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Supplementary Table 1. Key terms and phrases for EHR clinical notes-based Algorithm 1 (inclusion criteria)SourceKey terms and phrases for NLP searchResults of NLP from unstructured clinical recordsRRMSa multiple sclerosis (MS) relapsing remitting multiple sclerosis relapsing remitting relapsing remitting multiple sclerosisremittent-progressive multiple sclerosisa The IDN strongly discourages the use of acronyms and abbreviations; as such, the terms “MS” or “RRMS” were unlikely to be recorded.Abbreviations: EHR, electronic health records; NLP, natural language processing; RRMS, relapsing-remitting multiple sclerosis.Supplementary Table 2. Query Definitions for claims-based Algorithm 1 (inclusion criteria)Algorithm ComponentQuery Definition1. [at least 1 ICD-9-CM code 340] AND [at least 1 MS-indicated DMT]≥1 documented diagnosis of MS (ICD-9 code 340 <Multiple sclerosis>; any position; any encounter type) at any time during the study periodAND≥1 medication record for an MS DMTa (at any time during the study period2. [at least 1 ICD-9-CM code 340] AND [at least 1 Brain or Spinal MRI before]≥1 documented diagnosis of MS (ICD-9 code 340 <Multiple sclerosis>; any position; any encounter type) at any time during the study periodAND≥1 imaging record for a Brain or Spinal MRI at any time during the study period and prior to any MS diagnosis during the study period3. [at least 1 DMT AND at least 1 Brain or Spinal MRI] AND [ever history with at least 1 ICD-9-CM code 340][≥1 medication record for an MS DMTa at any time during the study periodAND≥1 imaging record for a Brain or Spinal MRI at any time during the study periodAND≥1 documented diagnosis of MS (ICD-9 code 340 <Multiple sclerosis>; any position; any encounter type) at any time prior to January 1, 20104. [at least 1 ICD-9-CM code 340] AND [at least 1 ICD-9-CM code 378.86] at least 30 days apart≥1 documented diagnosis of MS (by ICD-9 code 340 <Multiple sclerosis>; any position; any encounter type) at any time during the study periodAND≥1 documented diagnosis of MS (by ICD-9 code 378.86 <Internuclear ophthalmoplegia>; any position; any encounter type) at any time during the study period and at least 30 days apart from any MS diagnosis during the study period5. [at least 1 DMT] AND [at least 1 MS related symptom during a neurology visit] AND [ever history with at least 1 ICD-9-CM code 340]≥1 medication record for an MS DMTa at any time during the study periodAND≥1 documented diagnosis of any MS-related symptomb (any position; neurology-specific visit of any encounter type) at any time during the study periodAND≥1 documented diagnosis of MS (ICD-9 code 340 <Multiple sclerosis>; any position; any encounter type) at any time prior to January 1, 20106. [at least 1 DMT] AND [at least 1 MS related symptom therapy during a neurology visit] AND [ever history with at least 1 ICD-9-CM code 340]≥1 medication record for an MS DMTa at any time during the study periodAND≥1 medication record for any MS-related symptom therapyc (associated with a neurology-specific visit of any encounter type) at any time during the study periodAND≥1 documented diagnosis of MS (ICD-9 code 340 <Multiple sclerosis>; any position; any encounter type) at any time prior to January 1, 20107. [at least 1 ICD-9-CM code 340] AND [at least 1 MS related symptom therapy during a neurology visit]≥1 documented diagnosis of MS (ICD-9 code 340 <Multiple sclerosis>; any position; any encounter type) at any time during the study periodAND≥1 medication record for any MS-related symptom therapyc (associated with a neurology-specific visit of any encounter type) at any time during the study period8. [at least 1 ICD-9-CM code 340] AND [at least 1 MS related symptom during a neurology visit] at least 30 days apart≥1 documented diagnosis of MS (ICD-9 code 340 <Multiple sclerosis>; any position; any encounter type) at any time during the study periodAND≥1 documented diagnosis of any MS-related symptomb (any position; neurology-specific visit of any encounter type) at any time during the study period and at least 30 days apart from any MS diagnosis during the study perioda MS DMTs include alemtuzumab, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, interferon-beta-1a, interferon-beta-1b, natalizumab, peginterferon beta-1a, and teriflunomide.b MS-related symptoms include fatigue; spasticity; impaired ambulation; optic neuritis; paraesthesia; bladder and sexual dysfunction; facial weakness; muscle weakness; trigeminal neuralgia; diplopia; neuropathic pain; paraplegia; hemiplegia; depression; ataxia; tremor; gait disturbance during a neurology visit.c Therapy for fatigue; spasticity; impaired ambulation; bladder and sexual dysfunction; neuropathic pain; depression; gait disturbance during a neurology visit. Full list of specific therapies available upon request.Abbreviations: DMT, disease-modifying therapy; ICD-9-CM, International Classification of Diseases-ninth revision-Clinical Modification; MRI, magnetic resonance imaging; MS, multiple sclerosis; RRMS, relapsing-remitting MS.Supplementary Table 3. Key terms and phrases for EHR clinical notes-based Algorithm 2 (exclusion criteria)SourceKey terms and phrases for NLP searchResults of NLP from unstructured clinical recordsmultiple sclerosis (MS) primary progressive multiple sclerosis (MS) relapsing progressivemultiple sclerosis (MS) secondary progressivemultiple sclerosis primary progressivemultiple sclerosis, relapsing progressivemultiple sclerosis, secondary progressiveprimary progressive multiple sclerosisrelapsing progressive multiple sclerosissecondary progressive multiple sclerosisAbbreviations: EHR, electronic health records; NLP, natural language processing.Supplementary Table 4. Query Definitions for claims-based Algorithm 2 (exclusion criteria)Algorithm ComponentQuery DefinitionOption A: Medications used for progressive cases (mitoxantrone, cyclophosphamide, or methotrexate)≥1 documented medication record for those used in progressive cases at any time during the study periodOption B: Disease progression based on a specific change of EDSS scores in the last 12 months of the patient's most recent year of care coverage after index date and during the study periodStep 1. Look forward from the patient's index date to determine the patient's most recent 1-year period of care coverageaStep 2. Calculate 2 EDSS scores for each patient using the patient's KFSS scores and the EDSS scoring system:- 1st score during the 7th-12th months of the patients most recent 1-year period of care coverage- 2nd score during the 1st-6th months of the patients most recent 1-year period of care coverageStep 3. Patient qualifies for this criteria if they demonstrate disease progression, defined as:- an increase of ≥1.0 from the 1st score to the 2nd score where the 1st EDSS score is between 0 and <5.5or- an increase of ≥0.5 from the 1st score to the 2nd score where the 1st EDSS score is ≥5.5Option C: At least 12 months of recorded MS history and one of the following:- At least 10 of the last 12 months at the exacerbation level;- The last 12 months at the plateau/stable level with a final therapy type of nursing home, home health, selected rehabilitation/DME.Step 1. Look forward from the patient's index date to determine the patient's most recent 1-year period of care coverageaStep 2. Look for any records of MS Supportive Therapy during the most recent 1-year period of care coverageStep 3. then rank order each of the 12 months in the most recent 1-year period of care coverage based on documented records of MS Supportive Therapy in each month, according to the following hierarchical order:1) nursing home2) home health3) selected rehabilitation therapy/DME4) other/none- Month 1: if we don't see any records for "1", "2" or "3", then we will rank it as a 4- Other months: if we don't see any records for "1", "2" or "3", then we will assume the rank of the prior month with the following sub-rules: - at least 1 true rank of 1, 2 or 3 in the first 4 months (month 1 to month 4) and - at least 1 true rank of 1, 2 or 3 in the last 4 months (month 9 to month 12)Step 4. Flag all months following an increase in therapy as "exacerbation" (e.g., 4-->3, 3-->1) ... and flag all months following a decrease in therapy as "remission" (e.g., 3-->4, 1-->2). If all 12 months are the same ranking, then flag them as "plateau/stable".Step 5. The patient qualifies for this Option C criterion if they have- at least 10 of the 12 months flagged at the exacerbation level or having therapy type of nursing home (1), home health (2), or selected rehabilitation therapy/DME (3)or- all 12 months flagged at the plateau/stable level with a final therapy type of nursing home (1), home health (2), or selected rehabilitation/DME (3)a Care coverage is defined as at least one documented medical encounter (of any kind) for any given 12 month period = no more than 365 days between any documented medical encounter for the patient. For this criterion, we will look at all of the time after the patient's index date until the present time. If the patient has more than 365 days without a documented medical encounter at any time after the patient's index date, then we look at the date of the most recent documented medical encounter before the gap. If that date is within the study period, then it will be the end of the "most recent 1-year period of care coverage". If that date is after the study period, then the last date of the study period (i.e., 31 December 2014) will be the end of the "most recent 1-year period of care coverage". If the patient does not have a gap of 365 days, then the last date of the study period (i.e., 31 December 2014) will be the end of the "most recent 1-year period of care coverage".For example, if a patient's index date is 01 July 2010 and that patient has regular medical encounters after that until there is an encounter on 10 Feb 2014 and then not another encounter within 365 days afterwards. This results in a gap of > 365 days where there was not a medical encounter. Therefore, 10 Feb 2014 would be the end of the "most recent 1-year period of care coverage"... and the patient's "most recent 1-year period of care coverage" = 11 Feb 2013 - 10 Feb 2011.Abbreviations: DME, durable medical equipment; EDSS, Expanded Disability Status Scale; KFSS, Kurtzke Functional System Score; MS, multiple sclerosis. ................
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