Module 4 Flashcards
Randomized controlled trial
randomized comparison of two or more groups to evaluate medical interventions
interventions = drugs, surgeries, devices, programs
comparative nature of RCTs is important
we cannot judge an intervention unless we compare it to something else
three common indicators
to evaluate interventions that are controversial or that are widely used without adequate evidence
to evaluate a new intervention before it is given regulatory approval
to gain regulatory approval for a new intervention
Phase I trial
healthy volunteers that do not have the disease (low risk population)
N = 20-80 all get the new drug
assess toxicity and pharmacologic effects (does the drug hurt people, does it reach therapeutic levels as intended)
not an RCT
Phase II trial
persons with disease of interest
N = 100-200 all get the new drug
purpose is to assess safety and efficacy
not an RCT
Phase III trial
design assumptions depend on phase I and II trials
the RCT
assess the effectiveness of a new intervention
Phase IV trial
continuation of follow-up of RCT subjects past the official end of the RCT
observational study using medical databases where thousands of persons taking the intervention are followed for years
see if any adverse effects are reported
useful for detecting rare side effects
Comparisons in an RCT
new intervention versus placebo
new intervention versus standard intervention/standard of care
provides a more relevant answer to the public who have options
Drug approval
ideally, evidence for the efficacy of a medication, and regulatory approval, should be based on
placebo-controlled studies
new versus standard intervention studies
Clinical equipoise
genuine uncertainty among the expert medical community about the comparative therapeutic merits of each arm of a clinical trial
provides a clear moral foundation to the requirement that the health of participants not be harmed by participation in research
Design
begin with a defined population
randomize these persons to an intervention group
minimizes the differences among groups by equally distributing people with particular characteristics among all the trials arms
balances known and unknown confounders
allows isolation of the intervention effect
this makes RCTs the gold standard
randomization is typically performed by a statistician using a computer program
other things to consider
length of treatment
when to look for differences (end of follow-up, pre-defined point, interim analyses)
Stratified randomization
ensure that variables considered important to prognosis are equally distributed amongst the intervention groups
eg. if prognosis is worse in older males, then extra measures should be taken to distribute age and sex equally between treatment group
Blinding
not allowing study subjects to know what treatment they received
important because knowledge of treatment could affect patient response
for subjective outcome measures such as pain
in new drug versus standard drug comparisons, ask manufacturers to make the drugs identical
not likely to happen (cost, corporate pride, pharmacological reasons)
ability to blind does not preclude the use of an RCT
Types of blinding
single blind = blinding of participant only
double blind = blinding of data collectors and data analysis
done to prevent knowledge of treatment from influencing how data are collected or analyzed
triple blind = blinding physicians and hospital staff who treat study subjects
blinding of patients and physicians is not always possible when there are obvious differences between interventions
Single or multi-centered design
single centre = all patients are recruited from the same clinic or hospital
multi-centre = patients are recruited form more than one clinic or hospital
often necessary to recruit enough patients to meet sample size requirements
may span several countries
Planned crossover
patients are randomized to receive intervention A or B
after a predefined period of time, they are switched to the other intervention
advantages = patients serve as their own controls, sample size is smaller
potential disadvantages
washout period = the time between discontinuance of the first intervention and start of the second intervention must be long enough to eliminate any carry over effects
ordering effect = patients may react differently to the first intervention because of the psychological effect of being studied
not possible for surgical interventions or interventions that cure the disease
Factorial design
economical means of using the same population to test two different drugs
drugs must have different outcomes and independent modes of action
otherwise, drug interactions would prevent the independent study of the effects of each drug
