Clinical trials Flashcards
Phase 1 trials purpose
Healthy volunteers usually, but for cytostatic, anticancer, and immune suppressants this is not ethical, so must use patients with a known condition.
Determines pharmacokinetics
Maximum tolerated dose MTD
Dose limiting toxicity DLT
Initial dose 1/10 to 1/3rd of mouse LD 10.
Types of Phase 1 dosing regimines
SAD - Single ascending dose, separate groups receiving higher doses
MAD - Multiple ascending dose, same people receiving multiple doses.
Accelerated titration - 100% increase in dose for the first few steps. Stopped at 2 cases of toxicity or one case of limiting toxicity. Requires the fewest patients.
Food effect studies
Phase 2 trials purpose
To confirm effectiveness in specific malignancies.
Optimize dose
Continue to monitor side effects
Types of phase 2
Single arm non-randomized, comparing results to historical data
Randomized, blinded - Comparing it to historical control in random groups, reducing bias.
Non-comparative randomized trial. Comparing multiple drugs with historical data.
Pick the winner, multiple drugs, winner goes to phase 3
Phase 3 trails purpose
Confirm the new treatment against the best currently available.
Large, multicenter, and/or international data used.
Parallel groups,
Crossover design
Stratification
Double blind randomized
Phase 4
After the drug is registered and on the market.
Long term evaluation of late side effects and overall risk/benefit.
Evaluation of possible off label use.
Endpoints used for clinical trials.
Cancer specific survival - treatments effect on cancer induced death
Overall survival - effect on time to death from any cause
Disease Free survival - duration of remission before tumor reoccurence or death from any cause.
Overall Response Rate - Ratio of patients with a desired amount of tumor regression
Progression free survival
Time to progression
Time to treatment failure.
Quality of life evaluation.
