As editor of a psychology journal, I received a manuscript from a group of scholars. The authors describe a qualitative online study with adolescent girls, aged 15–18 years, who met in person with a stranger they first ‘met’ online. The girls describe their reasoning about the risks, the safety measures they used and reactions to discomfort they experienced in the meetings.
The authors noted on our required information form that they “Confirm that all the research meets the ethical guidelines, including adherence to the legal requirements of the study country.” They also note in their cover letter that the paper conforms to APA (American Psychological Association) standards.
In the paper, the authors note that “parental consent was not required” because “all of the participants were older than 15 at the time of the interview, which is the legal age in the country where the study was performed”.
Because they identified the source of a number of quotations from the interviews that they conducted as being from 15 year olds, I contacted the first author for clarification. I also asked where the statute is listed that states 15 years as the age of consent in your country and also asked if the study was reviewed by an ethical review board.
The author confirmed that the legal age is 15 years and the sentence should have read “all the participants were 15 years old or older.” They agreed to correct the paper. They stated 15 years was set in the project as the age where they would not require parental consent, but the youths themselves were informed about the procedure as well as their rights and agreed to participate. They said the law does not require informed consent when personal data (ie, data that could directly connect the information collected to the specific person) are not being gathered and stored during the process (with the exception of biomedical research). Hence institutional review board approval was not required and the project was therefore not reviewed by an ethical board. However, the project proposal contained a detailed description of the procedure, including the ethical aspects. The project proposal was approved by a university, and evaluated, approved and funded by a grant agency.
My concern is about the age of the participants. Does the Forum have a recommendation regarding the requirements for parental approval for participants as young as 15 years, even if the legal age of consent is 15?
Question(s) for the COPE Forum • What is COPE's position on research on 15–18 year olds without parental permission in a country where the legal age of consent is 15 years?
The Forum suggested there are two issues here: the age of legal consent without parental approval and the ethical issue.
While the study has institutional backing, some of the Forum were of the opinion that the study should have been reviewed by an institutional review board. Only an institutional review board or an ethical board can judge whether or not consent should have been obtained.
One view was that parents should have been informed for the younger aged participants (15 and 16 year olds). However, another view was that the benefits outweigh the risks, and that if the parents had been informed, that may have prevented the participants taking part in the study. The age of consent varies widely in different countries. If participants are over the age of consent for that particular country and the study was done according to national standards, then the authors should be allowed to publish. A suggestion was that if the paper is accepted for publication, the editor could put a statement or note on the paper around the issue of consent, in the cultural context. It may also be useful for the editor to write an editorial comment as readers may also have similar questions.
Since many journals have international authors, should the onus be on editors if there is lack of clarity to confirm the norms elsewhere. Do we need universal standards for issues like this?
The reviews for the article were returned and the article was rejected based on the merit of the paper. The matter regarding this specific submission is closed. The authors followed the letter of the law in their country, but the editor still wonders if there should be a universal age for consent of minors, without parental approval. There are many sides to the issue.
A manuscript was submitted to our journal that describes a social media advocacy campaign that was run by an international NGO for the purpose of eliciting public support for a new law in a low-middle income country. The authors are from the NGO and the government department in that country, that together funded and ran the campaign, and also collected and analysed the data used in the manuscript.
Some of the data reported in the manuscript were survey data collected from people who signed the online petition in support of the proposed law. The manuscript provides information that could be useful for others planning similar advocacy campaigns. The data are reported in grouped format (counts and percentages), such that participants are not able to be identified from the results. The nature of the data reported in the manuscript is not of a sensitive nature, and the study would generally be considered a low risk project (answering an online survey about how the participant found out about the campaign and demographics of respondents etc).
The authors state that all respondents agreed to participate in the research. However, the study has not been reviewed or approved by a human research ethics committee.
Question(s) for the COPE Forum • Would retrospective research ethics committee review be appropriate to consider in this situation?
The majority view from the Forum was that the editor should obtain retrospective ethics approval for the study. However, the Forum noted that it is up to the editor, and it is his judgement call; if the editor is happy with the current position, and common sense tells him that the study is sound, then he should publish.
Although low risk, some of the Forum cautioned that the editor should err on the side of caution as the study involves human subjects, and the advice was to go back to the authors and ask them to obtain ethics approval for the study. If retrospective approval is obtained, the Forum advised a note on the paper saying that retrospective approval was obtained, in the interests of full transparency. A poll of the (8AM) audience revealed that the majority were in favour of going back to the authors and asking them to obtain retrospective ethics approval.
Another view from the Forum was that editors should only seek retrospective review under extraordinary circumstances. As a norm, retrospective approval should not be used for any study that has been completed, unless there are exceptional circumstances (research conducted in a war zone for example). A suggestion was for the authors to provide more specific information on the type of consent that was obtained and for this to be published as an appendix to the paper.
The authors were advised by the editor that they needed to address the issue of lack of ethics approval for the study and it was recommended that they seek retrospective ethics approval from an institutional review board. However, the authors resubmitted the manuscript without ethics approval and stated that ethics approval is not required for this type of study (surveys) in the country where the study was conducted. The editor requested they supply further material, such as a letter from the research ethics authority in the country or other official document that confirms this type of study is automatically exempt from requiring ethics approval, and participant information and consent statements.
The journal is waiting on material from the authors to confirm the study meets accepted standards.
Follow up (October 2016): The authors submitted a response to the journal. Rather than evidence of exemption from ethical approval, they obtained retrospective ethics approval from a relevant institutional review board in the country and provided the certificate. The manuscript has now been accepted.
A paper was submitted to our journal. The managing editor was concerned about patient information in the paper and queried the authors. The authors responded that the data were collected from routine samples and so consent was never obtained. The patients were lost to follow-up, and there was no ethics committee approval as it involved the study of existing data, but they did discuss with the institutional review board who said it was exempt.
The cohort was 2500 patients, all with one syndrome, in one hospital. The paper contains two tables that display data from 12 patients: sex, age, presenting symptom, as well as laboratory parameters and outcome.
Question(s) for the COPE Forum • Are these patients identifiable? • If we remove, say, age and sex, would that be sufficient to render the data anonymous? Would we lose clinical significance by removing age and gender for those patients, although the paper does mention that of the 12 patients most were female and gives the median age group? • Should we publish this without patient consent? • The study also mentions controls who underwent biopsy, but what is not clear is whether those controls were also from the same cohort and perhaps underwent biopsy as part of routine screening. Would they need ethics approval for biopsy?
The Forum agreed that the case was concerning. With the sophisticated knowledge and information that can be trawled from the internet, the concept of anonymity is becoming more and more difficult. However, editors have to do their best to protect patients’ identities, and it is has to be an editorial decision on the risk–benefit of publishing.
Journals have different policies on publishing papers without consent or approval, although many of the Forum participants said that they would reject a paper if there was no patient consent and/or no ethics approval.
The advice from the Forum was to contact the authors and ask for the Institutional Review Board (IRB) documentation. The editor should ask the authors to clarify why the study was exempt from ethics approval. If the authors insist the study did not require ethics approval, then the editor should ask for proof—for example, a written statement from the IRB. The editor could also contact the IRB directly with their concerns.
The Forum also advised that the issue of consent should be raised with the authors—both consent to participate in the study and consent to have the data published. Was consent received from the whole cohort? Did the authors receive consent to publish from the patients whose data were published?
Following the discussion at the Forum, the journal asked the authors to provide any information that they had about informed consent at the time of treatment. The authors sent their translated form, which specifically mentioned they had consent for treatment and not for publication explicitly. Hence on these grounds, the editor decided to reject the paper. The editor informed the authors, who did understand and said that they could not find the patients to seek consent as they were lost of follow-up. The journal considers the case closed.
We routinely ask for ethics committee approval from every research manuscript submitted to our journal. Sometimes, studies from different countries may not have ethics committee approval and authors may claim that their study does not need approval. In such situations, we consult COPE’s “Guidance for Editors: Research, Audit and Service Evaluations” document and evaluate the study at the editorial board and decide whether or not it needs approval.
However, as an editor, what should I do in the following situation? Any research, be it a retrospective analysis of routine patient data, an in vitro study or a study on bacteria requires institutional ethics committee approval in country A. In country B, ethics committee approval is not required for such studies (this information is provided by the authors). The journal receives two such studies, one from country A and one from country B. Neither has ethics committee approval. The authors of both manuscripts claim that their studies do not need approval.
Question(s) for the COPE Forum • What should best editorial practice be in this situation? —Accept both papers for review. —Accept the paper from country B for review but reject the paper from country A (or ask the authors of the paper from country A to apply for institutional ethical approval). —Reject both papers (or ask the authors of both papers to apply for institutional ethical approval).
The Forum noted that editors cannot be expected to know the national guidelines for the conduct of research in individual countries. It is up to authors to make sure that they comply with their national guidelines. One suggestion was that the national standards where the research was done should apply here, or the editor could make a judgement on his own national standards, in the country where the journal is located, and based on his knowledge of what he thinks requires ethics approval. It is good that the journal has a process for discussing this issue among its editorial board, to uphold minimum standards when the authors declare that they do not need ethical approval.
For country A, where ethics committee approval is required, the Forum suggested that the editor investigate whether the research does need ethics approval. It may be that the research is exempt from approval. But if the editor discovers that the study did require ethics approval and the authors failed to obtain approval, he has a responsibility not only to reject the paper but to follow this up with the author's institution and/or the ethics committee. Otherwise, the authors may just submit the paper to another journal.
For country B, the Forum suggested asking for proof that the study did not require ethics approval—for example, a letter from their ethics committee stating that the study does not require ethics approval.
The editorial board of the journal reviewed the Forum’s recommendations and have decided to continue to ask ethics committee approval for every study submitted to the journal from all countries. If the study requires ethics approval, the authors will be asked to provide this. If they cannot provide ethics approval, the journal will reject the manuscript and contact the institutions or related bodies in the authors’ country, if necessary. If a study does not need ethics committee approval after review, the journal will ask authors for confirmation from an ethics committee or an independent committee indicating that the study does not need ethics committee approval according to the research integrity rules in their country. The journal has updated their instructions to authors with these details.
The author was the subject of his study. He depleted himself of a vital nutrient until he had overt clinical and biochemical signs of the deficiency. He monitored various biochemical parameters as he became more deficient and submitted two manuscripts presenting his results: one detailing the biochemical changes and one detailing the differences in results obtained from different commercially available assays for the nutrient.
Reviewers of the first manuscript raised some concerns about the experimental model used and also concerns about the ethics of the study, particularly the lack of any oversight from an institutional research board. The second manuscript was not reviewed and both were rejected on the basis of the ethical concerns raised by the reviewer and concerns about the scientific validity of the results obtained from one individual.
The author feels very strongly that his experiment was not unethical and argues for the autonomy of researchers. He provided the following arguments for his study: — The author is both experimenter and single subject, so the requirement for informed consent does not apply. — There is no institutional involvement, so there is no possibility of coercion. — The subject was assessed by a psychiatrist and found to be competent to evaluate the risks and benefits and to accept full responsibility for the conduct of the experiment. — The Declaration of Helsinki does not comment on self-experimentation; it is concerned with research in patients and healthy volunteers. The requirement for ethics approval therefore does not apply. The Declaration of Helsinki cannot be cited as a reason for rejecting reports of independent self-experimentation. The Declaration was not intended to prevent autonomous independent humans from performing and reporting self-experimentation — The subject was monitored by a qualified psychiatrist who continually assessed the condition of the subject. It was agreed in advance that the psychiatrist would intervene if, but only if, there was an immediate life-threatening condition. — The motivation for performing the experiment was ethical in that the subject wanted to investigate the gross differences between the immunoassays he found in an earlier experiment because he was aware of the potential severe consequences of such errors in measurement of this nutrient. There was no conflict of interest. — The need for IRB or ethics committee approval would totally exclude from publication any self-experimentation research performed by an independent researcher because they will not have access to any ethics committee or institutional review board. This would have prevented the publication of reports of highly useful reports (http://careers.bmj.com/careers/advice/view-article.html?id=20002566 and http://www.bmj.com/content/341/bmj.c7103.long)
The author appealed the decision to reject his manuscripts. Although the appeal was not upheld, we agreed to bring the author's arguments for self-experimentation to the COPE Forum for wider discussion. It is worth noting that the author’s two papers were eventually published in another peer reviewed journal without any negative response over the ethical issues.
Question(s) for the COPE Forum • Do other editors at the COPE Forum consider manuscripts on self-experimentation without formal IRB approval? • What criteria do editors use to determine whether such studies are acceptable?
The Forum suggested there are two issues here: the ethical issue of self-experimentation and whether the study warrants publication with an n of 1.
The Forum agreed that the author has the right to perform the experiments on himself, but he does not the right to have his findings published. There have been some highly publicised cases of self-experimentation, which in one case led to a Nobel prize for Barry Marshall after he infected himself with Helicobacter pylori (the causative organism of peptic ulcers). There was also the case of Spurlock’s documentary, Super Size Me, a social experiment in fast food gastronomy.
Regarding the second issue, the Forum agreed that this has to be a judgement call for any editor. Does the study warrant scientific publication? The author has the option of blogging about his experiments if he wants to disseminate his results.
The editor told the Forum that they were interested in learning if any journals had a specific policy on this issue, but among the Forum audience, no journal had such a policy. The discussion ended in agreement that this is a topic that needs further debate.
We have a query regarding institutional review board (IRB) approval for a paper in production.
The paper reports on a 2 year follow-up and cost-effectiveness evaluation for a treatment programme. A previously published paper reports on the original evaluation of the treatment programme. The authors have not obtained IRB approval for either body of research.
The initial research was described as a report of outcomes from 5 years of clinical experience with the programme, rather than as a clinical trial, and as such IRB approval was not sought. For the paper currently under consideration, the authors’ original statement in the paper was that “Institutional review board approval was not required as patients were treated with approved diagnostic and therapeutic procedures according to generally accepted standards of care”. We were unable to verify this as a valid reason for exemption from the requirement for IRB approval.
Having found no clear grounds for the exemption on the basis offered, we asked the author to provide a reference or further information regarding this basis for exemption. The author responded that the research was exempt under the following US federal regulation: “Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects”.
Our concerns with this justification are that the data are not publicly available, and that the data include follow-up telephone interviews, which seem in conflict with the requirement that the data should be de-identified, and that indeed the follow-up interview information are new data, not existing data or records.
Question(s) for the COPE Forum
Is this research publishable in the absence of IRB approval?
The majority of the Forum noted that they would err on the side of caution—if the editor is unable to verify that the study received IRB approval, then they suggest that he should not publish. The Forum advised contacting the authors and informing them of the journal’s decision. The Forum noted that this is a good opportunity to look at the journal’s instructions to authors. The instructions to authors should be very clear about the journal’s policy on IRB approval, and what type of ethical review is required by the journal.
If however, the editor did decide to publish, the Forum would advise publishing an explicit statement within the paper, outlining the ethics approval process and detailing the facts of the case and what the actions of the editor were.
The authors elected to ask a private institutional review board (IRB) to review the study, and the private IRB verified that the study was exempt (retrospective, de-identified data). We obtained a copy of the IRB’s decision and published the paper with an explanation of the exemption.
A graduate student submitted a paper to a journal and noted that in her country, unless the research is directly medical, institutional review board (IRB) approval is not required or completed. The journal has a policy of requiring IRB approval on any human subjects’ research. This study was looking at practitioners and their work with students having a particular diagnosis.
The editor received a note from the author with the information that in the country of origin, no ethical approval was required on a master’s thesis. The study was conducted in accordance with ethical principles of the Helsinki declaration. The author noted that the results of the master’s thesis might be of importance and could make a contribution to the literature. It was supported by the university that sponsored the thesis but had not gone through an IRB.
Question(s) for the COPE Forum
1. Is there ever a time when IRB approval should not be required before review and publication of research?
2. How strictly should the editor adhere to these requirements? With this submission, it would be an automatic reject without IRB approval.
The Forum advised common sense in approaching this case. Is the study of value? Does the editor have any concerns regarding the research or any other ethical concerns? If not, and the editor wishes to publish the paper, she should obtain proof from the authors that the study does not require ethics approval. This could be in the form of guidelines from the country in question, or a letter from an institutional review board (IRB) stating that the study does not require ethics approval. Hence the editor should ask the author to provide a written report on why the study did not require ethical approval.
The Forum agreed that it would be harsh to penalise the authors if they have done an ethical study within the framework of their local laws, which can vary greatly from country to country.
Of course, there is no guarantee that a study is ethical even if it does have approval from an IRB, so the editor should always be wary.
The Forum noted that transparency is important, and if the study is published, the editor may want to publish a notice explaining why it was published in the absence of IRB approval.
Another suggestion was for the editor to ask her editorial board members to review the paper and seek their opinion, and to help establish guidelines for future cases.
After receiving the Forum’s advice, the editor established an ethics committee of members of the editorial advisory board. The editor presented the question to them and also forwarded the submitted manuscript. The sample was small, and the editorial advisory board agreed that individuals could be identified in the community of origin which would negate the assurance of anonymity. The editor rejected the article.
A manuscript was submitted to our journal describing a study of a new drug. The manuscript had only one author who gave their affiliation as a company that we can find no record of online. It describes a study in which they appear to have developed a new drug, carried out a toxicology study in mice and then, because no adverse effects were seen, tested it on one patient and five healthy volunteers. There appear to have be no stages in between. There is no statement of informed consent in the manuscript. There is a statement that says the study was reviewed by the institution’s human subjects committee but we cannot find a record of the institution.
We had ethical concerns about the study so we asked the authors for more information, specifically: the details of the ethics committee that approved the study; whether they had informed consent from the patient and healthy volunteers; whether the trial had been registered before it commenced; how the patient and controls were recruited; what information the patient and controls were given before they agreed to participate; where the study took place; what safety/monitoring was in place in case of any adverse effects; what approval was obtained (eg, from the country’s drug regulatory body) before this drug was injected into a human for the first time; and what other research had already been carried out on this new drug? The author responded to our email asking to withdraw the manuscript but did not answer any of our questions. We responded that we had serious ethical concerns and therefore would not be withdrawing the manuscript at this time. We informed the author that we would be investigating the potential ethical issues and asked again for answers to our questions. We have heard nothing from the author since.
The author is based in a country that does not appear to have a national medical board and is not affiliated to an academic institution or hospital. The affiliation given is the company that we can find no record of. The author’s email address is not an institutional or company email address. We have contacted the professional society for the medical specialty of the author but they have informed us that the author is not a member and therefore they cannot investigate. We have also searched for the author on the registry of the regional medical board for the region in which the author is based, and they are not registered with them either. We do not want to reject the manuscript until an appropriate body has agreed to investigate but we are struggling as to how else to report this.
Questions for the COPE Forum (1) Does the Forum agree that we should continue to try and find someone to investigate this before we reject? (2) Does the Forum have any suggestions on how we can report this?
The Forum agreed that the editor had made a tremendous effort in trying to resolve this case. The Forum reiterated that in instances where a paper is rejected or withdrawn, there is still a responsibility to pursue any suspicions of misconduct. In this case, where the author wishes to withdraw the paper, it was agreed that the editor had probably done as much as he could. In some countries, this type of behaviour might be considered criminal, and a last resort might be to inform the legal authorities in that country.
The Forum advised that there is always the possibility that the paper is a hoax, but the editor has to assume, until otherwise proven, that the author has submitted the paper in good faith and should investigate this as far as possible. This is a particularly difficult case as it is a single author paper. If there had been more than one author on the paper, the journal could have applied the revised criteria of the International Committee of Medical Journal Editors (ICMJE). The fourth criterion states that all authors are accountable for all aspects of the work and are responsible for ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. However, this is not applicable in this case as there is only one author.
The only other suggestion was for the editor to write an editorial on this topic, emphasizing that this type of behaviour is unacceptable.
After the case was discussed at the forum, the journal made one further attempt to report the unethical research. This was successful and the case is now being investigated by the relevant governmental department in the country where the research was carried out. The editor also discovered that while he had been trying to resolve this case, the article had been published in another journal. He informed the editor of that journal of the duplicate submission and his concerns.
Follow up (June 2014):
After the relevant governmental department agreed to investigate, the manuscript was rejected by the journal. The journal did not receive a response from the editor of the other journal in which the article had been published.
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.
We became concerned that not all of the co-authors were aware of a research paper submitted to our journal due to the difficulty receiving responses from the email addresses that had been supplied and their nature, given that the authors all worked in a hospital/academic institution. Despite repeated requests and attempts we remained dissatisfied with the responses and did not feel certain that all of the authors were aware of the paper. We therefore requested further documentation signed by all of the authors, but all of the signatures appeared to be signed by the same person, and hand writing analysis suggested this was highly likely. In addition, the statement from the ethics committee also had a similar signature. The letter from the ‘head’ of the ethics committee was on blank paper, not letterhead, and was not received as an original hard copy.
We therefore contacted the head of the ethics review committee who was different to the head on the document we had received and about which we had some concerns. The current head eventually confirmed after a second request that the doctor who had signed the previously supplied document was not on the committee. Ethics committee clearance has since been granted retrospectively after the paper was submitted.
As a result we have significant concerns about this paper, its ethical clearance and some of the documentation that has been supplied. We have advised the authors that we have suspended processing of their paper and that we would seek further advice from COPE. Our intention is to report our concerns to the hospital director and formally reject this paper.
We would appreciate guidance on any further action we should take.
The Forum agreed with the proposed course of action of the editor. It would not be appropriate in this case to simply reject the paper. It is very clear that something serious has happened in relation to the governance of this paper, and if the editor were to simply reject it, it is quite likely that the authors will simply submit elsewhere. In these situations, COPE recommends that if an editor has a concern about a paper, even if they end up rejecting it, they must tell the authors that they will take it further and that it is highly likely that it will be referred to their institution for further investigation.
(COPE Council also discussed this case outside of the Forum). Council members agreed with the proposed course of action. This appears to be a very serious breach of ethics and the author may repeat this type of misconduct with another journal.
First you should inform all the authors of what you are going to do in a factual, non-accusatory way. As there may be legal implications, you should also ensure that the letter to the hospital director has to be purely factual, with dates and copies of letters between the journal and the ethics service and the authors. Claims about forged signatures need to be backed up by a report of handwriting analysis (or if you can't supply that you should not make the accusation directly). The journal should consider taking legal advice. You may want to pursue this issue further to a higher institutional level. Hence, in addition to the hospital director, if there is another head of the academic institution or some kind of oversight office then you might consider contacting them also. If the authors are working in an academy (university) and the hospital is affiliated to that university, then there may be a research regulatory body of that university that could be informed.
The journal followed the advice given by COPE and sought legal advice from their publishers before writing to the hospital director raising their concerns. The editor also rejected the paper and gave the authors the reasons for doing this. The editor has had no response and so he plans to write again and also write directly to the head of the ethics committee.
Update (September 2013):
The editor has still not had a response from the hospital director despite following up the original communication and copying in the ethical review chairman. It was agreed that the next step should be to contact the research integrity office.
Update (February 2014):
The editor has now had a response from the ethics committee, recognising the nature of their concern. The ethics committee is going to inform the university rector.