RWE 201 – Health Canada’s 15 Key Elements for Protocol Development


Health Canada acknowledges that RWE can be particularly useful in areas where conducting controlled clinical trials is challenging or not feasible. By leveraging RWE, regulatory authorities can gain additional insights into drug safety and efficacy, ultimately improving access to safe and effective drugs for patients.

Protocol development is a critical step in ensuring the quality and validity of RWE studies. When designing a research protocol, several key elements should be considered:

[1] Research Question: Define the objectives, aims, and rationale, supplemented by a literature review.

[2] Milestones: Include timelines for data collection, progress reports, and study registration.

[3] Research Design: Clearly specify data type, measures of occurrence, and adverse events reporting.

[4] Study Populations: Define the study group and discuss its generalizability.

[5 & 6] Exposure & Outcome Measurement: Define, measure, and validate the exposure and outcomes pertinent to the study.

[7] Bias Mitigation: Identify potential biases and strategies to counter them.

[8] Effect Measure Modification: The protocol should address the collection of items that could modify the effect being studied and explain how they are included in the analysis.

[9] Data Sources: Describe sources and methods of data collection, including coding systems.

[10] Statistical Analysis: Detail statistical approaches, handling of missing data, and sensitivity analyses.

[11] Data Management: Outline storage, software, and quality control mechanisms.

[12] Feasibility & Limitations: Discuss the study’s viability and prospective mitigation strategies.

[13] Ethics & Data Protection: Emphasize participant protection, confidentiality, and ethical compliance.

[14] Amendments & Deviations: Document any changes to the original protocol.

[15] Communication Plan: Address how study results will be communicated and ensure transparency.

Data Quality in RWE:

[1] Prospective Data: Ensure transparency, defined procedures, and documentation for high-quality data.

[2] Retrospective Data: Despite its challenges, maintain high standards and traceability to the source.

In conclusion, these key elements of protocol development provide a framework for conducting high-quality RWE studies. Protocol development and data quality are crucial factors in ensuring the validity and reliability of RWE studies. By following good research practices and addressing elements such as research question, milestones, study design, data sources, statistical analysis, and data management, stakeholders can generate high-quality evidence to support regulatory submissions. Incorporating RWE into the drug product life cycle improves access to safe and efficacious drugs for patients, ultimately benefiting public health [1].



[1] Health Canada – Elements of Real World Data/Evidence Quality throughout the Prescription Drug Product Life Cycle (March 2019)


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