Author A submitted a trial comparing the safety and feasibility of two delivery techniques in patients. The trial, which was done at author A’s institution, was assessed by inhouse editors, who decided to send it out for peer review.
During the peer review process, some reviewers pointed out that “this work seems premature, experimental and hard to believe”, and also expressed suspicion about the result (ie, 100% procedure success rate). One of the peer reviewers, reviewer X, who works with author A at the same institute in Europe, and who was also acknowledged in the author’s submission, provided further comment. In his letter to editor, he stated that “I have reviewed some of their manuscripts more than 10 times, and I have refused to be associated with their research, because I had no access to the raw data on which there is an embargo made by the military authority in this country.” He continued that “it is fair to say that the data are unbelievable, without a negative or positive connotation. If the data exist and are correct, they will deserve a Nobel Prize.....as a matter of fact, a fake document has been circulated and the hoax has been disclosed in a very elegant way by a young colleague”.
After discussion among editors at our journal, we decided to reject the manuscript and ask for an investigation by the author’s institute. However, since the European institute already seems to be aware of the likely fraudulent nature of these results, and we cannot find contact details for anyone at the institution, we would welcome your advice on to whom we might best direct the investigation.
The Forum cautioned that it is much more difficult to deal with authors and resolve an issue when you have rejected the paper, as the journal no longer has any say over the paper. It is much easier to obtain information from the authors before you reject the article. However, all agreed that this case should be pursued and the editor needs to give the authors an opportunity to respond to the accusations.
The advice was to give the authors one more chance to reply. The editor should contact all of the authors (not just the corresponding author) and inform them that because of the issues raised in peer review unless he hears back from them by a specified date, he will assume that the reviewer comments are correct and will then contact the author’s institution. The Forum advised contacting the institution if the authors fail to respond or if they respond in an unsatisfactory way. The European institute may be able to provide contact details for the initial institution. Also, the editor could ask the reviewer who works with author A at the same institute in Europe to provide contact details for the author’s present or previous institution. The Forum advised addressing the institution in a non-judgemental way, simply informing them of the facts of the case and asking them to investigate.
The editor continued to contact the institute about this matter, but there has been no response since February. The editor now feels there is little else he can do and considers the case closed.
A manuscript underwent peer review and the resulting reviewer comments raised grave concerns about the ethical legitimacy of the study. The reviewer:
questioned the authors’ impartiality, suggesting that there was an undeclared conflict of interest;
raised serious concerns about the extent to which participants gave informed consent;
strongly doubted that the study would have gained ethics committee approval; and
suggested that the study violates the World Medical Association’s 1964 Helsinki Declaration on Scientific Research with Humans, which states that the welfare of the research subject takes precedence over the interests of science and society.
The manuscript described a randomised controlled trial conducted on patients undergoing brain surgery. Participants were recruited between January 2010 and February 2012 in a single hospital.
The stated aim of the study was to establish the effect of varying the time for which blood flow to the brain is substantially reduced during surgery on postoperative function and disability. It is already well established that reducing the blood flow in this manner for a prolonged period of time is likely to lead to poorer postoperative outcomes due to reduced oxygen supply to the brain.
In order to avoid negative outcomes and improve patient safety, there already exists a warning criterion used in surgery of this type, which alerts the surgeon to the extent of oxygen starvation and indicates when blood supply should be restored.
In the manuscript, the authors outline their knowledge of the risks involved with the procedure itself and report that many surgeons feel that this procedure should only be used as a last resort due to the increased risks outlined above. However, if the procedure is deemed necessary, the risks can be reduced by employing the pre-established warning criterion.
The authors outline perceived flaws of the pre-existing criterion and go on to describe a novel warning mechanism —conceived by them—that they intend to test during the study. Testing this new criterion entailed increasing the time that blood supply in the brain is reduced—to the extent that, in some cases, the current recommended threshold was significantly exceeded. Additionally, while the procedure was underway, the authors ensured that the surgeon was blinded to the patient’s status with respect to the established risk threshold, making is impossible for them to gauge the level of danger the patient was being exposed to. This, as is noted within the manuscript itself, poses serious risk to the patients.
Participants were divided into three groups. In the control group risk was assessed using the normal criterion and blood supply was reinstated once this threshold was crossed. In the second group, blood supply was reduced for a longer period of time. In the third group, blood supply was reduced or completely cut-off for significantly longer.
In the results section, the authors state that in the control group one patient became severely disabled, and that all patients in the third group experienced negative outcomes. Of the patients in the third group, three were severely disabled as a result of the procedure and all of the others suffered some neurological deficit. As the reviewer points out, the pattern of outcomes raises serious ethical concerns about the study. The reviewer questions whether this was (and even should have been) tested on animals first, as this would have provided an upper limit and ‘red flag’ for testing.
The reviewer believes that this study violates the Helsinki Declaration on Scientific Research with Humans in that it appears that subjects randomly included in the third experimental group were subjected to an experimental condition that caused three of them to be severely disabled, and nine of them to be moderately disabled by the experimental manipulation. Because patients were assigned to intervention and control groups randomly and the outcomes between the groups differed significantly, it is highly unlikely that the negative outcomes among group 3 patients are attributable to technical surgical problems in one group only.
It appears that the negative outcomes found in group 3 patients were due to the blood supply being reduced or occluded for long periods of time. The reviewer also suggests that for the control group, there was an omission of a standard of care practiced by most modern medical centres that perform this procedure. The reviewer suggests these findings cannot be generalised to other procedures of this type and he wonders why the original warning criterion was not utilised in this study to further protect these patients.
Furthermore, the study raises serious concerns about the extent to which patient consent (for which consent forms were obtained from the patients) was properly informed. There is no indication that the risks to the participants inherent in an experiment such as this were properly conveyed to the individuals before participation was agreed.
Finally, the Declaration of Helsinki also states that “Physicians must immediately stop a study when the risks are found to outweigh the potential benefits…”; the authors did not stop this study for over a year. And, an unproven intervention should only ever be carried out if “it offers hope of saving life, re-establishing health or alleviating suffering” and that in the nature of research it is “designed to evaluate its safety and efficacy” not to establish a benchmark
The Forum were in agreement that this was very dangerous and very unethical research and that the editor should act quickly. The advice was for the editor to contact the authors informing them that there are substantial concerns with the content of the paper. The editor should copy in all of the authors, giving them a specific and short deadline in which to respond. The editor should tell the authors that he will contact the authors’ institution if no response or an unsatisfactory response is received.
The editor can ask to see proof of the ethics approval of the study, as well as the patient consent forms. Was the trial registered? If no response is received, the editor should contact the institution, copying in all of the authors. If there is no response from the institution, the editor should contact the general medical council or equivalent, or the funding body. For this form of potential misconduct, it is the editor’s responsibility to bring it to the attention of the institution or authority body that can investigate the case.
This single author manuscript describes the treatment of 300 women with psychological problems. The women were randomised to either therapy or pharmacological intervention, and this study reports the relative effectiveness of these strategies.
At submission, the manuscript did not contain any mention of ethics approval, consent or trial registration. When the author was queried on these issues, he claimed that the study was performed ethically, but that he did not have ethical approval because he did the study privately, and is not associated with any organization or institution. Since he had listed his affiliation with university X, we questioned how he had access to these patients. The author responded that he runs a private practice, and that he wanted to mention university X out of “personal interest”, and to please remove the name of the institution from his submission.
This author does not have a Scopus or PubMed record, or an institutional email address. Upon searching for his email address in Google, we identified two papers that appear to have been published by this author in journal A and journal B, neither of which is indexed in Scopus or PubMed.
We have contacted university X through their general email address to alert them of this individual, since he appears to be using their name in an unauthorized context, but have not received a response. We contacted the author to express our concerns and inform him that we would keep his file open until the issue has been resolved, but received no response. We attempted to contact the author’s medical council to report this individual, but were unable to find contact information as their website is not in English. We also contacted journal A and journal B to notify them of our concerns, in the event that they also wished to investigate this author; neither journal has responded.
Two months later, we re-sent the notification to university X general email address and received an out of office response.
We would greatly appreciate any suggestions on whether there is anything further we can do other than to reject the manuscript.
The Forum suggested that the editor has a duty to pursue this further and to continue to try and make contact with the author and the institution. Suggestions were to send an email to a specific person or department at the institution, not just use the general institution email; find out the name of the vice-chancellor or head of the department; locate a phone number or email contact for the secretariat in charge of the department; find someone to translate the information on the website. The university needs to know that their name is being used in this context by this author, and they need to start an investigation. The Forum also advised contacting journals A and B again. Are there any co-authors on the other papers? If so, the editor should try to contact them. Does the journal have any editorial board members in this country who could tell the editor the relevant person to contact?
If the editor still gets no response, another suggestion was for him to write an editorial on this issue.
Based on advice from the COPE forum, we have again attempted to contact the institution through their general email address—we have still not been successful in identifying a personal contact at the institution. Our next step will be to find someone to help us translate the website or an editorial board member who may be able to help us identify a committee or other point of contact in the author’s region.
A manuscript was published by journal X and submitted by author A (last author). Author B claims that fraud occurred in relation to authorship for the following reasons.
(1) Author A did not take part in producing the data for the paper and has never been a co-author on any version of the manuscript. (2) A paper with very similar content ,which was part of the PhD thesis of author C (first author), was accepted for publication in journal Y. (3) The figures in the paper published in journal X were identical to the figures in author C’s PhD thesis. (4) The name of author B was misspelt in the paper published in journal X to avoid identification of the article search in PubMed.
The editor of journal X contacted all of the authors by email and they responded as follows: author C (first author), author D and author E agreed with author B (claiming author). Author F did not respond, despite receiving five emails.
In addition, author B sent us a letter signed by the Vice-Rector at his University, agreeing and supporting the point raised by author B.
Author A (last author) disagreed with all of the allegations and pointed out the following. (1) Author A declared that he was the principle investigator of the project in country Z during 2004–2009, and the role of author B was to help in the analysis of the samples in his laboratory, located in country W. (2) Author A submitted an official complaint to author B’s university, alleging that they (authors B, C and D) had no right to use data without notifying or asking his permission. In addition, they did not have any patient consent. (3) The paper published in journal X was the original manuscript and it was circulated to all of the authors. (4) The name of author B was misspelled in journal X by mistake.
Author B requests that the paper must be retracted from journal X, and he also demands that the editors ensure that the paper will disappear from PubMed.
In summary, all of the authors confirm that the data are correct but they disagree regarding the issue of authorship?
Because of the quality of the phone line, it was not possible to discuss this case at the forum. Council instead gave the following advice on this case.
All agreed it was a complicated case and it would be useful to know which paper was submitted and published first, X or Y, although it seems likely it was X. Also what is the role of author F, is he/she affiliated with the institution of author A or authors B, C and D? Before dealing with the authorship dispute, it is essential to confirm whether patient consent was required and obtained. There are grounds for retraction of the paper if the study was not conducted ethically. Is journal Y aware of this dispute? As both parties disagree on the fundamental points, such as whether author A was involved at all in the study, official documentation and, if available, email conversations need to be produced to consider how to proceed. Hence more information gathering and a request for a formal investigation by the institution should be undertaken to find out exactly what the real issues are first. It might be useful for the journal to check or ask for information from both parties on national regulations and institutional policies for transfer of biological material and data sharing in this case of collaborative research.
The paper cannot “disappear” from PubMed, but at this point, most agreed that an “Expression of Concern” should be issued immediately and the editors need to investigate further the issues of (1) patient consent, (2) overlapping content and (3) the roles of each author on both manuscripts. Institutional input is also needed and the editor should clarify if the statements from the university vice rectors resulted from a formal inquiry.
The ethical issue can be compounded by the policy by some universities that if they conduct research outside of their own country, they require dual ethical approval by (1) that university and (2) whatever ethical system is in place in the countries where the research is undertaken.
The editor published an expression of concern in his journal, stating that one of the authors had questioned the authorship of the corresponding author. The submission is on hold and the authors have been all informed of the claim. The investigation by the journal has not yet reached a conclusion. Pending the results of the investigations, the journal decided to publish an expression of concern to alert readers to the fact that serious questions have been raised about the authorship of the paper.
Update (June 2013):
The paper was first submitted in journal Y, but it was first published in journal X.
Author F is affiliated with the institution of author A.
The institutional input from university of author B (Vice-Rector) stated that authors B, C and D are the legitimate owner of the data, and confirmed that authors B, C and D were not informed about the submission to journal X.
Ethical approval by the university in both countries was presented by author B, but not by author A.
Authors B, C and D stated that there has been no contact with author A for more than 7 years, and the research was performed long after author A left the research collaboration.
Further questions to COPE:
Author B stated that author A committed plagiarism and requested that the paper must be retracted. There is considerable evidence that plagiarism may have occurred by author A. What would the COPE suggest we do?
Advice on follow up:
(COPE council provided the following advice.) Publication of an expression of concern was the correct route but this now needs a resolution. It appears to Council that there is sufficient evidence that the paper should be formally retracted at this point.
Provided the editor is confident that the account they have is correct, ie, that there is no further information available from the institution, they could consider retraction on the following grounds according to the COPE guidelines: • “The findings have previously been published elsewhere without proper crossreferencing, permission or justification (ie, cases of redundant publication).” In this case the findings were not published previously but were submitted earlier. • “This constitutes plagiarism.”
However, it would be essential for the editors to do a timeline, listing the issues, so that the retraction statement is clear and accurate and can be agreed by the authors and the institution(s) involved before issuing the retraction, even if it is likely that only authors B, C and D will agree to the retraction notice. The retraction notice much also note who agrees to it.
We reviewed and published a randomised controlled trial in which children’s exposure to parental secondhand smoke (SHS) was either sustained (usual practice control) or parents were asked to avoid smoking around their children (intervention group). The study included more than 400 children averaging 9 years old. Parents provided written informed consent. The study was approved by the ethics committee of the researchers’ institution. Data were collected in a school setting by self-reported questionnaire and interviews. Children were classified according to amount of SHS exposure and baseline data about several types of symptoms were collected. The children with the symptom of interest and exposed to SHS were then randomly divided into two groups. Smoking members of families in group 1 were asked not to smoke in the child’s presence for a period of 6 months while those in group 2 were asked not to change their smoking habits. Parents were told prior to study enrolment that they would not be required to quit smoking as part of participation, rather they would be asked to reduce children’s SHS exposure. After 6 months, data were collected again in order to assess the proportion of children in the two groups who were still displaying the symptom of interest. Following this trial, all parents and children were asked to participate in a 5 month school project related to the risks of SHS exposure. The project included weekly lessons about the risk of SHS, attended by children with their parents to educate children about SHS risks and help parents to either reduce or cease smoking in their children’s presence.
Neither the handling editor nor reviewers raised questions about the study’s ethics during the review process. However, following publication, we received a letter questioning the study’s ethics on the basis that the known risks of SHS exposure outweighed any benefit to be gained by learning about whether SHS was a risk factor for the studied symptom and that the study procedures violated the Helsinki Declaration. The letter’s authors argued that the study’s advising of smoking parents in the control group to not change smoking habits could have unnecessarily exposed their children to additional SHS if parents who would have otherwise quit or reduced their children’s exposure did not do so because of the study. The authors of the letter claimed that they could not think of a single research question that would justify exposing children to SHS.
In discussion, one of the editors argued that the letter missed the important point that after the randomised controlled trial, all participants received the 5 month intervention to promote smoking cessation among parents and/or to reduce SHS exposure, and questioned the letter’s implication that the children would be better off if the study had not been conducted. S/he wrote that the letter seemed to argue against any controlled trial to reduce children's exposure to SHS, but that there were several dozen of these in the published literature.
The questions are twofold: was this an unethical study? And, if so, how should the journal proceed?
The editor told the Forum that questions raised during the review process were answered by the authors. The authors informed the editor that institutional review board (IRB) approval had been obtained but they did not provide evidence of IRB approval. The Forum advised the editor to publish the letter and give the original authors a chance to reply. The editor might also consider publishing the IRB approval statement. Another suggestion was to commission a commentary or write an editorial on this issue.
As advised by the Forum, the editor contacted the study authors to clarify the protocol instructions. In addition, the journal obtained a confidential consultation from an independent ethics body with four experts who summarised relevant ethical concerns. The journal also solicited a letter from the study authors to respond to the issues raised in the letter to the editor and solicited expert opinion from the department of bioethics of a major institution.
The letter to the editor, response from the authors and the expert commentary will be published in an upcoming issue along with a brief introductory statement from the editorial staff. The introduction invites the journal’s readers to review the materials in the interest of furthering reflection on the ethical implications of research on the effects of secondhand smoke and the ethics of the research enterprise more generally.
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.
As editor-in-chief of a journal (journal A), I was contacted by an individual (N) who indicated the following: authors of an article published in journal A were questioned as to the similarity of a figure and a table appearing in both journal A and in another journal (journal B). N noted that reanalysis of the data of the published work by the authors suggested errors and inconsistencies of the similar data across journal A and journal B.
Subsequently, N provided additional details, including notice of a third journal (journal C) that appeared to have published a table similar to those in journals A and B. The editor of journal B responded to this saying that although the authors had been contacted by the editor of journal B and a response from the authors was pending, they agreed that retraction from journals A, B and C was required. Of note, journal B had previously resolved a challenge from N with respect to the study in question as a letter to the editor regarding data interpretation with a response from the authors. The editor of journal B shared both of these publications with the other journals involved at the request of journal A.
Although the authors referenced journal B in the article they published in journal A and stated that it was an extension of the study published in journal B, they only indirectly referenced the figure and table. The figure and table did not include a reference or acknowledgment to indicate where they were initially accepted/published or submitted elsewhere. Hence it appears that a very similar figure and table appeared in three publications and a figure in two publications without appropriate assigning credit.
This appears to journal A to be a possible case of overlapping publications by the authors. Taking the first publication dates (including Epub dates) on PubMed, it appears all three articles were published at around the same time, with the article in journal C publishing first as an Epub article.
It should be noted that the authors retained the copyright to their article published in journal B. I am not sure about journal C.
Most recently, N sent another email to all three journals questioning the housing conditions of the animals used in the study and whether the statement indicating that the authors had received approval from their ethics committee of experimentation on animals is actually true.
As editor of journal A, I forwarded all the information to my publisher. I plan to contact the authors on review and after discussion with COPE. My publisher has also informed journals B and C of our plans to contact COPE before taking any initial action.
As well as asking for guidance on how best to handle this case, we would like COPE’s opinion on which journal should be taking the lead to resolve these concerns, as it involves multiple journals.
The advice from the Forum was to follow the COPE flowchart on redundant publication. Initially the editor should contact the authors and ask for a full explanation. If the editor feels that the explanation from the author is not satisfactory, he can then retract the paper, if his is the second journal which published the paper. If a paper is published online it should be considered as being published, so the epublication date is the date to go by. The first version of the paper should remain and the others should be retracted.
However, if the editor feels that there is only partial overlap and readers would benefit from the availability of new data, then the editor could issue a notice of redundant publication.
Another scenario would be if the editor accepts the explanation of the authors that they made a genuine mistake. In this instance, the editor could issue a correction (for example, figure 7 has appeared in a previous publication).
The Forum stressed it is important to contact all of the authors, not just the corresponding author. The Forum also agreed that regardless of whether or not N is acting in good faith, the editor should investigate the accusations by contacting the authors and asking for an explanation.
The Forum advised liaising with the other editors if possible, and jointly contacting the institution.
The Forum also suggested looking at the copyright issues (e.g. the date on which copyright was transferred to a journal, if applicable).
The editor retracted the paper. To the best of his knowledge the other papers in question have also been retracted.
I received a submission that had asked a series of questions of visitors to a website about a mental health issue. It was reviewed by a senior colleague and myself. While the science was fine we were both concerned that no mention had been made of any ethics approval. I raised this issue with the authors, especially given that deception was involved.
The authors then appear to have sought ethics approval from their institutional committee. The committee appears to have granted approval with the proviso that a notice be placed on the website indicating that the material from the questionnaires was to be employed in research, not in supporting the activities promoted by the website, as first indicated. The notice was to remain up for 3 weeks so that any of the participants could ask for their responses to be deleted from the study. No one asked that this be done.
We have discussed this issue 'in-house'. It has been suggested that publication is not necessarily precluded given that the institutional review board has approved the study and required the authors to notify participants of their intentions. Of course, the institutional review board and the authors would need to be able to produce full documentation relating to the submission and approval of the project.
We would be grateful for COPE's advice on this issue.
As mentioned many times at the COPE Forum, just because a study has been approved by an institutional review board does not mean that the editor has to consider it to be ethical or to publish it. Also, institutional review board approval does not guarantee that the study is not flawed.
Some questioned what kind of an institution would approve such a study in vulnerable patients. Others argued that they would not publish this study – the population was not fully informed of the study and so the research is misleading. It is unethical research in a vulnerable population.
The advice was not to publish the paper and write to the author telling him why. Another suggestion was to write to the ethics committee and ask why they approved the study.
The editor wrote to the authors with the Forum’s comments and indicated that the journal would not publish their paper and that they should not attempt to seek to publish it elsewhere. The authors have not replied.
Our journal received a manuscript describing a comparison of two different techniques for patients in the intensive care unit. There was no information on ethics committee approval and so we asked the authors if approval was obtained. They replied that they had not applied for ethics committee approval “as it was a clinical comparison of two existing methods, none of them experimental. All patients had an indication for the technique, and the technique was introduced in our intensive care units before the beginning of the study period”.
The study is described in the manuscript as a “prospective, comparative clinical study” conducted in 2009 and that “every other patient” who received the technique during the study period was assigned to “the technique of choice at our institution” or to a technique introduced in 2005. It is not clear whether informed consent was obtained.
We believe that this study was not conducted in accordance with the Helsinki Declaration where it is specified that “The research protocol must be submitted for consideration, comment, guidance and approval to a research ethics committee before the study begins".
Regarding informed consent, it is stated that “Research involving subjects who are physically or mentally incapable of giving consent, for example, unconscious patients, may be done only if the physical or mental condition that prevents giving informed consent is a necessary characteristic of the research population. In such circumstances the physician should seek informed consent from the legally authorised representative. If no such representative is available and if the research cannot be delayed, the study may proceed without informed consent provided that the specific reasons for involving subjects with a condition that renders them unable to give informed consent have been stated in the research protocol and the study has been approved by a research ethics committee. Consent to remain in the research should be obtained as soon as possible from the subject or a legally authorised representative.”
We have the following question for COPE: should we wait for the authors to apply for approval from the ethics committee at this stage or should we reject the manuscript and forward our concerns to the person responsible for research governance at the institution?
The Forum agreed that the described project was clearly research and not a service audit. It appeared, in fact, to be a prospective randomised trial and so it should have been registered and ethics approval obtained. Retrospective approval would not be appropriate. In addition, all participants should have given their informed consent. The lack of consent suggests a breach of the Helsinki declaration. All agreed that the editor should contact the author’s institution and inform them of the situation and ask them to investigate.
The editor contacted the professor who is responsible for research governance at the authors' institution. He agreed that this case raised significant concerns and an investigation has been initiated. Based on this, he has arranged a teaching programme in the department focusing on research principles and legislation. He has promised to keep us informed about other "whatever measures” that he deems necessary.
Follow Up (March 2011):
A departmental medical ethics programme has been organised in collaboration with the regional ethics board. The need for ethics committee approval has been emphasised and all clinical study protocols must be assessed by the person responsible for research. Violations of the department’s medical ethics program will lead to local manuscript retraction and freezing of intramural research funding and other support. A department publication and manuscript database system will be used for monitoring purposes.
We are seeking guidance on the ethical issues surrounding drug/medicine use evaluation (DUE or MUE) audit cycles, particularly with respect to the publication of findings but also perhaps with regard to the conduct of these audits in general.
DUE is a quality improvement activity that involves data collection and evaluation (usually by audit), followed by ‘action’ or intervention and a repeat or ‘follow-up’ audit to monitor changes in practice. DUE methodology was used for a recent national quality improvement activity overseen across approximately 60 hospitals by an independent organisation funded by the government to promote quality use of medicines. Participating hospital ‘project teams’ were asked to identify a predefined number of patients from their surgical lists for the baseline audit, obtain consent from the patient for inclusion (‘if required by local authorities’), conduct a brief postoperative patient interview regarding pain management and, after discharge, retrospectively collect pain management data from the medical record .
Data were submitted to the national project team for collation and assessment, with individual and combined results fed back to hospitals. An educational intervention was then conducted at each site, attempting to address medical, nursing and pharmacy issues, and utilising a number of tools, including one-on-one ‘academic detailing’, presentations and posters. A follow-up audit (same as the baseline) was then conducted at each institution.
A manuscript was submitted to our journal describing the conduct and outcome of the project in two hospitals, and comparing these with each other and with the national results. The hospitals were not specifically identified but were labelled A and B, although one could be assumed to have been the primary institution of the authors and the other probably one of two smaller institutions in the same area health network. The methods stated that formal patient consent was not required for the inpatient interview component because the questions asked fell within routine postoperative care. Institutional Ethics Committee approval appears not to have been sought for any aspect of the project in either of the hospitals concerned although the overall project appears to have been conducted with the approval of various state health bodies and presumably individual hospital administrations, although this is not clear.
The manuscript was rejected on a number of grounds, mainly relating to questions of methodology and partly related to the question of publishing a small subset of a much larger set of data (also to be published eventually according to the website of the national project). The submission did, however, raise other ethical questions that remain a matter of some debate among the editors concerned, and we seek the help of COPE in addressing these since it appears this sort of situation is likely to come up again with increasing regularity. Our first question relates to the study subjects study. In the submitted paper, the assumption appeared to be that the patients were the subjects and their ‘recruitment’ was discussed. However, we feel that the subjects of the investigation were the staff of the participating hospitals since it was their drug prescription administration and documentation behaviour that was being examined before and after a behavioural intervention.
Our second question regards the nature of the project. Is it a quality assurance/improvement activity that does not require ethics approval for its conduct and/or publication of results? Or is it actually a research study examining the behavioural effect of an educational intervention on hospital staff, and as such does require ethics committee consideration, approval and possibly individual participant (staff) consent?
This case prompted a discussion on the differences between a study and an audit. Most agreed that if there is an intervention, then it is a study, but it was pointed out that there are regional differences, and different countries have different policies on what type of studies need ethics approval. The Helsinki declaration discusses “human subjects” and so does not make a distinction between patients and staff. The advice from the Forum was for the journal to develop their own policy on this issue and to perhaps commission an ethical debate around the subject for publication in their journal. The Forum also reiterated the fact that even if a study has ethics approval, the editor does not have to publish it if s/he is unhappy about any of the aspects of the study.
COPE suggested we develop internal policies regarding situations like these, and this was discussed at our subsequent editorial board meeting. The Committee's advice was found to be very helpful by the board, and in particular the agreement with our assessment that the staff, not the patients, were the subjects of this particular “experiment”, and some discussion occurred surrounding this and other cases discussed at the COPE Forum meeting involving conflict of interest issues (new ICMJE guidelines) and Clinical Trial Registration.
Notices regarding conflict of interest and trial registration are being considered for inclusion in our instructions for authors and also for a new set of editorial guidelines.
The more difficult ethical question is yet to be fully resolved. However, we will continue to deal with such cases on a case by case basis and hopefully reach consensus among the editors.