epidemiological methods

Epidemiological

methods

Observational studies

Experimental studies

Descriptive studies

Analytical studies

Randomized controlled trials

Field trials

Community trials

 Experimental or intervention studies are studies carried out under the direct control of the investigator.

These studies involve some action,intervention or manipulation such as deliberate application or withdrawal of a suspected cause or changing one variable in the causative chain in the experimental group,

 no change in the control group May be conduced in animals or human beings.

 To provide scientific proof of etiological factors which may permit modification or control of those diseases. To provide a method of measuring effectiveness and efficiency of health services. Experimental reproduction of human disease to confirm etiological hypothesis.

Types of experimental studies

A. RANDOMIZED CONTROLLED TRIALS
{i.e. those involving a process of random allocation}

B. NON-RANDOMIZED OR NONEXPERIMENTAL {i.e. those departing

from the strict randomization for practical purposes, but in such a manner that nonrandomization doesn't seriously affect the theoretical basis of conclusion.}

 Well-designed RCTs are considered the gold standard for measuring an interventions impact across many diverse fields of human inquiry, such as education, welfare and employment, medicine, and psychology. This is based on persuasive evidence that they are superior to other methods in estimating an interventions true effect;

RCTs are studies that measure an interventions effect by randomly assigning individuals (or groups of individuals) to an intervention group or a control group.

Select suitable population {Reference or target population} Select suitable sample {experimental or study population} Make necessary exclusions.

Those not eligible

Randomize
Experimental group Control group Those who do not wish to give consent

Manipulation and follow-up assessment

 One of the essential feature of RCT is that the study is conducted under a strict protocol. The protocol specifies the aims and objectives of the study size of sample criteria for selection of study and the control groups the procedures for allocation of the subjects treatment to be applied. standardization of working procedures and schedules as well as responsibilities of parties involved in trial.

1.THE PROTOCOL

Once a protocol has been Evolved , it should be strictly adhered to throughout the study.

o Sometimes, before a protocol is completed, preliminary studies(pilot studies) have to be made to find out the feasibility or operational efficiency of certain procedures or unknown effects or on the acceptability of certain policies. o It is useful to have a short test run of the protocol to see whether it contains any flaws.

2.Selecting reference and experimental population

o It is the population to which the findings of the trial, if found successful,are expected to be applicable.{e.g.drug,vaccine or other procedure} It may be as broad as mankind or it may be geographically limited or limited to persons in specific age,sex,occupational or social groups. It may be a whole city, population of school children, industrial workers and so on according to nature of study.

B.EXPERIMENTAL OR STUDY POPULATION

It is the population that participates in the experimental study. from reference population, so that it has same characteristics as that of reference population. Important to whose cooperation is assured to avoid losses to follow up.

 The participants must fulfill the following three criteria: 1)They must give

that is they to participate in the trial after having been fully informed about the purpose, procedures and possible dangers of the trial. 2)They should be representative of the population to which they belong. 3)They should be or eligible for the trial.

3.RANDOMIZATION
It is a statistical procedure by which the participants are allocated into groups usually called and groups. It is an attempt to eliminate bias and allow for comparability.

By random allocation, every individual gets an equal chance of being allocated into either group or any of the trial group. It ensures that investigator has no control over allocation of participants to either study or control group, thus eliminating what is known as .

It is the

of a control trial.

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

4.MANIPULATION
Having formed the study and control groups, the next step is to intervene or manipulate the study by deliberate application ,withdrawal or reduction of suspected casual factor as laid down in protocol.

manipulation creates independent variables {drug or vaccine}whose effect is then determined by the measurement of final outcome, which constitutes the dependent variables {incidence of disease or survival time.}.

5.FOLLOW-UP
This implies examination of 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 the final assessment of outcome. Follow-up may be short or may require many years. Some losses to follow-up are inevitable due to factors such as death, migration and loss of interest , known as attrition.

6.ASSESSMENT
The final step is assessment of outcome of trial in terms of : a) POSITIVE RESULTS: That is, the benefits of the experimental measures such as reduced incidence or severity of disease. b) NEGATIVE RESULTS: that is, severity and frequency of sideeffects and complications. The incidence of positive/negative results is rigorously compared in both the groups,

BIAS
Bias may arise from errors of assessment of outcome due to human element. These may be from three sources; 1. Bias on the part of participants, who may subjectively feel better or report improvement if they knew they were receiving a new form of treatment. 2. there may be observer bias, that is the investigator measuring the outcome of a therapeutic trial may be influenced if he knows beforehand.

3.There may be bias in evaluation.-that is the investigator may subconsciously give a favorable report of the outcome of the trial. .

 In order to reduce these problems, a technique known as is adopted, which will ensure that the outcome is assessed objectively

BLINDING
Blinding can be done in 3 ways: a) SINGLE BIND TRIAL: The trial is so planned that the participant is not aware whether he belongs to study group or control group. b) DOUBLE BIND TRIAL: neither the doctor nor the participant is aware of the group allocation and the treatment received. c) TRIPLE BIND TRIAL: the partcipant,the investigator and the person analyzing data are all blind. Double blinding is the most frequently used method when a blind trial is conducted.

Concurrent parallel study designs Cross-over type of study designs

 In this situation, comparisons are made between two randomly assigned groups, one group exposed to specific treatment and the other group not exposed. Patients remain in the study group or the control group for the duration of the investigation.

 Here, each patient serves as his own control. The study and control group receives the treatment and the two groups are observed over time. Then the patients in each group are taken off their medication from the body and for the possibility of any carry-over effects. After this period ,the two groups are switched. Those who receive treatment under study are changed to the control group therapy or placebo,and vice versa.

Types of randomized controlled trials

1. Clinical trials 2. Preventive trials 3. Risk factor trials 4. Cessation experiments 5. Trial of etiological agents 6. Evaluation of health services

 Clinical trials have been concerned with evaluating therapeutic agents, mainly drugs. It may be done for various purposes, some common types are: a) Prophylactic e.g. immunization b) Therapeutic e.g. drug treatment c) Safety e.g. side effects of oral-contraceptives. a) risk factor trials e.g.withdrawing agent[smoking} through cessation Unfortunately ,not all clinical trials are susceptible to be blinded.

Phases of clinical trial

Phase 1 Phase 2 Phase 3 Phase 4

 Phase 1 It is preceded by considerable research, including pharmacological and toxicological studies in experimental animals to establish that new agent is effective and may be suitable for human use, and to roughly estimate the dose to be used in man includes studies on volunteers who are institutionalized occupy research beds

 Phase 2

It is also carried out on volunteers to assess the effectiveness of the drug or device, to determine the appropriate drugs dosage, to investigate its safety.

Phase 3
This is the classical phase the one usually referred to as clinical trial and reported in health research journals. It is performed on patients, who should consent to being in a clinical trial. The purpose of this phase is to assess the effectiveness and to assess the safety in continued use of drug or device in a larger and more heterogeneous population than in phase 2.

 It includes more detailed study and monitoring Usually carried out in hospital in patients, but may be performed on outpatients with intensive monitoring and follow-up. It requires superior clinical and epidemiological skills, laboratory technology, also requires proper planning, organization, proper follow-up and supervision. Results from phase3 trials are used by regulatory agencies to evaluate whether a new product or device should be licensed for general public use.

Phase 4 The purpose of phase 4 is to re-assess the effectiveness , safety ,acceptability and continued use of the drugs or devices under these conditions. It adds to the evidence of safety. It requires additional epidemiological and biostatistical skills, as well as research requirements, including record-keeping and computer facilities.

 Preventive trials implies trials of primary preventive measures. These trials are purported to prevent or eliminate disease on experimental basis. The most frequently occurring type of preventive trials are the trials of vaccines and chemoprophylactic drugs. It may be necessary to apply the trial to groups of subjects instead of to individual subjects.

 Analysis of preventive trial must result in a clear statement about: a) The benefit community will derive from the measure. b) The risk involved c) The costs to the health service in terms of money, men and material resources. since preventive trials involve larger number of subjects and sometimes a longer time span to obtain results, there may be a greater number of practical problems in their organization and execution.

 A type of trial is 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 in the disease;often this involves risk factor modification. These trials can be single-factor or multifactor trials. Both the approaches are complimentary and both are needed.

 In this type of study,attempt is made to evaluate the termination of habit{for removal of suspected agent},which is considered to be casually related to a disease. If such action is followed by a significant reduction in the disease,the hypothesis of cause is greatly strengthed. The familiar example is cigarette smoking and lung cancer.

 One of the aims of experimental epidemiology is to confirm or refute on etiological hypothesis. Since most diseases are fatal, disabling or unpleasant, human experiments to confirm etiological hypothesis are rarely possible.

 These 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. The necessity of choice arises from the fact that the resources are limited, and priorities must be set fir implementation of large number of activities, which could contribute to the welfare of society.

 CITs are usually carried out in the hospitals or clinics, and are usually directed at a patient group with specific health conditions. However randomized experiments are also sometimes done in the community. Classic example of community intervention trial would be that of testing a vaccine. Communities selected for entry to the study have to be similar as much as possible, especially since only a small number of communities will be selected.

 Very often blinding is not possible in these type of studies, and contamination and cointerventions become serious problems. Contamination occurs when individuals from one of the experimental groups receive the intervention from other experimental groups. The fact that these trial use randomization by communities also reduces sample size: the effective sample size is the number of communities, not the number of people in these communities.

They are time- and energy- intensive They are expensive They may not be feasible for all interventions or settings (e.g., some institutions have policies that prohibit random assignment)