18.4. clinical trials phases and design

give features of phase 1-4 clinical trials including their randomisation, their number of people and aim of trial

phase 1:

• 20-50 people

• not randomisaed

• finding best dose of treatment, side effects and what happens to the treatment in body

phase 2:

• >100

• sometimes randomised

• Explore efficacy, confirm dose, monitor more side effects,

phase 3:

• 100s/1000s of people

• usually randomised

• Compare new treatment with standard/dummy drug

phase 4:

• variable

• not randomised

• long-term benefits and side effects

What is translational research?

Research that translates laboratory discoveries into clinical applications, such as new diagnostic tools, treatments, or technologies.

4 examples of translational research

1. mapping breast cancer at cellular level

2. improving targeting biopsies

3. developing highly sensitive blood tests to track cancer

4. identifying comprehensive breast cancer risk effects

What is a Randomised Controlled Trial (RCT)

A study where participants are randomly allocated to different groups to compare interventions. It reduces:

• Bias (selection, observer)

• Confounding - external influences affecting outcomes

• Random chance - statistical randomness

What 5 features make a well-designed RCT?

1. selection of trial participants → eligibility, cohort size

2. effective allocation of intervention → blinded

3. Identical treatment protocols across groups (except for intervention)

4. Robust randomisation and blinding

5. analysis designed to answer the research question → not to just find statistically different results

What are the 8 key elements of a trial protocol?

1. Background → why is this study needed?

2. rationale, objectives → primary & secondary endpoints?

3. Trial design, setting, treatments → randomised, controlled, observational etc.

4. Eligibility criteria

5. trial procedures → treatment plans, follow ups

6. Data collection, safety monitoring → statistics, quality control

7. Regulatory and ethical considerations → informed consent

8. Dissemination plans → publication, sharing of results

what are common inclusion and exclusion criteria?

inclusion:

• Age 18+, appropriate disease status

• Adequate general health (e.g., performance status 0–2)

• No contraindicated medications

• Ability to give consent

Exclusion:

• Other serious illnesses or conditions

• Prior use of similar trial drugs

• Pregnancy risk not managed

What is valid informed consent?

Participants must receive adequate, understandable information about the trial before participation, including risks, procedures, and their rights.

Consent must be voluntary and documented.

What are 3 methods of randomisation?

1. comparable population → demographics and clinically)

2. large trials → Coin toss, computer-generated randomisation

3. smaller trial → Block randomisation or stratification (balances demographics like age, severity)

What are 4 challenges and considerations in blinding?

1. surgical trials

2. methods of administration may be different

3. make trial less attractive to participants

4. expensive to manufacture a placebo

What is safety reporting in clinical trials?

• ICP GHP principles provide sponosors & investigators responsibilities regarding safety reporting

• cancer trials use CTCAE grading for side effects

• serious adverse effects must be reported within 24hrs

What quality control systems are used in trials

• systems to maintain participant confidentiality

• central & on-site monitoring

• accreditation of hospital labs, processing blood samples

• manuals for imaging, processing trial blood or tissue samples

• established guidelines for determinign results e.g. histopathhology techniques

What are key changes in modern clinical trial design?

• More complex protocols (e.g., umbrella/basket trials)

• Increased use of AI and wearables

• Reduced paper and more digital data

• Emphasis on personalised medicine

• Flexibility through Bayesian/adaptive designs

What is an adaptive trial design?

A flexible study design that allows for pre-planned modifications based on interim data. It can:

• Adjust sample sizes

• Combine Phase II/III trials

• Add new treatments

• Change target populations
  Requires statistical simulation and robust analysis planning.