Study designs

For Pharmacy Students

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 Learning Outcome
• When you complete this session you will be able to
– Know and appreciate when to use descriptive study design
– Describe the characteristics and design of analytic
(observational) and experimental study
– Describe when to use the different types of analytic
observational study design
– Know the pros and cons the different types of study designs

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 Study designs
• Study design is the process that guides researchers on
– how to collect, analyze and interpret observations (data)

• It is a logical model that guides the investigator in the

various stages of the research
• Several classifications of study design are possible,
depending on what research strategies are used

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 Study designs…
The type of research design chosen depends on:
– The type of problem;
– The objective of the problem to be studied;
– The knowledge already available about the problem; and
– The resources available for the study
– The means of obtaining information
– The availability and skills of the researcher

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 Study designs…
There are two main categories of research design:
1. Observational (non-intervention) study, and
– The researcher just observes and analyses researchable objects
or situations but does not intervene

2. Experimental or intervention study

– The researcher manipulates objects or situations and measures
the outcome of his manipulations

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 Study designs…
An observational study may be exploratory, descriptive or
analytical
An exploratory study
• Is a small-scale study of relatively short duration, which
is carried out
– when little is known about a situation or a problem or
– If the problem and its contributing factors are not well defined

• It may include description as well as comparison

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 Exploratory…
Example
A national AIDS Control Programme wishes to establish
counseling services for HIV positive and AIDS patients, but
lacks information on specific needs patients have for
support

• it is advisable to do an exploratory study before

– embarking on a large-scale descriptive or comparative study

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 Descriptive studies

• Characterize the occurrence and distribution of

problems by time, place and person
• The information obtained in most descriptive studies
allows
– the generation of hypothesis, which can be tested by
analytical or experimental design

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 Types of descriptive studies:

• Case report: gives a detailed report of single patient

– can give the first clues in the identification of new disease
and effect of exposure
– Eg. unexpected new therapeutic effect or adverse events

• Case series: reports of a series of cases of a specific

condition,
– often used as an early means of identifying the presence of
epidemic
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 Types of descriptive…

Ecological descriptive studies:

• the unit of measurement is an aggregate (e.g., family,
clan, or school) or
– an ecological unit(a village, town or country)

Cross-sectional studies
• It involves the collection of data on a cross-section of the
population
– provide a prevalence rate at a particular point in time (point
prevalence) or over a period of time 10
 Types of descriptive…

• In this type of study, the status of an individual with

respect to the presence or absence of
– both exposure and disease is assessed at the same point in time

• Usually involve collection of new data

• Not good for studying rare diseases or diseases with
short duration;
– also not ideal for studying rare exposures

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 Types of descriptive…

• Often a cross-sectional study may have both descriptive

and analytical components
• If data are collected both on exposures and outcomes of
interest, and analyzed so as to demonstrate
– differences between exposed and non-exposed groups, this is
an analytical cross-sectional study

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 Advantages and disadvantages of cross-sectional studies

Advantages Disadvantage

They are relatively quick and Does not allow the true temporal
inexpensive sequence of exposure and outcome
to be ascertained, therefore unable
to shed light on cause and effect
association

Often a good step for cohort study Potential bias in measuring exposure
Provide prevalence information Not feasible for rare conditions
Can study several factors or
outcomes at one time
Often provide early clues for
hypothesis generation
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 Analytical studies

• Observational studies, where the primary goal of a study

is establishing a relationship (association)
– between a risk factor and an outcome

• Always require a comparison group

• There are two types of analytical studies: case control
and cohort studies (remember cross sectional!!!)

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 Observational Analytic Studies

exposure outcome cohort

exposure outcome case-control

exposure outcome cross-sectional

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 Case-control study: basic design concepts

 The first step in case control study is to detect a number of

people with the disease under study: the cases
 Then select the number of people who are free of the
disease: the controls
 The cases and controls are then investigated to see which risk
factors differ between them
 Most commonly used analytical strategy in epidemiology

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 Case-Control Study…

Exposure
Disease
? (Case)

? No disease
(Control)

Retrospective Nature

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 Case-Control Study….

• PAST PRESENT
• It is a type of an observational analytic study
• Compares one group among whom a problem is present
with another group where the problem is absent in order to
find out factors contributing to the problem
• Problem examples- lung cancer, hypertension, breast
cancer etc.

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 Application of Case-Control studies

• It is good to do for rare diseases or outcomes

• Better for diseases with long latency between exposure
and outcome
• It may be possible to explore a wide range of potential
exposures for a single outcome

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 Advantages and disadvantages of case-control study
Advantage Disadvantage

• Is inefficient for the evaluation of rare

• Is relatively quick and inexpensive exposures
• Is optimal for the evaluation of rare • Cannot directly compute incidence
diseases rates of disease in exposed and non-
• It can assess several exposures exposed individuals.
(determinants) of a single outcome
• Is particularly prone to bias compared
• It can also be done from available with other analytic designs, in
data particular, selection and recall bias.
• A small sample size may be needed

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 Cohort study
• Healthy subjects are classified on the basis of their
specific exposure status and are followed
– for a specific time to determine for the development of a
disease

• There is usually a follow up.

• Relatively expensive (time, cost)
• Measure of association is using Relative risk
• There are basically two types of cohort studies:
– prospective and retrospective (historical) 21
 Cohort study…

• In retrospective cohort, the starting point, i.e., the point

of initial exposure
– occurred sometime in the past and the experience of the
population is followed up to present

• At the time the study is initiated, both the exposure and

the outcome have occurred

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Steps of a Cohort Study

• Identify group of exposed subjects

• Identify group of non-exposed subjects
• Follow-up both groups for occurrence of disease
• Measure frequency of disease occurrence in both
groups
• Compare risks between exposed and non-exposed
group
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 Cohort study design
Time

Direction of
inquiry
Disease
Expose
Peopl d No disease
Population e with
out a
disea Disease
se Not -
Exposed No disease

Simple
Observation 24
 Prospective Cohort Study

Study starts Exposure Disease

occurrence occurrence

ill
+ -
+ +
exp exp
- -

Selection of Prospective assessment Time

population of exposure and disease

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 Rétrospective Cohort Study

Exposure Disease Study

occurrence occurrence takes place
ill
+ -
+
exp
-

Retrospective assessment Selection based

of exposure and disease on population

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 Cohort study…
Advantages Disadvantages

• Can examine multiple effects • Is inefficient for the evaluation

of a single exposure
• Can measure incidence and of rare diseases
risks
• Needs large sample size
• Good for rare exposures
• Clear temporal relationship • Dependent to latency period
• Less subject to selection bias • Lost to follow-up
• Ethical considerations

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 Experimental Study Design
 Experimental study designs are the primary method for
testing
 the effectiveness of new therapies and other interventions, including
innovative drugs

 An experiment is a study designed to compare benefits of

 an intervention with standard treatments, or no treatment, such as
 a new drug therapy or prevention program, or to show cause and
effect r/ship

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 Experimental….
 True experiment has the following elements:
 Manipulation, control, randomization (assignment and selection)

 Manipulated and controlled - manipulation caused the

outcome
 Highly controlled and systematic procedures – minimize error

and bias

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Flow Chart of an Experiment

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 Types of Experimental studies

 There are many different approaches used in experimental

studies,
 from very tightly controlled laboratory experiments to large scale
community intervention trials

 In broad terms there are two major types of experimental

study. Those where the unit of measurement and exposure is:
1. the individual
2. the population

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 Types of experimental…

 Individual-based experimental studies are sometimes sub

divided on the basis of the level of the outcome
 as clinical trials (or therapeutic, secondary, or tertiary prevention
trials), and field trials (primary prevention trials)

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 Types of experimental…

Community trials
 Experimental studies in whole populations (communities) are
usually
 referred to as community trials or community intervention studies

 Community trials focuses on mass education campaigns

 aimed at changing people’s knowledge and attitudes

 the exposure is usually given to subjects (for example, mass

prophylaxis, food fortification),

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 Randomized, controlled clinical trials (RCT)

 Patients are assigned to one of two or more groups that

receive a treatment or intervention
 are followed over time for a measured outcome

 The main objective of this method is to make certain that,

after the trial is over,
 the better (or best) of the studied treatments is identified

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 Terms in RCT

Experimental group: The group of patients that receives the

drug under investigation

Control group: The group of patients that receives a different

type of treatment,
 either a traditional one (already approved and used in therapy) or no
treatment (a placebo)

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 Terms in RCT
Randomization:
 The process of assigning individual patients to different
treatment groups
 in a way that each patient has the same chance, equal to and
 independent of every other patient, of being selected

 The idea is to make all study groups as equal as possible at

the beginning of the experiment

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 Terms in RCT..
Blinding:
 The process of ensuring that almost everyone involved in the
drug trial is unaware of
 who is receiving the experimental drug and
 who is receiving a traditional drug treatment, or a placebo,
throughout the duration of the study
 In experimental studies, lack of knowledge about which
patients are receiving which treatments may be
 limited to the patients (single-blind);
 patients and treating clinicians (double-blind); or
 patients, treating clinicians, and the scientific investigators (triple-
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blind)
 Terms in RCT…
Placebo: An inactive form of treatment, usually an inert sugar
pill, received by patients in the control group
 This treatment provides the basis for the controls to receive
 no (beneficial) treatment so that a good comparison can be made with
the results of the experimental group

 Its use in most clinical trials is declining due to ethical concerns

 The best method for determining the true therapeutic benefit

of a new unknown treatment is
 the randomized, controlled clinical trial
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 When can a Randomized Trial be used?

A randomized trial to be feasible and justifiable the

following requirements should generally be met:

 the exposure should potentially be modifiable
 (factors like genotype, family history, and demographic

characteristics cannot be altered so their impacts on disease

occurrence must be studied with observational designs)

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 When can a Randomized Trial ……

 The exposure should be potentially modifiable by the

investigator
 (exposure such as occupation, marital status, and smoking habits
can in principle be changed but often impossible or impractical to
assign people at random among the possible categories for research
purpose).

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 When can a Randomized Trial ……
 There is a genuine uncertainty about which intervention
strategy is superior

Example: It has often be observed that motorcyclists who wear a helmet are
much less likely to die of head injury in a motor cycle crash than un
helmeted motorcyclists. There is little doubt the mechanical protection
provided by the helmet is largely responsible for this difference. It would
almost certainly deemed unethical to withhold helmets at random for
some motorcyclists in order to get further evidence that helmets actually
do protect against fatal head injury.

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 When can a Randomized Trial ……

 The primary outcomes are relatively common and occur

relatively soon
 RCT can be expensive, especially when a large number of participants
is required, the period of follow up is lengthy and identification of
outcome is costly

 For this reason RCT are less well suited to studying rare and
delayed outcomes

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 Randomized Controlled Trial
 Advantages
 Utilizes a control group (strongest evidence)
 Bias is minimized
 Extraneous factors being responsible for outcomes is
minimized.
 Most reliable technique for evaluating treatments
 Most statistically powerful study design

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 Randomized Controlled Trial
 Disadvantages
Expensive
Patient enrollment can be difficult (time length)
Drop out rate is higher because of long term follow-up
Ethical problems in testing new therapies in humans
Time necessary to perform study can be long.
Most complex to interpret.

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 Assignment
Preclinical (animal) study in drug discovery and development:
principles and design options….

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Thank you

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