Week 3

Question 1

OUTCOMES
- ______________
-Years of life ________
-Quality-adjusted life years gained
-Intermediate outcomes (change in blood pressure,
LDL, HbA1c)

Answer 1

mortality, years of life gained

Question 2

Examples of Objectivity are lab values, _________rate (whether the pt died or stayed alive), marker blood concentration, physiological measurement (ECG),

Answer 2

survival rate is objectivity

Question 3

____________-a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathological processes, or pharmacological responses to a therapeutic intervention.

Answer 3

Biomarker

Question 4

Biomarkers for Drug Response
____________ (blood pressure, heart rate, QT interval)

Answer 4

physiological

Question 5

Biomarkers for Drug Response

_____________(tumor growth, HIV viral load)

Answer 5

Pathological

Question 6

_____________ is very certain, like a value of survival rate or marker blood concentration, physiological measurement (ECG)

Answer 6

Objectivity

Question 7

_____________is very open to interpretation and does not have such certain marks like objectivity

It can be effects perceived by an observer or wellbeing of a person

Answer 7

Subjectivity

Question 8

It is a scale between these things, so some can fall in the middle
something like an _________ which has a certain picture but can be interpreted or read differently

Answer 8

x-ray

Question 9

____________ (CD4 counts)

Answer 9

Immunological

Question 10

____________ (plasma glucose)

Answer 10

Biochemical

Question 11

__________- surrogate endpoint; substitute for clinically meaningful endpoint

Answer 11

Biomarker

Question 12

________ is statistically associated with and believed to be pathophysiologically related to clinical outcome

Answer 12

Surrogate

Question 13

Surrogate endpoints:
_______ may influence clinical
efficacy endpoints through
multiple pathways

Treatment/intervention may
lie in only one of the pathways

Treatment may have
mechanisms of action
independent of its intended
effects on disease process

Answer 13

Disease

Question 14

An antihypertensive may have a surrogate endpoint of lowering blood pressure, but a clinical endpoint of a CV event or death

Question 15

Surrogate Endpoints Example:
Ventricular Arrhythmia after MI to Sudden cardiac death

Hypothesis: suppression of ventricular
arrhythmias after myocardial infarction would reduce the rate of death

Antiarrhythmics encainide & flecainide suppressed arrhythmia & were thought to have positive effects on clinical endpoint sudden cardiac death through the effect on arrhythmias (about 0.5 mln patients were on the drugs each year)

Cardiac Arrhythmia Suppression Trial –the
agents not only did not improve survival
but tripled the death rate through
previously unrecognized mechanism

Question 16

• ______ endpoints reflect how a patient ‘feels,
  functions, or survives’

Examples:
❑ Death, myocardial infarction, stroke, bone
fracture
❑ Cure or failure (recurrence)
❑ Patient feelings, function, well-being

Answer 16

Clinical endpoints

Question 17

SURROGATE VS CLINICAL ENDPOINTS

Drugs:Statins

Clinical endpoint:CV death due to
arteriosclerosis

Surrogate endpoint:Cholesterol

Question 18

Drug Class:Antiretroviral agents

Clinical endpoint:Progression to AIDs,
death from HIV

Surrogate endpoint:Viral loads, CD4
counts

Question 19

Drug Class:Antihypertensive
agents

Clinical endpoint:CV events, death

Surrogate endpoint:Blood pressure

Question 20

Drug Class:Antihyperglycemic agents

Clinical endpoint:CV events, mortality

Surrogate endpoint:Blood sugar

Question 21

Biomarkers in Clinical research
Advantages:
-interim _______&
efficacy evidence

-allow __________
number of patients
to be enrolled in a
trial

-____________time to FDA
approval and patient access

Answer 21

safety, smaller, decrease

Question 22

Biomarkers in Clinical Research

Disadvantages:

-may not always be part of pathophysiological pathway resulting in an endpoint

-treatment effects on biomarkers do not always predict true ________

Answer 22

clinical outcome

Question 23

Surrogate endpoints that can completely replace
the clinical endpoint are rare

**Many medications are complex with
multifactorial ________ and_________

Understanding the __________ of surrogates is
important when examining data from clinical
trials of new products

Answer 23

efficacy

toxicity

limitations

Question 24

Basic Randomized Trial Design
o Patients within the study → treatment (intervention group) and no treatment (control group) → outcomes
o Treatment effect (benefit or harm to a patient) = comparison between intervention and control groups.
o The purpose of conducting clinical investigations of a drug is to distinguish the effect of a drug from other influences such as spontaneous change in the course of disease, placebo effect, or biased observation.