EPIDEMOLOGICAL STUDIES

BHUVANESH KUMAR .D.V,I - PG

Epidemiology ..?

• Epidemiology – Greek-- "the study of what is upon the people“

• Epi "upon, among",• demos "people, district“• logos "study, word, discourse",

suggesting that it applies only to human populations

Epidemiology is the study of distribution and determinants of disease frequency in human populations, with a particular focus on the occurrence of disease as categorized by time, place, and persons

Goal• A major goal of epidemiologic research

is to explain patterns of disease occurrence and causation (etiology)

• Epidemiologic measurements are aimed at quantifying 3 things:

• Exposures, Confounders & Outcomes

• Exposure - The process by which an agent comes into contact with a person or animal in such a way that the person or animal may develop disease.• Confounder – A variable that is

independently associated with the exposure of interest and the outcome(disease), and distorts the measurement of association

Exposure Disease

Confounder

• Once quantified, the association between exposure and outcome is the central focus of epidemiologic studies.

• There are many ways of evaluating the association between an exposure and an outcome: these are the different study designs

STUDY DESIGN..?

• A study design is a specific plan or protocol for conducting the study, which allows the investigator to translate the conceptual hypothesis into an operational one.

• The best epidemiologic study will be one that captures the causal effect of interest with minimal distortion (error)

Random error

Bias in Inference and

Publication

Bias in Knowledge use

Factors that cause distortion of the Causal Effect

Study Designs

Qualitative Quantitative

Descriptive Analytical

QUALITATIVE• A systematic subjective approach

used to describe life experiences and give them meaning.

• Goal is to gain insight; explore the depth, richness, and complexity inherent in the phenomenon.

Skills involved in this

• Observing

• Conversing

• Participating

• Interpreting

Basic Qualitative Research Characteristics

i. Design is generally based on a social constructivism perspective.

ii. Research problems become research questions based on prior research or experience.

iii. Sample sizes can be as small as one.

iv. Data collection involves • Interview - to generate participant

perspectives about ideas, opinions, and experiences.

• Observation - a variety of methods for observing, including taking general notes, using checklists, or time-and-motion logs to generate data on activities and behaviors

• Document (content data) Analysis- Print media has long been a staple data source for qualitative researchers, but electronic media (email, blogs, user Web pages, and even social network profiles) have extended the data qualitative researchers can collect and analyze

v. Interpretation is based on a combination of researcher perspective and data collected.

A Few Qualitative Research Designs

• Biographical Study For example, consider O’Brien’s John F. Kennedy: A Biography The author takes a collection of archival documents (interviews, speeches, and other writings) and various media (pictures, audio, and video footage) to present a comprehensive story of JFK.

Phenomenology Phenomenon refers to an occurrence or experience, logical refers to a path toward understanding. So, we have a occurrence and a path , which leads to a way of looking at the phenomenon from an individual’s point of view.

Gaston-Gayles, et al.’s (2005) look at how the civil rights era changed the role of college administrators is a good example.

The authors interview men and women who were administrators during that time to identify how the profession changed as a result.

• Grounded Theory Theory in which interpretations are continually derived from raw data. A keyword to remember is emergent as the story of this theory emerges from the dataFor E.g., Principal might want to know what effects the implementation of a dress code might have on discipline. Instead of formulating specific questions, a grounded theorist would begin by interviewing students, parents, and/or teachers, and perhaps asking students to write an essay about their thoughts on a dress code. The researcher would then follow the process of developing themes from reading the text by coding specific examples (using a highlighter, maybe) of where respondents mentioned common things

• Ethnography -- focuses on meaning, largely through direct field observation. Researchers generally (though not always) become part of a culture that they wish to study, then present a picture of that culture through the “eyes” of its members

• An ethnographic study for understanding children's oral health in a multicultural community.

• In which five ethnic populations were asked questions about their beliefs, attitudes, knowledge, and care practices regarding issues around children's oral health.

Case – study

• A case study is an in-depth analysis of people, events, and relationships, bounded by some unifying factor.

• An example is Principal’s leadership in Dental college.

• Important aspects include not only the principal’s behaviors and views on leadership, but also the perceptions of those who interact with her/him, the context of the college, outside constituents, comparison to other principals, and other quantitative “variables.”

Quantitative research

A formal, objective, systematic process for obtaining quantifiable information about the world presented in numerical form, and analyzed through the use of statistics.

• used to describe and to test relationships• used to examine the cause-and-

effect of relationships• So, quantitative research is

concerned with numbers, statistics, and the relationships between events/numbers.

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

Study Designs

Qualitative Quantitative

Descriptive Analytical

DESCRIPTIVE• FIRST phase of any Epidemiological

investigation.• Identify patterns or trends in a situation,

but not the causal linkages among its different elements.

• Descriptive studies help in generating hypothesis on which further research may be based.

• Descriptive epidemiology seeks to summarize conditions based on person, place, and time by analyzing disease (or other outcomes of exposure) patterns.

• Through data collection, this field seeks to understand a population’s health status, make hypotheses about the causes of diseases, and inform program planning and evaluation.

They are relatively in-expensive and less time consuming than analytical studies.They describe the pattern of disease occurrence by Who gets sick / who does not. Where the rates of disease are highest and lowest. Temporal patterns of occurrence.

Data provided are useful for, Public health administrators (for allocation of resources) Epidemiologists (first step in risk factor determination)

VARIOUS STEPS INVOLVED IN A DESCRIPTIVE STUDY ARE:• Defining the population to be studied.• Defining the disease under study.• Describing the disease in terms of 1. Time2. Place3. Person• Measurement of the disease• Comparing with known indices• Formulating an etiological hypothesis.

• For example, the rate of Completely Edentulous patients (person) reported to R.V.Dental college (place) in 2014 (time) was 21.3%

Descriptive

Case report

Prevalence surveys

Correlational studies

CASE REPORT{ CASE-SERIES}:• Report of a single individual or a

group of individuals with the same diagnosis.

• We can aggregate cases from disparate sources to generate hypotheses and describe new syndromes

• They are a first step for providing clues to identifying a new disease or adverse health effect from an exposure or clinical experience.

• Most common type of studies published in medical journals

• In comparison with case report, case series is a larger collection of cases of disease, often grouped consecutively and listing common features such as characteristics of affected patients.

CROSS SECTIONAL { PREVELANCE –INSTANTANEOUS-SIMULTANEOUS} STUDIES:• Measures disease and exposure

simultaneously in a well-defined population.• They cut across the general population,

not simply seeking dental care• Good for identifying prevalence of

common outcomes like Caries, Apthous, Pericoronitis ,etc.

CORRELATIONAL STUDIES• A correlational study determines whether or

not two variables are correlated.

• To study whether an increase or decrease in one variable corresponds to an increase or decrease in the other variable.

• It is very important to note that correlation doesn't imply causation

• There are three types of correlations that are identified:

1. Positive correlation2. Negative correlation3. No correlation

A correlation coefficient is usually used during a correlational study. It varies between +1 and -1.

• A value close to +1 indicates a strong positive correlation. If an increase in one variable tends to be associated with an increase in the other then this is known as a positive correlation . E.g., correlating Snacking and Caries development.

• A value close to -1 indicates strong negative correlation. If an increase in one variable tends to be associated with a decrease in the other then this is known as a negative correlation. E.g., correlating Brushing and Caries development.

• A value near zero shows that the variables have no correlation.

• When there is no relationship between two variables this is known as a zero correlation.

• For example their is no relationship between the amount of tea drunk and level of intelligence.

• Second major type of Epidemiological studies.

• Focus here is the INDIVIDUAL with in a population unlike Descriptive which focuses on entire population.

Analytical Study Design

• Attempt to establish a causal link between a predictor/risk factor and an outcome(occurrence of the disease).

Basic Question in Analytic Epidemiology

• Are exposure and disease linked?

Exposure Disease

Basic Questions in Analytic Epidemiology

• Look to link exposure and disease–What is the exposure?–Who are the exposed?–What are the potential health effects?–What approach will you take to study the

relationship between exposure and effect?

Analytical

Experimental {Intervention

al study}

Quasi- Experimental

Non Experimental

{ Observational study}

• Studies that entail manipulation of the study factor (exposure) and randomization of subjects to treatment (exposure) groups.

• Also termed as Interventional studies.

• They are carried out directly under the control of the Investigator on animals or human beings.

Experimental

AIM OF EXPERIMENTAL STUDIES:

1. To provide Scientific Proof of etiological {or risk} factors which may permit the modification or control of those diseases.

2. To provide a method of measuring the effectiveness and efficacy of health services for the prevention , control & treatment of disease and improve the health of the community.

Expe

rimen

tal D

esig

n

time

Study begins here (baseline point)

Studypopulation

Intervention

Control

outcome

no outcome

outcome

no outcomebaseline

future

RANDOMIZATION

Experimental {Interventiona

l study}

Uncontrolled Trials Controlled Trials

UNCONTROLLED STUDY • A study in which all the participants are given

a treatment and simply followed for a period of time to see if they improve, with no comparison against another group (control group) that is either taking another treatment or no treatment at all.

• The results of such studies can't be taken as evidence that a treatment works.

• Phase I and II clinical trials will be considered as Uncontrolled study

• One can be sure from the outset that most participants will improve { due to the placebo effect }.

• But it is impossible to tell how much (if any) of this improvement is due to the effect of the treatment itself.

• Uncontrolled studies can be quite useful, to find out whether a treatment causes any severe side effects.

CONTROLLED TRIAL• A controlled trial is a study testing a

specific drug or other treatment involving two (or more) groups of patients with the same disease.

Controlled

ClinicalUnit of

Randomization is an Individual

Community / Field

Unit of Randomization is a

community or a cluster

• One (the experimental group) receives the treatment that is being tested .

• Other (the comparison or control group) receives an alternative treatment, a placebo (dummy treatment) or no treatment .

• The two groups are followed up to compare differences in outcomes to see how effective the experimental treatment was .

• Phase- III clinical trial {e.g.}

Controlled

Randomized Quasi-Randomized

Non-Randomized

RCT• Randomized control trial• Clinical intervention involving two

groups i.e., the experiment group & the control / comparison group

• In which the interventions are allocated Randomly ---all participants or clusters have same chance of being allocated to the study group.

• They are considered as the “gold standard” of research designs.

• Since they provide the most convincing evidence of relationship between exposure and effect

Basic steps in Conducting a RCT :

1. Drawing up a protocol protocol specifies aims, objectives, criteria for selection of study and control groups, sample size , allocation procedure of subjects into study groups and control groups & standardization of entire procedure.

2. Selecting reference and experimental populations a) Reference or target population b) Study or experimental populationThe study population should ideally be randomly chosen from the Reference population

Once the participating members are sorted out , they should fulfill the criteria like 1. should give the informed consent 2. should be the representative of the population which they belong 3. should be qualified or eligible for the trial

3.Randomization:• A statistical procedure where populations

are allocated to the study and control groups • Done to eliminate bias and allow

comparability.• Best done using table of random numbers.4.Manipulation and Intervention: Once the groups been allocated randomly , manipulate or intervene the study group by deliberate application or withdrawal of the causal factor as laid down in the formulated protocol

Follow up: Examination of the experimental and control group subjects at defined intervals of time in a standard manner, under same given circumstances.

Assessment: Final step Outcome of the trial expressed with positive or negative results

• Study design basically includes # Concurrent parallel type # Cross- over type In the Concurrent parallel type , the study and the control groups will be studied parallel.

In the Cross over type all the participants will have the benefit of treatment after a particular period because the control group becomes the study group.

INTERVENTION

SUBJECTS

CONTROL

RANDOM

ALLOCATION

PERIOD 2

CROSS OVER DESIGN

PERIOD 1

Types of RCT• 1. Clinical trials – e.g., Drug trials,

• 2. Preventive trials – e.g., Trials of vaccines,

• 3. Risk factor trials – e.g., trials of risk factors for periodontal disease like Age , Smoking or tobacco use, Female hormonal changes , diabetes

• 4.Cessation experiments - e.g., smoking cessation experiments for studying lung-cancer.

Non randomized • Some conditions where RCT is not possible

i.e. like conditions where direct experimentation in human beings is not possible and where the frequency is low and the natural history is long

• The approach in this NON RANDOMIZED CONTROL TRIAL is crude whereas its sophisticated in RCT.

• Since there is no randomization in this, the degree of comparability will be low

• For e.g., in cig smoking , people naturally separated into smokers and non smokers,

• Taking this as an advantage we can look for the hypothesis regarding lung cancer and cig smoking.

QUASI EXPERIMENTAL• Quasi-experimental design is a form of

experimental research used extensively in the social sciences and psychology.

• Quasi experiments resemble quantitative and qualitative experiments, but lack random allocation of groups or proper controls, so firm statistical analysis can be very difficult.

• Especially in social sciences, where pre-selection and randomization of groups is often difficult, they can be very useful in generating results for general trends.

• E.g. if we study the effect of maternal alcohol use when the mother is pregnant, we know that alcohol does harm embryos. A strict experimental design would include that mothers were randomly assigned to drink alcohol. This would be highly illegal because of the possible harm the study might do to the embryos.

• So what researchers do is to ask people how much alcohol they used in their pregnancy and then assign them to groups.

NON EXPERIMENTAL

They are the observational studies.

Observational study investigators observe the subjects and measure variables of interest without assigning treatments to the subjects.

The treatment that each subject receives is determined beyond the control of the investigator

Observational studies are those that do not involve any intervention or experiment.

Observational because there is no individualintervention, treatment, exposures occur ina “non-study” environment (i.e. not randomly)

Individuals can be observed, prospectively,retrospectively or currently

Non Experimental{Observational}

cohort

Retrospective Prospective

Case-Control Cross sectional Ecological Hybrid

Nested Case

control

Case Cohort

Case crosso

ver

Cohort study

The analytic method of epidemiological study in which subsets of a defined population are identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factorshypothesized to influence the probability of occurrence of a given disease orother outcome.

• They are also termed as PROSPECTIVE / LONGITUDINAL/ INCIDENCE / FORWARD-LOOKING STUDIES.

• COHORT- group of people who share a common characteristic or experience within a DEFINED TIME PERIOD.

They are usually under taken to obtain additional evidence to support the existence of an association between the suspected cause and disease.

Features of cohort study:1. They are identified prior to the

appearance of the disease under investigation.

2. The study groups are observed over a period of time to determine the frequency of disease among them

3. The study proceeds from cause to effect.

Coho

rt D

esig

n

timeStudy begins here

Studypopulation

free ofdisease

Factorpresent

Factorabsent

disease

no disease

disease

no diseasepresent

future

TYPES OF COHORT STUDIES

3 types of cohort studies distinguished on the basis of the time of occurrence of disease in relation to time at which the investigation in initiated and continued:

1. Prospective 2. Retrospective3. Ambispective { combination}

Timeframe

• 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 STUDIES• CURRENT COHORT STUDY• The outcome { disease } has not

occurred at the time the investigation begins.

• Most prospective studies begin in the present and continue into the future.

• For example, one might follow a cohort of middle-aged truck drivers who vary in terms of smoking habits, to test the hypothesis that the 20-year incidence rate of lung cancer will be highest among heavy smokers, followed by moderate smokers, and then nonsmokers.

Timeframe

• Retrospective Study - “to look back”, looks back in time to study events that have already occurred

time

Study begins here

RETROSPECTIVE COHORT STUDIES • HISTORICAL COHORT STUDY / PROSPECTIVE STUDY

IN RETROSPECT / NON- CONCURRENT PROSPECTIVE STUDY / RECONSTRUCTED COHORT STUDY

• Investigator goes back in time to select his study groups { exposed / non exposed } from existing records of past and traces them forward through time { from past date fixed on the records to the present}

• They are generally more economical and produce results more quickly than the prospective cohort studies.

Example :-

• A study of relationship between asbestos and lung cancer was studied which assumed that the ship builders were directly exposed to asbestos that were used to line the interiors.

AMBISPECTIVE COHORT STUDIES

• In this study Both the retrospective and prospective elements are combined.

• The cohort is identified from the past records and assessed of date for the outcome.

• The same cohort is followed up prospectively into future for the further assessment of the outcome.

Analysis of cohort studiesRelative Risk { RISK RATIO}• Ratio of the incidence of the disease among

the exposed and the incidence among the non exposed.

• It is an important index for assessing the etiological role of a factor in disease.

• It is a direct measure of strength of the association between suspected cause and effect.

• Larger the relative risk , stronger the association between the cause and the effect.

Attributable risk { RISK DIFFERENCE }• It is the difference in the incidence rates of

the disease between an exposed and non exposed group.

• They are expressed in percent. • They indicate to what extent the disease

under the study can be attributed to the exposure.

• They give a better idea of the impact that a successful preventive or public health program might have in reducing the problem.

CASE- CONTROL STUDYCASE-REFERENT / RETROSPECTIVE / TROHOC STUDIES• They are a common first approach to test causal

hypothesis. • Three distinct features:• 1. Both exposure and outcome {disease} have

occurred before the start of the study.• 2. The study proceeds backwards from the effect

to cause.• 3. It uses a control or a comparison group to

support an inference.

Case

-Con

trol

Des

ign

Studypopulation

Cases(disease)

Controls(no disease)

factor present

factor absent

factor present

factor absentpresent

past

time

Study begins here

TWO CHARACTERISTICS OF CASES

1. REPRESENTATIVENESS:Ideally, cases are a random sample of all cases of interest in the source population (e.g. from vital data, registry data). More commonly they are a selection of available cases from a medical care facility. (e.g. from hospitals, clinics)

2. METHOD OF SELECTIONSelection may be from incident or prevalent cases:

• Incident cases are those derived from ongoing ascertainment of cases over time.

• Prevalent cases are derived from a cross-sectional survey.

 THREE QUALITIES NEEDED IN CONTROLS

• Key concept: Comparability is more important than representativeness in the selection of controls

• The control must be at risk of getting the disease.

• The control should resemble the case in all respects except for the presence of disease

Cases emerge within a study base. Controls should emerge from the same study base, except that they are not cases.

For example, if cases are selected exclusively from hospitalized patients, controls must also be selected from hospitalized patients.

If cases must have reached a certain age before they can become cases, so must controls. (thus we always match on age)

 1. Identify the pool from which controls may come. This pool is likely to reflect the way controls were ascertained (hospital, screening test, telephone survey).

2. Control selection is usually through matching. Matching variables (e.g. age), and matching criteria (e.g. control must be within the same 5 year age group) must be set up in advance.

SIX ISSUES IN MATCHING CONTROLS IN CASE-CONTROL STUDIES

3. Controls can be individually matched or frequency matched

INDIVIDUAL MATCHING: search for one (or more) controls who have the required MATCHING CRITERIA. PAIRED or TRIPLET MATCHING is when there is one or two controls individually matched to each case.

FREQUENCY MATCHING: select a population of controls such that the overall characteristics of the group match the overall characteristics of the cases. e.g. if 15% of cases are under age 20, 15% of the controls are also.

  4. AVOID OVER-MATCHING. match only on factors known to be causes of the disease.

5. Obtain POWER by matching MORE THAN ONE CONTROL PER CASE. In general, N of controls should be < 4, because there is no further gain of power above four controls per case.

6. Obtain GENERALIZABILITY by matching more than ONE TYPE OF CONTROL

Example:-

• A retrospective study of 46 mothers delivered deformed babies showed that 41 were found to have thalidomide during early pregnancy.

• This was compared with 300 mothers who had delivered normal babies.

Advantages:  1. only realistic study design for uncovering

etiology in rare diseases2. important in understanding new diseases3. commonly used in outbreak investigation4. useful if induction period is long5. relatively inexpensive

Disadvantages:  1. Susceptible to bias if not carefully

designed (and matched)2. Especially susceptible to exposure misclassification3. Especially susceptible to recall bias4. Restricted to single outcome5. Incidence rates not usually calculable6. Cannot assess effects of matching variables

Randomized Clinical Trials vs.Case-Control Studies

Exposure

No Exposure

Randomization

Patients in Baseline State

Patients with DiseasePatients without Disease

Nested case control (NCC) & Case- Cohort• A nested case control study is a variation of a case-control

study in which only a subset of controls from the cohort are compared to the incident cases.

• In a case-cohort study, all incident cases in the cohort are compared to a random subset of participants who do not develop the disease of interest.

• In contrast, in a nested-case-control study, some number of controls are selected for each case from that case's matched risk set.

• By matching on factors such as age and selecting controls from relevant risk sets, the nested case control model is generally more efficient than a case-cohort design with the same number of selected controls

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 time

Cross-sectional Design

timeStudy only exists at this point in time

Studypopulation

No Disease

Disease

factor present

factor absent

factor present

factor absent

• 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

META ANALYSISMeta analysis is a structured literature review technique that attempts to combine similar studies to determine the average effect size for a particular treatment under comparable circumstances with comparable participants.

Meta analysis is all about putting the different pieces of the puzzle together in a scientific way. It combines the findings of many different studies using statistical methods.

These studies offer a real, quantifiable sense of wherethe evidence is leading.

Meta analysis provides a systematic overview of quantitative research that has examined a particular question.

• Advantage :It combines all the research on one topic into one large study with many participants.

• Disadvantage : The danger is that in combining a large set of different studies the construct definitions can become imprecise and the results difficult to interpret meaningfully.

Example:-

• Do individuals who wear sunscreen have fewer cases of melanoma than those who do not wear sunscreen? A MEDLINE search was conducted using the terms melanoma, sun screening agents, and zinc oxide, resulting in 8 randomized controlled studies, each with between 100 and 120 subjects. All of the studies showed a positive effect between wearing sunscreen and reducing the likelihood of melanoma. The subjects from all eight studies (total: 860 subjects) were pooled and statistically analyzed to determine the effect of the relationship between wearing sunscreen and melanoma. This meta-analysis showed a 50% reduction in melanoma diagnosis among sunscreen-wearers.

References

• K. Park, Park’s Textbook of preventive and social medicine.18th edition.

• Hiremath S.S, Textbook of Preventive and Community Dentistry

• Peter.S Essentials Of Preventive Community Dentistry

• William A. Oleckno , Epidemiology: Concepts and Methods

• Nelson .K.E, William.C Infectious Disease Epidemiology

• Social constri--a theory of knowledge and learning which contends that categories of knowledge and reality are actively created by social relationships and interactions.