20. Clinical Trials Flashcards
What is a clinical trial in which the allocation is not random called?
quasi-experimental
what bias is removed by the investigator randomly allocating subjects to receive (or not) the treatment of interest in a RCT?
selection bias (if benefit is seen, it’s less likely to be due to confounding or other biases and thus more likely to be a true association)
heirarchy of study designs - what comes first vs last in investigation?
first: ideas, opinions, editorials, anectodal
- case series, case reports
- cross- sectional studies
- case control
- cohort
- RCTs
- systematic reviews (metanalysis)
ethical issues in investigator-assigned interventions
- when to conduct a RCT?
- clinical equipoise (at start of trial, there must be astate of clinical equipoise regarding the merits of the regimens tested, and teh trial must be designed in such a way as to make it reasonable to expect that, if successfully conducted, a clinical equipoise will be disturbed)
requirements of ethical trials
- social or scientific value
- scientific validity
- fair subject selection
- favorable risk-benefit ratio
- independent review
- informed consent
- respect for potential and enrolled subjects (*** PROTECTION OF HUMAN SUBJECTS MUST BE CONSIDERED BEFORE AND TRIAL STARTS)
nuremberg code (1947)
- in research “voluntary consent of the human subject is absolutely essential”
- subjects must have CAPACITY to consent, freedom from coercion, and comprehension of risks and benefits involved
- study must minimize risk and harm with a favorable risk/benefit ratio, have qualified investigators using appropriate study designs, and allow subjects to withdraw at any time
belmont report (1978)
- respect for persons (recognize personal dignity and autonomy of individuals, w/special protection of those with diminished autonomy)
- beneficence
- justice
IRB
- oversight to human subjects research and ensures conduct is ethical and scientifically sound
- empowered to approve (or disapprove) research
- period reviews and monitoring
Phase I drug/product development
- initial human trials
- small sample (10-100)
- healthy volunteers
- no comparison group
- primary goal to evaluate safety (adverse effects, maximum dose/toxicity, evaluate treatment mechanism)
phase II drug/product development
- expanded human trials
- small sample (100s)
- patients with disease
- comparator group (new drug vs placebo or standard)
- goals (expanded safety, determine optimal dosing/duration, efficacy)
Phase III drug/product development
- RCT
- large sample (100s-1000s) with disease
- comparator group
- expensive and costly (up to 50$ million)
- primary goal to determine efficacy (additional info on safety like adverse effects)
Phase IV drug/product development
post-market surveillance
- after FDA approval
- ongoing monitoring in real world setting
- identify additional adverse effects (low frequency reactions, high-risk groups, long-term effects)
- DRUGS CAN FAIL IN POST-MARKET SURVEILLANCE (eg thalidomide)
efficacy vs effectiveness
efficacy: benefit of the intervention or drug under ideal conditions
- RCT w/placebo comparison
- highly select population, strict inclusion/exclusion
- intervention is highly standardized
effectiveness: benefit of the drug/intervention in the real-world setting
- comparison to current standard
- generalize pop, few exclusions
- intervention implementation flexible
RCT “random allocation”
- what bias is eliminated?
must be unpredictable and concealed (allocation concealment) - investigator cannot know if the next person will be intervention vs control or bias can be introduced
- eliminates selection bias (removes potential for bias in allocation of subjects, on average makes groups comparable with respect to known and unknown confounders, but groups may be uneven by chance)
blinding
withholding info about allocation of interventino from those involved in the study (limits bias)
