Rigor and Reproducibility
Purpose: NIH research grant and mentored career development award applications must address rigor and transparency requirements outlined in the application instructions. Research Performance Progress Reports (RPPR) must emphasize rigorous approaches to ensure robust and unbiased results. The template below will help cores provide the necessary information to investigators on the best practices to assure rigor and transparency in research performed in core facilities. The first section provides general guidelines and the second section provides core-specific guidelines.
Click each section for more information.
- If using a core facility, consult with the core staff in the planning stage. Consult with a statistician if you need help developing a Power Analysis to assure that your results will be adequately powered.
- Design your experiment with sufficient controls (rigor) and replicates (reproducibility).
- Assure that ALL of your reagents (antibodies, cell lines, mice) are fully validated (see below).
- Have a clear and detailed protocol (SOP) and data analysis plan. Assure that the protocol is strictly followed or that any deviation is well documented.
- Assure that the staff or students performing the experiment are well trained and understand each step and the importance of performing them precisely.
- Use only well-maintained instrumentation, preferably maintained and operated in a core facility with expert staff (see #1 above).
- Document all steps, reagents, equipment and data analysis methods used in the experiment. Assure that the both the documentation and the data itself are properly stored in a safe data management repository.
- Acknowledge the Cancer Center Support Grant (P30 CA016086) (if applicable), other grants that support the core, the core (by name), and core staff in publications.
Guide to Rigor and Reproducibility for BSP Facility
The BSP operates under biorepository guidelines set forth by of the International Society for Biological and Environmental Repositories (ISBER) [https://www.liebertpub.com/doi/10.1089/bio.2018.0001] and NCI Best practices for Biospecimen resources [https://biospecimens.cancer.gov/bestpractices/2016-NCIBestPractices.pdf].
Noteworthy BSP Practices that address these guidelines include the following:
- Maintenance of a Facility General Manual of Operations (MOP)
- Maintenance of a QA/QC MOP
- Requirement for a signed study initiation document between the BSP and the project PI/Staff before work can begin
- Maintenance of individual equipment maintenance standard operating procedures (SOP)
- Maintenance of individual specimen processing SOP
- Use of a Laboratory Information Management System that maintains an audit for each sample processed in the system. The system provides data QA/QC control by validating data entered into the system. The system’s database is backed up on Lineberger Comprehensive Cancer Center-maintained servers
- Freezer maintenance and back-up policies
All specimens dropped off/sent to the BSP to be processed must have project approved IRB approvals and not contain any PHI.
- All specimens dropped off/sent to the BSP must adhere to agreed upon transfer temperatures and drop-off timing as specified in the signed project-specific BSP study initiation document.
Available for inspection upon request
Every instrument used in the BSP has a maintenance SOP that describes weekly, monthly, or longer maintenance tasks. Running hard-copy and electronic logs are preserved. Electronic logs are saved on a secure server that is backed up and maintained by the UNC Gillings School of Global Public Health. In addition, major pieces of equipment are covered by maintenance agreements with either the original or third-party vendors and yearly or bi-yearly preventative maintenance tasks are performed by certified technicians.
- Commercial standards are run on all DNA/RNA quantitation instruments on every run or once a day as appropriate. When originally purchased these standards are validated on more than one instrument
- Positive and negative controls are incorporated into runs as appropriate but at a minimum when a new lot of equipment commercial-purchased reagents are used.
Please Acknowledge the Cancer Center Support Grant (P30 CA016086) (if applicable), and the Center for Environmental Health and Susceptibility CEHS Grant number P30ES010126 that support the core, the core (BioSpecimen Processing Facility), and core staff (as applicable) in publications.
THE SECTION BELOW PROVIDES REFERENCE RESOURCES AND LINKS BUT DOES NOT HAVE TO BE INCLUDED ON THE CORE WEBSITE (UNLESS THE LINKS ARE USEFUL TO INVESTIGATORS)
Learn about the NIH Initiative to Enhance Reproducibility through Rigor and Transparency. (Video)
Resource Authentication Plan: https://grants.nih.gov/reproducibility/faqs.htm#V
What Kind of Information Should I Include in My Application’s Resource Authentication Plan? Check out instructions on NIH Nexus Blog.
What are ‘Key Biological and/or Chemical Resources’ that should be addressed your application’s authentication plan? Key biological and/or chemical resources include, but are not limited to, cell lines, specialty chemicals, antibodies and other biologics. More on NIH website
FASEB report on enhancing research reproducibility identifies three main gaps to research reproducibility:
- Lack of uniform definitions to describe the problem
- Insufficient reporting of key experimental details
- Gaps in scientific training