A clinical trial was conducted in a low income country. The trial involved two schools. At the first school (the control school), children would receive a one-off drug treatment for a common infection (such “mass drug administration” is the norm for treating and breaking the transmission cycle of this infection). At the second school, children would receive the same one-off drug treatment plus a long term oral nutritional supplement. The hypothesis being tested was that the supplement might boost the effectiveness of the anti-infective drug. The researchers also wanted to assess whether this supplement might have any side effects when administered in this way. The risk of side effects was low, but nevertheless there was a risk.
In the trial protocol, the researchers stated that children would be asked to invite their parent/guardian to the school on the day that the trial was due to begin, and the parent/guardian would be asked to sign an informed consent form. The consent form stated that the parent/guardian would be free to withdraw the child from the study at any time, and that the child would not be disadvantaged in any way from such withdrawal. The protocol also stated that if the parent/guardian was absent, a representative from the Parent Teachers Association (PTA) would sign the informed consent. An IRB approved the study.
However, in the clinical trial report, the researchers stated that they did not seek parental consent. Instead, they simply asked one PTA representative at each school to sign consent on behalf of all the children in the school. In the trial report submitted to the journal, the researchers justified bypassing the parents as follows: "some children could be excluded from participating in the study and hence disadvantaged from receiving treatment if their parents/guardians did not give consent." The editors feel that the parents themselves would have been best placed to assess the relative risks and benefits of allowing their child to participate in the trial.
We have been unable to find out from the authors whether they told the IRB that they deviated from the protocol and whether the IRB approved the deviation.
One of the researchers commented that he felt the type of consent used was appropriate for this particular country’s setting. Another of the researchers commented that the PTA representatives who gave “mass consent” were themselves parents.
However, the journal editors are concerned that (a) there was inadequate protection of a vulnerable group; and (b) the researchers appeared to use a consent process that made participation more likely rather than a process that fully protected the children. The paper has been rejected due to methodological weaknesses and the editors’ concerns about the informed consent process, but do the editors need to take further action?
The advice from the Forum was to contact the local IRB and determine whether they are aware that there was a discrepancy between the proposed study and what was carried out. Were the IRB aware that the investigators deviated from the initial protocol? If it transpires that the IRB did not approve the study that was eventually carried out, the advice was to contact the authors’ institutions informing them of the situation and asking them to investigate.
The editor wrote to the IRB’s secretary and chairman. Unfortunately, as is often the case with IRBs in low income settings, there was only a mailing address (no email, no fax, no telephone number). The editor sent his letter in the post by priority mail, and so assumes that it was received. He awaits a response.
However, in the mean time, the editor received a letter from the senior author of the paper. The letter stated that he has been in contact with the IRB and the IRB has now granted retrospective approval for the consent that was used in the trial (ie, asking one PTA representative at each school to consent on behalf of all the parents). The senior author wrote to the journal asking if we would now reconsider the paper. The editors gave a firm no, saying that (a) such retrospective approval from the IRB does not allay the initial concerns about mass consent by two individuals and (b) the paper had too many scientific weaknesses to merit publication.
This is how I dealt with an author who submitted a fabricated manuscript to my journal.
A junior doctor submitted a paper about the use of a drug in a particular condition. Three expert reviewers were sure that the author did not undertake the claimed study, emphasising that the drug was not available in our country (Middle Eastern country) and it had not been registered for clinical use or for use in clinical trials at the time when the paper was submitted. The author also mentioned using tests that were not available in our country at that time.
The author was advised that his paper was excellent and therefore he should publish it in a UK journal. The author took the advice. I contacted the editor of the UK journal and warned him about the author. The UK journal rejected the author’s paper.
This overseas editor was not available by telephone to discuss the case, so the Forum discussed it in his absence.
The general view of the Forum was that they could not support the conduct of the editor. The Forum wished to convey to the editor that his method of dealing with an author suspected of fabrication was not acceptable. If the editor expects authors to tell the truth, then he must set an example. The editor could have placed himself in a very difficult situation. There are clear guidelines in the flowcharts on what to do if you suspect data are fabricated and the editor is advised to follow these processes in the future. The Forum also pointed out that the editor has a role in educating the author on the seriousness of data fabrication and should have considered handling the matter himself rather than passing it on to another journal. The chair of COPE agreed to contact the editor of the UK journal to determine if the issue of data fabrication is being investigated by them.
A paper was submitted which described the outcomes of a clinical trial evaluating a particular device. The device was claimed to represent a placebo version of an active device intervention. The paper was reviewed fairly critically and one reviewer pointed out that from the reference list it did not seem that the authors had developed this type of placebo device, while the title of their paper suggested that they had. We invited the authors to respond, asking them to address this and other criticisms. The revised paper was then evaluated inhouse and by the academic editor, who commented that the authors still claimed development of the device in the revised paper, citing their US patent. However, the academic editor had previously published work suggesting that his team had developed a similar device before the patent was given (however, the academic editor had not contested this legally at the time). An inhouse editor compared the patent with the previously published papers and the devices did seem very similar.
Before we could write back to the authors with our decision, the corresponding author chose to withdraw the paper for unrelated reasons.
We think that the author will want to publish the paper elsewhere, but wonder what our obligations are as regards to following up the claims regarding who developed the device?
The general consensus of the Forum was that this was a patent issue between the authors and the academic institution. Although it is conceivable that two individuals could have come up with the same idea, the advice was that the journal should not get involved. The view of the Forum was that the editor should not pursue this issue further.
In April 2007, an original scientific article was published on line (ahead of print—it is now published in print, September 2007). In July 2007, the editors received the following request from a scientist who read this article: "Since I am interested in this subject and I already work with it, I need to know some technical information from the authors. I have called the group five times and wrote them several emails, but unfortunately there was no response. I have decided to write to the editor to help me get the information I need".
What should be the responsibility of the editors to try to influence the authors to comply? Note that the Instructions to Authors include a statement that the journal adheres to the COPE guidelines.
The Editors have already replied as follows:
"We agree that manuscripts should provide all information regarding the technical details to allow repetition of the scientific work. In addition, it is generally accepted scientific practice for investigators to share materials and reagents that are relevant to the experiments and are not publicly available to allow parallel work, once the research has been published. It is generally accepted that "publish-ahead-of-print" manuscripts are published work. However, the editors consider it beyond the scope of their activities to intervene in discussions or interaction between investigators regarding work published in the journal."
Is this response appropriate or should we have done more?
The Forum considered that the editor has a duty to write to the authors and remind them that they are obliged to provide technical details to any interested party. The editor might wish to try to establish whether the authors are just being uncooperative or if there is any more ominous reason as to why they are withholding the details. If the editor receives no response from the authors or the information is not available, then the scientist could be encouraged to write a letter to the journal with his complaint. In this way it will highlight the fact that the authors are not following good practice. The editor should ensure that the instructions to authors states that all data should be available to interested parties. COPE is generally not in favour of sanctions and would not recommend them in this situation
In response to the advice from COPE, the editor had made the following addition to the Instructions to Authors to make it clear what is expected: “Authors should fully describe their methods so they could be reproduced by others. Additional technical information, unique reagents, antisera, cell lines, and genetically modified animals necessary to replicate the work should be made be available to interested parties”.
The editors received a manuscript from a Far Eastern country ready to accept. The senior author (who has spent a lot of time in the West) was in the US when the editors asked for final signatures to be sent. The senior author instructed his team to collect and fax signatures while he was away and this was sent to the editors.
When the signatures were examined by the editors, it appeared that some of the signatures had been written by the same hand. The editors challenged the senior author who investigated immediately upon his return and a fax was sent:
“…The last copy was signed in my absence and not all signatures were signed by the authors personally but by other colleagues with oral permission from the relevant authors ……Some of the signatures may still look similar in writing style and this was due to the fact that some of the colleagues were not familiar to [sic] signing their names in English, but these were truly their signatures.”
The new batch of signatures show differences from the previous signatures and now appear to be signed by separate individuals.
This highlights a potential issue applicable to anyone not familiar with using non-European scripts.
Should the editors be worried about this? Should the explanation be accepted? If not, what is the next step?
Members of the Forum agreed that the editors should accept the explanation of the authors and believed that the case has probably arisen out of cultural differences. From an educational point of view, the editors could point out to the authors that it is not good practice for anyone to sign on behalf of an author. However, in the absence of any other evidence of misconduct, the Forum believed this was a minor discretion that could be overlooked.
Following the COPE meeting, the editor was greatly reassured and was happy to accept the signatures. The journal still insists on signatures but is now happy to accept signatures in the authors’ mother-tongue script.
A paper describing a novel technique was submitted. Three out of four external reviewers felt that the results could not be true. The manufacturers of the tool used in the technique provided evidence to support the reviewers’ claims that the results were not feasible.
The editor wrote to the authors asking them to explain their results. The authors replied saying that they were unable to replicate their initial results and wished to withdraw their manuscript.
The editor pressed the authors for a full explanation of the results, including the reasons for not ensuring that the results could be replicated prior to submission. The authors replied again to reassure the editor that they shared the concerns about not being able to replicate the initial results, and explaining that they had alerted their head of department who has appointed an investigation committee to look into the matter further. The authors have assured the editors that they will be informed of the outcome of the investigation.
This case has been brought to the committee for information only, as an interesting example of authors independently taking the appropriate steps to investigate anomalous results.
A team of Western researchers carried out a longitudinal study of pregnant nomadic tribeswomen in Africa between 2002 and 2003. They took blood samples during and after pregnancy to test for a specific disease. Those who tested positive were treated. An attempt was also made to trace contacts, and the women’s status was rechecked after pregnancy to ensure effective treatment.
The researchers also had institutional ethics approval and verbal consent from the women to take anonymous blood samples for antenatal HIV testing. These samples were unnamed and batch tested in a regional laboratory. Those who tested positive were not treated or told the results. Although low cost medications for the prevention of mother-to-child transmission of HIV were being recommended by the WHO and were being used in the region at that time, the research team made no attempt to provide an HIV service. They judged that any HIV testing or treatment should be implemented formally throughout the region and that it was “beyond the scope of their project”.
Did the research team fail in their ethical duty to the trial participants, and should the journal therefore refuse to publish their research?
The editor informed the Forum that although ethics committee approval was obtained for the study from respected institutions, he was not satisfied that the study was ethical. Members of the Forum shared the concerns of the editor and there was overwhelming support for the editor’s position, in that the research team may have failed in their ethical duty to the trial participants. It was also felt that funding to treat the women could have been made available at the time of the study as the costs of a single dose of HAART to avoid vertical transmission were low. Ultimately it is the decision of the editor whether or not to publish the study as ethical committee approval to conduct a research project does not extend to the editor’s duty to publish its results.
The editor wrote to the authors with their concerns and the authors replied that it had been a mistake for their researcher to have access to all of the results before the women delivered; this was not in the protocol approved by the ethics committee of the African country’s authorities). Apparently, there was a hiccup in their organisation of the study which gave this person the knowledge of the women’s test results before delivery. The proposal from the authors was to simply eliminate the section in the paper that mentioned that the researcher had access to all the results before delivery.
The editor thought this was unacceptable as it was obfuscating the truth, and moreover the authors had made matters worse by saying that in reality the study did not have ethics approval (a different one did, but not the one they actually carried out). On this basis, the paper was rejected and the authors’ supervisory bodies are being informed (the WHO said it wasn’t them, and the editor has yet to obtain the addresses of the supervisory bodies in the USA (where the researchers are based) and in Africa (where they had the approval of the governmental authorities)).
The editor of this journal, in common with other journals, requires that, where appropriate, studies published should have been approved by the relevant ethics committee. In some cases researchers have reported to the editor that they have found no committee willing to accept competence, or that different committees are taking different lines on which studies require approval.
As an example of the first case, a British university uses the local NHS ethics board. As far as the board is concerned, if the study does not involve NHS patients or staff it is not within their remit. What should researchers do if, as often happens in this field, subjects are involved who are not NHS patients or staff?
As an example of the second, some ethics boards consider that non-invasive biomonitoring, such as salivary cotinine monitoring, requires approval, and some do not.
On a broader note, members of the Forum cautioned that editors should consider IRB approval as only one indication of the ethical content of a study. It is not sufficient in itself. This is particularly relevant when considering studies performed in third world countries.
Biological monitoring is a common procedure in assessing the dose of contaminants from a workplace atmosphere. It may include measuring a contaminant, such as lead in blood, or a resulting metabolic product, such as mandelic acid in urine following styrene exposure. A related process is using adhesive tape to strip the surface layer of a small area of skin to measure the dermal deposit. Clearly these procedures require the consent of the person monitored, and this is not an issue. In Britain such procedures are included in various HSE regulations and guidance. They are commonly used in research.
The Human Tissue Act 2004 (http://www.opsi.gov.uk/acts/acts2004/20040030.htm) requires a licence from the Human Tissue Authority for the storage of material from a human body (section 16e), for purposes which include “obtaining scientific or medical information about a living or deceased person which may be relevant to any other person (including a future person)” (Schedule 1). Most of the Act came into force in April 2006.
The editor has been told by members of his Editorial Board that this is being deemed to include blood and skin samples taken for biological monitoring purposes. This is clearly an unintentional result of inadequate drafting.
This Act applies in England, Wales, and Northern Ireland. The Human Tissue (Scotland) Act 2006 focuses on tissue for transplants, and apparently does not cause a problem for biological monitoring. The BMA Medical Ethics Department has produced guidance on the Acts (http://www.hta.gov.uk/_db/_documents/Human_Tissue_Legislation_-_Sept_06_final.pdf) but this does not mention the biological monitoring problem.
Clearly this is more of a problem for researchers than for journals directly, except for the general ethical problem of supporting the law. For the moment the editor is thinking of adding to the paragraph on ethics in the instructions to authors a requirement that studies must comply with the law in the place where they are carried out, but is not proposing to question authors of English papers which include biological monitoring.
Has COPE any advice or comments, please?
Members of the Forum believed that in this situation, the onus is on the authors and the institutions to ensure that any procedures carried out are legal. Also, the ethics committees should be aware of whether or not an individual or institution has approval to carry out certain procedures. The Forum recommended that the editor write to the Health and Safety Executive explaining the issues and request further advice from them.
A manuscript was submitted from UK authors. The study was a case series of infants with a particular condition. A table in the manuscript contains descriptive data which are critically important for the readers with respect to understanding the risk of this condition in young infants and the likelihood of abuse.
The question is whether this table violates the law with respect to confidentiality/privacy. No IRB was obtained (case series/QI project). No consent was available from individual patients.
COPE’s advice would be appreciated.
Similar to case 07-10, members of the Forum felt the same issues of confidentiality and public interest applied in this case. Most were in agreement that consent would not be obtained, and as there was a chance that one or more infants could be identified from the data, the paper should not be published. Some of the members of the Forum suggested that perhaps the paper could be presented as a multivariate statistical analysis, removing individual identifying data. If this is not possible, the Forum again advised that the editor should consider not only the ethical and legal consequences involved in deciding to publish, but also the data protection issues.