2 Clinical Trials Flashcards
Identify the different stages in drug development as well as their associated duration
- Discovery research (4 years)
- Phase 1 (1 year)
- Phase 2 (2 years)
- Phase 3 (4 years)
- Regulatory review (1 year)
- Phase 4
With reference to drug action, what does the statement ‘scientifically proven to work’ mean?
“It is better than the other treatment” i.e. more people receiving this treatment are cured than those on the other treatment
What is a clinical trial?
A clinical trial is 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
What is the purpose of a clinical trial? Differentiate between the terms efficacy and safety in the context of a clinical trial.
The purpose of a clinical trial is to provide reliable evidence of treatment efficacy and safety
Efficacy: ability of a healthcare 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
In order to be able to give a fair comparison of effect and safety, which three features must a clinical trial have?
- Reproducible – in experimental conditions
- Controlled – comparison of interventions
- Fair – unbiased without confounding
What are non-randomised clinical trials?
Non-randomised clinical trials involve the allocation of patients receiving a new treatment to compare with a group of patients receiving the standard treatment
What are the two disadvantages and the advantage of non-randomised clinical trials?
Disadvantages:
- Allocation bias – by patient, clinician or investigator
- Confounding – known and unknown
Advantage:
-Convenient and easy to carry out
What are the three steps involved in a randomised controlled trial (RCT)
- Definition of factors
- Conduction of the trial
- Comparison of outcomes
Identify the 6 factors which need to be defined in an RCT
- The disease of interest
- The treatments to be compared
- The outcomes to be measured
- Possible bias and confounders
- The patients eligible for the trial
- The patients to be excluded from the trial
What are the seven sub-steps in conducting a RCT?
⇒ Identify a source of eligible patients
⇒ Invite eligible patients to be in the trial
⇒ Consent patients willing to be in the trial
⇒ Allocate participants to the treatments fairly, i.e. without bias or confounding
⇒ Follow-up participants in identical ways
⇒ Minimise losses to follow-up
⇒ Maximise compliance with treatments
Which four questions might one ask when comparing outcomes in an RCT?
- Is there an observed difference in outcome between the treatment groups?
- Could the observed difference have arisen by chance, i.e. is it statistically significant?
- How big is the observed difference between the treatment groups, i.e. is it clinically important?
- Is the observed difference attributable to the treatments compared in the trial? ie consider confoundings
Identify three types of clinical outcomes and provide examples for each
- Patho-physiological e.g. tumour size, thyroxine level, ECG changes
- Clinically defined e.g. mortality, morbidity, disability
- Patient-focused e.g. quality of life, psychosocial well-being, satisfaction
Describe the timing of measurements in a clinical trial
- Baseline measurement of relevant factors – monitoring for inadvertent differences in groups
- Monitoring outcomes during the trial – monitoring for possible effect / adverse effects
- Final measurement of outcomes – comparing final effect of treatments in trial
What are the two advantages of random allocation?
(works well with large groups- less well with small groups)
- 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 characteristics by chance
Blinding/masking is a method to ensure minimal allocation bias.
What are the two types of blinding?
- Single blind – one of: patient, clinician, assessor does not know the treatment allocation
- Double blind – two of: patient, clinician, assessor does not know the treatment allocation (usually patient + clinician/assessor)
(Can have triple blind studies)
(usually patient)
Identify five situations where blinding is difficult to achieve
- Surgical procedures
- Psychotherapy vs. anti-depressant
- Alternative medicine vs. Western medicine
- Lifestyle interventions
- Prevention programmes
What is the purpose of a placebo?
The aim of a ‘placebo’ is to cancel out any ‘placebo effect’ that may exist in the active treatment
Explain how one might conduct an explanatory trial – ‘as-treated’ analysis
- Analyses only those who completed follow-up and complied with treatments
- Compares the physiological effects of the treatments
BUT- Loses effects of randomisation → selection bias and confounding
Explain how one might conduct a pragmatic trial – ‘intention-to-treat’ analysis
- Analyses according to the original allocation to treatment groups, regardless of compliance/completion
- Compares the likely effects of using the treatments in routine clinical practice
- Preserves effects of randomisation → minimal selection bias and confounding
What are the features of an ‘ideal outcome’?
