Clinical Trial Design Flashcards
Clinical trials design has its roots in classical experimental design, with the following exceptions….
harder to control sources of variability compared to a process
Greater variability in human resources compared to aimals and plants and harder t measure
lengthy periods (follow ups)
ethical aspects
What can clinical research be used for?
Prevention
diagnosis
treatment
relieving symptom
creating new medical interventions and enhancing medical knowledge
What are the two types of studies in clinical research design?
Intervention and non intervention studies
What is a nonintervention study?
researchers don’t apply any treatment or procedures to the study participants instead observing in natural settings without manipulation.
Also known as observational studies
studies to observe and collect data on existing treatments on existing procedures without making changes to medical care.
name some types of non innervational studies
cross-sectional studies
case control studies
cohort studies
descriptive study
What is a descriptive study?
subset of non-interventional studies where the primary aim is to describe characteristics or occurrences within a specific population without manipulating variables or administering treatments
do not seek to establish cause or relationship but rather aim to provide a detailed account of a phenomenon as it naturally occurs
Give example of descriptive studies?
case reports and case series
ecological studies
survey set
questionnaire
what is an intervention based study?
known as clinical trials
designed to evaluate the effect of a intervention on a health related outcome
actively manipulate the variable to observe the resultant change
the intervention being tested is allocated by a investigator to a group of 2 or more study participants
interventional studies are the gold standard in determining efficacy and safety of a treatment of intervention
Give examples of types of interventional studies
randomised control trials
RCT
non randomised control trials
What are the 5 types of clinical trials?
Treatment trials
prevention trials
diagnostic trials
screening trials
quality of life trials
What are treatment trials?
evaluate the effectivness of new treatments or new combination of treatments
test new approaches to surgery or radiation therapy
aim to find more about the safety and side effects of new treatments
Give examples of treatments studies
trials testing a new chemotherapy drug
evaluating the efficacy of a new surgical method
What is a prevention trial?
explore ways to prevent the onset of diseases or health conditions
these approaches may include medicines, vitamins, vaccines, minerals or lifestyle changes
both healthy participants and those at risk of a particular condition may be involved
Give examples of prevention trials
trials in testing on new covid 19 vaccine
evaluating the efficacy of a mindfulness program in reducing stress
What are diagnostic trials?
evaluate the accuracy of diagnostic tests in detecting disease or its severity
aims to find a better test or procedures for diagnosing a particular disease or condition
focuses on accuracy, simplicity and safety of diagnostic methods
often involve comparison with gold standard diagnostic methods
Give examples of diagnostic trials
evaluate the efficacy of a new imaging technique for early detection of Alzheimer’s
assessing a new rapid diagnostic technique test for malaria
What are screening trials?
best way to detect certain diseases or health conditions
aim to either define the most effective, simplest and least invasive screening methods.
the target population are generally those at higher risk for a specific disease
Give examples of screening trials
trials to evaluate the effectiveness of different demographic techniques in detecting breast cancer
screening methods for early detection of prostate cancer
What are quality of life trials?
also known as supportive care trials
quality of life explores various ways to improve the comfort and quality of life for individuals with chronic illnesses
aim to understand how a disease affects patients and how they can manage it better
may involve physiological support, symptom release or management of side effects
Give examples of quality of life trials
trials exploring the effectiveness of cognitive behavioural therapy
managing chronic pain assessing the role of physical therapy improving mobility for stroke survivors
What is traditional trial (fixed) design?
the design is set in advance and remains unchanged throughout the study
all elements in the trials including the number of participants the treatment regiments the end points and the durations are predetermined and fixed before the trial begins
the parameter are predefined all aspects of the study such as treatment arms sample size and end points are defined in advance
the patient population is also fixed
primary end point is fixed, main outcome the study is designed to asses is specified before the study starts
The participants are tested in iterations to ensure safety
have a shorter planning phase but may run longer than necessary
corner stone of evidence based medicine for many years. very popular
what is flexible or adaptive design?
parameters and the ca of the candidate drug or vaccine are changed based on interim analysis
allow for modifications to the trial procedures like changing sample size, treatment allocations hypothesise after the start of trial without undermining its validity or integrity
can make trials more flexible by utilising resource accumulating in the trial to modify it in accordance with pre specified rules
wait and see iterative approach
data analysed and study changed accordingly
more time consuming
more ethical and efficient
high level of complexity to make sure the flexibility does not compromise the trials scientific validity
What is a Test population?
Group assigned for the Investigational Medicinal Product (IMP)
Whats a control population?
Group assigned for current treatment or placebo
What is a placebo?
IMP with no active therapeutic effect
Whats is a blind study?
Study conducted in a manner that neither test or control populations are aware of which treatment
has been assigned
What is randomisation in terms of a clinical trial?
Participants are randomly allocated to either of the groups.
To reduce bias
What is a two arm study?
Two treatments compared in the trial; three for three arm, etc
What are protocols?
A detailed plan that outlines the aims, design, and procedures of the clinical trial.
What is parallel design (parallel group study)?
Test and control groups are assigned treatment, and data collection is performed in parallel.
Each person is randomly assigned to one group.
Outcome: statistical comparison (efficacy and safety) between groups’ results: test vs. control or
treatment A vs. treatment B
Suitable for most therapeutic exploratory and demonstrative (Phase II and Phase III) studies working towards regulatory submission.
This study can be conducted in a blind manner
Subjects only are not aware to which group are assigned: single-blinded
Subjects and researchers not aware of group distributions: double-blinded
give a pro and a con of a parallel study
Pros: bias can be kept to a minimum
Cons: variability between patients and groups can affect the results
give an example of a parallel design study
American ginseng to improve HIV-associated fatigue
Population: 120 HIV-infected subjects
Control group: placebo
Test group 1: American ginseng 1000 mg/day
Test group 2: American ginseng 3000 mg/day
Treatment duration: 4 weeks
Study duration: 6 weeks
Primary outcome measures: changes in Fatigue Severity Score
what is a crossover design ?
Participants receive each treatment, e.g. control (A) and test (B), during different periods /
successively.
Randomisation of order in which the treatments are received: AB (first A, then B) or BA (first B, then A)
Popular design in various fields, including medicine, agriculture, manufacturing, education, etc.
In clinical trials, this design is suited for bioequivalence studies, to determine whether test and reference pharmaceutical formulations yield equivalent blood concentration levels, or metabolic or
tolerability studies
Give pros and con for a crossover design
Pros: each patient serves as his / her control, reduced variability, smaller population required
Cons: in most clinical trials, the disease must be stable and chronic, e.g. treatments/solutions. If
treatment A cures the patient, then treatment B (control) is not accurately assessed (potential for bias
+ a blinded study becomes unblended) treatment cannot have permanent effects or cure.
Need for “washout period” = break between the two treatments / solutions
More difficult analysis compared to parallel design
What is a group allocation design?
Group allocation design is a critical aspect that ensures the comparison of treatments is unbiased
Randomised Controlled Trials (RCTs):
Simple Randomisation:
Each participant has an equal chance of being assigned to any group.
Block Randomization:
Randomisation is performed within blocks to ensure that each group receives an equal number of participants.
Stratified Randomization:
Participants are divided into different strata based on one or more characteristics (e.g., age, sex, disease severity) and
then randomised within each stratum.
What is a factorial design?
The factorial design is a more economical way to approach multiple-arm
parallel design or several separate trials.
It can address more than one research question
The objective of a factorial design is to allow, in a single study, for the
evaluation of:
Two (or several) interventions / treatments, and / or Combinations of interventions interventions/treatments/ treatments
What is adaptive design?
An adaptive clinical trial design is a study design that allows for modifications
to the trial procedure.
These designs can be applied in various fields, including drug development,
medical devices, and other therapeutic interventions, offering a flexible and
efficient way to conduct clinical research.
who conducts clinical trials?
A cross functional team including: research scientists, healthcare
professionals, project manager
What factors are essential for the success of a trial?
a robust trial design and project planning are essential for the success of the study.
What determines success in a clinical trial?
measured via the result’s significance (and accuracy)
What are some common practices within the conduct of clinical trials?
robust and conceptually simple trial design, collaboration with statisticians, selection of (genuine) research questions
What are the 4 steps of conducting a clinical trial?
- Initial planning
- Trial setup
- Running the trial
- post-trial assessment
Explain the initial set up stage of a clinical trial
- Initial planning
Establish research questions to be answered by the study.
Steps required for the study and protocol development (design)
Ensure:
- sponsorship: project review and confirmed conduct/interest
- Feasibility of the study: trial population and conditions, protocol design, etc.
- Funding: grant applications (NHS, charity, private bodies, government, etc.)
- Approvals from regulatory bodies: local and national organisations (includes Ethical
requirements, e.g. Criminal Record Bureau (CRB) check of staff involved
Explain the trial setup stage of the clinical trial process
- Trial set up
Final (approved) protocol
Clinical study registration, e.g. International Standard Randomised Controlled Trial Number (ISRCTN)
Data management and analysis methodology
Site selection and contact initiation (booking)
Recruitment and information package for participants
Explain the “Running the trial” stage of the clinical trial process
- Running the trial
Informed consent form to be signed by participants
Interim reports per regulatory bodies and sponsor requirements (can differ); can involve audits/inspections
Accountability process required, especially for drugs: the path from supplier to participant (recording dates, product/batch number, etc.)
Monitoring the participants and data collection
Explain the “Post-trial assessment” stage of the clinical trial process
Notification of end of trial to regulatory body (within 90days)
Formal closure of trial centres –informing participants; destruction/return of unused
products (as per project plan)
Data analysis: quantitative and / or qualitative; exploration of relationships per
obtained scientific data
Reporting and publication
Archiving essential documents (for at least 5 years)
who should the study be benefiting when publishing?
trial must be published in the interest of the scientific community, participants and future patients, e.g. EU Clinical Trials Register (EEA), Clinical Trials Gov (US)
What is CONSORT?
(Consolidated Standards of Reporting Trials) is an international community working towards a (continuously improved) standard to assist investigators in reporting trial findings
