Lecture 5

Question 1

What are clinical trials?

Answer 1

controlled human studies to access dosage, administration, safety, efficacy

Question 2

What is phase 1 of clinical trials

Answer 2

• small scale, testing for tolerable dosing rages, bioavailability, excretion

Question 3

What is phase 2 of clinical trials

Answer 3

intermediate scale, testing for efficacy, monitoring for safety in greater number of patients

Question 4

What is phase 3 of clinical trials

Answer 4

large scale, randomized, double blind trial (both doctor and patient are blind to the treatment), compared against a placebo or current accepted treatment

Question 5

What is systematic review/meta analysis

Answer 5

approach to combine date from multiple trials, often after a drug has been approved. can increase our confidence of the effectiveness of a drug

Question 6

What is the odds ratio (OR)

Answer 6

ratio of the event rate in treatment vs control (which one is favoured in individual trials vs overall)

Question 7

What is the therapeutic index?

Answer 7

• a drug has to have a beneficial effect, but also a tolerable in terms of toxicity
• ratio of median toxic dose and effective dose)
• effect or toxicity is described as a quantal dose response curve

Question 8

What are some considerations with the therapeutic index

Answer 8

• big therapeutic index is usually good - drug is tolerated with minimal toxicity and gives a lot of flexibility for dosing
• may be a lot of individual variability in drug response
• other conditions (diet, liver + kidney function) might need to considered as they affect sensitivity
• useful in drug development, but should not be used as a rigid criteria for administration in clinical setting

Question 9

What is relative risk reduction

Answer 9

defined as 1 - (event rate in treatment group)/event rate in control group

Question 10

What is an event

Answer 10

defined in whatever study you are reading, examples are mortality cases, cardiovascular event

Question 11

What might relative risk reduction be misleading

Answer 11

• it does not convey the magnitude of the baseline risk, it doesn’t capture the difference between a large reduction in something that is very infrequent, verses something very frequent

Question 12

What is absolute risk reduction

Answer 12

• more descriptive way to report the benefit of taking a drug
• absolute risk reduction describes the absolute number of cases that are prevented by taking a drug
• absolute risk reduction = event rate in control - event rate in treatment group

Question 13

What is numbers needed to treat

Answer 13

another way to think about absolute risk
NNT = 1/ARR

Question 14

What are some things to consider when thinking about numbers needed to treat

Answer 14

• a low NNT is good = everyone taking drug receives benefit
• high NNT is not good = most people will not receive benefit
• we can also consider the number needed to harm, low NNH is bad, high NNH is good