Disutility of Cognitive Processing Speed (CPS) Impairment in the Context of Multiple Sclerosis: A Time Trade-Off (TTO) Elicitation Study

Figures & data

Figure 1 Overview flow chart of qualitative and quantitative study activities.

Abbreviations: CPS, cognitive processing speed; HCP, healthcare professional; MS, multiple sclerosis; UK, United Kingdom; US, United States.

Table 1 Advantages and Disadvantages of Potential Approaches Considered for Generation of Health State Utility Values

Potential approach to generate health state utility values:	Step 1. Measurement of changes in HRQoL: Administer a validated preference-based measure to affected patients and/or caregivers: EQ-5D, other generic preference-based generic measure, disease-specific preference-based measure.	Step 1. Measurement of changes in HRQoL: Develop health state descriptions (“vignettes”) according to best practice recommendations, using insights collected from affected patients, caregivers, and/or HCPs.
	Step 2. Valuation of changes in HRQoL: Apply an existing value set for the relevant preference-based measure, reflecting the preferences of the general public in the region of interest, derived using a choice-based method such as TTO.	Step 2. Valuation of changes in HRQoL: Use a choice-based measure such as TTO to gather utility values for each description, reflecting the preferences of the general public in the region of interest.
Advantages of approach:	Typically more accepted by HTA bodies.^Citation12–18 More commonly used and therefore more comparable.	Potential increased sensitivity to changes in specific domains of HRQoL that are not adequately captured by generic measures. Greater ability to isolate the effect of individual disease symptoms or transient health states.
Disadvantages of approach:	Generic measures may be relatively less sensitive to changes in some domains of HRQoL (eg vision, cognition).^Citation6,Citation19,Citation20 Limited ability to isolate the effect of individual disease symptoms or transient health states.	Typically less accepted by HTA bodies. Less commonly used, and therefore less comparable.

Abbreviations: EQ-5D, EuroQol five dimensions questionnaire; HCP, healthcare professional; HRQoL, health-related quality of life; HTA, health technology assessment; TTO, time trade-off.

Table 2 Health State Definitions (as per Qualitative HCP Insights, Normative SDMT Data, and UK Observational Data in MS)

“Mild CPS impairment”	Defined as performance on SDMT of ≥1.5 SD below average (for age) Performance on SDMT indicates a cognition deficit of ~22% versus average (for age) Impairment category defined as per normative data: SDMT 43-40*
“Moderate CPS impairment”	Defined as performance on SDMT of ≥2 SD below average (for age) Performance on SDMT indicates a cognition deficit of ~30% versus average (for age) Specific impairment category defined as per normative data: SDMT 39-32*
“Severe CPS impairment”	Defined as performance on SDMT of ≥3 SD below average (for age) Performance on SDMT indicates a cognition deficit of ~45% versus average (for age) Specific impairment category defined as per normative data: SDMT ≤31*

Notes: *Observational data in MS from Nicholas et al suggest that affected individuals in the UK are ~55 years of age on average, and that ~75% of patients are women.²⁷ Published normative data from Strober et al were subsequently used to derive SDMT values for a population aged ~55 who are 75% female: mean: 57; 1.5 SD below: 44; 2.0 SD below: 40; 3.0 SD below: 32.²⁶

Abbreviations: CPS, cognitive processing speed; HCP, healthcare professional; MS, multiple sclerosis; SD, standard deviation; SDMT, Symbol Digit Modalities Test.

Table 3 Demographic Characteristics of Participants in TTO Interviews (n=120) and UK Public

TTO Interview Demographics	n	%	UK Public Demographics	%
18 to 19	4	3.33%	18 to 29	19.77%
20 to 29	20	16.67%	30 to 39	17.06%
30 to 39	20	16.67%	40 to 49	16.41%
40 to 49	20	16.67%	50 to 59	17.31%
50 to 59	20	16.67%	60 to 64	7.09%
60 to 64	9	7.50%	65 to 74	12.83%
65 to 74	15	12.50%	75 to 89	9.53%
75 to 84	10	8.33%
85 to 89	2	1.67%
Female	61	50.83%	Female	50.48%
Male	59	49.17%	Male	49.52%
Married/civil partnered	61	50.83%	Married/civil partnered	50.63%
Other	59	49.17%	Single	34.99%
			Divorced	7.96%
			Widowed	6.42%
Degree/A-level/higher/further	73	60.83%	Degree-level	29.92%
Other	47	39.17%	A-level/higher/further (non-degree)	30.45%
			GCSE secondary	20.33%
			Other	19.30%
Scotland	9	7.50%	Scotland	8.15%
Northern Ireland	4	3.33%	Northern Ireland	2.28%
North West England	14	11.67%	North West England	10.98%
Yorkshire	9	7.50%	Yorkshire and the Humber	8.24%
North East England	3	2.50%	North East England	4.00%
Wales	6	5.00%	Wales	4.72%
West Midlands	11	9.17%	West Midlands	8.89%
East Midlands	8	6.67%	East Midlands	7.25%
East of England	12	10.00%	East of England	9.35%
South West England	10	8.33%	South West England	8.44%
Greater London	15	12.50%	Greater London	13.42%
South East England	19	15.83%	South East England	13.74%
Working full-time or part-time	72	60.00%	Working full-time	50.34%
Other	48	40.00%	Working part-time	9.24%
			Not working	18.66%
			Assumed retired (age ≥65)	21.76%

Notes: Data from these studies.^22–25 A-level: Advanced Level qualification studied at ages 16 to 18 (non-compulsory); GCSE: General Certificate of Secondary Education studied at ages 14 to 15 (compulsory); TTO: time trade-off.

Table 4 TTO Utility Value per Health State

Result	n	Mean	SD	Median	SE	95% CI
“Mild CPS impairment”	120	0.77	0.24	0.85	0.02	0.72	0.81
“Moderate CPS impairment”	120	0.57	0.26	0.65	0.02	0.52	0.62
“Severe CPS impairment”	120	0.34	0.28	0.33	0.03	0.29	0.39

Notes: “Mild CPS impairment”: SDMT 43-40 (indicating deficit of ≥22% versus average for a population aged ~55 who are predominantly women; deficit of ≥26% versus average for a population aged ~40); “moderate CPS impairment”: SDMT 39–32 (indicating deficit of ≥29% versus average for a population aged ~55; who are predominantly women; deficit of ≥33% versus average for a population aged ~40); “severe CPS impairment”: SDMT ≤31 (indicating deficit of ≥44% versus average for a population aged ~55 who are predominantly women; deficit of ≥47% versus average for a population aged ~40).

Abbreviations: CI, confidence interval; CPS, cognitive processing speed; n, sample size; SD, standard deviation; SE, standard error; TTO, time trade-off.

Figure 2 TTO utility value per health state (n=120 responses to each). HS1, “mild CPS impairment”: SDMT 43-40 (indicating deficit of ≥22% versus average for a population aged ~55 who are predominantly women; deficit of ≥26% versus average for a population aged ~40); HS2, “moderate CPS impairment”: SDMT 39-32 (indicating deficit of ≥29% versus average for a population aged ~55; who are predominantly women; deficit of ≥33% versus average for a population aged ~40); HS3, “severe CPS impairment”: SDMT ≤31 (indicating deficit of ≥44% versus average for a population aged ~55 who are predominantly women; deficit of ≥47% versus average for a population aged ~40).

Abbreviations: CPS, cognitive processing speed; n, sample size; TTO, time trade-off.

Table 5 VAS Score per Health State

Result	n	Mean	SD	Median	SE	95% CI
Own health today	120	68.01	19.95	75.00	1.82	64.40	71.61
“Mild CPS impairment”	120	55.17	14.89	60.00	1.36	52.47	57.86
“Moderate CPS impairment”	120	40.18	14.28	40.00	1.30	37.60	42.77
“Severe CPS impairment”	120	25.61	15.00	25.00	1.37	22.90	28.32

Notes: “Mild CPS impairment”: SDMT 43–40 (indicating deficit of ≥22% versus average for a population aged ~55 who are predominantly women; deficit of ≥26% versus average for a population aged ~40); “moderate CPS impairment”: SDMT 39-32 (indicating deficit of ≥29% versus average for a population aged ~55; who are predominantly women; deficit of ≥33% versus average for a population aged ~40); “severe CPS impairment”: SDMT ≤31 (indicating deficit of ≥44% versus average for a population aged ~55 who are predominantly women; deficit of ≥47% versus average for a population aged ~40).

Abbreviations: CI, confidence interval; CPS, cognitive processing speed; n, sample size; SD, standard deviation; SE, standard error; VAS, visual analog scale.

Figure 3 VAS score per health state (n=120 responses to each). HS1, “mild CPS impairment”: SDMT 43-40 (indicating deficit of ≥22% versus average for a population aged ~55 who are predominantly women; deficit of ≥26% versus average for a population aged ~40); HS2, “moderate CPS impairment”: SDMT 39-32 (indicating deficit of ≥29% versus average for a population aged ~55; who are predominantly women; deficit of ≥33% versus average for a population aged ~40); HS3, “severe CPS impairment”: SDMT ≤31 (indicating deficit of ≥44% versus average for a population aged ~55 who are predominantly women; deficit of ≥47% versus average for a population aged ~40).

Abbreviations: CPS, cognitive processing speed; n, sample size; VAS, visual analog scale.

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