Lack of trial registration leads to new concerns about study conduct and ethical review/approval
Case text (Anonymised)
Following publication of an article, the editors noticed that the paper reported results of a clinical trial, but no details of trial registration were included in the article. (The journal does have careful checks on trial registration by staff at submission but this paper was not well written and it took careful reading to work out that it did in fact report on a clinical trial).
We contacted the authors to request details on trial registration and the study protocol, which are journal requirements for clinical trials. The senior author (co-chair A of his institution) eventually acknowledged that the trial had not been registered and they provided a document for the study protocol which we considered unsatisfactory. The authors at that stage requested ‘withdrawal’ of the article.
We replied to the authors to indicate we had the intention of issuing a notice of concern based on lack of trial registration. Given the new issue about the lack of a satisfactory protocol for the study reported, we then requested a copy of the letter of approval issued by the ethics committee/institutional review board cited in the article. Around this time, we were spontaneously contacted by co-chair B of the authors’ institution (who is not an author on the paper) expressing serious concerns over the work reported given that:
(1) they considered the description of the work as potentially misleading given it fulfilled the criteria for a clinical trial; and
(2) the ethics committee/institutional review board cited in the article does not exist at the authors’ institution.
Co-chair B indicated they would like to remain anonymous but would be willing to publicly outline their concerns as part of an internal investigation if a formal request for an enquiry was sent to the institution. We did not hear back from the authors for some time after our request for a copy of the ethics committee approval, so we posted a comment on the article to make the readers aware about the fact that the article did not adhere to the journal’s requirements for clinical trials and replied to the authors to explain the implications of a retraction—versus a ‘withdrawal’—and also reiterate the request for the letter of approval issued by the ethics committee.
In a further development, the authors finally then contacted us to say that the study was not in fact done at their institution but in a separate part of the country, that they did have approval from an ethics committee other than the one stated in the paper and provided a copy of that ethical approval in a non-English language. They provided no explanation for the discrepancies in study setting and ethical approval. It is not clear to us who recruited the participants as no authors seem to be based at the institution now claimed as providing ethical approval.
We have been unable to independently verify the authenticity of the claimed ethical approval and have concerns about the discrepancies in the various accounts of what took place. We think it is important to retract the paper and propose to do that, highlighting the lack of trial registration, lack of an appropriate protocol and that the ethics committee named in the article did not seem to give approval.
Is it adequate to proceed to retract the article on the basis of the concerns raised and the lack of an adequate response from the authors, given that we have been unable to establish whether the trial did or did not receive ethical approval? We also propose to submit a formal request for investigation to co-chair B of the institution (who currently wishes to be an anonymous complainant) and update the retraction later should we receive further clarification from them.
The Forum agreed that the editor certainly has enough grounds to issue an expression of concern. However, most agreed with the suggestion that the editor should submit a formal request for an investigation to be carried out by the institution. If the investigation provides evidence of misconduct, then the editor should retract the paper.
However, some of the Forum argued that there are already grounds for retraction and that retraction is justified on the basis of the lack of appropriate protocol, lack of trial registration and possible lack of ethics committee approval. Hence, although ideally a formal investigation should be conducted and the editor should wait for the outcome, if the institution does not respond or if the response is unsatisfactory, the editor should retract the paper anyway.
The editor wrote to the co-chair of the institution to ask for a formal investigation, and received an acknowledgement to say this would be done. The editor has not yet received any further details from them but is following up to find out more.
The journal plans to issue an expression of concern and have had to set up the ability to do this as a new type of article in their production systems.
Follow up (December 2011):
We heard from the institution's investigation committee, which determined that the trial had not been conducted by the authors of the paper published in our journal. Rather, the authors of our paper had received samples from the investigators who had conducted the trial, and were reporting results of analyses done on those samples. The individual named in the investigation committee report as the principal investigator for the trial was not named in the manuscript published in our journal, either as an author or as an acknowledged person. The investigation committee reported that the oversight and conduct of the trial had been appropriate, but that ethics approval had in fact been given by a different ethics committee from the one named in the manuscript published.
The investigation committee reported that the trial, funded by a commercial company, had in fact been carried out at the company, recruiting as participants employees of the company. We were not aware of this fact when we published the paper and the setting and participant recruitment for the trial were not well described in the manuscript. The investigation committee reported that they would not have expected this study to have been registered as a trial, bearing in mind their country's local laws. This was because the intervention used in the trial was an approved medicinal product —essentially it was a postmarketing study. In that country, such studies do not need to be registered.
The journal editors have decided to proceed with an expression of concern, noting that the ethics committee named in the paper as giving approval in fact did not, and that a different ethics committee gave approval. We plan to describe the setting for recruitment of participants and state that the company employees were participants. We would like to state that the trial was not registered and should have been, under our journal's criteria and ICMJE criteria, even though it may not have been a legal requirement in that country.