Improving the measurement properties of the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R): deriving a valid measurement total for the calculation of change

Figures & data

Table 1. Demographic and clinical characteristics of the different samples.

Sample/Characteristics	Main	Calibration
Mean Age (SD)	65.0 (10.7)	65.7 (10.5)
% Male	60.3	63.1
Months since diagnosis – Median	9	14
Interquartile Range	3–24	7–30
Months since diagnosis – Mean (SD)	23.3 (41.6)	29.8 (45.4)
% Onset Type
Bulbar	25.9	23.8
Limb	68.3	71.9
Respiratory	2	1.7
Unknown*	3.8	2.6
ALSFRS-R – Median	35	32
Interquartile Range	28–39	25–38
Range	1–48	1–48
% King’s Stage 3–4	54.7	63.8
N	1120	1000

*Onset type at diagnosis, of limb, bulbar or respiratory, not specified (there was no option for mixed onset).

Table 2. Fit of ALSFRS-R (sub)scale to the Rasch model. Each sample N = 500.

Scale	Sample	SD of Fit residuals		Chi-Square			Reliability		Unidimensionality		DIF present
		Items	Persons	Value	df	p	PSI	Alpha	% t-test	ECV
Bulbar	Training	1.223	0.957	29.1	24	0.177	0.69	0.87	1.43	–	No
	Validation	1.064	0.872	32.4	24	0.117	0.71	0.89	3.25	–	O-speech
Fine-Motor	Training	1.669	0.891	30.9	24	0.157	0.80	0.88	2.43	–	G-handwriting
	Validation	1.382	0.868	21.1	24	0.634	0.80	0.88	2.20	–	No
Gross-Motor	Training	3.766	0.950	9.3 ^	4	0.054	0.72	0.71	1.35	0.83	No
	Validation	3.748	0.826	11.6 ^	4	0.020	0.69	0.70	1.14	0.83	G
Limb	Training	0.572	0.871	16.5 ^	16	0.417	0.71	0.80	1.1	0.89	G
	Validation	0.152	0.934	44.0 ^	16	0.002	0.69	0.78	1.6	0.88	G
Respiratory	Training	0.864	0.745	47.3	20	<0.001	0.54	0.82	0.3	–	No
	Validation	1.157	0.659	126.0	18	<0.001	0.65	0.84	1.3	–	D-respiratory support
Total	Training	0.301	0.798	40.9 ^	36	0.279	0.59	0.67	0.9	0.80	O
	Validation	0.013	0.817	32.8 ^	37	0.664	0.64	0.72	1.1	0.85	O
	Full Sample	0.238	0.824	42.3 ^	38	0.291	0.62	0.70	1.3	0.82	No
Ideal Values		1	1			>0.01	>0.7	>0.7	<5%	>0.85

Abbreviations: df: degrees of freedom; PSI: Person Separation Index; Alpha: Cronbach’s Alpha; ECV: Expected Common Variance (only available for testlet analysis); DIF: Differential Item Functioning - G Gender, O Onset, D Duration;  ^ Conditional Test of Fit.

Figure 1. Schematic diagram of 12 item confirmatory factor analysis.

Figure 2. The four domain confirmatory factor analysis.

Figure 3. Representation of the bi-factor model as applied within the Rasch measurement framework.

Figure 4. Raw score to metric ogive for ALSFRS-R Total.

Table 3. Transformation of raw scores to interval scale metric.

Raw score	Total	Bulbar	Fine-motor	Gross-motor	Limb
48	48.0
47	41.5
46	37.6
45	35.2
44	33.5
43	32.2
42	31.1
41	30.1
40	29.2
39	28.4
38	27.7
37	27.0
36	26.3
35	25.7
34	25.0
33	24.4
32	23.8
31	23.2
30	22.7
29	22.1
28	21.6
27	21.1
26	20.6
25	20.1
24	19.6				24.0
23	19.2				21.0
22	18.7				19.1
21	18.3				17.8
20	18.0				16.8
19	17.6				16.0
18	17.2				15.2
17	16.8				14.5
16	16.5				13.8
15	16.1				13.1
14	15.7				12.4
13	15.3				11.7
12	15.0	12.0	12.0	12.0	11.0
11	14.6	10.4	10.4	10.8	10.3
10	14.1	9.1	9.1	9.8	9.7
9	13.7	8.1	8.0	9.1	9.0
8	13.2	7.1	7.1	8.5	8.4
7	12.6	6.1	6.2	7.7	7.8
6	12.0	5.3	5.4	6.9	7.1
5	11.3	4.5	4.6	6.0	6.5
4	10.4	3.8	4.0	5.1	5.8
3	9.3	3.0	3.3	4.1	5.0
2	7.7	2.3	2.5	3.0	3.9
1	4.9	1.3	1.4	1.7	2.4
0	0.0	0.0	0.0	0.0	0.0

High score on ALSFRS-R indicates less disability.

Instructions for use of the nomogram.

Providing the respondent has answered all the items, take the raw score and look across to the interval scale estimate for the relevant (sub)scale.

For example, if you are converting the total ALSFRS-R, a raw score of 30 would give a standardized metric of 22.7.

A raw total ALSFRS-R score of 10 would give a standardized metric of 14.1.

A raw bulbar score (speech, salivation, swallowing) of 10 gives a standardized metric of 9.1.

A raw fine-motor score (handwriting, cutting food, dressing) of 10 gives a standardized metric of 9.1.

A raw gross-motor score (turning in bed, walking, stairs) of 10 gives a standardized metric of 9.8.

Table 4. Age-sex specific age, duration, ALSFRS-R interval level (metric) total, and EQ-5D-5L utility value in full sample at baseline (N = 1107).

Age	Sex	Age (Mean)	Duration/ Months (Median)	ALSFRS-R Metric (Mean)	EQ-5D-5L (Mean)	% Bulbar Onset	% King’s Stage >2	N
Under 50	Male	43.0	10	25.4	0.609	5.8	51.8	56
	Female	42.4	16	24.1	0.491	10.8	48.6	36
	Total	42.8	10	24.9	0.563	7.9	50.5	92
50-54	Male	52.3	9	26.0	0.580	21.2	43.4	53
	Female	52.4	8	25.4	0.608	17.7	47.2	36
	Total	52.3	9	25.8	0.591	19.8	44.9	89
55-59	Male	57.3	11	25.5	0.610	22.5	51.9	81
	Female	57.3	8	26.3	0.562	40.0	41.7	36
	Total	57.3	9	25.8	0.596	27.8	48.7	117
60-64	Male	62.2	8	25.0	0.574	17.5	54.0	125
	Female	62.2	9	24.0	0.565	41.1	59.0	61
	Total	62.2	8	24.7	0.571	25.0	55.6	186
65-69	Male	67.1	9	25.0	0.596	23.1	53.2	135
	Female	67.1	7	24.7	0.617	34.7	58.6	97
	Total	67.1	9	24.9	0.605	28.0	55.5	232
70-74	Male	71.9	10	25.7	0.619	22.4	50.9	112
	Female	71.9	8	24.7	0.623	43.3	60.0	90
	Total	71.9	9	25.2	0.621	32.0	55.0	202
75+	Male	78.9	7	24.8	0.606	25.4	63.0	106
	Female	80.0	6.5	23.7	0.590	43.2	62.7	83
	Total	79.4	7	24.6	0.601	33.5	62.5	189
TOTAL		65.0	9	25.0	0.696	26.7	54.7	1107

Abbreviation: ALSFRS-R: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised.

Table 5. Total and subscale interval level scores from ALSFRS-R by onset type (N = 1107).

Onset/Scale	Total	Subscales
		Bulbar	Fine-Motor	Gross-Motor	Limb
Bulbar	24.3	4.8	8.4	8.7	15.4
Limb	25.3	9.5	6.7	6.8	12.0
Respiratory	21.5	8.7	6.1	6.8	11.6
Total	25.0	8.2	7.1	7.3	12.9
Range	0–48	0–12	0–12	0–12	0–24

All domains show significant difference across onset groups (ANOVA p ≤ 0.001).

High score represents high functioning.

Table 6. Multi-level mixed regression.

ALSFRS-R	Coef.	St.Error		t-value	p-value	[95% Confidence Interval]		Sig
Age	−.001	.005		−0.11	.911	−.01	.009
Female	−.718	.128		−5.59	.000	−.97	−.467	***
Married	−.468	.305		−1.53	.125	−1.067	.13
Onset (limb reference)
Bulbar	−1.089		.262	−4.15	.000	−1.602	−.575	***
Respiratory	−3.737		.32	−11.69	.000	−4.364	−3.111	***
Duration	−.017		.006	−2.66	.008	−.029	−.004	***
Constant	24.842		.692	35.87	.000	23.484	26.199	***
Mean dependent var			24.354	SD dependent var		6.128
Number of obs			1908	Model Chi-square		12739.839
Prob > Chi-square			0.000	Akaike crit. (AIC)		12281.470

*** p<.01, ** p<.05, * p<.1.

Abbreviations: ALSFRS-R: Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised; Coef.: coefficient; St.Error: standard error; Sig: significance.

Table 7. Changes in ALSFRS-R (ordinal and interval) for those completing baseline and first two follow-ups.

	Interval	Ordinal	Time in study (months)	Interval average monthly change	Ordinal average monthly change	Duration since diagnosis (months)	N
Trilogy group
Baseline	27.5	36.4	0			23.3	231
First Follow-up	25.5	33.3	11.1	0.18	0.28	35.7	230
Second Follow-up	23.5	30.5	18.3	0.28	0.40	42.6	230
Baseline to second	−4.0	−5.9	18.3	0.22	0.34
Inception group
Baseline	28.8	38.3	0			1.4	108
First Follow-up	25.9	34.3	7.5	0.39	0.53	8.9	107
Second Follow-up	23.2	30.2	13.6	0.44	0.67	14.8	107
Baseline to second	−5.6	−8.1	13.6	0.41	0.60