By Dr.Nihal Salah ShihabProf. Of Public Health &

Community medicine

Observational Studies

Experimental Studies

Observational studiesExperimental or intervention studies

The study use existing phenomena to understand aspects of health or illness

Investigators study people and exposures “in nature

The study test the effect of some intervention on a certain aspect of health or illness.

Investigator assigns (intervene) treatment or exposure by Random allocation of study subjects

Observational studies Experimental or intervention studies

The investigator neither controls the population nor factors exposed

The investigator can control both the population & factors exposed

Observational

studies

Descriptive

Look at Distribution of

disease+ no

Comparison group

Analytic

Look at Determinants

of disease + have a

comparison group

Experimental

(intervention) or Quasi-

experimental Studies

Randomized

controlled Trial,

Community trial &

lab.trial

1. Health care planning

2. Hypothesis generation (constitutes an important

first step in the search for determinants or risk factors)

3. Trend Analysis

Descriptive

study

Case report+

case series

Cross

sectional

study

Ecological

Correlational

study

Analytic

study

Case control

study

Cohort

study

Observational

No comparison Group

Have a comparisonGroup

1-Case Report 2-Case series

Report a new or uniquefinding in a disease e.g. Previously un-described diseaseUnexpected link between diseasesUnexpected new therapeutic effectA rare feature in a disease

Describe Unusual characteristics of a number of patients with a given disease

1- Case Report 2-Case series

Example:

Pulmonary embolism among premenopausal female.

Example:

Kaposi sarcoma a disease of old age has been reported in young adult homosexual men .

1-Case Report 2-Case series

Strengths and limitation:It provides the first report of unexpectedevent, It Generate hypotheses for testing and for further study.

Strengths and limitations:It describe unusualvariation of a diseaseIt can generatehypothesis.

1-Case report 2- Case series

Generalization of the results are rarely

Generalization of the results is limited because:1-Selection of study subjects is unrepresentative2-No comparison group

An ecological study is an epidemiologicalstudy in which the unit of analysis is a population rather than an individual.

(uses data from the entire population to compare disease frequencies in relation to certain exposure during the same period of time or at different points in time.

It correlates between variables

Example: the relation between exposure to black cloud and chest infection in different citiesLack of water sources flourides and dental cares in different communities or countriesThe association between industrialization and

obstructive Pulmonary diseases or lung cancer in different countriescomparing several governorates based on state-wide average air pollution and state-wide average prevalence of respiratory diseases)

Strengths

Easy

Quick

In-expensive

Data about disease frequency or prevalence are available

They cannot prove that one variable causes a change in another variable.

(disease causation)

Does not allow for scientific control of variables.

Data of exposure/health is Unknown for

each individual

This is the observation of a definedpopulation at a single point in time or time interval. Exposure and outcome are measured at the same time point.It Collect data on a health problem from a group of subjects at a single point of time .

Study question :

Occurrence of disease in a single point of time

Example :

Number of female using contraceptive pills among those attending maternal and child health center

Advantages Advantages

SerengthsEasy, quick and notexpensive.

Estimate the overall prevalence of a diseaseEstimate exposure proportion in the population

Suitable to study prevalence of chronic disease.The first step to develop evidence for causal association.

Limitations

Not useful for establishing causal relationships.

It does not allow us to answer the question

,which came first(exposure or the disease)

It may be a coincidence

Data are susceptible to distortion through the bias انحياز وانحراف )in the research during sampling, questionnaire and interviewing.

Limitations

The population census.Market research organizations often use cross sectional studies (for example, opinion polls), the type of sampleused here may be a convenience sample or a quota sample.The prevalence study of skull fractures in childrenadmitted to hospital in Edinburgh from 1983 to 1989.Note that although the study period was seven years it was not a longitudinal or cohort study because information about each subject was recorded at a single point in time.

Descriptive

study

Case report+

case series

Cross

sectional

study

Ecological

Correlational

study

Analytic

study

Case control

study

Cohort

study

Observational

No comparison Group

Have comparisonGroup

What is the study?

It is an observational study that Provide a simple way to investigate causes of diseases,

especially rare ones. (behcet syndrome),

Arthritis, Juvenile reumatoid,( cystic fibrosis)

Study question:

Does the present outcome (disease), occurred due to certain exposure

In this study the investigator starts with the outcome and look backward to detect the history of exposure to the suspected cause.

Identify the cases according to standard criteria for diagnosis (study group) (case definition)

Control subjects must be:Free from the studied disease and should be Representative of the source population from which cases were derived.

They are Matched with cases especially for characteristics that may affect the disease occurrence e.g. age, sex, social class…..Ex, a case control study of asthma among high school students .

Advantages of case control study:

Disadvantages of case control study:

Easy, quick, and cheap.

Useful in studying rarediseases (breast cancer in men)Allows the study of several risk factorsCan prove that an exposure is related to an outcome

Can’t calculate ratesNot useful in rareexposure.

Recall bias as it depends on retrospective history.

A measure of association Can be used to:Measure effect size or quantify the strength of associationbetween a potential risk or protective factor (exposure) and an outcome.

Odds ratio (O.R):O.R. = Odds of exposure among cases / Odds of exposure among control

The result of dividing the proportion of individuals with an attribute by the proportion of individuals without the attribute in a population .

The probability of occurrence of an event as compared with (divided by) the probability of non-occurrence of the event in a population.

TotalControlCases

BAExposed

DCNot exposed

B / DA / C ÷

So, ex, among cases the odds would be

A/A+C ÷C/A+C = A/C

So, ex, among control the odds would be

B /B+D ÷ D/ B+D = B /D

a/ c

O.R. = _______ = AxD÷ BxC

b/ d=1 0r > 1 or < 1

OR=(a × d)/(b × c)O.R=1 means that the odds of exposure among the cases equal the odds of exposure among the control, so no evidence of association between exposure and outcome.

O.R >1 means that the cases have a higher odds of exposure to the risk more than the control.

Ex.,People who ate food from the bakery had 3 timesthe risk of developing hepatitis A compared to people who did not eat food from the bakery

It is used as a descriptive statistic .

Fisher’s Exact Probability test and

the Chi-Square tests.

1- Study of obesity as a risk factor for DM.

2- The effect of high salt intake on Hypertensive adults

3-The study of atrial fibrillation in middle aged men during exercise.

Cohort means a group of people having a common characteristic, e.g.Example: \

A group of female pharmacists working together in a lab and some of them work on certain chemicals(exposed) and others are not (unexposed). They are followed up for a period of time and studying disease(s) occurrence or unfavorable outcomes of pregnancy for example.Ex., A study of cancers and anomalies after atomic reactions

An example of an epidemiological question that can be answered by the use of a cohort study is:

Does exposure to X (say, smoking) associate with outcome Y (say, lung cancer)?

The exposure has already occurred

A cohort of people- with and without the exposure-are followed up over a period of time to see who develops the condition(s) of interest

A cohort study helps in establishing causation

With

exposure

Without

exposure

A cohort group

followed

Exposure( start of the study) outcome

Methodology

A population of exposed and non-exposeddetermined & followed prospectively for a certain period of time “e.g. one year”

Incidence rate of an event for both exposed & non-exposed calculated & relative risk is measured

Statistical analysis (by a test of significance )to assess that the observed difference is real not due to chance

TotalNot diseasedDiseased

A+bBAExposed

C+dDC ÷Not exposed

B+dA+c

-RR= A/(A+B) / C/(C+D) it is a risk measurement ,It measures the association between incidence of disease and certain exposure.

It answer the question:

How many times an exposed person is at risk of developing disease compared to non- exposed?

RR= incidence among exposed / incidenceamong non-exposed.

RR=1 : no association between exposure and the disease. Incidence rate is the same in both groups

RR = › 1 : positive association or increased risk ; exposed group has higher incidence than non exposed.

RR = ‹ 1: negative association or protective effect; non exposed group has higher incidence.

AR= incidence among exposed – incidence among non exposed.x100%

It study the rate of occurrence of the disease in exposed individuals that can be attributed to the exposure.(a real exposure and not by a chance)

Strengths Limitation

Valuable in rareexposure

Less bias in recall & observation

Allows for calculation

of Incidence rate” & Relative risk

Inefficient in evaluating rare diseases.Costly & time consuming Loss of follow up may affect validity of results.

Historical cohort study:

(Better than case control (incidence rate can be

calculated besides causal association)

Ex. Cancer in certain occupations

Nested case control study:

ExampleTo determine if H. pylori (HP) infection was associated with the development of gastric cancer,Parsonnet et al (N Engl J Med. 1991 Oct 17;325(16):1127-31) first identified a cohort of 128,992 persons who had been followed since the mid-1960’s. Of the original cohort, 189 patients developed gastric cancer. The investigators carried out a nested case-control study by selecting all of the 189 gastric cancer patients as cases and another 189 cancer-free individuals from the same cohort as controls. HP infection status was determined using serum obtained in the beginning of the follow-up. All total of 84% of the confirmed gastric cancer cases had been infected previously with HP, while only 61% of the controls had been infected; this indicated a positive association between HP infection and gastric cancer risk.

In cross-sectional study both the risk factor and outcome are present at time of study:

For example, a study finding an association between low CD4 counts and HIV infection does not demonstrate whether HIV infection lowers CD4 levels or low CD4 levels predispose to HIV infection.

For example cases of DM (outcome at present) are matched with a control group and the

History of risk factors are traced retrospectively (Exposure)

An experiment is a

A procedure carried out with the goal of verifying, or establishing the validity of a hypothesis. Experiments provide insight into cause-and-effect.

The investigator can control both the population & factors exposed

The experimenter control the independentvariable (ex. Treatment) Then he measure the dependent variable (ex., health status).

It is the best epidemiological study design to prove causation.

A true experiment is characterized by:

It Randomly allocates the subjects bias.

Controling all Confounding factors.

A comparison group :Assessing the efficacy and safety of the intervention before

being a standard practice through a Comparison with a standard intervention or therapy.

According to randomization; experimental studies are divided into:

Experimental studies

•(Randomized studies

Quasi experimental studies

•Non randomized studies

A- Before and after (Pretest-post test) experimental studies (with no control group):

B- Randomized controled trial (RCT) ;also called (Pretest-posttest control group design)

Post-test only control group design) (rarely)

C- Clinical trials

A-Before and after (Pretest-post test) experimental studies (with no control group):

The study subjects are randomly allocated

The researcher take the pretest measurements or variables

Then intervene with the drug or vaccine and follow up

The researcher take the posttest measurements or variables and then analyze the results

B- Randomized controlled trial (RCT) ;also called (Pretest-posttest control group design)

N.B In a few cases, a pre-test is impossible

because the participants have already been exposed to the treatment, or it would be too expensive or too time-consuming.

And it is called ( post-test only control group design)

1. Identify the target population. ( inclusion & exclusion criteria)

2. Consent (all participants)

3. Random Allocation

Each subject has an equal chance of being included in the control or experimental group.

1. The experimental group Intervention or drug

2. Control group Placebo or traditional therapy

3. Follow up for a specified period

4. The outcome (preventive or curative) is measured (often before and after intervention

5. The outcome is compared (experiment & control)

Examples of the outcomes in clinical trials:

Systolic blood pressure in a hypertension trial

Caesarean section rate in an obstetric trial

Survival time in a cancer trial

Clinical TrialsResearch activities in which: Administration of therapeutic or preventive intervention to evaluate its safety and efficacy.

Clinical trials are useful in evaluating new:

Drugs in treatment of diseases.

Medical technology.

Methods of prevention.

Program for screening and diagnosis.

A-Pre-clinical trials in animals and lab (in vitro)

B-Testing in human through 4 phases”Pharmacokinetics includes the study of the mechanisms of absorption and distribution of an administered drug, the chemical changes of the substance in the body (e.g. by metabolic enzymes such as CYP or UGT enzymes), and the effects and routes of excretion of the metabolites of the drug.[1] Pharmacokinetics is often studied in conjunction with pharmacodynamics , the study of a drug's pharmacological effect on the body.

Volunteers Small

doses

Short

period

Close

supervision

Small doses taken for short period

on severely ill or healthy volunteers

Patient

VolunteersSmall

doses

longer

period

Close

supervision

sometimes this phase is associated with a control group

Patient’s

consent

Usual

doses

longer

periodControl Gp

A classical phase,Mostly this phase is associated

with randomization, double blind and a controlgroup.

Patient’s

consent

Usual

doses

long

period for

20 years

Control gp

1. Single blind : studied persons don’t know whether they belong to the treatment or control group

2. Double blind : studied persons & experimenter not known

3. Triple blind : all the three studied persons, experiment & statistician not known

Single blind

Double blind

Experimental or control group

Triple blind

1.(S )Allows for control of other variableswhich affect outcomes under Investigation.

2.It is the best study design to provecausation and prove validity

3.(L)Insufficient number of subjects lead to

failure to detect true differences

Design a community trial

1. Single community design (before and after intervention).

2. Two Community design, one intervention community and control.

3. One-to-many, the intervention community has several control community.

4. In a many-to-many design there are study with multiple intervention communities and multiple control communities.

S It is useful in natural field circumstances.

LSelection biasPeople in the control community may receive the intervention under study on their own becauseThere is no strict control as occurs in laboratory experimental or animal studies is not possible with humans.

The Salk vaccine trial carried out in 1954 had 200,000 experimental group and 200,000 control groupThe aspirin-myocardial infarction study (as therapeutic) The intervention group received 1.0 gram of aspirin daily whereas the reference group received a placebo.

Two major types of quasi- experimental designs:

1. Pre test – post test, Nonequivalent control group designs with-no random assignment to groups

2. Before and after design- has pretest and posttest with no comparison group with non randomization to the study group

القائمين برعاية حيوانات الرنة

Definition:

It is a : Statistical technique that combine the findings of a set of studies addressingcommon research hypotheses to derive definite conclusion

It Combines contradictory results of several clinical studies on the same subject to derive definite conclusion.

Study question: used to

Describe the best clinical approach to a problem.

Identify new directions for research.

Qualitative aspects

Developing research question to be analyzed

Reviewing literature for relevant clinical studies

Selecting variable common to the studies

Evaluating studies to identify similarities or explain differences Quantitative aspects : statistical analysis of results

Common designObjective

Cross sectionalPrevalence

CohortIncidence

Controlled trial, Cohort, case-control, cross sectional

Cause (in order ofreliability)

CohortPrognosis (future or recovery

Controlled trialTreatment effect

Protection of human rights

Any person who is requested to consent toparticipate as a subject in a research study has the right to be

Informed of nature & purpose of experiment

Given description of any risks to be expected from experiment

Given explanation of expected benefitsfrom the experiment

Informed of medical treatment to subject after experiment if complicated

Given an opportunity to ask any questionsconcerning experiment or procedures involved

Informed that consent may be withdrawn at any time without prejudice.

Given a copy of a signed & dated written consent form when required.

Given an opportunity to decide to consent or not to consent to a medical experiment without intervention