Review of the FACT: Analytic
Strategies to Improve Sensitivity
David Cella, Ph.D.
Evanston Northwestern Healthcare
and Northwestern University
www.facit.org
Buchanan et al, JCO, 2005
• QOL assessment in Sx trials is rising without
good justification
• Single symptom improvement often fails to
improve overall QOL
• Acceptable rationales
– Gauge importance patients assign to symptom relief
– Gain dx information about offsetting tx effects
– Advance a compelling conceptual model of the
relationship between symptoms and QOL
Conceptual Framework: Relationship
Among Patient Outcome Measures
Characteristics of the Individual
Values / Preferences
Biological and
Physiological
Variables
Symptoms
Functional
Status
General
Health
Perceptions
Characteristics of the Environment
From: Wilson & Cleary (1995)
Overall
QOL
Symptom-targeted interventions can have
overall QOL benefits
FACT-G difference (score over time score at baseline)
FACT-G changes overtime
10
8
6
4
2
0
-2
-4
Baseline
1-3 months
Intervention
4-5 months
Attention-control
after 6 months
Control
Velikova et al., JCO, 2004.
Some, not all, benefit in emotional well-being
FACT-EWB difference (score over
time - score at baseline)
Changes in FACT-EWB over time
2.5
2
1.5
1
0.5
0
-0.5
Baseline
1-3 months
Intervention
4-5 months
Attention-control
After 6
months
Control
Velikova et al., JCO, 2004.
Some studies actually suggest
overall QOL benefit without target
symptom benefit
• Osterborg, JCO, 2002
– Placebo vs epo beta for CIA
– No difference in FACIT-Fatigue
– Significant difference in overall QOL
QOL Model
Total/Overall
(aggregated)
PWB
HRQoL
MWB
Global
(synthesized)
SWB
Symptoms Function Symptoms Function Concerns
Function
Adapted from WHO
Overall versus Global HRQL
Both have problems in symptom trials
• Overall (Total score)
– Tension between content validity and focused
relevance
– Unresponsiveness caused by mistargeted questions
• Global rating
– Intuitively appealing but coarse
– Vulnerable to several cognitive biases that affect
reporting of general well-being and satisfaction
Are we doomed to be happy?
• Life satisfaction research consistently places people near
the 75% of satisfaction/happiness scales
• Short term improvements in environmental conditions,
wealth, etc, have a modest effect
• Most human happiness is independent of life’s ups and
downs
• Implications for measuring GLOBAL QOL in cancer
trials
– May see small short term benefits, unlikely to see lasting effect
– Background noise caused by positive cognitive bias
– Background noise caused by “doing something”
Thoughts drawn from Cummins & Nistico, 2002
General
Population
Norms(n=2,236)
FACT
Profile of
Cancer Patients
Males and Females Combined
Referenced to General
(N=1075) Population (n=1,075)
70
28
60
27
26
25
24
23
50
T-Score
22
21
20
19
18
40
17
16
15
14
13
12
30
11
10
9
8
7
20
28
27
26
25
24
23
22
21
20
19
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
0
23
22
21
20
19
18
17
16
15
14
13
12
11
10
9
8
7
5
5
4
4
3
35
30
20
15
10
1
1
40
25
2
2
108
106 107
104 105
102 103
100 101
98 99
96 97
95
94 93
92 91
90
88 89
87
86 85
84 83
82
80 81
79
78
76 77
75
74
72 73
70 71
69
68 67
66 65
64
62 63
60 61
58 59
56 57
55
54 53
52
50 51
48 49
47
46 45
6
6
3
10
24
28
27
26
25
24
23
22
21
20
19
18
17
16
15
14
13
12
11
10
9
8
7
6
5
4
3
2
1
0
5
0
0
0
Mean for Cancer Patients
0
0
Physical
1
Well Being
Social
2 / Family
Well Being
Emotional
3
Well Being
Functional
4
Well Being
5Total
FA CT-G
6
Symptom Prevalence Among Patients
with Cancer or HIV
HIV (n=433)
Cancer (n=2791)
Nausea
Depression
Anxiety
Pain
Fatigue
0
20
40
60
80
100
Percentage Reporting Symptom, any severity
Cella D, 1998
FACT/NCCN Survey Results
Number of times symptom is in “top 5”
lack of energy (fatigue)
pain
nausea
losing weight
worry condition worse
content w/ QOL
certain areas experience pain
swelling/cramps in stomach
able to enjoy life
short of breath
trouble meeting needs of family
9/9
8/9
7/9
5/9
5/9
4/9
3/9
3/9
2/9
2/9
2/9
Clinically Significant Symptoms in NSCLC Patients
With Provider-Rated PS0-1 at Baseline (E5592)
45
Clinically Significant Symptoms (%)
40
35
30
25
20
15
10
5
0
Baseline
6 weeks
Fatigue
Pain
12 weeks
Weight loss
6 months
Appetite loss
Clinically Significant Symptoms in NSCLC Patients
With Provider-Rated PS0-1 at Baseline (E5592)
Clinically Significant Symptoms (%)
45
40
35
30
25
20
15
10
5
0
Baseline
Depression
Hopelessness
6 weeks
Anhedonia
12 weeks
6 months
Bothered by treatment side effects
Symptoms and QOL (N=1,163)
100
pain
FACT-G Total
90
insomnia
weakness
80
nausea
Diarrhea
70
60
50
Very much
Quite a bit
A little
Not at all
Side Effect Bother and QOL
100
FACT-G (26-items)
90
80
Breast (n=529)
Colon (n=254)
70
Head/Neck (n=233)
60
50
Very much
Quite a bit
Somewhat
A little
Not at all
FACIT measurement system
Functional Assessment of Chronic
Illness Therapy
An array of multidimensional self-report
quality-of-life questionnaires
Over 400 items
Over 50 languages (selected scales)
Over 30 targeted subscales
www.facit.org
Framework for FACT
Disease
Symptoms
Social
Functional
Emotional
Physical
Trial Outcome Index = Physical + Functional + Symptoms
(e.g., 36-item FACT-L includes 17 symptoms)
FACT-G (Version 4)
Below is a list of statements that other people with your illness have said
are important. By circling one (1) number per line, please indicate how true
each statement has been for you during the past 7 days
Physical wellbeing
Not at all A little bit Somewhat Quite a bit Very much
GP1 I have a lack of energy
GP2 I have nausea
GP3 Because of my physical
condition, I have trouble
meeting the needs of my
family
0
0
1
1
2
2
3
3
4
4
0
1
2
3
4
GP4 I have pain
0
1
2
3
4
GP5 I am bothered by side
effects of treatment
0
1
2
3
4
0
0
1
1
2
2
3
3
4
4
GP6 I feel ill
GP7 I am forced to spend
time in bed
FACT Cancer-Specific Scales
•
•
•
•
•
•
•
•
Breast cancer
Bladder cancer
Brain tumor
Colorectal cancer
CNS cancer
Cervical cancer
Esophageal cancer
Endometrial cancer
•
•
•
•
•
•
•
•
Head and neck cancer
Hepatobiliary cancer
Lung cancer
Leukemia
Lymphoma
Ovarian cancer
Prostate cancer
Vulvar cancer
www.facit.org
FACT-Lung Subscale
•
•
•
•
•
•
•
I have been short of breath
I am losing weight
My thinking is clear
I have been coughing
I have a good appetite
I feel tightness in my chest
Breathing is easy for me
FACT-Breast Subscale
Short of breath
Self-conscious about dress
One or both arms swollen or tender
Sexually attractive
Bothered by hair loss
Other family members might get same illness
Effect of stress on illness
Bothered by change in weight
Feel like a woman
FACIT symptom-specific subscales
Anorexia/cachexia
Anemia
Diarrhea
Endocrine symptoms
Fatigue
Fecal incontinence
Urinary incontinence
Fatigue subscale
Feel fatigued
Feel weak all over
Feel listless
Feel tired
Have trouble starting things
Have trouble finishing things
Have no energy
Able to do usual activities
Require sleep during day
Too tired to eat
Need help doing usual activities
Frustrated/too tired for usual activities
Must limit social activity because too tired
Littlewood et al (JCO 2000) Epoetin
alfa Trial Treatment Schema
150 IU/kg (if Hb 1 g/dL or
reticulocytes 40,000/mL)
at Week 4
150 IU/kg
epoetin alfa
300 IU/kg (if Hb <1 g/dL and
reticulocytes <40,000/mL)
at Week 4
or
Placebo (if Hb 1 g/dL or
reticulocytes 40,000/mL)
at Week 4
Placebo
Double placebo (if Hb <1 g/dL and
reticulocytes <40,000/mL)
at Week 4
0
Chemotherapy*
4
8
12
16
20
24
28
Weeks
*Chemotherapy duration 3-6 cycles; includes 3-4 weeks after the last dose of chemotherapy
FACT-G, FACT-An: Fatigue, and
FACT-An: Anemia Scores
Change From Baseline to Last Assessment
Epoetin alfa
5
n=200
n=200
n=192
Change in Score
Placebo
4.02
2.97
2.42
0
-3.31
-2.18
-2.64
n=90
n=90
n=87
-5
FACT-G:
Total
P<.05
FACT-An:
Fatigue
P<.01
FACT-An:
Anemia
P<.01*
Decrease in FACT-G Total Vs No History of Specified Illnesses
Decrease in FACTG (Effect size)
(-0.34)
(0)
(0.34)
(0.69)
(1.03)
(1.37)
1.71)
FACIT-Fatigue Subscale
Baseline
Final
Assessmen
26
EPO =
31
36
41
46
FACT-G Total
Baseline
Final
Assessment
68
EPO =
73
78
83
88
FACT-Endocrine Symptoms Subscale
Hot flashes
Cold sweats
Night sweats
Vaginal discharge
Vaginal itching/irritation
Vaginal bleeding or spotting
Vaginal dryness
Pain or discomfort with intercourse
Lost interest in sex
Gained weight
Lightheaded/dizzy
Vomiting
Bloated
Breast sensitivity/tenderness
Mood swings
Irritable
ATAC Trial: Trial Outcome Index
75
74
Mean TOI
73
72
71
Anastrozole
Tamoxifen
Combination
324
331
319
239
244
242
70
69
67
66
Entry
288
309
285
287
304
281
68
3
6
249
252
250
267
276
264
12
18
24
Visit (months)
Fallowfield
Fallowfieldet
etal.
al,2002,
JCO, 2003
2004
ATAC Trial: FACT-ES Scores
64
Anastrozole
Tamoxifen
Combination
322
330
Mean ES
63
323
286
309
286
62
61
292
306
295
271
279
269
6
12
60
252
254
257
244
249
241
59
58
57
Entry
3
18
24
Visit (months)
Fallowfieldetetal,al.JCO,
2002,
2003
Fallowfield
2004
ATAC Trial: Specific Symptoms
Fallowfield et
et al,
al. JCO,
2002,2004
2003
Fallowfield
E 5592: Overall Survival
Probability 1.0
CP/CP+G
CE
0.8
Log rank p=0.034
Wilcoxon p=0.012
0.6
0.4
0.2
0.0
0
5
10
15
20
Time (months)
25
30
Baseline to 12-week change in
LCS score by best overall response
LCS
change
3
2
1
0
-1
CR/PR > PD
-2
CR/PR (n=95)
SD (n=82)
PD (n=102)
Best response to treatment
CR/PR, complete response/partial response; SD, stable disease;
PD, progressive disease
Cella
Time to completion was 12 weeks
et al, JCE, 2002
Baseline to 12-week change in
LCS score by time to progression
LCS
change
2
Late > Early
1
0
-1
-2
Late
(>116 days)
(n=196)
Early
(<116 days)
(n=69)
Time to progression
Time to completion was 12 weeks
Cella et al, JCE, 2002.
E5592 - Lung Cancer Subscale
Progression status
(Range: 0-28)
24
22
20
Later
progressors
18
16
Early
progressors
14
12
10
base.
6 wk
12 wk
FACT Symptom Indexes:
Undoing the Original Structure
•
•
•
•
Most FACT site-specific scales assess about
50% symptoms and 50% function/perception
FACT-G includes most common symptoms
(e.g., pain; fatigue; nausea)
FACT disease subscales focus on sympoms
unique to that condition
Common and unique need to be brought
together to index the symptom burden of each
specific cancer
Colorectal
Distribution of Items (n=66)
lack of energy (fatigue)
losing weight
pain
diarrhea
nausea
Items
swelling/cramps in stomach
good appetite
content w/ QOL
enjoy life
feel ill
spend time in bed
(chance probability=21%)
control of bowels
able to work
worry condition worse
losing hope
0%
10%
20%
30%
40%
50%
60%
% Endorsed (top 5)
70%
80%
90%
100%
Head and Neck
Distribution of Items (n=65)
pain
swallow naturally/easily
lack of energy (fatigue)
pain in face/neck
trouble breathing
Items
communicate w/ others
nausea
eat solid foods
content w/ QOL
worry condition worse
unhappy w/ appearance of face/neck
(chance probability=19%)
losing hope
eat foods I like
worry about dying
trouble meeting needs of family
0%
10%
20%
30%
40%
50%
60%
% Endorsed (top 5)
70%
80%
90%
100%
Ovarian
Distribution of Items (n=60)
lack of energy (fatigue)
vomiting
pain
nausea
sw elling in stomach
w orry condition w orse
Items
content w / QOL
cramps in stomach
losing w eight
feel ill
w orry about dying
trouble meeting needs of family
control of bow els
(Chance probability=19%)
able to enjoy life
spend time in bed
good appetite
losing hope
0%
10%
20%
30%
40%
50%
60%
% Endorsed (top 5)
70%
80%
90%
100%
Lung
Distribution of Items (n=66)
short of breath
lack of energy (fatigue)
pain
losing weight
coughing
Items
bone pain
breathing easy for me
content w/ QOL
spend time in bed
able to enjoy life
nausea
(chance probability=20%)
tightness in my chest
good appetite
worry about dying
0%
10%
20%
30%
40%
50%
60%
% Endorsed (top 5)
70%
80%
90%
100%
Why is more precision needed?
• Cancer is many diseases and has many effects
upon HRQL
– Most instruments can’t cover all important content
• Disease trajectory includes
– Diagnosis (acute anxiety)
– Active treatment (various and chronic symptoms)
– Disease-free survivorship (emerging social issues and
stress responses, negative and positive)
– End of life (emerging physical, social and existential
issues)
• Most instruments have floor and/or ceiling effects
Looking ahead 5-10 years:
Standardizing Metrics and Improving
Precision
•Item Banking
•Computerized Adaptive Testing (CAT)
National Item Banks Are Coming
NIH Roadmap Cooperative Group:
Patient Reported Outcome
Measurement Information System
(PROMIS)
A Better Mousetrap?
• PROMIS and the future of (some)
outcome measures
–
–
–
–
–
–
Fatigue
Pain
Physical Function
Social Role participation
Emotional Distress
???
www.NIHPROMIS.org
