Virology Blog today published an open letter from six leading scientists calling on The Lancet to seek an independent re-analysis of data from the controversial PACE trial.
The Lancet published the first PACE trial paper in 2011, which examined psychological and exercise therapies aimed at getting chronic fatigue syndrome patients more active and was based on a “deconditioning” model of the illness. The authors claimed that the therapies had been effective in a substantial proportion of patients in the study.
An accompanying Lancet commentary stated that these patients had “recovered” and the widespread media coverage of the claim helped make the £5 million trial enormously influential in how chronic fatigue syndrome was perceived by the public, clinicians and researchers.
The six scientists who wrote the open letter say that “the PACE authors reviewed this commentary before publication.”
The scientists, all professors, are world-famous geneticist Ronald Davis, whose son is gravely ill with ME/CFS; immunologist Jonathan Edwards of University College London; psychologist Leonard Jason of DePaul University; epidemiologist Arthur Reingold of University of California, Berkeley; and biostatistician Bruce Levin and microbiologist Vincent Racaniello, both of Columbia University.
The group describe PACE as suffering from “major flaws that have raised serious concerns about the validity, reliability and integrity of the findings,” and say that “the patient and advocacy communities have known this for years.”
The letter condemns a series of serious faults in the trial, including thresholds for clinical effectiveness that were worse than those required for trial entry; the provision during the trial to patients of materials praising the authors’ favoured treatments; the changing of analytic methods partway through the trial and the refusal to provide data to assess their impact; the dismissal of objective findings that indicated the failure of the therapies; and violation of the Declaration of Helsinki, by failing to inform study participants of conflicts of interest due to the principal investigators’ insurance industry links.
The letter ends by urging The Lancet to “seek an independent re-analysis of the individual-level PACE trial data, with appropriate sensitivity analyses, from highly respected reviewers with extensive expertise in statistics and study design. The reviewers should be from outside the U.K. and outside the domains of psychiatry and psychological medicine. They should also be completely independent of, and have no conflicts of interests involving, the PACE investigators and the funders of the trial.”
The letter comes amid mounting criticism of PACE from many quarters, beginning in October with a detailed exposé of the trial by journalist and public health expert Dr. David Tuller. Other blogs condemning the trial swiftly followed from well-known psychologists Professor James Coyne (here) and Professor Keith Laws (here).
A patient-led petition calling on The Lancet and Psychological Medicine to retract misleading claims made in the PACE trial, and for the authors to release data allowing the originally-specified analyses to be performed, has almost reached its target of 10,000 signatures in only two weeks.