Concept Architecture
Concept
Theoretically, Global Sensitivity Analysis is a comprehensive framework for quantifying how uncertainty in multiple model input parameters contributes to uncertainty in model outputs across the entire parameter space. Unlike local or deterministic sensitivity analysis, it evaluates simultaneous variation in all uncertain inputs while accounting for parameter interactions and non-linear relationships. In health economics, global sensitivity analysis is used to identify influential parameters, assess model robustness and prioritise future research.
Mathematically, global sensitivity analysis partitions the variance of model outputs into contributions attributable to individual parameters and their interactions. Variance-based methods, particularly Sobol sensitivity analysis, estimate first-order, higher-order and total-order sensitivity indices that quantify the proportion of output variance explained by each source of uncertainty.
In practice, global sensitivity analysis is implemented using Monte Carlo or quasi-Monte Carlo simulation by repeatedly sampling from the joint probability distributions of uncertain model parameters. The resulting sensitivity indices are used to rank parameter importance, identify interaction effects and support model validation, uncertainty assessment and research prioritisation within health economic evaluations.
Purpose
Used to quantify the contribution of multiple uncertain parameters to model output variability, identify influential parameters and interactions, and evaluate the robustness of health economic models.
Mathematical Formulae
Primary Formula
First-order sensitivity index:
S? = Var(E(Y|X?)) / Var(Y)
Supporting Formulae
Total-order sensitivity index:
ST? = E(Var(Y|X??)) / Var(Y)
Variance decomposition:
Var(Y) = ?V? + ?V?? + ?V??? + ?
where:
V? = variance explained by parameter i
V?? = variance explained by the interaction between parameters i and j
Related Mathematical Methods
- Sobol Sensitivity Analysis
- First-Order Index
- Total-Order Index
- Monte Carlo Simulation
- Quasi-Monte Carlo Simulation
- Variance Decomposition
- Probabilistic Sensitivity Analysis
Example
A probabilistic sensitivity analysis of a Markov model evaluates uncertainty in treatment efficacy, costs, utility values and transition probabilities. Global sensitivity analysis estimates a first-order index of 0.48 and a total-order index of 0.61 for treatment efficacy, indicating that this parameter independently explains 48% of the model output variance and contributes a further 13% through interactions with other uncertain parameters.
Excel Implementation
| Function | Example Formula | Health Economics Application |
|---|---|---|
| VAR.S | =VAR.S(B2:B10001) | Estimate the total variance of simulated model outputs. |
| RANK.EQ | =RANK.EQ(C2,C$2:C$20,0) | Rank parameters according to calculated sensitivity indices. |
| AVERAGE | =AVERAGE(B2:B10001) | Calculate conditional means during variance decomposition. |
| SUMPRODUCT | =SUMPRODUCT(A2:A1001,B2:B1001) | Support variance decomposition calculations for sensitivity analysis. |
VBA (Optional)
VBA can automate Monte Carlo sampling, calculate Sobol sensitivity indices and generate ranked summaries of parameter importance for large health economic models.
Sources
- Sobol IM. Global sensitivity indices for nonlinear mathematical models and their Monte Carlo estimates. Mathematics and Computers in Simulation. 2001;55(1?3):271?280.
- Saltelli A, Ratto M, Andres T, et al. Global Sensitivity Analysis: The Primer. John Wiley & Sons.
- Briggs A, Claxton K, Sculpher M. Decision Modelling for Health Economic Evaluation. Oxford University Press.
- NICE. Health Technology Evaluation Manual.
- ISPOR-SMDM Modeling Good Research Practices Task Force Reports.
Related Concepts (3)
Library
Tools & Resources
1
SAVI — Sheffield Accelerated Value of Information — Mark Strong, Jeremy Oakley & Penny Breeze (University of Sheffield), Web application ed., 2024 (University of Sheffield)
A free, open-access web calculator that computes value-of-information measures (EVPI, partial EVPI/EVPPI and EVSI) directly from a model’s probabilistic sensitivity analysis output — no need to re-run the model. Also reports payer strategy-specific and uncertainty burden.
Web Tool (R Shiny)View source →
Frequently Asked Questions (6)
What is global sensitivity analysis?
Sensitivity analysis techniques assessing how a model's output responds to simultaneous variation across the full range of all uncertain inputs, unlike one-way analysis.
Source: Saltelli et al. 2008
What does global sensitivity analysis reveal that one-way analysis cannot?
One-way analysis moves a single input at a time, so it cannot detect effects that arise only when several inputs change together, nor does it weight inputs by how uncertain they actually are. Global sensitivity analysis varies all inputs simultaneously across their full plausible ranges, so it captures interactions between them and reflects their real uncertainty in apportioning influence. This gives a truer picture of what drives the output when everything is uncertain at once. It sees the combined behaviour a one-way sweep misses. Saltelli and colleagues (2008) describe these methods.
Source: Saltelli et al. 2008
How does global sensitivity analysis differ from local sensitivity analysis?
Global sensitivity analysis varies all inputs simultaneously across their full ranges, capturing interactions and non-linear effects, whereas local sensitivity analysis examines the effect of small changes in one input around a fixed base-case point, missing interactions and behaviour away from that point. Global methods explore the whole input space and can attribute output variance to inputs individually and jointly, while local methods give a limited, point-based view. The difference is between whole-range, simultaneous variation and small, one-at-a-time variation around a single point.
Source: Saltelli et al. 2008
What methods are used in global sensitivity analysis?
Global sensitivity analysis uses methods such as variance-based indices, including first-order and total-effect Sobol indices, which decompose output variance among inputs and their interactions; screening methods like the Morris method using elementary effects for efficient identification of influential inputs; and Monte Carlo filtering for factor mapping. These methods differ in cost and detail, from cheap screening to full variance decomposition. They share the feature of varying all inputs across their ranges, allowing influence, interactions, and the conditions producing particular outputs to be assessed.
Source: Sobol 2001
Why is global sensitivity analysis used?
Global sensitivity analysis is used because one-way, local methods can miss interactions and misjudge influence when inputs vary over wide ranges or act jointly, whereas exploring the full input space with all inputs varying together gives a more reliable picture of what drives output uncertainty. It supports prioritising influential inputs, fixing negligible ones, and identifying conditions producing particular outcomes. Where models are non-linear or inputs interact, global sensitivity analysis provides a sounder basis than local analysis for understanding and communicating the drivers of uncertainty.
Source: Saltelli et al. 2008
What are the limitations of global sensitivity analysis?
Global sensitivity analysis, especially variance-based methods, can be computationally intensive, requiring many model runs, which is demanding for complex or slow models, though screening methods reduce this cost. Its results depend on the assumed ranges and distributions of the inputs, so these must be chosen carefully. Interpreting joint and interaction effects can be complex. These limitations mean the method and effort are matched to the model, with input assumptions considered, and cheaper screening sometimes used before fuller variance-based analysis.
Source: Saltelli et al. 2008
Trust Record
Verified by Dr Darrin Baines
British health economist
Professional identity: darrinbaines.org
Verification date: 27 Oct 2025
Content version: 1.0.0
Canonical Identity
- Term code
- HE-EM-UA-030
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