Human Subjects Research

Summary of Requirements

Researchers submitting studies involving human participants must meet the following requirements:

• Obtain prior approval for human subjects research by an institutional review board (IRB) or equivalent ethics committee(s)
• Submit documentation from the review board or ethics committee confirming approval of the research. Identifying information about study participants must be redacted from the approval document before it is submitted to the journal
• Confirm upon submission that the study complied with ethical standards with ethical standards outlined in the Belmont Report and/or Declaration of Helsinki, as applicable
• Identify the review board or ethics committee that granted approval, and provide the approval number if one was obtained
• Report details on how informed consent for the research was obtained (or explain why consent was not obtained)
• Avoid including identifying information unless strictly necessary for the submission. If applicable, confirm that any identified individual has provided written consent for the use of that information
• For clinical trials, provide trial registration details, the study protocol, and CONSORT documentation

The above requirements apply to studies involving human subjects as well as human specimens and data, unless the study qualifies as exempt per applicable IRB/ethics committee regulations.

Policy Enforcement

All submissions describing clinical research and/or research on human subjects will be checked to ensure that the requirements above are met. Failure to meet requirements may be grounds for rejection. If issues are discovered after publication, we may issue a correction or retraction as appropriate. We also reserve the right to contact the author’s institution. 

Adherence to International Ethics Standards

All research involving human participants, biospecimens or data must be conducted according to the ethical principles put forth in the Belmont Report.

Clinical investigations must also be conducted according to the principles expressed in the Declaration of Helsinki.

Categorization

For studies involving humans categorized by race/ethnicity, age, disease/disability, religion, sex/gender, sexual orientation, or other socially constructed groupings, authors should:

• Explicitly describe the methods and criteria used to recruit and categorize human populations
• Define categories in as much detail as the study protocol allows
• Justify choices of definitions and categories, including for example whether any rules of human categorization were required by the funding agency
• Explain whether (and if so, how) the researchers controlled for confounding variables such as socioeconomic status, nutrition, environmental exposures, or similar factors in their analysis

In addition, current terminology should be used when referring to human participants and human participant groups/categories. Outmoded terms and potentially stigmatizing labels should not be used. Person-first language should be used in writing about people with diseases, disorders, or other conditions, except for communities that prefer identity-first terminology as their current standard. See https://www.nih.gov/nih-style-guide/person-first-destigmatizing-language for more information.

Examples:

• “white” or “of [Western] European descent” (as appropriate) should be used instead of “Caucasian”
• “people with [name of disease, condition, or disorder]” should be used instead of terms such as “diabetics”, “cancer victims”, or “lepers”

Clinical Trials

PLOS follows the World Health Organization’s (WHO) definition of a clinical trial:

Our policies for clinical trial submissions are designed to promote transparency and reproducibility and to ensure the integrity of the reporting of patient-centered trials. Compliance with our policies is required at submission in order for a manuscript to proceed.

Editors and reviewers should carefully review trial protocols and registration details and assess manuscripts according to CONSORT or other relevant guidelines. Most clinical trial submissions will also be reviewed by a statistician.

Concerns about clinical trial submissions should be brought to the attention of the editorial office as quickly as possible.

Registering clinical trials

All trials submitted to PLOS must be entered in a publicly accessible registry approved by the WHO or ICMJE. See the list of approved registries.

PLOS journals consider prospective trial registration (that is, registration before participant enrollment has begun) to be best publication practice, as recommended by the ICMJE. Clinical trials that began to enroll participants before ICMJE recommendations took effect on July 1, 2005 may be retrospectively registered.

Authors wishing to submit a clinical trial that was not publicly registered before participant enrollment began must register the trial retrospectively in a publicly accessible registry. They must also:

• Register all related clinical trials and confirm they have done so in the Methods section
• Explain in the Methods the specific reasons for failing to register before participant enrollment
• Confirm that future trials will be registered prospectively

PLOS journal editors may decline to further consider any clinical trial for which, in the editor’s judgment, absence of prospective registration raises concerns of selective publication or selective reporting of research outcomes. 

PLOS supports the public disclosure of all clinical trial results, as mandated, for example, by the 2007 FDA Amendments Act. Prior disclosure of results on a clinical trial registry site will not affect consideration.

Required documentation

Clinical trial reports must adhere to the relevant reporting guidelines for their study design, such as CONSORT for randomized controlled trials, TREND for non-randomized trials, and other specialized guidelines as appropriate.

For all clinical trial submissions, authors must include the following:

• Registration details (reported in the Abstract)
• CONSORT checklist or relevant reporting guideline (uploaded as supporting information)
• CONSORT flow diagram (uploaded as Fig 1)
• Trial protocol (uploaded as supporting information)
• Details of prior approval for human subjects research by an institutional review board (IRB) or equivalent ethics committee(s)

The submission will not be considered if documentation is not provided. The checklist, flow diagram, and protocol will be published with the article if the manuscript is accepted.

The manuscript file must include the following information:

• An explanation of any deviation from the trial protocol
• Description of informed consent obtained from participants
• Any information on statistical methods or participants not indicated in the CONSORT documentation

PLOS reserves the right to ask for a blank sample copy of any forms used in the trial.

Patient Privacy and Informed Consent for Publication

We uphold the right to anonymity and take all necessary steps to protect the privacy of those who participate in research.

Authors must avoid providing identifying information unless strictly necessary for the submission. For submissions that include identifying information, or potentially identifying information of patients or other participants, authors must confirm that the individual has provided written consent for the use of that information as per the Consent Form for Publication in a PLOS Journal.

All submissions are checked for documentation of patient consent for publication and for any potentially identifying information. Submissions that include identifying patient information without appropriate patient consent will not be considered for publication.

If identifying information is discovered after publication, or if it comes to light that an individual’s personal information was published without their consent, PLOS will remove content as needed to ensure the individual’s privacy and data are protected. Unlike standard corrections, details of changes made in this context are held as confidential and will not be disclosed in a public notice.

Additional guidance on preparing clinical data for publication can be found in our Data Availability policy.

Cell Lines

For de novo cell lines derived from human tissue, authors must confirm that they obtained approval from an institutional review board or equivalent ethics committee and consent from the donor or next of kin.

See our best practices in research reporting for further details on reporting the use of cell lines.

Manuscripts using cell lines are checked at initial submission. Those that do not meet the requirements for cell line research will be rejected. Issues with cell lines’ identity, ethical oversight, or potential contamination discovered after publication may lead to a correction or retraction.

Editors and reviewers should evaluate cell line information during peer review and notify the journal if any concerns arise.