Reference Case

Reference cases create a consistent methodological starting point for economic evaluations prepared for a particular institution or decision process. The sections below explain why institutions use them, what choices they commonly specify, how analysts assess compliance, and when a departure may be justified. They also distinguish a reference case from a reporting checklist and explain its relationship to health technology assessment.

A reference case does not perform an economic evaluation or make the final decision. It provides a consistent framework for conducting and reporting the analysis.

Why institutions use reference cases

Two analysts can study the same intervention and reach different results because they select different comparators, perspectives, time horizons, outcome measures or discount rates. A reference case reduces avoidable variation by stating which methodological choices should normally be used for a particular decision process.

Using a common framework makes submissions easier to compare and review. It also helps readers distinguish differences caused by evidence from differences caused by analytical choices.

• A reference case promotes consistency across economic evaluations prepared for the same institution.
• A reference case makes important methodological choices visible to analysts, reviewers and decision-makers.
• A reference case supports comparison across technologies without guaranteeing identical methods or conclusions.
• A reference case should be linked to a named institution, decision context, guidance version and effective date.

What a reference case commonly specifies

A reference case usually covers several connected parts of an economic evaluation. The exact requirements differ, so analysts must use the current guidance that applies to their jurisdiction and decision.

The following elements are commonly addressed, but the list should not be treated as a universal template.

• The reference case identifies the population and relevant subgroups for the decision.
• The reference case identifies the appropriate comparator or comparators.
• The reference case defines the analytical perspective and which costs and outcomes enter the evaluation.
• The reference case identifies the preferred form of economic evaluation.
• The reference case defines the preferred health-outcome measure, such as the QALY where applicable.
• The reference case specifies the appropriate time horizon.
• The reference case specifies discount rates for costs and health outcomes.
• The reference case identifies preferred evidence sources and methods for estimating effectiveness.
• The reference case addresses modelling, uncertainty analysis and validation.
• The reference case specifies how costs, resource use and health outcomes should be measured and valued.
• The reference case establishes reporting and transparency expectations.

How the reference case shapes an economic evaluation

The reference case influences how an economic evaluation is designed before the model is calculated. It connects the decision problem to a controlled set of methodological choices so the resulting evidence fits the institution's decision process.

Following a reference case does not guarantee that the evidence, model or conclusion is correct. The quality of the analysis still depends on appropriate data, assumptions, implementation, validation and interpretation.

1. Identify the institution and decision process.
2. Confirm the current reference-case guidance and effective date.
3. Translate each applicable requirement into a project-level analytical choice.
4. Record the evidence supporting the project's implementation.
5. Identify any requirement that cannot be followed exactly.
6. Explain each deviation and its expected effect.
7. Test influential alternative choices through sensitivity or scenario analysis.
8. Report compliance, deviations, limitations and results transparently.

How reference cases differ across institutions

Reference cases are created for particular institutions and decision settings. Requirements may differ because institutions have different legal responsibilities, budgets, perspectives, healthcare systems and views about appropriate methods.

An analyst should not combine preferred elements from several reference cases and present the result as compliant with one institution. Cross-country comparisons should identify both the similarities and the differences explicitly.

Important areas to compare include:

• Perspective: Whose costs and outcomes are included?
• Comparator: Which existing practice or alternatives must be evaluated?
• Outcome measure: Are QALYs, natural health units or other outcomes preferred?
• Time horizon: How long must relevant differences be captured?
• Discounting: What rates apply to costs and health outcomes?
• Costs: Which resources, price sources and price years are required?
• Evidence: Which clinical and observational evidence is acceptable?
• Uncertainty: Which sensitivity, scenario and probabilistic analyses are expected?
• Reporting: Which results, assumptions and deviations must be disclosed?

The Reference Case Comparison and Compliance Matrix preserves each institutional profile separately rather than creating an artificial blended reference case.

How to check whether an analysis follows the reference case

Reference-case compliance requires more than selecting yes or no beside a list of requirements. Each judgement should connect the institutional requirement to the project's implementation and supporting evidence.

Some requirements can be checked mechanically, such as whether separate cost and health discount rates match stated values. Other requirements, such as whether the time horizon is long enough, require documented expert judgement.

The compliance record can use the following statuses:

• Compliant: The project follows the applicable requirement and records supporting evidence.
• Partially compliant: The project follows only part of the requirement or the evidence is incomplete.
• Justified deviation: The project departs from the requirement and documents a defensible reason and its expected effect.
• Not compliant: The project departs from the requirement without an adequate justification.
• Not applicable: The requirement does not apply to the stated project and the reason is recorded.
• Review required: Available information is insufficient for a defensible determination.

A formula may flag a possible mismatch, but it should not make a final judgement when clinical, methodological or institutional interpretation is needed.

When an analyst may depart from the reference case

A reference case is the expected starting point, but some evaluations require justified departures. A deviation may be necessary when the standard method cannot represent the technology, population, evidence or decision problem adequately.

A deviation should never be hidden or chosen merely because it produces a more favourable result. The analyst should explain why the reference-case method is unsuitable, what alternative was used and whether the departure changes the conclusion.

• A deviation record should identify the exact reference-case requirement.
• A deviation record should state the alternative method used.
• A deviation record should explain why the alternative is more appropriate.
• A deviation record should identify the evidence supporting the departure.
• A deviation record should describe the expected direction and size of its effect.
• A deviation record should include a reference-case scenario when feasible.
• A deviation record should identify who reviewed and accepted the judgement.

How sensitivity analysis supports reference-case reporting

Sensitivity analysis can show whether the result depends on a methodological choice that differs from the reference case. It does not convert a non-compliant base case into a compliant one or remove the need to explain a deviation.

Where feasible, analysts should present the institution's required reference case alongside justified alternatives. This allows reviewers to separate the effect of the alternative method from other differences in the evaluation.

• A reference-case analysis should use the institution's preferred methodological choices.
• A deviation scenario should isolate the effect of an alternative methodological choice where feasible.
• Sensitivity analysis should show whether the ICER, net benefit or preferred alternative changes.
• Structural choices should be tested with explicit scenarios when parameter variation cannot represent them.
• Scenario labels should state exactly which reference-case choice has changed.

How a reference case relates to HTA

Health technology assessment may use economic evaluation as one source of evidence, and a reference case can define how that economic evidence should be produced. The reference case therefore supports the assessment process without determining the final recommendation.

HTA may also consider clinical effectiveness, safety, equity, ethical issues, organisational consequences, patient perspectives and implementation. Compliance with the economic reference case does not guarantee adoption, reimbursement or coverage.

• A reference case standardises selected methods used to produce economic evidence.
• Economic evaluation provides comparative evidence about costs and consequences.
• HTA combines economic evidence with other decision-relevant information.
• The responsible decision-making body retains authority over the final recommendation.

How a reference case differs from a reporting checklist

A reference case tells analysts which methodological choices are normally preferred for a defined decision context. A reporting checklist tells authors what information should be disclosed so readers can understand and assess a study.

The two tools can overlap, but they are not interchangeable. A report can describe a non-reference-case analysis clearly, while an analysis can claim compliance but still report its methods inadequately.

• Reference-case compliance concerns whether the selected methods follow applicable institutional requirements.
• Reporting compliance concerns whether the analysis describes its methods and results adequately.
• Transparent reporting should identify both reference-case compliance and justified deviations.
• A reporting checklist should not be used as evidence that the analytical choices match an institutional reference case.

Using the comparison and compliance workbook

The Reference Case Comparison and Compliance Matrix allows users to select an institutional profile and compare its requirements with the choices used in a project. The workbook separates institutional source information, project implementation, evidence, deviations and reviewer determinations.

Automated checks identify possible inconsistencies in fields such as discount rates. Qualitative requirements, including the adequacy of the time horizon or comparator, remain clearly marked as requiring evidence-based human review.

What should be reported

A transparent economic evaluation should identify the governing reference case and show how the analysis follows it. Readers should also be able to see where the analysis departs from the expected approach and whether those departures influence the result.

• Report the institution and decision context governing the evaluation.
• Report the reference-case guidance title, version, effective date and URL.
• Report how each applicable requirement was implemented.
• Report the evidence supporting compliance judgements.
• Report every material deviation and its justification.
• Report the expected effect of each deviation.
• Report reference-case and alternative scenarios where feasible.
• Report who reviewed qualitative compliance judgements.
• Report unresolved requirements and missing evidence.
• Report whether deviations change the decision result.

Common mistakes and how to avoid them

Reference-case errors often occur when analysts treat a framework as a generic checklist or rely on remembered requirements from an earlier guidance version. These errors can undermine comparability and make a submission appear compliant when important choices remain unsupported.

• Applying one institution's reference case to another jurisdiction can use the wrong methodological requirements.
• Combining requirements from different institutions can create a hybrid framework that no institution actually endorses.
• Using outdated guidance can produce incorrect comparator, perspective, horizon or discount-rate choices.
• Treating a formula flag as a final compliance decision can replace necessary expert judgement.
• Marking a requirement not applicable without a reason can conceal missing analysis.
• Reporting a deviation without its likely effect prevents reviewers from judging its importance.
• Using sensitivity analysis without explaining the base-case departure does not establish compliance.
• Treating reference-case compliance as proof of model validity overlooks evidence quality, implementation and validation.
• Treating reference-case compliance as an adoption decision ignores the wider HTA process.