Edinburgh Skeptics in the Pub talk on PACE chronic fatigue trial

A skeptical look at the PACE chronic fatigue

trial

James C. Coyne, PhD.@CoyneoftheRealm

Special thanks Julie Rehmeyer. Without her gentle nudging,

I would not be in this fight. David Tuller. Tom Kindlon. The many sufferers of CFS, ME, and PVF

who are teaching me a lot of what I am trying to teach others.

Government orders release of PACE trial data

The Information Commissioner’s Office (ICO) has ordered Queen Mary University of London to release anonymized PACE trial data to an unnamed complainant. Queen Mary has 28 days to appeal the decision.

St. Nicholas Church open to all

Where did this come from?

About me

Have published over 350 articles. Over 35,000 citations to my work,

H-index = 84. Academic Editor at PLOS One. Promoter of Open Access,

PubMed Commons.

About me

Teacher of scientific writing and critical appraisal skills.

Critic of quality of the scientific literature and publication practices.

Blogger with Science-Based Medicine and PLOS’s Mind the Brain.

I live in Philadelphia.

I'm a skeptic.

Controversies are to be resolved by looking at the available evidence.

I’m skeptical about the quality of that evidence.

I don't think these are controversial statements.

Many positive findings in biomedicine and science are ultimately shown to be exaggerated or outright false.

There is a crisis in the trustworthiness of the scientific literature.

Evidence based is…

“Evidence-based” is too often an ill-gotten branding based on weak evidence generated by promoters of treatments who want us to ignore their conflicts of interest.

Unpicking dodgy claims, unpacking the evidence behind dodgy claims, isn’t a kind of nasty carping activity; it socially useful, but it’s also extremely valuable explanatory tool. Because real science is all about critically appraising the evidence for someone else’s position.

--Ben Goldacre

Targets of skepticismQuestionable research practices

(QRPs).

Questionable publication practices (QPPs).

Institutional agenda that promote, reward, and protect QRPs and QPPs.

Politics

Bad science is being published with exaggerations of its significance and without challenge. This can often only be understood with reference to politics.

Politics

Who gets into what publications and which forums.

Who can be critical and be heard.Who gets ignored.Who suffers retaliation and by

whom.

Developing Citizen-Scientists

Citizen-scientists are bombarded by dubious claims and need to develop the critical skills and resources to decide for themselves.

Journalists and the mediaNeed to

Serve as trusted sources to interpret scientific and biomedical claims.

Avoid churnalism. Filter exaggerated claims of investigators and

their University press offices. Introduce independent evaluations from

experts who are not invested in particular claims.

My activism Identify and rectify questionable research

practices.

Promote open access and data sharing.

Strengthen post-publication peer review.

Develop innovative crowd-sourced post-publication peer-review such as Pubmed Commons and PubPeer.

My activism Identify, challenge, and change editorial

practices that make it easy to publish bad science and hard to do anything about it, once it is published.

Get corrections and erratum statements for undisclosed conflicts of interest.

Request retractions.

My skeptical engagementwith positive

psychology of cancer care

I Took on Claims Psychotherapy

Promoted the Survival of Cancer Patients...

“Fighting Spirit?”

Attitude Doesn’t Matter for Survival Time in Cancer

Patients.

This, however, was not the case with Charles.”

Charles’ friends saw that same lack of fighting spirit. “They say in times of great trial,a man’s true colors show,” said best friend Larry Ahrens, summing up the feelings of those who knew the man. “And, in Charles’ case, he had a yellow streak a mile wide.”

Loved Ones Recall Man’s Cowardly Battle With Cancer“It’s rare that you see someone give up that quickly and completely,” Dr. Wohlpert said. “Cancer is a powerful disease, but most people can, at the very least, delay its spread by maintaining a positive outlook and mental attitude.

Barbara Ehrenreich and the Negateers

A liberationist view Having a fighting spirit

or being positive does not matter for disease outcomes.

A full range of patient styles of coping need to be accommodated in cancer care.

A Lancet study of CBT for Psychosis article and the British Psychological Association’s Understanding Psychosis and Schizophrenia came onto my radar.

Prof Tony Morrison, director of the psychosis research unit at Greater Manchester West Mental Health Foundation Trust, said: "We found cognitive behavioural therapy did reduce symptoms and it also improved personal and social function and we demonstrated very comprehensively it is a safe and effective therapy.“

It worked in 46% of patients, approximately the same as for antipsychotics - although a head-to-head study directly comparing the two therapies has not been made.

A skeptical look at the Lancet CBT study

The study retained fewer participants receiving cognitive therapy at the end of the study than authors.

The comparison treatment was ill-defined, but for some patients

meant no treatment because kicked out of routine care for refusing medication.

A substantial proportion of patients assigned to cognitive therapy began taking antipsychotic medication by the end of the study.

There was no evidence that the response to cognitive therapy was comparable to that achieved with antipsychotic medication alone in clinical trials.

No evidence that less intensive, nonspecific supportive therapy would have achieved the same results as CBT.

Critique of a flawed Lancet study of CBT and its promotion

Challenging Oxford’s Psychiatry Department

Challenging UK Media

What is PACE? (Investigators answer)

This large-scale trial is the first in the world to compare effectiveness of 4 treatments currently available for people suffering from chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME). These are adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and standardised specialist medical care. All of the treatments offer ways for patients to deal with and improve the symptoms of CFS/ME and its effects on disability. The participants in the trial are randomly allocated to one of the treatments and then given a 12-month programme involving appointments with specialised doctors and, for three of the four treatment groups, therapists. Participants' progress is closely monitored by specially-trained research nurses or assistants. The 5-year trial will involve 600 participants, aged 18 and over, in Scotland and England. All have to be referred from the specialist hospital CFS/ME clinics involved in the trial and these are based in Edinburgh, Oxford and three London hospitals.

Bad science of PACE

Being badly mispresented by the investigators.

Going unchallenged. Uncritically passed on by journalists and the

media. With clear harm to patients. Murky politics about who can speak and who

is silenced.

What makes PACE long-term follow-up results uninterpretable?

Investigators ignored the finding of the follow up trial that they should have emphasized: Any differences between groups had evaporated during follow up period.

What makes PACE long-term follow-up results uninterpretable?

Investigators encouraged participants to freely switch treatments between the end of treatment they provided in the trial and subsequent follow-up.

Investigators attempted to influence participant reports of outcomes prior to enrollment even being completed.

What makes PACE long-term follow-up results uninterpretable?

Investigators analyzed follow-up data with respect to initial randomization, not the treatment patients received during follow-up.

Investigators used voodoo statistics to try to correct for loss of participants and crossover.

Keith Laws Dystopia Blog (1)Many patients initially dissatisfied with

their assignment to Standard Medical Care (SMC) and didn't find it credible.

Patients and their physicians likely to have been influenced by patients‘ initials dissatisfaction with SMC in deciding on treatment in the follow-up.

Keith Laws Dystopia Blog (2) Average group scores at follow-up are now from

a smorgasbord of PACE interventions, meaning that the group means lack... meaning!

GET is the only group not showing improvement during follow-up. Even with no additional therapy, both the SMC controls and the APT group improved, as indeed did CBT. The failure of GET patients to respond to adequate additional CBT therapy is curious.

So what? PACE investigators inappropriately attempted

to influence participants' reports of outcomes. PACE investigators allowed participants to

get other treatments in a way the results could no longer be analyzed as if from an randomized trial.

PACE investigators distorted interpretation of the results to make them look better than they were.

So what?

Essentially two prominent senior academics accuse the PACE investigators of serious mistakes in the conduct of a clinical trial and spinning so results appear to favor the interventions the investigators were invested in.

So? Principles by which we identified the serious

problems in conducting and reporting a clinical trial are non-controversial- Obvious to anyone who looks carefully.

That virtually no one else picked them up reflects badly on the editing and peer review at Lancet Psychiatry, as well as the commentary by Simon Wessely, and media portrayals of this trial.

Why QMUL should not appeal Withholding data no longer acceptable to a

scientific community and funding agencies committed to data sharing.

Withholding data in the context of criticism of the reporting of results looks like a cover-up.

Appealing the decision puts QMUL in a bad light: insisting on exceptional treatment and refusing to respond to criticism by producing relevant data.

What next for PACE and me?

Moral Equivalent Of War

From William James

Moral equivalent in the sense that other peacetime activities and priorities are harmonized in pursuit of goal as they would be in a war.

War is against practices and assumptions that guide them, not people.

My existing goals and activities refocused on Exposing more of the Bad Science (QRPs) of

PACE. Establish culpability of journal editors,

reviewers in Questionable Publication Practices (QPPs).

Educate media and journalists on responsibilities they have not exercised in reporting PACE.

Encourage use of PACE as example of QRPs, QPPs.

My existing goals and activities refocused on Expanding focus to QRPs, QPPs that have

maintained illusion that there is validity to psychosomatic model for treatment of ME, CFS, and PVS

Validate and legitimize what patients have been saying all along and bring them into conversation as credible citizen-scientists.

Identify and dismantle structure by which PACE investigators bullied and neutralized critics.

The story of PACE will be rewritten to Underscore necessity of strong

patient voice in design and conduct of clinical trials.

Mark turning point in use of language indicating greater respect for patient activism, healthy assertiveness, and self-determination.

Upcoming blog posts will be modest steps

To draw scientific community, especially junior scientists and trainees into noticing what was wrong about PACE in terms of design and conduct of research, reporting of results, silencing of legitimate patient voices, and the politics that allowed this to happen.

Auslander

Why it is important that I am an outsider to the British

establishment and to the patient community.

Charter of UK CFS/ME Research Collaborative states:

“3.2.3 Members will be required to sign a declaration that they will not take part in the harassment or abuse of researchers. Neither will they take part in orchestrated campaigns against those conducting peer-reviewed research.”

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