Transparency of manuscript reviewing is important and therefore some journals have started to use open review.

In all the medical BMC journals, reviewers are asked to sign their reviews and the pre-publication history of each paper is posted on the web with the published article.
http://www.biomedcentral.com/info/about/peerreview/

The comments of reviewers, and the replies by the authors may be informative for the readers of the published paper. All relevant considerations cannot be included in the final report, for example, because of space limitations. Therefore the reviewer comments and replies by authors are of additional interest to those readers who are seriously interested in the topic.

However, in the case of rejection the BMC policy is semi-transparent. Although the reviewer comments are made available as net versions (below), the refutations of the reviewer comments are not.

Since the comments of reviewers and replies by authors are important when considering the validity of a scientific paper, I am briefly describing the reviewer comments and their counter-comments for the paper below.

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In Spring 2010, I submitted my manuscript
“Subgroup analysis of large trials can guide further research: a case study of vitamin E and pneumonia”
to the journal “Trials” http://www.trialsjournal.com/

I received two reviewer comments:

Reviewer 1
http://www.trialsjournal.com/imedia/6765528423760221_comment.pdf
Reviewer 2
http://www.trialsjournal.com/imedia/1246630932376444_comment.pdf

The manuscript was rejected on the basis of these two reviewer comments.

However, the associate editor wrote that:
“If at some stage you are able to fully address all of the referees' concerns, you may wish to consider submitting a new manuscript to Trials. If you are able to do this, a full covering letter, explaining the revisions made, should accompany the submission.”

Editor's rejection letter:
http://www.mv.helsinki.fi/home/hemila/PPH/CE/Trials_Reject_1.pdf

Since the reviewer comments did not point out any fatal flaws in my manuscript, we followed editor's suggestion and wrote replies in which we fully addressed all of the referees' concerns:

Replies to Reviewer 1 comments:
http://www.mv.helsinki.fi/home/hemila/PPH/CE/Trials_Reject_1.pdf

Replies to Reviewer 2 comments:
http://www.mv.helsinki.fi/home/hemila/PPH/CE/Trials_Reviewer_2.pdf

These comments and replies describe which kinds of issues have been explicitly considered in addition to the text published in the final paper.

Since reviewer 1 and 2 comments were long, we wrote in the second submission letter:
“It is possible that we have missed or misunderstood some important issues, and in such a case we would hope for a possibility to reply to comments that still need our reply.”
http://www.ltdk.helsinki.fi/users/hemila/PPH/CE/Trials_Submission_2.pdf

The manuscript was rejected a second time:

Second editor's rejection letter:
http://www.mv.helsinki.fi/home/hemila/PPH/CE/Trials_Reject_2.pdf

This second rejection was based on a very short reviewer comment:

Reviewer 3
http://www.trialsjournal.com/imedia/6870941364447350_comment.pdf

The only points of reviewer 3 were:
1) the replies to reviewers 1 and 2 were too long
2) the approach of manuscript was “somewhat unorthodox”

Neither of these statements are scientific arguments pointing out errors or unjustified conclusions in the manuscript. Since I was puzzled by such kind of editorial policy, I wrote a commentary to several editors of the Trials journal. In the commentary I expressed my surprise that my manuscript was rejected on the basis that my replies were “too long” and approach “somewhat unorthodox”, which are subjective opinions and not scientific arguments.

Commentary on the editorial policy of “Trials”:
http://www.mv.helsinki.fi/home/hemila/PPH/CE/Trials_EdPolicy.pdf

I did not receive any replies to the above email.

The manuscript was finally published in another journal:
Hemilä H, Kaprio J.
Subgroup analysis of large trials can guide further research: a case study of vitamin E and pneumonia.
Clinical Epidemiology 2011;3:51-59
http://dx.doi.org/10.2147/CLEP.S16114

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Thus, it is surprising that a manuscript reporting strong evidence of heterogeneity in the effect of vitamin E supplementation is rejected on the basis of Reviewer 3 comments.

There seem to be two potential reasons for such an unscientific rejection.


1) In my manuscript I challenge the views of a senior editor of the Trials journal about subgroup analysis (ref. 2). Thus, it seems possible that the real reason for rejection was to prevent the publication of findings that challenge the wisdom of strongly opposing subgroup analysis. It is possible that the editors rejecting my manuscript simply wanted to stifle debate, although stifling debate has been criticized e.g. by a senior editor of Trials journal:
“The key characteristic of science is not its infallibility, a quality it clearly does not and cannot have, but its self-correcting ability. The decision by medical editors to stifle debate is misguided...”
http://dx.doi.org/10.1371/journal.pmed.0020126


2) Two of the senior editors of the Trials journal keep up citing a 1975 study which claimed that vitamin C does not have any effect on the common cold and claimed that the observed benefit was explained by the placebo effect. However, the 1975 study was shown to be erroneously analyzed over a decade ago. Citation bias is a common phenomenon which usually originates from preconceptions of the authors, when they pick “illustrative examples” to support their argument. Thus, citing a vitamin C paper that was shown erroneously analyzed over a decade earlier may be a reflection of general bias of the senior editors against vitamins in general, including vitamin E, which was the topic of the rejected manuscript.

The 1975 study:
http://jama.ama-assn.org/cgi/content/abstract/231/10/1038

Refutation of the 1975 analysis:
Hemilä H. Vitamin C, the placebo effect, and the common cold: a case study of how preconceptions influence the analysis of results.
J Clin Epidemiol 1996;49:1079-84
http://dx.doi.org/10.1016/0895-4356(96)00189-8
http://helda.helsinki.fi//handle/10250/8082 Links to references are added

Hemilä H. Response to the dissent by Thomas Chalmers
J Clin Epidemiol 1996;49:1087
http://dx.doi.org/10.1016/0895-4356(96)00191-6
http://helda.helsinki.fi//handle/10250/8079

Hemilä H. Analysis of clinical data with breached blindness
Stat Med 2006;25:1434-7
http://dx.doi.org/10.1002/sim.2347

The most influential trial on vitamin C and the common cold: Karlowski et al. (1975)
http://www.mv.helsinki.fi/home/hemila/karlowski

Citation bias by senior editor 1, see description in:
Assessment of the importance of double-blinding should be based on systematic reviews
http://dx.doi.org/10.1111/j.1538-7836.2008.03006.x
https://helda.helsinki.fi/handle/10138/25297 Links to references are added

Citation bias by senior editor 2, see description in:
Citation bias in the CONSORT comments on blinding.
http://www.bmj.com/content/340/bmj.c869/reply#bmj_el_235882

Harri Hemilä
harri.hemila@helsinki.fi