Trial By Error: Do All Clinical Trial Experts Love PACE?

By David Tuller, DrPH

Professor Michael Sharpe blocked me on Twitter many weeks ago but apparently can’t restrain himself from tweeting at me again. Maybe I’ve gotten under his skin.

Yesterday he tweeted what must have felt to him like a slam-dunk question: He wanted to know how many clinical trials I have conducted. The answer is none. But I don’t need to be a clinical trial expert to know that it is impossible to be recovered (or within normal range, per The Lancet) and disabled simultaneously on a primary measure, as happened in PACE. I don’t need to be a clinical trial expert to know that you can’t publish newsletters in which you promote therapies under investigation as already proven to be effective.

Like previous responses to criticism, Professor Sharpe’s challenge has nothing to do with the concerns raised about PACE. I have never positioned myself as a clinical trial expert, so whether I have ever run a clinical trial is irrelevant. I have always made clear that I am a journalist with an interdisciplinary public health doctorate from Berkeley. (Or a public health academic with a journalism background. Whatever.) I have vetted my claims about PACE with many clinical trial experts–including statisticians and epidemiologists at leading institutions. Without exception, they have found Professor Sharpe’s study to be a piece of crap.

Professor Sharpe himself triggered this recent exchange when he wrote, in his briefing for last month’s parliamentary hearing, that none of the public critics quoted in articles about PACE were clinical trial experts. For good measure, he added that such experts, including “the many peer reviewers of the paper when it was published in The Lancet,” regarded PACE as “a high quality trial.” The Lancet has never provided details about the peer review process. We also know that the paper was fast-tracked to publication, which would limit how many reviewers could possibly have scrutinized it. So it is hard to take Professor Sharpe’s comments here at face value.

In any event, it is perplexing that he would make such a blatantly false statement about the long roster of distinguished PACE critics. Bruce Levin, a biostatistics professor at Columbia, called aspects of PACE the height of clinical trial amateurism. Arthur Reingold, Berkeley’s head of epidemiology (and co-leader of the Center for Global Public Health, my home base), said that “an independent review of the trial conducted by experts not involved in the design or conduct of the study would seem to be very much in order. Jonathan Edwards, a professor emeritus from University College London, called PACE a mass of uninterpretability. All three men are certainly clinical trial experts.

In a tweet about Professor Sharpe’s briefing document, I noted that the claim that no critics were clinical trial experts was untrue. In his new tweet at me, which I saw yesterday on a patient forum, Professor Sharpe touted his 25 years doing trials with leading trialists and statsticians [sic] and asked about my own clinical trial experience. I don’t care how many years Professor Sharpe has worked with leading trialists and statisticians. Their collective wisdom didn’t stop him and his colleagues from publishing papers in which 13% of participants had met a primary outcome threshold at baseline. In The Lancet, that outcome was called being within normal range for physical function. In Psychological Medicine, it was called being recovered for physical function.

Professor Sharpe has never explained how it is possible to be simultaneously disabled and recovered (or “within normal range”) on the same measure, or why such participants were in the study in the first place. This and other anomalies rendered the reported PACE findings uninterpretable, at least from the perspective of dozens of experts who have signed open letters to The Lancet and Psychological Medicine. Given that some participants had met outcome thresholds at baseline, it is disturbing that the investigators did not reveal this salient fact in their published papers. That they chose not to disclose key information raises further questions–not just about their competence but about their scientific integrity.

Professor Sharpe is free to disagree. But as his briefing to Carol Monaghan MP made clear, he still has no acceptable answers to the concerns about PACE, he simply repeats versions of defenses that he and his colleagues have presented before. For example, he dismisses as “nonsense” the idea that any PACE participants were recovered at baseline. But that’s a straw person argument. No serious critics, as far as I know, have claimed that participants in PACE were fully recovered–that is, “recovered” on all four recovery criteria–at baseline. They have argued that 13 % were recovered or had already achieved the recovery threshold at baseline for the specific outcome of self-reported physical function. That is true, and it would be an unacceptable feature in any trial.

In short, Professor Sharpe appears unable to grasp how others could possibly view his beloved study as the garbage heap it really is. In this, he resembles his colleague Sir Simon Wessely, who recently scored an own goal when he invited an old buddy into the PACE debate. The invitee, American lawyer and commentator Mike Godwin, reviewed the PACE trial and then pronounced it so profoundly flawed that it cannot be trusted.”

In happier days, Professor Sharpe and his colleagues were successfully able to portray critics, most of whom were patients, as hysterical and/or anti-scientific zealots. That strategy no longer works, now that so many members of the international scientific community have rejected the claims of the CBT/GET ideological brigades. Professor Sharpe’s apparent fallback stance, that clinical trial experts all love PACE and that none of the critics are clinical trial experts, is obviously a non-starter. For reasons that remain a mystery, he continues to damage his already damaged credibility by disseminating this sort of transparently bogus defense.

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