Role of clinical trials Flashcards
(32 cards)
What are the strengths of RCTs?
- can determine causality
- quantification of chance or random error
only if RCT has been well-conducted
BIAS and confounders are generally not seen in RCTs
What kind of interventions can be tested in experimental studies?
[experimental = RCTs]
many:
- medical Rx
- Surgical Rx
- health promotion advice
- dietary change
What are the more difficult interventions to test via RCT?
- long term interventions
- ‘lifestyle’ change (other than advice)
What features would the ideal experimental study have?
- (placebo-) controlled
- randomised
- double blind
- large
- analysed by ‘intention to treat’ method
Why do patients tend to get better (with or w/o Rx)?
- natural tendency to recover
- probability: regression to the mean seen for individuals at the extremes of distribution
- placebo effect
- effect of Rx
Why are controls needed?
- because some patients will get better by themselves, need a comparison group
Why is a placebo control group needed?
- take account of the placebo effect
What are the nature of control groups in practice?
- sometimes receiving no active Rx
- sometimes receiving usual care (without new Rx)
- may be receiving placebo for ‘active’ intervention
How are individuals allocated to each group in RCTs?
Allocation must be RANDOM
[ reduces allocation bias and confounders ]
Why is random allocation in RCTs good?
- avoids allocation bias
- avoids confounding
- simplifies interpretation of differences between groups
- facilitates blinding process
What are the issues with assessing outcomes in RCTs?
- vested interest in trial outcomes
ASSESSMENT BIAS”
subjective outcomes:
- patient-assessed
- observer-assessed
What is the solution to making outcome assessment in RCTs robust?
keep ‘key people’ blinded to randomisation code
- patient
- outcome assessor
- statistician/analyst
What are the different levels of blinding in RCTs?
SINGLE BLIND
=> patient or outcome assessor
DOUBLE BLIND
=> patient AND outcome assessor
TRIPLE BLIND
=> patient AND outcome assessor AND statistician
What trial outcomes may be used in RCTs?
- Sx
- clinical sign
- biochemical sign
- clinical disease onset
- death
- objectively measured ideally
- may have several outcomes
What are the 3 basic design for RCTs?
RANDOMISED
- parallel group design (SINGLE INTERVENTION)
- Crossover trial design
(SINGLE INTERVENTION) - Factorial design
(>1 INTERVENTIONS)
What is the crossover trial design of RCTs?
- v. efficient: every participant acts as both intervention and control
- more precise estimate of effect (than in parallel group)
- only works for RAPIDLY ACHIEVED and REVERSIBLE outcomes
When can crossover RCT design NOT be used?
NOT for irreversible events
e.g. cancer, DM, death
What is the factorial RCT design?
2 interventions
4 equal sized randomised groups:
- None (control)
- A
- B
- A+B (dual intervention)
efficient design
all groups are involved in examining effect of A and B
What are RCTs usually applied to?
individual patients
can also apply to groups using many individuals (= CLUSTER RCTs)
used to examine impact of community intervention
What is the importance of trial size in RCTs?
RCTs are widely used, but sample size is often too small
- limited statistical power
- fail to detect Type 2 stats error (failing to see intervention effect)
- trial effect estimates are imprecise
What are the advantages of using a large sample size in trials?
- higher statistical power
- more precise effect size estimate
- can look at sub-categories for impact of intervention
What does a large trial sample size NOT achieve?
does NOT make trial more representative at large
=> dependent on SOURCE of trial population
What are the presumptions that patients make on entering trials?
- they will not come to any harm
- will not be excluded from the usual effective Rx
- fully informed re: prospects of benefit/risk
What are the implications of trials in practice?
- intervention must benefit rather than cause harm
- control group: should have usual care rather than no care
- informed consent
- monitoring safety, adverse effects
