Drug development and safety

Question 1

Outline aspects of Phase 1 in clinical trials (4)

Answer 1

Small numbers of participants
Healthy volunteers
Testing the safety and tolerability of drug
Looking at pharmacokinetics and pharmacodynamics

Question 2

Outline aspects of Phase 2 in clinical trials (4)

Answer 2

Small numbers of participants
Patients
Testing safety and efficacy of drug
Looking at dose-response relationship

Question 3

Outline aspects of Phase 3 in clinical trials (3)

Answer 3

Large numbers of participants - target population
Testing safety and efficacy
Comparison with existing drugs

Question 4

Outline aspects of Phase 4 in clinical trials (3)

Answer 4

Post-licensing of drug
Safety surveillance
Marketing

Question 5

Define a “side-effect” (4)

Answer 5

Any unintended effect of a pharmaceutical product
Side effects may be desirable, undesirable or inconsequential
Occurs at normal dosage, usually predictable/dose-dependent
Effect is related to pharmacological properties of drug

Question 6

Define “adverse drug event” (3)

Answer 6

Any untoward medical occurrence that may occur during treatment with a pharmaceutical product
Does not necessarily have a causal relationship with the treatment
Actual or potential damage resulting from medical intervention related to medicines

Question 7

Give 4 examples of an adverse drug event

Answer 7

Incorrect drug selection
Incorrect dosage of drug
Illegible/incorrect prescription
Unforeseen drug interactions

Question 8

Define “adverse drug reaction”

Answer 8

Harm caused by use of a drug at normal doses
“response which is noxious and unintended which occurs at normal doses for prophylaxis, therapy or diagnosis of a disease, or for the modification of physiological function” ~ WHO

Question 9

Name and define the two types of adverse drug reactions

Answer 9

Type A: Augmented

• Dose-dependent
• Common/predictable

Type B: Bizarre

• Dose-independent (allergic or idiosyncratic)
• Rare/unpredictable

Question 10

How to prevent ADRs (6)

Answer 10

Take full history (co-morbidities, medications, allergies)
Avoid unnecessary drugs
Avoid drug interactions
Use correct dose
Monitor appropriately
Report suspected ADRs

Question 11

Define pharmacovigilance (1) and outline the 4 components involved in this science

Answer 11

Pharmacovigilance = the study of ADRs

• Detection
• Assessment
• Understanding
• Prevention

Question 12

List 5 methods of post-marketing safety evaluation of a drug

Answer 12

• Passive surveillance (spontaneous reports)
• Stimulated reporting
• Active surveillance (sentinel sites, drug event monitoring, drug or disease registries)
• Comparative observational studies
• Targeted clinical investigations