Transcript Outcomes - Dr. Marcia Testa

Clinical Investigation and
Outcomes Research
Health Outcomes Research
Marcia A. Testa, MPH, PhD
Department of Biostatistics
Harvard School of Public Health
1
The Discipline of Health
Outcomes Research
• Scientific inquiry
evaluating the
results of medical
interventions and
health care services.
• Outcomes data are
direct measures of
whether medical
treatments are
beneficial
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How Are Outcomes Results Used?
• “Outcomes research seeks to understand the end results
of particular health care practices and interventions.
• Used to provide information on the quality of care so that it
can be improved by determining
– which health care services influence the probability of
optimal patient outcomes
– which produce optimal improvement in the patient's
physiologic status, physical function, emotional and
intellectual performance and comfort (comparative
effectiveness research)
1. Outcomes Research Resource Guide, 1996/97 Edition, American Medical
Association
3
Measuring Outcomes
• Outcomes are a function of
–
–
–
–
–
–
baseline health status
patient clinical characteristics
patient demographics
psychosocial characteristics
treatment
health care setting
• The GOAL of health outcomes research
analysis is to isolate the relationship between
outcomes and treatment.
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Outcome Measures
• Mortality – Survival time, Death event
• Morbidity – Time to an Occurrence of a
Clinical Events (e.g., Stroke, MI, Cancer)
• Health Status – Physical, Mental and
Emotional Health Functioning
• Quality of Life – Health Status as Perceived
by the Individual
• Patient Satisfaction – Distance between
Quality of Life and Individual Expectations
• Health Economic Outcomes – Cost utility,
cost effectiveness
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Hematologic Malignancies & Anemia
Comparative Effectiveness Trial
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Hb Changes
Figure 2. Mean hemoglobin (Hb) change (intent-to-treat; n = 269). aP < .0001 early versus late
group. Postrandomization Months 1, 2, 3, and 4 values correspond with mean Hb between Weeks
0 (baseline) to Weeks 4, 5-9, 10-14, and 15-20, respectively.
a
P < 0.0001
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Treatment, Fatigue, Symptoms
bP
< .01 late vs. early treatment. cP < .05 late
vs. early treatment.
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Treatment and Health Status
bP
< .01 late vs. early treatment. cP < .05 late
vs. early treatment.
9
Treatment and QOL
bP
< .01 late vs. early treatment. cP < .05 late
vs. early treatment.
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Measuring Outcomes
Death
Outcome
Full Health
11
Measuring Outcomes,
Measuring Performance
Improving Process
(how we perform)
Improving Outcomes
(the results of our
performance)
Measurement
12
The Consequences of Health Care and
Medical Intervention
Clinical
Economic
Patient
Centered
13
The Consequences of Health Care and
Medical Intervention –Types of Outcomes
Clinical
Labs, Clinical Events, Physician
Assessments
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The Consequences of Health Care and
Medical Intervention –Types of Outcomes
Symptom reports, health status,
quality of life, patient satisfaction
Patient
Centered
15
Multi-faceted QOL Domains
Well-being
General
Perceived
Health
Mental and
Emotional
Physical/
Symptoms
Cognitive
Work/Social
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Outcomes Research - 1996
QOL is Recognized as Important
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Outcome Measures
Functional Health Coverage
• Generic health instruments are address
larger health constructs and hence their
causal links to specific treatment events
may be more difficult to detect
• Condition-specific instruments will vary
with the condition being treated, and
hence are typically more sensitive to
treatment effects
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Outcome Measures
Format Influencing Coverage
• Fixed-Length or “Static” – number of
questions is fixed – greater coverage requires
greater number of questions
• Dynamic instruments - use computer
adaptive testing to restrict items based upon
a Bayesian approach which selects the next
question based upon the answer to the
previous question
• Combines the practicality of short form
instruments with the sensitivity and target
coverage of condition-specific instruments
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Questionnaires and Surveys
Generic Instruments
• Some outcomes survey questions, commonly
referred to as “instruments”, focus on describing how
individuals rate their health overall – or generic
instruments
• General health surveys such as the SF-36 are now
used in research studies, population surveys, and
some health plans to assess patients' overall level of
functioning.
• Translation of SF-36 into Arabic and the translation
methods references are given in the Additional
Resources Section of the Website.
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Questionnaires and Surveys
Condition-Specific Instruments
• Developing outcome instruments for
specific diseases has been an
especially prolific research area
• Such instruments are more likely than
general health survey measures to be
able to detect changes in the disease
due to treatment
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Steps in Designing an
Outcome Research Study
• Define a researchable question
• Develop a conceptual model
• Identify the critical dependent and independent
variables
• Identify appropriate measures for each
• Develop an analysis plan
• Indicate what is believed to cause the outcome
• Identify critical pathways and what other factors are
likely to affect the outcome
• Identify which variables (in the outcomes function
equation) are relevant to your hypothesis
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The Conceptual Health Model
Environmental
Behavioral, Social
•Income
•Social Support
•Education
•Health Access
•Lifestyle
Patient
Factors
•Age
•Gender
•Occupation
Medical Interventions
•Specific medications
•Surgery
•Diet and Exercise
•Case Management
Outcome
Measures
•Lab values
•Symptoms
•Functioning
•Quality of life
•Employment/Work
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The Outcomes Model
Patient
Characteristics
Risk Adjustment
OUTCOME
Structure
(Setting)
Change
Change
Process
(Treatment)
Measurement
24
Outcomes Research - 1998
Health Economic Benefits
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Diabetes Outcomes Model
Clinical
Factors
•Severity
•Duration
•Etiology
•Comorbidity
Patient
Factors
•Age
•Race
•Gender
•Occupation
Treatment
•Specific medications
•Diet
•Exercise
•Case Management
Outcomes
•HbA1c
•Symptoms
•Function
•Complications
•Quality of life
•Employment/Work
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Understanding Causal Pathways
REGIMEN BURDEN
• Pain, Life-style,
discomfort
HEALTH ECONOMICS
EFFICACY
• Productivity
• Clinical
1c
Treatment Satisfaction
HEALTH STATUS
• Self-Reported
• Health Care Utilization
Adherence
Symptom distress
QUALITY OF LIFE
SIDE EFFECTS
•Adverse reactions
• Functional status
• Physical, Mental,
Cognitive, Social
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Study Design
62 sites in the United States
Glipizide GITS + diet vs Placebo + diet
16-week multicenter, randomized, double-blind,
placebo-controlled, parallel titration study
o
o
• 1-week washout
o
o
o ooo
o
o
• 3-week single-blind
o ooooo oo
oo o
o
o
o
o
o oo
placebo
o
oo
o
o
• 4-week dose titration
o
o
o o
o
o
o
oo
• 8-week maintenance
o o
o
o
o
o
Testa MA, Simonson DC. JAMA 1998; 280:1490-1496.
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Study Design
Maintenance
Screening / Single-blind Dose titration
washout
placebo
5-20 mg
■

Week -1

0

1

2
■

3

4

5

6
Maintenance
■

7
 
8 9

10
■

11

12

13
■
 
14 15
Randomization to placebo & diet or
Glipizide GITS & diet (1:2)
 Clinical and Laboratory Assessment
■ Health Economic Assessment
Testa MA, Simonson DC. JAMA 1998; 280:1490-1496.
29
Multicenter, Randomized Clinical Trial
Screened/Placebo Wash
N=1007
Eligible for Clinical Study
n=594
Diet & Placebo
Inelig. QOL: n=9
Eligible QOL: n = 192
Week 4,8,
n=178,169
Early Withdrawal
Week 12
n=158
Completers
Diet and GLipizide GITS
Inelig QOL: n=16
Eligible: n = 377
Week 4,8
n=349,340
Early Withdrawal
WeeK 12
n=333
Completers
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Patient Population
Baseline Clinical Characteristics
Number of Patients
Placebo
201
Glipizide GITS
393
Gender (M / F) (%)
60 / 40
55 / 45
Race (W / B / O) (%)
70 / 18 / 12
70 / 18 / 12
Emp / Ret / Unemp(%)
50 / 38 / 12
48 / 40 / 12
Age (yrs)
58 ± 12
59 ± 11
Duration DM (yrs)
5±5
6±6
FPG (mg / dL)
HbA1c (%)
231 ± 66
8.7 ± 1.4
218 ± 62
8.5 ± 1.5
Testa MA, Simonson DC. JAMA 1998; 280:1490-1496.
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Clinical Results
End of Week 15
Placebo
Glipizide GITS
P-Value
FPG (mg / dL)
224 ± 66
161 ± 41
< 0.001
HbA1c (%)
9.3 ± 1.9
7.5 ± 1.2
< 0.001
Hypoglycemic
Symptoms (%)
4.8
6
NS
Glucose < 55
mg / dL (%)
0
0
NS
Testa MA, Simonson DC. JAMA 1998; 280:1490-1496.
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HbA1c and Symptom Distress
EFFICACY
• HbA1c
HEALTH STATUS
• Self-Reported
Symptom distress
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Pharmacological Side
Effects and Symptom Distress
EFFICACY
• HbA1c
HEALTH STATUS
• Self-reported
Symptom distress
SIDE EFFECTS
•Adverse reactions
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Mean HbA1c: 9.3  1.9%
Trembling
Low blood sugar reaction
Fast pulse, rapid heartbeat, palpitations
Heartburn
Wheezing or difficulty breathing
Gaining weight
Cold hands or feet
Feeling overweight
Constipation
Swelling of feet or ankles
Abdominal cramps
Skin rash
Decrease in appetite
Mood swings
Losing weight
Flushing, sensation of heat
Shortness of breath or breathing hard
Increase in hunger
Inability to sleep, insomnia
Pains in legs or calves
Lightheadedness
Lethargy, no energy to do things
Numbness or tingling of hands or feet
Vomiting
Nauseous, queasy, sick to stomach
Diarrhea
Itching, scratching
Heart pounding, beating hard
Nightmares
Headaches
Impaired or worsening vision
Tired, feeling weary
Muscle cramps
Vertigo, sensation of spinning
Dizziness when standing up
Tightness,pain in chest
Drowsy or sleepy
Cold sweat, clammy skin
Sugar in urine
Foot cramps, foot pain
Sweating, perspiring
Confusion
General weakness or fatigue
Numbness of lips or mouth
Blurred or double vision
Crabby, short-tempered
Getting up often during the night to urinate
Being Thirsty
Having to urinate frequently
Sweet taste in mouth
Drinking a lot of fluids
Dryness of mouth, eyes or nose
High blood sugar
-0.2
7.5  1.2%
Hypoglycemic
symptoms, weight gain,
feeling overweight
Symptom Worsening
With Glucose
Lowering
P = N.S.
Symptom
Improvement With
Glucose Lowering
P < .05
P < .01
P < .001
0
0.2
0.4
SD Units
Testa MA, Simonson DC. JAMA 1998; 280:1490-1496.
Hyperglycemic
symptoms,
thirst, nocturia,
blurred vision,
fatigue
0.6
0.8
1
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Impact on Quality of Life
EFFICACY
• HbA1c
HEALTH STATUS
• Self- Reported
Symptom distress
QUALITY OF LIFE
SIDE EFFECTS
• Adverse reactions
• Functional status
• Physical, Mental,
Cognitive, Social
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Change In QOL Scales With
Therapy in Type 2 Diabetes
0.4
QOL Score (SD units)
0.3
*
0.2
***
** **
Overall Rating
Mental Health
Cognitive Function
Perceived Health
Symptom Distress
0.1
0
* P < 0.05
** P < 0.01
*** P < 0.001
-0.1
-0.2
-0.3
Placebo
Glipizide GITS
Testa MA, Simonson DC. JAMA 1998; 280:1490-1496.
37
QOL Global Outcome (Z-score)
Change in HbA1c and QOL
0.2
In Patients with NIDDM
Favorable QOL
Response
0
*
*
-0.2
*
*
No Change in QOL
No Change in HbA1c
-0.4
*
Unfavorable QOL
Response
-0.6
log-linear regression, r = .95, p < .01
-0.8
>1.5
Worsened
HbA1c
1.5 to .5
.5 to -.5
-.5 to -1.5
HbA 1c (%) Change from Baseline
Testa MA, Simonson DC. JAMA 1998; 280:1490-1496.
<-1.5
Improved
HbA1c
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Understanding Causal Pathways
REGIMEN BURDEN
• Pain, Life-style,
discomfort
HEALTH ECONOMICS
EFFICACY
• Productivity
• Clinical
1c
Treatment Satisfaction
HEALTH STATUS
• Self-Reported
• Health Care Utilization
Adherence
Symptom distress
QUALITY OF LIFE
SIDE EFFECTS
•Adverse reactions
• Functional status
• Physical, Mental,
Cognitive, Social
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Change (Week 15 – Baseline)
Production Losses
Absenteeism
Bed Days
Restricted Activity Days
(US $ / worker / month)
(US $ / 1000 person days)
(US $ / 1000 person days)
$1000's
100
1000
4
50
500
2
0
0
0
P < 0.001
-50
P = 0.01
P = 0.05
-2
-500
Placebo Glipizide
GITS
$ Loss
Placebo Glipizide
GITS
Placebo
Glipizide
GITS
$ Savings
Testa MA, Simonson DC. JAMA; 1998;280:1490-1496.
40
Health Care Utilization
Percent of Patients
40
Percent of Patients Reporting 1 or More Non-studyrelated Ambulatory Visits (clinic, ER, physician office)
per Month
40
P = NS
P = 0.002
30
30
20
20
Baseline
Placebo
Week 15
Baseline
Week 15
Glipizide GITS
Estimated savings = $11 per patient per month (assuming cost of $66 per ambulatory visit)
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Testa MA, Simonson DC. JAMA; 1998;280:1490-1496.
Summary
• Use Outcomes Research to
– Improve the quality of health care by changing
treatment and services and by promoting
preventive strategies
• Outcomes are “probability statements”
– Multifaceted
– Requires integrating and consolidating many
different components of health functioning
• Outcomes may take time to develop, use
intermediate outcomes if necessary
42
Summary
• Use Outcomes Research to
– Improve the quality of health care by changing
treatment and services and by promoting
preventive strategies
• Outcomes are “probability statements”
– Multifaceted
– Requires integrating and consolidating many
different components of health functioning
• Outcomes may take time to develop, use an
intermediate outcomes
43
Additional Resources and
References
• Online Questionnaires: SF12, LASA, EQ-5D.
• SF-36 translated into Arabic by Saud Abdulaziz bin Al
Abdulmoshin, 1997
• Coons SJ, Reliability of an Arabic Version of the
RAND-36 Health Survey and Its Equivalence to the
US English Version
• Testa and Simonson, NEJM, 1996
• Testa and Simonson, JAMA, 1998
• Straus, Testa, Sarokhan et al., Cancer 2006
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