Scientists Demand Transparency on PACE Trial

Scientists Demand Transparency on PACE Trial

Queen Mary has been accused of “defending the indefensible” after they rejected requests to share the raw data of a controversial trial for the treatment of Chronic Fatigue Syndrome

PACE, a five year long trial instigated by researchers from QMUL and Kings College London, was the first to test the effectiveness of the four main treatments available for the condition. Adaptive pacing therapy, Cognitive Behavioural Therapy (CBT), graded exercise therapy, and standardised specialist medical care are all currently used to reduce symptoms in sufferers.

It is estimated that a quarter of a million people in the UK suffer from myalgic encephalomyelitis (ME) otherwise known as Chronic Fatigue Syndrome (CFS), but its causes are unclear.

In 2011, the medical journal The Lancet published the results of the trial, concluding that CBT and graded exercise therapy can be effective in treating CFS. A report by The Lancet the following year stated that “comparing the four treatments using a health care perspective, CBT had the greatest probability of being the most cost effective.”

However, the findings have been subject to ongoing criticism, as they contradict patient organisations’ claims that whereas patients found specialised medical care to be helpful, they believed CBT could be detrimental to recovery.

It is estimated that since 2011, some 150 requests have been made under the Freedom of Information Act (FOIA) to receive raw data from the trial. QMUL refused the requests on the grounds that they were “vexatious.”

In December 2015, four leading scientists, Professor Ronald Davis, Bruce Levin, Vincent Racaniello, and David Tuller wrote an open letter adding further pressure for transparency on the trial. Davis and his colleagues said they “assure Queen Mary University of London that the request is not “vexatious,” as defined in the Freedom of Information law, nor is it meant to harass. Our motive is easy to explain: We are extremely concerned that the PACE studies have made claims of success and “recovery” that appear to go beyond the evidence produced in the trial. We are seeking the trial data based solely on our desire to get at the truth of the matter.”

Ex BMJ editor Richard Smith expressed his objection to the handling of PACE in an article for the journal: “QMUL and Kings’ are making a mistake. As someone who has been abused by people who care passionately about chronic fatigue syndrome, I can sympathise with their decision, but I still think it’s wrong.”

He went on to say that he believed Kings and Queen Mary are “going against basic scientific principles.”

Investigators from QMUL have responded by releasing a statement stressing the need for patient confidentiality. “We have received many requests for access to individual patient data collected in the PACE trial.”

“We are, however, also concerned for the rights and welfare of trial participants. Participants did not give consent to the public release of their data when they entered the trial. In particular, we are concerned to ensure that there is no risk of misuse of the data such as through inadvertent personal identification.”

“We are currently seeking further ethical and scientific advice, as well as the advice of patients, on how best to provide independent decisions about appropriate access to relevant data in a way that balances the rights of trial participants, and future progress of the trial analysis and follow up, with the public interest in releasing trial data.”


Section: News

There are 15 comments for this article
  1. TSS at 3:11 pm

    The study was funded by £5 million of public money, yet the authors refuse to release the data and every request for them to do so is loudly dismissed as vexatious.

    What are they hiding? Could it be what every myalgic encephalomyelits sufferer already knows, that graded exercise worsens the symptoms of their neurological illness – often permanently?

    How could participants who had deteriorated on the trial be considered recovered? Why was the recovery criteria changed during the trial?

    Why was the only objective measurement of results withdrawn during the trial?

    http://www.sciforschenonline.org/journals/neurology/JNNB-2-124.php

    Why were participants not told that Prof Peter White works for a private health insurance company, and for the DWP?

    Why was this the only medical trial ever part funded by the DWP?

  2. Graham McPhee at 9:17 pm

    Thank you for publishing a clear and well-measured account of the situation. As a person who has ME, I have found it frustratingly difficult to get people to really look at the problems, and regret the way that abuse by a tiny minority of the quarter-of-a-million sufferers has been used to deflect genuine scientific concerns.

    There are a couple of updates to add to your account though: the open letter to The Lancet was signed by 4 leading scientists, but now there are 42 doctors, researchers and scientists from around the world behind it. (There are also 28 ME/CFS charities and organizations calling for the release of the data.)

    It is a bit misleading when the PACE team or QMUL claim 150 requests under the FoI Act though: here is the quote from the Information Commissioner’s Office “Since March 2011, following the publication of the trial results in the Lancet, QMUL has received 35 requests for information about the trial. These requests have askedfor 160 pieces of information. QMUL states that it has never experienced such quantities of requests on any one subject previously or since and cannot see an end to these requests.” Some of these 35 requests were re-edited requests, responding to the objections raised.

    If you would like to read an analysis of why there are so many concerns about the trial, then I can recommend the recent article in stats.org by Prof. Rebecca Goldin (http://www.stats.org/pace-research-sparked-patient-rebellion-challenged-medicine/)

  3. inexplicable at 3:37 am

    The authors of the PACE Trial follow-up at 2.5yrs, found a NULL EFFECT.

    “There was little evidence of differences in outcomes between the randomised treatment groups at long-term follow-up.”

    http://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(15)00317-X/abstract

    Professor Rebecca Goldin, director of Stats.org USA (American Statistical Association), has critiqued the PACE Trial study design :

    http://www.stats.org/pace-research-sparked-patient-rebellion-challenged-medicine/

  4. Lyn Gillame at 9:20 am

    You might be unaware:
    The FOI commissioner has already ruled that this information can be safely released in an anonymised form that would not breach the rules of patient confidentiality. QMUL are appealing that decision.
    28 patient support agencies from around the world have written to QMUL requesting the data be released for fully independent scrutiny.

  5. Ann at 9:52 am

    On behalf of all 250,000 sufferers, in the UK alone, I would like to say a big thank you for this article, as this data must be released in order to have transparency. It has been shown to be a flawed trial from start to finish and only by releasing the data will we get the correct treatment.

    Of course the patients anonymity must be respected, but from my understanding they were not told the full facts before entering the trial and the data can be released, without any personal information being revealed.

    US Scientists and others from around the world have open access to their trials, which promotes cooperation between them and patients, who know CFS more than most doctors. This is the quickest way to find the causes and ultimately a cure for these patients.

    Millions could be saved by governments, if patients can be cured by getting them back into schooling and work. Please help to relieve the suffering of the 25,000 who are very severely ill and were excluded from the trial. They have no treatment to relieve their suffering, just as Professor Ron Davis knows only too well.

    Also millions could be saved for patients who suffer primary mental health problems instead of on patients who need to be diagnosed correctly. Many are misdiagnosed ( up to 50%) and suffer for years without the proper care.

  6. Steve at 12:28 pm

    Release the data! The “researchers” behind this badly done study have offered only illogical reasons for not doing so. The data can be released without revealing characteristics about any of the participants. In fact, the data was given to a handful of other “scientists” not related to the study but who have a bias toward the study being “proven” correct – therefore, the researchers who designed this study have already released data to that select group – they have a moral obligation to now release it to the science community at large, to those withOUT bias. They are afraid to do so because it will reveal that the study FAILED.

  7. andy at 1:04 pm

    The pace trial was compared to a ship by a psychiatrist saying it wasn’t very safe a bit dodgy but still sea worthy .
    Everyone with ME CFS knows which ship he was referring as he enjoys pressing buttons fiddling wi
    The pace trial was compared to a ship by an award winning psychiatrist saying it wasn’t very safe a bit dodgy but still sea worthy . Everyone with ME CFS know which ship he was referring he enjoys pressing buttons fiddling with the steering and sailing to close to the wind .
    Queen Marys is worried about patient confidentiality like they were worried about the same vulnerable patients their pace trial creators slag off in the press as vile militants with guns .
    you can’t have us both evil and victims then stuff us up a funnel
    .
    CBT AND GET are treated as being cures and the only treatment for ME CFS in newspaper headlines such as exercise is best for ME CFS but when that is questioned or put under the spotlight its said only be appropriate for a minority of less severely ill me cfs patient’s .
    why are your psychiatrists locking up severely ill patient’s then and forcing CBT and GET onto them in locked psychiatric wards if it doesn’t help everyone the excuses can be used in reverse
    Patient confidentiality is a good excuse to patch up the pace trial titanic ship with is dodgy steering
    It barely floats above the credibility line.
    the pace trial results need released so that everyone can watch it sink it isn’t science its abuse and abuse and trauma supposedly causes ME CFS.

    I don’t want abuse and trauma give the pace trial to scientist’s who want it or are you just in this pace trial thing along with the rest of queen Marys to keep us in a sinking rat trap
    i have Aspergers AND ME CFS doctors also get ME CFS and scientists want the data released they dont have Aspergers . whats the problem then they are well educated normal people and well respected release the pace trial.

  8. Janet MacLennan at 1:37 pm

    Thanks for this article. As someone with ME/CFS who is currently undergoing Graded Exercise Therapy, the treatment that is actually most controversial amongst the ME/CFS community, I am left feeling deeply conflicted by my treatment- my physio assures me that it will benefit me, but this is countered by the experience of thousands of people with ME/CFS who feel their condition has been made worse by it.
    All I wish for is clarity.

  9. andy at 1:53 pm

    sorry for repeating the beginning what do you expect how do you educate the educated who aren’t bothering to educate themselves

  10. Anne Keith at 3:18 pm

    QMUL and PACE authors’ arguments against releasing patient data have many glaring flaws. Let me point out just a few.

    The first has already been pointed underlined last fall by the judge who ordered the release of data which QMUL is so desperately fighting. It is that properly anonymized data cannot lead back to a patient; it probably couldn’t even be identified by a patient as his/her own. Names, addresses, and other identifying information are removed before release. What is left is series of numbers, yes/no answers, etc., reading something like “pt. 234: 9, no, 52 meters, 14, yes, improved.” This kind of data does NOT cause someone to smack their head and say, “Ah ha, the neighbor across the way!”

    The second glaring flaw is the idea that any patient would volunteer for any medical study, much less “the definitive study” of hotly contested treatment theories, and not expect that data to be widely disseminated. The entire point of participating in a published medical trial is to further knowledge, which means sharing the acquired information. Such data sharing is becoming the norm, not the exception. Furthermore, authors voluntarily chose to publish in PLOS, which requires open data upon demand as a condition of publishing. Should one conclude that the prestige of being published in PLOS offset the authors’ deep, deep scruples regarding their poor, too-easily “outed” patients?

    Even if the reader somehow swallows that last sentence, the real regard the PACE author had for participants is shown by their highly unethical actions. All human studies legally require detailed informed consent documents, which spell out what the authors will and will not do and the risks therein. The PACE authors agreed to a set of rules known as the Helsinki Declaration which, among other things, requires that all conflicts of interest be disclosed to the patient prior to the study. Such a disclosure is standard practice. The authors failed to do this and not in an insubstantial manner. The authors had previously consulted for insurance companies which had openly sought to find ways to deny millions of pounds in benefits to ME/CFS patients. It was reasonable to assume these authors would do so again in the future and, in fact, they have. PACE’s results are already being manipulated for this purpose. Who would possibly say that being identified as a study participant holds a candle to be being denied decades of needed financial and medical benefits? Where are the authors’ crocodile tears for patients’ rights about this serious breach of informed consent? Entirely missing.

    Furthermore, PACE authors say they just are respecting patients’ wishes by withholding data. Nothing could be further from the truth. Participants, patient and patient groups all over the world have clamored for this data. What about the voices of those who object, especially the actual participants’? You can hear the crickets.

    Finally, there is a question of irreversible harms. ME/CFS is, despite how it is often portrayed in the press, extremely disabling and sometimes even deadly. The reason the British government put up so much money was to study whether or not the proposed treatments were effective and whether or not they caused harms. To the first question, despite the trumpeting of the authors, even the meager data disclosed shows definitively these treatments are ineffective after even a modest length of time. Whether or not the study showed if treatments cause harm is hidden by poor study design and blocked data. The vast majority (75% or more, according to many surveys) of patients who have been treated with the promoted treatments say it has caused them harm, often significant and permanent. NO drug with that statistic would continue to be used. There are estimated to be 17 million patients worldwide with this disease, most unable to work and many house or bedbound. It is utterly reprehensible, completely irresponsible to claim to have data regarding the matter of safety and refused to release it.

    The authors accepted public funds for this study. They failed to disclose very pertinent conflicts of interest. They continue to champion treatments patients say sicken them, which objective medical tests now show do at least short-term damage. They ignore scores of grave methodological and scientific questions which have been raised. They appear to utterly fail to “do no harm.” Honestly, how can one NOT question their motives?

    QMUL, it is time you fulfill your responsibilities to the public and stop shielding PACE authors who clearly care nothing about patients, science, or medical truth. It is time to stop opposing the release of data and to begin to demand its release instead. Will you finally do so?

  11. Lidia Thompson at 11:12 pm

    Rebecca Goldin is Professor of Mathematical Sciences at George Mason University and Director of STATS.org. She is well-acquainted with medical trial protocols. She writes, “The (PACE Trial) study is under increasing scrutiny by scientists and science writers about whether its conclusions are valid. The question of how all this happened and how the criticism is being handled have sent shockwaves through medicine”.
    She added, “The results from PACE… have been published in prestigious journals and influenced public health recommendations around the world; and yet, unraveling this design and the characterization of the outcomes of the trial has left many people, including me, unsure this study has any scientific merit. How did the study go unchallenged for five years?”

    Here is her critique of the study:
    http://www.stats.org/pace-research-sparked-patient-rebellion-challenged-medicine/

    Why are patients so angry?
    Because those of us who have genuine ME/CFS (and not depression or some sort of general fatigue) have what the biomedical field describe as post-exertional malaise (PEM), the hallmark feature of this disease. This post exertional amplification of symptoms in ME/CFS patients, is as a result of damage to the aerobic energy system and means that it is utterly counter productive to try to use aerobic exercise, such as is sometimes encouraged in graded exercise therapy (GET), to improve health:

    Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome: http://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-12-20

    Inability of myalgic encephalomyelitis/chronic fatigue syndrome patients to reproduce VO2peak indicates functional impairment:
    http://translational-medicine.biomedcentral.com/articles/10.1186/1479-5876-12-104

    Indeed a recent report from the ME Association indicates that 74% of patients have indicated that GET made their symptoms worse:
    http://www.meassociation.org.uk/how-you-can-help/introduction-to-our-cbt-get-and-pacing-report/

    It is therefore of the utmost importance that the PACE Trial results are re-evaluated as many patients are currently getting the wrong treatment – treatment which is causing their disease to get worse.

  12. Lara at 6:04 pm

    Thank you very much for writing about this, and writing about it objectively and fairly! We don’t always get much of that.

    As an M.E. sufferer I appreciate you taking this seriously, and being transparent journalists. I’m only 24 and I’ve been sick since I was 17. I managed to get my law degree mostly from my bed, but am still unable to work or leave my house more than once every 2 weeks. I tried both GET and a form of CBT, GET made me worse and CBT helped my mindset to cope with the illness, but did not improve any symptoms. We need effective treatment, not treatment that doesn’t work and when it doesn’t work you are told it was because you didn’t try hard enough or weren’t positive enough. Too much victim blaming going on in this field.

    So again thank you!

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