An article was submitted involving over 200 pregnant patients with a systemic illness (from 2010 to 2015) who were recruited and assigned to a control group or an active intervention group (of their systemic illness). The control group received routine antenatal care while the intervention group had active surveillance and management of their systemic illness during the pregnancy.
There was a significant increase in morbidity and mortality in the non-actively managed control group. We (reviewers and editors) are concerned about the ethics of this study design. Specifically, it seems pregnant patients who were assigned to the non-active treatment/control group did not have their systemic condition managed in what would today be regarded as 'standard of care'.
Question(s) for the COPE Forum
• Despite apparent local ethics board approval, and a statement from the authors declaring adherence to the Declaration of Helsinki, is it ethical to include a non-active intervention group for a disease which is known to have negative fetal and maternal outcomes?
The Forum advised that this appears to be unethical research conduct and egregious violation of human ethics.
Withholding known effective treatment for experimental purposes is not ethical in human subjects’ research. If there is a known effective treatment, the study cannot ethically be done, and any institutional review board would raise a question about such a protocol. If the active management (treatment) is not known to be effective, and the researchers are attempting to establish efficacy of the active management, then a rigorous research protocol should be in place. Such a protocol would ensure informed consent of all human subjects, as well as a process for breaking the randomisation if it becomes clear that the subjects in the control arm of the research are in any medical jeopardy. If this is not the case in this research, the authors should be reported to a research integrity office at their institution or at the country level.
Editors can reject a paper for ethical concerns despite local ethics approval, and a journal can ask the institution to reassess this approval. If it is known that a treatment/management is effective, withholding it is unethical.
The manuscript was rejected for a variety of reasons, including the concerns regarding the ethics of the study design.
This archived COPE Forum case is categorised under the COPE Core Practice of Ethical Oversight which states “Ethical oversight should include, but is not limited to, policies on consent to publication, publication on vulnerable populations, ethical conduct of research using animals, ethical conduct of research using human subjects, handling confidential data and ethical business/marketing practices." The content of this case is directly related to the ethical conduct of research using human subjects as research participants who may be considered members of a vulnerable population, namely, human subjects with a known and diagnosed systemic disease “which is known to have negative fetal and maternal outcomes.” This case might initially be interpreted as relevant only to biomedical research. However, it may equally apply to interventions and control groups in the social sciences where social science research is being studied on such persons as those diagnosed with PTSD or sexual assault survivors.
In this case, the researchers had received approval of the local ethics research approval committee and the authors had stated that their research adhered to the World Medical Association Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects. (WMA Declaration 2013. https://www.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects).
Despite these assurances, reviewers and editors of the journal were concerned about the ethics of the research design. The research was conducted with 200 pregnant subjects over a 5 year period (2010-2015). This allowed sufficient time for the researchers to observe “a significant increase in morbidity and mortality in the non-actively managed control group.” Concerns were consequently raised about the ethics in meeting basic standards of care that these diagnosed patients in the control group were receiving. Given that both the reviewers and the editors of the journal were concerned about the ethics of the research design, this case might be considered a good candidate for contacting the authors’ institution both to raise issues with respect to the research and to raise questions regarding the institutional vetting of research protocols through the research ethics committee. As the COPE guideline on the General Approach to Publication Ethics for the Editorial Office (October 2018) notes “Ethical issues are often complex and the approach will vary depending on the specific problem and the resources of the journal. In general, COPE expects that the member journals will adhere to these basic principles to resolve misconduct.” There are two relevant COPE documents which provide guidance with respect to contacting authors’ employers or the office of persons responsible for research governance at the institution. The flowchart “What to do if you suspect an ethical problem with a submitted manuscript.” (https://doi.org/10.24318/cope.2019.2.19) The other relevant COPE guidance is the document “Cooperation between research institutions and journals in research integrity cases.” (https://doi.org/10.24318/cope.2018.1.3)
In the latter case, COPE states with respect to journals, that journals should “inform institutions if they suspect misconduct by their researchers, and provide evidence to support these concerns.” In this case, the editors ultimately rejected the manuscript “for a variety of reasons, including the concerns regarding the ethics of the study design.”
Had this been a case where the article had been first published and then the ethical concerns had arisen, further ethical matters would have been germane. Given that the subjects of the research had the same systemic conditions, identification of the individuals would have been a relevant concern. As noted in “Journals’ Best Practices for ensuring consent for publishing medical case reports: guidance from COPE”, “publication consent forms should be required for any case report in which an individual or group of individuals can be identified. This requirement also includes when a report involves deceased persons.” (https://doi.org/10.24318/cope.2019.1.6) Given the mortality data noted in this study such concerns are directly relevant here.
Finally, this case would have been a good case for study preregistration in a data registry before the research was conducted. As noted in last month’s case discussion, “A precaution that editors can take is, for manuscripts on human subjects, to insist on study in a registry data base…to help maintain the integrity of decreasing publication bias and increasing transparency and reproducibility."
COPE Chair, Deborah Poff
Read November Digest newsletter with a focus on Ethical Oversight and a letter from the COPE Chair. We also share the new COPE Retraction Guidelines and invite members to join us on COPE Council to help with the work of COPE. Plus the monthly update on publication ethics in the news and upcoming events.