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Summer Learning Institute in Interdisciplinary HIV Research MaRS Centre, Toronto, July 13-17, 2009
Population Health and Cohort Research
Robert Hogg, PhD
Simon Fraser University, Faculty of Health SciencesBC Centre for Excellence in HIV/AIDS
OverviewObjectiveReadingsPopulation HealthEpidemiologyStudy Design
Descriptive, analytical, experimental and observational
Measures of Association
ObjectiveTo review the basic concepts of population health,
epidemiology and study design
ReadingsNational Center for Chronic Disease Prevention and
Health Promotion, US Centres for Disease Control and Prevention, EXCITE, Epidemiology in the Classroom. An introduction to epidemiology.www.cdc.gov/excite/classroom/intro_epi.htm)
Definition Population health is an approach to health that aims
to improve the health of the entire population and to reduce health inequities among population groups. In order to reach these objectives, it looks at and acts upon the broad range of factors and conditions that have a strong influence on our health.
- Public Health Agency of Canada
Canada versus United StatesLife expectancy at birth (years, both sexes)
Canada versus United StatesLife expectancy at birth (years, both sexes)
Explanation?Why does Canada have a higher life
expectancy than the United States?
Variation in life expectancy by US county
Income
It took the poorest fifth of urban Canadians until the mid-1990s to reach the life expectancy experienced by the richest fifth 25 years earlier.
Key elements of a Population Health approach
Address the determinants of health: The range of individual and collective factors and conditions (and their interactions) that have been shown to correlate with health status.
Determinants of healthIncome and Social Status Social Support Networks Education Employment/Working Conditions Social Environments Physical Environments Personal Health Practices and Coping Skills Healthy Child Development Biology and Genetic Endowment Health Services Gender Culture
Population and those affectedPopulation Affected Proportion
affected
Male 814 655 .805
Female 440 118 .268
Married 350 161 .460
Single 845 595 .704
Anglo Saxon 564 340 .602
Non-Anglo Saxon
634 416 .656
Tier one 324 126 .389
Tier two 271 153 .565
Tier three 712 526 .739
Total population = 1,307, total affected = 805, and proportion affected = .620
Create a theoryClass time 5 minutesDescribe the data (best way you can)Note variations between groupsWhy did they occur?What is the event?
The TitanicWhat is the event?
Sinking of the TitanicWhy did it occur?
Ship hit an ice berg and there were not enough life boats
Variations in those affected• Men more than women
Women and children were generally put on life boats first.
• Variation by class
First class had better access to life boats
What is epidemiology? “The study of epidemics”
Concise Oxford Dictionary, 1964
“The study of the distribution and determinants of disease in humans”MacMahon and Pugh, 1970
“The science of the occurrence of illness”Miettinen, 1978
“The study of the distribution and determinants of health related states and events in specified populations and the application of this study to control the health problems”John Last, Dictionary of Epidemiology, 2001
Simply: Who gets disease? Why do they get it? And what can we do about it?
What is epidemiology? Considered a cornerstone methodology of public health research.
Highly regarding in evidence-based medicine for determining optimal treatment approaches.
Each disease condition has its own “culture” of application of epidemiological tools, but all rest on the same foundation of epidemiological principles and methods.
Examples: Infectious disease epidemiology Environmental epidemiology Chronic disease epidemiology Injury epidemiology Molecular epidemiology Genetic epidemiology
Purposes of epidemiology Determine the extent of disease in a population.
e.g., What is the prevalence of Hepatitis C among injection drug users in the Downtown Eastside of Vancouver?
Assess risks of exposure on developing disease. e.g., What is the risk of exposure to Baby Tylenol in infancy on
the likelihood of developing childhood asthma?
Identify the cause of new syndromes (e.g., HIV causes AIDS) e.g., What was the cause of the unusually high incidence of
Kaposi’s sarcoma among homosexual men in San Francisco in the early 1980s?
Study the natural history and prognosis of disease e.g., In the absence of chemotherapy, how long do people
survive after a diagnosis of lung cancer?
Purposes of epidemiology Determine whether treatment “x” is effective
e.g., Is the herbal remedy Echinacea an effective treatment against the common cold?
Identifying practical disease prevention strategies and determining whether they are effective e.g., What is the effect of municipal smoking bylaws on the
prevalence of smoking and incidence of lung cancer?
Identifying health service use needs and trends e.g., What is the prevalence and incidence of HIV/AIDS in
British Columbia and what proportion of infected individuals will require antiretroviral therapy by 2015?
Descriptive studiesResearch that describes the occurrence of disease
and/or exposureRemember: Person, place and timeAsk: Who?, what?, when?, where?Example: National Population Health Survey
PersonCharacteristics of the individuals affected by the
disease. May vary by disease.age, gender, marital status, race/ethnicity, health
status, religion, occupation, socio-economic status, sexual orientation, travel history, education, health status, genetic predisposition, etc.
PlaceWhere did the events take place? Standard place characteristics include:
Location where the disease was acquired (e.g. country, province, city, postal code)
Description of the location (e.g. type housing, crowded living conditions, proximity to animals)
Surrounding characteristics of the environment (e.g industrial areas, farms)
TimeWhen did the events occur?When did symptoms first appearDate of event (day, week, month, year), clock time of
event, day versus night, seasonal variation, annual variation, etc.
Descriptive studiesCase reports / case series Detailed descriptions usually by a doctor or group of
doctors identifying diseases that are unusual/interesting; may be related to unusual exposure
Ecological studiesCompare the prevalence of exposures and disease
occurrence in populationsNote: observations collected/displayed at the group
level may not apply at the individual level
South AfricaWood et al. The Lancet, 2000
Antiretroviral use has a substantial impact on life expectancy
Analytic studiesTo evaluate the association between an exposure or
characteristic and the development of a particular diseaseThree essential characteristics that are examined to study
causes of disease: HostAgentEnvironment
Host
EnvironmentAgent
Epidemiologic Homeostasis
Intrinsic traits that influence the risk of exposure, susceptibility once exposed, and the responses to causal factors.
Host
EnvironmentAgent
Epidemiologic Homeostasis
Biological, physical, or chemical factors that
are necessary for disease occurrence.
Host
EnvironmentAgent
Epidemiologic Homeostasis
Extrinsic Factors that determine the level of exposure, likelihood of exposure, and susceptibility to disease once exposed.
Host
EnvironmentAgent
Epidemiologic HomeostasisAgent, host, and environmental factors interact to determine the distribution of disease in human populations. These factors may to form a steady state (epidemiologic homeostasis) or may readjust to lead to the elimination of disease or epidemics, depending on whether factors favor the host or the agent
Host
EnvironmentAgent
Epidemiologic HomeostasisPaul Farmer: “First you cure the family of TB. Then you start changing the conditions that made them especially vulnerable to TB in the first place.” (p293)
TB
Haitian family
Haiti
Overview of Analytic Study DesignsStudy Design Temporal Nature Characterization of
Subjects at Enrollment
Cross-sectional study Point in Time (snapshot). Exposure and disease status collected at same time.
Case-control study Point in Time or may collect retrospective data.
Disease and non-diseased. Look retrospectively to collect info on exposure.
Cohort Follow subjects over time (prospectively or retrospectively).
Exposed and not exposed. Follow over time to determine disease status.
Clinical Trial Follow subjects over time (prospectively).
Similar disease status but randomly assigned an exposure. Followed over time to determine outcome.
Epidemiological Study Designs
Experimental studies – researcher tries to change something and measure the effect on disease outcome – clinical trials, preventive trials
Observational studies – researcher does not intervene in any way
Randomized control trial
The North American Opiate Medication Initiative (NAOMI) A clinical trial that examined whether
medically prescribed heroin could successfully attract and retain street-heroin users who have not benefited from previous repeated attempts at methadone maintenance and abstinence programs
The trial showed remarkable retention rates and significant improvements in illicit heroin use, illegal activity and health for participants receiving heroin, as well as those assigned to optimized methadone maintenance.
Create a trialWhat is the outcome?What is the exposure?Who is at risk?What is the intervention/ treatment?What are the advantages and disadvantages?
Observational studiesMeasurement of disease occurrence or health
outcomeComparing patterns of exposure and disease
outcomesIdentifying risk factors associated with
health/disease
Observational studiesMeasurement of disease occurrence or health
outcomeComparing patterns of exposure and disease
outcomesIdentifying risk factors associated with
health/disease
Can be either descriptive or analytical
Cohort Studies• Cohort: any designated group or persons who are
followed or traced over a period of time, as in a prospective cohort study
• Cohort studies: compare rates of occurrence of disease or death in people with or without a particular exposure
CIHR Team in HIV treatment outcomes: The Canadian Observational Cohort (CANOC) Collaboration This emerging team collaboration is an essential first step to
evaluating the impact of antiretroviral care on the health and well being of persons infected with HIV/AIDS across various regions of Canada.
Participating cohorts
•BC Centre for Excellence in HIV/AIDS
•Clinique Medicale L’Actuel
•Canadian Co-infection Cohort Study
•EARTH
•Maple Leaf Medical Clinic
•Montreal Chest Institute IDS
•Ontario HIV Treatment Network
•Toronto General Hospital
•University of Ottawa
Inclusion criteriaCurrent criteria for inclusion:
First HAART therapy date ≥ Jan 1st, 2000Must have a baseline CD4 and baseline viral
load Baselines must be from within the six months
prior to therapy
Current ProjectClinical and socio-demographic characteristics associated with time to virological suppression among individuals on HAART in Canada.
Lead Investigator: Dr. Curtis Cooper
Background: What constitutes an adequate immunological response has been described variously as increases in CD4 cell counts of > 25 cells, 50 cells, or 100 cells from baseline or absolute CD4 cell count > 200 cells at 6 months after initiating therapy. Patients who achieve virologic suppression but do not achieve adequate immunologic responses have been shown to be at increased risk for disease progression. However, some of these patients may eventually reach immunological targets later in the course of their treatment.
Objective(s): To determine the length of time to virological suppression among individuals in the CANOC collaboration.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 12 24 36 48 60 72 84 96
Follow Up Time (Months)
PI single
NNRTI
PI boosted
Probability of not Achieving Viral Suppression
Initial Drug Regimen
Log-rank test: p-value < 0.0001
PI single
NNRTI
PI boosted
Month 0 12 24 36 48 60 72 84 96
PI single n=281 103 65 43 26 18 9 5 0
NNRTIn=110
3 260 159 102 72 34 15 0 0
PI boosted
n=1013 237 84 39 19 5 0 0 0
Viral load suppressionby initial HAART regimen
Measures of AssociationMeasures of association cannot tell you
whether an exposure causes a disease.Just how strongly the two are associated.
Measures of Association: 2x2 tableDisease Status
Diseased Not diseased
Total
Exposure Status
Exposed a b a+b
Not exposed
c d c+d
Total a+c b+d a+b+c+d
Measures of Association: 2x2 table
Cohort Study or Clinical Trial:Relative Risk (RR) = Proportion of people with
disease among the exposed / Proportion of people with the disease among the unexposed
RR = [a/(a+b)]/[c/(c+d)]
Explanations for Association
Real Cause and EffectChanceBiasConfoundingReverse Causation
Bradford-Hill criteria of causation (1965) Temporality: The effect has to occur after the cause.
Strength of Association: The stronger the association, the more likely it is that the relationship between an exposure and a disease is causal. However, a small association does not mean that there is not a causal effect.
Consistency: Consistent findings observed by different studies in different places with different populations strengthens the likelihood of a causal relationship.
Dose-Response Relationship: Greater exposure should generally lead to greater incidence of disease. However, in some cases, the mere presence of the factor can trigger the effect. In other cases, an inverse proportion is observed: greater exposure leads to lower incidence.
Biological Plausibility: A plausible biological mechanism between exposure and disease is helpful (but Hill noted that knowledge of the mechanism is limited by current knowledge).
Specificity: Causation is likely if an exposure influences a very specific outcome or population, with no other likely explanation. The more specific an association between a factor and an effect is, the bigger the probability of a causal relationship.
Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an effect. However, Hill noted that "... lack of such [laboratory] evidence cannot nullify the epidemiological associations" .
Experiment: Causation is more likely if evidence is based on randomised experiments
Analogy: Causation may be more likely if it has already been shown in an analogous exposure and outcome.
Create a studyWhat is the outcome?What is the exposure?Is it descriptive or analyticalIs it observational or experimentalWhat are the advantages and disadvantages?
5 minutes to design
CANOC Trainee awards• Application deadline: August 31st, 2009• One year funding up to $20,000• According to CIHR scales• Only those with scores above 3.5 will be considered• Visit:
http://www.ohtn.on.ca/Pages/Funding/Salary-Awards.aspx