RCTs Flashcards
What is Evidence-based clinical practice?
It is an approach to decision-making in which the clinician uses the best evidence available, in consultation with the patient, to decide upon the option which suits that patient best.
What should RCT focus on?
An RCT should focus on a single major objective, such as the comparison of a new therapy versus the standard therapy/placebo with respect to a specific outcome.
What is equipoise?
This concept states that ethically speaking we can only conduct clinical trials in areas of uncertainty and can only continue as uncertainty remains.
There can be differences of opinion as to the level of evidence required to state that there is ‘uncertainty’
It is unclear whether standard therapy is a local, national or international concept.
Selecting ppts
- When selecting the patient population, investigators should include patients who are likely to benefit from the intervention being tested.
- The population should also be selected such that the results of the trial can be generalised to patients in clinical practice.
- In order to study a population of the appropriate disease state and level of diversity, investigators define inclusion and exclusion criteria that determine whether or not a patient is eligible for a trial
=> not easy because often exclude everyone important
Advantages of randomization
- To ensure that the groups are alike as much as possible in ALL aspect except for which treatment they receive.
2.The best way to achieve such a balance is by the use of randomisation in which a chance mechanism determines the treatment assignment.
- The primary benefit of randomization is that it will eliminate selection bias. Baseline differences (if they exist at all) are due to chance rather than bias
- Confounding factors are assumed to be equally distributed
Disadvantages of randomization
- Many investigators feel that the action of randomisation interferes with the doctor-patient relationship.
- Clinician must admit to a patient that it is not known which of the therapies would be best for the patient.
- From and ethical perspective, a clinician should believe that these therapies are equivalent with respect to potential benefit.
- Physician and patient resistance/preference to randomization of participants to a specific arm.
What is Intention to treat (ITT) analyses ?
ITT analysis includes every subject who is randomized according to randomized treatment assignment. “once randomised, always analysed”.
ITT analysis avoids overoptimistic estimates of the efficacy of an intervention resulting from the removal of non-compliers by accepting that noncompliance and protocol deviations are likely to occur in actual clinical practice.
Advantages of RCTs
Gold standard: for establishing causation between a therapy and an outcome.
High internal validity: differences identified between randomized groups are a result of the intervention being tested.
Control of the intervention (timing, frequency, duration)
Rigorous experimental design:
Randomization (controls the effect of known and unknown factors)
Blinding minimises bias
ITT analyses
A true measure of efficacy
Disadvantages of RCTs
Limited external validity (i.e., extent to which study results can be applied to other individuals or settings): frequently, subjects with co-morbidities/elderly patients are excluded.
Missing data (threat to external validity): when data are missing because of aspects related to treatment or disease, major problems with bias can arise. Patients with missing outcome observations are more likely to be patients with poor outcomes.
Dose of the intervention: might be very strict in an efficacy trial and not suitable for all patients
Costs: complex to conduct, time consuming and expensive
Not always feasible or ethical
What is better than RCT?
Meta-analysis of RCTs
Before starting on meta-analysis:
PICO - Patient, Intervention, Comparison, Outcome
