DR m a thaher

Pg 1st year

COMMUNITY MEDICINE 07/04/2015

“THE SMOKING OF 30-40 CIGARETTS PER DAY CAUSES LUNG CANCER IN 10% OFSMOKERS AFTER 20 YEARS OF EXPOSURE”

HYPOTHESIS

EPIDEMIOLOGY METHODS

1.OBSERVATIONAL STUDIES

A.DESCRIPTIVE B.ANALYTICALSTUDIES STUDIES

1.ECOLOGICAL2.CROSS-

SECTIONAL3CASE-CONTROL4.COHORT

HYPOTHESIS

FORMULATION TESTING

2.EXPERIMENTAL STUDIES

INTERVENTIONAL STU

A.RCT

B.FIELD TRIALS

C.COMMUNITY TRIALS

CONFORMATION

EXPERIMENTAL EPIDEMIOLOGY

In the 1920s,”experimental epidemiology” meant thestudy of epidemics among colonies of experimentalanimals such as rats and mice.in modernusage,experimental epidemiology is often equatedwith RCT.

AIMSTo provide a scientific proof.

To provide a measuring method.

Animal studies

At the beginning of this century ,,WEBSTER(us)andTOPLEY,WILSONandGREENWOOD(england) carried out animal experiments.

ADVANTAGES

Experimental animals can be bred inlab,manpulatedeasily according to investigator wishes.

Multyply rapidly

Limitations:-

Not all the diseases reproduse in animals.

All the conclusions derived from animal experiments may not be strictly appicable

to human beings.

EX:-WHO trial on typoid vaccine.-Almorth WrightRCT trials.

Animal studies

HUMAN EXPERIMENTS

Human experiments will always be needed to investigate disease aetiology and to evaluate the preventive and therapeutic measures.

These studies are even more essential in the investigation of diseases that cannot be reproduced in animals.

Ex: JAMES LIND

EDWARD JENNER

GOLDBERGER’S EXPERIMENT.

Although the experimental method is unquestionably the most incisive approach to scientific problem, ethical and Iogistic considerations often prevent its application to the study of disease in humans.

Therefore, before launching human experiments, the benefits of the experiment have to be weighed against risks involved.

The volunteers should be made fully aware of all possible consequences of the EXPERIMENT.

Thus when an illness is fatal (e.g., excessive haemorrhage) and the benefit of treatment (e.g., blood transfusion) is self-evident, it would be ethically unacceptable to prove or disprove the therapeutic value of blood.

However, such instances represent only a small part of the total research effort.

On the other hand, in the present era of scientific medicine, many unscientific or scientifically unsound procedures are still being carried out.

EX;diethylstilbesteral-ca.vagina.

The WHO in 1980 has laid down a strict code of practice in connection with human trials.

Experimental studies are two types.

A. RCT

B. NON-RANDAMOISED.

It IS really an epidemiologic experiment.

Since its introduction. The RCT has questioned the validity of such widely used treatments as oral hypoglycemic agents, varicose vein stripping, tonsillectomy, ……etc

For new programmes or new therapies, the RCT is the No.1 method of evaluation.

RANDOMIZED CONTROL TRIALS

Basic steps in RCT conducting:

1.Drawing up a protocol.

2.Selecting reference and experimental populations.

3.Randomization .

4.Manipulation or intervention

5.Follow –up

6.Assessment of outcome

It specifies:-

Aims &objectives of study

Questions to be answered

Criteria for selection of study and control groups

Size of sample

The procedures for allocation of subjects into study and control groups.

Treatment to be applied.

Standardization of working procedures

Schedules and responsibilities of the parties involved

1.The protocol

AIM:-

preventing bias and to reduce the source of errors in the study.

Preliminary test runs: some times it is useful to have short test to run of the protocol to see any flaws

Protocol

REFERANCE POPULATION:-

Population to which the findings of the trail are expected to be applicable.

Ex :-specific age group people

geographically limited

population of school children

SELECTING REFERENCE &EXPERIMENTAL

POPULATION

it is derived from reference population.

It is the population that actully participates in experimental studies.

Participants must fullfil 3 criterias….

1.must give informed consent

2.should be representative of the population.

3.should be eligible for the trail.

EXPERIMENTAL POPULATION

it is a statistical procedure by which participents allocated in to study and control groups.

it is a heart of RCT

It is an attempt to eliminate bias and allow for comparability.

It will give greatest confidence that the groups are comparable so that”like can be compared with like”.

RANDOMIZATION

Randomization is done only after the participants

entered the study,that is after having been qualifiedfor the trial and has given informed consent toparticipate in study.

Randomization best done by using a table of randomnumbers.(simple random sample).random numbersare a haphazard collection of certainnumbers,arranged in a cunning manner to eliminatepersonal selection of unconscious bias in taking outthe sample.

Randomization

After selection of study& control group,intervene the

study group by deliberate application(vaccine, drug) as laid down in protocol.

This manipulation creates an independent varieble(e.g. drug,vaccine)whose effect is then determinedby measurement of the final outcome,whichconstitutes the dependent varieble(incidence ofdisease,survival time.)

MANIPULATION

This implies examination of the experimental &

control group subjects at defined intervals of time,ina standard manner,with equal intensity,under thesame given circumstances,in the same time frame tillfinal assessment of outcome.

Attrition:-some cases losses to follow-up due todeath,migration,loss of intrest.

If the attrition is substantial,it may be difficult togeneralise the results to refferens population.

FOLLOW-UP

POSITIVE RESULTS:-Benefits of experiment

measurers reduced incidence or severity ofdisease…..

NEGATIVE RESULTS:-Severity and frequency ofside-effects and complications,if any,including death.

ASSESSMENT

Bias may arise from errors of assessment of the

outcome due to human element.these may be from 3sourses.

First - bias from the participants,who maysubjectively feel better or report improvement if theyknew they were receiving a new form oftreatment.known as subjective variation.

Second –investigater measuring the outcome of atrial may be influnced if he knows beforehand theparticular therapy to which the pt hassubjected.(observer variation)

BIAS

BLINDING:-In order to reduce aboveproblems,blinding is adapted .it can be done in 3ways.

A.Single blind trials:-participant is not aware ofgroup allocation.

B.Double blind trials:-neither doctor norparticipant is aware of group allocation.& Rxreceived.

C.Triple blind trials:-participant,investigater andperson analysing data are blind.

Third there may be bias in evaluation.-theinvestigator may give subconsciously give a

favorable report of the outcome of trial.

1.Concurrent parallel study designs

2.Cross over type of study design.

STUDY DESIGNS

Concurrent parallal study designs.

Cross over type of study design

For the most part,”clinical trials” have beenconcerned with evaluting therapeutic agents,mainlydrugs.

Eg: trials of folate- to prevent NTD.

efficacy of tronsillectomy for recurrentthroat infections.

Many ethical, administrative, & technical problemsare involved in the conduct of clinical trials.

Types of RCT-1.clinical trials

It implies primary prevention.

Most common trials are done vaccines & chemoprophilactic

Eg: Medical research concil of UK – woophing cough

since preventive trials involve larger number of subjectsand longer time span to obtain results,there may begreater number of practical problems in theirorganisation and execution.

2.Preventive trials

A type of prevenive trials in which he investigatorinternvenes to interrupt the usual sequence in thedevelopment of disease for those individual who has

risk factor in developing the disease

Often this involves risk factor modification

Eg. CHD- 4 major risk factor- WHO study- clofibratetherapy

OSLO study, MRFIT in US

3.Risk factor trial

Another type of preventive trial is ihe cessation

experiment. In this type of study, an attempt is made to

evaluate the termination of a habit (or removal ofsuspectedagent) which is considered to be causallyrelated to a disease.

If such action is followed by a significant reduction in the disease, the hypothesis of cause is greatly strengthened.

Ex :cigarette smoking-lung cancer.

Cessetion experiments

One of the aim of experimental etiology is to confirm

or refute etiological hypothesis.

eg;: RLF

Since most disease are fatal,disabling, human experiments to conform an aetiological hypothesis are rarely possible.

5.Trial of etiological agents

RCT have been extended to assess the efectiveness &

efficiency of health services.

Eg: Domicilliary treatment- pulm. Tuberculosis.

Health services research studies.

6.Evaluaton of health services

Due to ethical, administrative, cost it is not always

possible to resort to RCT.

Approach is crude. As there is no randamisation, degree of comparability will be low and chances of spurious results will be high.

Non Randamized Trials

1. Uncontrolled trials:

Trials with no comparision groups.

Useful to known whether specific therapy is valuable for particular disease, to determine the appropriate dose, to investigate adverse reaction.

Eg:indirect epidemiological evidence that the pap test is effective in reducing mortality from cervical cancer.

Examples of non randamized trials

2. Natural experiments: Where experimental studies are not possible in human

beings, some natural circumstances mimics as experiment

Eg: smokers and non smokers- lung cancer. John snow discovery- cholera- water born disease.

Non-randomized trials

John snow’s experiment

3.BEFORE AND AFTER COMPARISON STUDIES:

These community trials fall into 2 distinct groups.

A.Before & after comparison studies without control.

B.Before & after comparison studies wth control

Non-Randomized trials

These studies centre round comparing the incidence

ofdisease before and after introduction of a preventive measure.

The events which took place prior to the use of the new treatment or preventive procedure are used as a standard for comparison.

In other words, the experiment serves as its own control; this eliminates virtually all group differences.

Before &after comparison studies without control

Ex:James Lind –scury experimentPrevention of polio by salk and sabin vaccine

In order to establish evidence in before and after comparison studies, the following are needed; (a) data regarding the incidence of disease, before and after introduction of a preventive measure must be available

(b) there should be introduction or manipulation of only one factor or change relevant to the situation, other factors remaining the same.

as for example, addition of fluorine to drinking water to prevent dental caries

(c) diagnostic criteria of the disease should remain the same

(d) adoption of preventive measures should be over a wide area

(e) reduction in the incidence must be large following the introduction of the preventive measure, because there is no control.

1970 1971 %change

deaths 564 464 -17.7

injuries 14620 12454 -14.8

Effect ofadoption of compulsory seat-belt legislation in vectoria,Aus-1971

In the absence of a control group, comparison

between observations before and after the use of a new treatment or procedure may be misleading.

In such situations, the epidemiologist tries to utilize a "natural" control group i.e., the one provided by nature or natural circumstances.

If the preventive programme is to be applied to an entire community. he would select another community as similar as possible, particularly with respect to frequency and characteristics of the disease to be prevented.

Before and after comparison studies with control

1970 1971 %change

DEATHS

Victoria 564 464 -17.7

Other states 1426 1429 0.2

INJURIES

Victoria 14620 12,454 -14.8

Other states 39,980 40,396 1.0

Effect of adaptation of compulsary seat-belt legislation in victoria comparing with other states(where legislation not

applied)

Scientifically ideal method.

Removes a large number of biases related to selection and measurement,

Ensures temporal relationship between exposure and outcome.

Builds up ‘faith ‘ in the findings of the study.

Advantages

In many situations, rspecially those which concern

study of risk factors or prognostic factors,one can not randomly allocate human beings into two groups.

Eg ;-smoking- lung cancer

Ethical issues.

Expensive

Long time need…..

Disadvantages

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