Lecture 57 – clinical evaluation of drugs

Question 1

Drug regulation policy’s

Answer 1

o Australia = TGA
o USA = FDA
o Europe = EMA (UK = MHRA)
o Regulates the manufacture, sale and advertising of medicines

Question 1

Biologics control act, 1902

Answer 1

o St Louis USA
o 10 children died
o Received injections of diphtheria-anti-toxin contaminated with live tetanus bacilli
o Subsequent act to ensure “good manufacturing” of drugs

Question 2

The federal food, drug and cosmetic (FDC) act, 1938

Answer 2

o Kansas City 1937
o 107 people died from renal failure after ingesting sulphanilamide diluted with diethylene glycol
o Subsequent act to ensure safety of drugs

Question 3

Birth defects from Thalidomide – Kefauver-Harris amendments

Answer 3

o Sydney, 1961
o Dr William McBride described 3 children with phocomelia
o Thalidomide identified as cause of this “unusual” birth defect
o Subsequent act to ensure “efficacy” of drugs

Question 4

Drug regulation overview

Answer 4

o Efficacy
o Safety
o Manufacturing
o GMP – good manufacturing practice
o GLP – good laboratory practice
o GCP – goof clinical practice
o Main role is to detect and prevent FRAUD

Question 5

FDA process of drug development

Answer 5

o Step 1 = discovery and development
o Step 2 = preclinical research
o Step 3 = clinical research
o Step 4 = FDA review
o Step 5 = FDA post-market safety monitoring

Question 6

Phase 1

Answer 6

o Study participants: 20-100 healthy volunteers or people with condition/disease
o Length of study: several months
o Purpose: safety and dosage
o Approximately 70% of drugs move to next phase

Question 7

phase 2

Answer 7

o Study participants: up to several hundred people with the disease/condition
o Length of study: several months to 2 years
o Purpose: efficacy and side effects
o Approximately 33% of drugs move to next phase

Question 8

phase 3

Answer 8

o Study participants: 300 to 3000 volunteers who have the disease or condition
o Length of study: 1 to 4 years
o Purpose: efficacy and monitoring of adverse reactions
o Approximately 25-30% of drugs move to next phase

Question 9

Phase 4 (post-marketing)

Answer 9

o Study participants: several thousand volunteers who have the disease/condition
o Purpose: safety and efficacy

Question 10

drug evaluation

Answer 10

o FDA
 Application of NDA
 Product IND
o Europe
 Application of CHMP
o Australia
 Application of ACPM (follow submission and report in EU format)

Question 11

Post-evaluation

Answer 11

o PI = product information (label)
o CMI = consumer medicines information
o Registered or listed on ARTG
o Funding

Question 12

Types of trial designs

Answer 12

o Parallel trial design
o Crossover trial design
o Matched pair trial design
o Withdrawal or enrichment trial design
o Factorial trial design (double dummy)

Question 13

Factorial trial design

Answer 13

o Two pairs 2X and 2Y
o One X gets active treatment, one X gets placebo
o One Y gets active treatment, one Y gets placebo

Question 14

Withdrawal or enrichment trial design

Answer 14

After the first specified period of time has elapsed, participants are randomised into two groups, one of which receives a placebo instead of continuing to receive the active treatment

Question 15

Matched pair trial design

Answer 15

After screening, participants are matched into pairs. Within each pair, one participant is randomised into treatment A whilst the other is randomised into treatment B

Question 16

Crossover trial design

Answer 16

o Patient X and Y are randomised into two different treatment arms Patient X receives treatment A during the first period of th study; patient Y receives treat B. after the first period is over, there is a washout period. Patient X then receives treatment B for the second period of the study while patient Y receives treatment A.

Question 17

Parallel trail design

Answer 17

o After screening, patients are randomised into separate treatment groups. They remain in these treatment arms for the duration of the trial, analysis and follow-up activities.

Question 18

Orphan drug act

Answer 18

Drug/biologic may be “designated” as an “orphan drug” if it is to prevent, treat or diagnose a disease/condition that occurs in <200,000 patients in US

Question 19

Dosage in children depends on:

Answer 19

Pharmacodynamics, pharmacokinetics, therapeutic window, idiosyncrasy

Question 20

Adverse events (AEs)

Answer 20

o During drug development:
 SAEs (serious adverse event)
 SUSARS (suspected unexpected serious adverse reaction)
o Post marketing
 ADRs (adverse drug reactions)
 Boxed warning (draw attention to the most serious of safety issues)