Medical Council of CanadaCertifying Exam Review April 16, 2007 Jeffrey P Schaefer MSc MD FRCPC
Commonest Clinical Questions • Harm • Diagnosis • Therapy • Prognosis • Prevention
Measures of Disease Frequency • Disease Incidence • refers to new cases of disease among a population at risk for that disease over a specified period of time.
Measures of Disease Frequency • Cumulative Incidence (CI) CI = new cases / population at risk / time interval 1 yr Population at risk 100 New cases 25 Population 120 Population not at risk 20 CI = 25/100/yr
Measures of Disease Frequency • Incidence Density ID = new cases . person-time population at risk per time period Useful when there is losses to follow-up among the population under observation
Measures of Disease Frequency • A study plans to observe 20,000 people for 1 years but 10,000 left town after 6 mo. 15 cases of disease were observed among the population. 10,000 observed x 1 yr = 10,000 p-yr 10,000 observed x 0.5 yr = 5,000 p-yr Total persons years = 15,000 p-yr
Measures of Disease Frequency 15 cases / 15,000 person years 1 cases / 1,000 person-years 10 cases / 10,000 persons per year
Incidence of Cancer of the Lung, Trachea, and Bronchus, Both Sexes Combined, All Ages, 1998 from Statistics Canada by Province or Territory.
Incidence Data • Challenge • ensure the denominator is truly at risk.
Measures of Disease Frequency • Disease Prevalence • refers to the proportion of individuals who have the disease at a specific time among a given population. (not a rate) Prevalence = existing cases at a point in time total population
Measures of Disease Frequency • Point Prevalence • ‘snapshot’ in calendar time or event related time • number of cases of diabetes on June 30, 2002 in Calgary • number of people with infected incision on post-operative day 3 on General Surgery unit at Foothills Hospital
Measures of Disease Frequency • Period Prevalence • longer duration under consideration • number of people with diabetes between Jan 1 and Dec 31, 2002 in Calgary • number of people with infected incision between surgery and post-operative day 90 on General Surgery unit at Foothills Hospital
Special Measures of Disease Frequency • Mortality Rate • incidence of death (cause specific vs all cause mortality) • Infant Mortality Rate • death of a live born infant within the 1st year of life • Neonatal Death • death of an infant under 28 days of age • Post-neonatal Death • death of an infant between 4 weeks and 1 year of age
Infant Mortality Rates by Income Quintile, Urban Canada, 1991
Prevention primary prevention secondary prevention tertiary prevention risk factors only subclinical disease clinical disease complicated disease time
Harm • Exposures that cause disease = Harm • Harmful exposures are Risk Factors • Risk Factors may be etiologies of disease.
Harm A harmful exposure is a RISK FACTOR EXPOSURE DISEASE
Robert Koch • Dec 11, 1843 - May 27, 1910 • Nobel Prize - 1905 • Anthrax • Tuberculosis • Cholera
Harm • Koch’s Postulates (1882) • Criteria for Causation • the organism must be present in every case of disease, • the organism be isolated from the diseased animal and grown in pure culture, • the organism causes the same disease when inoculated into a healthy animal, • the organism must be recovered from that animal (step 3) and identified.
Harm • Limitations of Koch’s Postulates • not all diseases are infectious • one risk factor may cause > 1 diseases • one disease may have > 1 risk factors
Harm Emphysema Chronic Bronchitis Smoking Lung Cancer Bladder Cancer Lip Cancer Coronary dx Stroke Ischemic Limb
Harm Hypertension Myocardial Infarction Hyper- cholesterolemia Smoking Male Sex Family History
Causality for the Modern Era • Austin Bradford Hill • July 8, 1897 - April 18, 1991 • English epidemiologist and statistician • pioneered the randomized clinical trial • published criteria for causality
Harm • Austin Bradford Hill’s criteria for causality. • Temporality • exposure precedes onset of disease • Strength of Association • exposure strongly associated with disease frequency
Harm • Dose – Response • more exposure associates with higher disease frequency or severity • Reversibility • reduction in exposure associates with lower rates of disease • Consistency • association between exposure and disease is observed by difference persons in different places during different circumstances
Harm • Specificity • one cause leads to one effect • Analogy • cause and effect relationship already established for similar risk factor or disease • Biological Plausibility • is the association biologically plausible (keeping in mind that plausibility changes with time)
Measures of Risk for Disease • 1964 cohort study data Lung Cancer Death Population Smokers RF+ Not Lung Cancer Death Not Smoker RF- Lung Cancer Death Not Lung Cancer Death Stratify on Smoking Status Observe for several years
Measures of Risk for Disease lung cancer mortality cigarette smokers 0.96 / 1000 / year non-smokers 0.07 / 1000 / year all subjects 0.56 / 1000 / year prevalence of cigarette smoking = 56%
Measures of Risk for Disease • Q: What is the additional risk (incidence) of disease following exposure, over and above that experienced by people who are not exposed? • Attributable Risk
Measures of Risk for Disease AR = Attributable Risk IEXP = disease incidence among exposed IUNEXP = disease incidence among not exposed AR = IEXP – IUNEXP
Measures of Risk for Disease lung cancer mortality cigarette smokers 0.96 / 1000 / year non-smokers 0.07 / 1000 / year 0.96 - 0.07 = 0.89 Attributable Risk = 0.89 deaths / 1000 / yr For every 10,000 smokers compared to 10,000 non-smokers there were 9 more deaths each year.
Measures of Risk for Disease • Q: How many times are exposed persons more likely to get the disease relative to nonexposed persons? • Relative Risk
Measures of Risk for Disease RR = Relative Risk IEXP = disease incidence among exposed IUNEXP = disease incidence among not exposed IEXP RR = ----------------- IUNEXP
Measures of Risk for Disease lung cancer mortality cigarette smokers 0.96 / 1000 / year non-smokers 0.07 / 1000 / year 0.96 / 0.07 = 13.7 Relative Risk = 13.7 Smokers are 13.7 times more likely to die from lung cancer than non-smokers.
Measures of Risk for Disease • Q: How much does a risk factor contribute to the overall rates of disease in groups of people, rather than individuals? • Population Attributable Risk
Measures of Risk for Disease • PAR = Population Attributable Risk • AR = attributable risk • P = prevalence of exposure PAR = AR x P
Measures of Risk for Disease lung cancer mortality cigarette smokers 0.96 / 1000 / year non-smokers 0.07 / 1000 / year smokers 56% of the population (0.96-0.07) x 0.56 = 0.4984 ~ 0.5 Population Attributable Risk = 0.5 / 1000 / yr Annually, smoking accounts for 1 lung cancer death per every 2000 people in the population.
Measures of Risk for Disease • Example of utility of Pop. Attributable Risk • Hypertension (high blood pressure) is a risk factor for stroke. What would be more effective in lowering the incidence of stroke in a population? Treating mild hypertension Treating severe hypertension Surprise! Treating Mild Hypertension The prevalence of mild hypertension far exceeds the prevalence of severe hypertension.
Measures of Risk for Disease • What fraction of disease in a population is attributable to exposure to a risk factor? • Population Attributable Fraction
Measures of Risk for Disease • PAF = Population Attributable Fraction • PAR = population attributable risk • ITotal = disease incidence in total population PAR PAF = ---------- ITotal
Measures of Risk for Disease lung cancer mortality all subjects 0.56 / 1000 / year PAR 0.4984 / 1000 / year 0.4984 / 0.56 = 0.89 Population Attributable Fraction = 0.89 Eighty-nine (89)% of the lung cancer deaths were accounted for by cigarette smoking.