Transcript CLPH 490N – Introduction to Clinical Research

Pharmacoeconomics
Research:
Its Role in Clinical Trials
Kent H Summers, PhD
Associate Professor
Purdue University, School of Pharmacy
May 14, 2008
Pharmacoeconomics
Goal & Objectives
Goal: To increase knowledge of
pharmacoeconomics research to
better understand the significance of
this data collected in clinical trials
Objectives
• Identify the role of economic and humanistic
studies in drug product development
• Identify the types of health outcomes studies
used in drug product development
• Identify where health outcomes studies are
performed in the drug development process
Economic Environment
Growing
Constrained
?
Why Clinical Trials ?
1. Registration
2. Safety
3. Efficacy
4. Inform prescribing decisions
5. Inform drug policy decisions ???
Clinical Pharmaceutical Research
Phase 1
Phase 2
Phase 3
Phase 4
Safety
Safety & Efficacy
Treatment decisions
Policy decisions
Can you assume that RCT results
will be reflected in actual practice?
EFFECTIVENESS
“Outcomes” studies
EFFICACY
RCTs
Effectiveness
The extent to which medical interventions
achieve health improvements in real-life
settings (usually differs from efficacy, as
determined in controlled clinical trials).
Efficacy
Can it work in
clinical practice?
(proven in RCTs 
ideal conditions)
Effectiveness
Does it work
in real life?
Efficiency
Does it contribute to a
more efficient use of
resources?
Managed care’s interest in
economic evaluations
Formulary management may involve (and economic
evaluations can inform decisions regarding):
1. requirement of prior authorization for payment of
certain drugs or unusual dosages
2. limits on the quantity of product dispensed
3. tiered copayments, in which patients are required
to pay less for cheaper medications (e.g., generic
medications) and more for expensive brands. (How
to select products for tier levels?)
Also, the Food and Drug Administration Modernization
Act of 1997 (FDAMA): promotion, AMCP-format
formulary submission
Pharmacoeconomics research
information
VALUE
• Is a pharmaceutical product worth its price?
• In which patients does it produce the
optimal benefit (both cost and quality) ?
AMCP-format Formulary Submission
Safety
Clinical
Studies
Efficacy
Disease and
Product
Description
Effectiveness???
Plan
Data
Published
Economic
Evaluations
Overall
Product
Cost and
Value
Economic
Modeling
Submission
Document
Resource
Utilization
Costs
Reporting
Potential
for Bias
Source: Mather et al, AJMC 1999.
ECHO Model of Outcomes Assessment
Economic
(Cost offsets,
Productivity)
Clinical
(BP, FEV
HbA1c)
Humanistic (QoL, Satisfaction)
Source: Kozma C, et al. Clin Ther 1993
Pharmacoeconomics
CLINICAL
ECONOMIC
Side
effects
Efficacy
HUMANISTIC
Satisfaction
Safety
Work
productivity
Resources
consumed
Direct Medical
Costs
Quality
of Life
Bothersomeness,
tolerability
Selection of costs (and outcomes) in an
analysis depends on perspective
Source: Lyles A, “Formulary Decision-Maker Perspectives: Responding to Changing
Environments” (Chapter 7) in, Economic Evaluation in U.S. Health Care: Principles
and Applications (Pizzi, Lofland, eds.), 2006
Economic Analysis
“A comparative analysis of alternative
courses of action in terms of both their
costs and consequences. ”
Drummond et al., Oxford University Press, 1987:8.
Types of Economic Analyses
Analytic
Method
Cost - benefit
(CBA)
Input (Cost) Consequences
Monetary
Costeffectiveness
(CEA)
Monetary
Cost-utility
(CUA)
Monetary
Costminimization
(CMA)
Cost-of-illness
Monetary
Monetary
Primary Concern
Maximal increment
in benefit for limited
resources
Clinical: life-year Least costly way to
gained, %
achieve objective;
patients
compare alternatives
reaching goal
within 1 therapeutic
category
Quality-adjusted Societal allocation;
life-year (QALY) compare alternatives
gained
across therapeutic
categories
Equal benefit
Efficiency (e.g.,
generic, therapeutic
ASSUMED
substitution)
Monetary
Total cost
identification
Cost Effectiveness Ratio Numerator
Costs included depends on perspective
Patients’ Perspective
Payer’s Perspective
Hospital costs
Employers’ Perspective
Physician costs
Lab costs
Hospital costs
Rx costs (if covered)
Physician costs
Lab costs
Rx costs (if covered)
Indirect (productivity) costs
Life-year Gained
Deductible costs
Co-insurance costs
Co-pay costs
Out-of-pocket costs
Transportation costs
Denominator: CEA v. CUA
Quality-adjusted
Life Years
1.0
0
CUA
QaLYs - patient 1
QaLYs - patient 2
Death
Death
Life-year Gained = CEA
Time
CUA ratio denominator
Healthy
Morbidity
Mortality
Quality-adjusted
Life Year (QaLY)
Gained
CUA:
Cost/QALY "League Table"
Warfarin v. ASA (lowrisk MI patients)
Surgical gall bladder
v. lithotripsy
Dual airbags v. driverside only
tPA v. streptokinase
Captopril v. none
$410,000
$140,000
$69,000
$32,000
$4,300
0
Pneumococcal
vaccination v. none
$0
$100,000 $200,000 $300,000 $400,000
Pharmacoeconomics
CLINICAL
ECONOMIC
Side
effects
Efficacy
HUMANISTIC
Satisfaction
Safety
Work
productivity
Resources
consumed
Direct Medical
Costs
Quality
of Life
Bothersomeness,
tolerability
Humanistic (“Intangible”) Outcomes
"Not everything that
counts can be counted,
and not everything that
can be counted counts."
An umbrella term that includes
outcome data reported directly
by the patient. It is one source
of data that may be used to
Patientdescribe a patient’s condition
reported
and response to treatment. It
Outcomes includes such outcomes as
(PrOs)
global impressions, functional
status, well-being, symptoms,
health-related quality of life,
satisfaction with treatment and
utilities.
Source: MC Glossary
What are PrOs?
Outcomes Assessment:
Sources and Examples
Clinician-reported
• Global impression
• Observation & tests
of function
Physiological
Caregiver-reported
• FEV
• HbA1c
• Tumor size
• Dependency
• Physical functional
status
• Emotional status
& functioning
Patient-reported
• Global impression
• Functional status
• Well-being
• Symptoms
• HrQoL
• Tmt satisfaction
• Utilities
 PrOs = patient’s reports of a health condition and its treatment
 Health-related Quality of Life (HrQoL) = patient’s evaluation of
the impact of a health condition and its treatment on daily life
 Therefore, validation of data collection instruments vitally
important!
Source: Acquadro, et al, ViH, 2003
The value of patient-reported outcomes (PROs):
• The patient’s perspective is a key element in medical diagnosis and
treatment.
• PRO data are unique and complementary indicators of disease activity.
• PROs in clinical trials provide important data for evaluating the
effectiveness of new treatment.
• Consistent with the definition of a scientific instrument, PRO measures
provide precise, reliable, valid, and reproducible data.
• PRO data are essential for evidence-based practice.
• For new pharmaceuticals, PRO data from clinical trials support
evidence-based practice.
• Professional organizations recognize the key role PRO data play in
diagnosis and treatment, as evidenced by their clinical practice
guidelines.
• The inclusion of PROs in clinical trials is sanctioned by professional
organizations, as evidenced by their trial guidelines, including FDA.
Why are PrOs important
in drug development?
 Clinical response endpoints, alone, can
underestimate treatment benefit
PrOs represent logical extensions of clinical
effects
To understand impact on quality, in addition to
quantity of life (esp. Oncology)
Why will PrOs become
increasingly important?
• IOM report (patient-centered care)
• FDA acceptance its use in promotion
(FDAMA)
• FDA guidance for its measurement
• Future drug development: from
chronic care (subject to price controls)
 “lifestyle” drugs (out-of-pocket, less
price restrictions, purchase decisions
based on desires of patients) ???
Multiple dimensions of HrQoL
Physical Function
Quality
of Life
General wellbeing
AFFECT
Psychological Function
FUNCTION
Social & Role
Function
HrQoL Measurement Issues
 Health status:
• Medical Outcomes Studies Short Form, 36 questions (MOS SF-36)
• Multi-dimensional measurement of treatment impact
• Impact on function, affect
• Cross-condition comparisons
• Responsiveness?
 Utilities (preference-based measures):
• EQ-5D
• Non-affected population’s understanding of disease impact?
• Single number (1 – 100)
• Cross-condition comparisons
• Responsiveness?
 Condition-specific instruments:
• Clinically sensible
• Responsiveness
• Cross-condition comparisons?
• Interpretation? Usefulness in medication utilization decisions?
Example: Selection of HrQoL data
collection instruments in eye disease
studies
• SF-36 (health status), EQ-5D (utilities)
– Validated and reliable
– Widely used in quality of life studies
– Not specific to ophthalmology
Generic
Instrument
------------------------------------------------------------------------------• National Eye Institute Visual Function Questionnaire
(NEI-VFQ-25)
Condition– Confirmed reliability and validity for a number of common
eye
specific
conditions
Instrument
– Validated in type 1 diabetes cohort of the Wisconsin
Epidemiologic Study of Diabetic Retinopathy (WESDR)
– Strongly associated with vision, independent of retinopathy
severity and other diabetic complications
Linder M, et al. Arch Ophthalmol. 1999;117:1611-1616.
Klein R, et al. Arch Ophthalmol. 2001;119:733-740.
Sharma S, et al. Br J Ophthalmol. 2002;86:493-496.
EQ-5D
By placing a checkmark in one box in each group below, please indicate which
statements best describe your own health state today.
Mobility
I have no problems in walking about o
I have some problems in walking about o
I am confined to bed o
Self-Care
I have no problems with self-care o
I have some problems washing or dressing myself o
I am unable to wash or dress myself o
Usual Activities (e.g. work, study, housework, family or leisure activities)
I have no problems with performing my usual activities o
I have some problems with performing my usual activities o
I am unable to perform my usual activities o
Pain/Discomfort
I have no pain or discomfort o
I have moderate pain or discomfort o
I have extreme pain or discomfort o
EQ-5D: Visual Analog Scale (VAS)
Information available at
product launch?
Phase 1
Phase 2
Phase 3
Phase 4
Registration
Safety & Efficacy

Effectiveness?
Treatment decisions
Policy decisions
Efficacy
(from RCTs)
Effectiveness
(CE projections)
Economic Models
Inputs
• Safety & Efficacy Data (RCTs)
• Epidemiology
• Cost of disease
Outputs
Cost / effectiveness
Basic Decision-analytic Model
Pharmacoeconomics
Goal & Objectives
Goal: To increase knowledge of
pharmacoeconomics research to
better understand the significance of
this data collected in clinical trials
Objectives
• Identify the role of economic and humanistic
studies in drug product development
• Identify the types of health outcomes studies
used in drug product development
• Identify where health outcomes studies are
performed in the drug development process
Pharmacoeconomic Research:
Product Examples
Brand
Generic
Indication
Prozac
fluoxetine
major depressive
disorder
Actos
pioglitazone
hyperglycemia in type 2
diabetes mellitus
Yentreve
duloxetine
stress urinary
incontinence
Example: Prozac (fluoxetine)
Phase 1
Phase 2
Phase 3
Phase 4
Registration
Safety & Efficacy

Effectiveness?
Retrospective studies
Prospective studies
Example: Prozac (fluoxetine)
Kupfer Curve
Kupfer DJ. 1991
Example: Actos (pioglitazone)
Phase 1
Phase 2
Phase 3
Phase 4
Registration
Safety & Efficacy

Effectiveness?
Economic Model
Example: Yentreve (duloxetine)
Example: Yentreve (duloxetine)
Urinary incontinence treatment
management decisions based on:
• Number of incontinence episodes
• Impact on quality of life
Example: Yentreve (duloxetine)
Phase 1
Phase 2
X
Phase 3
Phase 4
Registration
Safety & Efficacy
QoL instrument development
QoL in RCTs

Effectiveness?
Treatment decisions
Policy decisions
SUMMARY
Clinical trials as a model of
medication performance
The following data collected in RCTs is very
important:
• Side effects (even minor SEs, only potentially
bothersome SEs)
• Event rates: unscheduled phone calls (e.g.,
to answer patient questions about potential
SEs), physician office visits, ED visits,
hospital admissions
• Secondary study endpoints, such as those
collected in PrO instruments
Pharmacoeconomics
Goal & Objectives
Goal: To increase knowledge of
pharmacoeconomics research to
better understand the significance of
this data collected in clinical trials
Objectives
• Identify the role of economic and humanistic
studies in drug product development
• Identify the types of health outcomes studies
used in drug product development
• Identify where health outcomes studies are
performed in the drug development process