Background
Methods
Measures
Dataset
All baseline data | Estimation dataset | Validation dataset | Differencea | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Mean | SD | Observations | Mean | SD | Observations | Mean | SD | Observations | t statistic | p value | |
Measure | |||||||||||
FSS | 43.73 | 15.10 | 1054 | 43.44 | 15.16 | 787 | 44.60 | 14.91 | 267 | −1.085 | 0.278 |
EQ-5D | 0.596 | 0.295 | 1346 | 0.600 | 0.291 | 1005 | 0.584 | 0.309 | 341 | 0.831 | 0.406 |
SF-6D | 0.646 | 0.130 | 632 | 0.650 | 0.135 | 473 | 0.636 | 0.113 | 159 | 1.141 | 0.254 |
MSIS-8D | 0.646 | 0.185 | 690 | 0.647 | 0.190 | 523 | 0.641 | 0.172 | 167 | 0.412 | 0.681 |
Characteristic | |||||||||||
Age | 50.67 | 11.68 | 1400 | 50.74 | 11.73 | 1048 | 50.45 | 11.54 | 352 | 0.402 | 0.688 |
Duration (years) | 9.62 | 10.01 | 1347 | 9.61 | 10.00 | 1009 | 9.68 | 10.09 | 338 | −0.113 | 0.910 |
EDSS score | 4.30 | 2.31 | 289 | 4.32 | 2.34 | 218 | 4.22 | 2.24 | 71 | 0.324 | 0.746 |
Percentage | Observations | Percentage | Observations | Percentage | Observations | chi2 statistic | p value | ||||
Gender | |||||||||||
Female | 73.86% | 1040 | 74.62% | 788 | 71.59% | 252 | 1.256 | 0.262 | |||
Male | 26.14% | 368 | 25.38% | 268 | 28.41% | 100 | |||||
MS type | |||||||||||
Relapsing remitting | 41.97% | 572 | 42.66% | 439 | 39.82% | 133 | 7.572 | 0.109 | |||
Primary progressive | 19.37% | 264 | 18.56% | 191 | 21.86% | 73 | |||||
Secondary progressive | 16.95% | 231 | 17.69% | 182 | 14.67% | 49 | |||||
Benign | 3.3% | 45 | 3.69% | 38 | 2.10% | 7 | |||||
DK or combination | 18.42% | 251 | 17.40% | 179 | 21.56% | 72 | |||||
Missing | 45 | 27 | 18 | ||||||||
Recent relapseb | |||||||||||
Yes | 53.55% | 732 | 53.42% | 546 | 53.91% | 186 | 0.025 | 0.988 | |||
No | 33.28% | 455 | 33.37% | 341 | 33.04% | 114 | |||||
Don’t know | 13.17% | 180 | 13.21% | 135 | 13.04% | 45 | |||||
Missing | 41 | 34 | 7 |
Preliminary assessment of measures
Development of mapping algorithms
Exploration of model specifications
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Total FSS score (Model A);
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Total FSS score and total FSS score squared (Model B);
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Total FSS score, age and gender (Model C);
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FSS item scores (Model D);
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FSS item scores, age and gender (Model E).
Validation and model selection
Results
Preliminary assessment of measures
Conceptual framework | Fatigue severity scale | EQ-5D | SF-6D | MSIS-8D |
---|---|---|---|---|
Descriptions of fatigue | ||||
General fatigue or vitality | 3. Easily fatigued 5. Causes frequent problems 8. Among most disabling symptoms | – | 6. Vitality | – |
Physical effects | ||||
General | 4. Interferes with physical functioning 6. Prevents sustained physical functioning | – | 1. Physical functioning | 1. Physically demanding tasks |
Triggers- | ||||
Specific physical effects | 2. Exercise brings on fatigue | 4. Pain/Discomfort 1. Mobility | 4. Pain | 3. Being stuck at home |
Mental effects | ||||
General | – | – | – | 5. Feeling mentally fatigued |
Specific psychological effects | 1. Motivation is lower | 5. Anxiety/Depression | 5. Mental health | 6. Irritable, impatient, short-tempered 8. Feeling depressed |
Specific cognitive effects | – | – | – | 7. Problems concentrating |
Indirect effects | – | – | – | – |
Participation effects | ||||
General | 7. Interferes with duties & responsibilities 9. Interferes with work, family, social life | – | 3. Being stuck at home | |
Effects on specific activities | 2. Self-Care 3. Usual Activities | 1. Physical functioning 2. Role limitations 3. Social functioning 4. Pain | 2. Social and leisure activities 4. Work or other daily activities |
FSS total score and PBM dimensions | rho | Observations |
---|---|---|
EQ-5D versus FSS total score | ||
Mobility | 0.423 | 1035 |
Self-care | 0.385 | 1048 |
Usual activities | 0.524 | 1051 |
Pain/Discomfort | 0.361 | 1047 |
Anxiety/Depression | 0.292 | 1049 |
SF-6D versus FSS total score | ||
Physical functioning | 0.547 | 649 |
Role limitations | 0.424 | 645 |
Social functioning | 0.530 | 644 |
Pain | 0.429 | 642 |
Mental health | 0.324 | 648 |
Vitality | 0.615 | 654 |
MSIS-8D versus FSS total score | ||
Physically demanding tasks | 0.585 | 656 |
Social and leisure activities | 0.560 | 652 |
Mobility (being stuck at home) | 0.489 | 656 |
Work or other daily activities | 0.558 | 655 |
Feeling mentally fatigued | 0.582 | 656 |
Feeling irritable, impatient or short-tempered | 0.377 | 654 |
Problems concentrating | 0.450 | 654 |
Feeling depressed | 0.320 | 653 |
EQ-5D versus FSS item | ||
1 My motivation is lower | −0.285 | 1040 |
2 Exercise brings on my fatigue | − 0.382 | 1038 |
3 I am easily fatigued | − 0.464 | 1040 |
4 Interferes with physical functioning | −0.471 | 1033 |
5 Causes frequent problems for me | −0.498 | 1039 |
6 Prevents sustained physical functioning | −0.527 | 1040 |
7 Interferes with duties and responsibilities | −0.536 | 1038 |
8 Among my most disabling symptoms | −0.336 | 1035 |
9 Interferes with work, family or social life | −0.482 | 1039 |
SF-6D versus FSS item | ||
1 My motivation is lower | −0.400 | 614 |
2 Exercise brings on my fatigue | − 0.409 | 614 |
3 I am easily fatigued | −0.545 | 614 |
4 Interferes with physical functioning | −0.541 | 612 |
5 Causes frequent problems for me | −0.585 | 614 |
6 Prevents sustained physical functioning | −0.575 | 614 |
7 Interferes with duties and responsibilities | −0.623 | 613 |
8 Among my most disabling symptoms | −0.455 | 610 |
9 Interferes with work, family or social life | −0.603 | 614 |
MSIS-8D versus FSS item | ||
1 My motivation is lower | −0.387 | 659 |
2 Exercise brings on my fatigue | −0.423 | 659 |
3 I am easily fatigued | −0.560 | 659 |
4 Interferes with physical functioning | −0.554 | 656 |
5 Causes frequent problems for me | −0.615 | 659 |
6 Prevents sustained physical functioning | −0.606 | 660 |
7 Interferes with duties and responsibilities | −0.637 | 660 |
8 Among my most disabling symptoms | −0.428 | 656 |
9 Interferes with work, family or social life | −0.596 | 659 |
Mean | SD | Obs | SES | |
---|---|---|---|---|
EQ-5D vs FSS groups | ||||
Mild/no fatigue | 0.775 | 0.218 | 297 | 0.615 |
Moderate fatigue | 0.641 | 0.233 | 369 | 0.803 |
Severe fatigue | 0.454 | 0.3 | 357 | |
FFS total | 0.614 | 0.285 | 1023 | |
F-statistic | 131.84 | Prob < | 0.0001 | |
Bartlett’s chi2 | 40.065 | Prob < | 0.0001 | |
SF-6D vs FSS groups | ||||
Mild/no fatigue | 0.747 | 0.124 | 189 | 0.871 |
Moderate fatigue | 0.639 | 0.099 | 225 | 0.879 |
Severe fatigue | 0.552 | 0.083 | 193 | |
FFS total | 0.645 | 0.129 | 607 | |
F-statistic | 172.46 | Prob < | 0.0001 | |
Bartlett’s chi2 | 30.047 | Prob < | 0.0001 | |
MSIS-8D vs FSS groups | ||||
Mild/no fatigue | 0.764 | 0.115 | 202 | 0.739 |
Moderate fatigue | 0.679 | 0.134 | 240 | 1.381 |
Severe fatigue | 0.494 | 0.186 | 208 | |
FFS total | 0.646 | 0.184 | 650 | |
F-statistic | 180.71 | Prob < | 0.0001 | |
Bartlett chi2 | 51.434 | Prob < | 0.0001 |
Results of mapping analysis
Exploration of model specifications
EQ-5D | SF-6D | MSIS-8D | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CLAD A | CLAD C | OLS A | CLAD A | CLAD C | CLAD A | CLAD C | ||||||||
Coeff | SE | Coeff | SE | Coeff | SE | Coeff | SE | Coeff | SE | Coeff | SE | Coeff | SE | |
FSS total | − 0.006* | 0.0006 | − 0.006* | 0.0006 | − 0.006* | 0.0003 | −0.006* | 0.0004 | −0.006* | 0.0004 | −0.007* | 0.0007 | −0.008* | 0.0008 |
Age | −0.003* | 0.0007 | −0.0005 | 0.0005 | −0.001 | 0.0008 | ||||||||
Female | 0.012 | 0.0133 | −0.012 | 0.0107 | −0.024 | 0.0233 | ||||||||
Constant | 0.921 | 0.0256 | 1.058 | 0.0610 | 0.897 | 0.0151 | 0.913 | 0.0195 | 0.966 | 0.0374 | 0.985 | 0.0228 | 1.084 | 0.0719 |
Observations | 763 | 755 | 455 | 455 | 452 | 474 | 464 | |||||||
F statistic | 357.45 | |||||||||||||
Prob>F | < 0.0001 | |||||||||||||
R-squared | 0.451 | |||||||||||||
Pseudo R2 | 0.107 | 0.126 | 0.267 | 0.274 | 0.196 | 0.194 | ||||||||
Coefficients | 1 | 3 | 1 | 1 | 3 | 1 | 3 | |||||||
Significant coefficients | 1 | 2 | 1 | 1 | 1 | 1 | 1 | |||||||
Mean absolute error (MAE) | 0.175 | 0.173 | 0.078 | 0.078 | 0.077 | 0.117 | 0.116 | |||||||
Mean squared error (MSE) | 0.066 | 0.067 | 0.01 | 0.01 | 0.01 | 0.024 | 0.023 | |||||||
Root MSE | 0.257 | 0.258 | 0.1 | 0.1 | 0.1 | 0.154 | 0.152 | |||||||
Normalised root MSE | 16.12% | 16.19% | 14.31% | 14.31% | 14.31% | 19.18% | 18.93% | |||||||
Individuals with MAE < 0.25 | 78.37% | 79.34% | 98.68% | 98.68% | 98.45% | 89.05% | 90.41% | |||||||
Individuals with MAE < 0.1 | 47.05% | 49.14% | 68.13% | 69.01% | 70.13% | 51.93% | 51.84% | |||||||
Individuals with MAE < 0.05 | 26.47% | 29.14% | 41.32% | 41.98% | 42.48% | 28.40% | 29.39% |
Validation and model selection
EQ-5D | SF-6D | MSIS-8D | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CLAD A | CLAD C | OLS A | CLAD A | CLAD C | CLAD A | CLAD C | ||||||||
Coeff | SE | Coeff | SE | Coeff | SE | Coeff | SE | Coeff | SE | Coeff | SE | Coeff | SE | |
FSS total | −0.007* | 0.0012 | −0.008* | 0.0011 | −0.004* | 0.0005 | −0.004* | 0.0007 | −0.004* | 0.0008 | −0.006* | 0.0010 | −0.006* | 0.0011 |
Age | −0.004* | 0.0011 | 0.0004 | 0.0009 | −0.001 | 0.0020 | ||||||||
Female | −0.009 | 0.0260 | 0.002 | 0.0187 | 0.012 | 0.0395 | ||||||||
Constant | 1.001 | 0.0549 | 1.233 | 0.0979 | 0.81 | 0.0261 | 0.793 | 0.0394 | 0.827 | 0.0781 | 0.939 | 0.0432 | 0.974 | 0.1252 |
Observations | 260 | 258 | 152 | 152 | 152 | 157 | 157 | |||||||
F statistic | 54.71 | 0.185 | ||||||||||||
Prob>F | < 0.0001 | |||||||||||||
R-squared | 0.316 | |||||||||||||
Pseudo R2 | 0.119 | 0.141 | 0.169 | 0.169 | 0.180 | 0.185 | ||||||||
Coefficients | 1 | 3 | 1 | 1 | 3 | 1 | 3 | |||||||
Significant coefficients | 1 | 2 | 1 | 1 | 1 | 1 | 1 | |||||||
Mean absolute error (MAE) | 0.183 | 0.179 | 0.068 | 0.068 | 0.071 | 0.118 | 0.114 | |||||||
Mean squared error (MSE) | 0.076 | 0.071 | 0.008 | 0.008 | 0.009 | 0.023 | 0.022 | |||||||
Root MSE | 0.276 | 0.267 | 0.09 | 0.09 | 0.095 | 0.151 | 0.149 | |||||||
Normalised root MSE | 17.31% | 16.75% | 12.88% | 12.88% | 13.59% | 18.80% | 18.56% | |||||||
Individuals with MAE < 0.25 | 78.85% | 76.92% | 98.68% | 98.03% | 98.03% | 92.36% | 91.08% | |||||||
Individuals with MAE < 0.1 | 49.62% | 47.31% | 76.32% | 75.00% | 75.66% | 50.32% | 52.23% | |||||||
Individuals with MAE < 0.05 | 24.62% | 25.77% | 48.68% | 46.05% | 46.05% | 22.93% | 31.21% |
CLAD Model A | CLAD Model C | OLS Model A | |
---|---|---|---|
FSS to EQ-5D | |||
EQ_5D < =0.65 | 0.234 | 0.238 | |
EQ_5D > 0.65 | 0.123 | 0.115 | |
FSS to SF-6D | |||
SF_6D < =0.65 | 0.070 | 0.070 | 0.070 |
SF_6D > 0.65 | 0.088 | 0.088 | 0.088 |
FSS to MSIS-8D | |||
MSIS_8D < =0.7 | 0.154 | 0.154 | |
MSIS_8D > 0.7 | 0.082 | 0.082 |