Natural History of Disease: Prevention and Prognosis Dr. Namvar Zohoori Epidemiology Research Unit...

Natural History of Disease:Natural History of Disease:Prevention and PrognosisPrevention and PrognosisNatural History of Disease:Natural History of Disease:Prevention and PrognosisPrevention and Prognosis

Dr. Namvar ZohooriDr. Namvar Zohoori

Epidemiology Research UnitEpidemiology Research Unit

Dr. Namvar ZohooriDr. Namvar Zohoori

Epidemiology Research UnitEpidemiology Research Unit

Learning ObjectivesLearning ObjectivesLearning ObjectivesLearning Objectives

• Understand different stages of disease Understand different stages of disease development.development.

• Relate above stages to phases of prevention.Relate above stages to phases of prevention.• Describe advantages and disadvantages of Describe advantages and disadvantages of

population and high-risk prevention population and high-risk prevention strategies.strategies.

• Define and list methods of quantifying Define and list methods of quantifying prognosis.prognosis.

• Understand different stages of disease Understand different stages of disease development.development.

• Relate above stages to phases of prevention.Relate above stages to phases of prevention.• Describe advantages and disadvantages of Describe advantages and disadvantages of

population and high-risk prevention population and high-risk prevention strategies.strategies.

• Define and list methods of quantifying Define and list methods of quantifying prognosis.prognosis.

EpidemiologyEpidemiologyEpidemiologyEpidemiology

‘‘Epidemiology: the study of the Epidemiology: the study of the

occurrence of illness’occurrence of illness’

‘‘Epidemiology: the study of the Epidemiology: the study of the

occurrence of illness’occurrence of illness’

Gaylord AndersonGaylord Anderson

EpidemiologyEpidemiologyEpidemiologyEpidemiology

‘‘study of the distribution and study of the distribution and

determinants of health related states or events in determinants of health related states or events in

specified populations specified populations and the application of this and the application of this

study to the control of health problemsstudy to the control of health problems’’

‘‘study of the distribution and study of the distribution and

determinants of health related states or events in determinants of health related states or events in

specified populations specified populations and the application of this and the application of this

study to the control of health problemsstudy to the control of health problems’’

John Last, 2001John Last, 2001

Some Important RolesSome Important RolesSome Important RolesSome Important Roles

PreventionPrevention

DetectionDetection

PrognosisPrognosis

PreventionPrevention

DetectionDetection

PrognosisPrognosis

Disease ProcessDisease ProcessDisease ProcessDisease Process

• Diseases and other phenomena of interest in Diseases and other phenomena of interest in epidemiology are epidemiology are processesprocesses, not events., not events.

• Example of bronchogenic carcinoma:-Example of bronchogenic carcinoma:-– Several grades of abnormality (metaplasia, mild Several grades of abnormality (metaplasia, mild

dysplasia, mod dysplasia, severse dysplasia).dysplasia, mod dysplasia, severse dysplasia).– Most can regress spontaneouslyMost can regress spontaneously– Some can progress to Ca in situ and then invasive Some can progress to Ca in situ and then invasive

carcinoma.carcinoma.– Every disease has a natural course of progression.Every disease has a natural course of progression.

• Diseases and other phenomena of interest in Diseases and other phenomena of interest in epidemiology are epidemiology are processesprocesses, not events., not events.

• Example of bronchogenic carcinoma:-Example of bronchogenic carcinoma:-– Several grades of abnormality (metaplasia, mild Several grades of abnormality (metaplasia, mild

dysplasia, mod dysplasia, severse dysplasia).dysplasia, mod dysplasia, severse dysplasia).– Most can regress spontaneouslyMost can regress spontaneously– Some can progress to Ca in situ and then invasive Some can progress to Ca in situ and then invasive

carcinoma.carcinoma.– Every disease has a natural course of progression.Every disease has a natural course of progression.

Disease ProcessDisease ProcessDisease ProcessDisease Process

• Therefore, defining, observing and measuring Therefore, defining, observing and measuring health and disease require understanding of health and disease require understanding of concept of “concept of “natural historynatural history”:-”:-

““the evolution of a pathophysiologic the evolution of a pathophysiologic processprocess””

• Therefore, defining, observing and measuring Therefore, defining, observing and measuring health and disease require understanding of health and disease require understanding of concept of “concept of “natural historynatural history”:-”:-

““the evolution of a pathophysiologic the evolution of a pathophysiologic processprocess””

SusceptibilityPre-clinical

Pre-symptomaticClinical

Post-morbid

Biologic onset Signs and symptoms

Outcome

Natural History of DiseaseNatural History of DiseaseNatural History of DiseaseNatural History of Disease

Detection possible Care Dx Rx

Primordial & PrimaryPrevention

SecondaryPrevention

TertiaryPrevention

Prevention ParadoxPrevention ParadoxPrevention ParadoxPrevention Paradox

““A preventive measure which brings much A preventive measure which brings much benefit to the population often offers little to benefit to the population often offers little to

each participating individual.”each participating individual.”

““A preventive measure which brings much A preventive measure which brings much benefit to the population often offers little to benefit to the population often offers little to

each participating individual.”each participating individual.”

Primordial PreventionPrimordial PreventionPrimordial PreventionPrimordial Prevention

““Prevention of the emergence of living patterns Prevention of the emergence of living patterns that contribute to increased risk of disease that contribute to increased risk of disease

(e.g. the maintenance of low-fat diets in (e.g. the maintenance of low-fat diets in traditional societies)”traditional societies)”

““Prevention of the emergence of living patterns Prevention of the emergence of living patterns that contribute to increased risk of disease that contribute to increased risk of disease

(e.g. the maintenance of low-fat diets in (e.g. the maintenance of low-fat diets in traditional societies)”traditional societies)”

Primordial PreventionPrimordial PreventionPrimordial PreventionPrimordial Prevention

• Understanding of CVD epidemiology.Understanding of CVD epidemiology.

• Dietary patterns in China and JapanDietary patterns in China and Japan

• Socioeconomic development -> more Socioeconomic development -> more widespread risk factors.widespread risk factors.

• Have we missed the boat?Have we missed the boat?

• Understanding of CVD epidemiology.Understanding of CVD epidemiology.

• Dietary patterns in China and JapanDietary patterns in China and Japan

• Socioeconomic development -> more Socioeconomic development -> more widespread risk factors.widespread risk factors.

• Have we missed the boat?Have we missed the boat?

Primary PreventionPrimary PreventionPrimary PreventionPrimary Prevention

““Prevention of disease by controlling risk Prevention of disease by controlling risk factors (e.g. non-smoking promotion)”factors (e.g. non-smoking promotion)”

Two strategies:-Two strategies:-

PopulationPopulation

High-riskHigh-risk

““Prevention of disease by controlling risk Prevention of disease by controlling risk factors (e.g. non-smoking promotion)”factors (e.g. non-smoking promotion)”

Two strategies:-Two strategies:-

PopulationPopulation

High-riskHigh-risk


• The Population StrategyThe Population Strategy

– Advantages:-Advantages:-

• RadicalRadical

• Large potential for populationLarge potential for population

• Behaviourally appropriateBehaviourally appropriate



• RadicalRadical

• Large potential for populationLarge potential for population

• Behaviourally appropriateBehaviourally appropriate



– Disadvantages:-Disadvantages:-

• Small benefits to individualsSmall benefits to individuals

• Poor motivation of subjectPoor motivation of subject

• Poor motivation of physicianPoor motivation of physician

• Benefit-to-risk ratio may be lowBenefit-to-risk ratio may be low



• Small benefits to individualsSmall benefits to individuals

• Poor motivation of subjectPoor motivation of subject

• Poor motivation of physicianPoor motivation of physician

• Benefit-to-risk ratio may be lowBenefit-to-risk ratio may be low


• The High-risk StrategyThe High-risk Strategy


• Appropriate to individualsAppropriate to individuals

• Subject motivationSubject motivation

• Physician motivationPhysician motivation

• Benefit-to-risk ratio is favourableBenefit-to-risk ratio is favourable



• Appropriate to individualsAppropriate to individuals

• Subject motivationSubject motivation

• Physician motivationPhysician motivation

• Benefit-to-risk ratio is favourableBenefit-to-risk ratio is favourable




• High screening costsHigh screening costs

• Temporary effectsTemporary effects

• Limited effectLimited effect

• Behaviourally inappropriateBehaviourally inappropriate



• High screening costsHigh screening costs

• Temporary effectsTemporary effects

• Limited effectLimited effect

• Behaviourally inappropriateBehaviourally inappropriate

Secondary PreventionSecondary PreventionSecondary PreventionSecondary Prevention

““Reduction in consequences of disease by Reduction in consequences of disease by early detection, diagnosis and treatment (e.g. early detection, diagnosis and treatment (e.g.

cervical cancer screening)”cervical cancer screening)”

““Reduction in consequences of disease by Reduction in consequences of disease by early detection, diagnosis and treatment (e.g. early detection, diagnosis and treatment (e.g.

cervical cancer screening)”cervical cancer screening)”



Post-morbid


Outcome



Premordial & PrimaryPrevention

SecondaryPrevention

TertiaryPrevention

Tertiary PreventionTertiary PreventionTertiary PreventionTertiary Prevention

““Reduction of complications of disease (e.g. Reduction of complications of disease (e.g. role of ICU in MVA’s)”role of ICU in MVA’s)”

““Reduction of complications of disease (e.g. Reduction of complications of disease (e.g. role of ICU in MVA’s)”role of ICU in MVA’s)”

Levels of PreventionLevels of PreventionLevels of PreventionLevels of Prevention

Level of PreventionLevel of Prevention Phase of DiseasePhase of Disease TargetTarget

PrimordialPrimordial Underlying conditions Underlying conditions leading to causationleading to causation

Total population and Total population and selected groupsselected groups

PrimaryPrimary Specific causal factorsSpecific causal factors Total population, selected Total population, selected groups and healthy ind’sgroups and healthy ind’s

SecondarySecondary Early stage of diseaseEarly stage of disease PatientsPatients

TertiaryTertiary Late stage of diseaseLate stage of disease PatientPatient

PrognosisPrognosisPrognosisPrognosis

““A quantitative expression of the likelihood of a A quantitative expression of the likelihood of a specific outcome (survival)”specific outcome (survival)”

General issues:-General issues:-

1.1. At what point to begin counting survival?At what point to begin counting survival?

2.2. How is diagnosis made?How is diagnosis made?

““A quantitative expression of the likelihood of a A quantitative expression of the likelihood of a specific outcome (survival)”specific outcome (survival)”

General issues:-General issues:-

1.1. At what point to begin counting survival?At what point to begin counting survival?

2.2. How is diagnosis made?How is diagnosis made?



Post-morbid


Outcome



Premordial & PrimaryPrevention

SecondaryPrevention

TertiaryPrevention


Death Survival

Case-fatalityRate

5-yearsurvival

Observedsurvival Median

survival

Relativesurvival


• Case-fatality rateCase-fatality rate– DFN: # who die of dis./# who have dis.DFN: # who die of dis./# who have dis.– No explicit time frame.No explicit time frame.– Ideally suited for diseases that are short-Ideally suited for diseases that are short-

term, in which death occurs soon after term, in which death occurs soon after diagnosis.diagnosis.

– With chronic diseases of long duration, With chronic diseases of long duration, case-fatality rate becomes meaningless.case-fatality rate becomes meaningless.

• Case-fatality rateCase-fatality rate– DFN: # who die of dis./# who have dis.DFN: # who die of dis./# who have dis.– No explicit time frame.No explicit time frame.– Ideally suited for diseases that are short-Ideally suited for diseases that are short-

term, in which death occurs soon after term, in which death occurs soon after diagnosis.diagnosis.

– With chronic diseases of long duration, With chronic diseases of long duration, case-fatality rate becomes meaningless.case-fatality rate becomes meaningless.


• 5-Year survival5-Year survival

– DFN: % of patients still alive 5 years after DFN: % of patients still alive 5 years after diagnosis or treatment begins.diagnosis or treatment begins.

– Used most in cancer treatment.Used most in cancer treatment.

– Note problem with Note problem with ‘lead time’‘lead time’..

• 5-Year survival5-Year survival

– DFN: % of patients still alive 5 years after DFN: % of patients still alive 5 years after diagnosis or treatment begins.diagnosis or treatment begins.

– Used most in cancer treatment.Used most in cancer treatment.

– Note problem with Note problem with ‘lead time’‘lead time’..



Post-morbid


Death


Dx & Rx

19951991

Survival 4 years



Post-morbid


Death


Detected by screening

19951989

Survival 6 years


• Observed survivalObserved survival– DFN: probability of surviving x number of years.DFN: probability of surviving x number of years.– Use of life-table analysisUse of life-table analysis– Advantage of using data on all patients, Advantage of using data on all patients,

regardless of how long they survive.regardless of how long they survive.– 2 assumptions:-2 assumptions:-

• No temporal change in Rx efficacyNo temporal change in Rx efficacy• Those lost to follow-up have similar experience Those lost to follow-up have similar experience

to those followed up.to those followed up.

• Observed survivalObserved survival– DFN: probability of surviving x number of years.DFN: probability of surviving x number of years.– Use of life-table analysisUse of life-table analysis– Advantage of using data on all patients, Advantage of using data on all patients,

regardless of how long they survive.regardless of how long they survive.– 2 assumptions:-2 assumptions:-

• No temporal change in Rx efficacyNo temporal change in Rx efficacy• Those lost to follow-up have similar experience Those lost to follow-up have similar experience

to those followed up.to those followed up.


• Median survival timeMedian survival time

– DFN: length of time that half of the study DFN: length of time that half of the study population survives.population survives.

– Advantages of median versus meanAdvantages of median versus mean

• Effect of extremesEffect of extremes

• ““Sample size”Sample size”

• Median survival timeMedian survival time

– DFN: length of time that half of the study DFN: length of time that half of the study population survives.population survives.

– Advantages of median versus meanAdvantages of median versus mean

• Effect of extremesEffect of extremes

• ““Sample size”Sample size”


• Relative survival rateRelative survival rate

– DFN: ratio of observed survival rate to DFN: ratio of observed survival rate to expected survival rate if no diseaseexpected survival rate if no disease

– That is, compares survival to the survival That is, compares survival to the survival one would expect in the given age groupone would expect in the given age group

• Relative survival rateRelative survival rate

– DFN: ratio of observed survival rate to DFN: ratio of observed survival rate to expected survival rate if no diseaseexpected survival rate if no disease

– That is, compares survival to the survival That is, compares survival to the survival one would expect in the given age groupone would expect in the given age group

5-Year Observed and Relative Survival Rates5-Year Observed and Relative Survival Ratesby age for Colon Cancerby age for Colon Cancer

5-Year Observed and Relative Survival Rates5-Year Observed and Relative Survival Ratesby age for Colon Cancerby age for Colon Cancer

Age (yr)Age (yr) Observed rate (%)Observed rate (%) Relative rate (%)Relative rate (%)

<45<45 55.655.6 56.356.3

45-5445-54 57.157.1 59.259.2

55-6455-64 53.653.6 58.558.5

65-7465-74 47.847.8 57.857.8

>=75>=75 31.731.7 54.154.1

Natural History of Disease: Prevention and Prognosis Dr. Namvar Zohoori Epidemiology Research Unit...

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Transcript of Natural History of Disease: Prevention and Prognosis Dr. Namvar Zohoori Epidemiology Research Unit...