Psychometric validation of the SF-36 Health Survey in light chain amyloidosis: results from community-based and clinic-based samples

Figures & data

Table 1 Summary of criterion measures

PRO name	Description of items/domains	Recall period	Scoring	Data source
Numeric pain rating	Single item rating of pain	Past week	• Range: 0–10 • Direction: higher scores represent worse pain	Study #1
Global assessment of functioning	Single item of functioning	Nonspecific	• Range: 0–100 • Direction: higher scores represent better functioning	Study #1
WPAI questionnaire: specific health problem scales	Only administered to a subsample of patients who were currently employed Three subscales: • Absenteeism: % work missed due to disease • Presenteeism: % time spent at work that is impacted by disease • Overall work productivity loss: % work productivity loss (accounts for both absenteeism and presenteeism)	Past 7 days	• Range: 0–100 (presented as percentages) • Direction: higher scores represent worse outcomes	Study #1
KCCQ-12	Twelve-item disease-specific measure of HRQoL Four subscales: physical limitation, symptoms, quality of life, and social limitation Only administered to a subsample of patients with cardiac involvement	Past 2 weeks	• Range: 0–100 (presented as percentages) • Direction: higher scores represent better functioning	Study #1
PGI-S	Single item to measure patient’s perceived severity of disease	Past month	• Ordinal scale: not severe at all, mild, moderate, severe, very severe	Study #1
PGAC	Single item to guage and measure patient’s perceived change in severity	Since last survey	• Ordinal scale: very much improved, somewhat improved, no change, somewhat worse, very much worse	Study #1
Recent hematologic response	Single item to guage recent response to treatment	Current status	• Ordinal scale: no response, partial response, complete remission, or hematologic response	Study #1
SWOG performance status	Single item guaging the percent of day spent in bed	Nonspecific	• Ordinal scale: 0%, 25%, 50%, 75%, and 100%	Study #2

Notes: Study #1, community-based sample; Study #2, clinic-based sample.

Abbreviations: HRQoL, health-related quality of life; KCCQ-12, Kansas City Cardiomyopathy Questionnaire; PGAC, Patient Global Assessment of Change; PGI-S, Patient Global Impression – Severity; PRO, patient-reported outcome; SWOG, Southwest Oncology Group; WPAI, Work Productivity and Activity Impairment.

Table 2 Summary of the psychometric validation approaches for the SF-36 in an AL amyloidosis population

Psychometric property	Analysis/indicator	Data source	Criterion measure
Reliability
Test–retest reliability	ICCs ≥0.70	Study #1: patients with stable disease between baseline and 1-month followup (n=179)a	N/A
Internal consistency reliability	Cronbach’s alpha ≥0.70	Study #1: baseline sample Study #2: baseline sample	N/A
Validity
Scale convergent validity	Pearson’s moment-product correlation ≥0.40	Study #1: baseline sample	Numeric pain rating; global assessment of functioning; WPAI; KCCQ-12
Discriminant validity (known-groups approach)	ANOVA tests	Study #1: baseline sample Study #2: baseline sample	Response to treatment; PGI-S SWOG – performance status
Responsiveness
Ability to detect change	Paired t-tests	Study #1: 6-month follow-up sample (change from baseline) Study #2: follow-up sample (change from baseline)	PGAC SWOG – performance status

Notes:

a A 1-month interval was chosen for the assessment of test–retest reliability because: 1) it was long enough so that patients were unlikely to remember their previous responses and/or be affected by survey response fatigue and 2) it was short enough that substantial changes in health status were unlikely. To help ensure that no substantial change in health status occurred during that timeframe, we restricted this analysis to patients who reported their disease had been stable on the PGAC survey item. Study #1, community-based sample; Study #2, clinic-based sample.

Abbreviations: AL, light chain; ANOVA, analysis of variance; KCCQ-12, Kansas City Cardiomyopathy Questionnaire; ICC, intraclass correlation coefficient; N/A, not applicable; PGAC, Patient Global Assessment of Change; PGI-S, Patient Global Impression – Severity; SF-36, SF-36 Health Survey; SWOG, Southwest Oncology Group; WPAI, Work Productivity and Activity Impairment.

Table 3 Baseline sociodemographic and disease characteristics by study sample

Characteristic	Study #1, community-based sample (n=341)		Study #2, clinic-based sample (n=1,438)
	n	%	n	%
Age, mean years (SD)	60.6 (10.2)		61.6 (10.8)
Age range (median)	23–85 (61)		27–101 (62)
Gender
Male	160	47.1	870	60.5
Female	180	52.9	568	39.5
Race/ethnicity
White	304	89.1	1,275	88.7
Others	37	10.9	162	11.3
Education
≤ High school diploma or GED	26	8.1	319	26.6
Some college, associate degree, or technical certificate	99	30.7	212	17.7
Bachelor’s degree (BA, BSc)	109	33.9	306	25.6
Graduate degree	88	27.3	360	30.1
Marital status
Married	271	82.1	1,043	79.0
Others	59	17.9	274	21.0
Employment status
Currently employed for pay	115	38.3		N/A
Time since diagnosis, mean years (SD)	4.5 (4.0)		0.6 (1.3)
Time since diagnosis range (median)	1 month to 28 years (3.5 years)		0 days to 15.5 years (2.4 months)
Types of organs/systems impacteda
Heart (cardiac)	178	52.2	777	54.0
Kidney	214	62.8	1,038	72.2
Liver	49	14.4	389	27.1
Nervous system	126	37.0	432	30.0
Gastrointestinal	148	43.4	466	32.4
Number of organs involved
One	95	27.9	47	3.3
Two	89	26.1	346	24.3
Three or more	157	46.0	1,029	71.6
Most recent hematologic response status			N/A
No response to treatment	23	6.7
Partial hematologic response or partial remission	126	37.0
Complete hematologic response or complete remission	141	41.3
I do not know	51	15.0

Note:

a Multiple responses allowed.

Abbreviations: BA, Bachelors of Art; BSc, Bachelors of Science; GED, general educational development; N/A, not applicable; SD, standard deviation.

Table 4 Reliability of the SF-36 scales

Reliability	SF-36 scale
	PF	RP	BP	GH	VT	SF	RE	MH
Test–retest reliability
ICCa	0.85	0.77	0.78	0.86	0.77	0.73	0.76	0.78
Internal consistency
Study #1b – Cronbach’s alpha	0.93	0.97	0.91	0.78	0.87	0.90	0.95	0.88
Study #2c – Cronbach’s alpha	0.95	0.91	0.90	0.76	0.88	0.87	0.89	0.82

Notes:

a Calculated among the subsample of patients in the community-based sample (Study #1) who reported “no change” on the Patient Global Assessment of Change item on the 1-month follow-up survey (n=179).

b Community-based sample of AL amyloidosis patients (n=341).

c Clinic-based sample of AL amyloidosis patients (n=1,438).

Abbreviations: AL, light chain; BP, bodily pain; GH, general health; ICC, intraclass correlation coefficient; MH, mental health; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; SF-36, SF-36 Health Survey; VT, vitality.

Table 5 Convergent validity in Study #1: Pearson correlation coefficients between SF-36 scores and criterion measures

SF-36 scale/component summary	Criterion measure	N	r
BP	Numeric pain rating	341	−0.82
RP	WPAIa: absenteeism	108	−0.45
RP	WPAIa: presenteeism	94	−0.67
RP	WPAIa: work productivity	92	−0.68
RP	WPAI: activity impairment	341	−0.72
GH	Global functioning rating	341	0.60
PF	KCCQ-12b: physical limitation	153	0.73
PCS	KCCQ-12b: physical limitation	153	0.65
SF	KCCQ-12b: social limitation	153	0.73
MCS	KCCQ-12b: social limitation	153	0.58
PCS	KCCQ-12b: quality of life	153	0.61
MCS	KCCQ-12b: quality of life	153	0.51

Notes: All correlations are significant (P<0.001).

a Administered to a subsample of study participants who are currently employed.

b Administered to a subsample of study participants with self-reported cardiac involvement. r, Pearson correlation.

Abbreviations: BP, bodily pain; GH, general health; KCCQ-12, Kansas City Cardiomyopathy Questionnaire; MCS, mental component summary; PCS, physical component summary; PF, physical functioning; RP, role physical; SF, social functioning; SF-36, SF-36 Health Survey; WPAI, Work Productivity and Activity Impairment.

Table 6 Known-groups validity test: SF-36 scores by recent hematologic response (Study #1)

SF-36 scale/score	Most recent hematologic response
	No response to treatment (n=23)	Partial hematologic response (n=126)	Complete hematologic response/remission (n=141)	Raw P-valuea	Adjusted P-valueb	Do not know (n=51)
SF-36 norm-based scales
PF	35.0	41.1	45.6	<0.001	<0.001	40.9
RP	33.3	37.5	44.3	<0.001	<0.001	40.6
BP	38.6	44.5	49.2	<0.001	<0.001	47.9
GH	33.2	35.1	43.3	<0.001	<0.001	41.4
VT	40.7	41.7	47.9	<0.001	<0.001	43.6
SF	36.2	42.2	46.8	<0.001	<0.001	41.6
RE	40.3	43.8	47.6	0.005	0.009	45.0
MH	44.7	47.7	51.4	0.002	0.005	48.2
SF-36 summary scores
PCS	32.8	37.9	44.3	<0.001	<0.001	41.3
MCS	44.2	46.5	50.2	0.009	0.009	46.8

Notes:

a P-values for the ANOVA tests were based on the following groups: no response to treatment; partial hematologic response; and complete hematologic response/remission. The ANOVA tests did not include the “do not know” category.

b Adjusted for multiple comparisons using Hommel’s method.

Abbreviations: BP, bodily pain; GH, general health; MCS, mental component summary; MH, mental health; PCS, physical component summary; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; SF-36, SF-36 Health Survey; VT, vitality.

Table 7 Known-groups validity test: SF-36 scores by PGI-S scale (Study #1)

SF-36 scale/score	PGI-S scale
	Not severe at all (n=133)	Mild (n=92)	Moderate (n=81)	Severe/very severe (n=35)	Raw, P-value	Adjusted, P-valuea
SF-36 norm-based scales
PF	48.9	41.7	38.4	30.1	<0.001	<0.001
RP	47.3	40.7	34.5	27.8	<0.001	<0.001
BP	51.8	47.0	43.5	32.8	<0.001	<0.001
GH	45.1	39.2	34.6	27.9	<0.001	<0.001
VT	49.7	44.1	40.9	33.8	<0.001	<0.001
SF	49.8	44.5	37.8	31.1	<0.001	<0.001
RE	50.7	46.7	40.1	33.4	<0.001	<0.001
MH	53.5	50.3	45.7	37.0	<0.001	<0.001
SF-36 summary scores
PCS	47.0	40.0	36.4	28.5	<0.001	<0.001
MCS	52.4	49.3	43.7	36.9	<0.001	<0.001

Note:

a Adjusted for multiple comparisons using Hommel’s method.

Abbreviations: BP, bodily pain; GH, general health; MCS, mental component summary; MH, mental health; PCS, physical component summary; PF, physical functioning; PGI-S, Patient Global Impression – Severity; RE, role emotional; RP, role physical; SF, social functioning; SF-36, SF-36 Health Survey; VT, vitality.

Table 8 Known-groups validity test: SF-36 scores by SWOG performance status (Study #2)

SF-36 scale/score	Performance status (% of time spend in bed)
	0% (n=70)	25% (n=471)	50% (n=213)	≥75% (n=131)	Raw P-value	Adjusted P-valuea
SF-36 norm-based scales
PF	48.4	37.4	26.1	21.6	<0.001	<0.001
RP	48.2	36.6	30.8	29.0	<0.001	<0.001
BP	53.4	48.7	43.3	41.2	<0.001	<0.001
GH	46.6	40.7	35.7	33.0	<0.001	<0.001
VT	49.5	41.4	34.4	33.2	<0.001	<0.001
SF	47.8	40.4	32.3	27.9	<0.001	<0.001
RE	49.4	43.3	37.4	34.8	<0.001	<0.001
MH	49.4	46.9	43.5	43.3	<0.001	<0.001
SF-36 summary scores
PCS	49.1	39.0	31.0	27.6	<0.001	<0.001
MCS	48.9	45.8	41.7	40.5	<0.001	<0.001

Note:

a Adjusted for multiple comparisons using Hommel’s method.

Abbreviations: BP, bodily pain; GH, general health; MCS, mental component summary; MH, mental health; PCS, physical component summary; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; SF-36, SF-36 Health Survey; SWOG, Southwest Oncology Group; VT, vitality.

Figure 1 Change in SF-36v2 scores by self-reported patient global assessment of change in AL amyloidosis patients.

Notes: Data represent responses from patients in the community-based sample (Study #1; n=117). A total of 107 patients endorsed “no change” on the PGAC, data not shown. ^aP<0.05, adjusted for multiple comparisons.
Abbreviations: AL, light chain; BP, bodily pain; GH, general health; MCS, mental component summary; MH, mental health; PCS, physical component summary; PF, physical functioning; PGAC, Patient Global Assessment of Change; RE, role emotional; RP, role physical; SF, social functioning; VT, vitality.

Figure 2 Change in SF-36 scores by SWOG performance status in AL amyloidosis patients.

Notes: Data represent responses from patients in the clinic-based sample (Study #2; n=201). A total of 122 patients had “no change” in their SWOG performance status, data not shown. ^aP<0.01, adjusted for multiple comparisons. ^bP<0.05, adjusted for multiple comparisons.
Abbreviations: AL, light chain; BP, bodily pain; GH, general health; MCS, mental component summary; MH, mental health; PCS, physical component summary; PF, physical functioning; RE, role emotional; RP, role physical; SF, social functioning; SF-36, SF-36 Health Survey; SWOG, Southwest Oncology Group; VT, vitality.