Describes serious flaws in conduct and reporting of the PACE trial for chronic fatigue (ME/CFS) and why the data should be released for reanalysis

1. A skeptical look at
the PACE chronic
fatigue trial
James C. Coyne, PhD.
@CoyneoftheRealm

2. 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.

3. 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.

4. St. Nicholas Church open to all

6. Where did this come from?

7. 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.

8. 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.

9. I live in Philadelphia.

10. I'm a skeptic.
 Controversies are to be resolved
by looking at the available
evidence.
 I’m skeptical about the quality of
that evidence.

11. 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.

12. 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.

13. 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

14. Targets of skepticism
 Questionable research practices
(QRPs).
 Questionable publication practices
(QPPs).
 Institutional agenda that promote,
reward, and protect QRPs and QPPs.

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

16. 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.

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

18. Journalists and the media
Need 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.

19. 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.

20. 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.

21. My skeptical
engagement
with positive
psychology of cancer
care

22. I Took on Claims
Psychotherapy
Promoted the Survival
of Cancer Patients...

24. “Fighting Spirit?”
Attitude Doesn’t Matter for
Survival Time in Cancer
Patients.

25. 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.

26. Barbara Ehrenreich and the
Negateers

27. 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.

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

29. 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.

30. 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.

31. Critique of a flawed Lancet
study of CBT and its
promotion

32. Challenging Oxford’s
Psychiatry Department

33. Challenging UK Media

34. 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.

35. 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.

36. 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.

37. 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.

38. 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.

39. 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.

40. 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.

41. 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.

42. 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.

43. 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.

44. 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.

45. What next for PACE and
me?

46. Moral Equivalent Of
War

47. 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.

48. 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.

49. 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.

50. 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.

51. 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.

52. Auslander
Why it is important that I am an
outsider to the British
establishment and to the patient
community.

53. 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.”

54. Now live
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@CoyneoftheRealm