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Decision and cost-effectiveness analysis: Understanding sensitivity analysis. Advanced Training in Clinical Research Lecture 5 UCSF Department of Epidemiology and Biostatistics February 17, 2011. Objectives. To understand the purpose of sensitivity analysis.

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decision and cost effectiveness analysis understanding sensitivity analysis

Decision and cost-effectiveness analysis: Understanding sensitivity analysis

Advanced Training in Clinical Research

Lecture 5

UCSF Department of Epidemiology and Biostatistics

February 17, 2011

objectives
Objectives
  • To understand the purpose of sensitivity analysis.
  • To understand techniques used for sensitivity analysis.

Health Strategies International, UCSF

why do sensitivity analyses
Why do Sensitivity Analyses?
  • All CEAs have substantial uncertainty.
  • Sensitivity analyses deal with uncertainty systematically.
  • Convince audience that results are robust.
four topics
Four Topics
  • Types of uncertainty.
  • Deterministic sensitivity analyses.
    • One-way, multi-way, scenario.
  • Probabilistic sensitivity analyses.
    • Monte Carlo.
  • Uses of sensitivity analyses.

Health Strategies International, Super Models for Global Health

types of uncertainty
Types of Uncertainty
  • Truth uncertainty:
    • What are the correct input values?
  • Trait uncertainty:
    • What if population characteristics or other circumstances change?
  • Methodological uncertainty:
    • What if the analysis were done differently?

Health Strategies International, Super Models for Global Health

deterministic sensitivity analyses
Deterministic Sensitivity Analyses
  • One-way/univariate:
    • Vary one input at a time.
  • Multi-way/multivariate:
    • Vary 2+ inputs at a time.

Health Strategies International, Super Models for Global Health

deterministic sensitivity analyses1
Deterministic Sensitivity Analyses
  • Scenario (variant of multi-way):
    • Tests set of relevant conditions.
  • Threshold analysis (one-way or multi-way):
    • Input values beyond which cost-effectiveness is achieved (or lost).

Health Strategies International, Super Models for Global Health

slide8

One-way Sensitivity Analysis

Base case est. of annual rupture risk = 0.0005

slide9

Univariate Sensitivity Analyses:

Base case and range of outcomes for 1,000 FC users

slide10

Automating one-way SAs:

  • Male circumcision for HIV prevention in South Africa
three way sensitivity analysis adult male circumcision kahn at al plosmedicine 2006
Three-way Sensitivity Analysis Adult male circumcision (Kahn at al, PlosMedicine 2006)

Health Strategies International, Super Models for Global Health

slide13

Threshold Analysis: NVP for Prevention of Vertical Transmission of HIV in Sub-Saharan Africa Input values needed for $50/DALLYMarseille at a,l Lancet, 1999

using scenario analysis to quantify effect of unknown parameter marseille bmgf white paper 2009
Using scenario analysis to quantify effect of unknown parameterMarseille, BMGF White Paper, 2009,.

Health Strategies International, Super Models for Global Health

probabilistic sensitivity analysis
Probabilistic Sensitivity Analysis

What is it?

What is it good for?

probabilistic sensitivity analysis1
Probabilistic Sensitivity Analysis
  • Operational definition:
    • Outputs are calculated based on random assignment of values to inputs drawn from user-selected probability distribution.
  • Examples:
    • Monte Carlo, Latin Hypercube Software:

@Risk®; Crystal Ball® TreeAge ®

Health Strategies International, Super Models for Global Health

the problem with deterministic sas
The Problem with Deterministic SAs

No estimate of the probability of achieving

a particular outcome.

Probabilistic SAs are the remedy.

probabilistic sensitivity analyses
Probabilistic Sensitivity Analyses
  • Value:
    • Return the likelihood of attaining a particular outcome or outcome range.
    • Everything known about each input is expressed at once.
    • Particularly valuable when many inputs are important.

Health Strategies International, Super Models for Global Health

probabilistic sensitivity analyses1
Probabilistic Sensitivity Analyses
  • Drawbacks:
    • Need to be able to make decent estimates of the underlying probability distribution.
    • “Black box”

Health Strategies International, Super Models for Global Health

other uses of sa the inner teachings
Other Uses of SA:(The Inner Teachings)
  • Planning the analysis.
  • Debugging the model.
  • Documenting relationships between inputs and outputs.
  • Identifying thresholds.
  • Influencing policy.

Health Strategies International, Super Models for Global Health

planning the analysis
Planning the Analysis
  • Program software to permit SAs on likely SA variables.
  • SA curves provide a check on the integrity of the model.
  • Identify candidates for more data collection early.

Health Strategies International, Super Models for Global Health

debugging the model tricks of the trade
Debugging the ModelTricks of the Trade
  • One-ways are best: simple and intuitive.
  • Plug in extreme values.
  • Separate diagnosis of numerator from denominator.
  • Break outputs down further if necessary
  • (intervention versus control arms).
documenting relationships between inputs and outputs
Documenting Relationships Between Inputs and Outputs
  • Distinguish between ‘bugs’ and insights.
  • Examples of insights:
  • Slowing disease progression can increase costs.
  • Higher disease prevalence can mean lower benefits.
  • Benefits decrease with age.
identify thresholds influence policy
Identify Thresholds – Influence Policy

Preventing HIV vertical transmission in

sub-Saharan Africa

  • Cost of ARVs to prevent vertical transmission.
  • Universal versus targeted provision of NVP.
  • Hard-to quantify potential benefits of FC
slide26
Cost per DALY of HIVNET 012 NVP regimen as function of HIV seroprevalence and type of counseling/testing regimen
summary
Summary
  • SA is a set of techniques for the explicit management of uncertainty.
  • Essential part of establishing key findings.
  • Indispensable for convincing an audience that results are technically sound and policy-relevant.