I. Guiding Principles
Overview: Research in the Department of Pharmacology and Cancer Biology addresses a myriad of important scientific questions relevant to cancer, metabolism, nervous system function, drugs of abuse, and environmental toxicants. One unifying theme that has emerged in the department is cell signaling and the use of pharmacological approaches to define the key regulatory steps in relevant pathways that may be amenable to pharmaceutical exploitation or whose dysregulation may be involved in the pathogenesis of disease.
The challenge: The research enterprise is a continuum that starts with the genesis of an idea, design and implementation of approaches to collect/generate data, analysis and interpretation of processed data and reporting of conclusions. At each step there is the potential for errors in scientific design, execution, analysis and reporting, all of which can impact the integrity of the research. Each step is also vulnerable to the biases of the investigator and his/her colleagues. Pressures to publish in high impact journals, obtain funding to be competitive in the job market, obtain research grants and awards and the actions of competitors, can also impact scientific judgment. Mitigation of the impact of such influences on the rigor and reproducibility of research is the responsibility of everyone in the department. Science is generally self-correcting in that new insights/advances are usually reinforced by the findings of others. However, research that is not performed with the highest level of rigor results in wasteful efforts to reproduce findings and such efforts negatively impact progress.
Responsibility: In our department, each laboratory sets its own research agenda and goals and is responsible for ensuring the integrity and provenance of research data. However, it is the responsibility of each member in the department (faculty, staff, fellows, and students) to make sure that they actively participate in the establishment and maintenance of a work environment that fosters high quality rigorous research. Every person in the department should feel respected in their ability to express their opinions on research findings, and their suggestions should be entertained in a respectful, collegial manner. It is the responsibility of the principal investigator/laboratory head to ensure that best practices to promote these fundamental guiding principles are implemented and adhered to.
The Department of Pharmacology and Cancer Biology (PCB) comprises 24 primary faculty, 93 graduate students, 26 postdoctoral fellows with complementary research interests and expertise. Each primary faculty supervises the research direction of their own laboratory. In addition to graduate students, several laboratories also employ research faculty and research technicians. Within each laboratory, it is the responsibility of the primary faculty member to ensure that the environment supports the guiding principles of research integrity established by the department and the school of Medicine. To ensure that these principles are adhered to, each laboratory maintains a Standard Operating Procedures for Data Management and Processing plan. This plan outlines:
- The responsibilities of each lab member as it relates to the research mission of that laboratory
- Expectations for data recording and availability
- Expectations for sharing data with the principal investigator and other laboratory members
- Expectations for data availability and rigor as it pertains to research publications
- A statement on a vision of research integrity for each laboratory
- A training plan to ensure that new members/potential new hires are informed of and are able to adhere to the established practices
The primary faculty ultimately ensures that their laboratory-specific plan is adhered to by lab members. Further, the department chair reviews each laboratory-specific plan to ensure that it is in line with the research integrity vision of the department. The chair further ensures accountability by instructing each primary faculty member to conduct an annual review of the lab-specific plan with their lab (with revisions/updates if necessary), and the plan is then attested to by each lab member on an annual basis in the form of a signature page that is returned to the department chair.
At the departmental level, the overall standards for research integrity are further ensured by establishing the following organization with regards to the departmental SCAP plan.
Any proposed changes to the SCAP plan will be communicated to the departmental chair, who will direct the research integrity officer to hold a discussion at one of the recurring, bi-weekly faculty meetings.
II. Promoting a Culture of Accountability
A) Education of faculty, staff, and trainees
- All researchers are responsible for keeping their conflict of interest form up to date. Details on how to complete this form and information on who are required to fill such disclosures are available at https://medschool.duke.edu/research/ethics-integrity-compliance/research-integrity-office. As a general rule anyone who could benefit financially from research ongoing in a laboratory should complete this form.
- An essential component of compliance with this policy is verification that every researcher has completed the new responsible conduct in research requirements that have been implemented. Details as to how this requirement can be fulfilled can be found at https://medschool.duke.edu/research/ethics-integrity-compliance/responsible-conduct-research-program.
B) Scientific Rigor and Reproducibility
Within the department, honesty, transparency, and constructive scrutiny of research methods is encouraged in a variety of ways. At the laboratory level, it is standard practice for researchers to share unpublished data with lab members, most frequently with the primary faculty member. Additionally, it is the culture of the department that multiple laboratories will meet informally to share unpublished data and comment on on-going work. At a departmental level, for the past three years the department has established a works-in-progress series, where students and postdocs are encouraged to present to the entire department an unpublished, ongoing series of experiments. This is in addition to the annual poster and platform talks at our annual retreat.
2. Research methods, study design
Overview of general principles and best practices (discipline independent)
- Scientific integrity and the provenance of data is the collective responsibility of allfaculty, staff, fellows and students.
- Projects/experiments should be undertaken with the goal of rigorously testing a hypothesis and not designed to “prove a hypothesis”. Descriptions of research in presentations and publications should be balanced and accommodate the possibility of alternative interpretations and conclusions.
- It is expected that in the development of new research projects, or the design of experiments, scientists should be aware of and consider the relevant current literature. Knowledge of what has been done in the past by others in the laboratory in the specific area of interest is also a fundamental responsibility of a researcher.
- All details of an experiment should be recorded in such a manner that it can be reproduced by others and that the primary, unmanipulated, data are accessible for re-analysis. Such recordings should include a description of the rationale for the experiment, the experimental steps used, how data were collected and where they can be located, how the data were analyzed and a discussion of how the data were interpreted.
- Researchers have a responsibility to ensure that data from the laboratories of collaborators are performed in a rigorous manner and appropriately recorded. All primary data must be accessible to all members of a collaborative team.
- All researchers should be aware of what constitutes a conflict of interest (financial, intellectual and personal) and should ensure that such conflicts are managed and recorded appropriately.
- Scientists should be encouraged to present at professional meetings and events and all should be receptive towards, and feel empowered to participate in, constructive discussion of research findings and methodologies.
- Mechanisms should be established to allow concerns about integrity of data and/or the manner in which studies are performed to be discussed.
Consideration of Best Practices as they relate to our discipline
Experimental design and execution
- Unbiased hypothesis testing is a central principle that must be considered in the design of all experiments.
- Investigators have a responsibility to be trained and/or have established competency with techniques/equipment that will be used.
- All experiments should include the relevant positive and negative controls needed to validate/explain and allow interpretation of new findings.
- Validate reagents, or be aware of the validation strategy used, by vendors and collaborators. This could include sequencing of plasmids, testing of an antibody with appropriate controls or confirmation of the identity of cell lines and the purity of a chemical/drug.
- A statistical plan, where appropriate, and predefined endpoints should be established and recorded before experimentation begins. If deviations from protocol are required they must be recorded along with an explanation of the rationale why such deviations were deemed necessary.
- Where possible (and practical) blinding should be used to insulate the investigator to potential biases in measurement. This is particularly applicable to experiments where exact measurements are not possible (i.e. tumor measurements, gating in flow cytometry, staining intensity in immunohistochemistry) or where the experimental observations are quantified by an observer rather than an instrument or computer.
Analysis of experimental results
- Experimental design issues should be resolved before experiments are conducted: power analysis to determine appropriate sample size, determination of independent and dependent measures and confounds, set and defend technical criteria for data inclusion/exclusion.
- Conclusions should be tested by rigorous statistical procedures.
- Statistical tests should be selected in advance of the study as appropriate to the design and biological question being asked.
- Even if a biostatistician is consulted for data analyses, the investigator is ultimately responsible for understanding the meaning and interpretation of the statistical tests.
3. Data management, storage, provenance
- All primary data should be stored and appropriately indexed to allow access in the future by the investigator or others. Any and all transformations of primary data should be recorded and date stamped with an explanation of the reason for the modification(s).
- Published data, including both primary and processed data, should be archived in a read-only directory on an enterprise class storage system (e.g. Duke Isilon, Google Cloud Storage, Amazon S3, etc.) with a checksum calculated to ensure data integrity.
- Primary genomic, metabolomic, and proteomic data should be submitted and archived with field specific data repositories (e.g. NCBI Geo, Mendeley Data, etc.).
- Processing of large datasets should be scripted when possible to ensure reproducibility. All software tools and scripts developed in the course of a project should be under version control (e.g. GitHub).
4. Human subjects and vertebrate animals
- All departmental research involving human subjects should adhere to guidelines established by the Duke Human Research Protection Program (HRPP) and Duke Health Institutional Review Board (IRB), and should be regularly reviewed by these entities.
- All departmental research involving vertebrate animals should adhere to guildelines established by the Duke Institutional Animal Care and Use Committee (IACUC) and should be regularly reviewed by this entity.
C) Voicing concerns
The departmental chair and research compliance officer should be the primary points of contact in the case of any issues related to the departmental SCAP plan. There is also an anonymous whistleblower reporting tool in the departmental website that directly goes to the chair.
Additionally, the following are Duke resources for discussing concerns:
- Duke Health Integrity Line: (800) 826-8109
- Duke Misconduct Review officer: (919)-668-5115
- Duke University Compliance and Fraud Hotline: (800) 849-9793
- HIPAA Privacy Line: (800) 688-1867
- Animal Welfare Hotline: (919) 684-3535
- Financial conflicts of interest:https://medschool.duke.edu/research/research-support- offices/duke-office-scientific-integrity/conflict-interest-office
- Ombudspersons: Undergraduate, graduate, and professional students- Ada Gregory, 919-660-2444, Students and postdocs: Jean Spaulding, firstname.lastname@example.org, SOM faculty: Laura Svetkey, 919-681-6386.