Clinical trial designs can be categorized in several ways: 1. Based on the method used to allocate participants such as randomized controlled trials, non-randomized controlled trials, parallel group designs, crossover designs, and withdrawal designs. 2. Based on awareness of participants and researchers, such as blinded, unblinded, and double-blinded trials. 3. Based on the magnitude of activity being tested, such as superiority, inferiority, equality, and dose-response relationships. Common trial types include pilot studies, which test experimental design on a small scale, and placebo-controlled trials, which compare an intervention to a placebo. Randomized controlled trials are considered the gold standard for assigning participants randomly to treatment or

1. CLINICAL TRIAL DESIGNS
PREPARED BY:SINDHOORA D
FIRST MPHARM
DEPT.OF.PHARMACOLOGY
SCP,MANGALORE
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2. CONTENT
• Introduction
• Retrospective studies
• Prospective studies
• Pilot studies
• Placebo controlled studies
1. On the basis of method used
2. On the basis of awareness in participants
3. On the basis of magnitude of activity
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4. CLINICAL TRIAL DESIGNS:
• Formulation of trials and experiments, as well as
observational studies in medical, clinical and other
types of research involving human beings.
• Assess safety, efficacy, MOA of investigational
medicinal product and device in development and
not approved.
• Need for further investigation, with respect to long
term effects or cost effectiveness.
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7. • Retrospective Cohort Study: A study population is
defined and the medical history is reviewed to
identify associations between exposures and a given
outcome.
• Background for development of an interventional
trial.
• Example: Chart review of pediatric subjects with a
known diagnosis of late-onset congenital adrenal
hyperplasia to determine linear growth patterns
prior to diagnosis.
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8. • Prospective Cohort Study: A defined study cohort is
followed forward in time to determine how
factors/exposures affect a given outcome.
• Identification of risk factors for disease because data
is collected at set time intervals.
• Example of a prospective cohort study is the
Bogalusa Heart Study. This study began in 1973 to
determine the natural history of cardiovascular
disease in a group of 12,000 children from Bogalusa,
LA.
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9. Pilot Studies:
• Performed to test hypotheses in preparation for a
larger interventional clinical trial.
• Allow investigators to test experimental design,
obtain preliminary data for power analysis and
provide information about subject recruitment and
study management before investing resources to a
larger study.
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10. Placebo-Controlled:
• In placebo-controlled studies, subjects are
randomized to receive either placebo, inactive
or the active intervention.
• In addition, in cases where an established
therapy is already considered to be standard
of care, placebo-controlled trials may be
considered unethical if the usual treatment is
withdrawn while the subject is enrolled in the
study
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11. ADVANTAGES:
• Can be used for disease-modifying therapies, in
diseases with a rapid,unfavourable evolution.
• All patients receive active treatment
• DISADVANTAGES
1 Variable length of placebo period reduces statistical
power
2 Low and intermediate potency therapies show
large variability for response
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12. • There are several types of clinical trial designs:
• According to the method used to allocate
participants into treatment or control groups.
• According to the awareness of either participants or
researchers or both.
• According to the magnitude of activity.
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13. Non-randomised controlled clinical
trial designs
• In these trials, control groups can be concurrent
controls or historical controls. When using a
historical control, all subjects in the trial receive the
study medicine; the results are either compared to
the patient’s history (for example, a patient living
with a chronic illness) or a previous study control
group.
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14. Randomised controlled clinical trial
designs
• In randomised controlled trials, trial participants are
randomly assigned to either treatment or control
arms. The process of randomly assigning a trial
participant to treatment or control arms is called
‘randomisation’.
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15. Parallel group trial design
• In parallel group randomisation, after randomisation
each participant will stay in their assigned treatment
arm for the duration of the study.
• After screening, patients are randomised into
separate treatment groups. They remain in these
treatment arms for the duration of the trial, analysis,
and follow-up activities.
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17. ADVANTAGES:
1 Designsimpleto understand andto implement.
2 Treatmentgroupscanhave differentnumbersofpatients.
3 Analysisandinterpretation of resultsis simple
DISADVANTAGES:
1 Largersamplesize often required.
2 Difficultieswithrecruitment possible,ifplacebo-controlled.
3-Cannotestimatethe contributionofinter- and intra-patient
variabilitytothe overallvariability
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18. Cross-over trial design
• Cross-over randomisation is when participants
receive a sequence of different treatments (for
example, the candidate compound in the first phase
and the comparator/control in the second phase).
Each treatment starts at an equivalent point, and
each individual serves as his/her own control.
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20. ADVANTAGES
• Smallersamplesizethanparallelgroups.
• Resultsdependingonlyonwithinpatient variability.
• Often used in healthy volunteers (for phase I
clinical trials)
• low variance due to treatment and control
being the same participant, and the possibility
of including a number of treatments.
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21. DISADVANTAGES
1 Stable chronic diseases (assumes patient’s state is
comparableatthestartofbothperiodsof treatment).
2 Endpointmustnotbesensitivetolearning processes.
3 Requires a wash-out period between treatment periods.
4 Follow-up is at least twice as long compared with
correspondingparallelgrouptrials(attrition).
5 The analysis must confirm the absence of treatment - period
interaction(thecarry over)
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22. Matched pair trial design
• Participants are first matched in pairs according to
certain characteristics.
• Each member of a pair is randomly assigned to one
of the two different study subgroups.
• Allows comparison between similar study
participants who undergo different study
procedures.
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24. Stratification
• Stratification also allows for comparison
between similar study participants who
undergo different study procedures.
• Grouped according to one or more factors
before being randomised. This ensures
balanced allocation within each combination.
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25. Cluster sampling
• In cluster sampling, suitable geographical areas are
found (for instance, city, region, etc) and are then
randomly chosen.
• For each of these chosen geographical areas, a
proportionate sub sample from the members of the
study sample in that area are chosen, and these sub
samples are then combined into a sample group.
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26. Withdrawal trials
• In a withdrawal trial, the participant receives a test
treatment for a specified time and are then
randomised to continue either with the test
treatment or a placebo (withdrawal of active
therapy).
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28. ADVANTAGES:
• Reduces the time on placebo since only
responders are randomized to placebo.
• For use in chronic diseases,.
• Can assess if treatment needs to be continued or
can be stopped
DISADVANTAGES:
• Not suitable for unpredictable diseases (e.g.
spontaneous remission) or those with slow evolution
• Possible carry-over effect for adverse effect
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29. Factorial design:
• Factorial clinical trials test the effect of more than
one treatment. This allows assessment of potential
interactions among the treatments.
• An example of a trial using a 2×2 factorial design.
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31. ADVANTAGES:
1 Cananswertwoormorequestions withonetrial
2 Time-savingforthetrial sponsor
3 Requiresfewerpatients to obtain the answerto twoor more
question
DISADVANTAGES:
Need to be sure that there is no interaction between
treatmentsAandB
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35. 35

36. DOUBLE BLING TRIAL DESIGN:
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37. • Ssvhould
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38. ADVANTAGES
• Should be used whenever possible.
• Minimize both potential patient bias and
potential assessor bias.
• Standard studies
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41. 3.According to the magnitude of activity:
• Superiority
• Inferiority
• Equality
• Dose response relationship
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42. REFERENCES
• Williams, E.J. 1949. Experimental designs balanced for
the estimation of residual effects of treatments.
Australian Journal of Scientific Research 2: 149-168.
• https://www.eupati.eu/clinical-development-and-
trials/clinical-trial-designs/
• Zelen M. Randomized consent designs for clinical trials:
an update. Statistics in medicine. 1990 Jun;9(6):645-56.
• Byar DP, Simon RM, Friedewald WT, Schlesselman JJ,
DeMets DL, Ellenberg JH, Gail MH, Ware JH. Randomized
clinical trials: perspectives on some recent ideas. New
England Journal of Medicine. 1976 Jul 8;295(2):74-80.
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