Clinical Trials Flashcards
1
Q
Describe the stages of drug development
A
- Discovery research
- Patent needs to be acquired
- High-throughput screening - provides automated approaches to screening candidate compounds for pharmaceutical development
- Correct structure, chemically stable, selective for target screen, novel
- Lead optimisation - turning the lead drug to a candidate drug by optimising properties
- Lasts around 4 years
- Phase 1,2,3 evaluate drug in human testing
- Identify if it works, and if it is worth it
- Identify optimal dosage
- Lasts 1, 2, 4 years respectively
- Regulatory review to get MHRA approval for licence to market
- Phase 4 includes trials on thousands of patients
2
Q
Define a clinical trial
A
Any form of planned experiment which involves patients and is designed to elucidate the most appropriate method of treatment for future patients with a given medical condition
3
Q
What is the purpose of a clinical trial
A
- To provide reliable evidence of treatment efficacy and safety
- Efficacy - ability of a health care intervention to improve the health of a defined group under specific conditions
- Safety - ability of a health care intervention not to harm a defined group under specific conditions
4
Q
What are the requirements for a clinical trial
A
- Reproducible - in experimental conditions
- Controlled - comparison of interventions
- Fair - unbiased without confounding
5
Q
Differentiate between randomising and random sampling
A
- Randomising - equal chance of person being allocated to a group (A, B, C)
- Random sampling - every person has an equal chance of being chosen from the sample group
6
Q
State the disadvantages of non-randomised clinical trials
A
- Allocation bias - by patient, clinician or investigator
- Confounding factors as patients hand-picked
- Randomising trials reduces confounding factors
- The larger the sample size, the more randomised the trial will be
7
Q
Outline the steps involved in a randomised controlled trial (RCT)
A
- Definition of factors
- Define the disease of interest
- Define the treatments to be compared
- Define the outcomes to be measured
- Conduct of the trial
- Identify a source of eligible patients
- Invite eligible patients to be in the trial
- Gain consent for willing patients to be in the trial
- Comparison of outcomes
- Is there an observed difference in outcome between the treatment groups?
- Is it statistically significant?
- Could the observed difference have arisen by chance? - misleading results, problems with trial
- Is it clinically significant?
- How big is the observed difference between the treatment groups? - is the difference big enough to warrant a change in practice
8
Q
Define primary and secondary outcomes
A
- Primary outcome - preferably only one primary outcome
- Secondary outcome - other outcomes of interest
- Often includes occurrence of side-effects
9
Q
Describe the features of an ideal outcome
A
- Appropriate and relevant
- Valid and attributable - any observed effect can be reasonably linked to the treatments being compared
- Sensitive and specific
- Reliable and robust - outcome measurable by different people in various settings with similar results
- Simple and sustainable - method of measurement is easily carried out repeatedly
- Cheap and timely
10
Q
Describe the advantages of random allocation
A
- Minimal allocation bias - randomisation gives each participant an equal chance of being allocated to each of the treatments in the trial
- Minimal confounding - in the long run, randomisation leads to treatment groups that are likely to be similar in size and characteristic by chance
11
Q
Describe blinding and the advantage of it
A
- Knowledge of which participant is receiving which treatment may bias the results
- Behaviour effect - patient may alter their behaviour
- Non-treatment effect - clinician may alter their treatment, care and interest in the patient
- Measurement bias - investigator may alter their approach when making measurements and assessing outcomes
- Minimise allocation bias
- Single blind - one of patient, clinician or assessor does not know the treatment allocation
- Can also be double or triple blind
12
Q
Define placebo and placebo effect
A
- Placebo effect - even if the therapy is irrelevant to the patient’s condition, the patient’s attitude to his or her illness, and indeed the illness itself, may be improved by a feeling that something is being done about it
- Placebo - an inert substance made to appear identical in every way to the active formulation with which it is to be compared
- Aim of a placebo is to cancel out any placebo effect that may exist in the active treatment
13
Q
Describe losses to follow up and how to minimise it
A
- Not every participant remains in the trial
- Their clinical condition may necessitate their removal from the trial or they may choose to withdraw from the trial
- To reduce: maintain contact with participants, make the follow-up practical, minimize inconvenience, appointment reminders and scheduling future appointments at the previous session
14
Q
Describe non-compliance and how to minimise it
A
- Patients may have mis-understood the instruction, may not like the treatment, may think treatment isn’t working
- To reduce: simplify the instruction, ask about compliance, ask about effects and side-effects, monitor compliance
15
Q
Explain an explanatory trial
A
- Explanatory trial: ‘as-treated’ analysis
- Analyses only those who completed follow-up and complied with treatments
- Compares the physiological effects of the treatment (is new drug A better at lowering BP than drug B)
- However, loses effects of randomisation
- Non-compliers are likely to be systematically different from compliers
