insult. Last month, the National Institutes of Health ratified this perspective when it announced a major new push to seek biomedical answers to the disease, which it refers to as ME/CFS.
As in PACE, patients in the FINE trial were issued different treatment manuals depending upon their assigned study arm. The treatment manual for pragmatic rehabilitation repeatedly informed participants that the therapy could help them get better–even though the trial itself was designed to test the effectiveness of the therapy. (In the PACE trial, the manuals for the cognitive behavior and graded therapy arms also included many statements promoting the idea that the therapies could successfully treat the illness.)
“This booklet has been written with the help of patients who have made a full recovery from Chronic Fatigue Syndrome,” stated the FINE pragmatic rehabilitation manual on its second page. “Facts and information which were important to them in making this recovery have been included.” The manual noted that the patients who helped write it had been treated at the Royal Liverpool University Hospital but did not include more specific details about their “full recovery” from the illness.
Among the “facts and information” included in the manual were assertions that the trial participants, contrary to what they might themselves believe, had no persistent viral infection and “no underlying serious disease.” The manual promised them that pragmatic rehabilitation could help them overcome the illness and the deconditioning perpetuating it. “Instead of CFS controlling you, you can start to regain control of your body and your life,” stated the manual.
Finally, as in PACE, participants were encouraged to change their beliefs about their condition by “building the right thoughts for your recovery.” Participants were warned that “unhelpful thoughts”–such as the idea that continued symptoms indicated the presence of an organic disease and could not be attributed to deconditioning–“can put you off parts of the treatment programme and so delay or prevent recovery.”
The supportive listening manual did not similarly promote the idea that “recovery” from the illness was possible. During the sessions, the manual explained, “The listener, your therapist, will provide support and encourage you to find ways to cope by using your own resources to change, manage or adapt to difficulties…She will not tell you what to do, advise, coach or direct you.”
A qualitative study about the challenges of the FINE research process, published by the investigators in the journal Implementation Science in 2011, shed light on how much the theoretical framework and the treatment approaches frustrated and angered trial participants. According to the interviews with some of the nurses, nurse supervisors, and participants involved in FINE, the home visits often bristled with tension over the different perceptions of what caused the illness and which interventions could help.
“At times, this lack of agreement over the nature of the condition and lack of acceptance as to the rationale behind the treatment led to conflict,” noted the FINE investigators in the qualitative paper. “A particularly difficult challenge of interacting with patients for the nurses and their supervisors was managing patients’ resistance to the treatment.”
One participant in the pragmatic rehabilitation arm, who apparently found it difficult to do what was expected, attributed this resistance to the insistence that deconditioning caused the symptoms and that activity would reverse them. “If all that was standing between me and recovery was the reconditioning I could work it out and do it, but what I have got is not just a reconditioning problem,” the participant said. “I have got something where there is damage and a complete lack of strength actually getting into the muscles and you can’t work with what you haven’t got in terms of energy.”
Another participant in the pragmatic rehabilitation arm was more blunt. “I kept arguing with her [the nurse administering the treatment] all the time because I didn’t agree with what she said,” said the participant, who ended up dropping out of the trial.
Some participants in the supportive listening arm also questioned the value of the treatment they were receiving, according to the study. “I mostly believe it was more physical than anything else, and I didn’t see how talking could truthfully, you know, if it was physical, do anything,” said one.
In fact, the theoretical orientation also alienated some prospective participants as well, according to interviews the investigators conducted with some patients who declined to enter the trial. “It [the PR intervention] insisted that physiologically there was nothing wrong,” said one such patient. “There was nothing wrong with my glands, there was nothing wrong, that it was just deconditioned muscles. And I didn’t believe that…I can’t get well with treatment you don’t believe in.”
When patients challenged or criticized the therapeutic interventions, the study found, nurses sometimes felt their authority and expertise to be under threat. “They are testing you all the time,” said one nurse. Another reported: “That anger…it’s very wearing and demoralizing.”
One nurse remembered the difficulties she faced with a particular participant. “I used to go there and she would totally block me, she would sit with her arms folded, total silence in the house,” said the nurse. “It was tortuous for both of us.”
At times, nurses themselves responded to these difficult interactions with bouts of anger directed at the participants, according to a supervisor.
“Their frustration has reached the point where they sort of boiled over,” said the supervisor. “There is sort of feeling that the patient should be grateful and follow your advice, and in actual fact, what happens is the patient is quite resistant and there is this thing like you know, ‘The bastards don’t want to get better.'”
BMJ published the FINE results in 2010. The FINE investigators found no statistically significant benefits to either pragmatic rehabilitation or supportive listening at 70 weeks. Despite these null findings one year after the end of the 18-week course of treatment, the mean scores of those in the pragmatic rehabilitative arm demonstrated at 20 weeks a “clinically modest” but statistically significant reduction in fatigue–a drop of one point (plus a little) on the 11-point fatigue scale. The slight improvement still meant that participants were much more fatigued than the initial entry threshold for disability, and any benefits were no longer statistically significant by the final assessment.
Despite the null findings at 70 weeks, the authors put a positive gloss on the results, reporting first in the abstract that fatigue was “significantly improved” at 20 weeks. Given the very modest one-point change in average fatigue scores, perhaps the FINE investigators intended to report instead that there was a “statistically significant improvement” at 20 weeks–an accurate phrase with a somewhat different meaning.
The abstract included another interesting linguistic element. While the trial protocol had designated the 70-week assessment as “the primary outcome point,” the abstract of the paper itself now stated that “the primary clinical outcomes were fatigue and physical functioning at the end of treatment (20 weeks) and 70 weeks from recruitment.”
After redefining their primary outcome points to include the 20-week as well as the 70-week assessment, the abstract promoted the positive effects found at the earlier point as the study’s main finding. Only after communicating the initial benefits did they note that these advantages for pragmatic rehabilitation later wore off. The FINE paper cited no oversight committee approval for this expanded interpretation of the trial’s primary outcome points to include the 20-week assessment, nor did it mention the protocol’s caveat about the “misleading” nature of short-term assessments in chronic health conditions.
In fact, within the text of the paper, the investigators noted that the “pre-designated outcome point” was 70 weeks. But they did not explain why they then decided to highlight most in the abstract what was not the pre-designated but instead a post-hoc “primary” outcome point–the 20-week assessment.
A BMJ editorial that accompanied the FINE trial also accentuated the positive results at 20 weeks rather than the bad news at 70 weeks. According to the editorial’s subhead, pragmatic rehabilitation has a short term benefit, but supportive listening does not.” The editorial did not note that this was not the pre-designated primary outcome point. The null results for that outcome point–the 70-week assessment–were not mentioned until later in the editorial.
Patients and advocates soon began criticizing the study in the “rapid response” section of the BMJ website, citing its theoretical framework, the use of the broad Oxford criteria as a case definition, and the failure to provide the step-test outcomes, among other issues.
“The data provide strong evidence that the anxiety and deconditioning model of CFS/ME on which the trial is predicated is either wrong or, at best, incomplete,” wrote one patient. “These results are immensely important because they demonstrate that if a cure for CFS/ME is to be found, one must look beyond the psycho-behavioural paradigm.”
Another patient wrote that the study was “a wake-up call to the whole of the medical establishment” to take the illness seriously. One predicted “that there will be those who say that this trial failed because the patients were not trying hard enough.”
A physician from Australia sought to defend the interests not of patients but of the English language, decrying the lack of hyphens in the paper’s full title: “Nurse led, home based self help treatment for patients in primary care with chronic fatigue syndrome: randomised controlled trial.”
“The hyphen is a coupling between carriages of words to ensure unambiguous transmission of thought,” wrote the doctor. “Surely this should read ‘Nurse-led, home-based, self-help’…Lest English sink further into the Great Despond of ambiguity and non-sense [hyphen included in the original comment], may I implore the co-editors of the BMJ to be the vigilant watchdogs of our mother tongue which at the hands of a younger texting generation is heading towards anarchy.” [The original comment did not include the expected comma between “tongue” and “which.”]
In a response on the BMJ website a month after publishing the study, the FINE investigators reported that they had conducted a post-hoc analysis with a different kind of scoring for the Chalder Fatigue Scale.
Instead of scoring the answers as 0 or 1 using what was called a bimodal scale, they rescored them using what was called a continuous scale, with values ranging from 0 to 3. The full range of possible scores now ran from 0 to 33, rather than 0 to 11. (As collected, the data for the Chalder Fatigue Scale allowed for either scoring system; however, the original entry criteria of 4 on the bimodal scale would translate into a range from 4 to as high as 19 on the revised scale.)
With the revised scoring, they now reported a “clinically modest, but statistically significant effect” of pragmatic rehabilitation at 70 weeks–a reduction from baseline of about 2.5 points on the 0 to 33 scale. This final score represented some increase in fatigue from the 20-week interim assessment point.
In their comment on the website, the FINE investigators now reaffirmed that the 70-week assessment was “our primary outcome point.” This statement conformed to the protocol but differed from the suggestion in the BMJ paper that the 20-week results also represented “primary” outcomes. Given that the post-hoc rescoring allowed the investigators to report statistically significant results at the 70-week endpoint, this zig-zag back to the protocol language was perhaps not surprising.
In their comment, the FINE investigators also explained that they did not report their step-test results–their one objective measure of physical capacity–“due to a significant amount of missing data.” They did not provide an explanation for the missing data. (One obvious possible reason for missing data on an objective fitness test is that participants were too disabled to perform it at all.)
The FINE investigators did not address the question of whether the title of their paper should have included hyphens.
In the rapid comments, Tom Kindlon, a patient and advocate from a Dublin suburb, responded to the FINE investigators’ decision to report their new post-hoc analysis of the fatigue scale. He noted that the investigators themselves had chosen the bimodal scoring system for their study rather than the continuous method.
“I’m sure many pharmacological and non-pharmacological studies could look different if investigators decided to use a different scoring method or scale at the end, if the results weren’t as impressive as they’d hoped,” he wrote. “But that is not normally how medicine works. So, while it is interesting that the researchers have shared this data, I think the data in the main paper should be seen as the main data.”
The FINE investigators have published a number of other papers arising from their study. In a 2013 paper on mediators of the effects of pragmatic rehabilitation, they reported that there were no differences between the three groups on the objective measure of physical capacity, the step test, despite their earlier decision not to publish the data in the BMJ paper.
Wearden herself presented the trial as a high point of her professional career in a 2013 interview for the website of the University of Manchester’s School of Psychological Sciences. :”I suppose the thing I did that I’m most proud of is I ran a large treatment trial of pragmatic rehabilitation treatment for patients with chronic fatigue syndrome,” she said in the interview. “We successfully carried that trial out and found a treatment that improved patients’ fatigue, so that’s probably the thing that I’m most proud of.”
The interview did not mention that the improvement at 20 weeks was transient until the investigators performed a post-hoc-analysis and rescored the fatigue scale.
The Science Media Centre, a self-styled “independent” purveyor of information about science and scientific research to journalists, has consistently shown an interest in research on what it calls CFS/ME. It held a press briefing for the first PACE results published in The Lancet in 2011, and has helped publicize the release of subsequent studies from the PACE team.
However, the Science Media Centre does not appear to have done anything to publicize the 2010 release of the FINE trial, despite its interest in the topic. A search of the center’s website for the lead FINE investigator, Alison Wearden, yielded no results. And a search for CFS/ME indicated that the first study embraced by the center’s publicity machine was the 2011 Lancet paper.
That might help explain why the FINE trial was virtually ignored by the media. A search on the LexisNexis database for “PACE trial” and “chronic fatigue syndrome” yielded 21 “newspaper” articles (I use the apostrophes here because I don’t know if that number includes articles on newspaper websites that did not appear in the print product; the accuracy of the number is also in question because the list did not include two PACE-related articles that I wrote for The New York Times).
Searches on the database combining “chronic fatigue syndrome” with either “FINE trial” or “pragmatic rehabilitation” yielded no results. (I used the version of LexisNexis Academic available to me through the University of California library system.)
Other researchers have also paid scant attention to the FINE trial, especially when compared to the PACE study. According to Google Scholar, the 2011 PACE paper in The Lancet has been cited 355 times. In contrast, the 2010 FINE paper in BMJ has only been cited 39 times.
The PACE investigators likely exacerbated this virtual disappearance of the FINE trial by their decision not to mention it in their Lancet paper, despite its longstanding status as a “sister trial” and the relevance of the findings to their own study of cognitive behavior therapy and graded exercise therapy. The PACE investigators have not explained their reasons for ignoring the FINE trial. (I wrote about this lapse in my Virology Blog story, but in their response the PACE investigators did not mention it.)
This absence is particularly striking in light of the decision made by the PACE investigators to drop their protocol method of assessing the Chalder Fatigue Scale. In the protocol, their primary fatigue outcome was based on bimodal scoring on the 11-item fatigue scale. The protocol included continuous scoring on the fatigue scale, with the 0 to 33 scale, as a secondary outcome.
In the PACE paper itself, the investigators announced that they had dropped the bimodal scoring in favor of the continuous scoring “to more sensitively test our hypotheses of effectiveness.” They did not explain why they simply didn’t provide the findings under both scoring methods, since the data as collected allowed for both analyses. They also did not cite any references to support this mid-trial decision, nor did they explain what prompted it.
They certainly did not mention that PACE’s “sister” study, the FINE trial, had reported null results at the 70-week endpoint–that is, until the investigators rescored the data using a continuous scale rather than the bimodal scale used in the original paper.
The three main PACE investigators–psychiatrists Peter White and Michael Sharpe, and Trudie Chalder, a professor of. cognitive behavior therapy–did not respond to an e-mail request for comment on why their Lancet paper did not mention the FINE study, especially in reference to their post-hoc decision to change the method of scoring the fatigue scale. Lancet editor Richard Horton also did not respond to an e-mail request for an interview on whether he believed the Lancet paper should have included information about the FINE trial and its results.
Update 11/9/15 10:46 PM: According to a list of published and in-process papers on the FINE trial website, the main FINE study was rejected by The Lancet before being accepted by BMJ, suggesting that the journal was at least aware of the trial well before it published the PACE study. That raises further questions about the absence of any mention of FINE and its null findings in the text of the PACE paper.
37 thoughts on “Trial By Error, Continued: Why has the PACE Study’s “Sister Trial” Been “Disappeared” and Forgotten?”
I did the Pragmatic Rehabilitation Therapy. It was basically brainwashing. Non-scientific woo, dressed up as a plausible (to some), physiological explanation, with some anxiety about bodily symptoms, general anxiety and sleep disorder, thrown in.
So, a score at the end of the PACE trial of 70 on the sf-36 physical functioning scale, and a score of 5 on the Chalder Fatigue scale both hit the targets for recovery and would mean that, according to the changed criteria, that PACE would say that they no longer had CFS.
At the same time these were the scores appropriate for more severely ill ME/CFS patients to qualify for entry to the FINE trial. The “more severely ill” patients!
And the members of the PACE team wonder why patients have no confidence in them!
Thank you for yet another excellent article.
FINE isn’t something we hear about much, so it was every interesting to hear about the likely trigger of scoring changes in PACE. It’s another piece of the puzzle which makes the PACE investigators look a bit less like bumbling fools, and more like they were deliberately altering the protocol because they knew it was they only way they could get the results which they wanted.
Excellent article, very clear and illuminating, I look forward to the next installment!
Delighted to see another in this series, David, thank you – printing your article off now to study it properly. I wasn’t familiar with the FINE trial (and I guess that’s your point!)
I hope you wonâ€™t mind me mentioning (again!) the hugely successful, record-smashing #MEAction petition calling for the retraction of misleading claims of improvement and recovery in CFS patients in the PACE trial – and that followed your first in this series of blog posts.
PACE has been a monkey on patients’ backs for years and is a key reason why ME/CFS is viewed by many as maintained entirely by deconditioned patientsâ€™ fear of exercise.
The petition has gained over 8,800 signatures in only eleven days! And its target is 10,000.
Weâ€™re so nearly there â€“ please sign and send the petition to everyone you know.
And if youâ€™re part of an organisation, please do everything you can to get the petition out via your platforms.
Hereâ€™s the link:
Letâ€™s sink this appalling piece of “science”!
What a fascinating read – and what awful things to read about. The disrespect towards patients was astonishing.
How did the PACE and FINE investigators get away with this blind insistence that patients weren’t sick?
Both of these trials were MRC-funded and cost a lot of taxpayers’ money (PACE cost Â£5m and according to Invest in ME, FINE cost Â£1.1m).and yet the MRC seems to have no mechanism in place for checking whether study authors run riot and write up results in a misleading manner once the MRC has handed over our money.
Why is no one accountable?
Is David Tuller good or what? And he’s doing this all for free…..He gets the 2015 ME/CFS heroic journalism award IMHO….
It breaks my heart the way so many patients over so many years in so many countries have been so badly abused by these psychiatrists and other medical personal who fail to recognize this serious, devastating, physical disease for what it truly is, but instead hold on to and promote “theories” that have no evidence whatsoever. So much harm has been done. I hope their eyes will finally be opened so that they see what they have done to many, many very sick people suffering from a serious, physical disease. Thank you, David, for speaking the truth that must be heard. May their eyes be opened.
The FINE study and the PACE trial partake of the same sham scientific method that keeps a certain conclusion in view from the outset and, if the data turn out not to be so supportive of that view as was hoped, then the data are manipulated and talked up into something they’re not.
People who do not have ME/CFS such as myself are weary of seeing this sort of intellectual dishonesty still informing healthcare policy. People with the disease continue to suffer hardship whilst their health continues to be jeopardised. Charlatanism has held sway over this disease for long enough; its crude speculation has had ample opportunity to make discoveries but discovered nothing. It is time for science to take over.
Hear: Hear: Hear!
Thank you once again for keeping digging on this David. It’s hard to decide whether to be entertained or shocked!
I have to say that the whole shambles rather reminds me of a more apt nautical allusion than the one floated recently…
David, Did you ask the Science Media Centre to comment on their selective reporting? In last month’s PACE follow-up briefing they began: “CFS/ME affects around 250,000 people in the UK and in severe cases results in patients being mostly bedridden and unable to do more than minimal daily tasks.” This might even give the impression that PACE was concerned with patients who were recruited for FINE.
I just read your update about FINE being rejected by The Lancet before being accepted by the BMJ. Big journals have a bias against publishing null results: and it’s a disservice to science. A null result from a trial this size should have been given a prominent place in the literature. Disproving the nonsense is as important as proving the good stuff.
Thank you very much (again) David for an excellent investigative report. What gets me I think (since math has long departed my remaining brain cell), is the way in which authors of FINE and PACE overtly biased their preferred ‘treatment’ arms. If not the nurses – in this instance – and what they said to patients then by what was said in the manuals for patients to read and for therapists to use. Just imagine how different the results from both studies might have been had we – as experience patients – been able to talk about the benefitis of pacing in such a fashion!
I endorse the sincere thanks that many others have given, David. I so hope that all your hard work on this subject will reach a very wide audience, and that the time will come (very soon!) when mainstream medical thinking and treatment of ME/CFS will be entirely based on the biomedical evidence and not on flawed studies with questionable methodology – just increase your PACES and you’ll be FINE, as it were…..which brings me on to the worrying question of another happy-clappy named trial, namely SMILE. I’m not sure what stage this is at now, but some refs. to it:
Sorry – that middle ref. was meant to be the following:
I’m pretty sure I was treated as part of this trial or similar, same hospital around the same time and the woman who treated me is listed as a ‘collaborator’. I was put on a GET programme and I dropped out because I relapsed terribly. I was blamed for ‘not doing it right’ and my mum had many arguments with them as by this point I could barely move out of bed and she was dealing with the admin side for me. I’m curious as to how many others dropped out and why and if this was factored into the results. I seem to recall it wasn’t, I was just classed as non compliant or something but my memory is very hazy. I do know it was the worst relapse I have ever had and I was not given any help afterwards, I was pretty much blamed for ‘not doing it right’ – I tried everything they said. Ironically id probably be better if I hadn’t done it properly. Personal feelings aside the ethics of such research are questionable (I was not treated with any professional courtesy or respect once it became clear I was getting worse) and the methodology especially if people are dropping out because the treatment makes them worse and this is NOT factored into the results . I was given the whole ‘deconditiining’ explanation too, repeated like a mantra.
Here’s another label from the same brand: GETSET as in “Ready, get set, go!”
The Chalder Fatigue Scale was invented by Trudy Chalder. It has 11 questions. 6 yesses were the minimum requirement to get into the PACE study. I have ME, diagnosed in 1990 at the Royal Free Hospital by Wiliam Weir. I’d fail:
Do you have problems with tiredness? It all depends on what you mean by ‘tiredness’. If you mean the feeling that normally follows strenuous activity then – No.
If you mean the feeling that normally is associated with lack of sleep then – No.
If you mean the feeling that normally you get after an illess such as influenza, when you’re too tired to get out of bed then — Perhaps. However I don’t think you do mean that, so the fair answer is No.
Do you need to rest more? No, resting makes no difference. I don’t need to rest, I need to get things done.
Do you feel sleepy or drowsy? No. Sleepy and drowsy are the same thing and so is the tiredness we covered already. You can’t define my illness with labels that apply to things you feel.
Do you have problems starting things? No . Starting’s is the easy part. Keeping on to the end is the problem. If it gets done then it takes heroism.
Do you lack energy? Isn’t this the same as the question you just asked?
Do your muscles have less strength? No. I could probably pull your head off right now.
Do you feel weak? No. And that’s the same question you just asked.
Do you have difficulty concentrating? Put your thumb on the desk. Allow me to strike you on the thumbnail with a hammer thereby creating empathy between us. Then we’ll have a discussion about whether you’re having difficulty concentrating.
Do you make slips of the tongue when speaking? Yes, but that isn’t a major symptom, it’s more a side effect of other kinds of suffering, like the way your sore thumb is affecting your handwriting.
How is your memory? Fine thanks. I’m bothered about yours though – you keep on asking the same damn-fool questions.
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Posted on behalf of Margaret Williams:
In addition to its null result, the FINE trial may have been inconvenient to the PACE trial
principal investigators for other reasons.
In his letter to the West Midlands Medical Research & Ethics Committee (MREC) dated 9 February 2006 seeking ethical approval to change the eligibility and primary outcome criteria for the PACE trial after recruitment had begun, Professor Peter White wrote about his wish to change the SF-36 threshold:
“We therefore propose an increase of the categorical positive outcome from 70 to 75, reasserting a ten point score gap between entry criterion and positive outcome. The other advantage of changing to 75 is that it would bring the PACE trial into line with the FINE trial, an MRC funded trial for CFS/ME and the sister study to PACE.”
As readers of Dr Tuller’s articles will know, when the results of the PACE trial were published in The Lancet in 2011, the positive “ten point score gap” promised to the ethics committee had been replaced by a negative five point score gap, allowing participants to deteriorate yet still be described as “recovered”.
Consequently the “advantage” of bringing the sibling FINE and PACE trials “into line” â€“ which would have enabled direct comparison between the results of each trial â€“ was lost.
It is therefore reasonable to ask if this substantial amendment to the trial protocol would
have received ethical approval had the MREC known that these commitments, together with every other published primary outcome measure, were to be abandoned before the results were published.
It is also reasonable to ask if the PACE trial itself might also have yielded a null result had the primary outcome measures and statistical analysis not been changed mid-trial.
Margaret Williams, 11th November 2015
Excellent! I hadn’t looked to see exactly how vague the questionnaire actually was. This is yet another example of the mockery this whole fiasco makes of scientific research and review. There simply *should not even be* a Chalder ‘fatigue scale’! Well done for spelling it out for us. (y)
This. Null results may not be award-winners, but they are just as important to the scientific process and they should be celebrated for the thoroughness of the science if nothing else. Plus, publishing them makes it less likely that future researchers will waste their time replicating something already known to be a dead-end!
Only publishing/promoting positive results makes scientists more and more likely to buy into the idea that their reputation is based purely on the results they get and not on the quality of their work – and that leads to the temptation to massage results.
Incredible series of exposÃ©s from Mr. Tuller. We have very, very grateful for his work and support.
It’s worth noting the DWP classify CFS/ME from two separate chapters of the International Classification of Diseases: https://pbs.twimg.com/media/CTnCQu_WUAAIzZW.png
However, the World Health Organisation exclude F48.0 Neurasthenia from PVFS G93.3 – they cannot be diagnosed together (added within the images). So is there a breach of some kind?
It is this simply case of nomenclature which causes so much confusion for patients. When a person is diagnosed with ME, they are most likely told they have CFS today, even in the UK. An ambiguous diagnosis like this, which now doesn’t even include M.E., doesn’t help to inform the patient as to whether they have an incurable, neurological disease, as described after the Royal Free Hospital outbreak in 1955, or whether they have a neurotic disorder.
Surely, the treatment and management for both should be very different, rather than the same?
In this sense, any trial to treat and remedy symptoms, would need a definitive diagnosis. Is this not similar to designing a trial for people with both Multiple Personality Disorder and Multiple Sclerosis? Surely, any ethics committee wouldn’t allow it?
Another ethical issue is with diagnosis. I have children. If a child became sick and displayed M.E. symptomatology, wouldn’t it be normal practice for the diagnosing doctor to explain to the parent the precise diagnosis, based upon relevant tests and features?
If the diagnosing doctor or specialist can only hazard an educated guess based upon no permitted and relevant tests, and still include the term, M.E. in that diagnosis, surely that cannot refer to the incurable, neurological disease which occurred at the Royal Free Hospital in 1995?
No doctor would combine MPD/MS as one sole condition?
Much of the issue has been with lack of relevant testing to prove the symptomatology of M.E., along with the fact no known cause exists.
Yet there’s no one test for many Neurological diseases, and many of which don’t have a known cause, like M.E. So many believe the need for markers is of huge importance to identify people with Neurological ME. If Royal Free M.E. is no longer screened for, how do we know who is afflicted?
There’s much literature of tests for Neurological M.E., but as mentioned, they are not routinely permitted by NICE UK, as described in the added picture. Yet many M.E. awareness sites and experts from around the globe can confidentially diagnose Neurological M.E., as also added in the images.
Surely another ethical question has to be asked is why an untested diagnosis of M.E. is concealed from the patient, family and society? Why this restriction? If the UK DWP suggest CFS/ME can both mean a neurological disease and neurotic disorder, isn’t that a fundamental contradiction in terms? And surely either label is misdiagnosis, especially if the tests to prove either are unpermitted?
I ask these questions, because even as a sufferer, I can see from the outside it all seems very odd. I hope if more people involved in science ask these questions, we may be able to answer them clearly and unambiguously, and hopefully resolve and improve our situation.
Unfortunately, the PACE Trail makes me feel science has become more about proving an opinion or agenda, rather than a discovery for the truth. Is political medicine thriving in the 21st century?
I feel the truth about the Neurological M.E. first seen in 1955 has been untested and misdiagnosed out of existence, but this surely this doesn’t mean people are severely and hopelessly suffering with it today. If this is indeed what has occur, surely a full investigation by the authorities should be launched?
I fear how many have we lost over the last 60 years of ignorance? And surely this situation canâ€™t be permitted to continue?
Thank you again to Mr. Tuller, and to Mr. Racaniello too.
Love it -a brilliant piece
Excellent comment. Thank you for presenting so well the context in which ME/CFS has been mishandled for decades, the end result of which is patients being deprived of the medical care and respect they need and deserve. This has also prevented or derailed the pressing need for biomedical research into this disease. It makes me think of the saying that if you tell a lie, make it big enough, repeat it often, people will believe it. I think this is the quagmire we have been stuck in for a long time. I have to wonder what the motivation was for setting this tragedy in motion.
that scale is tragically funny.
a new ‘Tuberculosis Scale’ – Q1 “have you coughed or sneezed in the last few weeks ?”.
a new ‘ELMSRA scale’ (Ebola, Lupus, Multiple Sclerosis & Rheumatoid Arthritis) – Q1 “do you need to rest more ?”
that scale is tragically meaningless.
as relevant as a new ‘ELMSRA scale’ (Ebola, Lupus, Multiple Sclerosis & Rheumatoid Arthritis) – Q1 “do you need to rest more ?”
Peter White also provided input into the Swedish state
document, Fokusrapportâ€”Kroniskt TrÃ¶tthetssyndrom (2009). This report fulfills
criteria for research misconduct/fraud and is the Swedish state insurerâ€™s (â€œFKâ€â€™s)
bible used to deny social assistance, disability rights, and proper medical
care to people with ME/CFS in Sweden. The state courts back up whatever misinformation FK submits, ignore evidence and doctor statements that negate FKâ€™s misinformation, and then destroy court records shortly after they rule in favor of FK.
Additionally and according to Justice for Karina Hansen, Peter White also provided input into the Danish stateâ€™s abuse of ME patient, Karina Hansen. Denmarkâ€™s Hansen and the USâ€™ Justina Pelletier were seized by their respective states within two days of one another (in 2013), and while Pelletier is now long since free, Hansen remains imprisoned and denied the right to see her family or them her.
The proverbial keys to Hansenâ€™s literal cell are held by Danish psychiatrist Per Fink and his work, according to Danish physician Stig Gerdes, has received millions in funding from TryghedsGruppen of which the Scandinavian-wide insurer Tryg is a subsidiary. (Note too that according to Justice for Karina Hansen, Hansen’s state-appointed guardian is the same police chief who provided Fink with the armed police who forcefully took Hansen from her home.)
Consider that American-Dane Rick Steele has said,â€œThe common endpoint for these syndromes [â€œmedically unexplained syndromesâ€, described as including GWS, CFS PVS, etc.] is a disability pension. The enormity of this problem boggles the mind. Merely supporting this group of patients financially rivals half of the public outlays for health care or social benefits in northern European countries…”
And now–just as Swedish leaders admit to being out of money–politicians in the Swedish county of VG have voted to close an ME biomedical research clinic and redefine ME as a psychological illness to be diagnosed and â€œtreatedâ€ according to Finkâ€™s model.
Remember too that â€œthis group of patientsâ€ is made up primarily of women. And remember too that several decades ago, finances (perhaps too coupled with a culture of conformity and Jante rules) motivated Scandinaviaâ€™s high rates of lobotomizing women.
US psychiatrist Elliot Valenstein said in 1988: “When I began to summarize the factors responsible for the proliferation of lobotomy it became evident that all of them still influence the practice of medicine… desperate patients.. unreliable claims of cures.. flawed data… desire for “name and fame.”…media… Economic pressures… Competition between medical specialties.. and physicians and hospital administrators continue to search for new applications for new procedures once the staff and facilities
are in place. It is even possible to argue that some of the factors that shaped
the early history of lobotomy are more influential today..”
It seems that the environment which fostered lobotomy is
very similar to the environment which fosters CBT/GET today. And cash-strapped
politicians and ethics-deficient medical persons seem quite happy, now just as
then, to build their livelihoods upon human rights violations*– a decades-long
nightmare and narrative well-framed by the thirty-six stratagems. To how many
countries does White and co.â€™s influence extend?
(*The European Court of Human Rights states that member
states have a positive obligation to protect their citizens from harm. ME-targeted
CBT/GET = known harm = ECHR violation.)
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I doubt they wonder. It’s clear they’re trying to manipulate the situation, which indicates that their confusion is feigned.
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