The Conduct of Research

Seventh Edition 2021 Guidelines and Policies for the Conduct of Research in the Intramural Research Program at NIH National Institutes of Health Office of the Director A check mark (√) indicates that the section summarizes a specific policy i Preface It is an exciting, vital time to be a member of the Intramural Research Program (IRP) at the National Institutes of Health. Research is increasingly multidisciplinary and relies on innovative technologies that are developing almost too quickly to count. No better example of this is the intramural response to the COVID-19 pandemic, in which the IRP led the charge in understanding pathophysiology, in diagnosis, in treatment, and in the development of safe and effective vaccines. Team science is now the expected norm. Because of the technological advances, and team-science approaches, it is more important than ever to promote a culture of research integrity on intramural campuses. A culture of integrity is one in which every individual understands how to perform research ethically and does so. These guidelines were written to provide important information about how to perform ethical research and maintain a culture of research integrity in the IRP. I would like to draw your attention to the section on our “Research Environment,” and specifically to the chapter on IRP Commitment to Diversity, Equity, Inclusion, and Accessibility. The IRP is committed to carrying out its mission while breaking down barriers that prevent any member of our community from contributing their talents. We need and we value diverse perspectives, backgrounds, and skills, to be a successful program. We are committed to ensuring that every person in the IRP is welcomed, retained, and encouraged to be successful, and to experience a culture of respect and inclusion. It is essential that every investigator involved in research at NIH read, understand, and incorporate the Guidelines and Policies into everyday practice. The progress and excellence of NIH intramural research are dependent on our vigilance in maintaining the highest quality of conduct in every aspect of science. These guidelines were developed by the Scientific Directors in 2007 then revised in 2016, 2019 and 2021 by the intramural scientists serving on the Committee on Scientific Conduct and Ethics. This edition was approved on (date) by the Scientific Directors. Michael M. Gottesman, M.D. Deputy Director for Intramural Research, NIH 7th Edition November 2021 Contents Preface ........................................................................................................................................................... i Introduction .................................................................................................................................................. 1 Performing Research Scientific Record Keeping .............................................................................................................................. 2 Data Management ...................................................................................................................................... 10 Authorship .................................................................................................................................................. 14 Publications ................................................................................................................................................. 16 Mentoring and the Responsibilities of Research Supervisors and Trainees ............................................... 19 Collaborations and Team Science ............................................................................................................... 21 Scientific Rigor and Reproducibility ............................................................................................................ 24 Research Misconduct .................................................................................................................................. 25 Research Environment Harassment, Sexual Harassment, and Inappropriate Conduct ................................................................... 28 Peer Review and Privileged Information .................................................................................................... 31 Scientific Integrity at the NIH ...................................................................................................................... 32 Conflicts of Interest ..................................................................................................................................... 33 Social Responsibility, Media Inquiries, and Dual-Use Research ................................................................. 35 Ethical Leadership and Management ......................................................................................................... 37 IRP Commitment to Diversity, Equity, Inclusion, and Accessibility ............................................................ 40 Regulatory Compliance Animal Care and Use ................................................................................................................................... 41 Human Biospecimen Tracking and Storage ................................................................................................ 43 Health & Safety ........................................................................................................................................... 45 Fetal Tissue Research .................................................................................................................................. 48 Human Subjects Research........................................................................................................................... 50 Research Material Management and Research with High-Consequence Pathogens: Institutional Biosafety .................................................................................................................................................................... 53 Ethical Concerns Related to NIH Information Technology ......................................................................... 55 Whistleblowing and Whistleblower Protections ........................................................................................ 58 Concluding Statement................................................................................................................................. 60 1 Introduction Scientists in the Intramural Research Program of the National Institutes of Health (NIH) are responsible for conducting original research consonant with the goals of their individual Institutes and Centers. These Guidelines and Policies were developed to promote high ethical standards in the conduct and management of research by NIH intramural scientists. It is the responsibility of all supervisory personnel who oversee research groups, core facilities, and other entities, as well as successive levels of organizational leadership (especially Institute and Center Scientific Directors), to ensure that every NIH scientist is cognizant of these Guidelines and Policies and to resolve issues that may arise in their implementation. Intramural scientists at NIH, as is true for all scientists, should be committed to the responsible use of scientific tools and methods to seek new knowledge. While the general principles of scientific methodologies are universal—formulation and testing of hypotheses, controlled observations or experiments, analysis and interpretation of data, and oral and written presentation of all of these components to scientific colleagues for discussion, replication and further conclusions—their specific applications may differ across scientific disciplines and the specific context. All research staff in the Intramural Research Program should maintain exemplary standards of intellectual honesty in formulating, conducting, presenting, and reviewing research, as befits the leadership role of the NIH. Both OIR and NIH leadership expect that all members of our thriving community will conduct themselves in a manner that is consistent with NIH Policy. It is important to note that failure to adhere to the principles and expectations set forth by NIH Policy may result in disciplinary action. These Guidelines and Policies complement existing NIH regulations for the conduct of research such as those governing human subjects research, animal use, radiation, and chemical and other safety issues, as well as the standards of ethical conduct that apply to all NIH researchers and federal employees. ▲ 2 Scientific Record Keeping Good Record Keeping Practices There’s a saying in the law that “if it wasn’t written down, it didn’t happen.” This key idea also applies to scientific research. Good record keeping is essential to the validity, accountability, reproducibility, and integrity of scientific research. Research records document the entire research process, from formulating a question or hypothesis and applying for funding, to designing experiments and studies, developing research protocols, and generating, analyzing, and interpretating data. Research records are the property of the NIH and must be accessible at all times to the principal investigator (PI). Research records include, but are not limited to: • • • • • • • • • • • • • • • • Research data, including primary data, secondary data, and metadata Rules or procedures for collecting, labeling, annotating, storing, editing, cleaning, auditing, processing, excluding, and analyzing data Records of materials used in research Research protocols, such as protocols for conducting laboratory experiments or research with human or animal subjects Rules or procedures for calibrating scientific instruments Standard operating procedures for data collection, testing, animal care, patient care, and so on Research proposals and grant applications Computer software used in data processing, statistical analysis, and digital image manipulation Preliminary analyses of data Questionnaires Informed consent documents Audit reports Drafts of manuscripts and final publications Correspondence with journals Correspondence with research oversight committees and funding organizations Plans for future research Data are a tangible record of an observation made by a human being (e.g., clinical findings or observations of animal behavior) or a machine (e.g., DNA sequence data; MRI or electron microscopy images). Primary (raw, original) data are data that are directly related to the object of study; secondary (or derived) data are data that are indirectly related to the object of study; and metadata are data about or derived from the data. For example, for an MRI imaging study of traumatic brain injury, primary data could include MRI images and records of clinical laboratory tests and neurological examinations; secondary data could include spreadsheets, tables, figures, diagrams, and images derived from the data; A check mark (√) indicates that the section summarizes a specific policy 3 and metadata could include data about these data (such as height, width, pixels, kilobytes, and compression for the MRI images). Data may be recorded on different media and in different formats, including: • • • • • • • • • • Paper laboratory notebooks (bound or unbound) Electronic notebooks Electronic spreadsheets Word processing documents Digital imaging software Software on machines that produce data (e.g. MRI machines, DNA sequencers, flow cytometers) Software used in statistical analysis or mathematical or statistical modelling Photographs Audio and video recordings Medical records Research materials are physical entities, objects, and substances (other than equipment or instruments) that are used to generate data. For example, in gel electrophoresis, the macromolecules and the gel are materials, and the data would be a digital image of the gel. It is important to keep good records of materials for the same reasons that it is important to keep good records of data. For example, in animal drug safety experiments, it is important to keep records of the species and strain of the animal used, housing, the type of feed, the drug used, expiration data, lot number, and so on. Research materials include: • • • • • • • • • • • Tissues, tissue sections on slides, liquid biopsies Cells and cell lines Blood, saliva, hair DNA, RNA, proteins Microbes Gels Chemical reagents Dyes, stains Pharmaceuticals Laboratory animals Zoological and botanical collections There are at least five reasons why it is important to keep good records in scientific research. First, good record keeping is necessary for data analysis, publication, collaboration, peer review, and other research activities. Research records can help you to communicate with members of your research A check mark (√) indicates that the section summarizes a specific policy 4 team and collaborators, brainstorm for ideas, and draft or revise your research plans. When it is time to publish your research, you need to be able to find the data that support your conclusions and analyses. Editors and reviewers may also request additional data beyond what you submit. After publication, you may need to deposit your data in a data repository and share it with colleagues who want to repeat your experiments or examine your work more closely. Second, good record keeping is important for reproducing results (see Chapter on Rigor and Reproducibility, below).1 Third, good record keeping can help defend you against false allegations of research misconduct. Misconduct allegations commonly arise when other scientists are unable to repeat published research. Often, the underlying reason for this failure is that the original research was not described in sufficient detail in the publication. While good research records cannot prevent you from ever facing allegations of misconduct, they can help you to refute them. Fourth, good record keeping is mandated by federal law or NIH policy for some types of research, such as research involving hazardous radioactive or biological materials, recombinant DNA, products regulated by the Food and Drug Administration (FDA), laboratory animals, and human subjects. Researchers need to be aware of all applicable record keeping requirements that apply to their research and comply with them. Federal record keeping laws also apply to NIH research. Records containing information that personally identifies human subjects must comply with NIH policies and federal regulations that protect privacy and confidentiality as well as information technology (IT) security requirements. Federal human research regulations mandate that institutional review boards (IRBs) must determine that confidentiality and privacy will be adequately protected before approving a human research protocol. The Privacy Act also establishes standards for protecting private information collected by the federal government. Investigators who conduct research involving human subjects should contact the NIH’s IRB Office (IRBO) with questions about research record keeping storage and security requirements. See discussion of Clinical Research below. Fifth, good record keeping is necessary to support intellectual property (IP) claims. If you are conducting research that may be patentable, you need records to support your patent application and defend your patent if it is challenged. Record keeping for patentable inventions is much more stringent than other types of record keeping. See additional discussion of IP below. Responsibilities of the Principal Investigator 1 Enhancing Reproducibility Through Rigor and Transparency. Retrieved from https://grants.nih.gov/policy/reproducibility/index.htm A check mark (√) indicates that the section summarizes a specific policy 5 While every member of the laboratory or research group has a responsibility to keep good research records, data integrity is ultimately the responsibility of the PI. The PI may delegate some of these responsibilities to senior members of the laboratory or research group. The PI is responsible for: • • • • • • Establishing best practices for research record keeping in the laboratory or research group, including practices related to collecting, labeling, annotating, storing, editing, cleaning, auditing, processing, excluding, analyzing data, and sharing data Ensuring that members of the laboratory or research group receive proper instruction in record keeping practices Ensuring that there is an “index” record of all retrievable data sources related to individuals and projects in the research group Convening regular meetings to review data, discuss record keeping practices, and deal with any problems or questions that arise Deciding when and how to share and publish data Responding to requests for data and materials Elements of Good Record Keeping Although record keeping practices vary across scientific disciplines, some principles apply to almost all forms of research. The overarching principle for scientific record keeping is that another person or research group should be able to reproduce or reconstruct your research from your records. If you are an NIH researcher and you leave the NIH before your work is complete, for example, then another researcher should be able to continue your work by consulting your records. Research records should be: • • • • • • • • • • • • • Legible Clear Complete Thorough Consistent Properly annotated to make them accessible Well-organized Indexed (in some cases) In English (for NIH research) Dated Signed Recorded so that new entries or corrections can be identified and validated Secure A check mark (√) indicates that the section summarizes a specific policy 6 • Backed-up Records should describe or explain: • • • • • • • • • • Who conducted it (including the person making the record) What you did When you did it (clearly stating month, date, year, and time of day) Why you did it What project the research was part of How you did it (including the methodology) What materials were used The findings The interpretation The next step(s) Record Keeping Formats Bound Notebook One format for a lab notebook is a bound volume with numbered pages. Data not easily accommodated in this format (e.g., tissue sections, original microscope photos, computer printouts, X-ray films) may be kept in a separate storage place and clearly indexed to the lab notebook. A bound notebook should be signed and dated on the inside front cover to indicate the first day the recipient started using the notebook. A table of contents listing experiments and a list of abbreviations should be included at the beginning, leaving space/pages for future entries. Information should be kept in a linear fashion without skipped pages, except for the pages initially left blank. Writing should be in black or blue ink, never pencil. Errors should be lined through with a single line, never erased or obliterated. If corrections are made to previous entries, they should be initialed and dated. If insufficient space exists to make a correction, the correct information should be placed in the next available space, with an indication of where the error is. Loose-leaf Notebook The use of a ring binder and loose-leaf sheets is another acceptable form of laboratory notebook for many academic investigators. Loose-leaf notebooks may also be used as a supplement to bound notebooks in order to include original data, such as X-ray films, data sheets and electronic printouts. Using a loose-leaf notebook as an adjunct to a bound notebook necessitates appropriate and perhaps redundant references or keys to link the data and experimental protocols. Loose sheets should be dated and immediately added to your binder, in chronological order, to meet the standards of good science and assure research integrity. Other rules for record keeping that apply to the bound notebook also apply to the loose-leaf notebook; e.g., writing in blue or black ink, errors lined through and not erased, etc. A check mark (√) indicates that the section summarizes a specific policy 7 Electronic Notebooks An electronic notebook is a system used to create, store, retrieve and share electronic records. Instead of recording information on paper, the sketches, text, equations, images, graphs, and other data are recorded electronically. Adding to an electronic notebook can involve input from keyboard, other program output, imaging equipment, microphone, and directly from scientific instruments. Electronic notebooks can range in capability and complexity from the simplest types that use ordinary software (word processing, spreadsheet, graphics) on one’s computer to annotate and keep track of data files, to more notebook-like systems or special commercial software for authentication. Investigators are encouraged to contact the NIH Library Data Services Team for assistance with selecting and implementing an electronic laboratory notebook. Electronic notebooks facilitate data input, provide uniform formats for data recording, and allow collaborators to share data and add to the record. Commercial electronic notebook software varies in how much it resembles a paper notebook but usually includes all functions of a paper notebook. If personally identifiable and/or sensitive data are involved, appropriate Privacy Act and IT security standards must be met. The security of electronic records, including access to a particular electronic notebook, its contents, and authentication of entries in a notebook, is a fundamental issue that must be addressed. Every electronic notebook has a list of authorized users, one of whom should be the NIH PI or supervisor. A group notebook may be set up for collaboration on a project. Mechanisms to ensure that data are not altered after entry are important. In commercial software this can be done automatically, and the signature can be digitally authenticated. If notebooks use common software that does not provide for automatic archiving, the notebook should be stored on a secure NIH server with daily backups for archival purposes. Electronic Spreadsheets Many researchers record data on spreadsheets. Although spreadsheets are convenient and user-friendly, they often do not include mechanisms for authenticating changes to the data. For example, if one goes back and looks at a spreadsheet a day or two after entering data and finds a mistake, it may not be clear how to validate a correction to the spreadsheet. Researchers who work with spreadsheets should develop practices for promoting data integrity, such as: giving spreadsheets file names that clearly indicate the version date and the author; keeping track of spreadsheet versions; ensuring that spreadsheets that are shared with collaborators implement the same formats for recording data; storing spreadsheets on a server accessible only to team members; using the track changes function (if available) to indicate changes; and, periodically locking spreadsheets to preserve data. Record Keeping for Intellectual Property Purposes A check mark (√) indicates that the section summarizes a specific policy 8 While it is often the case that intellectual property (IP) rights are secured for research inventions documented using ordinary, good scientific record keeping practices, in cases of a challenge, a more stringent standard may be required as legal proof of IP claims. Thus, ideally a bound or appropriate electronic notebook is used for keeping research records related to IP, not a loose-leaf notebook or spreadsheet. In addition to the requirements for bound or electronic notebooks mentioned above, the following requirements apply to record keeping for IP purposes: • Each entry should be signed and dated. • Entries should be periodically witnessed with a signature and date. The witness should have an understanding or familiarity with the inventor’s work, but not be a co-inventor. The witness should be a person who is available or can be easily reached for the next several years. • Consecutive pages must be used. • Photos, drawings, graphs, and related documents should be clearly labelled, permanently attached, signed, dated, and witnessed. If an attachment cannot be stapled, it should be placed in an envelope and the envelope stapled to the notebook page. The envelope and page should then be signed, dated, and witnessed, making reference to the attachment being placed in the envelope. Alternatively, documents should be identified by book and page number and stored in a separate loose-leaf notebook. • Electronic notebooks used for intellectual property purposes must have backup, dating, appropriate IT security, and authenticity and verification capabilities, such as the ability to timestamp entries and record signatures. • Both bound and electronic notebooks must include the subject matter, experimental details, sketches, diagrams, test descriptions, control conditions, test results, an explanation of the results, and photos or sketches of the results or the test device. Conclusions should be short and supported by the factual data. Record Keeping in Clinical Research The principles of good record keeping that apply to all fields of science also apply in the clinical research setting, although their practical implementation varies, due to the requirements of patient care and FDA regulations. As noted earlier, confidentiality, privacy and IT security requirements in clinical research are much stronger than those in other types of research because clinical research involves the collection of private and sensitive information about human subjects. While the NIH is not a HIPAA covered entity, it does comply with all applicable laws, rules and regulations governing the privacy and security of health information, including the Privacy Act of 1974. Clinical Research Records The following record keeping practices are important for protecting the privacy and confidentiality of human research subjects in clinical or non-clinical research (e.g., natural history studies): • Access to research records should be restricted to authorized personnel. • Paper records should be kept in a secure place, such as a locked file cabinet. A check mark (√) indicates that the section summarizes a specific policy 9 • • • Electronic records should be password protected, stored on NIH computers or servers, and encrypted if stored on laptops. Breaches of confidentiality should be reported to the IRB according to policies concerning the reporting of non-compliance and unanticipated problems. Whenever feasible and appropriate, data to be shared with other investigators or contributed to databases should be de-identified. The IRBO provides additional guidance for determining what constitutes individually identifying information. Good Clinical Practice √ Paper and electronic records generated by clinical studies regulated by the FDA must follow Good Clinical Practice standards and adhere to regulations found in 21 CFR parts 11, 50, and 312. Guidance on FDA requirements for investigator record-keeping and record retention specify that an investigator must retain records for two years following the date a marketing application is approved for a drug. Investigators must also follow the NIH Records Management Schedule.2 The regulatory binder or file organizes all essential documents that demonstrate that the investigator, sponsor, and monitor have complied with Good Clinical Practice standards and with all applicable regulatory requirements. This central binder also allows research team members to reference information and provides easy access to essential documents by the trial monitor, auditor, IRB, or regulatory authorities for review or audit purposes. It also offers research team members the opportunity to document the reasons for corrective changes in operating procedures that occurred because of unforeseen events that occur during a trial. This documentation may be helpful in a future audit. The PI is ultimately accountable for the maintenance of the regulatory binder. Administration of all study drugs, including those that are self-administered, should be documented in the subject’s medical record. The PI is also ultimately accountable for record-keeping related to the investigational drug or product, including documentation drug stability and appropriate storage of drug, recording the distribution of drug, and maintaining accurate drug accountability records, such as receipts of drug shipments or invoices and drug accountability record forms. These responsibilities may be delegated to appropriate pharmacy staff. ▲ 2 NIH Records Management Schedule. Retrieved from https://oma.od.nih.gov/DMS/Pages/Records-ManagementSchedule.aspx A check mark (√) indicates that the section summarizes a specific policy 10 Data Management Storage of Research Records Research records should be carefully recorded and retained in a form that will allow for continuous access. Notebooks and documenting electronic information should be annotated and indexed to facilitate detailed analysis and review of data; i.e., a third party should be able to reconstruct the experiment based on the recorded information. In general, notebooks, other research data including computer files and supporting materials, such as unique reagents, should be maintained and made available by the laboratory in which they were developed. √ All intramural research records must be maintained for at least 7 years after completion of the project (e.g., publication of the final results); records that support IP rights must be maintained for 10 years after the patent expires or is abandoned; and, records of historical significance should be identified and transferred to the National Archives to be maintained permanently.3 No NIH records may be destroyed unless consistent with the NIH policies governing record maintenance and retention and applicable regulations. More details regarding research retention schedules can be found at the NIH Office of Management website.4 All primary data, including those from observations and experiments not directly leading to publication, must be retained.1 For example, all usable confocal microscopy imaging files should be retained in their original format, except for technically problematic data that had been discarded immediately. If acquired images or image sequences become prohibitively large, it may be acceptable to keep a subset of images as recorded, while compressing others if considered best practices for the field. The volume of imaging data continues to expand exponentially, creating challenges for their secure storage. To mitigate the risk of destruction or loss, electronic data should be backed up regularly and stored at a location away from the original data. Similarly, it is prudent to scan hard-copy notebooks periodically and to keep electronic copies at a different site. Archives of primary data and other important records should be stored in a manner that prevents subsequent alterations; copies of these files may be used for further research or reanalysis. NIH has remote sites that accept archival material. Researchers should only use storage mechanisms that are approved by the NIH Intramural Research Program (IRP) and their Institute or Center (IC). Physical research records must be securely stored in NIH facilities, such as offices or laboratories. Physical records should be protected from physical damage (such as damage due to water or sunlight), tampering, theft, or unauthorized access or alteration. 3 4 Manual Chapter 1743; Managing Federal Records. Retrieved from https://policymanual.nih.gov/1743 NIH Records Management. Retrieved from https://oma.nih.gov/dms/programs/rm/Pages/Home.aspx A check mark (√) indicates that the section summarizes a specific policy 11 Electronic records must be securely stored on government issued NIH devices, such as desktop or laptop computers, external hard drives, USBs drives, data servers, or data generating equipment (such as MRI machines, DNA sequencers, or flow cytometers). Electronic records should be protected by passwords, NIH firewalls, and, in some cases, encryption. Years ago, electronic data were kept on reel-to-reel magnetic tapes, then floppy discs, followed by CDs. Since electronic media continue to evolve in response to advances in technology, it is important to make sure that the medium used is reliable and that files can be read later and transferred to new media. Storing data on servers can help researchers accommodate changes in electronic media. A record of data locations must be maintained. That can be accomplished by entering the information in a database (which also needs to be maintained and backed up properly). Some new versions of modeling packages self-index the files that are created. There are commercial database systems where the backup may be done automatically. Ownership of Research Records and Materials All research records and materials are the property of the NIH. Research records may be copied (without personal identifiers) at the discretion of the supervisor. Departing scientists may take copies of notebooks and other data for further work, with the approval of their supervisor. The policy and process for taking copies of NIH records is described in Manual Chapter 1743, Managing Federal Records,5 which includes the requirement that the requestor complete Form NIH-30006 at least 45 days prior to departure. PIs should consider and are encouraged to document the intent to continue to work together with a Research Collaboration Agreement. Research materials must remain at the NIH. However, under special circumstances, such as when required for continuation of research, departing investigators may take unique reagents with them if adequate arrangements for their safekeeping and availability to others are documented by the appropriate Institute or Center official. The transfer of a reagent outside of NIH should be documented through a Material Transfer Agreement.7 Data Sharing After publication, data and any unique materials that form the basis of research should be shared to fullest extent possible consistent with laws, regulations, and NIH policies.8 Data sharing may be limited by the need to maintain confidentiality in research with human subjects or to abide by Cooperative Research and Development Agreements (CRADAs) that preclude sharing of unique research materials or proprietary data. However, researchers should strive to share data and 5 NIH Policy Manual Chapter 1743. Retrieved from https://policymanual.nih.gov/1743 NIH Form 3000. Retrieved from https://oma.od.nih.gov/Lists/DMSFormsList/Attachments/682/NIH-3000.pdf 7 CRADA & MTA FAQs. Retrieved from http://www.ott.nih.gov/crada-mta-faqs 8 Final NIH Statement on Sharing Research Data, NOT-OD-03-032. Retrieved from https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html 6 A check mark (√) indicates that the section summarizes a specific policy 12 materials, given these potential limitations. For example, confidentiality may be maintained by removing personal identifiers from human subjects data, using Data Use Agreements to share data, or both. Consent documents must inform research subjects about plans to share data with other researchers and allow subjects to consent to broad sharing of data. During CRADA negotiations with private companies or other outside organizations, NIH investigators and institutional officials can advocate for including plans for sharing of data and materials in the agreement. Currently, all intramural researchers who collect data pertaining to human subjects must develop Data Sharing Plans for their research.9 Effective January 25, 2023, the NIH Policy for Data Management and Sharing will extend this requirement to all NIH intramural and extramural researchers. Data Management and Sharing Plans should outline how scientific data and any accompanying metadata will be managed and shared, taking into account any potential restrictions or limitations.10 IRP-specific processes to comply with this policy will be developed and implemented prior to the deadline, and this chapter will then be updated to reflect that information. Recognizing that large genomic data sets are especially valuable to the biomedical research community, the NIH has established the NIH Genomic Data Sharing (GDS) Policy to ensure that such data are appropriately accessible to qualified scientists.11 Many scientific journals now require researchers to make data available to the public by depositing data on a repository supported by the journal, a government agency, or a research organization. The NIH supports several such repositories, including GenBank (a genomic data repository),12 dbGaP (a repository for human genotypic and phenotypic data),13 and a pediatric MRI data repository.14 Legally Authorized Requests for Data Research data and other records in the IRP are subject to a request from an outside party under the Freedom of Information Act (FOIA), which allows individuals or organizations to access records generated by the federal government.15 Investigators must cooperate with FOIA requests. However, not all information requested through FOIA is subject to release. FOIA does not apply to preliminary data or analyses, drafts of papers, information that identifies human subjects, or information protected by copyright, patent, or trade secrecy law. 9 NIH Policy Manual Chapter 3016 - Intramural Research Program Human Data Sharing (HDS) Policy. Retrieved from https://policymanual.nih.gov/3016 10 Final NIH Policy for Data Management and Sharing, NOT-OD-21-013. Retrieved from https://grants.nih.gov/grants/guide/notice-files/NOT-OD-21-013.html 11 NIH Notice No. NOT-OD-14-124; NIH Genomic Data Sharing Policy. Retrieved from https://grants.nih.gov/grants/guide/notice-files/NOT-OD-14-124.html 12 GenBank. Retrieved from https://www.ncbi.nlm.nih.gov/genbank/ 13 dbGaP. Retrieved from https://www.ncbi.nlm.nih.gov/gap/. 14 NIH Pediatric MRI Data Repository. Retrieved from https://www.nitrc.org/projects/pediatric_mri/. 15 5 USC § 552; Freedom of Information Act Statute. Retrieved from https://www.foia.gov/foia-statute.html A check mark (√) indicates that the section summarizes a specific policy 13 Research records are also subject to subpoenas from Congressional Committees, and research on FDAregulated products is subject to auditing or inspection by the FDA. NIH researchers must cooperate with requests from Congress or the FDA for access to research records. Research records may also be subject to subpoenas from a court of law. To help protect privacy in clinical research, the NIH IRP has a Certificate of Confidentiality (COC) that applies to all human subjects research conducted by NIH investigators. The COC allows researchers to refuse to release research records requested by a court of law. To protect privacy and confidentiality, NIH investigators should refuse to release information pertaining to human subjects that is requested by state or federal courts. ▲ A check mark (√) indicates that the section summarizes a specific policy 14 Authorship Authorship is the fulfillment of the responsibility to communicate research results to the scientific community for external evaluation. Authorship is also the primary mechanism for allocating credit for scientific advances and thus forms the basis for assessing a scientist’s contributions to developing new knowledge. Authorship potentially conveys great benefit to co-authors, but it also involves personal responsibility for the data published. Strictly speaking, authorship refers to the listing of names of study researchers in any communications, either oral or written, of experimental results and their interpretation. For each individual the privilege of authorship should be based on a significant contribution to the conceptualization, design, execution, or interpretation of the research, as well as to the drafting or substantively reviewing or revising the research article. Authorship also conveys responsibility for the study. Individuals who do not meet these criteria but who have assisted the research by their encouragement and advice or by providing space, financial support, reagents, occasional analyses, or patient material should be acknowledged in the text but not be authors. The Committee on Scientific Conduct and Ethics (CSCE) devised general guidelines to assist with determination of who deserves to be an author. These guidelines can be found in the NIH Sourcebook.16 Disputes over authorship inclusion and order are not uncommon, including in those cases where one or more contributor(s) has left the lab where the research was primarily performed. NIH developed processes for resolution of authorship disputes, using a four-tiered process involving discussion, mediation, the option for peer review of the publication and/or authorship, and if unsuccessful, a final decision by the IC Scientific Director or the Deputy Director for Intramural Research (DDIR). This process is outlined in detail in the NIH Sourcebook.17 It is expected that members of each research group and Laboratory or Branch will freely discuss and resolve questions of authorship, including the order of authors, before and during the course of a study. Further, each author has the responsibility to review and support their contributions to the manuscript and be willing to support the general conclusions of the study submitted (originally or in revision) for publication. The NIH recommends, and many journals now require, that the transmittal letter accompanying a manuscript submission identify the exact contribution of each author. The corresponding author should be considered the primary author (but is not necessarily the first author), with the additional responsibilities of coordinating the completion and submission of the work, satisfying pertinent rules of submission, and coordinating responses of the group to inquiries or 16 General Guidelines for Authorship Contributions. Retrieved from https://oir.nih.gov/sites/default/files/uploads/sourcebook/documents/ethical_conduct/guidelinesauthorship_contributions.pdf 17 Processes for Authorship Dispute Resolution. Retrieved from https://oir.nih.gov/sourcebook/ethicalconduct/responsible-conduct-research-training/processes-authorship-dispute-resolution A check mark (√) indicates that the section summarizes a specific policy 15 challenges. The corresponding author is responsible for confirming that: 1) the contributions of all collaborators (intramural and extramural) are appropriately recognized, 2) each author has reviewed and authorized the submission of the manuscript in its original and revised forms, 3) the data in the manuscript have been reviewed if revised, and 4) the data in the manuscript and all analyses are reproducible. √ All manuscripts and abstracts coming from the IRP must be cleared in accordance with the policy18 and instructions included in the Sourcebook.19 It is not unusual for a co-author to leave the NIH prior to the final submission of a manuscript. The senior and/or corresponding author must ensure that the departing co-author is fully included in the revision process and agrees to submission of the final version of the manuscript. If the senior author makes a good faith effort to contact the departed co-author but is unable to do so, they should consider consulting with a supervisor about removing the co-author and placing an acknowledgement of the contributions of the co-author in the manuscript. When the departing co-author is the senior and/or corresponding author of a manuscript that uses data collected in the Intramural Research Program (IRP), they must use the NIH IRP manuscript clearance process prior to an initial submission. In this case, the manuscript must clearly annotate that the work was performed in the NIH IRP, but that the departing author is no longer affiliated with NIH. The departing author must also obtain approval from their previous NIH supervisor prior to submitting a revision of a previously submitted manuscript. If the departing author is unwilling or unable to communicate with their prior supervisor, NIH has the authority to remove the departing author from the manuscript prior to submission or re-submission, and/or to contact the publisher requesting that the manuscript not be published or be corrected/retracted if already published, because the manuscript uses data collected in the IRP and was submitted without NIH approval. ▲ 18 Manual Chapter 1184; Preparation and Clearance of Scientific, Technical and Public Information Presented by NIH Employees or Produced for Distribution by NIH. Retrieved from https://policymanual.nih.gov/1184 19 Publication and Abstract Clearance. Retrieved from https://oir.nih.gov/sourcebook/submitting-researchpublications/publication-abstract-clearance A check mark (√) indicates that the section summarizes a specific policy 16 Publications Publication of results is an integral and essential component of scientific research. Other than presentation at scientific meetings, publication in peer-reviewed scientific journals is the appropriate mechanism for the first public disclosure of new findings. Timely publication of new and significant results is important for the progress of science. Guidelines for submitting research publications can be found in the Sourcebook.20 Although generally considered the end point of a research project, publication is also the beginning of a process in which the scientific community at large can assess, correct, and further develop any particular set of results. √ All NIH publications must be reviewed by each IC Scientific Director or a delegated official to assure quality and compliance with applicable requirements19 such as to identify dual-use concerns,21 described in the Sourcebook. If the publication describes a possible patentable invention, contact the IC Technology Transfer Office prior to public release. The legal standard for inclusion of a researcher as an inventor on a patent is more strict than the policy for naming a researcher on a publication. √ Each paper should contain sufficient information for the informed reader to assess its validity, including all the information that would be necessary for scientific peers to repeat the experiments.18 The NIH position on reproducibility states that all essential data should be included in the published paper or be deposited in appropriate public databases or made available online. It is an obligation of NIH intramural scientists to make reasonable amounts of expandable materials (e.g., monoclonal antibodies) and analytical amounts of limited reagents that are essential for reproducibility of the published experiments available to qualified scientists. More information on policies and guidance for sharing NIH-funded research resources can be found on the Office of Extramural website.22 Fragmentary publication of the results of a scientific investigation, sometimes referred to as “salami slicing,” or multiple publications based on the same or similar data are inappropriate. Each publication should make a distinct and substantial contribution to its field. As a corollary to this principle, tenure appointments and promotions should be based on the importance of the scientific accomplishments and not on the number of publications in which those accomplishments were reported. Equally, authors should avoid publishers who entrap researchers into submitting their work and then charge them publishing fees but do not undertake serious peer review. Publications in such venues are unlikely to be counted as legitimate. Authors should seek to publish in journals that are findable (indexed in authoritative resources, e.g., Medline, Embase, Web of Science, Scopus). √ All NIH-funded investigators are required to post their final peer-reviewed manuscripts, upon 20 Submitting Research Publications. Retrieved from https://oir.nih.gov/sourcebook/submitting-researchpublications 21 Dual-Use Research. Retrieved from https://oir.nih.gov/sourcebook/ethical-conduct/special-researchconsiderations/dual-use-research 22 NIH Sharing Policies and Related Guidance on NIH-Funded Research Resources. Retrieved from https://grants.nih.gov/policy/sharing.htm A check mark (√) indicates that the section summarizes a specific policy 17 acceptance for publication, to the NIH National Library of Medicine’s (NLM) PubMed Central (PMC) via the NIH Manuscript Submission System23 (NIHMS).24 Authors must select the option to release their manuscripts to the public immediately, or within 12 months after the official date of final publication, depending on the publisher’s embargo agreement. NIH expects that only in limited cases will authors deem it necessary to select the longest delay period. The NIH encourages researchers to use interim research products25, such as preprint servers, to speed the dissemination and enhance the rigor of their work. Interim research products are complete public research products that are not final. A common form is the preprint, a complete public draft of a scientific document. Preprints are typically unreviewed manuscripts written in the style of peerreviewed journal articles, but they can also include a preregistered protocol. The purpose of a preprint is to obtain feedback prior to submission for publication, and the typical mechanism for receiving feedback is through a blog-style posting on a platform that accepts interim research products, with some examples but not limited to BioRxiv.org26, MedRxiv.org27, ChemRxiv.org28, and ASAPbio.org29. NIH researchers are not required to use preprint servers, and these products do not need to be submitted to PubMed Central30, although they still fall under the NIH publication policies31 and require IC clearance prior to submission. It should be noted that the preprint version of the manuscript will remain in the public space even after the peer-reviewed paper is published. Consequently, some researchers may decide that they do not want to use an interim research product for their work. Preprint publications may be cited in BSC reports, NIH bio-sketches, and NIDB Annual Reports, and should include the Digital Object Identifier (DOI). An example of such a citation is shown below: Bar DZ, Atkatsh K, Tavarez U, Erdos MR, Gruenbaum Y, Collins FS. Biotinylation by antibody recognition- A novel method for proximity labeling. BioRxiv 069187 [Preprint]. August 11, 2016 [cited 2017 Jan 12]. Available from: https://doi.org/10.1101/069187. Researchers should use a reputable repository that: • • • • • ensures that the content is findable, accessible, interoperable and re-usable; supports open access; uses a Creative Commons license32; is regulated by rigorous policies and processes to prevent plagiarism or other types of research misconduct, and conflicts of interest; has a link between the preprint and the final publication; and, 23 NIH Manuscript Submission System. Retrieved from https://www.nihms.nih.gov/db/sub.cgi NIH Public Access Policy. Retrieved from https://publicaccess.nih.gov/policy.htm 25 NIH Notice Number NOT-OD-17-050. Retrieved from https://grants.nih.gov/grants/guide/notice-files/not-od-17050.html 26 bioRxiv. Retrieved from https://www.biorxiv.org/ 27 medRxiv. Retrieved from https://www.medrxiv.org/ 28 ChemRxiv. Retrieved from https://chemrxiv.org/ 29 ASAPbio. Retrieved from https://asapbio.org/ 30 NIH Public Access Policy. Retrieved from https://publicaccess.nih.gov/ 31 Submitting Research Publications. Retrieved from https://oir.nih.gov/sourcebook/submitting-researchpublications 32 Creative Commons licenses. Retrieved from https://creativecommons.org/licenses/ 24 A check mark (√) indicates that the section summarizes a specific policy 18 • ensures long-term preservation and access of the preprint. The preprint should acknowledge the IRP as the source of funding, clearly state that the work is not peer-reviewed and declare any competing interests. NIH manuscript clearance33 is required for submissions of interim research products. Manuscript clearance is expected for submission of public feedback on a repository site regarding a preprint, or for any other public blog posting that indicates your NIH affiliation34, in accordance with ethics guidance35 and IC-specific publication policies and procedures. Researchers are encouraged to consult with their supervisors prior to a public blog posting. ▲ 33 NIH Publication and Abstract Clearance policy. Retrieved from https://oir.nih.gov/sourcebook/submittingresearch-publications/publication-abstract-clearance 34 NIH Manual Chapter 1184. Retrieved from https://policymanual.nih.gov/1184 35 Official Duty Activities. Retrieved from https://ethics.od.nih.gov/official A check mark (√) indicates that the section summarizes a specific policy 19 Mentoring and the Responsibilities of Research Supervisors and Trainees Research training is a complex process, the central aspect of which is a period of research carried out under the primary supervision of an experienced scientist. This supervised research experience is not merely the performance of tasks assigned by the supervisor, but rather it is a process wherein the trainee takes on an increasingly independent role in the selection, conceptualization, and execution of research projects. The trainee should be provided with training in the skills and knowledge necessary for their research projects and should expect to receive training in the full range of professional skills necessary for success along whatever career trajectory they choose to follow. Importantly, it must be recognized that the trainee has unique, time-sensitive needs relevant to career progression and advancement. As such, guidance, advocacy, and sponsorship are essential components of training. In general, a trainee will have a single primary research supervisor who usually fills the role of primary mentor as well. However, trainees are encouraged to identify additional individuals (e.g., scientific staff, more senior trainees) who function as mentors for specific aspects of training or career development. Also, supervisors should encourage trainees to take advantage of the numerous NIH campus resources including Institute and Center training offices and directors, the NIH Office of Intramural Training and Education (OITE), the NIH Library, and the Foundation for Advanced Education in the Sciences (FAES). It is the responsibility of the primary supervisor to serve as a role model and provide a rich research environment in which the trainee has the opportunity to acquire both conceptual and technical skills in the research field of interest. In this setting, each trainee should have a clear research training plan (e.g., Individual Development Plan) with end goals and intermediate milestones. Progress should be assessed regularly. A “Welcome Letter” or “Lab Compact” is recommended as a useful tool for mentors or other supervisors to introduce trainees to the specific expectations and responsibilities of both trainees and mentors in their research groups. Several examples are available for supervisors in the NIH Sourcebook.36 The primary mentor should interact with the trainee personally on a regular basis (e.g., once a week) to review primary data and to give timely feedback on research designs, results, progress, and publications. Good communication is critical to a successful training experience. Supervisors must be sensitive to the fact that each trainee has preferred communication, learning, and work styles, as well as biases and norms shaped by their previous life experiences. A good mentor seeks to understand each trainee’s unique qualities and adapts his/her training approach accordingly. Specific aspects of the mentor–trainee relationship deserve emphasis. Mentors should impart to the new investigator appropriate standards of scientific conduct, including appropriate ethical conduct, both Introduction to “My Laboratory.” Retrieved from https://oir.nih.gov/sourcebook/ethical-conduct/responsibleconduct-research-training/instruction-responsible-conduct-research-postdoc-irta-crta-vf-research/introduction 36 A check mark (√) indicates that the section summarizes a specific policy 20 by instruction and by example. Mentors should promote career development by encouraging their trainee to present at scientific meetings, by facilitating opportunities for collaboration and networking, and by encouraging attendance at scientific seminars and other scientific and professional activities at NIH. Mentors should provide trainees with timely, objective, and realistic appraisals of their performance along with advice regarding career directions, opportunities, and advancement. Trainees have responsibilities to their supervisors as well as to their research institutions. These include adherence to these Guidelines and Policies and other applicable rules, and to programmatic constraints related to the needs of the research team and Institute or Center. The same standards of professionalism and collegiality apply to trainees as to their supervisors and mentors. Trainees should play active roles in seeking the tools and experiences necessary to accomplish their goals. √ All NIH supervisors have a special responsibility to cast a wide net to assure recruitment and retention of a diverse and talented scientific community. The NIH is committed to the development of a biomedical research workforce that is representative of the diversity in American society and seeks to promote diversity in all of its training and research programs. This includes following NIH requirements for broadly advertised searches, strict prohibition against giving preference to relatives and friends when filling trainee or employee positions at the NIH,37 and attention to assuring that all trainees and employees at the NIH are valued and included as respected members of the NIH community. At the Laboratory and Branch level, this includes keeping records, conducting research, and interacting with colleagues in English.38 ▲ 37 Manual Chapter 2300-301-1; Nepotism. Retrieved from https://policymanual.nih.gov/2300-310-1#transmittalsheet 38 Policy on Use of English for Official Scientific Communication in NIH Laboratories and Branches. Retrieved from https://oir.nih.gov/sourcebook/personnel/recruitment-processes-policies-checklists/policy-use-english-officialscientific-communication-nih-laboratories A check mark (√) indicates that the section summarizes a specific policy 21 Collaborations and Team Science Collaborative research and team science bring together investigators with distinct strengths to work together on defined problems or to address specific research goals. As research methods become more sophisticated team science is increasingly important, both within NIH intramural programs as well as in collaborations with extramural institutions. These arrangements are strongly encouraged and supported; the complex scientific questions that face us today often require interdisciplinary or multidisciplinary approaches. Successful collaborations are characterized by a strong sense of direction, a willingness to commit time and effort, an efficient communication strategy for discussion among the group members, a system in place for reevaluation as the project progresses, and a clear definition of roles and responsibilities. It is advisable that the ground rules for collaborations, including eventual authorship issues, be discussed openly among all participants from the project’s beginning. The NIH has developed a useful set of criteria to consider in establishing collaborations and a Field Guide for Team Science.39 Questions for Scientific Collaborators Although each research project has unique features, certain core issues are common to most of them and can be addressed by having collaborators consider the following questions compiled by the NIH Office of the Ombudsman: Overall Goals: • What are the scientific issues, goals, and anticipated outcomes or products of the collaboration? • When will the project be completed? Who Will Do What? • What are the expected contributions of each participant? • Who will write any progress reports and final reports? • How, and by whom, will personnel decisions be made? How and by whom will personnel be supervised? • How and by whom will data be managed? How will access to data be managed? • How will you handle long-term storage and access to data after the project is completed? Authorship, Credit: • What will be the criteria and the process for assigning authorship and credit? 39 Collaboration and Team Science: A Field Guide. Retrieved from https://www.cancer.gov/aboutnci/organization/crs/research-initiatives/team-science-field-guide A check mark (√) indicates that the section summarizes a specific policy 22 • How will credit be attributed to each collaborator’s institution for public presentations, abstracts, and written articles? • How and by whom will public presentations be made? • How and by whom will media inquiries be handled? • When and how will you handle intellectual property and patent applications? Contingencies & Communications: • What will be your mechanism for routine communications among members of the research team (to ensure that all appropriate members of the team are kept fully informed of relevant issues)? • How will you decide about redirecting the research agenda as discoveries are made? • How will you negotiate the development of new collaborations and spin-off projects, if any? • Should one of the principals of the research team move to another institution or leave the project, how will you handle data, specimens, lab books, and authorship and credit? Conflicts of Interest: • How will you identify potential conflicts of interest among collaborators? • Could a collaborator or any close family members or associates benefit financially from the research? • Is a collaborator receiving money from someone who could benefit financially from the research? Whenever collaborations with scientists outside of NIH involve the exchange of biological materials or research data, they are routinely formalized by written agreements developed by the Technology Transfer Office of your Institute. Material Transfer Agreements (MTAs) are used for the simple transfer of proprietary research material with or without collaboration.7 For example, an MTA is used if you request a reagent from, or give one to, a colleague outside the NIH, or provide blood samples to be analyzed as part of a multi-study collaboration. For transfers within the NIH, no MTA is required but the transfer should be documented, for example in an email, and retained for records. Data Transfer Agreements (DTAs) are used for the transfer of existing data collected from human subjects, clinical studies, or laboratory experiments for research purposes. Cooperative Research and Development Agreements (CRADAs) are used for agreements between one or more NIH laboratories and at least one non-federal group (private sector, university, not-forprofit, non-federal government). CRADAs provide a protected environment for long-term collaborations; they confer intellectual property rights to NIH inventions.40 Researchers should comply with the terms of any research agreements governing release of data collected under 40 NIH Office of Technology Transfer. Retrieved from https://www.ott.nih.gov/policy A check mark (√) indicates that the section summarizes a specific policy 23 the agreement. The Office of Technology Transfer developed a set of FAQs to help investigators determine which instrument is most appropriate.41 Foreign Influences Biomedical research is an international enterprise accelerated by international collaborations, training experiences in other than home countries, and the sharing of appropriately vetted information. Investigators are encouraged to carefully review Avoiding Undue Foreign Influence on IRP Research.42 Special attention is required when deciding to: 1. invite a foreign scientist to work or train in an NIH laboratory; 2. accept an invitation to establish, oversee, or advise on research programs in foreign countries; 3. write letters of reference for foreign scientists or to provide material support for foreign research activities; and, 4. establish a collaboration with scientists from another country. Most of our interactions with foreign scientists are beneficial to the NIH mission and lead to long-term collaborations and major scientific advances. It is important to enable continuing and future interactions among NIH scientific staff and foreign scientists where the NIH PI and NIH as an institution are satisfied that the circumstances of such interactions do not allow undue foreign influence on NIHsupported research. ▲ 41 CRADA & MTA FAQs. Retrieved from https://www.ott.nih.gov/faqs/crada-mta-faqs Avoiding Undue Foreign Influence on IRP Research. Retrieved from https://oir.nih.gov/sourcebook/personnel/recruitment-processes-policies/guide-nih-intramural-principalinvestigators-navigate-international 42 A check mark (√) indicates that the section summarizes a specific policy 24 Scientific Rigor and Reproducibility Scientific Rigor is the robust and unbiased application of the scientific method to well-defined research questions. To facilitate robust results, valid data are obtained by utilizing independent approaches to address research questions and ensuring that experiments are sufficiently controlled and documented to be reproducible. Reproducibility or replication of experiments, observations, and results is an integral component of the scientific method and allows science to be “self-correcting.” Combined, rigor and reproducibility are essential to the generation of knowledge and the elaboration of new principles.43 Rigor involves 4 areas of focus: 1. Careful assessment of prevailing knowledge in field of study to identify strengths and weaknesses in prior research and any gaps in knowledge. 2. How applications of the scientific methodology will ensure robust and unbiased experimental design, methodology, analysis, interpretation, and dissemination of information. 3. The careful consideration of biologic variables that can influence experimental design and scientific methodology; i.e., species, sex, age, weight, animal models, and environmental considerations. 4. Validation of reagents, chemicals, biologics, and tests used in the research. Reproducibility involves the reproduction of results by independent researchers that serves to both validate the original findings and develop the next phases of scientific investigation. Sufficiently detailed information must be provided in the Materials and Methods sections of research studies to enable the replication of experiments by independent individuals or research groups. Technical replicates as well as biologic replicates are necessary to ensure rigorous observations. Data sharing in a timely fashion utilizing publicly accessible databases is essential to ensure rigor and reproducibility. Approaches to Improve Rigor and Reproducibility Many journals now include a checklist to ensure appropriate methodologies are detailed. A separate statistical section and an independent statistical review are utilized by many journals to ensure rigorous statistical analyses. While journals have set word limits for research manuscripts, there should be few limits on the length of the methods section so that sufficient details are presented to enable reproduction of research results. Online supplemental methods sections are another mechanism to ensure sufficient details are included. Investigators should report how often technical and biologic replicates are preformed and whether graphs are representative or averages of several experiments. Computation of appropriate sample size should be performed as part of the experimental design. Issues related to randomization procedures and inclusion and exclusion criteria should be explicitly detailed for experimental and clinical data. ▲ 43 Enhancing Reproducibility through Rigor and Transparency. Retrieved from https://grants.nih.gov/policy/reproducibility/index.htm A check mark (√) indicates that the section summarizes a specific policy 25 Research Misconduct A positive research climate allows and encourages open debate about how data should be interpreted. Often there is more than one way to view the results of any given experiment and science is propelled forward by the discussion. To maintain a positive climate at NIH, differences of opinion should be expressed with civility and respect. Expressing disagreement or a differing interpretation of data is not equivalent to making an allegation of research misconduct. Research misconduct becomes an issue when the integrity or veracity of the actual data can be questioned. The scientific community and general public rightly expect intellectual honesty in the formulation, conduct, reporting, and reviewing of scientific research. Investigators must act with integrity when editing, analyzing, and presenting data. Deceptive manipulation of data, be it misreporting of data, inappropriate exclusion of data outliers, or inappropriate enhancement of images, are examples of research misconduct. The manipulated data need not be published or presented at a conference to constitute research misconduct. √ Research misconduct is defined as fabrication, falsification, or plagiarism (FFP) in proposing, performing, or reviewing research, or in reporting research results. Fabrication is making up data or results and recording or reporting them. Falsification is manipulating research data, materials, equipment, or processes, or changing or omitting data or results such that the research is not accurately represented in the research record. Plagiarism is the appropriation of another person’s ideas, processes, results, or words without giving appropriate credit. Research misconduct does not include honest error or differences of opinion. The research record is the record of data or results, both physical and electronic, that embody the facts resulting from scientific inquiry; including but not limited to emails, research proposals, laboratory records, progress reports, abstracts, theses, presentations, internal reports, and journal articles.44,45 Research records generated by NIH researchers are owned by NIH, may not be removed from the laboratory, and must be retained as an official NIH record. 3 Text recycling46 is the reuse of material in a new document, without quotations, and where at least one author of the new document is also an author of the prior document. Although this practice used to be referred to as self-plagiarism, text recycling is not plagiarism or self-plagiarism. Recent publications show that text recycling may be done ethically and appropriately, as long as there is full disclosure and the authors are careful to not recycle text in ways that might mislead the reader. 44 NIH Intramural Research Program Policies and Procedures for Research Misconduct Proceedings. Retrieved from https://oir.nih.gov/sites/default/files/uploads/sourcebook/documents/ethical_conduct/policynih_irp_research_misconduct_proceedings.pdf 45 42 CFR Parts 50 and 93; PHS Policies on Research Misconduct; Final Rule. Retrieved from https://ori.hhs.gov/sites/default/files/42_cfr_parts_50_and_93_2005.pdf 46 Text Recycling Research Project. Retreived from https://textrecycling.org/what-is-text-recycling/ A check mark (√) indicates that the section summarizes a specific policy 26 √ The NIH takes all allegations of research misconduct seriously. All NIH personnel are expected to report observed, apparent, or suspected research misconduct to the NIH Agency Intramural Research Integrity Officer (AIRIO).44 The procedures followed at the NIH are designed to permit allegations of research misconduct to be processed promptly, confidentially, and fairly. This helps minimize any harm to the public that could result if misconduct is found, and it prevents damage to the career of those who are incorrectly implicated. Allegations of misconduct are handled through three stages: an initial Assessment made by the AIRIO that the matter warrants an Inquiry; an Inquiry during which a panel of scientists determine if there is substantive, credible evidence of FFP to warrant further examination; and an Investigation during which a panel of scientists makes a recommendation to the Deciding Official that the institution make a finding of research misconduct. The procedures to resolve an allegation of research misconduct may include the following: interviewing the person making the allegation (i.e., the Complainant), the subject of the allegation (i.e., the Respondent) and possibly other key staff from the lab; identifying and taking possession of NIH research records contained in laboratory notebooks and electronic files and closely examining them; conferring with subject matter experts including “forensic” data analysts; deliberation of the committee (Inquiry or Investigation); and writing a final report(s). The entire process may take several months to complete. Although misconduct proceedings are confidential, a finding of misconduct may result in NIH taking administrative actions to remediate the harm, consistent with applicable personnel rules and regulations, which may entail notifying certain parties with a “need to know” the sensitive information. A finding of research misconduct may result in the disclosure of the misconduct by NIH to research collaborators, professional journals, professional societies, news media, and the public. Administrative actions taken may include requiring a correction or retraction of pending or published papers, removal of personnel from a project, suspension, salary reduction, reduction in rank, or termination of employment. √ The AIRIO will also take action to prevent retaliation against any complainant who brings forward an allegation in good faith.44 Although not research misconduct, poor scientific practices can impact the integrity and productivity of a research program. These practices are called Questionable Research Practices (QRPs) or Detrimental Research Practices (DRPs; a term coined by the 2017 NAS Report, Fostering Integrity in Research).47 Examples of troubling DRPs include: • • • • Honorary or ghost authorship Poor stewardship of the research record Neglectful or exploitative supervision in research Misleading statistical analyses that fall short of falsification 47 Fostering Integrity in Research. Retrieved from https://www.nap.edu/catalog/21896/fostering-integrity-inresearch A check mark (√) indicates that the section summarizes a specific policy 27 A critical part of training and mentoring is promoting explicit discussion of best practices in the laboratory. To that end, discussion of research ethics, including the required annual case studies found in the Responsible Conduct of Research (RCR) Training Program, should be held regularly by NIH Institutes and Centers.48 All personnel should understand the responsibilities and expectations relevant to recording and maintaining data in their laboratories, including the requirement to maintain research records for a minimum of seven years after completion of the project. PIs and supervisors should make a point to review experimental data frequently. Presentation of figures in group meetings should be accompanied by primary data for verification whenever possible. Perhaps most importantly, PIs must model ethical research practices and ensure that undue pressure to succeed does not create a climate that tolerates DRPs. ▲ 48 Annual Review of Ethics (Case Studies). Retrieved from https://oir.nih.gov/sourcebook/ethicalconduct/responsible-conduct-research-training/annual-review-ethics-case-studies A check mark (√) indicates that the section summarizes a specific policy 28 Harassment, Sexual Harassment, and Inappropriate Conduct √ Science depends on creativity, and research has shown that diversity in the workplace increases creativity. Consequently, an inclusive workplace is good for research. In recognition of the importance of fostering and maintaining the most inclusive environment, the NIH leadership in October 2018, initiated a campaign aimed at increasing awareness and elimination of harassment, including sexual harassment, in the research community. This issue is addressed in detail by NIH Policy Manual Chapter 1311 which opens with: “The contributions of each and every member of the National Institutes of Health’s community are vital to successfully improving people’s health and reducing the burden of disease. An environment where people feel welcome, respected, and valued is necessary for all individuals to contribute to their fullest potential. In alignment with this, the NIH is committed to creating and maintaining a work environment that is free of harassment and other inappropriate conduct. Harassment, bullying, intimidation, threats, or other disruptive behaviors are unacceptable and will be handled with administrative and/or legal action, as appropriate. Actions that run counter to our mission and goals will be met with consequences, no matter who the offender.” √ The NIH will not tolerate inappropriate conduct or harassment, including sexual harassment. Timely and appropriate action will be taken against any individual found to be in violation of the policy outlined in this document.49 The Civil Program, within the Workforce Relations Division in the Office of Human Resources, is responsible for conducting administrative inquiries into reports of harassment. Victims of or witnesses to harassment have multiple mechanisms for reporting.50 1. One can contact Civil directly by calling the Civil main line (301-402-4845), by reporting online, or by calling the NIH Anti-Harassment Hotline (833-224-3829). Hotline or on-line reporting can be done anonymously. 2. Confidential disclosures can be made to the NIH Office of the Ombudsman51 or the Employee Assistance Program.52 Trainees may also report to the Office of Intramural Training and Education (OITE).53 These offices provide a confidential setting to discuss and clarify your options. 49 Manual Chapter 1311; Preventing and Addressing Harassment and Inappropriate Conduct. Retrieved from https://policymanual.nih.gov/1311 50 The NIH Civil Program. Retrieved from https://hr.nih.gov/working-nih/civil/ 51 Office of the Ombudsman. Retrieved from https://ombudsman.nih.gov 52 Employee Assistance Program (EAP). Retrieved from https://www.ors.od.nih.gov/sr/dohs/HealthAndWellness/EAP/Pages/index.aspx 53 Office of Intramural Training and Education. Retrieved from https://www.training.nih.gov/ A check mark (√) indicates that the section summarizes a specific policy 29 3. It should be noted that all managers at NIH are required to contact Civil if they witness harassment or receive a report of harassment. Civil is available to help a manager understand how best to proceed. Important links to guidelines and resources dealing with how to report harassment, procedures and offices for remediation, and individual responsibilities can be found at the following: • The NIH Director: Changing the culture of science to end sexual harassment54 • NIH Manual Chapter 1311: Preventing and Addressing Harassment and Inappropriate Conduct49 ▪ Toolkit for Employees55 ▪ Toolkit for Supervisors56 ▪ Toolkit for Trainees and Fellows57 ▪ Toolkit for Contractors58 ▪ Additional Q&As for all staff can be found by visiting the NIH Civil website59 To learn more about ways to report a concern, please visit the “How I can Report Harassment or Inappropriate Conduct?” webpage at NIH Civil website.60 Disclosure of Personal Relationships Between Supervisor/Supervisee Learning to become an excellent researcher involves tutelage of junior scientists by more senior mentors. By definition, this process establishes a power differential between the junior researcher and the mentor, who will be evaluating the work and eventually providing references for future employers. Consequently, it is important that relationships are transparent and that there is disclosure of a romantic relationship between supervisor/supervisee in cases where the supervisor has an actual, perceived, or potential for perceived, influence over the professional relationship or workplace. 54 Changing the Culture of Science to End Sexual Harassment. Retrieved from https://www.nih.gov/about-nih/whowe-are/nih-director/statements/changing-culture-science-end-sexual-harassment 55 Toolkit for Employees. Retrieved from https://ohr.od.nih.gov/intrahr/Documents/civil/ManualChapter1311ToolkitforEmployees_508.pdf 56 Toolkit for Managers & Supervisors. Retrieved from https://ohr.od.nih.gov/intrahr/Documents/civil/ManualChapter1311ToolkitforSupervisors_508.pdf 57 Toolkit for Trainees. Retrieved from https://ohr.od.nih.gov/intrahr/Documents/civil/ManualChapter1311ToolkitforTraineesandFellows_508.pdf 58 Toolkit for Contractors. Retrieved from https://ohr.od.nih.gov/intrahr/Documents/civil/ManualChapter1311ToolkitforContractors_508.pdf 59 NIH Anti-Harassment Policy and Guidance. Retrieved from https://hr.nih.gov/working-nih/civil/nih-antiharassment-policy-and-guidance 60 “How Can I Report Harassment or Inappropriate Conduct?” Retrieved from https://hr.nih.gov/workingnih/civil/how-can-i-report-harassment-or-inappropriate-conduct A check mark (√) indicates that the section summarizes a specific policy 30 √ The NIH Personal Relationship Policy Statement addresses problems that arise when there is a power differential between persons within a personal relationship. As stated in the NIH Policy Statement: Personal Relationships in the Workplace:61 Personal relationships (including romantic and/or sexual) between individuals in inherently unequal positions, where one party has real or perceived authority over the other in their professional roles, may be inappropriate in the workplace and are strongly discouraged. If such a relationship exists or develops, it must be disclosed. This applies to all individuals in the NIH community, including employees, contractors, students, trainees, and fellows and includes anyone who holds a position of authority or perceived authority over another individual from a scientific or administrative perspective. Persons who are involved in such relationships are required to disclose the relationship to their IC. The agency can then 1) reassign the work of one party to eliminate the supervisor/supervisee relationship, 2) have the supervisor recuse themselves from all official matters that affect the subordinate, 3) inquire as to whether inappropriate actions have occurred, or 4) take other appropriate action to eliminate the potential risk of the relationship. It should be noted that relationships between senior staff and trainees are not appropriate. If you are involved in a personal relationship and are unsure whether you need to disclose, you can get help by contacting your IC’s Executive Officer, by contacting the NIH Office of the Ombudsman,51 or by reviewing: • √ NIH Policy Statement: Personal Relationships in the Workplace61 ▪ ▪ Toolkit for NIH staff, including trainees/fellows and contractors55,57,58 Toolkit for Managers and Supervisors56 ▲ 61 NIH Policy Statement: Personal Relationships in the Workplace. Retrieved from https://hr.nih.gov/workingnih/civil/nih-policy-statement-personal-relationships-workplace A check mark (√) indicates that the section summarizes a specific policy 31 Peer Review and Privileged Information Peer review is expert critique of either a written scientific work, such as an article prepared or submitted for publication, a grant proposal, or a clinical research protocol, or of an investigator’s research program, as in a site visit. Peer review requires that the reviewer be expert in the subject under review and it is an essential component of the conduct of science. Decisions on the funding of research proposals and on the publication of study results must be based on thorough, fair, and objective evaluations by recognized experts. Therefore, although it is often difficult and timeconsuming, scientists have an obligation to participate in the peer review process. In doing so, they make an important contribution to science. The review should be fair and unbiased and should uphold scientific quality consistent with appropriate publication policies. It should be based solely on scientific evaluation of the material under review within the context of published information and should not be influenced by information unavailable publicly, or by non-scientific information such as authors’ affiliations. The reviewer should avoid any real or perceived conflict of interest that might arise because of a direct competitive, collaborative, or other close relationship with one or more of the authors of the material under review. Such a conflict of interest would usually require a decision not to participate in the review process and to return (or not access) material unread. Potential conflicts should always be declared to the person managing the review, such as the editor of a journal or the scientific review officer of a grant review panel. Reviewers should refuse work with known predatory publishers. Reviewers must not review their own manuscripts and fake reviewer accounts should not be used. The transparency of the peer-review system must be maintained through all stages. Some specific review activities may require review and approval by a supervisor and/or deputy ethics counselor in an IC.62 An underlying principle for performing peer review is that reviewers should not benefit unfairly from the submitted information. All material under review is confidential information. Material from the review should not be used by the reviewer to guide their own research program. It should not be shared with anyone unless necessary to the review process, in which case the names of those with whom the information was shared should be made known to those managing the review process. Material under review should not be copied and retained or used in any manner by the reviewer unless specifically permitted by the journal or reviewing organization and by the author. ▲ 62 Official Duty Activities. Retrieved from https://ethics.od.nih.gov/official A check mark (√) indicates that the section summarizes a specific policy 32 Scientific Integrity at the NIH The National Institutes of Health (NIH) seeks fundamental knowledge about the nature and behavior of living systems through research that it funds and conducts. The mission of the NIH is to apply that knowledge toward enhancing health, lengthening life, and reducing the burdens of illness and disability. The NIH accomplishes this mission in two ways: 1) by being the nation’s largest single funder of biomedical research at universities and institutions throughout the U.S. and abroad through its Extramural Research Program; and 2) by conducting applied and basic biomedical research within the laboratories and clinics of its Intramural Research Program. √ At NIH, scientific integrity refers to maintaining the quality and objectivity of the research activities that the National Institutes of Health funds and conducts, such that they are sound and worthy of the public’s confidence.63 Upholding high standards of scientific integrity means maintaining the quality and objectivity of the research conducted and funded by the NIH. A commitment to sound, objective science strengthens public trust in policies informed by scientific data. In addition to federal and departmental requirements, the NIH has numerous policies in place to ensure the scientific integrity of its Intramural and Extramural Research Programs. The NIH also participates in a wide range of federal policy-making in the areas of clinical research, biotechnology, and biosecurity. Science seeks verifiable truth. The NIH policies are designed to ensure transparent processes that will lead to objective, credible, and readily available scientific findings. These policies also protect against fraud, waste, and abuse by identifying and addressing fabrication, falsification, and plagiarism thus providing effective stewardship of public funds. Inquiries about the NIH Scientific Integrity policy may be addressed to the Office of Science Policy.64▲ 63 NIH Policies and Procedures for Promoting Scientific Integrity. Retrieved from https://www.nih.gov/sites/default/files/about-nih/nih-director/testimonies/nih-policies-procedures-promotingscientific-integrity-2012.pdf 64 NIH Office of Science Policy. Retrieved from https://osp.od.nih.gov/ A check mark (√) indicates that the section summarizes a specific policy 33 Conflicts of Interest A conflict of interest (COI) is a situation in which a person has a financial, professional, personal, or other interest that may compromise judgment related to the performance of his or her ethical, legal, or professional duties. COIs are an important ethical concern because they can interfere with the objectivity and integrity of science and undermine the public’s trust in research. COIs can occur in many different areas of science, including research design and implementation, publication, peer review, service on advisory panels, recruitment of human subjects, and research oversight (e.g., service on institutional review boards or animal care committees). The three main strategies for dealing with COIs are: 1) disclosing the conflict to the affected parties, 2) avoiding the conflict, and 3) taking measures to manage the conflict and reduce its impact. When there is a potential COI, full disclosure and complete transparency is always the best policy. Most scientific journals and grant review organizations have rules concerning the disclosure of COIs, which NIH scientists should follow. The NIH Ethics Program has specific rules concerning COIs, outside activities (such as consulting and speaking), gifts, honorary awards, and investments, and these issues are an integral component of the federal government’s annual reporting and online ethics training.65 Intramural researchers should know these rules and, when in doubt, refer any questions to the Deputy Ethics Counselor of their Institute or Center. √ Scientists should disclose all relevant financial interests when required by the NIH Ethics Office, including those of the scientist’s immediate family, to: 1) the scientist’s Institute or Center during the planning, conducting, and reporting of research studies; 2) funding agencies before participating in peer review of applications for research support; 3) conference organizers before presentation of results; 4) journal editors when submitting or refereeing any material for publication; and 5) anyone receiving oral or written communications about the scientist’s research. Financial interests include, but are not limited to, ownership of stock or equity, patents, consulting arrangements, honoraria, service on advisory boards, or management appointments having fiduciary responsibilities.66 Another type of conflict that can occur in research is a conflict of commitment. Conflicts of commitment may arise when researchers devote excessive time to activities that have no direct bearing on their official employment duties. Outside activities (with or without compensation) are not permitted during work hours. Outside activities can take away time from official duties and, in general, all such outside activities require prior review from the Institute or Center (IC) ethics office. Examples could include excessive commitments of time for work on behalf of committees of scientific societies or journals or participating in outside clinical practice. Similarly, over commitment—even though well-intended—can become an ethical problem. For example, when researchers take on too many trainees, or oversee too many clinical trials, they may 65 66 NIH Ethics Program. Retrieved from https://ethics.od.nih.gov/ Manual Chapter 2400; Ethics. Retrieved from https://policymanual.nih.gov/2400-01 A check mark (√) indicates that the section summarizes a specific policy 34 be unable to give a best effort to all of them. Signs of over commitment include when advisors cannot find sufficient time to meet with their fellows or to review and critique first drafts of manuscripts within a few days or a week, or when PIs are unable to personally supervise the running of their clinical trials. Failure to personally oversee clinical research that uses FDA-regulated products is one of the most common findings cited in audit reports and FDA warning letters. Human Subjects √ The NIH Human Research Protection Program has standard operating procedures for dealing with COIs in research with human subjects.67,68 ▲ 67 18 USC §§ 203,205, and 207-209; 5 CFR Parts 2634-2641, 5 CFR Parts 5501-5502 HRPP Standard Operating Procedure/Policy Approval & Implementation. Retrieved from https://irbo.nih.gov/confluence/display/IRBO/HRPP+Policies+and+Procedures 68 A check mark (√) indicates that the section summarizes a specific policy 35 Social Responsibility, Media Inquiries, and Dual-Use Research According to the NIH mission statement, one of the goals of NIH is “to exemplify and promote the highest level of scientific integrity, public accountability, and social responsibility in the conduct of science.”69 Scientific research conducted by NIH intramural investigators often provides information and knowledge that can be used to inform the subsequent diagnosis, treatment, or prevention of diseases and advance human health and well-being. However, research may sometimes have unintended adverse social impacts. For example, publishing a study on sexually transmitted diseases and drug abuse in an identifiable community may lead to discrimination and bias against members of that community. Research that provides data on the risks of a vaccine might discourage members of the public from having their children vaccinated. Publicly sharing the sequence of a universal virulence factor might enable others to make a deadly bioweapon from an otherwise harmless organism. NIH intramural investigators therefore have a responsibility to anticipate the possible social and environmental consequences of their research and to take steps to minimize their potential for harm. Scientists who are studying identifiable communities or populations, for example, should be aware of the potential impact of their research on those communities and, when appropriate, work with community leaders to ensure that their research addresses important community needs. In some cases, it may be necessary to delay publication of research to allow for additional review and comment by NIH committees, journal editorial boards, or communities impacted by the research. When research may be readily misused by others to threaten public health and safety, agriculture, the environment, or national security, scientists should consider whether it should be published in full, in redacted form, or possibly not at all. Media Inquiries News media inquiries also raise issues concerning social responsibility for NIH scientists, since communications with the news media are an opportunity to educate the public about important advances in biomedical research.70 However, journalists and members of the public may sometimes misinterpret or misunderstand the results of research. Also, communications with the news media can have a significant impact on the public’s opinion of NIH research. Intramural investigators should contact their institute’s communications office prior to responding to inquiries from the news media. Investigators who are being interviewed by the news media should communicate their main points in a manner that is both accurate and understandable to the public. 69 NIH Mission and Goals. Retrieved from https://www.nih.gov/about-nih/what-we-do/mission-goals Guidelines on the Provisions of Information to the News Media. Retrieved from https://www.hhs.gov/sites/default/files/media_policy.pdf 70 A check mark (√) indicates that the section summarizes a specific policy 36 Dual Use √ The United States Government policy defines dual use research of concern as: “research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security.”71 The NIH Intramural Research Program requires that each publication be evaluated for dual use; and, if questions are raised, a central committee works with the author to ensure that information contained within the manuscript does not support nefarious use.72 Annual Dual Use Research of Concern (DURC) reviews must be completed in the NIH PI Dashboard (requires authorization for access).73 These reviews must be certified by the PI of record on the recombinant materials or pathogen registration document. ▲ 71 United States Government Policy for Institutional Oversight of Life Sciences Dual Use Research of Concern. Retrieved from http://www.phe.gov/s3/dualuse/Documents/durc-policy.pdf 72 Dual-Use Research. Retrieved from https://oir.nih.gov/sourcebook/ethical-conduct/special-researchconsiderations/dual-use-research 73 NIH PI Dashboard. Retrieved from https://oms.ors.nih.gov A check mark (√) indicates that the section summarizes a specific policy 37 Ethical Leadership and Management Ethical leadership and management play an indispensable role in research integrity and regulatory compliance. Good leadership and management can help prevent fabrication and falsification of data, poor recordkeeping, intractable authorship disputes, harassment, bullying, negligent mentoring, violations of animal or human subjects regulations, and many other ethical problems that can arise in research. Poor leadership and management, by contrast, can encourage or cause unethical behavior. Good leadership and management can also foster scientific productivity, discovery, and innovation, while poor leadership and management can have the opposite effect. While scientific organizations, such as the NIH, include many different leadership and management positions at different levels, from laboratory director to branch chief to director of Intramural Research, this chapter will focus on leadership and management of the scientific laboratory.74 The discussion in this chapter is very much in the spirit of the preface to this document, which emphasizes the importance of developing a culture of integrity throughout the NIH. Although almost anything involving conducting research or the environment within a lab can have ethical dimensions, the following issues can typically arise in managing a scientific laboratory: • Human resources and diversity: Recruitment, hiring, promotion, salaries; equity, diversity and inclusion; racial, ethnic, gender, disability and cultural issues; power structure and imbalance; harassment; romantic relationships in the lab; socializing outside the lab; family issues; physical and mental health; sick leave and parental leave • Laboratory management: Leadership; laboratory culture; priority-setting; data management, teamwork and collaborations; conflict management; work assignments and deadlines • Research integrity: Research misconduct; data integrity and management; sharing of data and materials; research recordkeeping, authorship; publication; conflict of interest; • Mentoring: Mentoring and training; advising and career development; skill building; career opportunities • Resources: Funding, budgeting, and purchasing; equipment, materials, and supplies • Compliance and Safety: Complying with laws, regulations, policies, guidelines, and best practices involving human and animal subjects and hazardous materials; adherence to material transfer and technology transfer agreements; laboratory safety, radiation safety, biosafety, and occupational health. From this list, one can see that scientists clearly face numerous complex ethical issues when managing a research laboratory. To deal with these issues appropriately and effectively, it is essential for investigators (and administrators) who occupy leadership positions to remain abreast of new developments and training in research ethics and management; to reflect on the ethical values that guide their leadership and decision-making; and to seek advice when faced with problems that are “Laboratory” is understood to mean a group of people working together to conduct research. A laboratory, in this sense, is not a physical place but an organizational unit. Many scientists at NIH, including epidemiologists, biostatisticians, clinicians, and bioethicists conduct research outside of traditional, physical laboratories. 74 A check mark (√) indicates that the section summarizes a specific policy 38 difficult to handle. The following are some ways that scientists can promote a culture of integrity within their laboratory: • Set an ethical tone within the laboratory by providing a good example of ethical behavior for others to follow; stress the importance of ethics during lab meetings and other activities and enforce ethics training requirements. • Promote effective communication within the laboratory by holding regular meetings; establishing clear expectations concerning responsibilities, performance, and evaluation; and instituting open door policies (i.e., keeping one’s office door open to encourages people to drop by to talk freely about problems or concerns) and open notebook policies (i.e., research records can be accessed by other members of the research group, especially the PI; see chapters on scientific recordkeeping and data management). • Respect and encourage diversity and inclusion within the laboratory; do not discriminate against people on account of race, ethnicity, gender, or any other personal characteristics that are irrelevant to scientific performance. • Treat all people fairly and avoid favoritism. Fairness can be an important concern in many different areas, including work assignments, authorship, allocation of resources, and sick leave. There is no simple formula for treating people fairly. Establishing clear expectations and policies that apply equally to all members of the lab is crucial for treating people fairly, but good mentoring can also consider each person’s needs, talents, or circumstances. • Develop written policies concerning recordkeeping, review of data, division of labor and authorship, allocation of resources, publication, parental leave, and other topics, provided they are consistent with laws, regulations, and NIH policies. • Strive for productivity and efficiency but not to the point where people cut corners, compromise quality, or feel pressured to work faster or harder than they are comfortable doing. • Respect the proprietary nature of research but encourage a collaborative environment in the laboratory. Encouraging researchers to assist each other with methods and ideas increases productivity and fosters goodwill within the laboratory. • Do not expect or imply that specific results must be obtained; scientific investigation should be conducted to answer a question, not to produce a particular outcome. Experiments that fail to turn out as planned can lead to innovation and novel discoveries. Pressuring people to obtain specific results can lead to fabrication or falsification. • Make good use of financial and other resources; don’t waste time, money, or materials. • Support activities that promote regulatory compliance and best practices, including training, auditing, and reporting of violations of laws, regulations, and NIH policies. A check mark (√) indicates that the section summarizes a specific policy 39 • Seek ethics advice, counsel, or coaching from an experienced, outside party, such as another PI, ethics official, or ombudsperson;75 or someone from the Employee Assistance Program76 or Civil Program.77 Executive coaching78 and an ethics audit79 can be useful tools for promoting ethical laboratory management. Participate in training activities that promote ethical management, such as training in conflict resolution, leadership, and business (e.g., accounting and budgeting).▲ 75 NIH Center for Cooperative Resolution. Retrieved from https://ombudsman.nih.gov/ NIH Employee Assistance Program. Retrieved from https://ors.od.nih.gov/sr/dohs/HealthAndWellness/EAP/Pages/index.aspx 77 NIH Civil Program. Retrieved from https://hr.nih.gov/working-nih/civil 78 An executive coach is a qualified professional who works with individuals to help them clarify their goals and objectives, gain self-awareness, and unlock their potential. An executive coach can also serve as a sounding board or mentor. The NIH offers executive coaching. Retrieved from https://hr.nih.gov/trainingcenter/services/executive-leadership-and-team-coaching. 79 An ethics audit is an audit of the ethical climate of an organization by an outside party. The auditor can interview members of the organization to identify ethical successes, problems, and concerns. 76 A check mark (√) indicates that the section summarizes a specific policy 40 IRP Commitment to Diversity, Equity, Inclusion, and Accessibility Research groups in the IRP are expected to foster and promote a culture of belonging and inclusion. “Belonging and inclusion” here refers to the IRP’s commitment to welcome, retain, and foster success in trainees and staff from a broad array of backgrounds, cultures, experiences, and perspectives. Examples of how principal investigators (PIs) and group leaders may achieve this include, but are not limited to: • • • • • • mentoring trainees from diverse backgrounds, including trainees with disabilities or from underserved communities (see the Notice of NIH’s Interest in Diversity); ensuring pay equity; advancing the principles of inclusion and equity in advertising positions and making hiring decisions; serving (or encouraging service by lab members) on diversity, equity, and inclusion committees at NIH or elsewhere (e.g., scientific societies, community organizations, etc.); creating an environment that welcomes frequent trainee and staff feedback; and participating, promoting, and engaging in training related to diversity, equity, inclusion, and/or social justice (e.g. implicit bias awareness, best practices for hiring, culturally-aware mentorship, etc.) and ensuring that workspaces and technologies are fully accessible. PIs and group leaders are expected to incorporate the principles of diversity, equity, inclusion, and accessibility into every aspect of leading and managing their groups, and should be held accountable for doing so. They should be able to document in their BSC reports the strategies they are using to make all team members feel equally appreciated and included, facilitate collaboration among group members, and act early on potentially discriminatory behaviors as soon as they emerge. Regarding best practices for hiring, PIs and group leaders should understand how to mitigate bias during recruitment and candidate selection, including but not limited to writing inclusive position advertisements, advertising broadly to a diverse array of institutions, standardizing the interview process, using diverse selection committees, and using rubrics or other standardized measures for candidate evaluation and selection. PIs and group leaders should also be able to outline future plans for how they will continue to improve in the fostering and promotion of a diverse, inclusive, and equitable research environment in their laboratory or research group and the IRP community over the next review period. Creating a culture that promotes the principles of diversity, equity, inclusion and accessibility is a joint responsibility shared by all laboratory and research groups. ▲ A check mark (√) indicates that the section summarizes a specific policy 41 Animal Care and Use The use of laboratory animals is an essential component of biomedical research, and humane and effective use of animals is a necessary and important element of such research activities. Animal research, for the purposes of these Guidelines and Policies, is defined as in vivo research performed on laboratory animals in order to develop knowledge that contributes to the improvement of health and well-being of humans as well as other animals. The NIH Office of Animal Care and Use (OACU) provides oversight of animal research in the NIH Intramural Research Program (IRP) and provides a full range of resources related to policy, training, guidelines, and regulations.80 The animal care and use program of each NIH Institute and Center is directed by an institute-appointed Animal Program Director who is a senior veterinarian possessing extensive research in animal medicine and care expertise. An Animal Care and Use Committee (ACUC) is appointed by the Institute Scientific Director to provide oversight of an institute’s animal care and use program. The ACUC consists of institute scientists, nonscientists, safety specialists, and non-IC affiliated individuals. All components of the intramural NIH Animal Care and Use program are accredited by AAALAC International; meet the Public Health Service Policy and standards for the care and use of laboratory animals; and comply with the US Animal Welfare Regulations.81 Before conducting research involving animal subjects, researchers must develop a detailed Animal Study Proposal (ASP) that is approved by an ACUC. The ACUC has responsibility for ensuring that the proposed research follows all pertinent regulations governing the ethical use of animals in research. This includes ensuring that personnel are properly qualified to conduct the study and trained in the specific animal procedures used in the study. √ When developing an Animal Study Protocol, investigators should adhere to the following principles:82 Reduce the number of animals requested to a minimum but adequate number required to achieve the experimental goals. Where applicable, this number should be dictated by the amount of data required to achieve significant statistical power to support the study’s conclusions. Refine the experimental methods to minimize the pain and stress experienced by the animal subjects. Replace study animals with animals of a lower phylogenetic ranking or non-animal models whenever possible: e.g., insects, cell lines, computational models. 80 NIH Office of Animal Care and Use. Retrieved from https://oacu.oir.nih.gov/ NIH Manual Chapters and Other Relevant NIH Policies on Animal Care and Use are Summarized. Retrieved from https://oacu.oir.nih.gov/nih-policies 82 PHS Policy on Humane Care and Use of Laboratory Animals. Retrieved from https://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf 81 A check mark (√) indicates that the section summarizes a specific policy 42 In addition, NIH expects that all animal studies consider sex as a biological variable, or an adequate explanation be provided addressing why this is not possible.83 All staff participating in animal research must initially complete the course “Using Animals in Intramural Research: Guidelines for Animal Users.”84 Refresher training is required every three years. Other training may be required for studies using certain animal species and employing particular experimental techniques. Principal investigators receive further training from the course “Using Animals in Intramural Research: Guidelines for Principal Investigators.” 85 Scientists should be mindful that views on animal research vary considerably. As such, it is absolutely critical that all research involving animals be conducted in accordance with the highest ethical standards as reduced to practice through the established guidelines and regulations (available, for reference, through the OACU). Furthermore, scientists should take responsibility for how their animal research is portrayed in the public domain, keeping in mind that communicating this high standard of practice and care is important for securing the public’s continued trust and support for these important activities. ▲ 83 NIH NOT-OD-15-102; Consideration of Sex as a Biological Variable in NIH-funded Research. Retrieved from https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-102.html 84 Training Resources. Retrieved from https://oacu.oir.nih.gov/training-resources 85 NIH Office of Animal Care and Use Training. Retrieved from https://oacutraining.od.nih.gov/public_menu.aspx A check mark (√) indicates that the section summarizes a specific policy 43 Human Biospecimen Tracking and Storage √ Biological specimens (or “biospecimens”) from study participants must be stored, tracked, shared, and disposed of according to the highest ethical and scientific standards to maintain the public’s trust, to preserve and protect the specimens and the substantial investment these resources represent, and to facilitate research by maximizing use of the specimens.86 All human biospecimens acquired by scientists in the NIH IRP should be handled and stored following the best practices available. Human biospecimens include blood and other body fluids, tissues, nucleic acids, and other direct derivatives from human tissues including human embryonic and induced pluripotent stem cells, and other immortalized human cell lines.87 NIH has developed detailed Guidelines for Human Biospecimen Storage, Tracking, Sharing and Disposal88 as is required by Congress, in Section 104 of the National Institutes of Health Reform Act of 2006 (Pub. L. 109-482), enacted on January 15, 2007.89 The Guidelines cover all aspects of human biospecimen storage and tracking and address legal and ethical considerations; collection and storage; inventory database systems and tracking; quality management practices, including standard operating procedures; shipping and sharing; and custodianship. The Guidelines reinforce the requirements that human biospecimens used by NIH researchers must be: • Collected in accordance with an IRB approved informed consent that is properly signed by the subject, or under an approved waiver of informed consent granted by an independent ethical review body, in accordance with 45 CFR Part 46, Protection of Human Subjects, as applicable and appropriate; • Used under prospective and continuing IRB review and approval or an exemption from IRB review from the NIH Office of the IRBO, as applicable and appropriate; • Stored and used in accordance with the Privacy Act, as applicable and appropriate; • Handled in accordance with the U.S. Occupational Safety and Health Administration's 86 Manual Chapter 1189; Policy for the Management of and Access to Scientific Collections. Retrieved from https://policymanual.nih.gov/1189 87 45 CFR 46; Protection of Human Subjects. Retrieved from https://www.hhs.gov/ohrp/regulations-andpolicy/regulations/45-cfr-46/index.html 88 Guidelines for Human Biospecimen Storage, Tracking, Sharing, and Disposal within the NIH Intramural Research Program. Retrieved from https://oir.nih.gov/sites/default/files/uploads/sourcebook/documents/ethical_conduct/guidelinesbiospecimen.pdf 89 Biennial Report of the Director. Retrieved from https://report.nih.gov/biennialreport1011/appendices/NIH_Appendix_A.html A check mark (√) indicates that the section summarizes a specific policy 44 Bloodborne Pathogens Standard and best practices to protect the integrity of biospecimens and protect the workers; • Packed and shipped conforming to all applicable regulations and standards, including the U.S. Department of Transportation and International Air Transport Association standards; and stored with an individual computer-generated label or electronic tracking device with a unique identifier, which enables the investigator to link to a basic set of information on specimen acquisition or the protocol and informed consent (or waiver) under which the specimen was collected, as well as the NIH Clinical Center Clinical Research Information System patient identification number, as appropriate, and which is able to withstand all potential storage conditions. When an investigator departs NIH, unless the IC has agreed to allow the investigator to properly transfer the biospecimens, the IC will coordinate with another investigator to assume custodianship of the biospecimens.▲ A check mark (√) indicates that the section summarizes a specific policy 45 Health & Safety √ The promotion of health and safety policies, practices, and procedures is the responsibility of each member of the NIH community. Each person in the laboratory has a vital role to play by ensuring that research is conducted in a manner that keeps personnel in the laboratory safe, protects that community from research-associated hazards, and maintains the public trust of scientific research.90 Employees are expected to perform their work in a safe manner and to ensure that they do not place themselves, coworkers, study participants, visitors, or support personnel at risk of injury or illness due to unsafe conditions. All employees are responsible for attending required safety training, wearing appropriate personal protective equipment (PPE), and following safety procedures established by the NIH, their IC, and their specific laboratory.91 √ Supervisors (e.g., principal investigators, laboratory directors, laboratory managers, etc.) must provide a workplace free of known hazards for their laboratory staff and visitors. Supervisors should conduct a risk assessment of all laboratory activities to identify potential hazards and implement control strategies for those hazards. They must ensure that their staff are aware of these hazards and are properly trained to minimize or eliminate the hazards.90 The NIH, through the Office of Research Services, has many resources available to assist the research community in conducting their research in a safe and responsible manner. These resources include: • The Division of Occupational Health and Safety (DOHS) provides expert guidance and technical support for the NIH research community. Each institute is assigned a safety specialist who serves as a safety resource for researchers, laboratory managers, supervisors, and IC senior management.92 • Additionally, the DOHS Occupational Medical Service (OMS) supports the research community with all occupational safety and health concerns. The NIH OMS provides support for medical emergencies, pre-placement evaluations, surveillance programs (e.g., the Animal Exposure Program), support for work-related travel, and basic care for work-related injuries 90 Manual Chapter 1340; NIH Occupational Safety and Health Management Program. Retrieved from https://policymanual.nih.gov/1340#06CAE9F2 91 NIH Office of Management; Training Requirements & Available Courses. Retrieved from https://www.safetytraining.nih.gov/ 92 Division of Occupational Health and Safety. Retrieved from https://www.ors.od.nih.gov/sr/dohs/safety/laboratory/Pages/safety_health_specialists.aspx A check mark (√) indicates that the section summarizes a specific policy 46 and illnesses. All injuries and illnesses must be reported to the OMS.93 • The Division of the Fire Marshal (DFM) proactively addresses the fire protection and life safety needs of the NIH community by mitigating risk through collaborative services such as design reviews, pre-occupancy inspections, fire safety consultative services, and a wide-range of other fire safety services.94 • The Division of Radiation Safety (DRS) specializes in radiation safety, regulatory compliance, and risk management for biomedical and clinical research efforts that directly support the NIH mission. They provide comprehensive services and innovative solutions to protect individuals, populations, and the environment from ionizing radiation.95 Other resources for help maintaining a safe and healthy research environment include: • The NIH Occupational Safety and Health Committee (OSHC). The OSHC provides safety policy recommendations to the Director of the NIH in matters pertaining to occupational health, accident control, and fire prevention.96 • Individual IC safety and health committees. Each IC has a safety and health committee that addresses specific safety needs of the IC. The IC safety and health committees turn the broader framework of NIH policy into practices and policies that work for their specific IC. • Safe Techniques Advance Research Science (S.T.A.R.S.) Training Program. This program is for NIH summer students, aged 21 and under. The S.T.A.R.S. program provides students with the knowledge of a broad range of safety topics applicable to a biomedical research facility in a hands-on "Learn by Doing" laboratory environment. It fosters critical thinking and problemsolving skills vital to potential hazard recognition and accident prevention through mock learning scenarios and challenges. Students learn how important it is to stop, think, and apply safe laboratory practices.97 Maintaining a safe and healthy research environment is an important responsibility that is shared by all NIH personnel. This includes regularly reviewing all stored materials, keeping an inventory of all biological materials, and appropriately disposing of materials no longer in use. It requires the support of everyone to ensure that research at the NIH is conducted in a manner that protects all NIH personnel and the community around us. It is consistent, well-planned, conducted by trained personnel, and is 93 DOHS Occupational Medical Service. Retrieved from https://www.ors.od.nih.gov/sr/dohs/HealthAndWellness/OccupationalMedical/Pages/oms_main.aspx 94 Division of the Fire Marshal. Retrieved from https://www.ors.od.nih.gov/ser/dfm/Pages/default.aspx 95 Division of Radiation Safety. Retrieved from https://drs.ors.od.nih.gov/Pages/default.aspx 96 Occupational Safety and Health Committee. Retrieved from https://www.ors.od.nih.gov/sr/dohs/safety/Pages/Occupational-Safety-and-Health-Committee.aspx 97 Student Laboratory Safety Training. Retrieved from https://www.ors.od.nih.gov/sr/dohs/safety/Training/Pages/student_labtraining.aspx A check mark (√) indicates that the section summarizes a specific policy 47 done using proper equipment that minimizes variables and compensates for the unexpected. Safe science is good science. ▲ A check mark (√) indicates that the section summarizes a specific policy 48 Fetal Tissue Research Human fetal tissue (HFT) has intrinsic cellular properties that make it invaluable for innovative, translational research, but its use also has profound ethical implications. NIH intramural investigators and contractors should be mindful that research involving HFT requires significant additional oversight, and must be conducted in accordance with applicable federal, state, and local laws, regulations, and policies.98 √ Researchers may acquire, use and store HFT for intramural research projects. Acquisition, from either a commercial source or from an academic institution, clinic, or hospital, requires prior approval.98 Researchers are also required to report annually on their acquisition, use or storage of HFT.88 Use of HFT is reported annually on the publicly facing Research, Condition, and Disease Categories (RCDC) by intramural project number.99 Intramural researchers with HFT projects are at times required to answer data calls on various aspects of their use of HFT. Research on transplantation of HFT for therapeutic purposes is permitted but requires additional intramural regulatory oversight because of the statutory provision(s) addressing such research. Please contact the Office of Intramural Research if you are considering research in which HFT or cells would be transplanted as part of clinical research. √ All experiments using HFT must be reviewed and approved either by the Office of Human Subject Research Protections, via a determination of “Not Human Subjects Research” for de-identified tissue, or when tissues have associated identifiable information via a protocol approved by the IRB.87,100 In association with human subjects review, the investigator will execute an Attestation document that must be filed with the IC (with a copy retained in the investigator’s records). A copy of the Attestation must accompany all requests for purchase of HFT from commercial sources. All commercial suppliers of research material must provide documentation that they comply with the applicable Federal law and policies. When HFT is received as part of collaborations with organizations outside of the NIH, either a Material Transfer Agreement or Collaborative Agreement must be executed, which contains specific language assuring that the materials were obtained in compliance with the applicable federal law and policies or alternatively provided information on comparable restrictions in force in their country if coming from outside the United States.98 Derivation of human Embryonic Stem Cells (hESCs) from human embryos in the intramural program is prohibited by the annual appropriations restriction on funding of human embryo research. Researchers 98 Special Research Considerations. Retrieved from https://oir.nih.gov/sourcebook/ethical-conduct/specialresearch-considerations 99 Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC). Retrieved from https://report.nih.gov/funding/categorical-spending#/ 100 NIH NOT-OD-15-143; NIH Policy on Informed Consent for Human Fetal Tissue Research. Retrieved from https://grants.nih.gov/grants/guide/notice-files/not-od-16-033.html A check mark (√) indicates that the section summarizes a specific policy 49 may acquire existing, approved hESCs from a commercial source or through an MTA, following intramural guidelines and processes. 101 ▲ 101 Human Embryonic Stem Cell (hESCs) Use in the Intramural Research Program. Retrieved from https://oir.nih.gov/sourcebook/ethical-conduct/special-research-considerations/human-stem-cell-use/humanembryonic-stem-cell-hescs-use-intramural-research-program A check mark (√) indicates that the section summarizes a specific policy 50 Human Subjects Research √ Research involving human subjects conducted by NIH intramural researchers is governed by various federal regulations, ethical standards, and policies that protect the rights and welfare of individuals who participate in research and promote the public’s trust in the research enterprise. These include federal regulations, most notably 45 CFR 46, the DHHS Protection of Human Subjects (Subpart A, the "Common Rule" and Subparts B-E )87 and Food and Drug Administration (FDA) regulations (where applicable); the ethical principles found in the Belmont Report; NIH policies; and HRPP Standard Operating Procedures/Policies (SOPs) developed by the Office of Human Subjects Research Protections (OHSRP). OHSRP administers the NIH Human Research Protection Program (HRPP), with support from NIH Institutes and Centers, NIH officials, NIH Institutional Review Boards (IRBs), researchers, and staff of the Intramural Research Program (IRP) who conduct and support research. The NIH HRPP is accredited by the Association for the Accreditation of Human Research Protection Programs (AAHRPP). The OHSRP, in support of the Deputy Director for Intramural Research, develops and maintains the NIH HRPP SOPs.102 The NIH HRPP SOPs can be found on the Office of Institutional Review Board Operations (IRBO) website. √ No research involving human subjects, including their identifiable data or specimens, may commence until after the investigator has obtained IRB review and approval or a determination that the proposed activity is exempt from IRB review.103 Human Subjects Research refers to activities in which an investigator, for research purposes: i. ii. Obtains information [about the individual] or biospecimens through intervention or interaction with the individual, and uses, studies, or analyzes the information or biospecimens; or Obtains, uses, studies, analyzes, or generates identifiable private information or identifiable biospecimens [from living individuals]. 87 For information on whether a specific activity might constitute human subjects research or not, refer to guidance available on the Office of IRBO website.104 All intramural investigators conducting human subjects research that will not be directly overseen by an NIH Institutional Review Board (IRB) are expected to consult with the Office of IRBO. √ All IRP investigators who conduct human subjects research are required to complete CITI human subjects research protections training in order to assure that they understand what is required when 102 HRPP Policy and Procedures. Retrieved from https://irbo.nih.gov/confluence/pages/viewpage.action?pageId=36241835 103 HRPP SOP 7; Requirements for the Ethical and Regulatory Review of Research by NIH Institutional Review Boards (IRBS). Retrieved from https://irbo.nih.gov/confluence/display/ohsrp/Step+1 104 Decision Tree: Is the Activity Research Involving Human Subjects? Retrieved from https://irbo.nih.gov/confluence/display/ohsrp/Step+1 A check mark (√) indicates that the section summarizes a specific policy 51 they conduct this type of research.105 Additionally, investigators, who conduct non-exempt human subjects research, must also complete CITI Good Clinical Practice (US FDA Focus) training. The NIH HRPP requires that each protocol approved by an NIH IRB have a single PI who is responsible for its design and conduct.106 PIs also have special responsibilities to provide leadership and oversight over the conduct of their research protocol(s) and the research team. Upon IRB approval, the PI may delegate specific aspects of the conduct of the research to other members of the research team in writing, but the PI retains overall responsibility. Collection, Storage, and Sharing of Data √ Investigators must ensure the integrity and confidentiality of data collected in the course of clinical research and protect the privacy of human subjects. Attention should be paid to: • Appropriate safeguards to protect the confidentiality of subject data; for example, by removing personally identifiable information (PII) from data, specimens, and records; utilizing secure electronic systems and locations; and limiting who may have access to the specimens or data. • Appropriate storage and retention of research records, data, and specimens, in accordance with NIH policy and FDA regulations, as applicable. 3 • A Plan for Data Sharing, approved by the IC Scientific Director or designee, as required by the Intramural data sharing policies, including: o Human Data Sharing (HDS) Policy (July 31, 2015);22 and o Genomic Data Sharing (GDS) Policy: The GDS policy applies to all NIH IRP research that generates large-scale human or non-human genomic data as well as the use of these data for subsequent research. Large-scale data include genome-wide association studies (GWAS), single nucleotide polymorphisms (SNP) arrays, and genome sequence, transcriptomic, metagenomic, epigenomic, and gene expression data. These data must be submitted to a repository (e.g., dbGaP). Individual ICs may have additional interpretations and requirements.22 More information about Intramural data sharing policies can be found in the Sourcebook.107 105 HRPP Policy Number 201; Education Program. Retrieved from https://irbo.nih.gov/confluence/display/IRBO/Policies+and+SOPs 106 HRPP SOP 19; Investigator Responsibilities. Retrieved from https://irbo.nih.gov/confluence/display/IRBO/Policies+and+SOPs 107 Intramural Data Sharing. Retrieved from https://oir.nih.gov/sourcebook/intramural-programoversight/intramural-data-sharing A check mark (√) indicates that the section summarizes a specific policy 52 Registration and Results Reporting of Clinical Trials √ The Clinical Center Office of Protocol Services registers all IRB-approved NIH human clinical trials108 at ClinicalTrials.gov when NIH is identified as the responsible party. Clinical trials must also comply with the Food and Drug Administration Amendments Act (FDAAA)109 and NIH policy requirements for reporting of results.110 The PI must ensure that trial results and informed consent documents are submitted within the required time frames. The PI may consult the IC Clinical Director for additional information. ▲ 108 42 CFR 11; Clinical Trials Registration and Results Information Submission. Retrieved from https://www.federalregister.gov/documents/2016/09/21/2016-22129/clinical-trials-registration-and-resultsinformation-submission 109 FDA Amendments Act (FDAAA) Section 801: “Basic Results” Provisions. Retrieved from https://www.govinfo.gov/content/pkg/PLAW-110publ85/pdf/PLAW-110publ85.pdf#page=82 110 42 CFR 11 402(j); Clinical Trials Registration and Results Information Submission. Retrieved from https://www.govinfo.gov/content/pkg/CFR-2017-title42-vol1/xml/CFR-2017-title42-vol1-part11.xml A check mark (√) indicates that the section summarizes a specific policy 53 Research Material Management and Research with High-Consequence Pathogens: Institutional Biosafety √ The NIH Institutional Biosafety Committee (IBC) oversees intramural use of microbiological agents, their vectors, and associated recombinant and synthetic molecular technology. These are powerful research tools but can pose significant risk to the research personnel who use them as well as to the environment during their use, storage, and disposal; therefore, researchers using these tools share the responsibility for their ethical use with the NIH IBC.90 It is a requirement at NIH that Principal Investigators register with the NIH IBC any recombinant DNA experiments covered under the NIH Guidelines For Research Involving Recombinant Or Synthetic Nucleic Acid Molecules.111 Work involving potentially infectious human, plant, or animal materials, and human pathogens, human and non-human primate blood, tissues, and body fluids, including primary human cell cultures, must also be registered with the IBC. √ All potentially hazardous biological materials must be inventoried prior to long-term storage in any freezer, refrigerator, cold room, or other location. This requirement applies to all NIH federally owned or leased facilities and all NIH contractor or subcontractor facilities. Inventory data should be recorded at the time of registration. Accurate inventories should be maintained in each laboratory and reviewed at least annually during the registration review process. ICs must develop policies that assure that unneeded or unwanted materials are not abandoned by research personnel. Annual inventory updates are required.112 The DOHS implements various programs and policies that address conducting high-risk infectious disease research. Among other activities, the DOHS is responsible for implementing the NIH Biological Surety Program, the NIH Select Agent Program (see below), and the NIH Quarantine Permit Service Office (QPSO). All questions related to requirements of these programs can be directed to the DOHS at 301-496-2960.113 Select Agent Program √ Select Agents are biological agents and toxins that the Federal Select Agent Program (SAP) (HHS and USDA) has determined to pose a severe threat to both human and animal health, to plant health, or to animal and plant products known as select agents/toxins.114 Any microorganism or toxin capable of harming living organisms or the environment, regardless of its origin (naturally occurring, engineered, or synthesized) can be classified as a select agent. Anyone planning to work with select agents/toxins must 111 NIH Guidelines. Retrieved from https://osp.od.nih.gov/biotechnology/nih-guidelines/ Manual Chapter 3035; Working Safely with Potentially Hazardous Biological Materials. Retrieved from https://policymanual.nih.gov/3035 113 Biological Safety. Retrieved from https://www.ors.od.nih.gov/sr/dohs/safety/laboratory/BioSafety/Pages/bio_chem_safety.aspx 114 NIH must comply with the regulations and requirements of 42 CFR 73, 7 CFR 331 and 9 CFR 121. 112 A check mark (√) indicates that the section summarizes a specific policy 54 enroll in the SAP and receive approval prior to the possession, use, and transfer of select agents/toxins. If unescorted access is required to areas containing select agents or areas associated with the biocontainment of select agents, individuals must contact the SAP. Additional information can be found at the Federal Select Agent Program on the Center for Disease Control website115 and the DOHS Select Agent Program website.116 Biological Surety Program √ The NIH Biological Surety Program (BSP) was established to ensure that work pertaining to high risk infectious disease research is performed in the safest and most responsible manner possible by a trained, responsible, and reliable workforce. The Biological Surety Program applies to all intramural NIH personnel, Federal and non-federal, and visitors assigned to work in BSP spaces. BSP spaces are defined as all NIH ABSL-4, BSL-4, ABSL-3, and BSL-3 facilities, including areas of critical infrastructure, and information systems that support these laboratories.117 Quarantine Permit Service Office (QSPO) √ Individuals wishing to import any biological material (infectious or non-infectious) from outside the United States to the NIH must contact the QPSO.118 Upon review of submitted forms, QPSO determines whether the intended importation requires the issuance of a CDC import permit and label or an NIH Letter for Non-Infectious Importation. QPSO provides the required documentation to the applicant. Individuals wishing to export any biological material (infectious or non-infectious) from the NIH to a destination outside of the United States must submit a "Declaration for Exportation of Biological Materials" (NIH 2388) to QPSO and secure the necessary approvals prior to shipment.119 ▲ 115 Federal Select Agent Program. Retrieved from https://www.selectagents.gov/ Select Agent Program. Retrieved from https://www.ors.od.nih.gov/sr/dohs/safety/laboratory/BioSafety/Pages/select_agents.aspx 117 Manual Chapter 3037; NIH Biological Surety Program. Retrieved from https://policymanual.nih.gov/3037 118 Biological Materials Shipping. Retrieved from https://www.ors.od.nih.gov/sr/dohs/safety/laboratory/BioSafety/Pages/shipping_biological_material.aspx 119 Manual Chapter 1340-1; Permits for the Import, Transfer, or Export of Biological Materials. Retrieved from https://policymanual.nih.gov/manage/chapter/view/1340-1 116 A check mark (√) indicates that the section summarizes a specific policy 55 Ethical Concerns Related to NIH Information Technology As a science, research, and information-based organization, the NIH relies on computers, networks, and a variety of other information technology (IT) systems to fulfill its mission. Information technology touches every aspect of research and discovery, including the acquisition of data, the processing of data, the archiving of data, and the dissemination of our research to the public. Accordingly, the NIH works continuously to improve our information security posture, and proactively manage risk while supporting and safeguarding the NIH community, culture, and mission. From an ethics perspective there are four major IT topics that members of the NIH community should be aware of: IT security, accessibility, compliance, and privacy. These are discussed below.120 IT Security √ Our first line of defense of our IT infrastructure is our researchers. The rigorous measures needed to protect research data often seems to be in marked contrast to the open, collaborative nature of science. Information security is a balancing act, weighing openness and transparency against the risk that always accompanies the choices we make, our behaviors, and the care we take with our security. Regular IT Security and Privacy Awareness Training is taken seriously at the NIH and is required of all staff.121 Internal Risks. Be aware that security breaches that occur within the institution are often accidental or the result of complacency, but they also may be malicious, with intent to harm. • Accidental breaches may occur as a result of inappropriately directed emails that include sensitive documents or personally identifiable information. How often do you get bounce-back emails that ask, “Did you mean to send this to me?” • Complacency stems from taking a “this rule doesn’t apply to me and won’t affect what I do” attitude. How often do you forget about data security and send sensitive information inappropriately to your own personal email or download it to a USB drive? • We seldom think about the potential for malicious threats from our scientists and trainees. We may know coworkers who seem permanently dissatisfied, want to take shortcuts, or look for information not related to their job online, regularly surfing the Internet and perhaps even downloading inappropriate information. 120 IT Governance & Policy; IT Policy, Standards and Guidance. Retrieved from https://ocio.nih.gov/ITGovPolicy/Pages/spec_policy.aspx 121 Manual Chapter 2813; NIH Information Security and Privacy Awareness Training Policy. Retrieved from https://policymanual.nih.gov/2813. The training may be accessed at https://irtsectraining.nih.gov/ A check mark (√) indicates that the section summarizes a specific policy 56 Know When and How to Get Help • When? Get help immediately if you encounter problems with system access, cannot connect using VPN, lose a laptop or mobile device, get caught in a phishing scheme, or accidentally disclose sensitive information. Report lost or stolen equipment within one hour. • How? Contact the NIH IT Service Desk http://itservicedesk.nih.gov/. Select Tips • Use a strong password or pass-phrase containing a sequence of upper and lower-case letters and characters that is easy to remember and type. • Use two-factor authentication when available. • Be conscious of any sensitive information or data to which you have access. If you do need to distribute sensitive information, make use of government-approved encryption procedures. • When using portable equipment, be extra-careful. Oftentimes, this type of equipment vanishes from cars, homes, airports, and public transportation. • When using social media, be careful not to blur your professional and private lives. Remember that once you post something, it is virtually impossible to remove it. IT Accessibility √ Because all Americans are entitled to the same access to government-generated resources, such as NIH web pages, announcements, web movies, pictures, and directives, it is our shared responsibility to ensure that NIH-generated IT resources are accessible to people with disabilities (such as vision and hearing impairment).122 IT Compliance √ The Department of Health and Human Services (HHS) permits limited personal use of HHS IT resources (including government-furnished equipment such as mobile devices), which involves no more than minimal additional expense to the government, as long as the personal use123 is minimally disruptive to personnel productivity; does not interfere with the mission or operations of HHS; and follows the guidance provided by the Cybersecurity Information Security and Privacy Program 124 and the Rules of Behavior for Use of HHS Information Resources.125 It is important to remember that the privilege of using NIH computers, tablets, phones, networks, and other IT resources comes with the mandatory 122 IT Governance & Policy; Section 508: Accessibility at NIH. Retrieved from https://ocio.nih.gov/ITGovPolicy/NIH508/Pages/default.aspx 123 HHS Policy for Personal Use of Information Technology Resources. Retrieved from https://intranet.hhs.gov/sites/default/files/s3fs-public/s3fs-public/pol-pers-use-it-rsrc.pdf 124 Cybersecurity Information Security and Privacy Program. Retrieved from https://www.hhs.gov/about/agencies/asa/ocio/cybersecurity/index.html 125 Rules of Behavior for Use of HHS Information Resources. Retrieved from https://www.hhs.gov/about/agencies/asa/ocio/cybersecurity/rules-of-behavior-for-use-of-hhs-informationresources/index.html A check mark (√) indicates that the section summarizes a specific policy 57 acceptance of a set of general rules of behavior designed to safeguard these resources and assure for their ethical use.126 IT Privacy √ There are several facets to IT privacy. First, we need to protect information acquired in the course of our work and whose disclosure could harm others: personally identifiable information (PII), sensitive information (SI), and protected health information (PHI). Secondarily, we must be aware that we have no guarantee of privacy in our own communications such as e-mails when we use government-owned equipment (computers, tablets, telephones). We must keep all this in mind when posting any documents on the Web; on a social network for example. We also have to be aware of where we store documents; our own computer, a local server, or on the Cloud.127 ▲ 126 NIH Information Technology General Rules of Behavior. Retrieved from https://irtsectraining.nih.gov/CSA/0301010_BehaviorRules.aspx 127 Manual Chapter 1745; NIH Information Technology (IT) Privacy Program. Retrieved from https://policymanual.nih.gov/1745 A check mark (√) indicates that the section summarizes a specific policy 58 Whistleblowing and Whistleblower Protections As a community of scientists, we share a responsibility to disclose wrongdoing that impacts the integrity of NIH research, public health and safety, our government’s honesty, accountability, and efficiency. Federal law protects “whistleblowers” (those who make a good faith allegation of a wrongdoing) from retaliation. Reporting Concerns HHS employees and agents (contractors, visiting scientists) can report a violation of any law, rule, or regulation; mismanagement; a gross waste of federal funds; or a substantial and specific danger to public health or safety through the following reporting web forms: • • HHS Office of Inspector General hotline128 U.S. Office of Special Counsel hotline129 Allegations involving NIH programs and activities, including misuse of NIH grant or contractor funds, grantee or contractor conflicts of interest, and other misconduct or misuse of NIH resources by NIH employees or others doing business with NIH, can be reported via: • Division of Program Integrity, Office of Management Assessment, Submit Allegations130 Intramural employees may also report concerns related to the NIH research environment using the following reporting web forms: • • • • • • Intramural Animal Welfare Concerns131 Intramural Human Research Subject Protections87 Intramural Unsafe or Unhealthful Conditions132 Intramural Research Misconduct concerns133 Intramural Harassment or Civility concerns134 Intramural EEO discrimination concerns135 128 HHS Office of Inspector General; Submit a Hotline Complaint. Retrieved from https://oig.hhs.gov/fraud/reportfraud/index.asp 129 U.S. Office of Special Counsel Complaint & Disclosure Form. Retrieved from https://osc.gov/Pages/FileComplaint.aspx 130 Division of Program Integrity. Retrieved from https://oma.od.nih.gov/DPI/Pages/Home.aspx 131 Anonymous Reporting of Animal Welfare Concerns. Retrieved from https://oacu.oir.nih.gov/nihpolicies/reporting-animal-welfare-concerns/anonymous-reporting-animal-welfare-concerns 132 Unsafe or Unhealthful Conditions Reporting. Retrieved from https://www.ors.od.nih.gov/sr/dohs/safety/incidents_accidents/Pages/Report-of-Unsafe-Condition.aspx 133 Anonymous Reporting of Research Misconduct Concerns. Retrieved from https://oir.nih.gov/sourcebook/ethical-conduct/research-misconduct/anonymous-reporting-research-misconductconcerns 134 Civil Intake Form. Retrieved from https://hr.nih.gov/working-nih/civil/intake-form 135 EEO Efile. Retrieved from https://nihefile.icomplaints.com/efile-nih-prod/login/ A check mark (√) indicates that the section summarizes a specific policy 59 Reporting Retaliation √ The Whistleblower Protection Act prohibits retaliation. This means it is unlawful for NIH to take or threaten to take a personnel action against an employee because he or she made a protected disclosure of wrongdoing. A protected disclosure is defined as a disclosure of information that the individual reasonably believes evidences a violation of law, rule, or regulation; gross mismanagement; gross waste of funds; and abuse of authority; or a substantial and specific danger to public health or safety. Personnel actions that are covered by this can include poor performance review, demotion, suspension, termination, or revocation or downgrade of a security clearance.136 In addition, the law prohibits retaliation for: • • • • filing an appeal, complaint, or grievance; helping someone else file or testifying on that person's behalf; cooperating with or disclosing information to OSC or an Inspector General; or refusing to obey an unlawful order. If you believe whistleblower retaliation has occurred, you may get more information from the HHS Office of Inspector General (OIG) website,137 including: • • • • Information on the Whistleblower Ombudsman, with helpful FAQs Information on how to report whistleblower retaliation Information on who is eligible for whistleblower protections Information on what complaints are investigated by the OIG (including whistleblower disclosures). Do not assume that telling someone within NIH that you feel retaliated against (making an informal complaint) substitutes for claiming retaliation under the Whistleblower Protection Act through a formal process. ▲ 136 5 U.S.C. 2302(b)(8)-(9), Pub.L. 101-12; Whistleblower Protection Act of 1989. Retrieved from https://www.govinfo.gov/content/pkg/STATUTE-103/pdf/STATUTE-103-Pg16.pdf 137 Office of Inspector General. Retrieved from https://oig.hhs.gov/about-oig/about-us/index.asp A check mark (√) indicates that the section summarizes a specific policy 60 Concluding Statement These Guidelines and Policies remind NIH scientists of the applicable rules, policies, and ethical standards to be incorporated into and maintained in the scientific culture of the Intramural Research Program. They provide a framework for the fair, open, and responsible conduct of research without inhibiting scientific freedom or creativity. Advice on any of the topics covered in this document can be obtained from the offices cited. You can also consult with members of the NIH Committee on Scientific Conduct and Ethics,138 with your Scientific Director, or with your Training Director. Support is also available from the NIH Office of the Ombudsman.51 ▲ 138 Committee on Scientific Conduct and Ethics (CSCE). Retrieved from https://oir.nih.gov/sourcebook/committeesadvisory-ddir/committee-scientific-conduct-ethics-csce A check mark (√) indicates that the section summarizes a specific policy