Epidemiological study designs

The 6 D’s of Health Outcomes Death

Disease

Discomfort

Disability

Dissatisfaction

Destitution

A bad outcome if Untimely

A set of Symptoms, Signs and Lab results

Symptoms such as pain, nausea and itching

Impaired ability to go about usual activities

Emotional reaction to disease and its care

Financial Cost of Illness

Clinical QuestionsAbnormality Is the patient sick or wellFrequency How often does disease occurDiagnosis How accurate are the diagnostic testsCause What conditions lead to diseaseRisk What factors are associated with the

diseasePrognosis What are the consequences of diseaseTreatment How does treatment change the coursePrevention Does an intervention prevent disease

Does an early detection improve the course

Cost How much will care cost

Non Interventional StudiesNon Interventional Studies(Observational)

Interventional StudiesInterventional Studies

(Experimental)(Experimental)

Epidemiological StudiesDescriptive Studies

Describes Disease occurrence in a population Incidence Prevalence Survivial

Analytic StudiesTo determine etiology of disease

Cohort Case Control Cross Sectional

EPIDEMIOLOICAL METHODS

OBSERVATIONAL STUDIES

(NON INTERVENTIONAL)

EXPERIMENTAL STUDIES

(INTERVENTIONAL)

Descriptive studies

AnalyticalStudies

Cross Sectional Case Control

Cohort

Randomized Controlled Trials

Field trials

Community TrialsLongitudnal

Descriptive•Case report•Case series•Survey

Analytic

Observational•Cross sectional•Case-control•Cohort studies

Experimental•Randomized controlled trials

Strength of evidence for causality between a risk factor and outcome

Epidemiological sequence Observation – data collection

Counting cases and events

Relating cases and events to population at risk

Making comparison

Developing hypothesis

Testing of hypothesis by analytical studies

Making scientific inferences

Conducting experimental studies

Interventions/Evaluation

1. DESCRIPTIVE STUDY

FIRST THING’S FIRST…..!!!!

Definition

It involves the systematic collection and presentation of data to give a clear picture of a particular situation.

Descriptive can be carried out on small or large scales in community

ConcernsDescriptive study is concerned with the following questions:a. When is the disease occurring (Time)b. Where it is occurring (Place)c. Who is getting the disease (Person)

T.P.P

UsesProvides data regarding

The magnitude of the disease load

The types of disease problem in the community in term of morbidity and mortality rate and ratio

Provides “clues” to the disease etiology

Helps in Formulation of etiological hypothesis

Helps in planning, implementation and evaluation of health services/programmes

ProceduresDefining the population to be studiedDefining the disease under studyDescribing the disease by

Time Place Person

Measurement of the disease Cross Sectional Study Logitudinal Study

Comparing with known indicesFormulation of an etiological hypothesis

Measurement of Diseasea. Cross Sectional Study

b. Longitudinal Study

Cross sectional studies

Based on a single examination of a cross section of population at one point in time, results of which can be projected on the whole population provided the sampling has been done correctly.

Uses

a. More useful in chronic diseases

b. To find more about disease rather than its etiology

CharacteristicsPhysical characteristics of people, material

and environment

Socio-economic characteristics e.g., age, education , marital status, number of children and income

Behavior of people like knowledge, attitude and beliefs (KAP)

Events that occur in population

Advantages of CSSMay study several outcomes

Control over selection of subjects

Control over measurements

Relatively short duration

First step for cohort study

Yields prevalence

Disadvantages of CSSDoes not establish cause/effect ratio

Potential bias in measuring exposure

Potential survival bias

Not feasible for rare disease

Does not yield incidence

Longitudinal Study

Based on multiple observations in the same population over a prolong period of time.

Uses of Longitudinal Study

Natural History of Disease

Identifying Risk factors

Finding out incidence rate

Cross Sectional Vs Longitudinal

COMPARATIVE or ANALYTICAL STUDY

An ANALYTICAL STUDY attempts to establish causes or risk factors for certain problems. This is done by comparing two or more groups, some of which have or develop the problem and some of which have not.

Analytic EpidemiologySecond major type of epidemiological studies

Subject of interest is individual within the population

The objective is to test hypothesis

The study determines whether or not a statistical association exists between a disease and suspected factor

Strength of association, if it exists

CASE CONTROL STUDY

In a CASE-CONTROL STUDY, the investigator compares one group among whom a problem is (e.g., malnutrition) with another group, called a control or comparison group, where the problem is absent to find out what factors have contributed to the problem.

CASE CONTROL STUDY

Often called retrospective study

First approach to test causal hypothesis

PropertiesBoth exposed and outcome (Disease) have

occurred before the start of study

The study proceeds backward from effect to cause

It uses a control or comparison group to support or refute an inference

MethodSelection of cases and Controls

Matching

Measurement of Exposure

Analysis and Interpretation

Exposure Rates

Estimation of Risk (Relative Risk & Odds Ratio)

A

C D

B

Cases

Exposure -

Exposure +

Controls

A+C B+D

2 x 2 Contingency Table for Cases and Controls

Total Cases

Exposure Among Cases

A/(A+C)

Exposure Among Controls

B/(B+D)

Advantages of case control studyRelatively easy to carry outRapid and inexpensiveParticularly suitable to investigate rare

diseasesNo risk to subjectReveals the study of several different

etiological factorsRisk factors can be identifiedNo follow up in the futureMinimum ethical problems

Disadvantages of case control study

Problems of bias

Selection of appropriate case control group may be difficult

Cannot measure incidence, only relative risk is measured

Randomized controlled trialsInvestigator controls the predictor variable

(intervention or treatment)Major advantage over observational studies

is ability to demonstrate causalityRandomization controls unmeasured

confoundingOnly for mature research questions

PopulationPopulation

SampleSample

TreatmentTreatment Dx No Dx

ControlControl Dx No DxPlaceboPlacebo

RandomizationRandomization

Steps in a randomized controlled trial

1. Select participants high-risk for outcome (high incidence) Likely to benefit and not be harmed Likely to adhere

2. Measure baseline variables3. Randomize

Eliminates baseline confounding Types (simple, stratified, block)

Analysis of randomized controlled trial

Analyzed like cohort study with RRIntention to treat analysis

Most conservative interpretationInclude all persons assigned to intervention

group (including those who did not get treatment or dropped out)

Subgroup analysisGroups identified pre-randomization

Steps in a randomized controlled trial

4. Blinding the intervention As important as randomization Eliminates

co intervention biased outcome ascertainment biased measurement of outcome

5. Follow subjects Adherence to protocol Lost to follow up

6. Measure outcome Clinically important measures Adverse events

What is Blinding?What is Blinding?Single blind - participants are not aware

of treatment groupDouble blind - both participants and

investigators unawareTriple blind - various meanings

persons who perform tests outcome adjudicators safety monitoring group

Single blind - participants are not aware of treatment group

Double blind - both participants and investigators unaware

Triple blind - various meanings persons who perform tests outcome adjudicators safety monitoring group

Why blind?: Co interventions Unintended effective interventions

participants use other therapy or change behavior study staff, medical providers, family or friends

treat participants differently

Nondifferential - decreases power Differential - causes bias

Why blind?: Biased Outcome Ascertainment or adjudicationWhy blind?: Biased Outcome

Ascertainment or adjudication If group assignment is known

participants may report symptoms or outcomes differently

physicians or investigators may elicit symptoms or outcomes differently

Study staff or adjudicators may classify similar events differently in treatment groups

Problematic with “soft” outcomes investigator judgement participant reported symptoms, scales

If group assignment is known participants may report symptoms or outcomes

differently physicians or investigators may elicit symptoms

or outcomes differently Study staff or adjudicators may classify similar

events differently in treatment groups

Problematic with “soft” outcomes investigator judgement participant reported symptoms, scales

High Quality Randomized TrialsTamper-proof randomizationBlinding of participants, study staff, lab staff, outcome ascertainment and adjudication

Adherence to study intervention and protocol

Complete follow-up

COHORT STUDYIn a COHORT STUDY, a group of individuals

that is exposed to a risk factor (study group) is

compared with a group of individuals not

exposed to the risk factor (control group).

The researcher follows both groups over time

Compares the occurrence of the problem

related to the risk factor in the two groups

Determines whether a greater proportion of

those with the risk factor are indeed affected

CONCEPT OF COHORT

The term Cohort is defined as group of people who share a common characteristic or experience within a defined time period e.g., age, occupation, exposure of a drug or vaccine, birth cohort and marriage cohort etc.

Distinct features of cohort studyThe cohort are identified prior to the

appearance of disease under study.The study groups so defined observed over a

period of time to determine the frequency of the disease among them

The study proceeds forward from cost to effect

A

C D

B

Disease +

Risk Factor -

Risk Factor +

Disease -

A+B

C+D

2 x 2 Contingency Table for Cohort Study

Total

Exposed

Incidence Among Exposed

A/(A+B)

Incidence Among Unexposed

B/(B+D)

Elements of a cohort studySelection of the study groupObtaining data on exposureSelection of the comparison groupFollow upAnalysis

Strengths of cohort studiesKnow that predictor variable was present before

outcome variable occurred (some evidence of causality)

Directly measure incidence of a disease outcome

Can study multiple outcomes of a single exposure (RR is measure of association)

Weaknesses of cohort studiesExpensive and inefficient for studying rare

outcomesHERS vs. WHI

Often need long follow-up period or a very large populationCARDIA

Loss to follow-up can affect validity of findingsFramingham

Selection of the study groupGeneral populationSelected group of population e.g.; doctors,

teachers, nurses, school children etc.

Exposure DataPersonal interviewMailed

questionnaireReview of recordsMedical

examinationEnvironmental

survey

Follow upPeriodic examination of each member of the

cohortReviewing physician and hospital recordRoutine surveillance of death recordsMailed questionnaireTelephone callsPeriodic home visit (on annual basis)

Follow up can be done through

• Mail

• Email

• Online

Email

Interviews may be conducted

Face-to-face

• Over the Telephone

Analysis

Relative Risk

Attributable Risk

Odds ratio

Relative Risk (RR)

Ratio of incidence of the disease (or

death) among exposed and the incidence

among non-exposed.

It is a direct measure (or index) of the

“strength” of the association between

suspected cause and effect

Odds Ratio (OR) Measure of the strength of the association between

risk factor and outcome.

The derivation of the Odds Ratio is based on three assumptions:

- the disease being investigated must be relatively rare

- the cases must be representative of those with the disease

- the controls must be representative of those without disease

Analysis

Relative risk (RR)Ie

RR = -----Io

Attributable risk (AR)

Ie-IoAR = -------- X100

Ie

• WhereasIe : Incidence among

exposedIo : Incidence among non

exposed

Difference between BIAS and CHANCE

BIASIt is deviation of results, or inferences from the truth or processes leading to such deviation. It is a systematic error

CHANCEIt is a random error and may account for an apparent association and make it appear real when it is not (Type I or alpha error). It may lead to an association being overlooked or missed when it truly exists (Type II or Beta error)

Comparison Case control

Retrospective Hospital based Quick Easy to conduct Small sample size Less expensive Rare diseases None

Cohort Prospective/

longitudinal Community based Time consuming Logistically difficult Large sample size Very expensive Common disease Incidence

Case Control VS Cohort Study

FactorsPresent

Absent

Risk FactorsExposed

Unexposed

DiseasePresent (Cases)

Absent (Controls)

DiseasePresent on Followup

Absent on Followup

CASE CONTROL STUDY

COHORT STUDY

TIME LINE

INTERVENTIONAL STUDIES

INTERVENTIONAL STUDIESIn Intervention Studies the researcher

manipulates the situation and measures the effects of this manipulation.

Usually (But not Always) 2 Groups are compared, one in which the Intervention takes place and the other group that remains “Untouched”

INTERVENTIONAL STUDIESThe 2 categories of Intervention Studies are:

1. Experimental Studies

2. Quasi-Experimental Studies

Experimental StudiesIndividuals are randomly allocated to atleast 2 groups. One group is subject to Intervention or Experiment while the other group is not. Then the outcome of the intervention is obtained by comparing the 2 groups

Diagram of Experimental Study

Study Group(Experimental)

1st Data Collection(Before Intervention)

Intervention

Last Data Collection(After Intervention)

Study Population (Sampling)

Sample Population (Randomization)

COMPARE

Control Group(Comparison)

1st Data Collection(Same Time)

No Intervention

Last Data Collection(Same Time)

Quasi-Experimental Studies

In this at least one characteristic of a true experiment is missing. This may be Either:

Missing of RandomizationMissing of separate Control group

This however always includes manipulation of independent variable that serves as intervention

Diagram of Quasi Experimental ModelStudy Group before Intervention Study Group

After

COMPARE

Control Group Before Control Group After

THANK YOU

What is IncidenceNo. of new cases of a disease or

health related event in a given population in a given time

___________________________

Total Population at risk in a given time

X 1000

What is PrevalenceNo. of new as well as Old cases of a

disease or health related event in a given population in a given time

___________________________

Total Population at risk in a given time

X 1000

What does Incidence SignifiesIt shows the RATE at which new diseases or

health problems occur in a population.

Prevalence shows the proportion of a population at risk which is affected by a disease at a specific point in time.

It is further of 2 typesPoint PrevalencePeriod prevalence.

Case 1

Case 2

Case 3

Case 4

Case 5

Case 9

Case 8

Case 6

Case 7

Case 10

1Jan,2004 28 Dec,2004

Total No of Patients admitted during this 1 year = 100

What is the prevalence of Hepatitis B on 1st January 2004.

What is prevalence of Hepatitis B during the year 2004.

Relation between Incidence and PrevalencePrevalence = Incidence x Duration of the

Disease

PREVALENCE

INCIDENCE

RECOVERY DEATH

Variations in Incidence and PrevalenceSince Incidence depends on the occurrence

of new cases of a disease, a DECREASE in Incidence may be due toEnhanced Resistance to the diseaseA change in Disease EtiologyAn effective prevention program that reduces

exposure to a known risk factor for the disease.

A DECREASE in Prevalence may be due toA decrease in IncidenceA shorter duration of the disease due to either

improved treatment methods leading to more rapid recovery or an increase in virulence leading to more rapid death.

Risk Factor and CausalityWhat is a Risk Factor

A condition, physical characteristic, or behaviour that increases the probability that a currently healthy individual will develop a particular disease.

A Risk Factor may be a causal factor of the disease in question or merely a marker for the increased probability of disease.

E.g while poor antenatal acre and drug use constitute causal factors for neonatal mortality, socioeconomic status would be considered a marker for neonatal mortality.

Risk AssessmentA number of epidemiological research

designs are used to evaluate the association between a disease and a suspected risk factor.

Types of Epidemiological StudiesDescriptive Studies

Also termed as Cross-sectional studies they determine the disease frequency or prevalence of a condition. Surveys are one example

Analytic StudiesObservational StudiesExperimental Studies

Analytical StudiesObservational

Case Control StudiesCohort Studies

Prospective Cohort Studies Retrospective Cohort Studies.

Case control studies: Case-control studies are those in which persons with a specified condition (the cases) and pesons without the condition (the controls) are selected for study. The proportion of cases and controls with certain characteristics or exposure is then measured and compared. For example, knowing that there are 10 school children with purple spots in grade 3, a set of other third grade children from the same school but without purple spots would be identified as controls, and analysis done to see what different exposures the purple-spotted children had than the non-spotted

Cohort studies: groups of individuals with some common feature (age and geography, for example) are identified for study over time to learn about differing health and illness experiences. For example, one might enroll in a study all third graders in a school and follow them until graduation, attempting to identify the differences in experiences of those who maintained a body weight close to recommended and those who did not.

EXPERIMENTAL STUDIESQuasi-Experimental StudiesTrue Experimental Studies

RandomizationControl Group

ExcerciseIn 1998 an outbreak of Cholera in a

Peshawar Suburb shows the following Data.

Cases presenting Cases presenting with loose motions, with loose motions, vomiting of acute vomiting of acute duration in the last 48 duration in the last 48 hourshours

People in the same People in the same area who didn’t have area who didn’t have gastrointestinal gastrointestinal symptomssymptoms

Using community Using community water supplywater supply 135135 5555

Using own dugged Using own dugged wellswells 22 103103

From 1960 to 1992, 35250 adults aged 20-25 years were followed up for habits of smoking and were assessed for presence of Bronchogenic Carcinoma with following results.

CT Scan evidence of CT Scan evidence of Ca LungCa Lung

No evidence of ca No evidence of ca LungLung

People who started People who started and continued with and continued with SmokingSmoking

435435 2016520165

People who didn’t People who didn’t SmokeSmoke 1010 1464014640