We had a paper submitted reporting results of a randomized trial. The trial seemed to look at immune responses in lung fluid in participants receiving either a particular vaccine or placebo. We got a copy of the trial protocol before going to peer review as per our normal editorial policy, and made sure the trial was registered.
One reviewer pointed out major discrepancies (principally in sample size and outcome measures) between the trial report, and the protocol document and registration record. We asked the authors to revise and to explain why these discrepancies had happenned. The authors explained that that the protocol and registry record originally sent were actually for a totally different study, and they had now separately registered the trial reported here. They also sent a new protocol document apparently now corresponding to the study in question.
This revised paper then went to re-review and the reviewers were happy. However in house journal staff were still worried about differences between the new protocol and the study reported in the paper. The new protocol did not seem to describe the conduct of a trial but rather a case-control study. There were also differences in the number and timing of invasive procedures being used to assess outcomes in the study, and there seemed to be more of these in the study report than in the protocol.
We went back to the authors to say we were very concerned about this and would need their explanation. If they weren't able to provide an explanation then we would alert their ethics committee.
The authors wrote back to us, cc'ing the heads of their two research ethics committees, to say that indeed, the manuscript did not match the two different protocols they sent us. They explained that there was a fault in the manuscript and not in the work carried out. They explained that the paper they sent us did not describe a single study but rather parts of 4 different approved studies taking place over the same time frame and being carried out on overlapping study populations. They then detailed aspects of these studies and explained that the different interventions, assessment of outcomes, etc, that were reported in the paper indeed corresponded to sections of approved protocols. (Although, no single protocol explained all of the aspects reported in the paper).
At this point we are very concerned about the following things:
Individual participants being recruited into many different ongoing studies - were the ethics committees aware of this and is it wise?
Selective reporting of findings. Presumably the main outcomes for the protocol describing a trial (ie the one involving randomization to vaccine or placebo) have gone unreported. Why? We are also very worried about validity of the data and analyses (even to the point of suspecting fabrication, of a sort), because of this level of selectivity.
Misrepresentation in the original manuscript. Our assumption when we see the report of a trial is that, unless it is presented as a secondary, follow up, or other type of ancillary or nested analysis, then the report describes all of the main aspects outlined in the approved protocol. This wasn't the case here, but how serious is this? Is it a form of scientific misconduct and if so who should we report it to? (The ethics committee may not care - are there any "rules" that a trial, once approved, has to be published in the form it's approved?)
At this point we are considering rejecting the paper essentially on the grounds of protocol deviations, and sending all relevant documents and correspondence to the ethics committees (who are already aware of the issues raised).
The committee warned that the ethics committees could be part of the problem, and so seeking help from them (who are already aware of the issues raised) may not be very useful. The editor provided the update that the paper has now been rejected and that the author has made a formal complaint about the editor on the grounds that the paper was mishandled. The committee were unanimous in their support for the editor who they said should remain firm in the face of the authors’ allegations. Further advice was to contact the authors’ institutions and inform them of the issues. The committee cautioned that this case highlights the need for trial registration for all studies.
The paper was rejected. The editor wrote to the chairs of both ethics committees enclosing a copy of the paper and protocol documents. The Director of Publishing dealt with the author’s complaint about the editor, and wrote back to the author to uphold the editor’s handling of the paper. We did not hear back from one of the chairs of the ethics committees but the editor did speak to the other chair, who felt that we had not understood the realities of conducting clinical research, in which protocols may change. We decided not to go to the authors’ institution to pursue this case further.