Epidemiological Studies

Dr. Md. Rizwanul Karim [ Shameem ] Asst. Prof.Department of epidemiology NIPSOM

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.

Specific Objects of Epidemiology

1. To identify the etiology or the cause of a disease and the risk factors 2. To determine the extent of disease found in the community 3. To study the natural history and the prognosis of disease

4. To evaluate new preventive and therapeutic measures and new modes of health care delivery

5. To provide the foundation for developing public policy and regulatory decisions relating to environmental problems

Epidemiological Studies aimed at

Epidemiological studies or investigations are aimed to: Explain the disease pattern and describe the natural history of a disease;

Understand the causal mechanism of a disease;

Evaluate intervention measures; Plan for further course of action for a health problem

Most important facets of study design

Whether observational or experimental

Directionality of the study (cross-sectional, case control, cohort)

Timing of data collection (concurrent, historical, or mixed) The sample selection criteria (fixedexposure, fixed-disease, non-fixed)

Epidemiology Study Types

Broadly, epidemiological studies may be classified into two types, depending upon the type of exposure. Experimental studies Where the researcher controls the exposure. Observational (Non-Experimental) Studies Where the researcher has no-control over the exposure.

Types of Epidemiological Study

Type of Study Observational Studies Descriptive Studies Analytical Studies Ecological Cross-sectional Case-Control Cohort Experimental studies Randomized controlled Field Trials Community Trials Alternative name Unit of Study

Correlational Prevalence Case-reference Follow-up Intervention studies Clinical trials

Populations Individuals Individuals Individuals

Patients Healthy people Community intervention Communities studies

Observational Studies
non-experimental

observational because there is no individual intervention

treatment and exposures occur in a noncontrolled environment individuals can be observed prospectively, retrospectively, or currently

Experimental Studies
treatment and exposures occur in a controlled environment planned research designs clinical trials are the most well known experimental design. Clinical trials use randomly assigned data.

Community trials use nonrandom data

Types of primary studies

Descriptive studies
describe occurrence of outcome

Analytic studies
describe association between exposure and outcome

Descriptive versus Analytical

Descriptive Epidemiology:

Generates idea(s) or hypothesis for associations between risk factor and illness Analytical Epidemiology
Uses a comparison group to establish an association between risk factors and illness in the two groups.

Things to remember
To prevent and control disease In a coordinated plan, look to identify hypotheses on what is related to disease and may be causing it formally test these hypotheses Study designs direct how the investigation is conducted

Basic Question in Analytic Epidemiology

Are exposure and disease linked?

Exposure

Disease

Basic element in analytic study

Presence of comparative group

Case-series Individuals Descriptive Populations Cross-sectional Co relational

Epidemiological studies Case-control

Observational

Prospective Cohort

Analytical Intervention

Retrospective

Clinical Trials

Descriptive
Case report Case series Descriptive Epidemiology RCT

Analytic
Cohort study Case-Control study Case-Crossover study Cross-sectional study Before-After study

Ecologic study

Timeframe of Studies
Prospective Study - looks forward, looks to the future, examines future events, follows a condition, concern or disease into the future

time
Study begins here

Timeframe of Studies
Retrospective Study - to look back, looks back in time to study events that have already occurred

time
Study begins here

Observational Designs
Retrospective (Case-control)
E(-) Controls

Prospective (Cohort)

Today
Participants, Patients, Subjects

E(+)

No Expo.

E(-)

E(+)

Exposure

Cases

Controls E(+) E(-)

Retrospective Cohort

E(+)

E(-)

Cross-sectional

Time

Case

Control

Cases

Case

Control

Descriptive Studies
The essential features of descriptive studies are: To describe present or past characteristics of persons with a particular outcome or a particular exposure and / or to determine prevalence of an outcome or exposure. Only one group is studied. No comparison group is used.

 No conclusion can be made about the association between exposure and outcome. Information derived from such studies may suggest possible association which require further study using analytic study design They may be prospective or retrospective in time.

Descriptive Epidemiology
Cases Person
54 04 53 03 52 02 51 01 5 0 3 2 1
8 7 6 5 4 3 2 1

Time Place

54 04 53 03 52 02 51 01 5 0

Microbiology

Evaluate information

Virology

Pathogen?

Source?

Transmission?

Case Reports
Detailed presentation of a single case or handful of cases Generally report a new or unique finding
e.g. previous un-described disease

e.g. unexpected link between diseases

e.g. unexpected new therapeutic effect e.g. adverse events

Case Series
Experience of a group of patients with a similar diagnosis Assesses prevalent disease Cases may be identified from a single or multiple sources Generally report on new/unique condition

May be only realistic design for rare disorders

Case Series
Advantages
Useful for hypothesis generation Informative for very rare disease with few established risk factors

Characterizes averages for disorder

Disadvantages
Cannot study cause and effect relationships Cannot assess disease frequency

Ecologic Studies
Aggregates of individuals. Aggregates often defined by units: geographic region, school, health care facility. Does the overall occurrence disease in a population correlate with occurrence of the exposure.

No individual data

Ecologic Studies: Data collection

Exposure data and disease data are often collected at different times for different reasons. Environmental measures/ Global measures. Incidence and mortality data vs working in a factory. Ecologic Falacy is an important factor.

Ecologic Studies: Advantages

Hypothesis generating.

Low cost and not time consuming.

Limited data for individuals (environmental studies). Achieves substantial variation. If inferences are to be made about groups. Useful for social scientists as well as epidemiologists. Evaluation of new policies.

Ecologic Studies: Disadvantages

Ecological Fallacy. Inappropriate conclusions regarding relationships at the individual level based on ecological data/aggregate data. Inappropriate conclusions about causation. No causal conclusions can be drawn. Temporal ambiguity. Lack of adequate data Additional studies do and dont support ecological conclusions.

Case Report

One case of unusual injury finding Multiple cases of injury finding Population-based cases with denominator

Case Series

Descriptive Study

Cross sectional study

Cross-sectional studies
An observational design that surveys exposures and disease status at a single point in time

time Study only exists at this point in time

Cross-sectional Design
factor present No Disease

factor absent
Study population factor present

Disease
factor absent

time Study only exists at this point in time

Uses: Cross-sectional Studies

Often used to study conditions that are relatively frequent with long duration of expression (nonfatal, chronic conditions) It measures prevalence, not incidence of disease Example: community surveys Not suitable for studying rare or highly fatal diseases or a disease with short duration of expression

Features
Study at a point (cross-section) in time

Easy and economical

Useful for Investigation of exposure that are fixed characteristics e.g. ethnicity, bloodgroup. Sudden outbreaks - often most convenient 1st step into Investigation of cause.

 Regular C.S surveys (in several countries ) for determining extent of health related problems and socio- demographic characteristics. Not easy to assess reasons for associations.

More common types of research in medicine (health)

Approx. >1/3 of original articles in major medical journals.

Cross Sectional Studies

Advantages

Good design for hypothesis generation

Can estimate overall and specific disease prevalence and sometimes rates Can estimate exposure proportions in the population

Can study multiple exposures or multiple outcomes or diseases

Cross Sectional Studies

Advantages Relatively easy, quick and inexpensive No issue of subjecting any animals or producers to particular treatments Best suited to studying permanent factors (breed, sex, blood-type)

Often good first step for new study issue

Cross Sectional Studies Disadvantages

Impractical for rare diseases

Not a useful type of study for establishing causal relationships Confounding is difficult to control No control over sample size for each exposure by disease subclass

Cross Sectional Studies

Disadvantages

Problems with temporal sequence of data

hard to decide when disease was actually acquired disease may cure the exposure miss diseases still in latent period recall of previous exposure may be faulty

Application: Cross Sectional Study

Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. Cross-sectional studies are used to estimate the prevalence of diseases or the prevalence of exposure to risk factors or both.

Application: Cross Sectional Study

Other applications of cross sectional surveys lie in planning health care. For example, an occupational physician planning a coronary prevention programme might wish to know the prevalence of different risk factors in the workforce under his care so that he could tailor his intervention accordingly.

Cross Sectional Study

A cross sectional study is fast and can study a large number of patients at little cost or effort. Also, you don't have to worry about patients dropping out during the course of the study. This study is efficient at identifying association, but may have trouble deciding cause and effect.

Steps: Cross Sectional Study

The following steps have to be completed to perform the study: Define target population: Usually defined by age, sex and place of residence. Take sample: This requires a population register as a sampling frame usually the electoral register or the general practice list maintained by the Family Health Service Authority (FHSA).

Steps:

Cross Sectional Study

Devise case-definition: define fixed criteria by which the condition is identified. Complete case-ascertainment: apply the case-definition to the sample, obtaining a high response rate. Analysis: Estimate the prevalence rate.

Case control study

Case-Control Studies
an observational design comparing exposures in disease cases vs. healthy controls from same population the comparison groups are selected according to outcome (presence or absence of a particular health problem of interest).

Case-control study
Those with the problem are known as cases and those without the problem are known as controls.

Entry into these groups are not influenced by the investigators.

Case-control study
exposure data collected retrospectively. Study subjects in each group are interviewed or their records are reviewed to determine any previous exposure to the causal agent. most feasible design where disease outcomes are rare

Case - Control Study

In a case-control study, the comparison groups are selected according to outcome (presence or absence of a particular health problem of interest). Those with the problem are known as cases and those without the problem are known as controls. Entry into these groups are not influenced by the investigators. Study subjects in each group are then interviewed or their records are reviewed to determine any previous exposure to the causal agent.

Case-Control Studies
Cases: Disease Controls: No disease

factor present
factor absent

Cases (disease) Study population Controls (no disease) present

Case-Control Design

factor present factor absent past

Study begins here

Design of a Case - Control Study

Time Direction of inquiry Start with
Exposed Not exposed Exposed Not exposed
Cases (People with disease) Controls (People without disease) Population

Use Estrogens
(a)

Cases of Endometrial Cancer

(a+c)

Dont use Estrogens

(c)

Use Estrogens
(b)

Controls
(b+d)

Dont use Estrogens

(d)

Advantages : Case Control Studies

1. Low cost 2. Can be accomplished quickly since events of interest have already occurred 3. Small sample size 4. Best design for rare diseases 5. Can study several potential exposures at the same time 6. Lends itself well to hospital-based studies and outbreaks 7. Available data 8. No ethical problems

Disadvantages:

Case-control studies

Problems with temporal sequence of data Hard to decide when disease was actually acquired Disease may cure the exposure Miss diseases still in latent period Cant calculate incidence, population relative risk or attributable risk HIGH potential for bias Do not estimate risks and rates Selection of controls difficult Not suitable for rare exposures Data dredging

A case-control study is performed as follows:

Identify cases of disease. Ideally all the cases in the population should be recruited because there may be a selection biases which influence attendance at hospitals. New (incident) cases of the disease should be used because previously diagnosed (prevalent) cases represent long term survivors.

A case-control study is performed as follows:

Recruit control subjects without the disease from the same population. Usually the number of controls is the same as the number of cases, but two or more controls per case may be used to increase statistical power. Controls may be matched with cases e.g. for age and sex.

 Test cases and controls for prior exposure to the suspected risk factor. The same method should be used in cases and controls. Analyse results. For case control studies the rate of disease in the population is unknown so the relative risk cannot be calculated. We have to assume that the disease is rare (low incidence) and that the odds ratio estimates the relative risk.

Cohort studies

Cohort A group of people who shares a common experience

Birth cohort, smokers cohort, exposed cohort Can be open cohort, fixed cohort, closed cohort.

Cohort study
an observational design comparing individuals with a known risk factor or exposure with others without the risk factor or exposure The comparison groups are selected according to previous exposure to a suspected causal agent. Study subjects in each group are then followed to determine their outcome.

Cohort study
Most straight forward

Goal is to measure and usually to compare the incidence of disease (outcome) in one or more cohorts
Can begin with one, two or more than two cohorts; free from disease; differ according to extent of exposure.

Cohort Studies
looking for a difference in the risk (incidence) of a disease over time best observational design data usually collected prospectively (some retrospective)

Cohort Design

Study population free of disease

Factor present

disease
no disease disease no disease future

Factor absent

present

time Study begins here

Design of a Cohort Study

Time Direction of inquiry

Disease People without the Disease Exposed No disease Disease Not Exposed No disease

Population

Case Endomentrial cancer

(a)

Use Estnogens (a+b) Non-case (b)

Post-menopausal Women Free of Endometrial cancer

Cases Endometrial cancer (c) Dont use Estrogens (c+d) Non-cancer

(d)

Different Types of Cohort Studies

Prospective Cohort Study Retrospective Cohort Study Mixed Cohort Study Nested Case-control Study

Timeframe of Studies
Prospective Study - looks forward, looks to the future, examines future events, follows a condition, concern or disease into the future

time
Study begins here

Prospective Cohort study

Exposed
Measure exposure and confounder variables

Outcome

Baseline

Non-exposed time

Outcome

Study begins here

Timeframe of Studies
Retrospective Study - to look back, looks back in time to study events that have already occurred

time
Study begins here

Retrospective Cohort study

Exposed
Measure exposure and confounder variables

Outcome

Baseline

Non-exposed time

Outcome

Study begins here

Advantages : Cohort Studies

Can get best assessment of exposure and can deal with changes in exposure

May be only design if exposure needs to be measured directly

Allows study of rare exposures Only way to get prospective information for rapidly fatal diseases Good for establishing temporal sequence and natural history of disease Can examine multiple outcomes linked to exposure often find other effects than

Advantages : Cohort Studies

Can estimate overall and specific disease rates, usually incidence Researcher selects, measures & records data Lower potential for bias than a case-control study no recall and selection bias Results are considered more conclusive than results from case-control studies The longer a cohort study continues, the stronger it can become

Disadvantages : Cohort Studies

Large sample size Losses to follow-up Multiple exposure- difficult Exposure can change Ethical problems Cost Time consuming

The following steps are required for Cohort study

Define hypothesis. Define population. Take sample.

The following steps are required for Cohort study

Establish exposure status: apply test to the sample to identify the presence or absence of risk factor in each individual. Exclude cases who already have the disease (may be unnecessary if disease is rare). Follow up: maintaining a high response rate. Monitor for outcome events: Detect cases of disease or death.

Experimental study

Experimental Studies
investigator can control the exposure akin to laboratory experiments except living populations are the subjects generally involves random assignment to groups clinical trials are the most well known experimental design the ultimate step in testing causal hypotheses

Experimental Studies
In an experiment, we are interested in the consequences of some treatment on some outcome. The subjects in the study who actually receive the treatment of interest are called the treatment group. The subjects in the study who receive no treatment or a different treatment are called the comparison group.

Randomized Clinical Trial

The basic study design of the randomized clinical trial consists of having subjects in two groups, either exposed to two different treatments or to a treatment and a control, the assignment been random. Subjects from both the groups are followed till they reach a particular end point.

Clinical Trial: Parallel Group Design

Experimental Treatment
With Outcome Without Outcome With Outcome Without Outcome

Participants screened for entry criteria Control Treatment

Time
Screening Baseline Treatment

Participants screened for entry criteria

Screening B/L Control Treatment Experimental Treatment Treatment (Phase 1)

Without Outcome With Outcome Without Outcome With Outcome

Clinical Trial: Crossover Design

{Washout} Control Treatment Treatment (Phase 2) Experimental Treatment

Without Outcome With Outcome Without Outcome With Outcome

Randomized Clinical Trial

The basic study design of the randomized clinical trial consists of having subjects in two groups, either exposed to two different treatments or to a treatment and a control, the assignment been random. Subjects from both the groups are followed till they reach a particular end point.

Randomized Controlled Trials (RCTs)

a design with subjects randomly assigned to treatment and comparison group provides most convincing evidence of relationship between exposure and effect not possible to use RCTs to test effects of exposures that are expected to be harmful, for ethical reasons

Have outcome of interest

Exposure Study population without the outcome of interest Do not develop outcome of interest

Randomisation
Have outcome of interest

No exposure Do not develop outcome of interest

Time

Key features of RCT Randomisation

Removes selection bias or confounding Alternation or other assignment schemes are bad idea

Use of concurrent control groups

Vs Before/After studies

Blinding whenever possible

Blind investigators: prevents information biases Blind participants: prevents selective behaviour change during the trial Not just in trials

 RCTs are important tools But can encounter major problems that hinder interpretation of results
Generalizability: Trial participants are highly selected individuals often not representative of general population at risk Complexity: Trials procedures can be complex (and costly) when key design features breakdown, the experiment is compromised

Characteristics of Classical Experimental Study

Manipulation-The researcher does something to one group of subjects in the study. Control- The researcher introduces one or more control group(s) to compare with the experimental group. Randomization- The researcher takes care to randomly assign subjects to the control and experimental groups.

RANDOMIZATION

outcome
Intervention no outcome

Experimental Design

Study population Control

outcome no outcome

baseline future

time Study begins here (baseline point)

Randomized Controlled Trials (RCTs)

the gold standard of research designs provides most convincing evidence of relationship between exposure and effect trials of hormone replacement therapy in menopausal women found no protection for heart disease, contradicting findings of prior observational studies

Randomized Controlled Trials

Disadvantages Very expensive Not appropriate to answer certain types of questions it may be unethical, for example, to assign persons to certain treatment or comparison groups

Comparing two or more intervention groups with regard to outcome- comparing what with what?
A new intervention Vs. nothing
A new intervention Vs. placebo One intervention Vs. another ( new & standard intervention) One intervention Vs. the same plus something else One intervention at specified dose Vs. same intervention at a higher dose (amount, duration, greater intensity) Intervention now Vs. later

Intervention refers to
A drug (or drug regimen) Surgical procedure A medical device A therapeutic modality

A micronutrient
A diet A behavioral intervention

Clinical approach to diagnosis

Withdrawal of risk factors

Masking or blinding
By design, the study may be single blind -when the subject does not know the treatment he is assigned to, double blind -when both the subjects as well as the investigators do not know which treatment a particular subject is being assigned or triple blind - when study subjects, investigators as well as the data analysts do not know which treatment a particular subject is being assigned.

Study Design Sequence

Hypothesis formation Descriptive epidemiology

Case reports

Case series

Analytic epidemiology Clinical trials Hypothesis testing Cohort Casecontrol

Animal study

Lab study

Crosssectional

Descriptive Studies

Develop hypothesis

Increasing Knowledge of Disease/Exposure

Case-control Studies

Investigate its relationship to outcomes

Cohort Studies

Define its meaning with exposures

Clinical trials

Test link experimentally

Key Factors for Design Quality

1. Adequate experimental control through randomization and reducing bias, confounding and extraneous variables. 2. Lack of artificiality: Results must be applicable to real problems. 3. Basis for comparison: Must build into the design a way to measure the effect of the treatment (control group design). 4. Adequate information (data) must be gathered so that conclusions can be drawn about the hypotheses.

Key Factors for Design Quality

5. Data should not be contaminated by poor measurement or errors in procedure.
6. Eliminate confounding variables from study or minimize their effects on variables. 7. Representativeness: Can you say that your sample represents the population you are studying? Must use random sample techniques. 8. Parsimony: Clean, Lean, and Mean. Keep the design simple.

Categories of intervention studies: Experimental studies In an experimental study, individuals are randomly allocated at least two groups. One group is subject to an intervention, or experiment, while the other group(s) is not. The outcome of the intervention is obtained by comparing the the two groups.

Quasi-experimental studies
In a Quasi-experimental study, at least one characteristic of a true experiment missing, either randomization or the use of a separate control group. A quasi-experimental study, however always includes manipulation of an independent variable that serves as the intervention

Other designs: Time series - test if incidence of disease changes in a

population over time Hybrid - often what is seen in practice Can be efficient and match necessity Can lead to bias and disaster

Meta-analysis
Combining results from a range of published studies Established methodology, not just literature review

Other experimental designs

For an experiment, need to compare 2 states: with intervention vs without Before/after studies
Introduction of Pfizer fluconazole donation programme at GFJ

Median survival of cryptococcal meningitis in HIV+ before

Median survival of cryptococcal meningitis in HIV+ after

Controlled before/after studies

BEFORE
New training in sterile procedures

AFTER

MMH
intervention

vs

Rate of postoperative sepsis No new training

Rate of postoperative sepsis

NSH
control

Rate of postoperative sepsis

Rate of postoperative sepsis

Time-series studies
25000 300

Rate of advanced cervical cancer cases per 100,000

20000

250

200 15000 150 10000 100 5000

# of pap smears performed in Western Cape

50

0
1980 1984 1990 1995 2000

What type of study to chose depends on:

what is the research question/ objective Time available for study Resources available for the study Common/rare disease or production problem Type of outcome of interest Quality of data from various sources Often there are multiple approaches which will all work Choosing an established design gives you a huge head start in design, analysis and eliminating biases

THANK YOU