In 2008, our journal published a phase 2 randomised controlled trial of a new medicine. In 2011, the regulatory authority in the country where the study was performed decided to undertake routine monitoring of completed studies and this trial was selected for random inspection. The author informed the journal of the inspection and provided a translation of the report (independently verified as accurate by our journal).
The following concerns were raised by the regulatory authorities:
(1) There was no medical involvement in the process for informed consent, which was delegated to a non-medical practitioner. The country’s regulations require that a medical practitioner informs a participant and confirms this. The local ethics committee has been informed by the regulator about this lapse.
(2) The integrity of blinding was questioned in an earlier inspection in 2007 and because of comments about the treatment’s efficacy and side effects by one of the investigators while the trial was underway.
(3) The recording and assessment of adverse events was incomplete and the inspectors felt that the table of adverse events published in our journal did not reflect the clinical records for product safety.
The manuscript had two rounds of peer-review (seven reviews by four clinicians and a statistician). The only point of relevance to the above concerns was the comment that “the main weakness of the study is inadequate data on safety and adverse effects (in part unsurprising as this was a proof of efficacy study) and a rather overly positive presentation of the data”. The manuscript was revised and re-reviewed by this reviewer and a statistician; both were satisfied that the points had been addressed in the revision. After publication of the research article, our journal published two letters as correspondence. In one, the possibility of certain adverse events was raised, to which the authors replied that these had not been observed.
The authors have submitted a correction that states incorrect instructions by the contract research organisation resulted in under-reporting of adverse events for headache, migraine, stress and depression in people who had experienced these conditions before enrolling in the trial. They also state that comments about the medicine made to local media were based on another study. The editors are concerned that taken in their totality, the issues raised by the regulator question the soundness of our publication. As we gather more information and await the ethics committee’s decision about the process for informed consent, the editors would be interested in learning what actions COPE would recommend.
The Forum advised that if the editor cannot decide what to do, a statement of concern could be published in the interim. If the editor thinks the methodology was insufficient (to detect side effects), then he should consider retracting the paper. Clearly a correction needs to be done. The expression of concern should mention the fact that the table of side effects may not be correct, in addition to the issue relating to consent. The editor told the Forum that he does not believe there has been any misconduct and the authors wrote the paper in good faith.
On a show of hands, nine people suggested that the editor should do an expression of concern detailing the chain of events. Only two people thought the paper should be retracted. Hence the consensus was that it would be appropriate to put a statement of concern on the paper.
The journal has received a letter from the author that responds to the expression of concern and the inspection report. At present, the precise wording is being negotiated with the author.
Update (September 2013):
The journal published an expression of concern and a letter from the authors that responded to the expression of concern and the inspection report. Although there was insufficient evidence to retract the publication, the editors felt that uncertainties about the study persisted and therefore decided that the expression of concern should remain part of the published record.