Session 1: Introduction

Beth Potter
Epidemiology I, Fall 2011 September 8, 2011

Acknowledgements:

Julian Little
Nick Birkett

Ian McDowell

Thursdays, 1pm-4pm Julian Little (jlittle@uottawa.ca) Beth Potter (bpotter@uottawa.ca) Denise Landry (dland029@uottawa.ca)

Office hours: by appointment

https://maestro.uottawa.ca

https://maestro.uottawa.ca

https://maestro.uottawa.ca

https://maestro.uottawa.ca

https://maestro.uottawa.ca

Course overview
13 sessions

Some didactic teaching in the first two hours of each session - but please read all material in advance of session and contribute actively to discussion Critical appraisal of a discussion paper in the last hour of each session led by instructors for sessions 2 and 3, then led by students for remaining sessions On-line discussion forum (lightly moderated)

Course schedule
Session 1 2 3 4 5 6 Date September 8 September 15 September 22 September 29 October 6 October 13 Topic Introduction Measures of disease frequency Overview of primary study designs Comparing disease frequencies Overview of concepts of causation and association Infectious disease epidemiology and outbreak investigation

Course schedule
Session 7 Date October 20 Topic Diagnostic test evaluation, screening

8
9 10 11 12

October 27
November 3 November 10 November 17 November 24

Selection bias, confounding

Measurement error and information bias Cohort studies 1 Cohort studies 2 Case-control studies 1

13
EXAM

December 1
December 8

Case-control studies 2, Review

In-class final exam location TBA - Likely to be open book

To provide a grounding in the basic concepts and methods of epidemiology

to understand epidemiological investigation, especially in the area of disease etiology, including genetic factors to be able to define and use main measures of mortality, morbidity and comparison between groups validity avoiding bias controlling confounding detection of effect modification critical appraisal causal inference

Course overview
We will follow outline of text by Ann Aschengrau and George Seage, with some re-ordering No single book covers all of material, so additional core readings and suggested readings

Epidemiology journals
American Journal of Epidemiology Annals of Epidemiology Cancer Epidemiology, Biomarkers and Prevention Community Dentistry and Oral Epidemiology Emerging Themes in Epidemiology Epidemiology Epidemiology & Infection European Journal of Epidemiology Genetic Epidemiology International Journal of Epidemiology Journal of Clinical Epidemiology Journal of Epidemiology and Community Health Journal of Exposure Analysis and Environmental Epidemiology Journal of Public Health & Epidemiology Paediatric and Perinatal Epidemiology Social Psychiatric and Psychiatric Epidemiology Spatial Epidemiology Journal

Evaluation
Three assignments on specific concepts: collectively account for 60% Group leadership in discussion of a journal article: 10% Final examination (December 8): 30%

Towards end of course

PLEASE complete evaluations of the teaching provided

Assignments: further details

Assignment 1 (due: September 29) Assignment 2 (due: October 27) Assignment 3 (due: November 24) 10% 25% 25%

Each assignment will examine primarily material covered in sessions since the previous assignment. Assignment questions will be posted on the website one week before the deadline. Please submit a hard copy of your completed assignment in class, or send it by email to Denise Landry (please do not submit assignments via the course website).

Discussion papers: further details

Please form groups of 3-5 students. A contact person should email Denise by Sept 15 with names and email addresses for group. Denise will assign each group to a discussion session. When it is your groups turn to lead, please develop a set of discussion questions based on the journal article (pre-selected article listed in syllabus) and send these questions to Denise by the Monday before your session. The discussion questions will be uploaded to the website. All students are expected to review questions before every session.

During class, group will lead discussion of the article: ~45 min.
Everyone in the group will receive the same grade (worth 10%). Our expectations will evolve over the course of the semester.

Overview and Introduction

Definitions and classifications:
Epidemiology Health Disease

Historical roots of epidemiology The future of epidemiology: challenges and priorities Research ethics

What is epidemiology?
the study of the distribution and determinants of disease frequency in human populations, and the application of this study to control of health problems. (Aschengrau & Seage)

What is epidemiology?
the study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to control of health problems. (Last)

Uses of epidemiology
Studying the natural course of disease from onset to resolution Determining the extent of disease in a population Identifying patterns and trends in disease occurrence Identifying the causes of disease Evaluating the effectiveness of measures that prevent and treat disease
(Aschengrau)

Traditional Epidemiology Questions

Who gets disease X?
Why did someone get disease X? What is going to happen to someone who has disease X?

What can we do to prevent someone getting disease X?

What can we do to help someone with disease X? Why are more (or fewer) people getting disease X now than before? Why do people living in Y get more (or less) of disease X than people living in Z?

Modern Epidemiology Questions

How can we help someone be healthier?
Why did this person get ill while that person didnt when they both smoked, etc.? What is the role of government policies on health? What is the role of research in directing policy? How can we improve the health care system? When is a community healthy? How can we empower people to make informed decisions about their health? How do we make sense of conflicting research results?

Defining health
Medical definitions:
Health is the absence of disease Health is "A state characterized by anatomic, physiologic and psychological integrity; ability to perform personally valued family, work and community roles; ability to deal with physical, biologic, psychological and social stress..."
(Stokes J. J Community Health 1982;8:33-41)

Defining health (2)

Holistic definition:
A state of complete physical, mental and social well-being and not merely the absence of disease or infirmity"
(WHO, 1948)

Defining health (3)

Wellness definition:
"The extent to which an individual or group is able to realize aspirations and satisfy needs, and to change or cope with the environment. Health is a resource for everyday life, not the objective of living; it is a positive concept, emphasizing social and personal resources, as well as physical capacities."
(Health promotion: a discussion document. Copenhagen, WHO, 1984)

Defining health (4)

Ecological definition:
A sustainable state of equilibrium or harmony between humans and their physical, biological, and social environments that enables them to coexist indefinitely. Population-level
(Last J. Dictionary of public health. Oxford, N.Y., 2007)

Defining health: clarifying disability

WHO, 1976:
Impairment Disability Handicap
(International Classification of Impairments, Disability, & Handicap: ICIDH)

WHO, 2001:
Impairment Activity Participation
(International Classification of Functioning: ICF)

Defining health: quality of life

Generally defined in terms of being able to function in desired social roles, even if you have a health problem; subjective perception of the patient

Defining health for populations

Health in the population: average of the health of individuals (e.g., how many had a heart attack last year?)
Health of the population: health of the population as a whole: is it a caring society? Are peoples rights respected? Does the system function well: do things get fixed on time? (relates to ecological definition)

Who is healthy? Who is ill?

Shah, 1998

The Iceberg of Disease

Clinically evident disease
Sub-clinical disease; often more common (some may be detectable by screening)
The iceberg idea has been turned into a pyramid when talking of injuries: a few injuries kill; more come to the ER; lots are very minor

(The iceberg metaphor proposed by John Last, 1963)

Clinical Course of a Disease (1)

Preclinical Phase

Clinical Phase

Biological onset of disease

Symptoms appear

Therapy begun Diagnosis

Outcomes (died; living with disease; deteriorated, cured, etc)

Clinical Course of a Disease (2) Pre- and post-disease stages

Etiological Phase
Social & Environmental Determinants Risk & Protective Factors Preclinical Phase Clinical Phase Postclinical Phase

Initial outcome
Biological onset of disease Symptoms

Therapy
Diagnosis

Longer-term outcome: Impact on family work; economic impact, etc.

Clinical Course of a Disease (3) Prevention stages

Etiological Phase
Social & Environmental Determinants Risk & Protective Factors Preclinical Phase Clinical Phase Postclinical Phase

Primordial prevention: (poverty) Alter societal structures & thereby underlying determinants

Primary prevention: (smoking cessation) Alter exposures that lead to disease

Secondary prevention: (screening) Detect pathological process at an earlier stage when treatment can be more effective

Tertiary prevention: Prevent relapses & further deterioration via follow-up care & rehabilitation

Who is healthy? Who is ill? (2)

Expanding scope of concept of disease:
The focus of prevention has always been on diseases. As the concept of disease is changing over time (with lowering thresholds for designation of disease)28 and risk factors are considered equivalent to disease, the boundaries between prevention and cure are becoming increasingly indistinct. Example of stages of heart failure: first two stages of disease defined as: (1) obesity; (2) at risk for heart failure (Starfield B et al., J Epidemiol Community Health, 2008; p.581) - In suggested readings

Who is healthy? Who is ill? (3)

Expanding scope of concept of disease :
Screening and the at-risk health status (Kenen, 1996)
e.g., genetic screening for disease susceptibility (healthy versus prediseased) genomic profiling (direct marketing: e.g., 23andMe)

Who is healthy? Who is ill? (4)

Sodefining health and disease is not straightforward and is not static
This has implications for disease classification and for measuring health at the population level

Disease Classification
ICD, International Classification of Diseases
Developed from Farrs work: first version around 1900 Updated about every 10 years (changes impact interpretation of time trends) Current: ICD-10 (and ICD10-CA, Canadian enhancement)

Other Disease Classification Systems

Examples: Cancer: International Classification of Diseases for Oncology (ICD-O) Mental health: Diagnostic and Statistical Manual of Mental Disorders (DSM)

International Classification of Impairments, Disability, and Handicap (ICIDH); International Classification of Functioning (ICF)

Some key dates in epidemiology

400BC 1660s 1660s 1753 1774 1830s 1840s 1850s 1880 1900s 1946 1950s 1930-70 Hippocrates John Graunt (birth of vital statistics) Thomas Sydenham (Classification of fevers) James Lind (Studies on Scurvy) Jenner and Jesty (smallpox immunization) William Farr (concept of rates, population health) Ignaz Semmelweis (childbirth infections) John Snow (studies on cholera) Germ theory of Disease Mosquitoes and malaria Streptomycin RCT Smoking and health Tuskegee Syphilis study

Hippocrates (400 BC)

Died aged 97 Concerned with finding causes to prevent disease Emphasized the need for clear observation time, place, season, environmental circumstances Role of water, diet, physical activity Works include
The Aphorisms, summing up his observations and deductions Airs, Waters, and Places, which recognized a link between environment and disease

Some key dates in epidemiology

400BC 1660s 1660s 1753 1774 1830s 1840s 1850s 1880 1900s 1946 1950s 1930-70 Hippocrates John Graunt (birth of vital statistics) Thomas Sydenham (Classification of fevers) James Lind (Studies on Scurvy) Jenner and Jesty (smallpox immunization) William Farr (concept of rates, population health) Ignaz Semmelweis (childbirth infections) John Snow (studies on cholera) Germ theory of Disease Mosquitoes and malaria Streptomycin RCT Smoking and health Tuskegee Syphilis study

John Graunt, 1620-74

Natural and Political Observations Made upon the Bills of Mortality (1662) analysis of mortality rolls in London to create system to warn of onset and spread of bubonic plague in the city Never fully created, but resulted in first statisticallybased estimation of London population

John Graunt
Most greatly feared causes of death (e.g. starvation, leprosy) were uncommon Common causes: old age, consumption, smallpox, plague, diseases of teeth, worms Autumn is most unhealthy season Distinguished between epidemic and endemic diseases

Some key dates in epidemiology

400BC 1660s 1660s 1753 1774 1830s 1840s 1850s 1880 1900s 1946 1950s 1930-70 Hippocrates John Graunt (birth of vital statistics) Thomas Sydenham (Classification of fevers) James Lind (Studies on Scurvy) Jenner and Jesty (smallpox immunization) William Farr (concept of rates, population health) Ignaz Semmelweis (childbirth infections) John Snow (studies on cholera) Germ theory of Disease Mosquitoes and malaria Streptomycin RCT Smoking and health Tuskegee Syphilis study

William Farr
Concepts of population denominators and rates Developed classification system for causes of death

Living in densely populated areas gives increased mortality Living at lower elevations associated with higher cholera mortality than higher elevations Mortality decreased following improvements to sanitation Widowers had higher marriage rate than bachelors

Some key dates in epidemiology

400BC 1660s 1660s 1753 1774 1830s 1840s 1850s 1880 1900s 1946 1950s 1930-70 Hippocrates John Graunt (birth of vital statistics) Thomas Sydenham (Classification of fevers) James Lind (Studies on Scurvy) Jenner and Jesty (smallpox immunization) William Farr (concept of rates, population health) Ignaz Semmelweis (childbirth infections) John Snow (studies on cholera) Germ theory of Disease Mosquitoes and malaria Streptomycin RCT Smoking and health Tuskegee Syphilis study

John Snow
Investigated cholera outbreaks in London: focused on potential role of polluted water
Broad Street outbreak: Snows analysis of geographic distribution and drinking habits of those who died from cholera supported hypothesis of polluted water from the Broad Street pump; the pump handle was removed (although the outbreak was already waning) Analysis of cholera mortality in association with water supply companies: compared death rates in populations supplied by two different companies; and then compiled and analysed household-level data on water supply from districts served by both companies

Some key dates in epidemiology

400BC 1660s 1660s 1753 1774 1830s 1840s 1850s 1880 1900s 1946 1950s 1930-70 Hippocrates John Graunt (birth of vital statistics) Thomas Sydenham (Classification of fevers) James Lind (Studies on Scurvy) Jenner and Jesty (smallpox immunization) William Farr (concept of rates, population health) Ignaz Semmelweis (childbirth infections) John Snow (studies on cholera) Germ theory of Disease Mosquitoes and malaria Streptomycin RCT Smoking and health Tuskegee Syphilis study

1946 - Streptomycin & TB

First RCT
Designed by Sir Austin Bradford Hill

Four key features:

1.Random allocation to two treatment groups 2.Clear eligibility criteria 3.Precise endpoints (death) and blinding of MDs reading x-rays (treatment arm unknown) 4.Addressed ethical issues. Introduced concept that not doing RCT would be unethical
Doll R. Int. J. Epidemiol. (2003) 32 (6): 929-931

Some key dates in epidemiology

400BC 1660s 1660s 1753 1774 1830s 1840s 1850s 1880 1900s 1946 1950s 1930-70 Hippocrates John Graunt (birth of vital statistics) Thomas Sydenham (Classification of fevers) James Lind (Studies on Scurvy) Jenner and Jesty (smallpox immunization) William Farr (concept of rates, population health) Ignaz Semmelweis (childbirth infections) John Snow (studies on cholera) Germ theory of Disease Mosquitoes and malaria Streptomycin RCT Smoking and health Tuskegee Syphilis study

Smoking & lung cancer

Doll & Hill (1950) Marked lung cancer mortality post WW1 Unclear why:
Better diagnosis Environmental cause

Doll and Hills work moved Epi from infectious diseases to chronic diseases

Smoking & lung cancer

One of first uses of case-control design 709 cases and 709 controls
Used personal interview to recall smoking and other behaviours 99.7% of male cases smoked 95.8% of male controls smoked OR=16

British Doctors study

Cohort 20 years of follow-up

Framingham study
Prototypical cohort study Respondents from random sample of 2/3 of adults, 30-62 years, residing in Framingham, Mass, in 1948 Followed up every two years for 50 years
Interview Physical exams Various lab tests

Offspring now being followed Shows power of long-term follow-up with physical measures.

Summary
Epidemiology has a long history but most active in past 50 years Many successes
smoking and lung cancer infectious disease outbreak control

Must be careful that bias doesnt affect judgment

The future of epidemiology: challenges and priorities

Challenges
Only weak associations remain to be discovered
Greater susceptibility to false positive findings (chance, confounding, bias) Boffeta, 2008 Non-replication

Poor assessment of exposure

Challenges
Only weak associations remain to be discovered
Greater susceptibility to false positive findings (chance, confounding, bias) Boffeta, 2008 Non-replication

Poor assessment of exposure

Lung cancer risk factors

RR Smoking 15-30 PAR 90%

Radon

1.1 (per 100Bqm-3)

1% (alone) 5.5% (jointly with tobacco)

Family history (after controlling for smoking)

2.5

Thun et al., Oncogene 2002; Boffetta & Nyberg, BMB 2003; Amos et al., Recent Results in Cancer Research 1999;

Boffetta et al., 2008

Lawlor et al., 2004

June 22, 2000

Randomized Trials or Observational Tribulations? (Pocock & Elbourne)

A Comparison of Observational Studies and Randomized, Controlled Trials (Benson & Hartz)
Randomized, Controlled Trials, Observational Studies, and the Hierarchy of Research Designs (Concato, Shah & Horwitz) 22 May, 2004

Beyond randomised versus observational studies (Concato & Horwitz) Those confounded vitamins: what can we learn from the differences between observational versus randomised trial evidence? (Lawlor et al.) When are observational studies as credible as randomised trials? (Vandenbroucke)

The scandal of poor epidemiological research Reporting guidelines are needed for observational epidemiology (von Elm E & Egger M BMJ. 2004; 329:868-9.)

http://www.strobe-statement.org/

Solutions / Priorities
Improved methodology and reporting of observational studies (STROBE)
Epistemological modesty (Boffetta et al, 2008)

Continued development of theory and methods to allow for rigorous study and focus on importance of health of populations (Davey Smith, 2001; Last, 2010)

Ethics policies and guidelines

Ethical issues for research involving human subjects came to the forefront in the 1970s in North America, following concerns about violations of research subjects rights in several prominent situations, e.g.:
Biomedical experiments by German scientists in the Nazi era Tuskegee syphilis study in the US

Social science studies (prison experiments, Milgrams electric shock study)

Policies in Canada/Ontario/Ottawa
Tri-Council Policy Statement: Ethical conduct for research involving humans (original 1998; latest major revision: 2010) From national research funding bodies in Canada: Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada http://www.pre.ethics.gc.ca (tutorial available on site) Ontario legislation (Freedom of Information & Protection of Privacy Act, FIPPA; Personal Health Information Protection Act, PHIPA) Research Ethics Boards (U Ottawa, Ottawa Hospital, CHEO): policies comply with tri-council policy and with relevant legislation

Tri-Council Policy Statement (TCPS)

Core principles: Respect for human dignity as underlying value:
requires that research involving humans be conducted in a manner that is sensitive to the inherent worth of all human beings and the respect and consideration that they are due. In this Policy, respect for human dignity is expressed through three core principles Respect for Persons, Concern for Welfare, and Justice.

Respect for persons: emphasis on respect for autonomy (e.g. informed consent) and protection of those with diminished autonomy Concern for welfare: focus on benefits and risks of research for individuals and groups Justice: emphasis on fairness, equitable distribution of benefits and burdens, special considerations for vulnerable people and groups

REB review
Factor in time for preparation of the REB application and for the review itself Faculty of Medicine projects are reviewed by the OHREB (http://www.ohri.ca/ohreb/) (or CHEO REB if based there) Some projects (e.g., many self-report surveys) can be considered minimal risk and thus may undergo expedited review: check with REB if uncertain With expedited review, can submit to OHREB anytime (do not have to consider deadlines)

REB review contd

Ethical practice includes using sound scientific methods so the REB will review a project in terms of the study design, etc.
The REB will consider the particular circumstances of a study when making judgments e.g., the purpose of the research, the nature of the population, the kind of information that will be collected

REB review contd

Additional tips: Pilot tests must be reviewed by REB in addition to full protocols (but no bilingual requirement for pilot studies) Research vs quality assurance: if plan to disclose findings outside organization, project is considered to be research and requires REB approval If uncertain about whether something requires REB approval, check with REB (err on side of caution) Bilingual requirement (both OHREB and CHEO REB): all studies must offer participation in English and French unless strong justification can be provided otherwise