Introduction to study Designs

Dr Ajithkumar KDean (Research)

KUHS

23/01/2015---Cochin--Ay

23/01/2015---Cochin--Ay

Pigment reduction in nevus of Ota following leech therapy Sanjeev Rastogi1, Priyanka Chaudhari2

• Nevus of Ota is a congenital blue-gray color nevus afflicting unilaterally, the area near the eyes. It poses a huge cosmetic concern besides being a potential threat for developing melanoma sometime in the course of the disease. The treatment options are neither many nor promising besides they are too expensive. We have treated a case of nevus of Ota with leech therapy where leech was applied upon the lesion for five times spanned in a period of 2 months. The results in terms of change in the color of lesion were evaluated with the help of serial photographs following every treatment session to mark the level of color changes in the lesion. A substantial reduction in color of the nevus was reported following the completion of the therapy. The results were demonstrated with the photographs. Although, recommended as the classical Ayurvedic management for skin diseases, leech therapy is not reported earlier in such conditions. It proposes a novel approach to deal with such congenital pigment lesions where other options are not promising.

23/01/2015---Cochin--Ay

23/01/2015---Cochin--Ay

23/01/2015---Cochin--Ay

Case Reports

• Detailed presentation of a single case or handful of cases

• Generally report a new or unique finding• e.g. previous undescribed disease• e.g. unexpected link between diseases• e.g. unexpected new therapeutic effect• e.g. adverse events

23/01/2015---Cochin--Ay

Case Reports/ Case Series

• The most basic descriptive study• Link between clinical medicine and

epidemiology• Hypothesis generating• feasible study designs, are easy to conduct

and require less time and financial resources than randomised-controlled trials, case-control, or cohort studies

23/01/2015---Cochin--Ay

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

23/01/2015---Cochin--Ay

Case Report

Case Series

DescriptiveEpidemiology Study

One case of unusualfindings

Multiple cases of findings

Population-based cases with denominator

23/01/2015---Cochin--Ay

• Case series represents an observational study that reports on data from a subject group without a comparison population.

23/01/2015---Cochin--Ay

Case series also need methodology

• Clear study objective/question• Well-defined study protocol• Explicit inclusion and exclusion criteria for study

participants• Specified time interval for patient recruitment• Consecutive patient enrollment• Clinically relevant outcomes• Prospective outcome data collection• High follow-up rate23/01/2015---Cochin--Ay

• Selection bias• Placebo effect, • Hawthorne effect: tendency of some people to work

harder and perform better when they are participants in an experiment

• Rosenthal effect: the greater the expectation placed upon people,

the better they perform. • Natural history effect

23/01/2015---Cochin--Ay

23/01/2015---Cochin--Ay

23/01/2015---Cochin--Ay

Cross-Sectional Study

23/01/2015---Cochin--Ay

Cross-sectional studies

• An “observational” design that surveys exposures and disease status at a single point in time (a cross-section of the population)

time

Study only exists at this point in time23/01/2015---Cochin--Ay

Cross-sectional Design

time

Study only exists at this point in time

Studypopulation

No Disease

Disease

factor present

factor absent

factor present

factor absent

23/01/2015---Cochin--Ay

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

23/01/2015---Cochin--Ay

Cross-sectional studies• Disadvantages

• Weakest observational design, (it measures prevalence, not incidence of disease).

• Prevalent cases are survivors• The temporal sequence of exposure and

effect may be difficult or impossible to determine

• Usually don’t know when disease occurred• Rare events a problem. • Quickly emerging diseases a problem

23/01/2015---Cochin--Ay

SURVEYS

• Prevalence and incidence are obtained from surveys

• The denominator i.e. the population at risk should be clearly defined.Cross sectional survey• a one time measurement conducted on a sample derived from a

populationPrevalence = No. of persons with disease

Population at riskLongitudinal Survey

A group of subjects under surveillance over a period of time.

Incidence rate = Number of new cases occurring over the period Population at risk X time of observation

23/01/2015---Cochin--Ay

The exposure and disease status are examined for a sample from a defined population at the same time point. The prevalence as well as the OR can be determined.OR= No of diseased exposed/no of diseased non exposed -------------------------------------------------------------------- No exp.control /non exposed control

cross-sectional studies

23/01/2015---Cochin--Ay

Cross-Sectional Study

Steps in Cross-Sectional Study 1.     Select a sample from the population2.     Simultaneously measure predictor and outcome variables

Population

+ Risk Factor

- Risk Factor

+ Risk Factor

+ -

-+

- Risk Factor

Present

23/01/2015---Cochin--Ay

23/01/2015---Cochin--Ay

Case-Control Study

Steps in Case Control Study • 1.   Select a sample of patients who already have the disease (Cases)• 2.   Select a sample of patients at risk but do not have the disease (Controls)• 3. Measure predictor variables

Population with Disease

-

Population without Disease

Risk Factor

++-

+-

PresentPast

23/01/2015---Cochin--Ay

• Case-Control Studies–an “observational” design comparing

exposures in disease cases vs. healthy controls from same population

–exposure data collected retrospectively–most feasible design where disease

outcomes are rare

23/01/2015---Cochin--Ay

Case Control Studies

23/01/2015---Cochin--Ay

Case Control Studies

23/01/2015---Cochin--Ay

Case

-Con

trol

Des

ign

Studypopulation

Cases(disease)

Controls(no disease)

factor present

factor absent

factor present

factor absent

presentpast

time

Study begins here23/01/2015---Cochin--Ay

Case-Control Study• Strengths

– Less expensive and time consuming

– Efficient for studying rare diseases

• Limitations– Inappropriate when disease outcome for a specific

exposure is not known at start of study

– Exposure measurements taken after disease occurrence

– Disease status can influence selection of subjects

23/01/2015---Cochin--Ay

case-control studies

• Persons suffering from the studied disease are compared with controls who do not have the disease.

• The odds ratio (OR) is calculated as a comparative effect measure.

• = OR=• No of diseased exposed/no of diseased non

exposed• --------------------------------------------------------------------• No exp.control /non exposed control

23/01/2015---Cochin--Ay

Cohort Study

Steps in Cohort Study Design:1.     Select a sample from the population2.     Measure predictor variables3.     Follow-up the cohort4.     Measure outcome variables

Population

+ Risk Factor

- Risk Factor

Disease

+ -

-+

Present Future

Epidemiologic Study Designs• Cohort Studies

– an “observational” design comparing individuals with a known risk factor or exposure with others without the risk factor or exposure

– looking for a difference in the risk (incidence) of a disease over time

– best observational design– data usually collected prospectively (some

retrospective)

23/01/2015---Cochin--Ay

Coho

rt D

esig

n

time

Study begins here

Studypopulation

free ofdisease

Factorpresent

Factorabsent

disease

no disease

disease

no disease

presentfuture

23/01/2015---Cochin--Ay

Prospective Cohort study

Measure exposureand confounder

variables

Exposed

Non-exposed

Outcome

OutcomeBaseline

time

Study begins here

23/01/2015---Cochin--Ay

Retrospective Cohort study

Measure exposureand confounder

variables

Exposed

Non-exposed

Outcome

OutcomeBaseline

timeStudy begins here

the investigator collects data from past records and does not follow patients up as is the case with a prospective study. However, the starting point of this study is the same as for all cohort studies

23/01/2015---Cochin--Ay

Cohort Study• Strengths

– Exposure status determined before disease detection– Subjects selected before disease detection– Can study several outcomes for each exposure

• Limitations– Expensive and time-consuming– Inefficient for rare diseases or diseases with long latency– Loss to follow-up

23/01/2015---Cochin--Ay

Cohort studies

• Persons exposed to specific risk factors are compared with persons not exposed to these factors.

• The occurrence of diseases or deaths in these two groups is observed prospectively.

• incidence rate and mortality rate • Relative risk (RR) or hazard ratio (HR) Standardized

incidence ratios (SIR) or standardized mortality ratios (SMR) are used for comparison with the general population.

23/01/2015---Cochin--Ay

Cohort studies

No: disease in exposed / Total no: exposed

RR= -------------------------------------------

No: disease in non exp /Total no: of non exposed

23/01/2015---Cochin--Ay

ECOLOGICAL STUDY

TIME

Direction of injury

Population

E D+

E D-

ED+

ED-

Not Exposed

Exposed

23/01/2015---Cochin--Ay

studies of risk-modifying factors on health or other outcomes based on populations defined either geographically or temporally. Both risk-modifying factors and outcomes are averaged for the populations in each geographical or temporal unit and then compared using standard statistical methods.

Broad street –London

23/01/2015---Cochin--Ay

Ecological studies

Measures combined occurrence of risk factors and disease

in a population

Individual exposure and disease relationship cannot be

assessed

Eg: Occupational and industrial exposure to toxins,

Environmental risk

23/01/2015---Cochin--Ay

Epidemiologic Study Designs

23/01/2015---Cochin--Ay

Descriptive Study Design

• To determine the frequency & Burden of the Disease • To generate Hypotheses

23/01/2015---Cochin--Ay

Evidence Pyramid

23/01/2015---Cochin--Ay

Are you going to observe or experiment?

• Observational – cross sectional, case-control studies, cohort studies – identify participants– observe and record characteristics– look for associations

• Experimental – before and after, comparative trials (controlled or randomised trials) – identify participants– place in common context– intervene– observe/evaluate effects of intervention

23/01/2015---Cochin--Ay

So……..

• To identify the risk factors:

Case-Control Study Design

• To confirm the risk factors:

Cohort Study Design

23/01/2015---Cochin--Ay

Intervention Study

Essential Feature:

• Intervention Group Vs Control Group

• Comparison

• Prove the Causation/ Effect

23/01/2015---Cochin--Ay

Intervention /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.

23/01/2015---Cochin--Ay

Randomized Controlled Trials

Defined Population

Randomization

Treatment Group

Improve Do Not Improve

Standard Therapy

Improve Do Not Improve

23/01/2015---Cochin--Ay

Expe

rimen

tal D

esig

n

timeStudy begins here (baseline point)

Studypopulation

Intervention

Control

outcome

no outcome

outcome

no outcome

baselinefuture

RANDOMIZATION

23/01/2015---Cochin--Ay

Epidemiologic Study Designs

• 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

23/01/2015---Cochin--Ay

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

23/01/2015---Cochin--Ay

Secondary Analysis• Systematic Review• Meta-Analysis

23/01/2015---Cochin--Ay

Meta-Analysis

23/01/2015---Cochin--Ay

Stu

d y D

esig

ns Case report

Case series

DescriptiveEpidemiology/survey

Descriptive

RCT

Before-Afterstudy

Cross-sectionalstudy

Case-Crossoverstudy

Case-Controlstudy

Cohort study

Analytic

Ecologic study

Qualitative study

23/01/2015---Cochin--Ay

Epidemiological Study Designs

Descriptive studies answer “what’s happening?” Analytic observational studies answer “why or how is it happening?”Analytic experimental studies answer “can it work?”

Descriptive Studies

Case-control Studies

Cohort Studies

Develop hypothesis

Investigate it’srelationship to

outcomes

Define it’s meaning with exposures

Clinical trialsTest link

experimentally

Incr

easi

ng K

now

ledg

e of

D

isea

se/E

xpos

ure

23/01/2015---Cochin--Ay

Research Designs…..Descriptive To: Describe an experience, programs, treatment, unusual observation

AnalyticExamine etiology, efficacy

ObservationalAssociation of cause and effectComparison between 2 treatments

ExperimentalEvaluate the efficacy of a therapeutic , or other interventions

Examples:1) Case Reports or series Side effect of a drug Cluster of cases 2) Population Prevalence or incidence of disease in populations3) Ecological study

Examples:

1) Cross-sectional2) Case-control3) Cohort

Examples:

1) Clinical Trial2) Community education

23/01/2015---Cochin--Ay

Hierarchy of Epidemiologic Study Design

23/01/2015---Cochin--Ay

Chance/Confounder/bias

• While the results of an epidemiological study may reflect the true effect of an exposure(s) on the development of the outcome under investigation, it should always be considered that the findings may in fact be due to an alternative explanation.

• Observational studies are particularly susceptible to the effects of chance, bias and confounding, and these need to be considered at both the design and analysis stage of an epidemiological study so that their effects can be minimized.

23/01/2015---Cochin--Ay

Confounding

23/01/2015---Cochin--Ay

Bias

23/01/2015---Cochin--Ay

Bias results from systematic errors in the research methodology

Information bias ---differences in the way data on exposure or outcome are obtained

Observer bias --differences in the way information is collected

Recall bias---in retrospective studies

Selection bias-- differences in the characteristics between those who are selected in both groups

Important epidemiological frequency measures and comparative measures;

23/01/2015---Cochin--Ay

Thank You

23/01/2015---Cochin--Ay