ClinicalTrials Designs Epidemiology

Clinical Trial Design: Randomized controlled clinical trial
Definition
“Clinical trials are a special kind of cohort study in which interventions

are specifically introduced by the investigators in ways that improve
the possibility of observing effects that are free from bias”
• Provides evidence of causality
• Gold standard for clinical decisions about treatment efficacy

Purposes of Clinical Studies
• Further scientific knowledge
• Prove concept: Theory not always best path (Akililu Lema’s experiment)
• Evaluation of product features, capabilities

[[[[[[
• Determine dose and toxicity profile of a new drug/procedure

• [
• Obtain initial safety data and
– Gather ancillary data (prognostic and predictive factors)

– [
• Substantiate claim/indication for use

• [
• Establish degree of efficacy or effectiveness
• Compare with competitor product; marketing evaluation

3
How You do?? Epidemiological study designs
Type of study Alternate name Unit of study

Observational studies
Descriptive studies
Analytical studies
Ecological Correlational Populations
Cross-sectional Prevalence Individuals
Case-Control Case-Reference Individuals
Cohort Follow-up/ Longitudinal Individuals
Experimental/interventional Studies
Randomized Controlled Clinical Trial Patients
Studies
Field Trial Healthy person
Community Trial Community intervention Communities
studies
Veterinary Clinical/field Trials
• Test Drugs or Devices
• Could Initiated by
– Company
• Human Pharma
• Veterinary Pharma
– Investigator
• Test vaccine efficacy

Requirements for Veterinary Clinical Trials???
• Patient Safety is Paramount!
– Drug test (ethical and well-fare issue)
• Informed client (owner) consent
– Regardless of who initiates
• Safeguards
– Good Clinical Practice (GCP) compliance (agreement)
• Guidance document for the design and conduct of all clinical

studies
Randomized controlled trials
• An epidemiological experiment in which subjects in a population are
randomly allocated into groups.
• Usually called study and control groups to receive and not receive
an experimental preventive or therapetuic procedure, or
interventition
• Randomized: Schemes used to assign participant to one group
(simple, systematic….)
• Procedure: Units are allocated into study and control groups
• Best done by using table of random numbers
• Ex: Every 3 gets higher dose

Randomization: Importance
• Produce study groups comparable with respect to known and

unknown risk factors,
• Removes investigator bias in the allocation of subjects and guarantees

that statistical tests will have valid significance levels (Eliminates
bias)
- Heart of the control trial

How randomization works
Suppose you want to determine whether a

particular diet (the exposure) is associated
with improved weight gain in lab animals
(outcome)
So, Randomization encourages equal numbers of fast-growing rats in

each group
9
The Possible Clinical Trial Designs
Types of Randomized Controlled Trials
• Blinded: Participants do not know if in
1. Clinical Trial: experimental or control group
For: Diagnostic, • Double Blinded: Participants and staff do
Therapeutic,
not know group assignment
Prophylactic,
Procedures, Regimens, • Placebo: Inactive pill w/no therapeutic
Protocols value
2. Preventive Trial • Crossover Trial: In this design each
3. Risk Factor Trial experimental unit receives all treatments
4. Trial of etiologic agents • Withdrawal trial: Refers to the withdrawal of
treatment during one or more phases of a
study to demonstrate the effects that it has on
the target behavior
Types of Randomized Controlled Trials
1. Clinical Trial
- Concerned with evaluating therapeutic agent, mainly drugs
– eg. Evaluation of beta-blockers in reducing cardiovascular disease
2. Preventive Trials:
- Trial of primary preventive measures: eg. Vaccines
3. Risk Factor Trials:
- Investigator intervenes to interrupt the usual sequence in the

development of disease for those individuals who have risk factor for
developing the disease
11
4. Cessation Experiment:
- An attempt is made to evaluate the termination of a habit which is

considered to be causally related to disease
- Exam. Cigarette smoking and lung cancer
5. Trials of Etiological Agents:
- To confirm or refute an etiological hypothesis
12
Steps in conduct of RCT
1. The protocol: Tells about the Study design – instructions

– A study design is a specific plan or protocol for conducting the study,
which allows the investigator to translate the conceptual hypothesis into an
operational one.
2. Selecting reference and experimental populations
a. Reference or target population - population to which the findings of
the trial, if found successful, are expected to be applicable (eg.
drugs, vaccines, etc.)
b. Experimental or study population - actual population that
participates in the experimental study
3. Randomization
4. Intervention
5. Follow up
– Implies examination of the experimental and control group subjects (Attrition: Inevitable losses to follow up)
- Assessment
- Positive results
- Negative results
Stages of experimentation
– Phase I: dose-finding
– Phase II: preliminary evidence of efficacy
– Phase III: comparisons to standard therapy
– Phase IV: post-marketing surveillance

PHASES OF TRIALS
Phase I Trials:
• Initial studies to determine:
• The metabolism and pharmacologic actions of drugs in target
animals,
• the side effects associated with increasing doses,
• and to gain early evidence of effectiveness;
usually conducted on healthy animals
Safety – must be performed prior to any clinical trial in humans or
client owned animals
• Pharmacokinetics
• Pharmacodynamics
15
PHASES OF TRIALS
Phase II Trials: Safety and efficacy (SE) trials
• Controlled clinical studies:
• Conducted to evaluate the

effectiveness of the drug for a
particular indication or indications in
patients with disease or condition
under study and
• Helps to determine the common short-

term side effects and risks
16
PHASES OF TRIALS
Phase III Trials: Comparative Efficacy Trials (CET)
• Large scale
• Comparison of Drug/device
• Randomized with controls
• Expanded controlled and uncontrolled trials after preliminary
evidence of effectiveness of the drug
• Are intended to gather additional information to evaluate the overall

benefit-risk relationship of the drug
• Aimed at definitive assessment of how effective the drug is,

comparison to 'gold standard' treatment.
17
PHASES OF TRIALS
Phase IV Trials: Post Marketing Surveillance Trial
•Large scale field trials
•Post marketing
• Phase IV trials involve the safety surveillance
• Post-marketing studies
• to delineate additional information including the
drug’s risks, benefits, and optimal use
• The safety surveillance is designed to detect any rare or
long-term adverse effects over a much larger patient
population and longer time period.
18
How do we Limit Bias?
• Randomization
– Equal chance of being in treatment vs control group
– Baseline data
• Blinding or masking
– Prevents differences in interpretation of outcomes or
data collection between groups
• Placebo controlled
Field Trials With Veterinary Vaccines
Field trial
• Definition: is a scientific investigation of a
veterinary vaccine under field conditions
and in target animals, using the product as
recommended.
• It is common trial in Veterinary medicine
– Undertaken under the field
– The trial frequently prophylactic
(vaccine)
• The results from laboratory trial shall be

supplemented with data from field trial.
• Vaccine efficacy:
– Definition: Efficacy of vaccination is usually defined as the reduction in the
chance or odds of developing clinical disease after vaccination relative to the
chance or odds when unvaccinated.
• Challenge of vaccinated animal by exposure to natural infection
• Implementation of field trial:

– Field efficacy trial (is the vaccine effective)
– Field safety trial (is the strain used safe, (killed, life vaccine; which is safe?))
– Animal welfare consideration (not good to try the vaccine with major
suffering)
Its major ways of uses
• critical route of adm.,
• Method (by syringe, oral drop etc) and
• regimen (how long or how many times) of vaccination to be
recommended in the most relevant category of target species
1‐ parameters of study
How do you measure vaccine efficacy??
Two types of parameters: After vaccination
• Main parameters ( mortality, morbidity, lesions, weight gain)
• Indicators ( serological response) qualitative and quantitative or

clinical sign, pathology
Control and trial design (important)
• Vaccinated animals with an
equivalent group of unvaccinated
or placebo control
•The environment in which the two
• Preferably investigated at the same groups of animals are housed shall be
time as equivalent as possible or at least as
similar as possible
The animals of both groups have to be • The challenge shall be as similar as

randomized according to the possible in the two groups of animals.
experimental unit
Exposure to infection: (both groups)
• The level and moment of exposure shall be the same in both groups of animals.
• Don’t conclude based on absence/presence of signs about the infection
– laboratory tests are needed
• The agent itself shall be detected and identified
• In live vaccine, isolated field strains shall be differentiated from the

vaccine strains.
Safety measures: parameters of safety
• Local reaction: the size, duration and nature of any lesions at the
site of injection
• Systemic reaction: e.g. mortality, changes in behavior, feed

conversation,……
• Other Side‐effects
Analysis and Interpretation
• The analysis of the data of field efficacy trials shall be related to or
explain the parameters measured.
The analysis of the data of field safety trials shall be related to the
recommendation for the administration of the vaccine.
Limitations of Field Trials
• Major logistic considerations
• Major financial considerations
• Think of how much work is required to randomize and

allocate participants to various treatment groups!
Community Trials
• Entire communities rather than individuals comprise the
treatment groups
• Appropriate for diseases that have their origins in social

conditions that can be influenced by intervention directed at
group behavior as well as individuals
• Ex. Fluoridation of public potable water to reduces dental

caries
Limitations of Community Trials
• Random allocation of communities is not practical
• Only a small number of communities can be included
• Other methods are needed to ensure any difference found can be

attributed to the intervention rather than to any inherent differences
between the communities studied (because they may exercise
different behavior) or you don’t consider with in community
differences
31

ClinicalTrials Designs Epidemiology

Uploaded by

Copyright:

Available Formats

ClinicalTrials Designs Epidemiology

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

ClinicalTrials Designs Epidemiology

Uploaded by

Copyright:

Available Formats

Clinical Trial Design: Randomized controlled clinical trial

“Clinical trials are a special kind of cohort study in which interventions

• Provides evidence of causality

• Gold standard for clinical decisions about treatment efficacy

• Evaluation of product features, capabilities

• Determine dose and toxicity profile of a new drug/procedure

• Obtain initial safety data and

– Gather ancillary data (prognostic and predictive factors)

• Substantiate claim/indication for use

• Establish degree of efficacy or effectiveness

• Compare with competitor product; marketing evaluation

Type of study Alternate name Unit of study

• Test vaccine efficacy

– Drug test (ethical and well-fare issue)

• Informed client (owner) consent

– Regardless of who initiates

– Good Clinical Practice (GCP) compliance (agreement)

• Guidance document for the design and conduct of all clinical

• Ex: Every 3 gets higher dose

• Produce study groups comparable with respect to known and

• Removes investigator bias in the allocation of subjects and guarantees

- Heart of the control trial

Suppose you want to determine whether a

So, Randomization encourages equal numbers of fast-growing rats in

3. Risk Factor Trials:

- Investigator intervenes to interrupt the usual sequence in the

- An attempt is made to evaluate the termination of a habit which is

5. Trials of Etiological Agents:

- To confirm or refute an etiological hypothesis

1. The protocol: Tells about the Study design – instructions

– Phase II: preliminary evidence of efficacy

– Phase III: comparisons to standard therapy

– Phase IV: post-marketing surveillance

• Controlled clinical studies:

• Conducted to evaluate the

• Helps to determine the common short-

• Are intended to gather additional information to evaluate the overall

• Aimed at definitive assessment of how effective the drug is,

• The results from laboratory trial shall be

• Implementation of field trial:

Two types of parameters: After vaccination

• Main parameters ( mortality, morbidity, lesions, weight gain)

• Indicators ( serological response) qualitative and quantitative or

The animals of both groups have to be • The challenge shall be as similar as

• Don’t conclude based on absence/presence of signs about the infection

– laboratory tests are needed

• The agent itself shall be detected and identified

• In live vaccine, isolated field strains shall be differentiated from the

• Systemic reaction: e.g. mortality, changes in behavior, feed

• Major logistic considerations

• Major financial considerations

• Think of how much work is required to randomize and

• Appropriate for diseases that have their origins in social

• Ex. Fluoridation of public potable water to reduces dental

• Only a small number of communities can be included

• Other methods are needed to ensure any difference found can be

You might also like