MIST Investigator to Face UK Fitness-to-Practice Hearing Over Trial Misconduct

Shelley Wood

September 24, 2012

September 21, 2012 (Manchester, United Kingdom) — One of the coprincipal investigators for the controversial Migraine Intervention with STARflex Technology (MIST) trial will face a fitness-to-practice hearing by the UK Medical Practitioners Tribunal Service for his conduct related to the trial, heartwire has learned.

As previously reported by heartwire , Dr Andrew Dowson (Kings College Hospital, London, UK), a "headache specialist," was listed as lead author of the MIST trial when it was published in Circulation in 2008 [1]. The other principal investigator for the study, Dr Peter Wilmshurst (Royal Shrewsbury Hospital, UK), refused to sign off on the MIST paper in part because he was never given full access to the trial data. He also protested the fact that the Circulation paper made no mention of a second echo review that the trial sponsor had, in fact, asked him to conduct.

One MIST investigator, Dr Michael Mullen (Royal Brompton Hospital, London, UK) told heartwire in 2009 that Wilmshurst's review was "totally unsafe" and that it "would have been wrong to include it in the manuscript." Wilmshurst has kept emails indicating that it was Mullen himself who originally recommended to the sponsor that Wilmshurst conduct a review of all MIST echocardiograms. Wilmshurst's echo review, never published, pointed to a higher residual shunt rate than the 6% reported in the MIST manuscript.

NMT Medical, the trial sponsor, subsequently sued Wilmshurst over concerns he voiced to heartwire about the trial, and at the TCT 2007 meeting; the lawsuit was dropped when NMT went bankrupt in 2011.

Wilmshurst, who took his concerns about MIST's management to the General Medical Council (GMC), is also urging the editors of Circulation to issue a more complete correction to the paper. (A first correction printed in 2009 did not, he says, go far enough [2].) Specifically, Wilmshurst points out that a vice president at NMT helped draft the paper, but is not listed as an author or contributor, while a physician who died before the trial got underway is among the listed authors. Wilmshurst also points out that Dowson had previously owned shares of NMT Medical that were not disclosed to the trial's Multicentre Research Ethics Committee (MREC) or in the subsequent manuscript. In fact, Dowson acknowledged during his TCT presentation that he had received funds from NMT; NMT vice president and chief financial officer Richard Davis had estimated to heartwire that up to 10 investigators or steering committee members had received consulting fees from the company. Both the Circulation manuscript and subsequent correction state that only two study authors--Mullen and Dr David Hildick-Smith (Brighton and Sussex University Hospitals NHS Trust, UK)--had ownership interests in NMT Medical and other payments, but that the remaining authors reported no disclosures.

Both authorship and financial conflicts are among the misconduct questions deemed appropriate for review by the GMC panel, as are Dowson's false/misleading reports of MIST outcomes in presentations, abstracts, and publications, and his failure to adequately explain to Shrewsbury site investigators--including Wilmshurst--why they were suspended from the trial.

NMT's Davis had previously told heartwire that Wilmshurst was removed from the trial for committing "protocol violations and violations of the investigator's agreement." The chief executive for the clinical research organization that coordinated MIST has since confirmed to Wilmshurst by email, however, that there was no record of any protocol violation committed by him during the course of the trial.

The American Heart Association press office recently issued a statement saying that it will consider "any new relevant substantiated information about the situation and to cooperate with any investigating body," and that it, in fact, responded to questions from the GMC in March and April 2011.

The decision to refer Dowson to the fitness-to-practice panel was the result of a review by a medical and lay-case examiner, both senior staff at the GMC. No date has been set for the hearing.