By David Tuller, DrPH
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Professors Peter White, Trudie Chalder and Michael Sharpe seem to have embarked on what could be called the PACE Rehabilitation Tour.
This is an apparent effort to salvage their reputations and save professional face now that the UK’s National Institute for Health and Care Excellence (NICE) has officially rescinded its previous recommendations for graded exercise therapy and cognitive behavior therapy as treatments for what the agency currently calls ME/CFS. It is also an effort by these professors to gain a foothold in the long Covid marketplace. They hope their crumbling GET/CBT treatment paradigm for ME/CFS can revive its fortunes in a post-coronavirus world.
Last week, HealthSense, a UK watchdog group formerly called HealthWatch, posted Professor White’s umpteenth defense of the £5.000,000 PACE trial, which he co-led with Professors Sharpe and Chalder. The trial purported to show that GET and CBT were effective treatments. Professor White’s article was a feeble response to a cogent HealthSense commentary by Caroline Struthers, a Senior EQUATOR Research Fellow at Oxford University (also a friend and colleague), called “It is not only drugs and devices that can harm.”
And yesterday, The Guardian published a letter from the PACE trio in response to a compelling personal account of long Covid from Ravi Veriah Jacques, a 23-year-old who has been disabled from the illness. In discussing ME/CFS, Veriah Jacques included information about the debunking of the PACE trial findings. He also mentioned the publication last fall by NICE of new clinical guidelines for the illness, which reversed the agency’s earlier position. (Apparently, the letter was in The Observer, The Guardian‘s Sunday sister paper, but it was published on The Guardian‘s website, so from my perspective that means it was published by The Guardian as well, whatever The Observer‘s editorial role.)
In their response, the PACE trio suggested that Veriah Jacques was “misinformed” about the trial. (This is their routine response to criticism—it is based on a misunderstanding or miscommunication or on mistaken assumptions or on the other person’s failure to have read the article in question.) They acknowledged that NICE no longer recommends the treatments. (The guidelines allow for CBT as supportive care.) Their counter-argument was that objections to the NICE decision were raised by four trade groups of doctors. Since these trade groups essentially serve as campaigners and lobbyists for advancing physicians’ professional and financial interests and preserving their status, their testimony is not necessarily convincing, especially when they argue against the evidence.
(In the UK, such trade groups are grandiosely referred to as “royal colleges.” The groups appear to believe, for unclear reasons, that they are owed some particular deference and should be seen as objective and above reproach in all matters.)
The PACE investigators ended their letter to The Guardian with an explicit appeal to extend their domain to long Covid. “CBT and GET may help some sufferers from long Covid but, unless we fund research to test them, we will never know for certain,” they write.
Let’s pause to reflect on that statement. It was clear from the start of the pandemic to anyone who was paying attention to this arena of activity that the long-term sequelae of Covid-19 would likely be the new frontier for the GET/CBT ideological brigades. Now here it is. They see research with long Covid patients as the means to revive the fortunes of the PACE approach.
A methodological and ethical disaster
It cannot be stated often enough that the PACE trial was a methodological and ethical disaster—a case of egregious research misconduct, in my opinion.
Its failures are now widely known. It has been taught in Berkeley graduate epidemiology seminars as a case study of how NOT to conduct a clinical trial. Its findings have been refuted effectively in a re-analysis in BMC Psychology. (I was a co-author.) A 2018 letter to The Lancet, signed by more than 100 experts from around the world, referenced the trial’s “unacceptable methodological lapses.” The letter triggered coverage in The Times and BMJ, disseminating news of international dismay about the PACE trial to the general public.
After years of having their study lauded as a “thing of beauty” (Professor Sir Simon Wessely) and “a great, great” trial (Professor Esther Crawley), Professor White and his colleagues appear to find it difficult to adjust to the new reality. Perhaps like President Trump, they are surrounded by like-minded believers who reinforce their biases and delusions. I’ve been rebutting their claims since 2015, so I’m not going to bother doing it again here.
Anyway, the PACE investigators’ admirable persistence can’t change the fact that the trial they are defending is indefensible on multiple levels. I want to highlight one issue that has been generally overlooked. They promised in their protocol to adhere to the Declaration of Helsinki—and they violated that promise. The Declaration of Helsinki, an international convention created to protect human research subjects, includes a mandate that investigators must disclose to trial participants “any possible conflicts of interest.”
Although the declaration has been revised over the years, this mandate was already part of the document at the start of the PACE trial. It is explicit and very clear. The phrase “any possible conflicts of interests” means what it says. There is little wiggle room.
The PACE trial was launched in 2005. At that time, the lead investigators had advisory and/or financial ties with leading insurance companies. For decades, they have told insurers that the treatments being tested in PACE could get people back to work. These links certainly should have fallen under anyone’s interpretation of “any possible conflicts of interests.”
However, the investigators failed to disclose these business interests to potential participants during the process of obtaining their consent for being in the trial. That means participants gave their consent without knowing key information—that the lead investigators had compelling reasons apart from scientific curiosity to prove that GET and CBT were effective.
In other words, the consent obtained from participants by the PACE investigators was not informed consent per their own promise to adhere to the Declaration of Helsinki. That everyone involved in research oversight in the UK has ignored this very, very serious issue is extremely disturbing. Despite all that money invested in PACE, no one bothered to ensure that the the lead investigators followed their own protocol promise to disclose “any possible conflicts of interest” to potential participants. And no one seems to care after-the-fact about this unexplained breach of an international human rights document. I have found it hard to understand this dereliction of responsibility when it comes to ensuring that human research subjects have been provided with all appropriate and required information.
The list of derelicts in this instance includes the Medical Research Council and the other funders, the research ethics committee or committees that approved the consent forms, the various trial-affiliated committees stuffed with allies of the PACE team, and the journals that published PACE results obtained without legitimate informed consent. And this violation of the Declaration of Helsinki is just one of the many problems with the trial.
Lancet editor Richard Horton, who presents himself as the scourge of bad science, has never acknowledged publicly that PACE was a debacle. He’s a very smart guy. He can’t possibly believe at this point that he was right to champion the 2011 paper.
Or maybe he does. We all have blind spots.
In any event, every day The Lancet does not address this embarrassment, it is failing to perform its basic function–safeguarding the medical literature and the public from crap.