COMPARATIVE OBSERVATIONAL

STUDY-

Observational study designs are suitable for

validating signals from spontaneous reports or case
series. Traditional epidemiologic methods are
important in the evaluation of adverse events.

Types of designs:
1) Cross-sectional study.
2) Case-control study.
3) Cohort study (both retrospective and prospective).

Cross-sectional

Study Data collected on inhabitants of patients during

a specified interval of time is irrespective of exposure
or disease status establishes a cross-sectional study.
These types of study are mainly used to collect data
for surveys or for ecological analyses.
When data for serial time points can be collected then
these studies are par amounted to scrutinise the
prevalence of a disease at one time point or to inspect
trends over time. Cross-sectional studies are utmost
important when exposures do not change over time.

These studies can also be used to observe the crude

relationship between exposure and outcome in
ecological analyses.

The cross-sectional studies are the temporal

relationship between exposure and outcome that
cannot be straight addressed which a major
disadvantage of this study.
 Case-Control Study

In a case-control study, cases of disease (or events)

are recognised in patients or the control having
disease or event of interest that has not occurred.
These controls and patients are carefully chosen from
the source population that gave rise to the cases. The
control is selected in such a way that the prevalence of
exposure among the controls exemplifies the
prevalence of exposure in the source population.

The status of exposure for the two groups is paralleled

using the odds ratio, which is an evaluation of the
comparative risk of disease in the two groups. For the
purpose of the study the patients can be recognised
from an existing database or using data collected
unambiguously.

In case a safety data is sought for special populations,

the cases and controls can be stratified on the basis of
the population of interest. For rare adverse events,
prevailing large population-based databases are a
valuable and effective method of providing the
required data on medicine exposure and medical
outcome is relatively quick.

To examine whether there is a relationship between a

medicine (or medicines) and one specific rare adverse
event, as well as to identify risk factors for adverse
events then case-control studies are mainly effective.
Risk factors can include conditions like renal and
hepatic dysfunction, which might alter the relationship
between the medicine exposure and the adverse event.
A case-control study can deliver the complete
incidence rate of the event under particular conditions.
 Cohort Study

A population at risk for the disease (or event) is

observed over time to record the occurrence of the
disease (or event) in a cohort study. Exposure status
information is available during the follow-up period
for each patient. A patient might be exposed to a
medicine at one time during follow-up, but not
exposed at another time. Meanwhile the population
exposure during follow-up is acknowledged,
incidence rates can be calculated, concerning
medicine exposure, appraisal cohorts of interest are
selected on the basis of medicine use and monitored
over time in many cohort studies.
Objectives

CEM and spontaneous reporting has the same

objective which is more effective.
1) To provide incidence rates for adverse events as a
measure of risk.
2) To characterise the known adverse reactions.
3) To identify signals of unrecognised reactions.
4) To detect interactions with other medicines,
complementary and alternative medicines,
foods and concomitant diseases.
5) To identify risk factors and therefore offer evidence
on which to base effective risk management.
6) To evaluate safety in pregnancy and lactation.
7) To give a measure of comparative risks between
medicines.
8) To provide cohorts for additional study of safety
issues.
9) To detect inefficacy, which might be due to:
i) Faulty administration;
ii) Poor storage conditions;
iii) Poor quality product;
iv) Counterfeit product; and
v) Interactions.
Epidemiology

The main epidemiological characteristics of CEM can

be described as follows:

1) Observational: Observational studies are “non-

interventional” and are undertaken in real-life
situations. Patients are not selected as per any criteria
- all patients who receive ART are considered until the
desired cohort size is reached. This contains patients
of all ages, those with other diseases and those on
other medicines. Treatment is given according to the
usual local strategies.

2) Prospective: This means that CEM is planned

before the patients are treated and ART is observed
until the end of the programme, or until they cease to
receive treatment for whatever reason.

3) Inspectional: It is similar to prospective i.e., from

the time of commencement of their treatment every
patient is followed-up for adverse events.
4) Dynamic: This means that due to sufficient
numbers in the cohort new patients are added as the
study continues until dynamic time.

5) Longitudinal: This means that the events

occurrence in patients are evaluated over a period of
time until the end of the programme, or until they
cease to receive treatment with the monitored
medicines.

6) Descriptive: This means that all events are

recognised and termed, their frequency is calculated
and their distribution in different subgroups of interest
in the cohort is recorded and analysed.
 Advantages and Disadvantages

Advantages

1) They can produce rates.

2) They can produce a new profile of the adverse
events and/or adverse reaction for the interested
medicines.
3) They can recognise signals very effectively at an
early stage.
4) They can characterise reactions in terms of age, sex
and duration to onset, and dose, and other related
factors. Other important data can be collected like
weight, comorbidity or region to provide the
opportunity for determining other risk factors.
5) They are capable of making accurate comparisons
between medicines.
6) The are capable of establishing a pregnancy register
and recognising problems with pregnancy and
common congenital abnormalities.
7) The method, can detect reduced or failed
therapeutic effect by using routine follow-up and
therefore increase the suspicion of inaccurate
diagnosis of disease, poor prescribing, inadequate
adherence to treatment, emerging resistance or poor
quality or counterfeit medicines.
8) The ability to record and examine data of all deaths
and provide rates of death.
9) This method collects comprehensive and near-
complete data that will offer all the special needs of
the HIV programme, including effects of ART in
pregnancy, specific toxic ides and safety in children.
10) It looks intensively at new drugs of great interest
in a specific area of requirement, and provides quick
clinically significant results, thus stimulates interest in
drug safety in over-all.

11) The method offers sound evidence to deal with

any drug scares.

Disadvantages
1) It is more costly and more labour intensive than
spontaneous reporting.
2) Training in its use will be necessary as it is new to
healthcare Experts and PvCs.