Drug Safety and Risk Management Advisory Committee

1
Overview of Drug Safety Challenges

• Gerald J. Dal Pan, MD, MHS
• Director
• Division of Surveillance, Research
  Communication Support
• Office of Drug Safety
• FDA

2
Post-marketing Drug Safety Risk
AssessmentMultifaceted Challenges

• Identification of new adverse events
• Investigation of risk
• Characterization of context

3
Post-marketing Drug Safety Risk
AssessmentIdentification of New Adverse Events

• A fundamental goal of post-marketing drug safety
  programs
• Must account for many different types of risk
• Must account for many potentially confounding
  factors
• Must account for time course of events

4
Post-marketing Drug Safety Risk AssessmentWhat
Pre-marketing Safety Data Tell Us
Pre-clinical Pharmacology And Toxicology
Clinical Pharmacology
Pre-Marketing Safety Data
Clinical Safety Data Open-label Studies
Clinical Safety Data Controlled Studies
5
Post-marketing Drug Safety Risk
AssessmentIdentification of New Adverse Events
Pre-marketing Safety Data
6
Post-marketing Drug Safety Risk
AssessmentIdentification of New Adverse Events
?
?
?
7
Post-marketing Drug Safety Risk
AssessmentIdentification of New Adverse Events
Rare but serious adverse event

• Aplastic anemia
• Drug-induced liver injury

8
Post-marketing Drug Safety Risk
AssessmentIdentification of New Adverse Events
Also common in the population

• Myocardial infarction

9
Post-marketing Drug Safety Risk
AssessmentIdentification of New Adverse Events
Also a manifestation of the underlying disease

• Myocardial infarction

10
Post-marketing Drug Safety Risk
AssessmentIdentification of New Adverse Events
How do we separate a potential signal from the
background?
11
Post-marketing Drug Safety Risk
AssessmentIdentification of New Adverse Events
Long latency between drug exposure and event
12
Post-marketing Drug Safety Risk
AssessmentIdentification of New Adverse Events
Drug-drug, drug-disease, drug-herbal, drug-food
interactions
13
Post-marketing Drug Safety Risk
AssessmentIdentification of New Adverse Events
Medication Errors
14
Post-marketing Drug Safety Risk
AssessmentInvestigation of New Adverse Event
Risk
15
Post-marketing Drug Safety Risk
AssessmentInvestigation of New Adverse Event
Risk
16
Post-marketing Drug Safety Risk
AssessmentInvestigation of New Adverse Event
Risk
Clinical Trial
17
Post-marketing Drug Safety Risk
AssessmentInvestigation of New Adverse Event
Risk
Clinical Trial
18
Post-marketing Drug Safety Risk
AssessmentInvestigation of New Adverse Event
Risk
Clinical Trial
19
Post-marketing Drug Safety Risk
AssessmentInvestigation of New Adverse Event
Risk
Epidemiological Study - Case-Control
20
Post-marketing Drug Safety Risk
AssessmentInvestigation of New Adverse Event
Risk
Epidemiological Study - Cohort Study
21
Post-marketing Drug Safety Risk
AssessmentInvestigation of New Adverse Event
Risk
Registry
22
Post-marketing Drug Safety Risk
AssessmentInvestigation of New Adverse Event
Risk
Registry
23
Post-marketing Drug Safety Risk
AssessmentUnderstanding Context - Duration of
Exposure
24
Post-marketing Drug Safety Risk
AssessmentUnderstanding Context - Population
Exposure
25
Post-marketing Drug Safety Risk
AssessmentUnderstanding Context - Population
Exposure
26
Post-marketing Drug Safety Risk
AssessmentUnderstanding Context - Population
Exposure
27
Post-marketing Drug Safety Risk
AssessmentUnderstanding Context
28
Post-marketing Drug Safety Risk
AssessmentUnderstanding Context Concomitant Use
A
B
A
B
A
B
No concomitant use
High level concomitant use
Low level concomitant use
29
Post-marketing Drug Safety Risk
AssessmentSummary

• Multifaceted challenges
• Many ways to explore risk
• Context can be important