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Estimating the Global Health Impact of Improved Diagnostic Tools. Jeffrey Wasserman Federico Girosi Emmett Keeler November 2006, April 2007. Outline. Introduction to Diagnostic Tools Project for BMGF Better diagnosis might reduce the burden of disease - PowerPoint PPT Presentation
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Estimating the Global Health Impact of Estimating the Global Health Impact of Improved Diagnostic ToolsImproved Diagnostic Tools
Jeffrey WassermanJeffrey Wasserman
Federico GirosiFederico Girosi
Emmett KeelerEmmett Keeler
November 2006, April 2007November 2006, April 2007
2 3/2008
Introduction to Diagnostic Tools Project for BMGFIntroduction to Diagnostic Tools Project for BMGF
Better diagnosis might reduce the burden of disease Better diagnosis might reduce the burden of disease
Modeling the Benefits of New DiagnosticsModeling the Benefits of New Diagnostics
Basic approachBasic approach
Key issues and decisionsKey issues and decisions
FindingsFindings
Benefits of New Diagnostics for TuberculosisBenefits of New Diagnostics for Tuberculosis
Selected Findings from Other DiseasesSelected Findings from Other Diseases
OutlineOutline
3 3/2008
The Burden of Disease Remains Large in The Burden of Disease Remains Large in the Developing Worldthe Developing World
0 1,000,000 2,000,000 3,000,000
Malaria
Child diarrhea
Child respiratory
Tuberculosis
HIV/AIDS
* World Health Organization, 2003 (HIV) and 2002 (all others)* World Health Organization, 2003 (HIV) and 2002 (all others)
Annual Deaths Worldwide*Annual Deaths Worldwide*
4 3/2008
Diseases Are Concentrated in Some Diseases Are Concentrated in Some RegionsRegions
LatinLatinAmericaAmerica
AfricaAfrica
AsiaAsia
5 3/2008
Many Factors Might Contribute to Improved Many Factors Might Contribute to Improved Health Outcomes in the Developing WorldHealth Outcomes in the Developing World
GoodGoodHealthHealth
LifestyleLifestyleNutritionNutrition
Public HealthPublic HealthProgramsPrograms
Clinical CareClinical Care
DiagnosisDiagnosis TreatmentTreatment
6 3/2008
How Better Diagnostics Could HelpHow Better Diagnostics Could Help
More accurate tests could help target therapy to More accurate tests could help target therapy to those who need it and eliminate wasteful treatmentsthose who need it and eliminate wasteful treatments
Earlier diagnosis could allow therapy to start sooner, Earlier diagnosis could allow therapy to start sooner, reducing impact on the individual and reducing reducing impact on the individual and reducing spread of the diseasespread of the disease
Simpler, easy-to-use tests could help increase Simpler, easy-to-use tests could help increase access to diagnostics to those who currently have no access to diagnostics to those who currently have no carecare
7 3/2008
But Barriers Exist to Using Many Current But Barriers Exist to Using Many Current Diagnostic Tools in Resource-Poor CountriesDiagnostic Tools in Resource-Poor Countries
Tests often require Tests often require advanced infrastructureadvanced infrastructure
High-performing tests High-performing tests are expensiveare expensive
Some existing tests are Some existing tests are inadequate and slow inadequate and slow
Cultural and political Cultural and political considerations may considerations may impede acceptance impede acceptance
Needs may vary across Needs may vary across countriescountries
8 3/2008
We were asked two Key QuestionsWe were asked two Key Questions
What are the global health benefits of better clinical diagnostic tools?
What performance specifications and infrastructure requirements does a test need to achieve the estimated benefits?
9 3/2008
IntroductionIntroduction Better diagnosis might reduce the burden of Better diagnosis might reduce the burden of
disease disease
Modeling the Benefits of New DiagnosticsModeling the Benefits of New Diagnostics Basic approachBasic approach Key issues and decisionsKey issues and decisions
FindingsFindings Benefits of New Diagnostics for TuberculosisBenefits of New Diagnostics for Tuberculosis Selected Findings from Other DiseasesSelected Findings from Other Diseases
OutlineOutline
10 3/2008
We Worked with the Gates Foundation to We Worked with the Gates Foundation to Create a Global Health Diagnostics ForumCreate a Global Health Diagnostics Forum
MalariaMalaria TuberculosisTuberculosis
Acute LowerAcute LowerRespiratoryRespiratoryInfectionsInfections
HIV and HIV and Sexually-Sexually-
TransmittedTransmittedDiseasesDiseases
DiarrhealDiarrhealDiseasesDiseases
Forum Working GroupsForum Working Groups The Forum’s RoleThe Forum’s Role
Provide expertise on Provide expertise on relevant diseases, relevant diseases, diagnostic needs, emerging diagnostic needs, emerging technologiestechnologies
Identify key intervention Identify key intervention points for each diseasepoints for each disease
Refine the approach for Refine the approach for assessmentassessment
Serve as conduits to the Serve as conduits to the broader scientific broader scientific communitycommunity
11 3/2008
Status quo
Model for calculating benefits of new TestModel for calculating benefits of new Test
• Population characteristicsPopulation characteristics• Health statusHealth status• Access to diagnostics Access to diagnostics and treatment and treatment
HealthHealthoutcomesoutcomes
With new diagnostic test
HealthHealthoutcomesoutcomes
Difference in outcomes =
Gains from improved diagnostic tests
12 3/2008
Access to a New Diagnostic Depends on Access to a New Diagnostic Depends on the Level of Infrastructure Availablethe Level of Infrastructure Available
Advanced/Advanced/ModerateModerate
• Hospitals andHospitals and urban clinics urban clinics
• Electricity,Electricity, clean water, clean water, well-equipped well-equipped laboratories, laboratories, trained clinicians trained clinicians
MinimalMinimal
• Health clinics (Africa),Health clinics (Africa), rural clinics (Asia, rural clinics (Asia, Latin America) Latin America)
• No reliable electricityNo reliable electricity or clean water, no or clean water, no laboratory, minimal laboratory, minimal expertise expertise
NoneNone
• Village or Village or community community
• No electricity,No electricity, clean water, clean water, physical physical infrastructure, or infrastructure, or trained staff trained staff
13 3/2008
Characteristics of potential new testsCharacteristics of potential new tests
Accuracy = sensitivity, specificityAccuracy = sensitivity, specificity
AccessAccess
Time to diagnosis ( related to loss to follow-up)Time to diagnosis ( related to loss to follow-up)
Cost of equipment and operationCost of equipment and operation
Other (specimen type, multiplex diseases….)Other (specimen type, multiplex diseases….)
14 3/2008
Introduction to Diagnostic Tools Project for BMGFIntroduction to Diagnostic Tools Project for BMGF
Better diagnosis might reduce the burden of disease Better diagnosis might reduce the burden of disease
Global Health Diagnostics ForumGlobal Health Diagnostics Forum
Modeling the Benefits of New DiagnosticsModeling the Benefits of New Diagnostics
Basic approachBasic approach
Key issues and decisionsKey issues and decisions
FindingsFindings
Benefits of New Diagnostics for TuberculosisBenefits of New Diagnostics for Tuberculosis
Selected Findings from Other DiseasesSelected Findings from Other Diseases
OutlineOutline
15 3/2008
Key modeling issues and decisionsKey modeling issues and decisions
Get intervention points from experts or models?Get intervention points from experts or models?
Decision trees are good for studying diagnostic testsDecision trees are good for studying diagnostic tests
Static vs. Epidemic Models, future trendsStatic vs. Epidemic Models, future trends
What about costs, especially of over-treatment?What about costs, especially of over-treatment?
Potential vs probable access, diffusion Potential vs probable access, diffusion
Where can we get data to populate the models?Where can we get data to populate the models?
16 3/2008
Static or dynamic modelsStatic or dynamic models
For TB and HIV, state of the art is dynamic models: people flow For TB and HIV, state of the art is dynamic models: people flow between states according to diff. equations, researchers calculate between states according to diff. equations, researchers calculate long-run policy impacts.long-run policy impacts.
states: no disease, treated early dis., untreat dis.,…states: no disease, treated early dis., untreat dis.,…
decision trees give some parameters for models decision trees give some parameters for models
An alternative is static decision trees: calculate costs and effects in An alternative is static decision trees: calculate costs and effects in one year, with incidence assumed unaffected by new DX tool.one year, with incidence assumed unaffected by new DX tool.
long run effects ~ proportional to one year effectslong run effects ~ proportional to one year effects
our main interest is comparative performanceour main interest is comparative performance
transmission handled by multiplierstransmission handled by multipliers
Static model can be used for all five diseasesStatic model can be used for all five diseases
Simpler method allows us to do project with limited time and money. Simpler method allows us to do project with limited time and money.
Susceptiblepeople
Each case infects kn-1 others
Sn-1 Sn
The difference equations Sn = Function(Sn-1, other “n-1” conditions)
show how the system evolves over the generations.
EpidemicsEpidemics
1
2
0
If k = 2
Let Sn be the number of cases in generation n
18 3/2008
A dynamic model:A dynamic model:Diseases in Equilibrium (TB)Diseases in Equilibrium (TB)
Active TB TB Death
curesHealthy
Latent TB
Each active case “infects” about 20 people on average.- they then have latent TB, but a few progress
Some active cases are cured, some dieA generation is ~ 4 years from activation to resolutionIf Disease is in equilibrium, what % p of latent cases
progress to be active each generation?What happens if a higher % progresses?
New diagnostic tool affects the transitions from active TB.
20
p?p?
19 3/2008
What are the costs of over-treatment?What are the costs of over-treatment?
BMGF said not to consider costs, but…BMGF said not to consider costs, but…
If no cost of treatment, no need for Dx, just treat all If no cost of treatment, no need for Dx, just treat all equivocal patients.equivocal patients.
What are the costs?What are the costs?
Side-effects of treatmentSide-effects of treatment
Possible super-germs?Possible super-germs?
Opportunity costsOpportunity costs
20 3/2008
Methods to calculate C = Methods to calculate C = cost*cost*of over-treatmentof over-treatment
Ask panel of experts: identifying one more person with Ask panel of experts: identifying one more person with TB justifies the costs of tagging N more people who TB justifies the costs of tagging N more people who don’t have TB as having it?don’t have TB as having it?
Use opportunity costs of wasted money, assuming we Use opportunity costs of wasted money, assuming we can save a life by spending $x on another program.can save a life by spending $x on another program.
Girosi: Use treatment guidelines to bound C Girosi: Use treatment guidelines to bound C
If we don’t treat when p(dis) < PminIf we don’t treat when p(dis) < Pmin then C > lower bound Lthen C > lower bound L
If we treat whenever p(dis)>PmaxIf we treat whenever p(dis)>Pmax then C < upper bound Uthen C < upper bound U
* This cost is called the Harm in Hunink.* This cost is called the Harm in Hunink.
21 3/2008
Girosi’s Method to calculate C = Girosi’s Method to calculate C = cost of over-treatment (2)cost of over-treatment (2)
Girosi: Often, recommended treatment involves a test Girosi: Often, recommended treatment involves a test and then only the positives get treated. for ARI it’s a and then only the positives get treated. for ARI it’s a clinical judgment with TPR = .9, TNR =.7, the benefit of clinical judgment with TPR = .9, TNR =.7, the benefit of treatment = .2 -.1 = .1 death averted, and prior p =.015.treatment = .2 -.1 = .1 death averted, and prior p =.015.
costs of treating everyone = H(1-p)~Hcosts of treating everyone = H(1-p)~H
costs of treating no one = Bpcosts of treating no one = Bp
costs of following clin judgment: (1-.9)pB + (1-.7) (1-p)Hcosts of following clin judgment: (1-.9)pB + (1-.7) (1-p)H
If the last is best .1pB +.3H <H and also <pB.If the last is best .1pB +.3H <H and also <pB.
So .7 H> .1pB and .3H<.9pBm so pB/7<H <3pB. So H=pB So .7 H> .1pB and .3H<.9pBm so pB/7<H <3pB. So H=pB is a reasonable guess. H = .015x.1 = .0015is a reasonable guess. H = .015x.1 = .0015
22 3/2008
Potential vs Actual accessPotential vs Actual access
Actual: people currently being tested for disease X in Actual: people currently being tested for disease X in Level L facilitiesLevel L facilities
Potential: people who could get to a facility of level L Potential: people who could get to a facility of level L with a certain amount of time and effortwith a certain amount of time and effort
We used potential:We used potential:
with better tests and treatment, demand would with better tests and treatment, demand would riserise
thinking about the post diffusion futurethinking about the post diffusion future
Fit potential access using geographic data from a few Fit potential access using geographic data from a few countries, and data on actual access to TB clinics in a countries, and data on actual access to TB clinics in a regression and estimate for all countries of interest.regression and estimate for all countries of interest.
23 3/2008
Data ProblemsData Problems
Models need incidence of disease of interest, incidence Models need incidence of disease of interest, incidence of seeking treatment for symptoms, outcomes of treated of seeking treatment for symptoms, outcomes of treated and untreated cases, accuracy of status quo testsand untreated cases, accuracy of status quo tests
Future test characteristics can be whatever we choose.Future test characteristics can be whatever we choose.
24 3/2008
Introduction Introduction
Better diagnosis might reduce the burden of disease Better diagnosis might reduce the burden of disease
Modeling the Benefits of New DiagnosticsModeling the Benefits of New Diagnostics
Basic approachBasic approach
Key issues and decisionsKey issues and decisions
FindingsFindings
Benefits of New Diagnostics for Bacterial Lower RIBenefits of New Diagnostics for Bacterial Lower RI
Selected Findings from Other DiseasesSelected Findings from Other Diseases
OutlineOutline
25 3/2008
Respiratory Infections Are the Leading Cause Respiratory Infections Are the Leading Cause of Childhood Mortalityof Childhood Mortality
Respiratory infections contribute to the deaths of Respiratory infections contribute to the deaths of more than 2 million children each year, mostly in more than 2 million children each year, mostly in Africa and Southeast AsiaAfrica and Southeast Asia
Most of these 2 million children die of bacterial Most of these 2 million children die of bacterial pneumonia, which is treatable with antiobioticspneumonia, which is treatable with antiobiotics
In developing countries, the main form of diagnosis In developing countries, the main form of diagnosis is clinical assessment is clinical assessment
A large number of children are not being diagnosed, A large number of children are not being diagnosed, while others are being treated unnecessarily, leading while others are being treated unnecessarily, leading to wasted treatments and antibiotic resistanceto wasted treatments and antibiotic resistance
26 3/2008
Child withChild withsymptomssymptoms
Access toAccess toclinical diagnosisclinical diagnosis
Self-treatSelf-treat
No careNo care
StatusStatusQuoQuo
New New TestTest
Access to Access to new testnew test
No accessNo accessto new testto new test
We Modeled the Status Quo and Access to a New We Modeled the Status Quo and Access to a New Test for Bacterial Pneumonia in Children Under 5Test for Bacterial Pneumonia in Children Under 5
Disease YesDisease Yes
Disease NoDisease NoTest + TreatTest + Treat
Test – No TreatTest – No Treat
SurvivesSurvivesDiesDiesSurvivesSurvivesDiesDiesSurvivesSurvivesDiesDiesSurvivesSurvivesDiesDies
Disease YesDisease Yes
Disease NoDisease No
27 3/2008
We Traded Off Test Performance and We Traded Off Test Performance and Infrastructure RequirementsInfrastructure Requirements
AdvancedAdvancedinfrastructureinfrastructure
Good Good PerformancePerformance
Lives saved by new test forLives saved by new test forbacterial pneumonia*bacterial pneumonia*
PerfectPerfectPerformancePerformance
MinimalMinimalinfrastructureinfrastructure
*Results *Results assumeassumeaccess toaccess totreatmenttreatment
28 3/2008
Easier Tests Produce Large Health Benefits, Easier Tests Produce Large Health Benefits, Even with Less Than Perfect PerformanceEven with Less Than Perfect Performance
AdvancedAdvancedinfrastructureinfrastructure
Good Good PerformancePerformance
261,000261,000142,00142,0000
596,000596,000405,000405,000
SignificantSignificantgains,gains,potentiallypotentiallyachievableachievable
PerfectPerfectPerformancePerformance
MinimalMinimalinfrastructureinfrastructure
*Results *Results assumeassumeaccess toaccess totreatmenttreatmentLives saved by new test forLives saved by new test for
bacterial pneumonia* bacterial pneumonia*
29 3/2008
Our Recommendations for a New DiagnosticOur Recommendations for a New Diagnosticfor Bacterial Lower Respiratory Infectionsfor Bacterial Lower Respiratory Infections
• Requires minimal infrastructureRequires minimal infrastructure
• Preferred samples types include saliva, urine, or Preferred samples types include saliva, urine, or dried blood spot dried blood spot
• Results should be available within 2 hours or lessResults should be available within 2 hours or less
30 3/2008
Much of the Benefit of the New Diagnostic Much of the Benefit of the New Diagnostic Would Be Due to Reductions in OvertreatmentWould Be Due to Reductions in Overtreatment
0
50
100
150
200
250
300
Developing WorldDeveloping World
LivesLivesSavedSaved(1000s)(1000s)
ReductionReductionin overtreatmentin overtreatment
ReductionReductionin diseasein disease
burdenburden
Benefits of New Test forBenefits of New Test forBacterial PneumoniaBacterial Pneumonia With C = .001 !With C = .001 !
31 3/2008
Most Lives Saved from Reducing Disease Burden Most Lives Saved from Reducing Disease Burden Accrue to Africa, While Other Regions Benefit Accrue to Africa, While Other Regions Benefit
from Reducing Overtreatmentfrom Reducing Overtreatment
0
50
100
150
200
250
0
50
100
150
200
250
300
Developing WorldDeveloping World AfricaAfrica AsiaAsia Latin Latin AmericaAmerica
LivesLivesSavedSaved(1000s)(1000s)
ReductionReductionin overtreatmentin overtreatment
ReductionReductionin diseasein disease
burdenburden
ReductionReductionin overtreatmentin overtreatment
ReductionReductionin diseasein disease
burdenburden
Benefits of New Test forBenefits of New Test forBacterial PneumoniaBacterial Pneumonia Benefits of New Test by RegionBenefits of New Test by Region
32 3/2008
All Disease Models Show a Significant All Disease Models Show a Significant Benefit from New DiagnosticsBenefit from New Diagnostics
0 500,000 1,000,000 1,500,000 2,000,000
TB
Children under age 5 (Africa)Children under age 5 (Africa)
Children under age 5Children under age 5
Pregnant women (Africa)Pregnant women (Africa)
Adults with persistent coughAdults with persistent cough
Lives Saved Annually from New Forum-Recommended TestsLives Saved Annually from New Forum-Recommended Tests
Additional benefits were found for other diseases studiedAdditional benefits were found for other diseases studied
Malaria
Syphilis
Bacterialpneumonia
33 3/2008
Study Findings Highlight Other ThemesStudy Findings Highlight Other Themes
Tests that are more accessible have greater benefitsTests that are more accessible have greater benefits
Access can be more important than test performanceAccess can be more important than test performance
For many diseases, a more accurate test is not neededFor many diseases, a more accurate test is not needed
For example, current rapid tests for malaria could lead For example, current rapid tests for malaria could lead to significant benefits if made more widely availableto significant benefits if made more widely available
Current diagnostics do not pay enough attention to harm of Current diagnostics do not pay enough attention to harm of overtreatmentovertreatment
Tests are typically better at identifying people with Tests are typically better at identifying people with disease than identifying those withoutdisease than identifying those without
Reducing overtreatment provides a public health benefitReducing overtreatment provides a public health benefit