1.40 Trial Design

Question 1

Describe stages used in development + introduction new drugs to clinical practice

Answer 1

1. Initial stages
2. Pilot Study
3. Phase 0
4. Phase 1

Question 2

1. Initial stages

Answer 2

• Product design and development
• lit review id previous data
  (may alter product - other sim research)
• Involve market research
  id competing interest and suitability drug dev
• Alter design product / trial / aim study

Question 3

2. Pilot Study

Answer 3

Pilot Study

1 meet w/. statistician
id numbers needed for adequate power and significance

2 ID hypothesis and how tested

3 Apply ethical approval
reg w/ IRAS

Question 4

IRAS req info on

Answer 4

IRAS req info on
Study design method analysis

Logistical structures
Where trial will be conducted
who is involved

BG data results of lit review

Safety
possible risks and example of PIL used in Rx

Question 5

Phase 0

Answer 5

Animal studies id LD50 and LD95

Question 6

Phase 1

Answer 6

1. Drug admin small group
   healthy volunteers
2. Aim ID pharm traits
   - activity
   - tolerance
   - PK
   - Safety
3. ID potential routes which admin
4. Performed safe clin setting
   subjects monitored s/e and desire response

Question 7

Phase 2

Answer 7

1. Drug admin to those w/ disease / condition
2. Magnitude of hundreds
3. Aim ID ED 50 and ED95
4. Involve specialist in field - assess clin affect drug

Question 8

Phase 3

Answer 8

1. Only after satisfactory phase 2
2. Extended clin trials
   involving large - 000’s patients
   multiple site
   double blinded RCT (DBRCT)
3. Aim compare drug
   vs gold standard tx
   ?superior / ?efficacy
   Ensure all S/E + ADR occur at acceptable rate

Question 9

Phase 4

Answer 9

1. Post marketing analysis
2. Often most adverse reactions detected
   statical power by large number of admins
3. Adverse events recorded via yellow sheets in BNF
4. No fixed duration

Question 10

Type 1 error

Answer 10

False positive

Incorrectly rejecting Null hypothesis when true
states difference observed -
No diff

Determined by P value

Smaller P value - ↓ chance

Question 11

Type 2 or B error

Answer 11

1. False negative
2. Incorrectly accepting null hypothesis when not true
3. fails to observe difference when exists
4. small sample size

Question 12

Power

Answer 12

Refers to ability study
reject false null hypothesis
Not make type 2 error

Power = 1
probability of type 2 B error = sensitivity

Routinely B is accepted as 0.2
20% chance null hypothesis being falsely accepted

Therefore power usually accepted at 80%

Power calculation performed initial stages

• ID trial numbers reqd detect results
• reduce chance type 2 error occur

Question 13

Importance high power study

Answer 13

↓ chance a and b errors

increase chance find results

detecting result if present

prevent unnecessary exposure to repeat trials