Lecture 24: Drug Development (Clinical Trials)

Question 1

What is a clinical trial?

Answer 1

prospective experiment

human subjects

testing a defined intervention

compared to a control group

with defined outcomes

Question 2

What are features of clinical trials?

Answer 2

informed consent: risks and benefits to the subject

randomization to treatment group: removes bias in treatment assignment, distributes other variables (which affect outcomes) evenly between groups

blinding

placebo

Question 3

Why do we need clinical trials?

Answer 3

best method to determine if a therapy works (i.e., has the intended effects

diseases generally not well understood enough to know with certainty if a therapy will work, based upon pharmacology alone

e.g., just because a drug strengthens the heart’s pumping action doesn’t mean it improves patient outcomes

individual clinician’s “experience” is insufficient to know whether a therapy works

Question 4

What is Phase 1 of clinical trials?

Answer 4

dosing studies

maximally tolerated dose

pharmacokinetic/pharmacodynamic studies

small number of subjects enrolled

usually enroll healthy subjects (exception is cancer drugs)

Question 5

What is Phase 2 of clinical trials?

Answer 5

biologic activity, adverse effects

generally 14-30 subjects

first use in patients with disease

check for biologic activity

safety

Question 6

What is Phase 3 of clinical trials?

Answer 6

effectiveness trials

establish its role in clinical practice

requirement for Notice of Compliance (NOC), i.e., drug approval

focus is on effectiveness and adverse effects

control group required (control = placebo or standard of care)

Question 7

What is Phase 4 of clinical trials?

Answer 7

long term effectiveness and adverse effects (observational studies without control groups)

evaluation across populations

detection of rare adverse effects

also called post marketing surveillance