Study Design Overview

Question 1

When Observation > RCT

Answer 1

RCT might be unethical…

• In vulnerable populations (pregnant)
• Address research questions (use lithium and risk of motor vehicle accidents)
• Examine the risk/benefit of the medication which is considered a standard of care (unethical to deny medicine in RCT)

Question 2

Study Design

Answer 2

• Descriptive

- Analytic: Observational or Experimental

Question 3

Descriptive Studies

Answer 3

• Correlation (ecologic)
• Case reports
• Case series
• Cross-sectional analysis

Question 4

Observational Studies

Answer 4

• Case-cohort

- Cohort

Question 5

Experimental Studies

Answer 5

-Clinical Trials

Question 6

Descriptive Studies used for…

Answer 6

• Describing novel or unusual signs, symptoms, or events (case reports/series)
• Describing the distribution of a disease in relation to person, place and time (cross-sectional, correlation)
• Hypothesis generation (all descriptive studies)

Question 7

Cross-Sectional

Answer 7

“Snapshot” of information on disease outcomes and exposures at a single point of time

Question 8

Analytic Studies used for….

Answer 8

-Testing research hypotheses formulation from descriptive studies

Question 9

Observational Research Design

Answer 9

• Investigator simply observes the natural course of events

- Notes who is exposed/unexposed has or has not developed the outcome

Question 10

Experimental Research Design

Answer 10

• Investigate allocate the exposure

- Follow subjects for subsequent development of disease

Question 11

Cohort

Answer 11

• Observational study
• Start with people free of disease
• Identify exposed and unexposed subjects
• Follow them up until disease develops
• Compares the incidence of disease among exposed and unexposed (RR)

Question 12

Case-Control

Answer 12

• Start with people who have a disease (cases)
• Identify appropriate controls
• Look back in time to identify exposure status among cases and controls
• Compare the odds of exposure among cases and controls (OR)

Question 13

Comparative Effectiveness Studies

Answer 13

• Compare two+ agents or interventions that are considered therapeutic alternatives
• Examination of effects in actual practice
• Conventional approach for CER-observational studies

Question 14

Determining Causality - Case Reports

Answer 14

• Drug adverse event algorithm

- Naranjo Algorithm

Question 15

Evaluating Drug Safety- Post Market

Answer 15

• Inherited limitations

- New ADRs are discovered postmarket in most drugs

Question 16

Safety Signals

Answer 16

Concern about an excess of AE comparedto what would be expected to be associated with product’s use

Question 17

Adverse Events

Answer 17

Undesirable outcome which may or may not be due to the drug itself (causality unknown)

Question 18

Adverse Drug Reaction

Answer 18

Reasonable possibility of a causal relationship between drug use and the event exists

Question 19

Serious ADE

Answer 19

• Results in death
• Life-threatening
• Hospitalization, disability, or congenital abnormality
• Required intervention to prevent permanent impairment or damage

Question 20

Evaluating Safety Signals

Answer 20

Spontaneous Reporting

• Health professionals can report to FDA or manufacturer
• Manufacturer reports to FDA (within 15 days if serious)
• Patients may also report directly to FDA

Active Surveillance
-Integrated administration claims databases

Pharmacoepidemiology methods are used to evaluate safety signals

Question 21

FDA Evaluation of Signals

Answer 21

• Factors which determine whether a signal requires further investigation
• SNIP Criteria

Question 22

SNIP Criteria

Answer 22

S - Strength
N - New?
I - Importance clinically
P - Preventative measures

Question 23

FDA Responses to Signals

Answer 23

• Label changes
• Name change - to avoid confusion (baby aspirin)
• Package change
• Issue “Dear Health Professional” Letter
• Restrict use of drug
• Work with manufacturer regarding possible withdrawal from US market