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Variance-Based Sensitivity

Global sensitivity analysis techniques, including Sobol indices, decomposing total output variance into components attributable to each parameter and their interactions.

Last reviewedDarrin Baines IP Ltd

Concept Architecture

Concept


Theoretically, Variance-Based Sensitivity Analysis is a global sensitivity analysis framework that quantifies the contribution of uncertain model inputs to the variance of model outputs. It is founded on variance decomposition and functional analysis of variance (ANOVA), allowing both direct parameter effects and interaction effects to be quantified. In health economics, variance-based sensitivity analysis is used to identify the principal drivers of uncertainty in decision models and to prioritise future evidence generation.

Mathematically, variance-based sensitivity analysis partitions the total variance of a model output into components attributable to individual parameters and combinations of parameters. The resulting first-order, higher-order and total-effect sensitivity indices express the proportion of output variance explained by each source of uncertainty. These indices are typically estimated using Monte Carlo or quasi-Monte Carlo methods.

In practice, variance-based sensitivity analysis is implemented by repeatedly sampling uncertain model parameters from their probability distributions and evaluating the resulting model outputs. Methods such as Sobol sensitivity analysis are routinely applied to health economic models to rank influential parameters, identify interaction effects and determine which uncertainties most strongly influence costs, quality-adjusted life-years and cost-effectiveness.

Purpose


Used to quantify the contribution of uncertain parameters and their interactions to model output variability, supporting global sensitivity analysis and prioritisation of influential sources of uncertainty.

Mathematical Formulae

Primary Formula

First-order sensitivity index:

S? = Var(E(Y|X?)) / Var(Y)

Supporting Formulae

Total-effect sensitivity index:

ST? = E(Var(Y|X??)) / Var(Y)

Variance decomposition:

Var(Y) = ?V? + ?V?? + ?V??? + ?

Second-order sensitivity index:

S?? = V?? / Var(Y)

Related Mathematical Methods

  • Global Sensitivity Analysis
  • Sobol Indices
  • First-Order Index
  • Total Effect Index
  • Variance Decomposition
  • Monte Carlo Simulation
  • Quasi-Monte Carlo Simulation

Example


A global sensitivity analysis evaluates uncertainty in treatment efficacy, treatment cost and utility values. Variance-based sensitivity analysis estimates first-order indices of 0.44, 0.28 and 0.10, respectively, with treatment efficacy having a total-effect index of 0.61. These results indicate that treatment efficacy contributes substantially to model uncertainty through both direct effects and interactions with other parameters.

Excel Implementation

FunctionExample FormulaHealth Economics Application
VAR.S=VAR.S(ResultRange)Estimate the total variance of simulated model outputs.
AVERAGE=AVERAGE(ConditionalRange)Calculate conditional expectations for variance decomposition.
SUMPRODUCT=SUMPRODUCT(Array1,Array2)Calculate weighted variance components.
RANK.EQ=RANK.EQ(B2,$B$2:$B$20,0)Rank parameters according to their sensitivity indices.

VBA (Optional)


VBA can automate Monte Carlo sampling, estimate Sobol sensitivity indices and generate ranked summaries of parameter importance for 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.
  • Saltelli A, Annoni P, Azzini I, Campolongo F, Ratto M, Tarantola S. Variance based sensitivity analysis of model output: design and estimator for the total sensitivity index. Computer Physics Communications. 2010;181(2):259?270.
  • Briggs A, Claxton K, Sculpher M. Decision Modelling for Health Economic Evaluation. Oxford University Press.

Library

Publications

1
  • Book

    Statistical Analysis of Cost-Effectiveness Data — Willan & Briggs, 1st Edition ed., 2006 (John Wiley & Sons)

    A synthesis of statistical methods for analysing cost-effectiveness data, including net-benefit regression, confidence intervals for the ICER, cost-effectiveness acceptability curves, and covariate adjustment. Part of the Wiley Statistics in Practice series.

Frequently Asked Questions (6)

  • What is variance-based sensitivity?

    Global sensitivity analysis techniques, including Sobol indices, decomposing total output variance into components attributable to each parameter and their interactions.

    Source: Sobol 2001

  • Why is variance-based sensitivity considered a rigorous approach?

    Variance-based sensitivity analysis is regarded as rigorous because it defines an input's importance by the exact share of the output's total variance it accounts for, a precise and additive measure rather than an informal impression. It captures effects across the whole range of every input at once, including interactions, and does not assume the model responds in any particular way, such as linearly. This generality and precision make it a benchmark, at the cost of needing many model runs. Sobol indices are its central tool. Saltelli and colleagues (2008) describe it.

    Source: Saltelli et al. 2008

  • How does variance-based sensitivity work?

    Variance-based sensitivity works by decomposing the output variance into contributions from each input and their combinations, estimated by Monte Carlo procedures using structured samples that vary subsets of inputs while averaging over the rest. First-order indices give the variance from each input alone, and total-effect indices give each input's full contribution including interactions. Comparing them reveals interactions. The result is a set of measures, each a share of output variance, quantifying how the inputs and their joint effects drive the uncertainty in the output.

    Source: Saltelli et al. 2008

  • What measures does variance-based sensitivity provide?

    Variance-based sensitivity provides first-order sensitivity indices, giving the share of output variance from each input varying alone; total-effect indices, giving each input's full contribution including all interactions; and higher-order indices, giving the variance from specific groups of inputs acting jointly. The first-order index suits ranking inputs for prioritisation, and the total-effect index suits identifying inputs that can be fixed. Together these measures quantify individual and joint influences on output uncertainty, offering a complete decomposition of the variance among the inputs and their interactions.

    Source: Sobol 2001

  • Why is variance-based sensitivity used?

    Variance-based sensitivity is used because it gives a rigorous, quantitative decomposition of output uncertainty among the inputs, valid for non-linear models and capturing interactions, unlike simpler local or one-way methods that can misjudge influence. It supports prioritising influential parameters, fixing negligible ones, and detecting interactions, informing where to focus data collection and how the model behaves. Where a precise understanding of the drivers of uncertainty is needed, variance-based sensitivity provides a thorough basis, justifying its greater computational cost over cruder sensitivity measures.

    Source: Sobol 2001

  • What are the limitations of variance-based sensitivity?

    Variance-based sensitivity can be computationally expensive, since estimating the indices accurately requires many model runs, which is demanding for complex or slow models, though screening can reduce the inputs first. It depends on the assumed input distributions, so the decomposition changes if these change, and correlated inputs complicate interpretation. It characterises uncertainty through variance, which may not capture all aspects of interest. These limitations mean variance-based sensitivity is applied where its precise decomposition justifies the cost, with attention to input assumptions and, often, prior screening.

    Source: Saltelli et al. 2008

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British health economist

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Verification date: 30 Oct 2025

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