Table e1. List of Patient-reported outcomes and performance tests included in the Smartphone suite.

Patient-reported Outcomes / Domain Assessed / Ref
Short Form-36 Mental Component Score / Mental Function / 1
Short Form-36 Physical Component Score / Physical Function / 1
Perceived Deficits Questionnaire (PDQ) / Cognition / 1
MOS Pain Effects Scale (PES) / Sensory / 1
Mental Health Inventory (MHI)-Depression / Affective / 1
Mental Health Inventory (MHI)-Anxiety / Affective / 1
Modified Fatigue Impact Scale (MFIS) / Fatigue / 1
Impact of Visual Impairment Scale (IVIS) / Vision / 1
MOS (Medical Outcomes Study) Modified Social Support Survey (MSSS) / Social Support / 1
Sexual Satisfaction Scale (SSS) / Sexual Function / 1
Bladder Control Scale (BLCS) / Bladder / 1
Bowel Control Scale (BWCS) / Bowel / 1
Self-Assessment of Body Temperature Survey / Temperature
Performance Tests / Smartphone-based details or modifications
9-Hole Peg Test (9-HPT) / Peg dragged across the screen; 2x per hand. / Motor / 2
n-Back Task- correct number - letters / n= 2 / Working Memory / 3
n-Back Task- correct number - numbers / n= 2 / Working Memory / 3
Trail Making Test Version A / 1-14 numbers were included / Processing speed / 4
Trail Making Test Version B / 1-7 and A-G / Executive Function / 4
Verbal Fluency Test / Verbal responses recorded and processed using speech-to-text software / Verbal / 5
Color Vision Test (Ishihara) / None / Visual / 6
Continuous Performance Task / 60 random letters displayed, for 750 mseconds each; then a dot for 250 ms;
subject asked to touch subsequent “target” button if specific letter (e.g. A) displayed, otherwise “non-target” button / Attention / 7

Table e2. Completion status and reasons for discontinuation in 76 subjects enrolled in a 12-month Smartphone assessment study.

MS Subject / Cohabitant
Completion Status
Completed / 22 (58%) / 17 (45%)
Did not complete / 16 (42%) / 21 (55%)
Individual reasons for discontinuation, N
Non compliance / 12 / 14
Other member of pair dropped out / 0 / 2
Withdrawal of consent (e.g no longer interested, did not want to be reminded of the disease) / 2 / 2
Moved out of area / 0 / 1
Disconnected accidentally / 1 / 1
Lost telephone, never replaced / 1 / 0
No reason provided / 0 / 1

Table e3. Logistic regressions comparing subjects with MS to cohabitants for each outcome measure. All regressions adjusted for subject age and sex.

All Subjects (N=38 MS subjects and 38 cohabitants) / Completers (N=22 MS subjects and 17 cohabitants)
Measure / Estimate / StdErr / ProbChiSq / OddsRatioEst / LowerCL / UpperCL / Estimate / StdErr / ProbChiSq
MFIS Total / 0·072 / 0·017 / 0·00003 / 1·1 / 1 / 1·1 / 0·061 / 0·023 / 0·0068
SF36 PCS / -0·19 / 0·048 / 0·00008 / 0·83 / 0·75 / 0·91 / -0·39 / 0·14 / 0·0059
PES / 0·34 / 0·087 / 0·00009 / 1·4 / 1·2 / 1·7 / 0·29 / 0·11 / 0·011
MFIS COG / 0·12 / 0·034 / 0·00058 / 1·1 / 1·1 / 1·2 / 0·083 / 0·042 / 0·049
PDQ Total / 0·06 / 0·019 / 0·0015 / 1·1 / 1 / 1·1 / 0·047 / 0·023 / 0·041
IVIS / 0·5 / 0·18 / 0·0071 / 1·6 / 1·1 / 2·4 / 0·54 / 0·3 / 0·074
BLCS / 0·25 / 0·1 / 0·012 / 1·3 / 1·1 / 1·6 / 0·26 / 0·13 / 0·048
BWCS / 0·27 / 0·11 / 0·013 / 1·3 / 1·1 / 1·6 / 0·29 / 0·14 / 0·045
9 Hole Peg / 0·00016 / 0·00007 / 0·014 / 1 / 1 / 1 / 0·0001 / 0·00009 / 0·29
SF36 MCS / -0·058 / 0·027 / 0·029 / 0·94 / 0·9 / 0·99 / -0·026 / 0·032 / 0·42
MHI MHA / -0·024 / 0·013 / 0·058 / 0·98 / 0·95 / 1 / -0·025 / 0·018 / 0·16
MHI MHD / -0·023 / 0·014 / 0·087 / 0·98 / 0·95 / 1 / -0·016 / 0·018 / 0·37
N-Back Letter / -0·057 / 0·039 / 0·14 / 0·94 / 0·88 / 1 / -0·037 / 0·044 / 0·4
N-Back Number / -0·032 / 0·034 / 0·34 / 0·97 / 0·91 / 1 / -0·036 / 0·046 / 0·44
Trails A / 0·00004 / 0·00003 / 0·14 / 1 / 1 / 1 / 0·00008 / 0·00005 / 0·12
Trails B / 0·00003 / 0·00002 / 0·11 / 1 / 1 / 1 / 0·00003 / 0·00003 / 0·37
Ishihara R / -0·19 / 0·14 / 0·19 / 0·83 / 0·63 / 1·1 / -0·068 / 0·17 / 0·69
Ishihara L / -0·19 / 0·16 / 0·24 / 0·83 / 0·6 / 1·1 / 0·07 / 0·22 / 0·75
SSS / 0·058 / 0·057 / 0·31 / 1·1 / 0·95 / 1·2 / 0·14 / 0·11 / 0·21
MSSS TOT / -0·0075 / 0·012 / 0·52 / 0·99 / 0·97 / 1 / -0·0038 / 0·016 / 0·81

Figure e1.

Title. Example of an adaptation of standard clinical tools for Smartphone assessment.

Legend. Screenshots are provided of the following tests. A. Standard Ishihara plate depicting the number “15”.B. Trails Making Test A. C. Nine Hole Peg Test right hand. D. Individual question from Short-Form 36 quality of life questionnaire.

Figure e2. Principal component (PC) analysis of all responses provided by all subjects during the observation period.

There are 5 (3 MS subjects, 2 cohabitants) who lie outside 2 times the interquartile range for PC 1 or PC2. The outliers are highlighted by labeling the circle using their unique study number.

Figure e3. Learning curve effects observed across additional performance tests.

The apparent learning curve is less striking in additional performance tests than in the Trails A test (A), but appears to be present for the Trails B (B), Ishihara test (# correct responses in left (C) and right (D) eyes), n-Back (correct for Letters (E) and Numbers (F)), and 9-Hole Peg Test duration (G).

Figure e4. Inflection point analysis for performance on Trails making test.

The trajectory of MS subjects (A) and cohabitants (B). Each individual’s individual inflection point is depicted as a separate line.

Figure e5. A representative pair of subjects’ data for two tests, the Trails A test (Panel A) and the MFIS total score (Panel B), that illustrates the fluctuation in performance over time.

Figure e6. Illustration of the importance of considering study duration and practice effects.

Additional correlation matrices illustrating the number of pairwise correlations reaching p<0·05 significance threshold when using selected measures from MS subjects who completed the study. (A) The first value for all measures is used. (B) The last value provided for all measures is used. (C) The mean of all provided values is used. The last three matrices present the results using the mean of all provided measures, after our recommended 3-test run-in (D), a 1- test run-in (E), and a 5- test run-in (F).

Supplementary Figure 7.Supplementary Figure 6.Comparison of number of significant pairwise correlations using data from 12 months (Panel A) or 6 months (Panel B), for subjects who completed the study.

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