Questionable ethics related to clinical trial raised by peer-reviewer

Case number: 
10-34

Case text (Anonymised)

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We received a paper describing a clinical trial comparing treatment X with treatment Y. Treatment Y is the standard treatment for the indication under investigation (indication 1); treatment X is a combination treatment not recommended for treatment of the indication under investigation. One of treatment X's components has shown some efficacy against indication 1 and is widely used as a second line treatment for a different indication (indication 2).

The handling editor invited four clinical peer-reviewers (one of whom had been recommended by the authors) and a statistical reviewer. Reviewer A responded to the invitation explaining that he had a conflict of interest with the pharmaceutical company who were financial sponsors of the trial, but s/he would still be happy to peer-review the paper if the editor would like to receive her/his comments. The editor asked reviewer A to send their comments but to note the conflict of interest on the peer-review report so that it could be taken into account.

Three clinical reviewers and one statistical reviewer were broadly positive about the paper. However, reviewer A recommended rejection; the concerns were that treatment X was being marketed without proper good clinical practice assessment and had not been licensed by any country with rigorous assessment standards and that the component of treatment X should be reserved solely for indication 2. Reviewer A claimed that the study was unethical.

Treatment X is licensed for the treatment of indication 2 in the country where the study was done (and several others); all the components of the treatment are licensed for use; and the study was given ethical approval and legally sponsored by an institutional review board. Following discussion with colleagues, and considering the conflict of interest indicated by reviewer A and taking into account the fact that another reviewer was recommended by the authors, the editor invited an additional reviewer (B) to assess the paper, specifically asking about the ethical concerns. Reviewer B unreservedly recommended publication and thought the design was more than adequate with adequate safety and IRB coverage.

Given the overall feedback from reviewers and considering the licensing status of treatment X and that the study had ethical approval, the editor invited the authors to revise the paper; in the invitation to revise, the editor suggested that the authors could discount the comments of reviewer A.

The authors revised the paper satisfactorily, choosing not to respond to the comments of reviewer A, and the paper was published. Since publication, reviewer A has contacted the journal to express again their ethical concerns and querying why the paper was published and how the author had responded to the the comments that s/he made at peer review.

Was it appropriate for the editor to recommend that the authors could choose not to respond to the comments of reviewer A? And what should be the procedure from here to investigate the concerns regarding the ethics of the study?

Advice: 

The advice from the Forum was that the editor should reply to reviewer A and explain why he thinks the study is ethical and why he went ahead and published the paper. The forum agreed that the editor should not have recommended that the authors do not respond to the comments of reviewer A. The Forum also suggested that when reviewer A responded to the invitation explaining that he had a conflict of interest, the editor should not have asked him to peer-review the paper. When the paper was accepted, the editor should have written to the reviewers and explained why the paper was being accepted.

The Forum suggested that really the discussion should now be in the public domain and the editor should encourage reviewer A to publish his comments as a letter and then the authors can respond.

Follow up: 

The editor wrote to the complainant explaining the processes that led to the decision and how the journal had satisfied themselves before publication that the ethical concerns raised should not prevent publication of the paper. The editor suggested that they write a letter to the journal so that the authors could answer their concerns specifically in a public forum. The person thanked the editor for the explanation and the opportunity to write a letter, suggesting that they would do so. So far a letter has not been received.

Resolution: 
Case Closed
Year: