EXPERIMENTAL EPIDEMIOLOGY

DR SAKSHI KAUR CHHABRA

2ND YR PG STUDENT

DEPARTMENT OF PUBLIC HEALTH DENTISTRY

PACIFIC DENTAL COLLEGE AND HOSPITAL,DEBARI2

[1] INTRODUCTION

[2] AIMS

[3] EXPERIMENTAL STUDIES – TYPES

[4] RANDOMIZED CONTROLLED TRIALS

[5] NON- RANDOMIZED TRIALS

[6] USES OF EXPERIMENTAL EPIDEMIOLOGY

[7] ADVANTAGES AND DISADVANTAGES

[8] CONCLUSION

[9] REFERENCES

• In the 1920s, "experimental epidemiology" meant the study of epidemics among colonies of experimental animals such as rats and mice. In modern usage, experimental epidemiology is often equated with RANDOMIZED CONTROLLED TRIALS .

• Experimental or intervention studies are similar in approach to cohort studies excepting that the conditions in which study is carried out are under the direct control of the investigator.

An experiment is the best epidemiological study design to prove causation.

It can be viewed as the final or definitive step in the research process.

A mechanism for confirming or rejecting the validity of ideas, assumptions, postulates and hypotheses about the behaviour of objects, or effects upon them which result from interventions under defined sets of conditions.

[A] TO PROVIDE SCIENTIFIC PROOF

[B] TO PROVIDE A MEASURING METHOD

Experimental studies are of two types :

[1] Randomized controlled trials

[2]Non-randomized or "non-experimental" trials

One of the essential features of a randomized controlled trial is that the study is conducted under a strict protocol.

The protocol specifies:-

[a] the aims and objectives of the study[b] questions to be answered[c] criteria for the selection of study and control groups[d] size of the sample[e] the procedures for allocation of subjects into study and control groups[f] treatments to be applied

The protocol also specifies:-

[g] standardization of working procedures

[h] schedules as well as responsibilities of the parties involved

The protocol aims at preventing bias

to reduce the sources of error in the study.

Selecting reference and experimental populations

Population to which the findings of the trial, if found successful, are expected to be applicable. EXAMPLE• geographically limited • population of a whole city • a population of school children• industrial workers

[A] REFERENCE OR TARGET POPULATION

Selecting reference and experimental populations

• It is derived from the reference population. • It is the actual population that participates in the experimental study.• Ideally, it should be randomly chosen from the reference population, so that it

has the same characteristics as the reference population. • If the study population differs from the reference population, it may not be

possible to generalise the findings of the study to the reference population.

[B] EXPERIMENTAL OR STUDY POPULATION

Randomization is a statistical procedure by which the participants are allocated into groups usually called "study" and "control" groups, to receive or not to receive an experimental preventive or therapeutic procedure, manoeuvre or intervention.

Randomization is an attempt to eliminate "bias" and allow for comparability.

Randomization is the "heart" of a control trial.

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

In other words, by random allocation, every individual gets an equal chance of being allocated into either group or any of the trial groups.

The entire study population can be stratified into subgroups according to the variable, and individuals within each sub-group can then be randomly allocated into study and control groups.

Randomization is done only after the participant has entered the study, that is after having been qualified for the trial and has given his informed consent to participate in the study.

Manipulate the study (experimental) group by the deliberate application or withdrawal or reduction of the suspected causal factor.

This manipulation creates an independent variable whose effect is then determined by measurement of the final outcome, which constitutes the dependent variable.

This implies examination of the experimental and control group subjects at defined intervals of time, in a standard manner, with equal intensity, under the same given circumstances, in the same time frame till final assessment of outcome.

ATTRITION - some losses to follow-up are inevitable due to factors, such as death, migration and loss of interest.

Every effort, should be made to minimise the losses to follow-up.

The final step is assessment of the outcome of the trial in terms of :

(a) Positive results : that is. benefits of the experimental measure such as reduced incidence or severity of the disease, cost to the health service or other appropriate outcome in the study and control groups.

(b) Negative results : that is, severity and frequency of side-effects and complications, if any, including death. Adverse effects may be missed if they are not sought.

The most commonly encountered experiment in health science

research, and the research strategy by which evidence of effectiveness is

measured, is the randomized, controlled, double-blind clinical trial,

commonly known as an RCT.

[A] CLINICAL TRIALS

[B] PREVENTIVE TRIALS

[C] RISK FACTOR TRIALS

[D] CESSATION EXPERIMENTS

[E] TRIAL OF ETIOLOGICAL AGENTS

[F] EVALUATION OF HEALTH SERVICES

For the most part, "clinical trials" have been concerned with evaluating therapeutic agents, mainly drugs.

Recent examples include –

1. Evaluation of beta-blockers in reducing cardiovascular mortality in patient surviving the acute phase of myocardial infarction.

2. Trials of folate treatment before conception to prevent recurrence of neural tube defects.

3. trials of aspirin on cardiovascular mortality and beta carotene on cancer incidence.

The intervention in a clinical trial may include:-

1. Drugs for prevention, treatment or palliation.

2. Clinical devices, such as intrauterine devices.

3. Surgical procedures, rehabilitation procedures.

4. Medical counselling.

5. Diet, exercise, change of other lifestyle habits.

6. Hospital services, e.g. integrated versus non-integrated, acute versus chronic care.

7. Risk factors.

8. Communication approaches, e.g. face-to-face communication versus pamphlets.

9. Different categories of health personnel, e.g. doctors versus nurses.

10. Treatment regimens, e.g. once-a-day dispensation versus three times a day.

It means primary prevention.

These trials are purported to prevent disease on an experimental basis.

The most frequently occurring type of preventive trials are the trials of vaccines and chemo-prophylactic drugs.

For example, in 1946, the Medical Research Council of UK conducted an extensive trial to test whooping cough vaccine from three manufacturers in ten separate field trials.

PREVENTIVE TRIAL

A type of preventive trial is the trial of risk factors in which the investigator intervenes to interrupt the usual sequence in the development of disease for those individuals who have "risk factor" for developing the disease.

For example

1. the major risk factors of coronary heart disease are elevated blood cholesterol, smoking, hypertension and sedentary habits.

RISK FACTOR TRIAL

In this type of study, an attempt is made to evaluate the termination of a habit which is considered to be causally related to a disease.

The familiar example is cigarette smoking and lung cancer.

If in a randomized controlled trial, one group of cigarette smokers continue to smoke and the other group has given up, the demonstration of a decrease in the incidence of lung cancer in the study group greatly strengthens the hypothesis of a causal relationship.

A large randomized controlled trial has been mounted to study the role of smoking cessation in the primary prevention of coronary heart disease

Cessation experiments

One of the aims of experimental epidemiology is to confirm or refute an aetiological hypothesis.

The best known example - retrolental fibroplasia (RLF). Retrolental fibroplasia, as a cause of blindness, was non-existent prior to 1938. It was originally observed and reported by T.L. Terry. a Boston ophthalmologist in 1942 (78). and later in many other countries outside the USA.

Trial of aetiological

agents

Randomized controlled trials have been extended to assess the effectiveness and efficiency of health services. Often. choices have to be made between alternative policies of health care delivery.

An excellent example - controlled trials in the chemotherapy of tuberculosis in India, which demonstrated that "domiciliary treatment" of pulmonary tuberculosis was as effective as the more costlier "hospital or sanatorium" treatment. The results of the study have gained international acceptance and ushered in a new era - the era of domiciliary treatment, in the treatment of tuberculosis.

Evaluation of health services

NON

[A] UNCONTROLLED TRIALS

[B]NATURAL EXPERIMENTS

[C]BEFORE AND AFTER COMPARISONS STUDIES

NON

There is room for uncontrolled trials (i.e., trials with no comparison group).

Uncontrolled trials may be useful in evaluating whether a specific therapy appears to have any value in a particular disease, to determine an appropriate dose, to investigate adverse reactions, etc.

For example – indirect epidemiological evidence that the pap test is effective in reducing mortality from cervical cancer.

UNCONTROLLED TRIAL

Where experimental studies are not possible in human populations, the epidemiologist seeks to identify "natural circumstances" that mimic an experiment.

For example,1. In respect of cigarette smoking, people have

separated themselves "naturally" into two groups, smokers and non-smokers.

2. John Snow discovery - cholera – water borne disease

NATURAL EXPERIMENTS

These are community trials which fall into two distinct groups: -

A. Before and after comparison studies without control

B. Before and after comparison studies with control.

Before and after

comparison studies

• These studies centre round comparing the incidence of disease 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.

• The classic examples of "before and after comparison studies" were the prevention of scurvy among sailors by James Lind in 1750 by providing fresh fruit; studies on the transmission of cholera by John Snow in 1854; and more recently, prevention of polio by Salk and Sabin vaccines.

Before and after comparison

studies without control

This table gives an example of a "before and after comparison study" in Victoria (Australia) following introduction of seat-belt legislation for prevention of deaths and injuries caused by motor vehicle accidents.

Before and after comparison studies with

control 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.

IN THIS EXAMPLE, THE EXISTENCE OF A CONTROL WITH WHICH THE RESULTS IN VICTORIA COULD BE COMPARED STRENGTHENS THE CONCLUSION THAT THERE WAS DEFINITE FALL IN THE NUMBER OF DEATHS AND INJURIES IN OCCUPANTS OF CARS AFTER THE INTRODUCTION OF COMPULSORY SEAT-BELT LEGISLATION.

• [A] It is scientifically ideal method .

• [B] It removes large number of biases .

• [C] It build up ‘faith’in the findings of study .

• [D] It ensures temporal relationship between exposure and outcome.

• [A] It needs long time.

• [B] It has ethical issues.

• [C] It is expensive.

• [D] In many situations especially those which concern study of risk factors, one can not randomly allocate human beings into 2 groups .

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