Code of Conduct for Medical Ethics: Animal and Human Research Participants:
- Research Principles
- Research Pros and Cons
- Research Ethics for Animal Research
- Research Ethics for Human Research Participants
- Research on Human Populations
- Race, Ethnicity and Racism
- Sex, Gender (Identity/ Presentation), and Sexual Orientation
- Studies Involving Vulnerable Groups
- Publishing Images from Human Research Participants
- Clinical Trials
- Tumor Marker Prognostic Studies
- Human Biospecimens
- Human Transplantation Studies
- Studies Involving Human Embryos, Gametes and Stem Cells
Researchers should be free to pursue lines of inquiry and the communication of knowledge and ideas without fear of repression or censorship. At the same time, they have the ethical obligation to uphold intellectual integrity and avoid preventable harms that may arise in the course of research or its communication (adopted/adapted from science must respect the dignity and rights of all humans Nat Hum Behav 6, 1029–1031 (2022). https://doi.org/10.1038/s41562-022-01443-2).
There are several reasons why it is important to follow ethical norms in research (adapted/ adopted from David B. Resnik, Bioethics, National Institutes of Health (NIH), December 23, 2020):
- promote the aims of research, such as knowledge, truth, and avoidance of error.
- promote the values that are essential to collaborative work, such as trust, accountability, mutual respect, and fairness.
- help to ensure that researchers can be held accountable to the public. For instance, federal policies on research misconduct, conflicts of interest, the human subject’s protections, and animal care and use are necessary in order to make sure that researchers who are funded by public money can be held accountable to the public.
- help to build public support for research. Some authorities are more likely to fund a research project if they can trust the quality and integrity of research.
- promote a variety of other important moral and social values, such as social responsibility, human rights, animal welfare, compliance with the law, and public health and safety.
Research Pros and Cons:
Research should respect the dignity and rights of human research participants; of individuals or groups connected either with the research participants or the research topic; and of the communities in which research is carried out. Research should also respect the rights of non-human life, tangible and intangible heritage, natural resources, and the environment.
Harms can arise as a direct result of the conduct of research – for instance, injury to human participants in the course of participating in a research project; unnecessary suffering of non-human animals as a result of experimentation; material compromise of tangible heritage; ecosystem disruption etc. Harms can also arise indirectly, as a result of the publication of a research project or a piece of scholarly communication – for instance, stigmatization of a vulnerable human group or potential use of the results of research for unintended purposes (e.g., public policies that undermine human rights or misuse of information to threaten public health).
Non-maleficence and beneficence are two fundamental principles in research ethics requiring the maximization of benefits and minimization of potential harms. These principles form a core part of general frameworks for the ethical conduct of research across the sciences and humanities (for example, The World Medical Association Declaration of Helsinki; The Belmont Report; the International Ethical Guidelines for Health-related Research Involving Humans; Ethics in Social Science and Humanities).
Human and animal research both operate within established standards. In the United States, criticism of the human research environment and recorded abuses of human research subjects served as the impetus for the establishment of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and the resulting Belmont Report. The Belmont Report established key ethical principles to which human research should adhere: respect for autonomy, obligations to beneficence and justice, and special protections for vulnerable individuals and populations. While current guidelines appropriately aim to protect the individual interests of human participants in research, no similar, comprehensive, and principled effort has addressed the use of (nonhuman) animals in research. Although published policies regarding animal research provide relevant regulatory guidance, the lack of a fundamental effort to explore the ethical issues and principles that should guide decisions about the potential use of animals in research has led to unclear and disparate policies. (adopted/adapted from Cambridge Quarterly of Healthcare Ethics, Volume 29, Issue 1, January 2020, pp. 19 – 37, DOI: https://doi.org/10.1017/S0963180119000732, under license CC-BY-4.0)
Research Ethics for Animal Research:
A statement indicating that the protocol and procedures employed were ethically reviewed and approved, as well as the name of the body giving approval, must be included in the Methods section of the manuscript. Authors are encouraged to adhere to animal research reporting standards, for example the ARRIVE guidelines for reporting study design and statistical analysis; experimental procedures; experimental animals and housing and husbandry. Authors should also state whether experiments were performed in accordance with relevant institutional and national guidelines for the care and use of laboratory animals:
- US authors should cite compliance with the US National Research Council’s Guide for the Care and Use of Laboratory Animals.
- US Public Health Service’s Policy on Humane Care and Use of Laboratory Animals, and Guide for the Care and Use of Laboratory Animals.
- UK authors should conform to UK legislation under the Animals (Scientific Procedures) Act 1986 Amendment Regulations (SI 2012/3039).
- European authors outside the UK should conform to Directive 2010/63/EU.
- Guidelines for Animal Research:
The guidelines cover laboratory animals, as defined in the regulations relating to the use of animals in research, but also include all animals that are otherwise affected by research activities. Ethical guidelines for the use of animals in research include but are not limited to (adopted/adapted National Research Ethics Committee (NREC), Ethical Guidelines for the Use of Animals in Research:
- Respect for animals’ dignity: Researchers must have respect for animals’ worth, regardless of their utility value, and for animals’ interests as living, sentient creatures. Researchers must provide care that is adapted to the needs of each laboratory animal.
- Responsibility for considering options (Replace): Researchers are responsible for studying whether there are alternatives to experiments on animals. If no good options are available, researchers should consider whether the research can be postponed until alternative methods have been developed. When justifying experiments on animals, researchers therefore must be able to account for the absence of options and the need to acquire knowledge immediately.
- The principle of proportionality (responsibility for considering and balancing suffering and benefit): Researchers must consider the risk that laboratory animals experience pain and other suffering and assess them in relation to the value of the research for animals, people or the environment. Researchers are responsible for considering whether the experiment may result in improvements for animals, people or the environment. The possible benefits of the study must be considered, substantiated and specified in both the short and the long term. The responsibility also entails an obligation to consider the scientific quality of the experiments and whether the experiments will have relevant scientific benefits.
- Responsibility for considering reducing the number of animals (Reduce): Researchers are responsible for considering whether it is possible to reduce the number of animals the experiment plans to use and must only include the number necessary to maintain the scientific quality of the experiments and the relevance of the results.
- Responsibility for minimizing the risk of suffering and improving animal welfare (Refine): Researchers are responsible for assessing the expected effect on laboratory animals. Researchers must minimize the risk of suffering and provide good animal welfare. Suffering includes pain, hunger, thirst, malnutrition, abnormal cold or heat, fear, stress, injury, illness and restrictions on the ability to behave normally/naturally.
- Responsibility for maintaining biological diversity: Researchers are responsible for ensuring that the use of laboratory animals does not endanger biological diversity. This means that researchers must consider the consequences to the stock and to the ecosystem as a whole. The use of endangered and vulnerable species must be reduced to an absolute minimum.
- Responsibility when intervening in a habitat: Researchers are responsible for reducing disruption and any impact on the natural behavior of individual animals, including those that are not direct subjects of research, as well as of populations and their surroundings. Certain research and technology-related projects, like those regarding environmental technology and environmental surveillance, may impact on animals and their living conditions, for example as a result of installing radar masts, antennas or other measurement instruments. In such cases, researchers must seek to observe the principle of proportionality and minimize the possible negative impact.
- Responsibility for openness and sharing of data and material: Researchers are responsible for ensuring that there is transparency about research findings and facilitating the sharing of data and material from experiments on animals. Such transparency and sharing are important in order to avoid unnecessary repetition of experiments. Transparency is also important in order to ensure that the public are informed and is part of researchers’ responsibility for dissemination.
- Requirement of expertise on animals: Researchers and other parties who handle live animals must have adequately updated and documented expertise on animals. This includes specific knowledge about the biology of the animal species in question, and a willingness and ability to take care of animals properly.
- Requirement of due care: There are national laws and rules and international conventions and agreements regarding the use of laboratory animals, and both researchers and research managers must comply with these. Any person who plans to use animals in experiments must familiarize themselves with the current rules.
- Clinical Trial Registration:
Authors should ensure that clinical trials are prospectively registered in a publicly accessible database and clinical trial registration numbers should be included in all articles that report their results. Authors should also include the name of the trial register and his/her clinical trial registration number at the end of your abstract. If trial is not registered, or was registered retrospectively, please explain the reasons for this.
- Research Reporting Guidelines:
Accurate and complete reporting enables readers to fully appraise research, replicate it, and use it. It is recommended to authors to adhere to the following research reporting standards: CONSORT, SPIRIT, PRISMA, PRISMA-P, STROBE, CARE, COREQ, STARD, CHEERS, The EQUATOR Network, Future of Research Communications and e-Scholarship (FORCE11), ARRIVE guidelines, REFLECT Statement
- Summary of Laboratory Animal Oversight:
Adopted/ Adapted from Regulation of Animal Research, National Library of Medicine (NLM), Washington (DC): National Academies Press (US); 2004.
Regulatory Main Points Animal Welfare Act Protects all warm-blooded animals except rats, mice, and birds bred for research. This includes zoos, circuses, research labs, hospitals, businesses, federal agencies, dealers, breeders, etc. Each research institution that uses a covered species must have an IACUC review all animal experiment protocols. The USDA licenses research facilities and conducts annual, unannounced inspections. Violations are punished with fines, cease-and-desist orders, and license suspension or revocation. PHS Policy Protects all vertebrate animals (including fish, reptiles, rats, mice, and birds) used in research funded by the Public Health Service. Each research facility provides a written plan for complying with PHS Policy and the Guide. PHS Policy Each research institution that receives PHS funding must have the IACUC review all animal experimental protocols and inspect the facilities.
No routine, unannounced inspections, but all allegations of misuse are investigated by NIH’s Office of Laboratory Animal Welfare.
Violations or loss of AAALAC accreditation can result in loss of PHS funding.
IACUC A committee, organized at every research facility subject to the AWA, PHS Policy, or AAALAC accreditation, which must review and approve or deny every proposed animal protocol.
Each animal protocol must include:—A justification for using animals, the number of animals to be used, and the species chosen—The procedures or drugs to be used to eliminate or minimize pain and discomfort—A description of the methods and sources used to search for alternative to painful procedures—A description of the search used to ensure that the experiment does not unnecessarily duplicate previous research
Members must include: a veterinarian, a professional not involved in research (ethicist, lawyer, etc.), and a community representative (clergy, teacher, etc.).
IACUC members must inspect their research facility twice a year.
AAALAC International Nonprofit organization that accredits research facilities for compliance with the Guide.
Accreditation is on a voluntary basis only.
Announced site visits are conducted every 3 years.
- Guidelines for Animal Research:
Research Ethics for Human Research Participants:
Research involving human research participants must have been performed in accordance with the Declaration of Helsinki. Authors must identify the ethics committee approving the research, including the name and reference number of the committee in submitted manuscripts. If the study has been granted exemption from requiring ethics approval, details of the committee granting exemption should be included in the manuscript. Articles must also include a statement affirming that informed consent was obtained from all human research participants.
The Declaration of Helsinki was revised in 1975, 1983, 1989, and 1996, and is the basis for Good Clinical Practices used today. Issues addressed in the declaration of Helsinki include:
- Research with humans should be based on the results from laboratory and animal experimentation.
- Research protocols should be reviewed by an independent committee prior to initiation.
- Informed consent from research participants is necessary.
- Research should be conducted by medically / scientifically qualified individuals.
- Risks should not exceed benefits.
- Research on Human Populations (including reporting standards)
For studies involving humans categorized by race, ethnicity, national or social origin, sex, gender identity, sexual orientation, religion, political or other beliefs, age, disease, (dis)ability, socio-economic status, or other socially constructed or socially relevant groupings, authors should (adopted/ adapted from Nature Guidelines for Research Ethics):
- Explicitly describe their methods of categorizing human populations.
- Define categories in as much detail as the study protocol allows.
- Justify their choices of definitions and categories, including for example whether any rules of categorization were required by their funding agency.
- Explain whether (and if so, how) they controlled for confounding variables in their analyses.
- Research on Human Populations (including reporting standards)
Additionally, it is required that all content submitted for publication be respectful of the dignity and rights of individuals and human groups. Researchers are asked to carefully consider the potential implications (including inadvertent consequences) of research on human groups defined by attributes of race, ethnicity, national or social origin, sex, gender identity, sexual orientation, religion, political or other beliefs, age, disease, (dis)ability or other status, to be reflective of their authorial perspective if not part of the group under study, and contextualize their findings to minimize as much as possible potential misuse or risks of harm to the studied groups in the public sphere.
Finally, authors should use inclusive, respectful, non-stigmatizing language in their submitted manuscripts. Authors should ensure that writing is free from stereotypes or cultural assumptions. We recommend avoiding the use of descriptors that refer to attributes such as race, ethnicity, national or social origin, sex, gender identity, sexual orientation, religion, political or other beliefs, age, disease, (dis)ability or other group descriptors unless they are relevant. We advise that authors writing in English follow the guidance on bias-free language provided by the American Psychological Association when preparing their manuscripts for submission.
Regardless of content type (research, review or opinion) and, for research, regardless of whether a research project was reviewed and approved by an appropriate institutional ethics committee, editors reserve the right to request modifications to (or correct or otherwise amend post-publication), and in severe cases refuse publication of (or retract post-publication):
- Content that is premised upon the assumption of inherent biological, social, or cultural superiority or inferiority of one human group over another based-on race, ethnicity, national or social origin, sex, gender identity, sexual orientation, religion, political or other beliefs, age, disease, (dis)ability, or other socially constructed or socially relevant groupings (hereafter referred to as socially constructed or socially relevant human groupings).
- Content that undermines – or could reasonably be perceived to undermine – the rights and dignities of an individual or human group on the basis of socially constructed or socially relevant human groupings.
- Content that includes text or images that directly or indirectly disparage a person or group on the basis of socially constructed or socially relevant human groupings.
- Submissions that embody singular, privileged perspectives, which are exclusionary of a diversity of voices in relation to socially constructed or socially relevant human groupings, and which purport such perspectives to be generalizable and/or assumed.
- Race, Ethnicity, and Racism:
Race and ethnicity are sociopolitical constructs. Humans do not have biological races, at least based on modern biological criteria for the identification of geographical races or subspecies. Studies that use the constructs of race and/or ethnicity should explicitly motivate their use. Race/ethnicity should not be used as proxies for other variables – for example, socioeconomic status or income. For studies involving data collected from human participants, researchers should explain: (i) who provided the classification terms (the participants, the researchers or third parties (ii) b. what the classification terms are: how racial/ethnic identity was determined (by the participants, the researchers or third parties).
Biomedical studies should not conflate genetic ancestry (a biological construct) and race/ethnicity (sociopolitical constructs): although race/ethnicity are important constructs for the study of disparities in health outcomes and health care, empirically established genetic ancestry is the appropriate construct for the study of the biological aetiology of diseases or differences in treatment response. If race/ethnicity are used in the context of disease aetiology due to the unavailability of genetic ancestry data, this should be done with caution and clarification.
Racism is scientifically unfounded and ethically untenable. Editors reserve the right to request modifications to (or correct or otherwise amend post-publication), and in severe cases refuse publication of (or retract post-publication), racist content. Editors use the guiding criteria I-IV set out in the section Research on human populations (see above) to identify content that potentially undermines the equal dignity and rights of humans of all races/ethnicities.
- Sex, Gender (Identity/ Presentation), and Sexual Orientation:
Researchers are encouraged to follow the ‘Sex and Gender Equity in Research – SAGER – guidelines’ and to include sex and gender considerations where relevant (overview can be found here). It is recommend consulting the full guidelines when designing research studies and before submission. These guidelines apply to studies involving humans, vertebrate animals and cell lines. Authors should use the terms sex (biological attribute) and gender (shaped by social and cultural circumstances) carefully in order to avoid confusing both terms.
Working definitions (adopted/adapted from the SAGER guidelines and other sources):
Sex – refers to currently understood biological differences between females and males, including chromosomes, sex organs, and endogenous hormonal profiles. Sex is usually categorized as female or male, although there is variation in the biological attributes that constitute sex.
Gender – refers to socially constructed and enacted roles and behaviors which occur in a historical and cultural context and vary across societies and over time. Gender is usually incorrectly conceptualized as a binary (man / woman or feminine/masculine) factor. In reality, there is a spectrum of gender identities and expressions defining how individuals identify themselves and express their gender.
Gender Identity – an individual’s conception of self as being a man, woman, masculine, feminine, nonbinary, ambivalent, etc., based in part on physical, psychological and social factors. It is the internal experience of a gender role. There is a broad range of gender identities including, but not limited to, transgender, gender-queer, gender-fluid, non-binary, gender-variant, genderless, agender, nongender, bi-gender, trans man, trans woman, trans masculine, trans feminine and cisgender.
Gender Presentation – how a person publicly expresses or presents their gender identity. This can include behavior and outward appearance such as dress, hair, make-up, body language and voice. A person’s chosen name and pronouns are also common ways of expressing gender. Others perceive a person’s gender through these attributes. Another term is “gender expression.”
“Gender” refers to a set of cultural norms and expectations and not a “biologically defined variable”. Such norms are not fixed but evolve across time and space. As such, definitions will require frequent revisiting, as the exercise of defining gender (and sexuality) is under constant flux and evolution, as is the area of study in itself.
Researchers are encouraged to promote equality between men and women in their academic research which by nature should be grounded on the recognition of merit, competences and creativity, regardless of any other personal attributes or orientation.
Sexist, misogynistic and/or anti-LGBTQ+ content is ethically objectionable. Regardless of content type (research, review or opinion) and, for research, regardless of whether a research project was reviewed and approved by appropriate ethics specialists, editors may raise with the authors concerns regarding potentially sexist, misogynistic, and/or anti-LGBTQ+ assumptions, implications or speech in their submission; engage external ethics experts to provide input on such issues as part of the peer review process; or request modifications to (or correct or otherwise amend post-publication), and in severe cases refuse publication of (or retract post-publication) sexist, misogynistic, and/or anti-LGBTQ+ content, using the guiding criteria I-IV in the section Research on human populations.
- Studies Involving Vulnerable Groups:
For manuscripts reporting studies involving vulnerable groups where there is the potential for coercion or where consent may not have been fully informed, extra care will be taken by the editor. The manuscript may be referred to an internal editorial oversight group for further scrutiny. Consent must be obtained for all forms of personally identifiable data including biomedical, clinical, and biometric data. Documentary evidence of consent must be supplied if requested.
- Publishing Images from Human Research Participants:
When publishing identifiable images from human research participants in the journal, authors include a statement in the published paper affirming that they have obtained informed consent for publication of the images. All reasonable measures must be taken to protect patient anonymity. Black bars over the eyes are not acceptable means of anonymization. In certain cases, we may insist upon obtaining evidence of informed consent from authors. Images without appropriate consent will be removed from publication.
- Clinical Trials:
All interventional trials must be registered before enrollment of the first participant. Trial registration records must be available in a primary register of the WHO International Clinical Trials Registry Platform (ICTRP), in ClinicalTrials.gov, or in any publicly accessible database that meets the minimum 24-item trial registration dataset, including the ISRCTN registry. The trial number must be clearly indicated in the abstract and methods section of the manuscript.
Authors reporting phase II and phase III randomized controlled trials should refer to the CONSORT Statement for recommendations to facilitate the complete and transparent reporting of trial findings. Reports that do not conform to the CONSORT guidelines may need to be revised before formal review.
- Tumor Marker Prognostic Studies:
For describing Tumor marker prognostic studies, authors are referring to REporting recommendations for tumor MARKer prognostic studies (REMARK). Nat Rev Clin Oncol 2, 416–422 (2005). https://doi.org/10.1038/ncponc0252.
- Human Biospecimens:
For describing human biospecimens, authors are referring to the BRISQ reporting guidelines (doi: 10.1002/cncy.20147).
- Human Transplantation Studies:
Authors must also include a statement in their manuscript attesting that no organs/tissues were procured from prisoners and providing details of the institution(s)/clinic(s)/department(s) via which organs/tissues were procured while taking care to not violate privacy of donors. For retrospective transplantation studies, authors must include a testament confirming that informed consent was obtained from all participants or that the need for informed consent was waived by the ethics committee/institutional review board.
- Studies Involving Human Embryos, Gametes and Stem Cells:
Articles that report experiments involving the use of human embryos and gametes, human embryonic stem cells and related materials, and clinical applications of stem cells must include confirmation that all experiments were performed in accordance with relevant guidelines and regulations.
The manuscript must include an ethics statement identifying the institutional and/or licensing committees approving the experiments and describing any relevant details. The ethics statement must also confirm that informed consent was obtained from all recipients and/or donors of cells or tissues, where necessary, and describe the conditions of donation of materials for research, such as human embryos or gametes. Copies of approval and redacted consent documents may be requested by the editors.
Authors should follow the principles laid out in the 2016 ISSCR Guidelines for Stem Cell Research and Clinical Applications of Stem Cells. Editors are guided by these principles in their evaluation of the ethical and regulatory aspects of the reported research. When appropriate, ethical and regulatory advice is sought in parallel with the scientific peer review process.