Epidemiology And Evidence-Based Medicine - Columbia University
Epidemiology andEvidence-BasedMedicineCharles DiMaggio, PhD, MPH, PA-CColumbia UniversityDepartments of Anesthesiology andEpidemiology
Course Objectivesn n n n n n n Define epidemiology and its applicationsIdentify the most commonly used study designsUnderstand the importance of measurementApply coursework in evaluating the medicalliteratureDefine evidence-based medicineCreate a searchable clinical questionsSearch medical databases to answer clinicalqueries.
Course Overviewn n n n n n n n n 1. Hx / ID / Biostatistics2. Study Designs: RCTs, Cohorts3. Study Designs: Ecologic, X-Sectional4. Case-Control, Bias, Confounding5. EBM: Intro and Concepts6. EBM: Sources and Searches7. Dx: Sens / Spec, PPV, NPV, LR8. Tx: NNT9. Oral Presentations
What is Epidemiology?What epidemiologists don Epidemiologists countn Definea population Count cases of diseases in the population andcompute rates Compare those rates to another population Make inferences regarding patterns andsuggest interventions
Case 1August 2nd, 1976n Robert Craven, CDC viral diseasesbranch, recieves report of 2 cases ofsevere respiratory illness (1 fatality) fromPhiladelphia ICNn By August 3rd, 71 more cases, 18 deathsn Legionella pneumophelian
Case 2October 30th, 1989n New Mexico MD informs state DOH of 3cases of severe myalgia and markedeosonophelia è EMSn Intense investigation reveals commonvehicle: L-tryptophan supplementsn Remove from shelvesn
n Epidemiologists are like clinicians for acommunity Gatherinformation, make informed diagoses,suggest and implement interventions
What is Epidemiology?n The study of the distribution and determinants of diseasein human populations.n Study n Distribution n Descriptive Epi – person, place, timeLook for patterns among different groupsDeterminants n Methods are intended to be scientific (basic science of public health)“Epidemiology is reasoned argument.”Epi Triad – Agent, Host, EnvironmentCausality – Criteria (AB Hill), Induction vs. Deduction (Popper)Populations Probability (chance) and StatisticsStudy Designs
StudyBasic Science of Public Healthn Quantitative, based on principles ofstatistics and research methodologiesn Methods are intended to be scientific(Reasoned Argument)n
DistributionFrequencies and patterns of health eventsin groupsn Descriptive epidemiology – person, placeand timen E.g. age, sex, pre-existing conditions(COPD, DM, smoking, SES) how dx made(lab, culture, clinically) location (restaurant,gathering)n
DeterminantsSearch for Causes and Risk Factorsn Analytic Epidemiologyn Causality, inductive vs. deductivereasoning, Popperian refutationn What is a cause and how do we know it?n What is a disease?n IDʼs,chronic diseases, injuries, disasters
PopulationsDistinguishing characteristic ofepidemiologyn Need for specialized study designsn Medicine is a social science, and politicsnothing but medicine on a grand scale.n (Virchow, 1848)
A Brief 3000-Year Timeline of EpiDavid and King Nebuchadnezzarn James Lind and Scurvyn HMSn Salisbury, 1740-1744John Snow and Cholera 19th Century London ( 1856)the importance of rates and comparisonsimpressions are not good enoughn not a matter of “luck”n begins with observation (like any good detectivework)n
Snow on CholeraWATERCOMPANYNUMBER OFHOUSESDEATHSFROMCHOLERADEATHS PER10,000 HOUSESSouthwarkand Vauxhall40,0461263315Lambeth26,1079837Rest ofLondon256,423142259
Lessons from SnowNeed numbers; impressions not goodenoughn Can intervene well before the actualcausative variable is fully characterizedn Smoking,n HIVDiligence and perseverance
Austin Bradford Hilln “Nature makes the experiments, and wewatch and understand them if we can”n “The highest returns can be reaped byimagination in combination with a logicaland critical mind, a spice of ingenuitycoupled with an eye for the simple andhumdrum, and a width of vision in pursuitof facts that is allied with an attention todetail that is almost nauseating”
Evidence-Based Medicinen Whatʼs old is new again.n Classic epidmiologic principles applied toclinical care (Clinical Epidemiology)
Concepts in Infectious DiseaseEpidemiologyn KuruNeurodegenerative Disease (Scrapie, BSE) Fore Tribe Papua New Guinea Women and childrenn Temporally related to deathsn Cultural practices?n Prions?
Commonly Used TermsEpidemicn Outbreakn Clustern Endemicn Pandemicn
Epidemic vs. OutbreakEpidemic - the occurrence of more casesof disease than would normally beexpected in a specific place or group ofpeople over a given period of timen Outbreak – basically the same thing, butmay have less serious connotations inpublicʼs mindn
ClusterGroup of cases in a particular place andtime; may or may not be more thanexpectedn Aim of investigation is to determine if thereis an increases raten Sometimes used incorrectly in place ofepidemic or outbreakn
n Endemic – high background rate ofdiseasen Pandemic – widespread, often globaldisease
The Epidemiologic TriadNutritive, Chemical,Physical, Infectious(e.g. child vs. 80 y/o falling, TBCavitation, PolioBreast CA on LI?Gastric CA AsiaInborn, Acquired,BehavioralMuch Overlap e.g. KuruDescriptive Epidemiology gives clues to interventions.
Bubonic Plague (14th Century)n Mortality in Florence up to 70% (Host) Whynot the other 30%? Why humans not dogs?n Mostly in the Summer (Agent) Whyn not in winter?Mostly in the cities (Environment) Whynot in countryside?
Agentn Entity necessary to cause disease in susceptibleperson Infectiousn viruses (HIV), bacteria (TB), protozoa (malaria), rickettssia(Rocky Mountain Spotted Fever) Chemical- Tylenol, CO, heroin Physical – cars, ionizing radiation Nutritionn cholesterol è CAD, protein è kwashiorkor
Terms associated with infectiousdiseasesInfectivity - the capacity to cause infectionin a susceptible host.n Pathogenicity - the capacity to causedisease in a hostn Virulence - the severity of disease that theagent causes in the host.n
Hostn Individual susceptibility is key to diseaseprocess E.gTB cavitation due to immune process;consequences of falls vary by agen Factors may be Inborn– thallasemia and Mediterraneandescent; gender and MI Aquired – immunlogical experience and age Behavioral – cigarettes, exercisen Host status susceptible,immune or infected
Environmentn Often among the most challenging clues cann be misleadingWide variety of potential factors physical,climatologic, biologic, social, andeconomic E.g MVC – speed, weather, road conditions,local law enforcement, community views ofdrinking Stomach CA in Japan due to pickled andsmoked foods?
Breast Cancer on Long Islandn “I have just come from the breast cancercapital of the world, and that is LongIsland.” 1991 News Conference, prior to 30 Million 1993Congressional authorization to study breast cancer on LIn Statistical anomoly? Pesticides in water? Fatty foods?n 1.1%Percentage above the national average of breast cancer rates inNassau County, LI. (115.6/100,000 vs. 114.3 cases / 100,000, 1994-1998)
Mode of transmissionn Direct contactn with soil, plants, other peopleIndirect Airborne– agent carried from source to hoston air particle Vector borne – tranmitted by live vehicle e.g.tse tse fly (African Trypanosomiasis) reduvidbug (American Trypanosomiasis) anophelesmosquito (malaria) ticks (Lyme disease) Vehicle borne – inanimate objects, e.gbedding, surgical instruments
Time è Epidemic Curve
Selected GI Differential DxʼsTPredominant SxOrganism or toxinUpper gastrointestinal tract symptoms (nausea, vomiting) predominate24hN/V, retching, diarrhea, abdominal pain, prostration.Staphylococcus aureus and its enterotoxinsLower GI tract symptoms (abdominal cramps, diarrhea) predominatet18-36hAbdominal cramps, diarrhea, vomiting, fever, chills, malaise,nausea, headache, possible. Sometimes bloody or mucoid diarrhea.Salmonella species (including S. arizonae), Shigella,enteropathogenic Escherichia coli, other Enterobacteriacae,Neurological symptoms (visual disturbances, vertigo, tingling, paralysis)12-36hVertigo, double or blurred vision, loss of reflex to light, difficulty inswallowing. speaking, and breathingClostridium botulinum and its neurotoxinsAllergic symptoms (facial flushing, itching) occur1hNumbness around mouth, tingling sensation, flushing, dizziness,headache, nausea.Monosodium glutamateGeneralized infection symptoms (fever, chills, malaise, prostration, aches, swollen lymph nodes) occur9dayGastroenteritis, fever, edema about eyes.Trichinella spiralisJanuary 1992
Measuring Disease (Frequency)“ when you can measure what you arespeaking about, and express it innumbers, you know something about it ”Lord Kelvin
Why Numbers CountNYT, 14 August, 2005
Rationumerator and denominator are separateNumeratorDenominator1:12:1Odds: # chances for vs. # chancesagainst
Proportionnumerator is included in the denominator½ 0.50 50%probability or risk: fraction (0è 1) of # chancesfor over total # chances
Odds è ProbabilityOdds Probability / 1 – ProbabilityProbability Odds / 1 Oddse.g. 4 marbles: 1 blue, 3 redProbability ¼ 0.25Odds 1:3 0.333Probability Odds / 1 Odds 0.333 / 1.333 0.25Odds Probability / 1 – Probability 0.25 /0.75 0.33
Raten a measure of change perunit of another quantity(time)n In epidemiology, oftenmeasure people (ill ordead) per year N.B. many numbers calledrates are actuallyproportions e.g. infantmortalityMiles (first unit) perhour (second unit)
Relative RatesCompare one rate to anothern Often compare the experience of onegroup of people with a particular exposurewith that of a group that lacks thatexposuren E.g. # Lung CA deaths per year insmokers vs. non-smokersn
How do epidemiologists measuretime?n Person Years14 Persons7 (½) 7 10.5 PersonYears
Difference between Rates andRisks100 persons alive at beginning of yearn 40 die over the course of the yearn Risk (proportion) 40/100 0.40n How many person years?n 60n (½) 40 80 person yearsRate 40/80 .50Pay attention to units of measurement
Incidence and Prevalence1. Prevalence - measure all current casesof diseasen 2. Incidence -measures the rapidity withwhich a disease occurs or the frequency ofaddition of new casesn
Incidence – Prevalence BiasTIME ON AFDC1-2YRS3-7YRS 7 YRSPERCENT WHO HAVE 30%EVER RECEIVEDAFDC40%30%PERCENT RECEIVING 7%AFDC ATPARTICULAR TIME28%65%
Incidence Rate and CumulativeIncidencen Incidence Rate - “measure of theinstantaneous force of disease”n Cumulative Incidence – proportion whobecome ill (or die) during a specified timeinterval; it is a measure of average risk,dimensionless, from 0 to 1 (like a trueprobability)
Measures of Effect:n Absolute differences I(E)n – I(e)Relative ratios I(E)– I(e) / I(e) I(E) / I(e) – 1 I(E) / I(e)n Attributable Proportion – proportion of thediseased for whom exposure is acomponent cause I(E)– I(e) / I(E) RR – 1 / RR
Absolute vs. Relative EffectsRates per Lung 7169.541.7125.13Measure of Effect Driven by Aim ofResearch (Etiology or Public Health)
Standardized Rates: A way tocompare two populationsCountry A: (population 7,496,000; deaths 73,555) Crude death rate 7,496,000 / 73,555 x1000 9.8 per 1000Country B: (population 1,075,000; deaths 7,871) Crude death rate 1,075,000 / 7,871 x 1000 7.3 per 1000Which is the healthier country?Country A Sweden Country B Panama
Leveling the FieldThe standardized rate is a weightedaverage of the category specific ratesn Weights taken from “standard” populationn 4steps: 1) calculate age-specific rates for eachpopulation 2) multiply those rates by age distributionstandard population 3) add the total deaths 4) divide by population of the standard
The Health of Nations:Sweden vs PanamaYEARLY MORTALITY PER 1000AGESWEDENPANAMA0-291.15.330-593.65.2 6045.741.6
Choose standard agedistributionAGEWEIGHT0-293, 145, 00030-593, 057, 000 601, 294,000
Multiply age-specific mortalityrates* by the standardAGE SWEDENPANAMA0-291.1 x 3145000 3459.55.3 x 3145000 16668.530-593.6 x 3057000 11005.25.2 x 3057000 15896.4 6045.7 x 1294000 59135.841.6 x 1294000 53838.4*Rates per 1000 e.g. 1.1 0.0011
Compare Ratesn Add deaths divide by total (standard)populationn Sweden 73599.5 / 7, 496, 000 x 1000 9.8 per 1000n Panama 86403.3 / 7, 496, 000 x 1000 11.5 per 1000
A word about standardsn Choice may be arbitrary or hypothetical e.g.Sweden (note crude standard) US Standard Caution comparing standardized rates (samestandard?)n You ʻstandardizeʼ by the variable you useto categorize E.g.ʻage standardizedʼ rates
Direct vs. Indirect Standardizationn Direct: Ratesn Weighted by Standard PopulationIndirect PopulationsWeighted by Standard Rates Results in ʻExpectedʼ Rate of Occurrence Standardized Mortality Ratio (SMR) Observed Rate / Expected Rate X 100 Greater than 100 More than Expected Caution comparing SMRs that use differentstandards
Indirect StandardizationAge Group .4ExpectedCancerDeaths0.10.61.53.14.7
The Importance of Significancen n Much of biostatisticsis concerned with howlikely or unlikely it isthat our results aredue to chance aloneMuch of statisticalchance is based onsample size.
P Valuesn n n n n What is the probability that our results are due tochance?Presented as Decimal. The smaller the p value,the less likely the results were due to chance.E.g. p 0.1 means that given our null hypothesis(H0) we can expect our result to occur 1 time outof 10 (10%) by chance aloneP 0.05 the (arbitrary) cut off for statisticalsignificanceAgain, the smaller the p value, the greater thesignificance
Confidence Intervalsn n n n n Gives same information as P values i.e. whetherthe results are likely due to chanceGives the information using a relevant metricTells us something about how important theresults areForm: Point Estimate Critical Value x StandardError e.g. z (95% CI x, y)Caution: CI includes zero (absolute effects) orone (relative effects)
Significant. But important?Treatment prolongs life. (p 0.0001)n Average increased life expectancy 3 days(95% CI 2.5, 4.5)n Cost? SideEffects Compared to What? (no treatment, alternativetreatments)n Average increased life expectancy 3 days(95% CI -2.5, 6.5)
More fun with Confidence Intervalsn RR 2.5 (95% CI 1.5, 3.5) Ourresult was 2.5, but it could have, with95% statistical certainty (confidence) beenanywhere between 1.5 and 3.5n RR 2.5 (95% CI 0.5, 4.5) Oneis the loneliest number.
Chronic Disease Epidemiology:Eras and Paradigmsn n n n Sanitary Statistics and MiasmaGerm Theory and Infectious DiseaseTransition to Chronic Disease EpidemiologyStudy Designs that Arose from Chronic DiseaseEpidemiology
Sanitary Statistics and Miasma(18th-19th Centuries)n Arose from social concern Problemsn Foul emanations from ground or water Theoryn incorrect but approach workedWilliam Farr – statistics “Deathn (and solutions) societal and environmentalrate is a fact ”Edwin Chadwick poverty è disease
Germ Theory and InfectiousDisease (19th – 20th Centuries)Lab based, narrow – ʻsilver bulletʼn Downfall of population/environmental epin 1546– Hieronymous Fracastori 1849 - John Snow 1865 – Louis Pasteur 1882 – Robert Koch
Henle-Koch Postulatesn Epitome of infectious disease era 1)occur in every case 2) occur in no other disease 3) induce the disease when introduced into a “virgin”organismn n Viruses?Chronic Diseases?
Chronic Disease EpidemiologyWWII watershedn “epidemic transition”n “diseases of civilization”n “Black Box Epidemiologyn “web of causation”n Richard Doll and Sir Austin Bradford Hillsmoking and lung cancern
Study Designs that Arose fromChronic Disease Epidemiologyn n n n n 1. Experiments and Quasi-Experiments2. Cohort Studies3. Case-Control Studies4. Cross Sectional Field StudyMilestones: Dolland Hill – Lung CA 1951 – Cornfield – OR can approximate the RR 1959 – Mantel-Haenszel –multivariate to C-C 1973 – first text for 2x2 table by Joe FleissComplexValid
The Four-Fold TableExposedNotExposedDiseaseNo B(Exposed,notDiseased)D(NotExposed, NoDisease)
What is Epidemiology? ! The study of the distribution and determinants of disease in human populations. ! Study " Methods are intended to be scientific (basic science of public health) " "Epidemiology is reasoned argument." Distribution " Descriptive Epi - person, place, time " Look for patterns among different groups .
Introduction to Epidemiology Epidemiology yIs the process to study the distribution and determinants of disease frequency yIs a discipline which approaches problems systematically and quantitatively yIs the basic science of public health The Public Health Cycle Measure/Evaluate Epidemiology Analyze Epidemiology Communicate Intervene Epidemiology
Introduction to Epidemiology and Genetic Epidemiology. Major goals in Epidemiology To obtain an unbiased & precise estimate of the true effect of an exposure or intervention on outcome in the population at risk To use this knowledge to prevent and treat disease.
Key words Epidemiology: , Familial aggregation, Genetic dominance, Genetic epidemi ology, Heritability, Popperian philosophy, Sampling, Shared environment, Twins. INTRODUCTION What is genetic epidemiology? Epidemiology has been defined as the "study of the distribution and determinants of health-related states and events in populations" [32].
Introduction to Genetic Epidemiology Different faces of genetic epidemiology K Van Steen 2 DIFFERENT FACES OF GENETIC EPIDEMIOLOGY 1 Basic epidemiology . Clayton D. Introduction to genetics (course slides Bristol 2003) Bon
Health Professionals FOURTH EDITION Now in its fourth edition, Essential Epidemiology is an engaging and accessible introduction to the foundations of epidemiology. This text introduces the core concepts and shows the essential role of epidemiology in public health and medicine across a broad range of
This presentation provides an introduction to epidemiology activities during a foreign animal disease (FAD) outbreak. It defines disease characteristics and occurrence as it applies to epidemiology. An overview of measuring disease in a population based on understanding collected data is discussed. S l i d e 3
about evidence-based practice [2] Doing evidence-based practice means doing what the research evidence tells you works. No. Research evidence is just one of four sources of evidence. Evidence-based practice is about practice not research. Evidence doesn't speak for itself or do anything. New exciting single 'breakthrough' studies
equine medicine b. Food animal or large animal medicine c. Exotic animal medicine d. Marine animal medicine (mammal and fish) e. Poultry medicine f. Wildlife medicine and aquaculture medicine 2. Discuss with your counselor the roles a veterinarian plays in the following: a. Public health medicine and zoonotic disease surveillance and control b .
