Protocol Development Tips and Resources
Download UNC Master Protocol Document Template: This document is a comprehensive guide to protocol development for UNC investigators.
What is a protocol and how is it used in scientific research and review?
(Excerpted from “Designing your Research for Speedy IRB Approval”
Paul W. Stewart, PhD, Professor of Biostatistics, UNC-CH)
- A Master Protocol Document (‘MPD’ or ‘protocol’) is a repository for accumulated ideas, information, literature review, and references. It is a working document that specifies all the details, algorithms, procedures, strategies, and plans for study conduct, and serves as a master source of text used for reference and guidance. Beginning in the earliest stages of study planning, it is highly efficient to use a MPD template as a tool for collecting ideas, references, information, and evolving text for subsequent use in grant proposals, IRB applications, and publications.
- Increasingly, funders, IRBs, and journals are requiring submission of a protocol as part of their review processes. For example: “The Good Clinical Practice (GCP) guidelines of the International Council for Harmonization (ICH E3 GCP 6) require a research protocol for any study that involves human participants. In addition, Title 21 Part 312 of the Code of Federal Regulations (21 CFR 312) describes both a research protocol and protocol amendments for studies conducted under an Investigational New Drug application.” — NDAT GCP
- All phases and sizes of studies should have a protocol that describes the essential elements of sound research practices – background/rationale, objectives, specific aims, study design, procedures, data collection/validity/quality, safety monitoring/management, a rationale for the chosen sample size choice, and a complete and adequately-detailed statistical analysis plan for each specific aim. The MPD should be as simple or as complex as the study it represents.
- A grant proposal or IRB application cannot be substituted for an MPD because they do not provide comprehensive detail. A grant proposal is meant to convince funders of the need, relevance and innovation of a research concept as well as the suitability of the research setting and investigators. An IRB application is intended to describe the planned study procedures, related risks and benefits, how participants’ identities and data will be protected, the informed consent process, and other issues related to protection of human subjects. A study protocol details all these aspects of the research project, with special focus on clearly stated aims, specification of outcome measures and other variables of interest along with their units of measure (or the range of valid values if the variable is categorical), comprehensive description of the data to be collected, a rationale for the chosen sample size, and aim-specific statistical analysis strategies and methods to be used to analyze data.
- In the MPD, the specific aims, study design, variables of interest, and aim-specific statistical analysis plans should be aligned; e.g., if assessing feasibility is a specific aim, then the protocol should specify outcome measures and plans for analysis of feasibility data.
- Protocol reviewers are tasked with assuring that studies involving human subjects are founded on good science, are reasonable in terms of participant burden, and will yield valuable information to better understand, diagnose, treat or manage a disease, condition, or behavior. A comprehensive and carefully constructed MPD is a sign to others that the investigative team takes seriously their scientific and ethical responsibility to participants, funders, and their institution.
- It is highly recommended that the research team includes a professional statistician as a co-investigator to collaborate on the development and execution of all aspects of the study protocol; e.g., study design, specific aims, measures of interest, statistical analysis strategies and methods, and justification of the choice of sample size in terms of anticipated precision of estimators and anticipated power levels of test procedures.
- Statistical consultation through NC TraCS can be extremely helpful and is highly recommended; however, a brief statistical consultation does not necessarily guarantee that scientific review will be free of substantial concerns. In contrast to comprehensive scientific review, a brief statistical consultation has the potential to address only the delimited specific questions you ask.
- It is recommended that UNC investigators use the HIPAA-compliant REDCap software system. UNC investigators can access REDCap and its training sessions at no cost. For the collection and management of human research data, spreadsheet software like MS Excel is not advised. For more details, please visit the UNC Research REDCap homepage.
- Final checks prior to SRC submission should assure: information in the Synopsis is fully detailed in the protocol; text is internally consistent; boilerplate language has been replaced with study- and setting-specific details; version number and date are current; all acronyms have been included in a table of abbreviations; and pages have been numbered.
- It is advisable to use a protocol builder tool or template tailored to the specific study type/design to ensure that all necessary elements are included and well-described for scientific review.
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- You can access UNC-Chapel Hill’s instance of Protocol Builder here.
- Below are the recommended templates from UNC-Chapel Hill:
- UNC Master Protocol Document Template (for observational and interventional studies)
- NIH-FDA Protocol Template
- BSSR Protocol Template
- Registry Repository Protocol Template