Clinical Trial Design

Question 1

Clinical trials design has its roots in classical experimental design, with the following exceptions….

Answer 1

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

Question 2

What can clinical research be used for?

Answer 2

Prevention
diagnosis
treatment

relieving symptom

creating new medical interventions and enhancing medical knowledge

Question 3

What are the two types of studies in clinical research design?

Answer 3

Intervention and non intervention studies

Question 4

What is a nonintervention study?

Answer 4

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.

Question 5

name some types of non innervational studies

Answer 5

cross-sectional studies

case control studies

cohort studies

descriptive study

Question 6

What is a descriptive study?

Answer 6

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

Question 7

Give example of descriptive studies?

Answer 7

case reports and case series

ecological studies

survey set

questionnaire

Question 8

what is an intervention based study?

Answer 8

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

Question 9

Give examples of types of interventional studies

Answer 9

randomised control trials
RCT

non randomised control trials

Question 10

What are the 5 types of clinical trials?

Answer 10

Treatment trials

prevention trials

diagnostic trials

screening trials

quality of life trials

Question 11

What are treatment trials?

Answer 11

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

Question 12

Give examples of treatments studies

Answer 12

trials testing a new chemotherapy drug

evaluating the efficacy of a new surgical method

Question 13

What is a prevention trial?

Answer 13

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

Question 14

Give examples of prevention trials

Answer 14

trials in testing on new covid 19 vaccine

evaluating the efficacy of a mindfulness program in reducing stress

Question 15

What are diagnostic trials?

Answer 15

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

Question 16

Give examples of diagnostic trials

Answer 16

evaluate the efficacy of a new imaging technique for early detection of Alzheimer’s

assessing a new rapid diagnostic technique test for malaria

Question 17

What are screening trials?

Answer 17

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

Question 18

Give examples of screening trials

Answer 18

trials to evaluate the effectiveness of different demographic techniques in detecting breast cancer

screening methods for early detection of prostate cancer

Question 19

What are quality of life trials?

Answer 19

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

Question 20

Give examples of quality of life trials

Answer 20

trials exploring the effectiveness of cognitive behavioural therapy

managing chronic pain assessing the role of physical therapy improving mobility for stroke survivors

Question 21

What is traditional trial (fixed) design?

Answer 21

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

Question 22

what is flexible or adaptive design?

Answer 22

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

Question 23

What is a Test population?

Answer 23

Group assigned for the Investigational Medicinal Product (IMP)

Question 24

Whats a control population?

Answer 24

Group assigned for current treatment or placebo

Question 25

What is a placebo?

Answer 25

IMP with no active therapeutic effect

Question 26

Whats is a blind study?

Answer 26

Study conducted in a manner that neither test or control populations are aware of which treatment has been assigned

Question 27

What is randomisation in terms of a clinical trial?

Answer 27

Participants are randomly allocated to either of the groups. To reduce bias

Question 28

What is a two arm study?

Answer 28

Two treatments compared in the trial; three for three arm, etc

Question 29

What are protocols?

Answer 29

A detailed plan that outlines the aims, design, and procedures of the clinical trial.

Question 30

What is parallel design (parallel group study)?

Answer 30

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

Question 31

give a pro and a con of a parallel study

Answer 31

Pros: bias can be kept to a minimum Cons: variability between patients and groups can affect the results

Question 32

give an example of a parallel design study

Answer 32

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

Question 33

what is a crossover design ?

Answer 33

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

Question 34

Give pros and con for a crossover design

Answer 34

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

Question 35

What is a group allocation design?

Answer 35

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.

Question 36

What is a factorial design?

Answer 36

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

Question 37

What is adaptive design?

Answer 37

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.

Question 38

who conducts clinical trials?

Answer 38

A cross functional team including: research scientists, healthcare professionals, project manager

Question 39

What factors are essential for the success of a trial?

Answer 39

a robust trial design and project planning are essential for the success of the study.

Question 40

What determines success in a clinical trial?

Answer 40

measured via the result’s significance (and accuracy)

Question 41

What are some common practices within the conduct of clinical trials?

Answer 41

robust and conceptually simple trial design, collaboration with statisticians, selection of (genuine) research questions

Question 42

What are the 4 steps of conducting a clinical trial?

Answer 42

1. Initial planning 2. Trial setup 3. Running the trial 4. post-trial assessment

Question 43

Explain the initial set up stage of a clinical trial

Answer 43

1. 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

Question 44

Explain the trial setup stage of the clinical trial process

Answer 44

2. 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

Question 45

Explain the "Running the trial" stage of the clinical trial process

Answer 45

3. 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

Question 46

Explain the "Post-trial assessment" stage of the clinical trial process

Answer 46

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)

Question 47

who should the study be benefiting when publishing?

Answer 47

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)

Question 48

What is CONSORT?

Answer 48

(Consolidated Standards of Reporting Trials) is an international community working towards a (continuously improved) standard to assist investigators in reporting trial findings