Interventional studies Flashcards
Experimental intervention
-one group remains control (or standard) and the other receives some intervention
Randomisation
-after a subject enters the study they are randomly allocated to either control arm or intervention arm through a process of randomisation
Simple randomisation
-randomising each entrant separately using a computer generated list
Block randomisation
- where randomisation occurs in a set of specified numbers, say blocks of 6, to ensure equal number distributed between two arms
- the larger the block size the lesser the ability to predict allocation
Stratified randomisation
- baseline characteristics which may have an implication on final outcome are stratified so that equal distribution across groups is enforced
- does not eliminate the need for adjustment for differences in the baseline composition
Cluster randomisation
- where a unit of randomisation and analysis is various centers or catchment zones, not individual patients
- all patients in that arm receive the same intervention
- this leads to a loss of statistical power in comparison with a patient randomised trial
Effective sample size
- used in cluster RCTs in the place of actual sample size when undertaking a power calculation
- to calculate ESS the intracluster correlation is used which represents the degree to which the various individuals in a cluster resemble each other in the outcome measure
Minimisation
- useful in 2 situations
1. you want to do a stratified randomisation but your trial is too small
2. you are conducting a cluster randomisation - minimisation is used to achieve a balance between treatment groups
- in minimisation schemes, the next allocation depends on characteristics of those already allocated
- the allocation of each participant aims to ensure a balance of prognostic factors between groups
- not actually random and can be biased
Quasi-randomisation
- refers to randomising using even/odd numbers of the date of birth, day of the week etc
- not reproducible
- sequences cannotensure equal distribution of variables
- must be avoided
Use of randomisation
- permits use of probability theory in making inferences
- eliminates effects of bias
- facilitates blinding
- distributes baseline characters in an unpredictable fashion
Cross over trial
- refers to an interchange of study and control groups after a washout period so that all subjects in a study receive both placebo and treatment but in a different order
- cannot be used for curable diseases
Parallel RCT
-both control and intervention happens in a parallel with no cross-over
N of 1 trial
- here a single subject is administered placebo and active intervention in tandem under double blind controlled conditions
- optimises treatment schedule for a patient but cannot be generalised to other patients
Factorial trials
- most RCTs evaluate a single therapeutic factor of interest compared to a placebo
- 2x2 factorial design involves participants being allocated to one of the four possible combinations
- tests independent effect of a drug and combined effect in 2x2x2
Patient preference trials
- patients are allocated the therapy they prefer
- only those who have no preference are randomised
- maximises recruitment
- complex consent
Zelen’s modified RCTs
- generally informed consent is obstained before randomising a sample for RCT but patients withdraw if they don’t feel they are getting treated
- in Zelen’s approach the randomisation occurs before consent
- not felt to be ethical
Non-inferiority trials
- most RCTs are conducted to show superiority of one intervention over another but sometimes drug companies only want to demonstrate the new intervention is not inferior
- also known as an equivalence trial or non-inferiority
- higher sample size is needed
Uncontrolled trials
- no control group
- study inference is made using a historical control like the treated group before intervention
Before and after trials
- the outcome is assessed before and after some intervention in one group of subjects
- the observed change may be attributable to a factor other than the intervention itself-makes the design inherently weak
- no randomisation occurs in this design
Multi-arm trial
- more than one study arm is included
- easy to design and allows intervention-1 vs intervention 2 comparison
- requires a large sample size and power may be reduced as a consequence
Efficacy
- how well a drug can work under optimal circumstances
- trial undertaken to meet regulatory approval
Effectiveness
- how well it works under usual practice circumstances
- trial helps with formularies of usefulness of the drug
Efficiency
-measures whether health care resources are being used to maximise value for money
Pragmatic RCTs
- aka practical clinical trials
- looks at effectiveness
- CATIE
Characteristics of pragmatic RCTs
- select clinically relevant alternative interventions to compare
2. include diverse population
3. recruit patients from heterogenous practice settings
4. collect data on a broad range of health outcomes
5. they do not tell how well a drug works (efficacy) they inform how effective the intervention is in the real world
Problems with pragmatic designs
- substantial drop outs
- blindings can fail
- less rigorous methodology
- higher rates of non-specific treatment effects
Key points for pragmatic RCTs
- reflect heterogeneity of patients in clinical practice
- minimise exclusion criteria
- focus on groups with a wide range of diagnoses
- define pateitns on presentation
- may not employ placebos
- may not be blinded
- must carefully conceal allocation during randomisation
- may evaluate real world, function based outcomes
