L5 Drug Evaluation & Surveillance

Question 1

What are clinical trials and what are the three phases to clinical trials?

Answer 1

• Clinical trials:
  
  • Controlled human studies (after considerable pre-clinical development, optimization, animal testing) to assess dosage, administration, safety, efficacy
• Phase 1:
  
  • small scale (dozens of subjects)
  • testing for tolerable dosing ranges, bioavailability, excretion (pharmacokinetics)
• Phase 2:
  
  • Intermediate scale (100’s) testing for efficacy
  • monitoring for safety in greater numbers of patients
• Phase 3:
  
  • Large scale, randomized, double-blind
  • Compared against a placebo or current accepted treatment

Question 2

What are systematic reviews, meta-analysis and why are they important?

Answer 2

An approach to combine data from multiple trials, often after a drug has been approved.

• Meant to increase confidence in our view of the effectiveness of a drug and to help guide future policy regarding drug use

Question 3

What kind of data do forest plots provide?

Answer 3

Forest plots provide data on:

• Number of trials,
• Size of each trial
• Outcome of each trial
• OVERALL SUMMARY of ALL TRIALS

Question 4

What is the Odds Ratio?

Answer 4

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

Question 5

What is the therapeutic index?

Answer 5

Ratio of the median toxic dose and effective dose

TI = TD50/ED50

Question 6

In patient studies, how is effect or toxicity often shown?

Answer 6

Using a Quantal Dose-Response Curve

Question 7

Which is better, a big therapeutic index or small therapeutic index?

Answer 7

Big TI is usually good as it means the drug is tolerated with minimal toxicity and gives a lot of flexibility for dosing (Low risk)

Question 8

What is relative risk reduction?

How is it calculated?

Answer 8

Common parameter that indicates how well a drug reduces the likelihood of an undesirable event

• RRR = 1- (Event rate in treatment group/ event rate in control group)

Question 9

Why might reporting the relative risk reduction be considered misleading?

Answer 9

The main reason is that 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 vs something that is frequent

Question 10

What is absolute risk reduction?

Answer 10

Parameter that describes the absolute number of cases that are prevented by taking a drug (rather than a percentage relative to baseline as with Relative Risk Reduction)

Question 11

How do you calculate absolute risk reduction?

Answer 11

ARR = Event rate in control - event rate in treatment group

eg:

1000 subjects take a placebo and 250 experience >25% hair loss

1000 subjects take Drug X and only 125 experience >25% hair loss

ARR = (250/1000) - (125/1000)

ARR = 12.5%

Question 12

What does the Number Needed to Treat (NNT) describe?

How is it calculated?

Answer 12

The Number Needed to Treat (NNT) is the number of patients you need to treat to prevent one additional bad outcome (death, stroke, etc.). For example, if a drug has an NNT of 5, it means you have to treat 5 people with the drug to prevent one additional bad outcome.

NNT = 1/ARR

ARR = absolute risk reduction

Question 13

Do you want a low NNT or a high NNT?

Answer 13

A low NNT is good

eg a NNT of 1 means that just about everybody taking th drug will recieve the desired benefit

Question 14

What is NNH?

Do you want this to be high or low?

Answer 14

Number needed to Harm

Low NNH is BAD

High NNH is GOOD