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

2. Learning Objectives Understand different stages of disease development.Understand different stages of disease development. Relate above stages to phases of prevention.Relate above stages to phases of prevention. Describe advantages and disadvantages of population and high-risk prevention strategies.Describe advantages and disadvantages of population and high-risk prevention strategies. Define and list methods of quantifying prognosis.Define and list methods of quantifying prognosis. Understand different stages of disease development.Understand different stages of disease development. Relate above stages to phases of prevention.Relate above stages to phases of prevention. Describe advantages and disadvantages of population and high-risk prevention strategies.Describe advantages and disadvantages of population and high-risk prevention strategies. Define and list methods of quantifying prognosis.Define and list methods of quantifying prognosis.

3. EpidemiologyEpidemiology Epidemiology: the study of the occurrence of illness Gaylord Anderson

4. EpidemiologyEpidemiology study of the distribution and determinants of health related states or events in specified populations and the application of this study to the control of health problems study of the distribution and determinants of health related states or events in specified populations and the application of this study to the control of health problems John Last, 2001

5. Some Important Roles PreventionDetectionPrognosisPreventionDetectionPrognosis

6. Disease Process Diseases and other phenomena of interest in epidemiology are processes, not events.Diseases and other phenomena of interest in epidemiology are processes, not events. Example of bronchogenic carcinoma:-Example of bronchogenic carcinoma:- –Several grades of abnormality (metaplasia, mild dysplasia, mod dysplasia, severse dysplasia). –Most can regress spontaneously –Some can progress to Ca in situ and then invasive carcinoma. –Every disease has a natural course of progression. Diseases and other phenomena of interest in epidemiology are processes, not events.Diseases and other phenomena of interest in epidemiology are processes, not events. Example of bronchogenic carcinoma:-Example of bronchogenic carcinoma:- –Several grades of abnormality (metaplasia, mild dysplasia, mod dysplasia, severse dysplasia). –Most can regress spontaneously –Some can progress to Ca in situ and then invasive carcinoma. –Every disease has a natural course of progression.

7. Disease Process Therefore, defining, observing and measuring health and disease require understanding of concept of natural history:-Therefore, defining, observing and measuring health and disease require understanding of concept of natural history:- the evolution of a pathophysiologic processthe evolution of a pathophysiologic process Therefore, defining, observing and measuring health and disease require understanding of concept of natural history:-Therefore, defining, observing and measuring health and disease require understanding of concept of natural history:- the evolution of a pathophysiologic processthe evolution of a pathophysiologic process

8. Susceptibility Pre-clinical Pre-symptomatic Clinical Post-morbid Biologic onset Signs and symptoms Outcome Natural History of Disease Detection possible CareDxRx Primordial & Primary Prevention Secondary Prevention Tertiary Prevention

9. Prevention Paradox A preventive measure which brings much benefit to the population often offers little to each participating individual.

10. Primordial Prevention Prevention of the emergence of living patterns that contribute to increased risk of disease (e.g. the maintenance of low-fat diets in traditional societies)

11. Primordial Prevention Understanding of CVD epidemiology.Understanding of CVD epidemiology. Dietary patterns in China and JapanDietary patterns in China and Japan Socioeconomic development -> more widespread risk factors.Socioeconomic development -> more 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 widespread risk factors.Socioeconomic development -> more widespread risk factors. Have we missed the boat?Have we missed the boat?

12. Primary Prevention Prevention of disease by controlling risk factors (e.g. non-smoking promotion) Two strategies:- PopulationHigh-risk Prevention of disease by controlling risk factors (e.g. non-smoking promotion) Two strategies:- PopulationHigh-risk

13. Primary Prevention The Population Strategy The Population Strategy –Advantages:- RadicalRadical Large potential for populationLarge potential for population Behaviourally appropriateBehaviourally appropriate The Population Strategy The Population Strategy –Advantages:- RadicalRadical Large potential for populationLarge potential for population Behaviourally appropriateBehaviourally appropriate

14. Primary Prevention The Population Strategy The Population Strategy –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 The Population Strategy The Population Strategy –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

15. Primary Prevention The High-risk Strategy The High-risk Strategy –Advantages:- Appropriate to individualsAppropriate to individuals Subject motivationSubject motivation Physician motivationPhysician motivation Benefit-to-risk ratio is favourableBenefit-to-risk ratio is favourable The High-risk Strategy The High-risk Strategy –Advantages:- Appropriate to individualsAppropriate to individuals Subject motivationSubject motivation Physician motivationPhysician motivation Benefit-to-risk ratio is favourableBenefit-to-risk ratio is favourable

16. Primary Prevention The High-risk Strategy The High-risk Strategy –Disadvantages:- High screening costsHigh screening costs Temporary effectsTemporary effects Limited effectLimited effect Behaviourally inappropriateBehaviourally inappropriate The High-risk Strategy The High-risk Strategy –Disadvantages:- High screening costsHigh screening costs Temporary effectsTemporary effects Limited effectLimited effect Behaviourally inappropriateBehaviourally inappropriate

17. Secondary Prevention Reduction in consequences of disease by early detection, diagnosis and treatment (e.g. cervical cancer screening)

18. Susceptibility Pre-clinical Pre-symptomatic Clinical Post-morbid Biologic onsetSigns and symptoms Outcome Natural History of Disease Detection possibleCareDxRx Premordial & Primary Prevention Secondary Prevention Tertiary Prevention

19. Tertiary Prevention Reduction of complications of disease (e.g. role of ICU in MVAs)

20. Levels of Prevention Level of Prevention Phase of Disease Target Primordial Underlying conditions leading to causation Total population and selected groups Primary Specific causal factors Total population, selected groups and healthy inds Secondary Early stage of disease Patients Tertiary Late stage of disease Patient

21. PrognosisPrognosis A quantitative expression of the likelihood of a specific outcome (survival) General issues:- 1.At what point to begin counting survival? 2.How is diagnosis made? A quantitative expression of the likelihood of a specific outcome (survival) General issues:- 1.At what point to begin counting survival? 2.How is diagnosis made?

22. Susceptibility Pre-clinical Pre-symptomatic Clinical Post-morbid Biologic onsetSigns and symptoms Outcome Natural History of Disease Detection possibleCareDxRx Premordial & Primary Prevention Secondary Prevention Tertiary Prevention

23. PrognosisPrognosis Death Survival Case-fatality Rate 5-year survival Observed survival Median survival Relative survival

24. PrognosisPrognosis Case-fatality rateCase-fatality rate –DFN: # who die of dis./# who have dis. –No explicit time frame. –Ideally suited for diseases that are short- term, in which death occurs soon after diagnosis. –With chronic diseases of long duration, case-fatality rate becomes meaningless. Case-fatality rateCase-fatality rate –DFN: # who die of dis./# who have dis. –No explicit time frame. –Ideally suited for diseases that are short- term, in which death occurs soon after diagnosis. –With chronic diseases of long duration, case-fatality rate becomes meaningless.

25. PrognosisPrognosis 5-Year survival5-Year survival –DFN: % of patients still alive 5 years after diagnosis or treatment begins. –Used most in cancer treatment. –Note problem with lead time. 5-Year survival5-Year survival –DFN: % of patients still alive 5 years after diagnosis or treatment begins. –Used most in cancer treatment. –Note problem with lead time.

26. Susceptibility Pre-clinical Pre-symptomatic Clinical Post-morbid Biologic onsetSigns and symptoms Death Natural History of Disease Dx & Rx 19951991 Survival 4 years

27. Susceptibility Pre-clinical Pre-symptomatic Clinical Post-morbid Biologic onsetSigns and symptoms Death Natural History of Disease Detected by screening 19951989 Survival 6 years

28. PrognosisPrognosis Observed survivalObserved survival –DFN: probability of surviving x number of years. –Use of life-table analysis –Advantage of using data on all patients, regardless of how long they survive. –2 assumptions:- No temporal change in Rx efficacyNo temporal change in Rx efficacy Those lost to follow-up have similar experience to those followed up.Those lost to follow-up have similar experience to those followed up. Observed survivalObserved survival –DFN: probability of surviving x number of years. –Use of life-table analysis –Advantage of using data on all patients, regardless of how long they survive. –2 assumptions:- No temporal change in Rx efficacyNo temporal change in Rx efficacy Those lost to follow-up have similar experience to those followed up.Those lost to follow-up have similar experience to those followed up.

29. PrognosisPrognosis Median survival timeMedian survival time –DFN: length of time that half of the study population survives. –Advantages of median versus mean Effect of extremesEffect of extremes Sample sizeSample size Median survival timeMedian survival time –DFN: length of time that half of the study population survives. –Advantages of median versus mean Effect of extremesEffect of extremes Sample sizeSample size

30. PrognosisPrognosis Relative survival rateRelative survival rate –DFN: ratio of observed survival rate to expected survival rate if no disease –That is, compares survival to the survival one would expect in the given age group Relative survival rateRelative survival rate –DFN: ratio of observed survival rate to expected survival rate if no disease –That is, compares survival to the survival one would expect in the given age group

31. 5-Year Observed and Relative Survival Rates by age for Colon Cancer Age (yr) Observed rate (%) Relative rate (%) <4555.656.3 45-5457.159.2 55-6453.658.5 65-7447.857.8 >=7531.754.1