expanded disability status scale calculator

Numerous assessment scales have been devel-oped over the past several decades to meas-ure the impact and progression of multiple

sclerosis (MS).1 Some have focused specifically onambulation by having clinicians measure speed and useof assistance (eg, the Ambulation Index [AI]) or refine-ments such as differentiating stages of cane use (eg, dis-ease steps), whereas others have been designed aspatient-reported indices of symptoms and disability(eg, Symptom Inventory, performance scales, Patient-Determined Disease Steps).2-5 By far the most widelyused method for assessing neurological disability inclinical trials has been the clinician-rated Kurtzke func-tional system and Expanded Disability Status Scale

(EDSS), which measures disability in several domainsin addition to ambulation.1 Developed as a 10-stepscale and subsequently expanded to include half steps,6-8

EDSS has been the primary method used to rate dis-ability in phase 3 clinical trials of therapies for MS.9-14

It has also been used in natural history studies to deter-mine long-term disability progression and in studiescorrelating disability with other markers of diseaseactivity (eg, brain atrophy and cytokine activity).15-18

Its near-universal familiarity among neurologists con-ducting MS research in academic settings around theworld is one of the main strengths of EDSS in theresearch arena.19 Despite widespread international adoption, however, EDSS has several limitations; eg,researchers have raised questions about the strength of itspsychometric properties and have reported difficultiesrelated to administration and scoring.20

EDSS is a traditional pen-and-paper assessment toolof some degree of complexity. Seven functional systems(pyramidal, cerebellar, brain stem, sensory, bowel and

Expanded Disability Status Scale Calculator for Handheld Personal Digital

Assistant: Reliability StudyClyde E. Markowitz, MD; Mary D. Hughes, MD; Daniel D. Mikol, MD, PhD; Lisa Shi, PhD;

MerriKay Oleen-Burkey, PhD; Douglas R. Denney, PhD; on behalf of the EDSS Calculator Study Group

Through a standard neurological examination, the Expanded Disability Status Scale (EDSS) score istraditionally determined by a pen-and-paper method. The objectives of this study were to compare theinterrater/method reliability of EDSS scores obtained through the pen-and-paper method with thoseobtained with the EDSS Calculator, evaluate test-retest reliability of the EDSS Calculator, and exam-ine the validity of EDSS Calculator scores through correlation with the Ambulation Index (AI). Dur-ing a single office visit, 62 subjects with multiple sclerosis (MS) from six study centers had disabilitylevels evaluated by separate raters using the EDSS calculator and pen-and-paper methods in randomorder. Seven days later, subjects returned for reevaluation with the EDSS Calculator; AI was also eval-uated. Mean EDSS scores for the sample were 3.5 ± 2.2 with the calculator and 3.4 ± 2.0 (range 0–8)with the traditional method. Interrater reliability between scores with the two methods was high (κ = 0.84; confidence interval [CI], 0.74–0.94). Test-retest reliability with the calculator was also high(κ = 0.93; CI, 0.86–0.996). Correlation between disability scores from the EDSS Calculator and AIwas 0.73 (P < .001). Relative to the pen-and paper method, the EDSS Calculator was found to behighly reliable and provide valid results when measuring disability in MS patients. Int J MS Care.2008;10:33–39.

From the MS Center, University of Pennsylvania, Philadelphia, PA(CEM); Department of Neurology, Medical College of Georgia,Augusta, GA (MDH); Department of Neurology, University of Michi-gan, Ann Arbor, MI (DDM); Information Solutions and OutcomesResearch, Teva Neuroscience, Inc., Kansas City, MO (LS; MOB);and Department of Psychology, University of Kansas, Lawrence, KS(DRD), USA.

International Journal of MS Care33


Markowitz et al.

bladder, visual, and cerebral or mental) plus “other”functions are rated in a standard neurological examina-tion with ordinal scales ranging from 0 to 5 or 6.6,8 Theresults are recorded on printed worksheets. These obser-vations are used together with information concerninggait and need for assistive devices to derive the EDSSscore on an ordinal scale ranging from 0 (normal neuro-logical examination) to 10 (death from MS) in 0.5-pointincrements. The scale includes a set of predefined rulesfor calculating the EDSS score from the functional sys-tem findings, as outlined by Kurtzke.8 Although EDSSscoring time varies, the neurological examination offunctional systems and subsequent determination of theEDSS score generally take between 15 and 30 minutes.21

The EDSS Calculator program was developed to offerMS clinics a means of consistently recording patients’functional system scores, which are then used by thesoftware program to compute EDSS scores. The softwarewas designed for handheld personal digital assistants(PDAs) using the Palm or Windows operating system.The software can also be used on desktop or laptop com-puters to serve as a backup for the resulting database.The EDSS Calculator program enables the examiner toenter the functional system scores directly into the PDA.The predefined set of rules originally established inKurtzke’s 1983 article has been incorporated into thesoftware. The calculator program computes the EDSSscore and records it in a database stored on the PDA; it isalso readily transferable to any personal computer. Areport of the functional system scores and the EDSSscore can also be printed for the patient’s chart.We designed the current study to determine the inter-

rater/method reliability of the EDSS Calculator programrelative to the standard pen-and-paper method of EDSSdetermination. We also examined the test-retest reliabili-

ty of the EDSS Calculator program when used by thesame rater to assess patients on two different occasionsseparated by ~1 week. A secondary purpose was to per-form a preliminary assessment of the validity of theEDSS Calculator for measuring MS-related disability bycomparing it with findings on the AI for the samepatient.

Materials and MethodsThis was a multicenter study of patients with a clini-

cally definite diagnosis of MS who were not currentlyexperiencing exacerbations of disease. The protocol andinformed consent were approved by the ethics commit-tees or institutional review boards of the participatingresearch sites. Men and women at least 18 years oldwere eligible for enrollment if they had a diagnosis ofMS and EDSS scores between 1 and 9. Patients wereexcluded if they could not be evaluated with the EDSS,had significant comorbid illnesses that may have affect-ed the EDSS rating, or had any condition that, in theinvestigators’ judgment, would interfere with studyparticipation. Concomitant medication use wasallowed during the study. Participants could be with-drawn from the study for reasons including seriousadverse events, noncompliance with the protocol orother protocol violations, and loss to follow-up. The study consisted of two clinic visits (Figure 1).

At the first visit, written informed consent was ob -tained from all eligible patients who were not currentlyexperiencing an exacerbation of disease. Patients whomet these criteria became study subjects and were ran-domized in a 1:1 manner to an initial disability assess-ment with either the EDSS Calculator program or thetraditional pen-and-paper method. All EDSS Calcula-tor assessments were performed with a handheld

Figure 1. Study design Note: Both study visits included monitoring for serious adverse events.

!

±


EDSS Calculator for Handheld PDA

device. After this initial assessment, the subjects wereevaluated by a separate rater with the opposite EDSSassessment method. The order of these two evaluationswas counterbalanced across subjects. The subjects were given an appointment to return

for a second clinic visit after 7 days. (A window of 2days was permitted for scheduling this second visit.) Atthe second visit, subjects were reexamined to verify thatthey were still free of exacerbations. The same clinicianwho had assessed disability with the EDSS Calculatorat the first visit performed the disability assessmentusing the EDSS Calculator program at the second visit.This clinician also administered the 25-Foot TimedWalk to assess disability with AI. All six of the primary grading investigators for this

study were neurologists; two were MS specialists, andthe others were general neurologists who manage MSpatients in their neurology practices. Most performedEDSS assessments daily, and all had experience with a handheld device and were willing to use it inconjunction with patient care. Coinvestigators could beneurologists or nurse practitioners who also hadexperience with handheld devices and performed EDSSassessments at least occasionally. The coinvestigatorswere mostly general neurologists, although a few wereneurology subspecialists, in other than MS (eg, neuro -ophthalmology, movement disorders, pediatric neu -rology), and at one study site, the rater was a nursepractitioner. Among all investigators, experience with neurologi-

cal disability assessment ranged from ~7 to 25 years,although for some, EDSS assessment was not a routinepart of current practice. For this reason, a prestudy site initiation training program by a clinical researchassociate was implemented that covered EDSS assess -ment in general and the use of the PDA and its EDSSprogram. Administration of EDSS was reviewed byhaving all grading clinicians view a training CD thatincluded three complete neurological examinations onvideo, six variations, and several special problems. Thegrading clinicians assessed the neurological status, func-tional systems, and EDSS for each of three cases.Administration and coding of AI were also reviewed. Inaddition, grading clinicians were trained on the use ofone of the two handheld PDAs used in this study: thePalm Zire with the Palm operating system or the IPAQh1935 Pocket PC with the Windows CE operating sys-tem. Each study center was assigned only one of the

two PDA models, and the EDSS Calculator programperformed the same on each model. During trainingon the PDA, an EDSS Calculator User Training Manualand Quick Reference Guide were introduced and givento each study center. The full training program took ~2hours per person at each center.The primary objective of this study was to compare

the interrater/method reliability of EDSS disabilityscores obtained with the EDSS Calculator with the tra-ditional pen-and-paper method. Interrater/method relia-bility was assessed with the κ statistic, where 1 representsperfect agreement and 0 represents agreement no betterthan would be obtained by chance.22,23 A 95% confi-dence interval (CI) was constructed for the κ statistic.Agreement between the two methods of EDSS evalua-tion was also assessed with the intraclass correlation coef-ficient (ICC).24 Categorical agreement was defined as thepercentage agreement with no difference, a difference of0.5 point (1 EDSS step), or a difference of 1.0 point (2EDSS steps). Secondary objectives of this study were to evaluate

the test-retest reliability of the EDSS Calculator pro-gram in a handheld device when used by the same raterwith the same patient on two occasions 1 week apartand to examine the validity of EDSS scores obtainedwith the EDSS Calculator program through correlationwith the AI. For test-retest reliability, the same analyseswere used as for interrater/method reliability.Because EDSS scores are heavily influenced by ambu-

lation, AI was also determined for each subject to serveas a preliminary basis for assessing the validity of theEDSS Calculator program. AI uses the time and levelof assistance required to walk a marked 25-foot courseto rate the individual’s disability on a scale of 0 (asymp-tomatic and fully active) to 10 (bedridden).2,21 Like theEDSS itself, AI has been used to measure disability inpopulation-based surveys and clinical trials.25,26 Thecorrelation coefficient between the EDSS Calculatorprogram score and AI was determined with Spearman’srank-order correlation. Our initial predictions of interrater reliability for pur-

poses of designing an adequately powered study werebased on findings by Sharrack and colleagues,27 whoreported an interrater reliability of 0.65 with repeateduse of the pen-and-paper EDSS. The assumption usedfor the sample size was that the correlation between thetwo EDSS assessments in this study would be at least0.68. The determination was made that sample size


Markowitz et al.

needed to be in the range of 26–55 to provide a lowerlimit for a 95% CI of at least 0.41–0.50.

ResultsA total of 62 subjects at six study sites were enrolled

and randomized into the study. The subjects ranged inage from 20 to 63 (mean 43.8 ± 10.4 [SD]) years.Forty-six (74%) of the subjects were women. The sub-type of MS was not recorded for one of the subjects,but of the remaining sample, 51 (82%) had relapsing-remitting, 5 (8%) had primary progressive, and 5 (8%)had secondary progressive MS. The κ value reflecting the level of agreement be -

tween EDSS scores determined via the EDSS Calcula-tor program versus the pen-and-paper method was0.84 (95% CI, 0.74–0.94). Values of κ > 0.80 indicatenear-perfect agreement. The level of agreement washighly significant (P < .0001). The distribution of differences between EDSS scores

obtained with the two methods is shown in Figure 2.Forty-five percent of the subjects had exact agreement,and the scores fell within 0.5 EDSS point for 69% andwithin 1.0 EDSS point for 84% of the sample. TheICC was 0.86 (95% CI, 0.78–0.91). Across the fullsample, the mean (SD) EDSS score was 3.5 (2.2) whenobtained with the EDSS Calculator program and 3.4

(2.0) when obtained with the pen-and-paper EDSSassessment. For both methods, the median score was3.0, ranging from 0 to 8. Sixty subjects returned the following week for the

second clinic visit; none was experiencing an exacerba-tion of symptoms at the time. For these subjects, κindicated an extraordinarily high level of test-retest reli-ability for the EDSS Calculator program (κ = 0.93;95% CI, 0.86–0.99; P < .0001). The distribution ofdifferences in scores between the two assessments isshown in Figure 3. Exact agreement between the twoEDSS scores occurred for 70% of the subjects, with thescores falling within 0.5 EDSS point for 83% andwithin 1.0 EDSS point for 92% of the sample. TheICC was 0.92, with the 95% CI ranging from 0.87 to0.95.Noteworthy outliers included two cases whose

EDSS scores with the EDSS Calculator program andthe pen-and-paper method differed by 3.0 points andone whose scores differed by 4.5 points. The 4.5-pointdifference occurred when an EDSS score of 5.5 wasobtained with the pen-and-paper method and theEDSS Calculator method produced a score of just 1.0,suggesting a possible error in the entry of functionalsystem ratings into the handheld device. This was

affirmed a week later, when the EDSSCalculator program administered bythe same rater produced an EDSSscore of 5.5 for this subject, matchingthe pen-and-paper method of the pre-vious week. For the 3.0-point discrep-ancies, the functional system ratingsfor each of the subjects led to higherEDSS scores with the EDSS Calcula-tor program than the pen-and-papermethod of assessment. In one case, therater agreed with his rating using theEDSS Calculator program a weeklater. In the other case, the rater dis-agreed with his earlier rating andagreed with the pen-and-paper methodresult of the prior week. In both ofthese instances, the discrepancies prob-ably stemmed from differences in thesubjects’ presentations during the twoexaminations that occurred during thefirst visit.

Figure 2. Score differences between EDSS Calculator andtraditional EDSS evaluationsNote: κ = 0.84 (CI, 0.74–0.94; P < .0001).

EDSS Calculator < EDSS traditional

EDSS score difference(Calculator minus traditional)

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–4.5 –4.0 –3.5 –3.0 –2.5 –2.0 –1.5 –1.0 –0.5 0 0.5 1.0 1.5 2.0 2.5 3.0

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Spearman rank-order correlationsbetween the scores determined withthe EDSS Calculator program andboth the elapsed time and the AI basedon the 25-Foot Timed Walk could becomputed for 58 subjects. The correla-tion coefficients were 0.42 (P = .001)and 0.73 (P < .001), respectively. Twoof the 60 subjects who reported for thesecond visit of the study did not com-plete the 25-Foot Timed Walk.

DiscussionThe primary finding of this study

was the high interrater/method reliabili-ty between the EDSS scores obtainedwith the EDSS Calculator program in ahandheld device and those obtainedwith the pen-and-paper method. The κstatistic of 0.84 indicated almost perfectagreement between the two methods ofassessment. Test-retest reliability withthe EDSS Calculator program was sim-ilarly impressive, with κ = 0.93 and the observers pro-ducing identical EDSS scores on the two assessments in70% of the subjects. The consistently close agreementbetween both the methods of EDSS determination andthe scores derived from the EDSS Calculator programon two occasions demonstrated the feasibility of convert-ing the EDSS assessment into a semiautomated processaided by a handheld device.Sharrack and colleagues27 reported an interrater relia-

bility of 0.65 for the pen-and-paper EDSS; other groupshave reported even lower levels of interobserver agree-ment, ranging from 10 to 69%.19,28-31 Clinicians mayarrive at an inaccurate EDSS score for various reasons.First, errors in the detection and recording of symptomsduring the neurological examination may lead to inaccu-rate functional system scores, which affect the EDSS cal-culation. Second, clinicians may miscalculate the EDSSscore despite an accurate assessment of the functionalsystems. Third, clinicians may misapply the predefinedrules for combining these functional system componentsinto the overall EDSS score. Although not rectifying thefirst source of error, the EDSS Calculator program elimi-nates the possibility that an accurate assessment of thefunctional systems could nevertheless result in an inaccu-rate EDSS score for the second or third reasons. Much of

the information on EDSS mistakes is anecdotal, makingan estimate of how often such errors occur difficult.However, note that in the case of 3 (9%) of 34 subjectswith disagreements between the two methods, the func-tional system scores were identical, yet the resultingEDSS scores were different. Such a result could notoccur were it not for errors of the second or third typedescribed above.The functional systems workup with the EDSS Cal-

culator program is conducted in the same manner aswith the pen-and-paper method. Therefore, the EDSSCalculator does not address the potential for errorsresulting from the rater’s lack of neurological expertiseand training. The need to devote substantial time toEDSS training has been raised as a limitation of the rat-ing scale,32,33 and lack of adequate training has been citedas an underlying cause of low interrater reliability.1 Theclinician’s competence at evaluating the functional sys-tems is an important issue that must be addressedregardless of the method used. In this study, EDSS train-ing was conducted at all participating research sites, andvideotaped review materials were available as an ongoingeducational resource. The time required for additionaltraining on the use of the PDA itself was minimal andwas accomplished during the study initiation visit for

Figure 3. Score difference between first and second EDSSCalculator evaluations Note: κ = 0.93 (CI, 0.86–0.99; P < .0001).

Visit 2 < Visit 1 Visit 2 > Visit 1

EDSS score difference(Visit 2 minus visit 1)

Patie

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–2.5 –2.0 –1.5 –1.0 –0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5

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Markowitz et al.

each site. This should be reassuring, especially for clini-cians who may be reluctant to incorporate computer-based technologies into their everyday practice routines. The adequacy of the EDSS itself as a tool to measure

MS-related disability has elicited considerable debateamong MS researchers,20,34 and alternative disabilityscales have been introduced with purportedly morerobust psychometric properties.35 In this study, the corre-lation between the EDSS Calculator and AI was deter-mined to be 0.73. Other studies have reported correla-tions between the AI and the traditional pen-and-paperEDSS ranging from 0.55 to 0.79.36,37 Although a widelyused measure of disability in population-based surveysand clinical trials,25,26 AI is certainly not considered thegold standard against which to establish the validity ofalternative disability measures. Further study of thevalidity of the EDSS Calculator program is thus war-ranted, but its validity may prove to be equivalent to thatof the traditional EDSS. It may in fact be slightly better,in that reliability is one of the properties of a measurethat limits its validity, and use of the EDSS Calculatorprogram appears to improve the reliability of the EDSS.This article is believed to be the first pertaining to the

use of a computerized tool for assessing MS-related dis-ability; however, the benefits of using electronic versionsof rating scales have been demonstrated in other areas ofmedicine, including pain management,38,39 behavioraldisorders,40 and asthma.41 For example, Cook et al.39

compared paper and electronic versions of the Short-Form McGill Pain Questionnaire and Pain DisabilityIndex. With both instruments, both the written andelectronic formats were shown to have good psychomet-ric properties, and scores obtained with the two formatswere highly correlated. In conclusion, the EDSS Calculator program is an

innovative tool contributing to the ease and consistencyof EDSS determination. The high level of interrater andtest-retest reliability demonstrated in this study supportsits use as a substitute for the traditional pen-and-paperversion of the EDSS in research settings and clinicalpractice. Computerized storage of and access to EDSSinformation may enable clinics to more easily considerpatients’ EDSS over time, thereby helping to identifydisability trends at the patient level, for patient popula-tions overall, or for various treated segments of thosepopulations.

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Acknowledgments: We acknowledge the members of the EDSSCalculator Study Group: Bruce Cleeremans, MD, Marshall Gross-man, MD, and Michael Cummings, MD, NervePro Research, Irvine,CA; Mariko Kita, MD, Michael Elliott, MD, and Lynne Taylor, MD,Benaroya Research Institute at Virginia Mason, Seattle, WA;Richard Shubin, MD, and Jai-Hyon Rho, MD, Neuro-Therapeutics,Inc., Pasadena, CA; Clyde Markowitz, MD, and Ruth Brobst, MSN,CRNP, MS Center at University of Pennsylvania, Philadelphia, PA;Mary Hughes, MD, and Elizabeth Sekul, MD, Department of Neu-rology, Medical College of Georgia, Augusta, GA; and DanielMikol, MD, PhD, and Wayne Cornblath, MD, Department of Neu-rology, University of Michigan, Ann Arbor, MI. Additionally, HaroldSchombert, JD, Thought Leaders Medical Communications, Inc.,and Pippa Loupe, PhD, Scientific Communications, Teva Neuro-science, Inc., assisted in developing this manuscript.

No patents or royalties are associated with the EDSS Calculatorprogram. Dr. Oleen-Burkey and Dr. Shi are employed by Teva Neu-roscience. Dr. Mikol has received consulting fees and speaker’shonoraria from Biogen Idec, Serono, and Teva Neuroscience. Dr.Denney has received consulting fees and grant support from TevaNeuroscience. No conflicts of interest have been submitted by Drs.Markowitz and Hughes.

expanded disability status scale calculator

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