Transcript Endpoints in Clinical Trials

Fundamentals of Clinical Trials
Endpoints
Betsy Garofalo MD
Michigan Technology and Research Institute
Clinical Trial Features
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Study objective – hypothesis testing
Type of study comparisons
Primary and secondary endpoints
Measures taken to minimizing bias
Treatment groups (drug & control),
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dosage and dose regimen
Objectives and Endpoints by Phase
Phase
Objective
Efficacy/Endpoint
Phase I
Safety evaluation
Patient tolerance
None
Phase II
Identify efficacy
endpoints and doses for
Phase III
“Exploratory”
Primary
Secondary
Phase III
Efficacy & Safety
Evaluate for general use
Primary- Indication
Secondary- may be
described in label
Phase IV
Expand efficacy &
safety
Expand patient
reported outcomes
Endpoint Definition
“Results, condition or events associated with
individual study patients that are used to
assess study treatments”
Characteristics of Endpoint Measures
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Easy to diagnose
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Free of measurement error
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Reliable with repeated measure
Internal validity
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Easy to identify no evaluator judgment needed
Directly linked to property of interest
External validity
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Ability to generalize to a wider population
Characteristics of Endpoint Measures
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Clinically relevant
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Influence Rx choices by physicians and patients
“How” and “When” to prescribe the drug
Surrogate Endpoint
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Surrogate endpoint – used instead of direct
endpoint – ex BP or Cholesterol LDL
Reduction as 1˚ endpoint as opposed to a
reduction in CV morbidity or mortality
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“The difference between a surrogate and a
true endpoint is like the difference between a
check and cash. You often get the check
earlier but then, of course, it may bounce.”
Primary, Secondary, Tertiary…..
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Primary – single (may be co-endpoint)
endpoint parameter for rejection of the null
hypothesis – regulatory implication in PhIII
Secondary- other endpoints pre-specified,
may be powered for hypothesis testing
Tertiary – exploratory and all other
Example
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Epilepsy
“Event” of interest: Seizures
 Maintain seizure diary for study
 Video EEG in infants for accurate counts
 Global Impression of Change
 QOL scales
Example
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Depression/Anxiety
“Result” of Interest: Functional improvement/
symptom relief
 Hamilton Scale for Depression (HAM-D)
 Hamilton Scale for Anxiety (HAM-A)
 Global Impression of Change
 Suicide rates (small numbers of events, efficacy
and safety issue)
Example
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Multiple Sclerosis – Relapsing Remitting
“Result” of interest: Neurological Disability
 “Episodes” of focal Neuro signs and symptoms
 Disability rating scales
 MRI changes
 CSF changes
Example
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Diabetic Neuropathy
“Event” of Interest: Foot ulcers, foot injuries
 Nerve conduction velocity changes
 Surrogate
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measurement
Sensory changes
Rating scales
Conclusions - Endpoints
Critical and challenging study design decision
 Consider
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Phase of development
Disease under study
Characteristics of measure
Question to be answered by trial