Participant consent

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?

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 research article investigated the effect of the widespread administration of a homeoprophylactic preparation against a bacterial zoonotic disease in a developing country after a period of particularly heavy rainfall. The authors claim to have given this oral preparation to all members of the population over 1 year of age, in three provinces of the country where this disease is prevalent (over 2 million people). This was done in parallel to the country’s conventional vaccination and surveillance programme. The authors claim that this intervention significantly reduced the incidence of the disease in the treated provinces compared with the non-treated provinces.

We asked the authors to provide more information on how they had addressed the ethical aspects of this study and to provide supporting documentation. They stated they would include a paragraph on ethical considerations in the text, but argued that the principle aim of the study was to report the results of a healthcare intervention as a response to an emergency situation and was not classical clinical trial research. They further argued that the product used in the intervention is a registered product of common use on the public health system of the country in question and all the administration was approved and regulated by the “National Regulatory Agency” and “Competing Health Authorities”. They also claimed that they had obtained ethics committee approval from four different ethics committees.

Despite repeated requests from us, the authors failed to provide documentation from the ethics committees or the National Regulatory Agency or to explain how they had obtained consent. They eventually did supply a document in Spanish purporting to be “approval from the National Regulatory Agency for the intervention that was granted after the analysis of proposals by ethic committee and meeting National Regulations from the Minister of Public Health”. However, on translation by one of our Spanish speaking members of staff, it turned out to be a statement of their intention to obtain ethics approval and consent.

We contacted the CDC to enquire whether such an intervention was known to be in use in this country. We were told that they were not aware that this intervention is in use in any official capacity. We rejected the manuscript on ethical grounds explaining to the authors why we were not prepared to consider it. All authors are affiliated to a private institute. The last author is its founder.

We would welcome advice from the committee on whether and how we should take this further, given the scale of the study and the conflicting statements of the authors and the CDC.

A letter was sent to the chief editor of our journal in response to a recently published article in our journal. The author had serious concerns about the ethics and consent obtained as a result of this study and the follow-up by the researchers.

The author explained that he was the physician of two of the “volunteers” who participated in this study and was concerned about informed consent procedures in the trial. Specifically, workers never provided informed consent that their tests, mandated by a company medical monitoring program, be used in any “research” study. His concerns were in four areas.
(1) The researchers failed to inform both the company and the injured workers that they should have been removed from further exposures when their test results showed severe impairment.
(2) The researchers failed to report abnormal findings to the workers in a timely and appropriate manner, a failure that placed these workers’ health in jeopardy.
(3) The researchers failed to fully inform the workers of the known risks of exposure.
(4) The timing and location that the researchers used to obtain signatures on the informed consent forms did not permit the workers to adequately question the researchers and become informed.
One of the author’s patients who was studied was a previously (pre-employment) healthy 40-year-old woman who was found after a period of time at work to have abnormal results. However, no doctor contacted her to explain the results and written communication did not describe them as serious, and so she did not seek further medical attention. Her tests were repeated again one and two years later. The two year test indicated more severe disease. These findings were reported to her 10 months later by one of the researchers who failed to mention their significance in his cover letter to the radiologist’s report. Given the patient’s history, she should have been removed from work immediately, and the researchers should have reported this case of occupational disease to the state authorities. The following year, she sought care from a non-corporate physician and was removed from work the same day.

Another patient of the author’s had abnormal test results in 2005, which were markedly worse on repeat tests conducted in the same year. The researchers wrote to her in September of 2005 and advised her to have a CT scan and repeat testing. A year later, a member of the researcher’s group ordered a CAT scan. In November 2006, the CAT scan revealed moderately severe disease. The patient requested that these results be forwarded to her personal physician. At the time of the author’s first visit with her in late August 2008, she had never seen the results, and neither the company nor the researchers had communicated with her about her condition or continued occupational risk. The author requested that the researchers send him her complete medical records, including communications with the company and the research protocol. However, only incomplete records were sent, omitting the research protocol and including none of the communications with the company.

In October 2008, the author wrote to the IRB Director and filed a formal complaint concerning these matters informing them that one of the researchers was both a paid consultant advising on occupational health procedures while simultaneously conducting the research/monitoring program. This researcher based his published paper on a mandated monitoring program in which the “volunteer” workers had to participate as a “condition of work” in order to keep their jobs. The “research” was based on test results for which full consent had not been obtained. The Director of the Office of Research Compliance and Regulatory Affairs responded in February of 2009, stating that although the committee’s investigation determined that “no misconduct occurred” with respect to any violation of IRB policies, their findings prompted them to institute “modifications to our processes that will help us to continue to raise that bar.” The author concluded that “IRB protocol modifications” were based on an acknowledgment that the researcher’s study violated patient rights, even if the study did not violate IRB rules. The author believes that journal editors have a responsibility to investigate allegations like these.

The authors carried out a study. A homeopathic treatment was given to people with HIV/AIDs. The outcome was quality of life, as measured by a questionnaire after 1 month and 18 months of treatment. Participants were selected for inclusion if they had a HIV seropositive status at the time of study and were not taking any other kind of HIV/AIDs treatment.

The participants were stratified into severely ill (including those who could not walk and were cachectic) and not severely ill. The authors said that they had obtained ethics approval for this study from their own institution in their country of origin and that the Ministry of Health in the country where the trial was conducted had “authorised” the study.

We asked the authors whether the participants had been offered antiretroviral treatment at any time and if not why not? The authors confirmed that the study protocol did not include antiretroviral therapy because “There is no obligation of the ARVs use and conventional medicine is expensive. Many patients...were afraid of white people and of the side effects”.

We asked what the participants were told when they gave consent. The participants were given details of the homeopathic treatment but no mention was made of the existence of antiretroviral treatment. We asked to see copies of the protocol submitted to their ethics committee and the actual approval. The document, which was translated by a member of our staff, did not mention antiretroviral treatment. We asked to see documentation of “authorisation” from the Ministry of Health of the country in which the trial was conducted. There was no written documentation. It was verbal.

We asked why they sought approval from their native country and not the country where the study was carried out. The authors told us that once they had approval from their country, the authorities in the country where the trial was conducted did not require local approval.

We asked how the study was funded and what the authors’ relationship was with the funding body. They provided the names of two funding bodies but no documentation (funding came from funding for a Master’s degree of one of the authors). They did not clarify whether they had any relationship with the funding bodies.

We felt that all participants should have received standard care with antiretroviral therapy, that ethics approval should have been sought from a local ethics committee and that the participants should have been informed about antiretroviral therapy when consent was sought. We were also concerned that this protocol apparently was approved by an ethics committee. We rejected the manuscript and wrote to the authors’ institution expressing our concerns and requesting they investigate further and keep us updated on their progress.

Is there further action we should take?

The issue here is whether formal ethics approval has been granted in order to satisfy publication criteria. By way of some background information, a lot of screening data are collected on many athletes in many sports, both nationally and internationally. Historically, clubs and associations have disclaimers whereby athletes sign consent for their data to be used for audit purposes on the proviso they will not be identified individually. This study appears to do exactly that, except that this is not a retrospective audit, this is an interventional study whereby these players have been subjected to a specific regimen.

In my opinion, there are several issues here.
(A) A blanket proforma that these players were asked to sign does not constitute formal ethics approval for this interventional study.
(B) These players are under age and therefore warrant additional protection.
(C) These players are vying for selection and there is no obvious protection from them being coerced into participation

Whilst new training regimens are being introduced into clubs all the time, if the findings are intended to be disseminated through formal publication, then ethics approval should be sought beforehand. I would be very grateful for the Forum’s opinion on this matter.

A was a researcher in C’s lab for 1 year, during which time they published a joint research paper in a third party journal (journal S). After leaving C’s institute (henceforth called institute X), A published in the journal (journal T as a sole author). The affiliation provided by A on the paper was institute X. All of the data reported in this paper were obtained while A was still employed at institute X, of which C is a senior faculty member and in whose laboratory A was a research associate.

C contacted journal T with several allegations regarding A’s paper in journal T. These were:
(1) A submitted the paper after having left institute X
(2) A never discussed with C his intention to publish these data from C’s laboratory
(3) Material published in journal T is “fully based” on data they had previously published together
(4) A did not have approval to use material published in journal T
(5) Questions two of A’s methods/techniques and the data that resulted
(6) A never acknowledged a funding body

An editor on journal T reviewed these allegations and believes that A’s paper was a follow-up paper, and that it appears to take further the research A and C had previously published in journal S. The paper had undergone peer review on journal T by one specialist referee, who provided a full and penetrating report.

A admits to claims:
(1) The work was conducted at institute X
(6) A admits to a mistake here

A disputes points:
(2) A claims to have raised publication multiple times with C, C’s role in generating the “results were almost non-existent” but indicates that C claimed the data were C’s for C to decide
(3) The paper is a follow-up to their previously published work
(4) A personally analysed the material with the material produced by a technician
(5) A claims that the materials are different images of different samples

Journal T submitted relevant correspondence to the dean at institute X and asked them to investigate. Institute X’s dean responded 4 working days later endorsing C’s position on the basis that A had duplicated material, had misrepresented its novelty and did so both without permission or agreement from C.

The investigation by institute X failed to communicate with A or ask for A’s response to the matter. When the findings were presented to A by journal T, A strongly refuted its key points.

Journal T’s position has been to ask institute X to investigate fully the above allegations (including communicating with A) and to make an official statement linked to the case.

However, we seek COPE’s recommendation whether this should be our position or whether they would advise a different approach.

We would appreciate COPE Forum’s advice with regard to consent and confidentiality in the publication of case histories.

Our journal is published three times a year and has a relatively small circulation but also goes to some postgraduate medical libraries, so is potentially available to a much wider audience.

Our subscribers are doctors working with patients presenting with sexual difficulties in a variety of settings. Training is experiential, through the presentation of cases in seminar groups with a designated leader. Case presentation at our meetings and in the journal articles also provides learning opportunities and peer review.

As well as addressing (in an ordinary medical way) the physical aspects of the sexual problem presented, our work explicitly uses the study of the doctor–patient relationship to shed light on the presenting difficulties. In other words, the doctor–patient relationship is one of our key treatment ‘tools’ allowing connections to be made between the body and the mind in relation to the sexual problem.

These consultations almost always include intimate and sensitive information. Therefore, it had previously been felt that asking for permission to present cases would disrupt the very doctor–patient relationship on which our work depends. As a result, we have tended instead to seek to ensure anonymity by disguising personal details in presentations at meetings and in the journal rather than asking for consent from the patient.

We recognise that this practice is out of line with that recommended by the BMA and the GMC.

Our main concern relates to the possibility of limiting the availability of suitable case material for teaching purposes in presentations and in the journal if doctors felt unable to comply with a requirement to obtain patient consent. This would seriously interfere with the training.

We would prefer to continue using our current guidance where consent is recommended rather than mandatory. Indeed, we would like to suggest that where the doctor is satisfied that the information can be anonymised, he/she does not need to try to obtain consent.

We have considered adding a statement in the journal for patients who might read it, and recognise or believe that they recognise themselves, or their story. One of our founder members addressed this very idea in the preface of a book, asking patients to accept that no-one but themselves would be able to recognise them and to understand that, although each is unique, there are many like them who share similar problems; they are not alone.

We would appreciate your advice on the following points:

1) Is there any justification for continuing the current practice of ensuring anonymity by altering elements of the case history—for example, name, occupation, family details, appearance, geographical location, etc—and continuing to avoid an absolute requirement to obtain consent from patients? As a training body can we claim ‘special case status’ in view of the need to use case material to further training aims for future generations of doctors?

2) It has been suggested by a lawyer who is however not a medicolegal expert that we might interpret the GMC guidance and the NHS Code of Practice on Confidentiality to mean that consent is not needed where the doctor is satisfied that he or she can anonymise the data to be used (bearing in mind that the symptoms might be an identifier).

3) If you feel that we do need to change our practice and require authors to obtain consent from patients whose case histories they wish to present; it would be very helpful to have your advice on how this might be implemented.