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• Study design is a process where in the trial
methodology and statistical analysis are organized
to ensure that the null hypothesis is either
accepted or rejected and the conclusions arrived
at reflect the truth. 2




• Randomized Controlled Trials (RCTs) are used to test the
efficacy or effectiveness of a specific, treatment, therapy,
or medication. RCTs are considered to be the Gold
Standard in clinical trials. The design involves the creation
of two distinct groups the “treatment” and the “no
treatment” groups. Participants in the study are randomly
assigned to one group or the other. 3


• Controlled Clinical Trials are similar to RCTs, except that
subjects are not randomly assigned to the treatment or
control groups. This increases the chance for “bias”–that is,
that people with similar qualities ended up in each of the
groups which could influence the final results.

• Case-Control Studies are an observational study where two
groups are identified and divided based on whether or not
they have a specific disease or condition (cases v/s. control).
The researcher then explores retrospectively (i.e. back in time)
for clues (i.e. exposure to certain risk factors) as to the cause
of that disease or condition. Ex. Case-Control study
determined that people who suffered from depression lacked
a strong network of support. 4 5


• Cohort Studies are an observational study in which a group of
individuals – a cohort – are followed over a period of time in
order to determine either the incidence rate of certain
diseases or the risk factors that lead to those diseases.

• These studies can be either prospective or retrospective. In
prospective studies, the cohort of individuals are divided into
two groups based on exposure to a specific risk factor and
then followed over a period of time to determine how many
people from each group develop the disease (incidence rate).

• In retrospective studies, the cohort is selected from the past
and data is collected either in the past or present on the
number of individuals who were exposed to a certain risk

www.fDaulocMtix.ocomr and who developed the disease. 6 7



• Qualitative research is used to explore and understand
people’s beliefs, experiences, attitudes, behaviour and
interactions. It generates non- numerical data, e.g. a
patient’s description of their pain rather than a measure of
pain. Research is typically conducted using a smaller
number of participants as the investigation is usually a lot
more detail-oriented.

• Common types of qualitative studies involved in health
research are:

• Case studies- detailed examination of an individual, group,
www.oDulroM eix.cvoment. 8


• Grounded Theory studies-
Designed to discover what problems exist in a given social
environment and how the persons involved handle them.
It involves formulation, testing, and reformulation of proposition
s until a theory is developed.

• Ethnography studies- the study of a cultural or social group
or system. 9



• A complete crossover design is usually employed, in which
each subject receives the test drug product and the
reference product.

• Period refers to the time period in which a study is
performed. A two-period study is a study that is performed
on two different days (time periods) separated by a washout
period during which most of the drug is eliminated from the

Ex- of Latin-square crossover designs for a bioequivalence
study in human volunteers, comparing three different drug
formulations (A, B, C) or four different drug formulations (A,
B, C, D). 10


Latin-Square Crossover Design for a Bioequivalence
Study of Three Drug Products in Six Human
Volunteers 11


Latin-Square Crossover Design for a Bioequivalency
Study of 4 Drug Products in 16 Human Volunteers 12



• Replicated crossover designs are used for the
determination of individual bioequivalence, to estimate
within-subject variance for both the test and reference
drug products, and to provide an estimate of the subject-
by-formulation interaction variance. 13


This design have four-period, two-sequence
and two-formulation

In this design, the same reference and the same test are each 14

given twice to the same subject.



• Narrow therapeutic index (NTI) drugs, also referred to as
critical dose drugs, are drugs in which small changes in
dose or concentration may lead to serious therapeutic
failures or serious adverse drug reactions in patients. 15



(a) Sub therapeutic concentrations may lead to serious
therapeutic failure.

(b) There is little separation between therapeutic and toxic
doses (or the associated plasma concentrations);

(c) They are subject to therapeutic monitoring based on
pharmacokinetic or pharmacodynamic measures.

(d) They possess low-to-moderate within-subject variability

(e) In clinical practice, doses are generally adjusted in very
small increments (<20%). 16



• A non replicate, parallel design is used for drug products that
contain drugs that have a long elimination half-life or drug
products such as depot injections in which the drug is slowly
released over weeks or months.

• In this design, two separate groups of volunteers are used. One
group will be given the test product and the other group will be
given the reference product. It is important to balance the
demographics of both groups of volunteers.

• Blood sample collection time should be adequate to ensure
completion of gastrointestinal transit (approximately 2–3 days) of
the drug product and absorption of the drug substance.

• Cmax and a suitably truncated AUC, generally to 72 hours after
dose administration, can be used to characterize peak and total
drug exposure. 17



• Multiple doses of the same drug are given consecutively
to reach steady-state plasma drug levels. The multiple-
dose study is designed as a steady-state, randomized, two-
treatment, two-way, crossover study comparing equal
doses of the test and reference products in healthy adult
subjects. 18


• Pharmacokinetic analyses for multiple-dose studies include
calculation of the following parameters for each subject:

• AUC—Area under the curve during a dosing interval

• tmax—Time to Cmax during a dosing interval

• Cmax—Maximum drug concentration during dosing interval

• Cmin—Drug concentration at the end of a dosing interval

• Cav—The average drug concentration during a dosing interval

• Degree of fluctuation = (Cmax− Cmin)/Cmax

• Swing = (Cmax− Cmin)/Cmin 19



1. Applied Biopharmaceutics and Pharmacokinetics, 7th
Edition by Leon Shargel , Andrew B.C YU ; page no:490-495 20


Thank you 21