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PURPOSE: A market research study was conducted to characterize perceptions of intramuscular (IM) and subcutaneous (SC) routes of injection, including use of autoinjectors, and how these perceptions affect adherence to injection regimens. The perspectives were from women of childbearing age (18-45 years old; consumers) and health care providers (HCPs) involved in women's health care. METHODS: Two telephone surveys, one of HCPs and the other of consumers, were conducted by KRC Research (New York, NY, USA) between May and July 2017. HCPs were recruited across the US; the consumer survey was administered to a nationally representative sample. Survey questions identified potential challenges of IM and SC administration, their impact on treatment adherence, and perceptions of autoinjectors. Results are reported using descriptive statistics and reflect an unweighted sample; margin of error is ±3% for the consumer survey. RESULTS: HCP respondents included 100 generalist OB/GYNs, 101 maternal-fetal medicine specialists, and 519 nurses; there were 1,012 female consumer respondents. Nurses reported more experience than physicians in administering injections, including with autoinjectors. Consumers reported having received treatments via both IM and SC injections; 26% had received treatment with injections at regular intervals. Most HCPs (58%) said they preferred to administer SC injections, which was also the preference for receiving injections among consumers, who reported needle size as a concern regardless of administration mode. Other major concerns were perceptions of pain and fear/anxiety, and seeing the needle, all of which were greater for IM than for SC injections. HCPs and consumers both reported greater likelihood of adherence to therapy administered SC using an autoinjector because they believe that this method provides substantial HCP and patient benefits. CONCLUSION: HCPs and consumers identified similar challenges with adherence to injections. However, there was consistently higher preference for SC relative to IM. HCPs and consumers believe that autoinjectors may increase adherence.
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OBJECTIVES: The aim of this study was to evaluate relationships between serum uric acid (SUA) and newly emergent acute myocardial infarction (AMI), congestive heart failure (CHF), coronary artery disease (CAD), composite cardiovascular (CV) events (AMI, CHF, CAD), hypertension, hyperlipidemia, and renal disease in gout patients. METHODS: Retrospective analysis of electronic medical records from Humedica identified adults (≥18 years) with 2 or more International Classification of Diseases, Ninth Revision, Clinical Modification codes for gout 30 days or more apart (first diagnosis = index event) having 1 or more SUA assessment on or after the index date, and at least 6 months preindex and at least 12 months postindex enrollment. Outcomes were measured during 12 months postindex; patients with preindex events were excluded from analysis of those events. The SUA level (0.01-4.00 mg/dL, 4.01-6.00 mg/dL, 6.01-8.00 mg/dL, and ≥8.01 mg/dL) was determined using the closest laboratory assessment before or on the date of the CV event. Tukey-Kramer comparisons were performed for pairs of SUA strata and Cox proportional model estimated hazard ratios. RESULTS: A significantly higher incidence of AMI, CHF, and renal disease was observed for patients with 8.01 mg/dL or greater relative to other SUA levels (P < 0.0001), and a significantly higher incidence of composite CV events (AMI, CHF, and CAD) was observed for hypouricemia (SUA, 0.01-4.00 mg/dL) compared with other SUA levels (P < 0.0001). Cox models confirmed the increased risk associated with SUA 8.01 mg/dL or greater; hazard ratios ranged from 1.16 for hypertension to 2.04 for renal disease. Hyperlipidemia and hypertension were diagnosed concurrently with gout in 24% and 28% of patients, respectively. CONCLUSIONS: Hyperuricemia and hypouricemia were associated with an increased risk of CV events.
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Gota , Insuficiencia Cardíaca/epidemiología , Enfermedades Renales/epidemiología , Infarto del Miocardio/epidemiología , Ácido Úrico , Adulto , Registros Electrónicos de Salud/estadística & datos numéricos , Femenino , Gota/sangre , Gota/diagnóstico , Gota/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Estadística como Asunto , Estados Unidos/epidemiología , Ácido Úrico/análisis , Ácido Úrico/sangreRESUMEN
PURPOSE: To map relationships between painDETECT, a neuropathic pain (NeP) screening tool, and EQ-5D-3L health status in a real-world setting. METHODS: Patients with physician-confirmed NeP and painDETECT score classifications of nociceptive (n = 79), transitional (n = 141), and NeP (n = 386) completed the EuroQol (EQ-5D-3L), which evaluates Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression with three ordinal response levels ("no problem," "some problems," or "extreme problems/unable to do"), and has a health status thermometer (0 = worst health, 100 = perfect health). Multiple linear and logistic regressions were performed (adjusted for age, gender, race, ethnicity, time since NeP diagnosis, number of comorbidities, NeP conditions). RESULTS: Unadjusted mean (±SD) EQ-5D-3L thermometer scores showed poorer health status across painDETECT classifications from nociceptive (67.3 ± 22.1) to transitional (62.3 ± 20.9) to NeP (53.7 ± 21.8), as did utility scores, 0.695 ± 0.206, 0.615 ± 0.216, and 0.506 ± 0.216. In general, the highest odds of health problems were observed for NeP and the lowest for nociceptive, e.g., the NeP group was 6.2 (95 % confidence interval 3.4-11.4) times as likely to have a more severe problem of Usual Activities compared with the nociceptive group. Relative to nociceptive and transitional, NeP had lower adjusted mean thermometer scores, by 12.1 (P < 0.0001) and 7.8 (P = 0.0004) points, respectively, and lower mean utility scores by 0.157 (P < 0.0001) and 0.092 points (P < 0.0001). CONCLUSIONS: This study, the first to map relationships between painDETECT and the EQ-5D-3L in a real-world setting, indicates that the patient burden with respect to pain classification can be characterized and quantified by decrements in health status overall and in specific domains. These data support the psychometric soundness of painDETECT, enhancing its use in pain management.
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Neuralgia/diagnóstico , Psicometría/métodos , Calidad de Vida/psicología , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Manejo del Dolor , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
Objective: To identify variables correlated with a diagnosis of diabetic peripheral neuropathy (DPN) using random forest modeling applied to electronic health records. Design: Retrospective analysis. Setting: Humedica de-identified electronic health records database. Subjects: Subjects ≥ 18 years old with type 2 diabetes from January 1, 2008-September 30, 2013 having continuous data for 1 year pre- and postindex with DPN (n = 35,050) and without DPN (n = 288,328) were identified. Methods: Demographic, clinical, and health care resource utilization variables (e.g., inpatient and outpatient encounters, medications, and procedures) were input into a random forest model to identify the most important correlates of a DPN diagnosis. Random forest modeling is a computationally extensive, robust data mining technique that accommodates large sets of variables to identify associated factors using an ensemble of classifications trees. Accuracy of the model was evaluated using receiver operating characteristic curves (ROC). Results: The final random forest model consisted of the following variables (importance) associated with a DPN diagnosis: Charlson Comorbidity Index score (100%), age (37.1%), number of pre-index procedures and services (29.7%), number of pre-index outpatient prescriptions (24.2%), number of pre-index outpatient visits (18.3%), number of pre-index laboratory visits (16.9%), number of pre-index outpatient office visits (12.1%), number of inpatient prescriptions (5.9%), and number of pain-related medication prescriptions (4.4%). ROC analysis confirmed model performance, with an area under the curve of 0.824 and accuracy of 89.6% (95% confidence interval 89.4%, 89.8%). Conclusions: Random forest modeling can determine likelihood of a DPN diagnosis. Further validation of the random forest model may help facilitate earlier diagnosis and enhance management strategies.
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Minería de Datos/métodos , Neuropatías Diabéticas/diagnóstico , Registros Electrónicos de Salud , Adolescente , Adulto , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: painDETECT is a screening measure for neuropathic pain. The nine-item version consists of seven sensory items (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure), a pain course pattern item, and a pain radiation item. The seven-item version consists only of the sensory items. Total scores of both versions discriminate average pain-severity levels (mild, moderate, and severe), but their ability to discriminate individual item severity has not been evaluated. METHODS: Data were from a cross-sectional, observational study of six neuropathic pain conditions (N=624). Average pain severity was evaluated using the Brief Pain Inventory-Short Form, with severity levels defined using established cut points for distinguishing mild, moderate, and severe pain. The Wilcoxon rank sum test was followed by ridit analysis to represent the probability that a randomly selected subject from one average pain-severity level had a more favorable outcome on the specific painDETECT item relative to a randomly selected subject from a comparator severity level. RESULTS: A probability >50% for a better outcome (less severe pain) was significantly observed for each pain symptom item. The lowest probability was 56.3% (on numbness for mild vs moderate pain) and highest probability was 76.4% (on cold/heat for mild vs severe pain). The pain radiation item was significant (P<0.05) and consistent with pain symptoms, as well as with total scores for both painDETECT versions; only the pain course item did not differ. CONCLUSION: painDETECT differentiates severity such that the ability to discriminate average pain also distinguishes individual pain item severity in an interpretable manner. Pain-severity levels can serve as proxies to determine treatment effects, thus indicating probabilities for more favorable outcomes on pain symptoms.
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PURPOSE: To psychometrically evaluate painDETECT, a patient-reported screening questionnaire for neuropathic pain (NeP), for discriminating among sensory pain symptoms (burning, tingling/prickling, light touching, sudden pain attacks/electric shock-type pain, cold/heat, numbness, and slight pressure). METHODS: The seven-item version of painDETECT provides an overall score that targets only sensory symptoms, while the nine-item version adds responses on two items to the overall score, covering pain course pattern and pain radiation. Both versions have relevance in terms of characterizing broad NeP. The nine- and seven-item versions of painDETECT were administered to subjects with confirmed NeP across six conditions identified during office visits to US community-based physicians. Responses on the sensory symptom items were dichotomized into "at least moderate" (ie, moderate, strongly, very strongly) relative to the combined other responses (never, hardly noticed, slightly). Logistic regression of dichotomized variables on the total painDETECT score provided probabilities of experiencing each symptom across the range of painDETECT scores. RESULTS: Both painDETECT versions discriminated among the symptoms with similar probabilities across the score ranges. Using these data, the probability of moderately experiencing each pain sensory item was estimated for a particular score, providing a pain profile. Additionally, the likelihood of experiencing each sensation was determined for a discrete increase in score, ie, the odds of at least a moderate sensation of burning (versus less than a moderate sensation) was 1.29 for a 1-point increase, 3.52 for a 5-point increase, and 12.42 for every 10-point increase in the nine-item painDETECT score. CONCLUSION: painDETECT differentiates pain profiles across the range of scores such that, for a particular score, the probability of experiencing at least a moderate sensation of each symptom was determined and compared. These results can help characterize NeP symptomatology, enrich interpretation of painDETECT scores, and provide a basis for individualizing NeP management.
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BACKGROUND: Similarities and differences on the nine-item and seven-item versions of painDETECT, a patient-reported screener to identify neuropathic pain (NeP), have not been psychometrically explored across NeP conditions. METHODS: Scores on the nine-item painDETECT (seven pain symptom items, one pain course pattern item, one pain radiation item) range from -1 to 38; scores ≥19 indicate NeP is likely (>90% probability). The seven-item version (only pain symptoms) score range is 0 to 35. painDETECT was administered to subjects with confirmed diagnoses of human immunodeficiency virus-related peripheral NeP (HIVP) (n=103), spinal cord injury-related NeP (SCI) (n=103), small fiber neuropathy (n=100), painful diabetic peripheral neuropathy (n=112), posttrauma/postsurgical NeP (n=100), and NeP in chronic low back pain (n=106) identified during office visits to US community-based physicians. Analysis of covariance compared mean scores (adjusted for age, sex, race, ethnicity, time since NeP diagnosis, and number of comorbidities) on the nine-item and seven-item versions of painDETECT. Cronbach's alpha assessed internal consistency reliability, and corrected item-to-total correlations assessed item-level discrimination. RESULTS: The adjusted mean nine-item scores ranged from 21.0 (SCI) to 24.3 (small fiber neuropathy). Differences between conditions were either trivial or small-to-medium in magnitude. Cronbach's alpha gave overall internal consistency reliability of 0.76, with a range of 0.63 (SCI) to 0.82 (HIVP). Mean scores and Cronbach's alphas for the seven-item version were generally similar to the nine-item version. Corrected item-to-total correlations adequately discriminated all pain symptom items on both painDETECT versions for each condition (0.3-0.7), but the two nonsensory items on the nine-item version showed lackluster discrimination (<0.3). CONCLUSION: painDETECT scores were within the range indicating high probability of NeP. Differences between conditions were generally modest or not large. Both versions showed evidence of internal consistency reliability and item-level discrimination, suggesting that painDETECT is a useful screening measure for identifying NeP across NeP conditions.
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AIMS: Diabetic peripheral neuropathy (DPN) accompanied by painful symptoms is known as painful DPN (pDPN). This study characterized healthcare resource utilization and costs in patients with DPN, pDPN, and severe pDPN relative to diabetes only. METHODS: Four adult cohorts were identified from the Humedica database: type 2 diabetes without DPN (n=288,328); DPN (n=35,050); pDPN (DPN subjects with a pain score ≥1 on a 0-10 numeric rating scale; n=3449); and severe pDPN (pain scores 7-10; n=1824). Resource utilization and costs for 12-months post-diagnosis were compared for diabetes relative to the other cohorts. RESULTS: Demographic characteristics were different across cohorts. Relative to diabetes alone, DPN, pDPN, and severe pDPN were characterized by significantly higher proportions of patients with resource utilization for all resource categories (all P<0.0001); the highest resource use generally observed for severe pDPN. Total annual direct medical costs were $6632 for diabetes only, with costs for DPN ($12,492), pDPN ($27,931), and severe pDPN ($30,755) significantly higher (all P<0.0001); outpatient costs were consistently the primary driver of total costs. CONCLUSIONS: Patients with DPN, pDPN, and severe pDPN had significantly greater healthcare resource utilization and costs than patients with diabetes only, with the highest burden associated with severe pDPN.
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Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/terapia , Aceptación de la Atención de Salud , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Terapia Combinada/economía , Costo de Enfermedad , Costos y Análisis de Costo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/economía , Diabetes Mellitus Tipo 2/terapia , Neuropatías Diabéticas/tratamiento farmacológico , Neuropatías Diabéticas/economía , Neuropatías Diabéticas/fisiopatología , Registros Electrónicos de Salud , Femenino , Costos de la Atención en Salud , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Since the burden of neuropathic pain (NeP) increases with pain severity, it is important to characterize and quantify pain severity when identifying NeP patients. This study evaluated whether painDETECT, a screening questionnaire to identify patients with NeP, can distinguish pain severity. MATERIALS AND METHODS: Subjects (n=614, 55.4% male, 71.8% white, mean age 55.5 years) with confirmed NeP were identified during office visits to US community-based physicians. The Brief Pain Inventory - Short Form stratified subjects by mild (score 0-3, n=110), moderate (score 4-6, n=297), and severe (score 7-10, n=207) average pain. Scores on the nine-item painDETECT (seven pain-symptom items, one pain-course item, one pain-irradiation item) range from -1 to 38 (worst NeP); the seven-item painDETECT scores (only pain symptoms) range from 0 to 35. The ability of painDETECT to discriminate average pain-severity levels, based on the average pain item from the Brief Pain Inventory - Short Form (0-10 scale), was evaluated using analysis of variance or covariance models to obtain unadjusted and adjusted (age, sex, race, ethnicity, time since NeP diagnosis, number of comorbidities) mean painDETECT scores. Cumulative distribution functions on painDETECT scores by average pain severity were compared (Kolmogorov-Smirnov test). Cronbach's alpha assessed internal consistency reliability. RESULTS: Unadjusted mean scores were 15.2 for mild, 19.8 for moderate, and 24.0 for severe pain for the nine items, and 14.3, 18.6, and 22.7, respectively, for the seven items. Adjusted nine-item mean scores for mild, moderate, and severe pain were 17.3, 21.3, and 25.3, respectively; adjusted seven-item mean scores were 16.4, 20.1, and 24.0, respectively. All pair-wise comparisons of scores between pain-severity groups showed sizable and statistically significant differences (P<0.0001). Cumulative distribution functions showed distinct separation between severity (P<0.0001). Cronbach's alphas were 0.76 and 0.80 for the nine- and seven-item scales, respectively. CONCLUSION: This study provides strong psychometric evidence on the validity and reliability of painDETECT for distinguishing average pain severity in patients with NeP.
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INTRODUCTION: Dalfampridine extended release tablets (dalfampridine-ER; known as prolonged-, modified or sustained-release fampridine in some countries) is a potassium channel blocker approved at 10 mg taken every 12 h, for the improvement of walking in patients with multiple sclerosis (MS). This has been demonstrated by an increase in walking speed. Its mechanism of action and narrow therapeutic range suggest the need to evaluate the seizure risk in treated MS patients. AREAS COVERED: This paper discusses the seizure risk in clinical trials, and postmarketing experience of dalfampridine, relative to that in patients with MS. Electroencephalography as a predictive screening tool for seizure risk in dalfampridine-treated patients is also discussed. EXPERT OPINION: The apparent seizure risk at the recommended dose of dalfampridine among patients with no prior seizure history may not be greater than the risk already present in the MS population. For MS patients, dalfampridine represents a promising new therapy for the improvement of walking impairment; its quick onset of action allows rapid determination of therapeutic response. The lack of prognostic value of electroencephalography for determining seizure risk suggests that treatment can be initiated without further screening when patients have no other contraindications. Strict adherence to the prescribed dosing regimen is essential.
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4-Aminopiridina/efectos adversos , Bloqueadores de los Canales de Potasio/efectos adversos , Convulsiones/inducido químicamente , Electroencefalografía/efectos de los fármacos , Humanos , Esclerosis Múltiple/complicaciones , Selección de Paciente , Vigilancia de Productos ComercializadosRESUMEN
BACKGROUND: Dalfampridine (fampridine outside the United States) is a broad-spectrum potassium channel blocker. Dalfampridine extended-release tablets have been approved by the US Food and Drug Administration to improve walking in patients with multiple sclerosis (MS). OBJECTIVE: The objective of this article is to review the safety profile of dalfampridine extended-release tablets with respect to its expected use in patients with MS. METHODS: We reviewed published data relevant to patient safety profiles based on searches of articles in PubMed published up to December 31, 2010, using the search terms fampridine OR dalfampridine OR 4-aminopyridine AND (multiple sclerosis) in combination with toxicity, safety, clinical trial, pharmacokinetics, and seizures. These searches were supplemented with data derived from the approved package insert and relevant sections of the New Drug Application (22-250) as submitted to the US Food and Drug Administration. RESULTS: The literature searches returned 58 unique citations, of which 26 were considered relevant for characterizing the safety profile of dalfampridine; excluded citations were as follows: reviews (19), evaluation of 3,4-diaminopyridine (4), intravenous dosing (2), inadequate information on patient doses (2), preclinical models (2), and "other" (3). Dalfampridine is nearly completely (approximately 96%) eliminated unchanged in urine, with limited transformation to 2 inactive metabolites and low risk for interaction with drugs metabolized by hepatic P450 cytochromes. However, in patients with renal impairment (creatinine clearance [CrCl], ≤80 mL/min), mean peak plasma concentrations were 68%-101% higher and apparent clearance was 43%-73% lower relative to those without impairment, precluding dalfampridine use in patients with moderate (CrCl, 30-50 mL/min) or severe renal impairment (CrCl, <30 mL/min). Dalfampridine has a narrow therapeutic range. At the therapeutic dose of 10 mg twice daily, adverse events were generally mild to moderate and, consistent with the mechanism of action of dalfampridine, were primarily related to stimulatory effects on the nervous system. A thorough QT study suggested a low risk of induction of QT prolongation and associated cardiac arrhythmias in healthy individuals at therapeutic (10 mg, twice daily) or supratherapeutic (30 mg, twice daily) doses. Although the incidence of seizures was dose related, data from the clinical trials of dalfampridine extended-release tablets suggest that the risk of seizure at the therapeutic dose, in patients with no history of seizure, is not likely to be higher than background rates in MS. CONCLUSION: In patients with MS, dalfampridine has a narrow therapeutic range but an acceptable safety profile when used at the therapeutic dose of 10 mg twice daily.
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4-Aminopiridina/efectos adversos , Esclerosis Múltiple/tratamiento farmacológico , Bloqueadores de los Canales de Potasio/efectos adversos , 4-Aminopiridina/administración & dosificación , 4-Aminopiridina/uso terapéutico , Ensayos Clínicos como Asunto , Preparaciones de Acción Retardada , Relación Dosis-Respuesta a Droga , Humanos , Esclerosis Múltiple/fisiopatología , Bloqueadores de los Canales de Potasio/administración & dosificación , Bloqueadores de los Canales de Potasio/uso terapéutico , Comprimidos , CaminataRESUMEN
OBJECTIVE: To provide a systematic literature review of the responsiveness of patient-reported health outcomes measures for the evaluation of low back pain (LBP). METHODS AND DESIGN: Searches of MEDLINE and EMBASE were performed for articles published in English through June 29, 2009 using the search terms "back pain" or "low back pain" and "questionnaires" or "instrument" or "survey" or "measure" or "patient report outcome." Information on responsiveness was gathered through additional measure-specific searches that included the measure name, first author of the original paper, and "respons*" or "sensit*." Responsiveness was determined based on use of a receiver operating characteristics curve or effect size statistics. RESULTS: Of 43 identified measures, 31 were reported as being responsive to treatment or clinical change, 25 of which were evaluated for responsiveness using methods considered adequate. When considering both the responsiveness evaluation and the underlying factor structure, 13 measures were identified as being adequately validated for use in evaluating responsiveness in the research or clinical practice setting. The majority of the LBP outcome assessment studies were comprised of patients undergoing physical and interventional therapies from clinical practice and clinical trials. The Roland Morris Disability Questionnaire and the Oswestry Disability Index were the most comprehensively validated measures with respect to responsiveness. CONCLUSIONS: We identified 13 measures of LBP that can be used to evaluate responsiveness to change. Choice of a measure warrants careful evaluation of its construct and responsiveness properties in order to maximize the observed impact on pain and functional improvement in subjects with LBP.
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Dolor de la Región Lumbar/fisiopatología , Dolor de la Región Lumbar/terapia , Evaluación de Resultado en la Atención de Salud , Dimensión del Dolor , Bases de Datos Factuales/estadística & datos numéricos , Evaluación de la Discapacidad , Humanos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
BACKGROUND: Multiple sclerosis (MS) is associated with a substantial economic burden resulting from direct medical costs associated with health and disability-related resource utilization and indirect costs relating to reduced productivity. However, reduced health-related quality of life (HR-QOL) may be associated with additional costs, often termed 'intangible costs,' that should be considered as part of the economic burden from the societal or patient perspectives. OBJECTIVES: To review the contribution of intangible costs to the overall economic burden of MS. METHODS: Medline was searched through March 2010 for relevant articles that included the terms 'multiple sclerosis' in combination with 'intangible costs,' 'QALY,' 'quality-adjusted life year,' 'willingness-to-pay,' and 'WTP.' Other than the restriction that the articles were published in English, there were no other exclusionary criteria for the search. Identified references were hand-searched to determine if intangible costs were estimated. RESULTS: Thirteen studies across ten countries were identified that estimated intangible costs based on the number of quality-adjusted life-years (QALYs) lost due to a reduction in HR-QOL multiplied by accepted willingness-to-pay (WTP) thresholds. Although absolute costs varied depending on thresholds used and year of evaluation, the intangible costs accounted for 17.5-47.8% of total costs of MS. Furthermore, evidence suggested intangible costs are positively correlated with worsening disability. The largest increase in intangible costs occurred at the transition between mild and moderate disability. However, since no value has been established as being acceptable to pay for a QALY, a limitation of these studies was their dependence on the definition of the WTP threshold. CONCLUSIONS: Intangible costs substantially add to the economic burden of MS. There is not only a need to further characterize these costs and incorporate them into economic studies, but also to determine how these costs can be reduced through appropriate management strategies.