L3 Pharmacovigilance and Adverse Drug Reactions

Question 1

Side Effect vs. Adverse Drug Reaction

Answer 1

ADR: Harmful, unintended reactions to medicines that occur at doses normally used for treatment

Side Effect: effect, therapeutic or adverse reaction secondary to one intended

Question 2

Type A vs. Type B ADRs?

Answer 2

“Type A” ADRs: exaggerated pharmacologic effect caused by high drug concentration. Ie. drug (and/or metabolite) accumulation due to renal failure

“Type B” ADRs: “idiosyncratic” reaction, which is not dose-dependent, such as drug allergy

Question 3

Type A versus Type B ADRs for Aspirin?

Answer 3

Type A: bruising, bleeding (anti-platelet effects)

Type B: gastrointestinal toxicity (inhibition of GI mucosal prostaglandin synthesis/integrity)

Question 4

Study of the role of inherited and acquired genetic variation in drug response?

Application?

Answer 4

Pharmacogenomics

Can identify biomarkers that optimize drug selection, dose, and treatment duration and minimize the possibility of ADEs: either ADRs or therapeutic failures caused by under-dosing

Question 5

Nucleoside reverse transcriptase inhibitor for HIV associated with fatal hypersensitivity reactions?

Answer 5

Abacavir: Biomarker Use to Prevent ADRs

HLA-B 57:01 is associated with the reaction. Pre-screening for allele before treatment

Question 6

Organs that need better clinical monitoring of drug-induced injuries according to SAFE-T Consortium?

Answer 6

Kidney (DIKI)
Liver (DILI)
Vascular System (DIVI)

Question 7

Frequency of ADRs from medication?

Answer 7

• Very common (>1 in 10 patients)
• Common ( < 1 in 100 patients)
• Uncommon (1 in 100 to 1 in 1,000)
• Rare (1 in 1,000 to 1 in 10,000)
• Very rare (<1 in 10,000 )

Question 8

Sedative and anti-emetic available OTC in West Germany that lead to teratogenic-angiogenesis limb formation

What is it now used for?

Answer 8

Thalidomide

Now used in Multiple Myeloma

Question 9

Clinical Phase aimed primarily at establishing tolerated dosing, usually in healthy volunteers, with pharmacokinetic-pharmacodynamic (PK-PD) analysis?

Answer 9

Phase I studies: “first in man”

Question 10

Clinical Phase consisting of an assessment of efficacy (effects on physiologic endpoints), with additional safety information, in a small sample of the target population?

Answer 10

Phase II studies

Question 11

Clinical Phase focused on effectiveness (effects on clinical outcomes) for the proposed indication in the target population, to support drug approval

Answer 11

Phase III studies

Question 12

Clinical Phase occurring post-approval, aimed at new indications, additional safety assessments, or for other purposes

Answer 12

Phase IV Studies

Question 13

Efficacy vs. Effectiveness

Answer 13

EFFICACY: effects on physiologic endpoints (ie. degree to which a vaccine prevents disease under ideal and controlled circumstances – comparing a vaccinated group with a placebo group)

EFFECTIVENESS: effects on clinical endpoints, i.e. How well a vaccine performs in the real world.

Question 14

What to do if Serious Adverse Drug Event is Observed?

Answer 14

Report all SAEs to Sponsor (Company, Other) immediately (<24 hours), and to regulatory agencies (FDA, EMEA, etc) within 7 days

Question 15

Many ADRs previously classified as Idiosyncratic (____________ )are now explained by ______________ and may be preventable with clinical tools in development

Answer 15

Many ADRs previously classified as Idiosyncratic (Type B) are now explained by pharmacogenomics and may be preventable with clinical tools in development