CLINICAL TRIAL
DESIGN
Mintac, Lesley Ann D.
Penuliar, Niel Jairus
Soriano, Kristine Claire M.
CLINICAL TRIAL DESIGN
It is a formulation of trials and experiments, as well as observational studies in
medical, clinical, and other research involving human beings.
Assess safety, efficacy, and MOA of investigational medicinal products and
devices in development and not approved
Need for further investigation, with respect to long-term effects or cost-
effectiveness.
it is generally accepted that an appropriate trial design includes a sufficiently
large sample size and statistical power, and methods for minimizing bias to
enable the results to be reliably interpreted.
the randomized, parallel-group controlled clinical trial design is generally
considered as the gold standard, but in some situations it is difficult to use this
design.
Study Design
Observational Studies Experimental Studies
Cohort studies Randomised Controlled trials
Case-control studies (RTCs)
Cross-sectional studies Non-Randomised Controlled
trials (Non-RCT)
OBSERVATIONAL STUDIES
COHORT STUDIES
a population at risk for the disease events is followed over time for the occurrence of
disease and events.
this study is used to estimate how often disease or life events happen in a certain
population
these are the best methods for determining the incidence and natural history of a
condition
CASE-CONTROL STUDIES
An observational study that compares patients who have a disease or outcome
interest (cases) with patients who do not have the disease or outcome (controls), and
looks back retrospectively to compare how frequently the exposure to a risk factor is
present in each group
CROSS-SECTIONAL STUDIES
is a type of observational study that is primarily used to determine the prevalence
prevalence equals the number of cases in a population at a given point in time
all the measurements of each person are made at one point in time
ADVANTAGES OF CLINICAL TRIALS
Often provides the strongest evidence in support of cause-effect
relationships
basis for clinical and public health policy
minimize/ eliminate bias and confounding
EXPERIMENTAL STUDIES
RANDOMISED CONTROLLED TRIAL (RTCs)
often used to evaluate the efficacy of new drugs against standard
treatments or against placebos, but they are also used to evaluate other
therapeutic procedures such as a new form of surgery, a dietary regimen, or
an exercise program for persons with pre-existing disease.
NON- RANDOMISED CONTROLLED TRIAL (Non-RCT)
participants are allocated into treatment and control arms by the
investigator.
It is appropriate to use a non-randomised controlled trial design when the
act of random allocation may reduce the effectiveness of the intervention.
There are several types of clinical trial designs. These may be classified as follows:
Regarding the presence (or absence) of a control group as a comparator to the
investigational treatment:
Based on the presence or absence of a control group:
Uncontrolled trials - In this type of trial, the efficacy or toxicity of a medication is
compared in a group of patients without a control group. Results obtained can be
compared with those obtained in previous studies or with results published by
other investigators. Uncontrolled trials are typical in Phases I and II to investigate
tolerated dosing intervals or pharmacokinetic characteristics of a new drug.
Controlled trials - In these trials, the study group is compared with a control
group, which may receive placebo or another effective treatment. Both groups
are studied simultaneously. This type of trial is the most common in phase III.
According to the method used to allocate participants to a treatment or control group
we will have:
Based on the method used for participant allocation:
Non-randomized Clinical trials - In this type of trials, it is the investigator who
allocates participants to the different treatment groups or arms, or to control.
Randomized Controlled Clinical trials - In these trials, participants are
randomly allocated to treatment groups or arms, or to control. The process of
randomly allocating a participant to either the treatment arms or to control is
called randomization. In order to do this, different tools can be used, such as
closed envelopes, computer-generated sequences, random numbers, etc.
Randomization prevents participants from decoding the sequence and
learning what group they were assigned to, and it prevents investigators from
allocating patients to the different groups in a biased way.
Based on participants' or investigators' awareness of the treatment
group to which participants have been allocated, we will have:
Open-label studies - Trials in which investigators are aware of what
group patients were allocated to. In this type of studies, the use of
subjective variables by investigators may involuntarily condition results
based on the information that the investigator has regarding the
patient’s treatment.
Blind studies - This is a method used in clinical trials to reduce the risk of
bias, which may be intentional or not, when trial participants and/or
investigators are aware of which participants are receiving treatment (or
placebo).
Single-Blind Study: In this case, participants do not know to which group they
have been assigned, but investigators do.
Double-Blind Study: Neither the research team nor the participants are aware of
which group patients were assigned to, so no one knows what treatment the
patient is receiving.
Based on the significance of the result expected to be found between treatment
and control groups:
Superiority trials - Studies intended to show that the investigational drug is
better than the control.
Bioequivalence trials- Studies intended to show that the final result is similar
(neither worse nor better) than the control.
Non-inferiority trials - Studies intended to show that the investigational drug is
not worse than the control.
Based on the treatment structure:
Parallel trials - In this type of design, each group of patients receives only
one treatment. It is used for comparative trials.
Cross-over trials - Each patient consecutively receives each of the study
treatments. Cross-over designs may raise an ethical issue when a patient that
was improving with one treatment is switched over to the other.
Sequential trials - Patients are arranged in pairs; one being allocated to the
investigational group and the other to the control group. Results are
analyzed as they are obtained and added to previous data. The size of the
sample (the number of patients to be included) is not predetermined but
depends on accumulated results.
PHASES OF CLINICAL TRIALS
PHASE I PHASE II PHASE III PHASE IV
placebo randomized
Single, controlled controlled
ascending dose
Design
comparisons
2-3 treatment uncontrolled
tiers active controlled
Features: unblinded comparisons
broader observational
well-defined entry eligibility
uncontrolled
criteria criteria
ongoioing
Duration up to 1 month several months several years (following FDA
approval)
healthy volunteers or individuals with target
individuals with the target individuals with individuals with disease, as well as new
Population disease (such as cancer target disease target disease age groups, genders,
of HIv) etc
Factors to Consider in Design Selection
Number and characteristics of treatments to be compared
Characteristics of the disease under study
Study objectives
Timeframe
Treatment course and duration
Carry over effects
Cost and logistics
Patient convenience
Ethical considerations
Statistical considerations
Study subject availability (disease rarity)
References
https://www.bioclever.com/types-of-clinical-trial-designs-n-39-en
https://www.slideshare.net/Tawfikzahran/clinical-trials-designs
https://www.slideshare.net/uttara2024/clinical-trials-types-and-design
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434767/
