In 2013, our journal published a paper describing an observational study comparing two drugs (A and B) for the management of a chronic disease over a period of 10 years. The conclusion in the paper was that mortality was higher in group A (97 deaths) compared with the other group B (52 deaths) (hazard ratio 1.76, 1.22 to 2.53; P=0.003). This analysis was done after adjustment for a large number of confounders, and was approved by our statistical advisor. The authors of the papers did acknowledge that this was an observational study, and did state that residual confounding might be present.
In 2014 we received a letter of concern by a researcher, employed by the company selling drug A, who felt that the authors of the 2013 paper omitted essential information that might impact on the conclusions. It appears that the routine management of this disease has changed substantially over the 10 year period, and this should have been treated as a confounder for which statistical adjustments should have been made. This change in routine management of the disease is documented in a paper published in 2014, but the researcher felt that these authors were probably aware of this much earlier and should have disclosed this information during the review process of their 2013 paper.
In our initial response in July 2014 to the letter of concern, we asked the researcher who sent us the letter of concern to send us a detailed rapid response to the 2013 paper, which we could publish. We have also asked advice of our statistical advisor who reviewed the 2013 paper, and he acknowledged that this information might impact on the statistical calculations and thus the conclusions of the paper. But with the data available to him, he is not able to make a definitive assessment of how much impact it would have. He has suggested to put these questions to the authors of the 2013 paper.
Question(s) for the COPE Forum
The researcher who raised the concern has not made his concerns public by sending us a rapid response that we could put to the authors and publish, with their response, on our website. We will certainly put the questions to the authors of the 2013 paper, but we wonder if we should publish these concerns?
Another problem is that, due to the complexity of the statistical calculations, we are entirely dependent on the authors to judge whether the routine management data would have seriously impacted the conclusions of the 2013 paper.
The Forum agreed with the course of action of the editor to date—namely, inviting the researcher to write a formal note, stating his concerns, that can be made public and the authors can then be invited to make a response. This ensures the process is transparent. But if the researcher who raised the concern does not want to make his concerns public, there may be little that the editor can do.
One suggestion was that the editor could publish the concerns anonymously and invite the authors to respond. Another suggestion was to treat this as you would a whistleblower by investigating the issue, and asking the authors to respond specifically to the questions raised by the researcher if necessary. It is clear that the editor has concerns about the paper and these should be addressed in some way.
So, the best option may be for the journal to publish the concerns, not necessarily revealing the researcher’s identity, and invite the authors to respond.
The researchers who sent a letter of concern sent a letter to the editor which was published, and which was answered by the authors of the original paper.
The journal’s statistical advisor has found the response satisfactory. The editor considers the case now closed.
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.
A meta-analysis was conducted of about 1000 patients included in a number of small trials of a drug for emergency management administered by route X compared with route Y. The report concluded that administration by route X improves short term survival.
The paper was submitted to our journal in September 2011 and after peer review was returned to the authors for revision in November 2011.
In the letter sent to the authors, the editor stated: “Before coming to a final decision on your paper we will need to see your responses to our referees' comments. We will also need you to discuss the preliminary results of the large randomised controlled trial (RCT) recently presented at a national meeting which conflict with and may negate the conclusions of your meta-analysis.”
The revised version was sent back to us in January 2012. It contained only one mention of the large RCT without quoting any of its findings. The covering correspondence discussed the RCT findings that had been recently presented and speculated as to why they appeared different from the findings of the meta-analysis.
We accepted the meta-analysis in January 2012. We considered that the differences described by the authors were irrelevant, because the large RCT had not, at that time, been published in a peer-review journal and the only information available was from data presented at a meeting.
We now know that the authors of the meta-analysis were fully aware of the findings of the large RCT at the time they submitted the revision because the RCT paper had already been accepted by a high profile journal and the lead author was co-author on the meta-analysis submitted to our journal. None of this was revealed to the journal prior to accepting the meta-analysis
In March 2012, the high profile journal published the large RCT which randomized more than 2000 patients to drug treatment by the two different routes. The main conclusion was of no difference in survival for route X versus route Y. This finding rendered meaningless the finding of the meta-analysis accepted by our journal 6 weeks previously.
The authors of the meta-analysis were then emailed asking if they would now update their meta-analysis with inclusion of the RCT data.
The response was negative but an email from another co-author (who wrote the editorial accompanying the RCT in the high profile journal) agreed “it makes no sense to report a meta-analysis claiming death reduction considering available data”. He then copied us in an email he had sent to the lead author of the meta-analysis in January 2012, before it was sent back to our journal: “just to let you know that I am finishing an editorial on (the RCT) which will likely come out very soon with the main Ms....I would suggest that you try to include (the data from the RCT) into your meta-analysis ASAP”
The authors chose not to include the data from the RCT in the revised version of the meta-analysis they submitted to our journal, even though they had available those data. Since then the authors of the meta-analysis have steadfastly refused to update their paper. Meanwhile the editorialist for the high profile journal has asked that his name be removed from the meta-analysis in our journal.
The authors of the meta-analysis, one of whom was the lead author of the high profile journal report, had full access to the RCT data at the time they were preparing their revised paper for our journal. They knew that the main finding of the RCT contradicted the conclusion of their meta-analysis and ignored the suggestion of a co-author (the editorialist) to include the RCT data in their revised paper to our journal.
COPE states that journal editors should consider retracting a publication if they have clear evidence that the findings are unreliable. The authors of the meta-analysis knew their findings were unreliable at the time they submitted their revised paper and we now wish to have the paper retracted
The Forum agreed there were grounds for retraction of the paper. Clinical decisions are often based on meta-analyses and the editor cannot rely on all readers being aware of the newly published meta-analysis in the other journal. However, the ideal situation would be for the author to correct the published paper. Although the author has refused to do this, the Forum suggested that the editor should contact the author again, asking him to correct the paper. The editor should tell the author that if he refuses to correct the paper, then the editor will be left with no option but to retract the paper.
The Forum suggested that the fact that the editor did not ask the authors to wait until the results of the RCT were available before submitting their final paper has contributed to the confusion surrounding the case. Going forward, the editor should consider revising journal policy to request authors to send any related papers under submission to them when they submit an article.
Following the Forum’s advice, the editor emailed the corresponding author of the paper, copying in the co-authors, stating that he hoped the authors would agree to update the meta-analysis whereupon the matter would be concluded. He told the authors that if they did not agree to provide an update, he would retract the paper. The editor received no reply and therefore retracted the paper. The retraction notice stated that the findings of the paper were unreliable because they failed to address data from the large RCT, to which the authors had access prior to submission and which contraindicated the paper's conclusion. The notice said that authors were asked to update the paper to include the RCT findings but, with the exception of one of the authors, they declined. Owing to this difference of opinion, this author asked to be removed from the list of authors, a request to which the journal acceded. The notice stated that under these circumstances, the matter was considered by COPE who recommended retraction and this paper has now been withdrawn.
In May 2011 a letter from the Vice-Rector for Personnel of a reputable university was sent to the editor mentioning that two articles published in the journal contained two statements not supported by documented evidence. The two statements related to: (1) approval of the local ethics committee and (2) representation of the experimental evidence.
With regard to point (1), the authors stated in the article that they had approval in 1995 for their research protocols but the authorities state that there is no written documentation of this agreement and that this cannot substitute for formal approval of the research. The journal and the university rules indicate that formal approval of an ethics committee is required.
With regard to point (2), a statement in both articles cannot be sustained for one of three patients in one of the articles and for one case in the second article. Laboratory analysis revealed contradictory evidence from the authors’ statements in the articles. The authors gave three reasons why they ignored this information. Unfortunately, the samples kept in the authors’ laboratory were destroyed in a fire.
According to the letter from the academic authorities, “the authors have been kept informed of these facts, which are in breach of the rules of good scientific conduct”.
One of the articles is coauthored by three colleagues from another university. They have asked the journal that their names be removed.
The author of the articles, who received a copy of the letter from the Vice-Rector, asked to have some time to send in his rebuttal of the accusations. For both issues the answers provided by the authors were submitted to the university and were judged as unsatisfactory.
Long discussions within the publications committee of the journal with representatives of the publisher and the scientific society led to the decision that an “expression of concern” should be published. Prior to publication, the expression of concern was sent to the authors and the university for their comments. Just before the deadline, a letter arrived from the university (signed by the Vice-Rector and the Rector). The conclusion of the letter was that the university believed an expression of concern was not needed. The university believed that the authors recognized that they made mistakes in relation to both issues but since they acted “in good faith” the university had closed the case and did not consider an expression of concern appropriate.
So the journal was faced with an author admitting two serious “mistakes” in two articles. The institution that originally raised the concerns backed off in the end. After consulting with the editorial team I wrote to the author asking him to send a letter to the editor signed by all authors correcting the serious mistakes in the literature. A confidential draft letter was received from the author, and edited and completed by the editor so that both issues were mentioned. This letter was signed by all authors at this author’s institution. Three authors at a different institution refused to sign the letter as they believed that the letter to the editor did not clarify the situation. These three authors confirm their initial position and encourage the other authors to retract both articles. A copy of the email correspondence between the author and a spokesman for the other institution indicates that the author does not want to do this.
A possible conclusion would be to publish the letter to the editor signed by the authors from the institution of the first author as well as a letter to the editor from the three authors from the other institution. This would be accompanied by an expression of concern or an editorial by the editor, highlighting the necessity of proper ethics approval and reporting all experimental data.
An additional question to COPE: should other editors be informed of this? In a sister journal, an article was submitted mentioning the same very outdated ethics approval.
The Forum agreed that this was a very interesting but complicated case. There are two issues here: (1) approval of the local ethics committee and (2) representation of the experimental evidence.
Regarding the first point, the Forum suggested that if the validity of the ethics approval is not in question, then this may not be an issue. The editor does have a right to expect a higher standard from the authors, but they do not seem to have broken the rules as at the time of submission (in 1995), formal approval was not considered mandatory.
In terms of the data, the Forum agreed that the editor needs to decide whether the basic findings of the study are sound. By leaving out some of the data, were the readers mislead? If the data that have been omitted are incidental and do not change the findings of the study, then the advice was for the editor to issue a correction. If however, the editor feels that the study is flawed and the findings were presented in a misleading way, then the article should be retracted.
Some felt that as the authors at the second institute want the article retracted, then the editor should consider retracting it (since these authors no longer stand by the findings). As these three authors believe there are grounds for removing their names because they were unaware of the lack of ethics approval and the omitted data, then the editor should consider this option too.
In the end, it is up to the editor to decide. If s/he decides to issue a correction, s/he could detail in the correction notice which authors were aware of (or responsible for) the errors that occurred. But if the editor has doubts about the underlying science, then s/he should retract the paper.
After the COPE Forum discussion, a decision was taken to correct the literature by publishing two letters to the editor. The first letter from all of the authors recognises the errors made and explains the reason why the omission of the experimental evidence did not put into question the validity of the work. The letter was signed by all of the authors except the three authors from the other institution; they had asked that their names be removed as authors and they explain in a letter to the editor why they requested this. An editorial was written in relation to these two letters, reiterating the facts and insisting that proper ethical approval is required and that all experimental evidence needs to be reported. The conclusion of the editorial is that the journal decided not to retract the paper but to publish a correction. Both letters to the editor and the editorial will be linked to the two articles in the literature.
We have been contacted by a reviewer after he spotted a paper he had reviewed for us (journal 1) now published in a second journal (journal 2). Both journals are members of COPE. The reviewer had advised we reject the paper when it was sent to him to review in September 2008. This was based on his assessment of the paper and also the supplementary material he was sent by us: protocol, CONSORT statement and trial registration details. Seeing the paper now published in journal 2 (April 2010), he still has the same concerns about the conduct of the trial and validity of the data presented—for example, the study was not really randomised (subjects were allocated alternately to treatment or control and participants’ trial numbers were known to the outcome assessors)—and reporting of the outcomes was inconsistent with scores given in the raw data.
Following the original rejection from journal 1, the authors appealed against our rejection and we declined their appeal. The letters from us made it clear that we had concerns about the methods and reporting, and both external reviewers’ reports were available for the authors to see.
So in spite of making it clear that there were problems with their paper, the authors still went ahead and submitted to journal 2.
When contacting us, the reviewer wanted to know if he could contact the editor of journal 2, make it known that he had seen supplementary material when he had reviewed the paper and explain his concerns to the editor. We advised him to write to the editor of journal 2 in confidence, explain what had happened and say that we had reservations about breaching confidentiality in this way but thought that the benefits of doing so outweigh the risks.
The editor of journal 2 has now contacted us asking to see the supplementary material. Unfortunately, we no longer have the files available (we do not archive them that long) but we do have the reviews. Questions for COPE • Should we share with journal 2 the reviews we still have? • In principle, could we have shared the supplementary files and original submission (although they are no longer available)?
The Forum’s advice was that the journal should not share reviewer comments with another journal without first asking the reviewer’s permission. However, it is quite acceptable for the reviewer him/herself to decide to send their comments to another journal if they think this is the right thing to do (since the review belongs to the reviewer). Most people felt that the material submitted by the author to the journal (ie, the protocol) should not be sent to another journal, as this is privileged/confidential information. It is up to the second journal to contact the author and ask for this material. If the author does not respond, then the journal that had actually published his work (journal 2) should contact the author’s institution.
The editor of journal 2 contacted the author of the paper who provided some, but not all, of the answers which he sought. So, after discussions with the reviewer and a member of the editorial board, they decided not to dig deeper with the author but instead publish the letters that had been sent to the journal about the paper.
The editor of journal 2 published six letters in total: two letters about the paper with replies from the author, and a further letter about the commentary accompanying the paper, together with a reply from the author of the commentary.
We received a paper reporting a trial. There has only been one previous trial of this intervention in this condition that we know of (which was also done by these investigators). There were substantial issues with the reporting of that trial but the end result, as reported by them, favoured the intervention.
The trial we received, presumably approved after that result had come out, had the complication that most patients also received another treatment, and on an intention to treat (ITT) analysis of all patients, those given the intervention did no better and there was increased mortality in the intervention arm. The only positive outcome was from a per-protocol subgroup analysis of patients who did not have the other treatment (which they say is the only group comparable to the previous trial, and hence shows that the first trial was correct).
Although the trial was investigator led, it seemed to us that the authors were trying very hard to make something positive out of this actually rather worrying result. We sent the paper for review, including to a statistician; the reviewers raised a number of issues about the interpretation (eg, the overemphasis on subgroup analysis) and the analysis and reporting.
We felt that this was an important trial that needed to be reported, mainly because of the excess mortality in the intervention arm, but we had the rather odd situation that the authors wanted to emphasise the positive, and the need for further trials of this intervention, whereas the reviewers and editors saw the paper as delivering a negative message and feel actually that the paper will be the death knell for this treatment.
We therefore rejected the paper but offered to see a revised version if it was written more in line with our concerns.
The authors revised and the paper was re-reviewed. The paper was felt to be more balanced, but not yet completely satisfactory (ie, there was still too much emphasis on the positive result in one subgroup and not enough on the mortality).
A further issue then arose in that a reviewer spotted (on re-review) that three of the authors were noted as being on the DSMB for this trial. In their author contributions all are listed as having been involved in “analysing the data” and one, X, as “supervising the statistical analysis”
We asked the authors about these points and they replied: "(1) We are fully aware that it is unusual for members of the DSMB to be listed as authors, as independence is obviously important for such boards. In our case, the DSMB’s independence was not affected for the following reasons:
(a) Members of the DSMB worked for the entire study period (ie, between 2003 and 2008) completely independent and without any promises or expectation that they would be credited later by a coauthorship.
(b) My personal decision to include three of the four DSMB members in the list of authors was made a significant time after the final database lock. This decision was long after completion of the clinical study and its analysis. It credited three members of the board who made some significant advisory contributions to the present manuscript. Only for this reason they were included as coauthors, and it was quite unexpected for them. This decision from December 2008 has in no way influenced their independence and objectivity at the time when the study was running.
(2) As to the contribution of X (one of the members of the DSMB), we have to admit a simple language problem. In our use of the word “supervision”, the word meant that he took a final comprehensive look at our data analysis before the paper was submitted for publication. Importantly, he never supervised (like an academic supervisor) data analysis at any time point before database lock and processing of the data by the clinical research organization. We will change the terminology accordingly.”
We subsequently found that X was also an author on the previous trial.
Finally, the authors did not declare initially any competing interest but after we enquired specifically, they declared that the corresponding author “holds a patent on the use of t[he intervention] for treatment of [the condition]”.
Our concerns overall therefore were that this paper not only reports the outcomes in a way that is not appropriate, but also the composition of the DSMB and the presence of some DSMB members as authors means that the trial may not have had adequate independent oversight.
We felt we had two possible options with regard to publication:
(1) We reject the paper because it was inappropriately conducted and not appropriately reported.
(2) We publish the trial after further revision to ensure it is reported appropriately and publish alongside it an editorial that lays out our concerns with the conduct of the trial, but notwithstanding those, our reasons why we think it should be published.
We also discussed whether we needed to raise the issue of the DSMB with the authors’ institution.
We discussed the paper with our internal ethics board and they unanimously agreed we should reject the paper (mainly because of the concerns over the DSMB) and inform the authors' institution. We have as yet heard nothing from the institution.
We are bringing this to COPE as this paper raised a number of serious issues we had not come across before. We would appreciate the Forum’s opinion on whether we handled this correctly.
Some of the members of the Forum suggested that perhaps the journal should have a formal policy that DSMBs should be independent and not involved in the study in any way. The Forum questioned whether these authors fulfil the criteria for authorship, as outlined in the ICJME guidelines. One opinion was that perhaps the paper should not have been rejected until the outcome of the investigation was known. However, most agreed that rejecting the paper was the correct decision and the editor might consider contacting the ethics committee who approved the study if no response is received from the authors’ institution.
The editor reported the case to the author’s institution but no response has been obtained. The editor is pursuing the case.
We published a randomised trial by six authors. Some years later, we received a letter from a researcher who had been looking into the trial in the context of a meta-analysis. She noted “implausibilities of serious concern”, including “a highly unusual balance in the distribution of baseline characteristics”, 95% CIs that were non-symmetrical about the effect estimate, and use of a stratification variable the value of which could not have been known in all patients if the trial was conducted in the way reported.
We asked the corresponding author to write a letter of response, which he eventually supplied a few months later. Owing to the author’s poor English and the level of statistical knowledge needed to assess the response, we sent the exchange of letters to a statistical reviewer. The reviewer said that the letter of concern was “completely correct” in everything it said and that the author’s explanation for the unusual degree of balance in the covariates was “rubbish”, and that the 95% CIs had either been “doctored” or “incompetently estimated”.
In the meantime, an exchange of to-and-fro letters between a different researcher and the same author was published in another journal, relating to a paper reporting on a subset of the same trial data. We were alerted to this by the editor of that journal.
We sent the reviewer’s remarks to the author of our trial, who then consulted two independent statisticians of his own. He soon contacted us to say that, “surprisingly and regretfully”, these statisticians agreed that there were implausibilities and inconsistencies in the data, and asked for more time to investigate more fully. During this time, the author of the letter expressed concern that we had not made the possibility of these problems know to our readership, so we published her letter.
The author has now sent us a more comprehensive response, admitting that the randomisation process was not as described, the 95% CIs were all wrong (he supplied a recalculation), and the trial report had omitted some details of the protocol necessary for understanding it properly (now supplied). Our reviewer suspects that, given his free admission of all this, the author is probably incompetent rather than fraudulent, but that the extent of the incompetence could not give us confidence in any of the data. What now?
The Forum agreed with the editor’s opinion that the author is probably incompetent rather than fraudulent and should be given the opportunity to redeem himself. It was suggested that perhaps the paper should be submitted for review again. The Forum noted that this was probably a good internal learning exercise in that the statistical errors should have been picked up when the statistical review of the data was performed by the journal. A suggestion was made for the journal to set up a “sin bin”. Some journals operate a “sin bin” or “publication review committee” where once a year papers which readers or others have expressed serious doubts about post-publication are reviewed to determine whether or not it was “a mistake” to publish the paper.
However, some members of the Forum argued for stronger action and suggested contacting the author’s institution. But most agreed that the paper should be retracted as the research may be unethical.
August 2008 We have managed to find details of whom to contact regarding informing the author's institution, and the deputy editor has written to him. We await a reply with anticipation.
May 2009 The institute has responded to say that an investigation is under way and will take another couple of months to conclude.
November 2009 Following an internal investigation by the author’s institution, a number of serious problems were encountered, including: lack of ethics approval, lack of written consent, lack of treatment-allocation concealment and an inability to verify the authenticity of the data. We therefore retracted the paper on 10 October 2009.
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.
We received a case report describing the diagnosis and treatment of a middle-aged woman who presented to a gastroenterology service in England with weight loss and a right iliac fossa mass. The authors did a barium swallow, duodenal and gastric biopsies, and diagnosed Crohn’s disease by the radiological appearances on follow-through. They did not do a colonoscopy, or biopsy the mass in the terminal ileum. They treated the patient with immunosuppression, and she came back four times over the following year with no improvement, and died of small-bowel obstruction due to her leiomyosarcoma. The editor who received this case report telephoned the corresponding author to ask if he wished to resubmit it to the section on medical error, but he did not feel that the case indicated any error on their part. The editor then sent the case for peer review, and the reviewer pointed out that it was standard care in his country (Australia) to do a colonoscopy and biopsy a tumour before diagnosing Crohn’s disease, and that in the developing world, tuberculosis of the terminal ileum was a more likely diagnosis, one that the authors hadn’t considered. The file was discussed at the editorial meeting, and the editors decided to reject the case report, but felt that their duty as doctors had not been adequately fulfilled, but were unsure as to how to proceed. What should they do now?
The editor should contact the institution and request an investigation. The editor should inform the authors of the editor’s intention to contact the institution.
We contacted the Medical Director of the Hospital (with the knowledge of the author) and he undertook an investigation. This investigation revealed that the corresponding author had in fact never seen this patient and omitted the important information that the patient had refused invasive diagnosis and was therefore managed in the way as described.