HARmonized Protocol Template to Enhance Reproducibility of hypothesis evaluating real‐world evidence studies
The HARPER template is a standardized format for planning and documenting real-world evidence studies that evaluate treatment effects. It helps researchers clearly describe how they will collect and analyze data so that others can understand, reproduce, and trust their findings.
At a glance
Use when
Designing hypothesis-testing real-world evidence studies on treatment effects, especially when reproducibility, regulatory acceptance, or multi-stakeholder alignment is important.
Avoid when
Conducting exploratory or hypothesis-generating analyses where full pre-specification is not feasible, or when studying non-treatment interventions without a clear estimand.
Inputs
Study objectives, data source characteristics, population definitions, exposure and outcome specifications, statistical analysis plans, assumptions about data quality and completeness.
Outputs
A standardized, transparent protocol document that enables reproducibility, facilitates peer review, supports study registration, and guides implementation and reporting of RWE studies.
How it works
The HARmonized Protocol Template to Enhance Reproducibility (HARPER) is a standardized framework developed by a joint ISPE/ISPOR task force to improve transparency and reproducibility in real-world evidence (RWE) studies assessing treatment effects. It provides a structured format encompassing data provenance, study design, analysis plans, and implementation details. The template supports alignment with causal inference principles by emphasizing clear specification of the target estimand and key methodological choices, enabling assessment of bias, replication in independent datasets, and informed decision-making. It integrates prior transparency initiatives and adds granular detail necessary for RWE reproducibility.
- HTA domains
- Clinical Effectiveness, Costs & Economic Evaluation, Patient and Social Aspects
- Assumptions
- That increased standardization and transparency in protocol development will improve the credibility, reproducibility, and utility of RWE for healthcare decision-making; and that stakeholders will adopt the template if properly supported.
- Strengths
- Promotes clarity and consistency in RWE study planning and reporting,Facilitates external review, replication, and regulatory assessment,Integrates best practices from epidemiology, statistics, and health outcomes research,Supports alignment with causal inference frameworks through explicit estimand definition
- Limitations
- May require adaptation for non-treatment-effect RWE questions,Adoption depends on stakeholder buy-in and integration into regulatory and publication workflows,Does not guarantee methodological validity if misapplied
- Also known as
- HARPER, HARPER Template
Questions this answers
- › What is the target estimand and how is it defined?
- › Which data sources are used and what is their provenance?
- › How are study populations defined and selected?
- › What methods will be used to control for confounding?
- › How will missing data and time-varying exposures be handled?
- › What sensitivity analyses are planned to assess robustness?
References & sources
Related methods
Similar by meaning
- CADTH Guidance for Reporting Real-World Evidence
- REPEAT Initiative (Reproducible Evidence: Practices to Enhance and Achieve Transparency)
- ISPOR Prospective Observational Studies to Assess Comparative Effectiveness Good Research Practices Task Force Report
- STEER (Structured Expert Elicitation Resources)
Beta record. Generated from the primary source via AI extraction and independent audit, pending final human review.