Transcript QoL to Symptom Relief - PowerPoint presentation

Quantifying Treatment Benefit
from the Patient’s Perspective:
From quality of life to symptom relief
David Cella, Ph.D.
Evanston Northwestern Healthcare and
Northwestern University
FDA Position: Oncology
 Two primary endpoints
– Survival
– Quality of Life
 Secondary endpoints
– Response rate
– Disease free survival
– Time to progression
Key Strategies in Trial Design
 Concealed randomization
 Controlled by placebo
 Clinically-relevant assessment
– reliable
– valid
– responsive to familiar anchors
 Concomitant medications
 Complete data
 Controls in design
– QoL assessment pre-disclosure
– Control for pre-study impact
– Control for improvements in emotional well-being
Evolution of QOL Studies in Oncology
• Old idea (cytotoxic): “Chemotherapy makes
patients worse in the short run; justified in the
long run.”
• Discovery: Symptomatic patients who respond
to cytotoxic chemotherapy usually improve even
during chemotherapy
• New idea (cytostatic): “Chemotherapy can
make patients better in the short and long run.”
Quality-of-life dimensions
Physical wellbeing
– disease symptoms
– treatment side effects
Emotional
wellbeing
– coping
– distress
Quality of life
– enjoyment
Social wellbeing
– social activity/support
– relationship quality
– family wellbeing
Functional wellbeing
– ADLs
– role performance
FACIT measurement system
Functional Assessment of Chronic
Illness Therapy
An array of multidimensional self-report
quality-of-life questionnaires
 Over 400 items
 Over 40 languages (selected scales)
FACT includes:
FACT-G:




Physical wellbeing (7 items)
Social/family wellbeing (7 items)
Emotional wellbeing (6 items)
Functional wellbeing (7 items)
Plus...
 Additional questions specific to the disease,
treatment or condition
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 well-being
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
FACIT disease-specific subscales
Cervical
Breast
Hepatobiliary
Colon
Bladder
Lung
Esophageal
Brain
Ovarian
Head and neck
CNS
Prostate
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
Anorexia/Cachexia subscale - 12
 Appetite
 Ability to eat a sufficient quantity
 Worry over weight
 Unpleasantness of food
 Body image concern
 Loss of interest in food
 Difficulty with “heavy” foods
 Pressure to eat from family
 Vomiting
 Early satiety
 Stomach pain
 General health rating
Lung Cancer Subscale Questions







I have been short of breath
I have been coughing
I feel tightness in my chest
Breathing is easy for me
I am losing weight
My thinking is clear
I have a good appetite
Overall score range is 0-28 (severe to asymptomatic).
Phase III Trial of 5-FU vs Gemcitabine in Advanced
Pancreatic cancer
• Randomized clinical trial of 126 patients
• End-points
Clinical benefit
 Pain
 Performance status
• Weight
Survival
Burris, H.A., et al, (1997). J Clinical Oncology. 15 (6), 2403-2413.
5-FU vs Gemcitabine Results
Improvement in clinical benefit index
5-FU
Gemcitabine
(p=.0022)
Survival
5-FU
Gemcitabine
4.8%
23.8%
4.4 mos.
5.6 mos.
(p=.0025)
Burris, H.A., et al, (1997). J Clinical Oncology 6), 2403-2413
Baseline to 12-week change in Lung Cancer Subscale score
(best overall response)
LCS change
3
2.4
2
1.1
1
0
-0.03
-1
CR/PR > PD
-2
CR/PR (n = 95)
SD (n = 82)
PD (n = 102)
Best Response to Treatment
Initial TOI and improvement at
6 weeks* (n=352)
Proportion 1.0
surviving
0.8
0.6
0.4
Initial, improved?
0.2
<58, no
>58, no
<58, yes
>58, yes
0.0
0
1
2
3
4
*Patients with missing QoL excluded
5
6
7
8
9
10
11 12
What is a (clinically) meaningful change?
 Meaningful change: A difference or change in score
on a health-related quality of life (HRQoL)
questionnaire that is important to the involved person
or people
 “Clinically” meaningful corresponds to a clinically
important difference or change in patient status.
E5592 - Lung Cancer Subscale
Best overall response to treatment
(Range: 0-28) 26
24
22
CR/PR
20
SD
18
PD
16
14
12
base.
6 wk
12 wk
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
E5592 - Shortness of Breath
Very
much
4
Early
progressors
3
Later
progressors
2
1
Not
at all
0
Baseline
6 weeks
12 weeks
E5592 - Weight loss
Very
much
4
Early
progressors
3
Later
progressors
2
1
Not
at all
0
Baseline
6 weeks
12 weeks
E5592 - Cough
Very
much
4
Early
progressors
3
Later
progressors
2
1
Not
at all
0
Baseline
6 weeks
12 weeks
Tumor Sites
Advanced
– Bladder
– Brain
– Breast
– Colorectal
– Head & Neck
– Hepatobiliary
– Lung
– Ovarian
– Prostate
Revised
Summary
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
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=20.8%)
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%
Hepatobiliary
Distribution of Items (n=61)
pain
losing weight
lack of energy (fatigue)
feel fatigued
nausea
discomfort/pain stomach
bothered by jaundice
Items
swelling/cramps in stomach
have/had itching
pain in back
good appetite
diarrhea
losing hope
have/had fever
(chance probability=14.3%)
content w/ QOL
spend time in bed
able to do usual activities
bothered by constipation
feel ill
0%
10%
20%
30%
40%
50%
60%
% Endorsed (top 5)
70%
80%
90%
100%
FACT Hepatobiliary
Symptom Index
(FHSI)
FACT Hepatobiliary Symptom Index - 8
item (FHSI-8)








pain
weight loss
fatigue (I feel fatigued)
nausea
jaundice
back pain
stomach pain/discomfort
fatigue (I lack energy)
Performance Comparison
FHSI-8 versus FACT-Hep
ECOG PSR 0, n=16
[1] discrimination between (PSR=0) v (PSR=1 or 2/3);
[2] discrimination between (PSR=0) v (PSR=1) v (PSR=2/3)
[3] discrimination between (PSR=0 or 1) v (PSR=2/3)
ECOG PSR 2/3, n=23
** [1]
120
*
** [2]
** [1]
** [1]
** [2]
** [3]
100
80
60
40
20
FI
SH
-8
ut
co
m
e
In
de
x
al
e
Tr
ia
lO
HE
P
su
bs
c
TG
FA
C
el
l-b
ei
ng
W
Fu
nc
tio
na
l
W
ot
io
na
l
Em
So
ci
al
/F
am
ily
W
el
l-b
ei
ng
el
l-b
ei
ng
el
l-b
ei
ng
0
Ph
ys
ic
al
W
Scale Response (0-100)
ECOG PSR 1, n=12
*p<.05, **p<.0001
Scale
Yount et al, 2002
So
l/F
al
Scale
In
d
ex
le
120
*
FH
SI
-8
m
e
ca
bs
*
lO
ut
co
Su
-G
ng
ing
l- b
ei
-b
e
FA
CT
W
el
HE
P
tio
n
nc
lW
ell
**
Tr
ia
Fu
na
g
ing
in
-b
e
l-b
e
W
ell
lW
el
am
ily
ica
ys
Scale Response (0-100)
100
Em
ot
io
cia
Ph
Performance Comparison
FHSI-8 versus FACT-Hep
Not on treatment, n=18
On treatment, n=33
*
80
60
40
20
0
*p<.05, **p<.01
Colorectal and Hepatobiliary Cancer
QOL studies: What to evaluate?
 Definitely
–
–
–
–
–
General pain and abdominal cramping
Fatigue
Appetite and weight loss
Diarrhea
Nausea
 Probably
–
–
–
–
–
Other bowel concerns (e.g., constipation)
Other side effects (e.g., mucositis, fever, alopecia)
Activity limitation; Life enjoyment
Worry, Distress, Hope
Overall (global) quality of life
 Maybe
– Multidimensional health status
Internal Consistency Reliability and 2 Week Reproducibility of the GCSI Total and
Subscale Scores
Reproducibilityb
Subscale
Number
Of Items
Cronbach’s
Alphaa
ICC
Mean Score
Difference (SD)
GCSI Total
9
0.84
0.76b
-0.02 (0.72)
Bloating
2
0.84
0.69
-0.14 (1.29)
Post-prandial fullness/Early satiety
4
0.83
0.68
-0.05 (0.94)
Nausea/Vomiting
3
0.85
0.81
0.10 (0.82)
aN=159-166,
with variation due to missing data
stable patients over 2 week period
Source: Revicki et al. (2002)
bN=23
References
Cella, D.F., Bonomi, A.E., Lloyd S.R., Tulsky, D.S., Kaplan, E., Bonomi, P. (1995).
Reliability and validity of the Functional Assessment of Cancer Therapy - Lung (FACTL) quality of life instrument. Lung Cancer, 12, 199-220.
Yellen, S.B., Cella, D.F., Webster, K.A., Blendowski, C., & Kaplan, E. (1997).
Measuring fatigue and other anemia-related symptoms with the Functional
Assessment of Cancer Therapy (FACT) Measurement System. Journal of Pain and
Symptom Management, 13 (2), 63-74.
Ribaudo, J.M., Cella, D., Hahn, EA, Lloyd, S.R., Tchekmedyian, N.S., Von Roenn,
J., & Leslie, W. (2001). Re-Validation and Shortening of the Functional Assessment of
Anorexia/Cachexia Therapy (FAACT) questionnaire. Quality of Life Research, 9, 11371146.
Cella, D., Lai, J-S., Chang, C-H., Peterman, A., & Slavin, M. (2002). Fatigue in
Cancer Patients Compared with Fatigue in the General United States Population.
Cancer, 94(2), 528-538.
Cella, D., Hahn, E., & Dineen, K. (2002). Meaningful change in cancer-specific
quality of life scores: Differences between improvement and worsening. Quality of Life
Research, 11 (3), 207-21.