RWE Framework: An Interactive Visual Tool to Support a Real-World Evidence Study Design.

OBJECTIVES: Real-world evidence (RWE) is essential for the development of pharmaceutical and medical technologies and informs treatment-related decisions by regulatory agencies, payers, healthcare providers, and patients. Given that planning RWE studies present diverse challenges, we developed the RWE Framework, a concise, visual, interactive tool designed to align multidisciplinary stakeholders toward common goals and encourage a methodical approach to RWE study planning. METHODS: A search of published literature and internet-based resources was performed to identify guidance on RWE study planning with decision and/or visual aids. A conceptual framework for a study design tool was developed based on best practices for RWE studies, enhanced with an infographic design, and refined by multidisciplinary input from RWE researchers. RESULTS: The searches confirmed an unmet need for a concise tool to support a broad range of RWE study designs: only two sources with decision/visual aids were identified. The novel RWE Framework comprises sequential decision steps with instructions to guide users through consideration of research objectives, product approval status, study setting, outcomes of interest, data availability in routine practice, need for primary data collection and/or randomization, study type and methodology, and applicable regulatory standards. Pilot testing using case studies of pharmaceutical assets demonstrated the utility of RWE Framework and applicability for use in team environments. CONCLUSIONS: The RWE Framework is a novel, concise, visual, and interactive tool to inform RWE study planning. It addresses a broad range of real-world study types and research objectives and was found to enhance RWE decision-making by multidisciplinary teams. Further validation is warranted.

Progression of fibromyalgia: results from a 2-year observational fibromyalgia and chronic pain study in the US.

BACKGROUND: A previous fibromyalgia (FM) research reports that 20%-47% of diagnosed patients may not meet the study definition of FM 1-2 years after diagnosis. The aim of this study was to gain a better understanding of the progression of FM in a geographically diverse cohort over a 2-year time period. METHODS: This cohort study followed 226 subjects recruited online to assess FM and chronic widespread pain (CWP) diagnosis stability over time. At enrollment (baseline), subjects provided informed consent, completed an online questionnaire consisting of the London Fibromyalgia Epidemiology Study Screening Questionnaire to screen for CWP (bilateral pain above/below waist lasting ≥1 week in the past 3 months), visited a site for physician evaluation for FM, and completed a questionnaire with validated patient-reported outcome instruments. Subjects were classified into mutually exclusive groups: FM+CWP+ (screened positive for CWP and received physician diagnosis of FM), FM-CWP+ (screened positive for CWP but did not receive physician diagnosis of FM), and FM-CWP- (screened negative for CWP). Approximately 2 years later (follow-up), subjects were reassessed at the same study site and completed a questionnaire with the same patient-reported outcomes. RESULTS: Seventy-six FM+CWP+ subjects completed assessments at both time points; 56 (73.7%) met the FM study definition at follow-up. Twenty subjects no longer met the FM study definition (eleven became FM-CWP- and nine became FM-CWP+). Ten subjects (two from FM-CWP- and eight from FM-CWP+) transitioned into the FM+CWP+ group at follow-up; they reported more tender points and pain interference with sleep and worse physical function at baseline compared with subjects who did not transition to FM+CWP+. Most (76.7%) of the subjects who transitioned into/out of FM+CWP+ experienced changes in CWP, number of positive tender points, or both. CONCLUSION: The results suggest that some FM+CWP+ patients experience fluctuation in symptoms over time, which may reflect the waxing and waning nature of FM and affect diagnosis and treatment.

Fibromyalgia Outcomes Over Time: Results from a Prospective Observational Study in the United States.

BACKGROUND: Longitudinal research on outcomes of patients with fibromyalgia is limited. OBJECTIVE: To assess clinician and patient-reported outcomes over time among fibromyalgia patients. METHODS: At enrollment (Baseline) and follow-up (approximately 2 years later), consented patients were screened for chronic widespread pain (CWP), attended a physician site visit to determine fibromyalgia status, and completed an online questionnaire assessing pain, sleep, function, health status, productivity, medications, and healthcare resource use. RESULTS: Seventy-six fibromyalgia patients participated at both time points (at Baseline: 86.8% white, 89.5% female, mean age 50.9 years, and mean duration of fibromyalgia 4.1 years). Mean number of tender points at each physician visit was 14.1 and 13.5, respectively; 11 patients no longer screened positive for CWP at follow-up. A majority reported medication use for pain (59.2% at Baseline, 62.0% at Follow-up). The most common medication classes were opioids (32.4%), SSRIs (16.9%), and tramadol (14.1%) at Follow-up. Significant mean changes over time were observed for fibromyalgia symptoms (modified American College of Rheumatology 2010 criteria: 18.4 to 16.9; P=0.004), pain interference with function (Brief Pain Inventory-Short Form: 5.9 to 5.3; P=0.013), and sleep (Medical Outcomes Study-Sleep Scale: 58.3 to 52.7; P=0.004). Patients achieving ≥2 point improvement in pain (14.5%) experienced greater changes in pain interference with function (6.8 to 3.4; P=0.001) and sleep (62.4 to 51.0; P=0.061). CONCLUSION: Fibromyalgia patients reported high levels of burden at both time points, with few significant changes observed over time. Outcomes were variable among patients over time and were better among those with greater pain improvement.

Health care resource use, productivity, and costs among patients with moderate to severe plaque psoriasis in the United States.

BACKGROUND: Comprehensive studies on costs of moderate to severe plaque psoriasis (MSPP) have not been conducted in the United States. OBJECTIVE: We sought to evaluate current health care resource use, productivity, and costs among patients with MSPP in routine practice. METHODS: A total of 200 adults seeking MSPP treatment enrolled in 9 US sites. Consented patients reported symptoms, treatment, lost productivity, and costs; 6-month retrospective chart review captured health care resource use and clinical characteristics. Costs were assigned to health care resource use and lost productivity using standard algorithms. Differences by Psoriasis Area and Severity Index (PASI) group, based on PASI score (≤10, >10-≤20, >20) at enrollment, were evaluated. Analyses included descriptive statistics and analysis of variance or Kruskal-Wallis tests. RESULTS: Most patients (79.5%) were prescribed 1 or more MSPP medications (mean: 1.5); 36.0% and 9.0% received self-administered biologics and systemic therapies, respectively. Mean number of nonprescription treatments was 12.3. Differences by PASI group were observed for overall work and activity impairment (P < .02). Six-month total MSPP direct costs per patient were $11,291; indirect costs were $2101 and differed across PASI groups (P = .0008). LIMITATIONS: This study enrolled patients with MSPP actively seeking care. CONCLUSION: Despite treatment, a number of patients with MSPP continue to experience moderate to severe PASI scores, impaired functioning, and high costs suggesting a need for new treatment options.

Clinical and economic outcomes in Medicare beneficiaries with stage 3 or stage 4 chronic kidney disease and anemia: the role of intravenous iron therapy.

BACKGROUND: Anemia in patients with chronic kidney disease (CKD) is associated with increased morbidity and mortality, decreased quality of life, and substantial health care costs. Iron therapy is recommended, usually in combination with an erythropoiesis-stimulating agent (ESA), in many CKD patients with anemia and low iron levels to raise hemoglobin levels to a range of 10 to 12 grams per deciliter; iron deficiency is defined by a ferritin score less than 100 micrograms (mcg) per liter and transferrin saturation (TSAT) less than 20%. OBJECTIVE: To examine the use of intravenous (IV) iron and its associated economic and clinical outcomes in Medicare beneficiaries with stage 3 or stage 4 CKD and anemia. METHODS: This was a retrospective cohort analysis using 2006 and 2007 Medicare 5% Standard Analytic Files (SAF). Use of therapy with IV iron and/or ESAs was identified among patients diagnosed with CKD and anemia. The study index quarter was the first quarter in 2006 during which the patient had primary or secondary diagnoses of both CKD and anemia. Based on the receipt of IV iron or ESA treatment in the index quarter, patients were classified into 1 of 4 treatment groups: IV iron and ESA; IV iron without ESA; ESA without IV iron; neither IV iron nor ESA. Therapy with oral iron was not measurable with this database. Clinical and economic outcomes, including the progression to advanced CKD stages, development of anemia, mortality, hospitalization, and net Medicare reimbursement (i.e., not including patient or supplemental plan contribution) for all-cause health care services, were examined for 1 year following the index quarter. Between-group differences were tested using Pearson chi-square for categorical variables and the Kruskal-Wallis nonparametric test for reimbursement. Multivariate logistic regression models were estimated to assess the associations of mortality, inpatient hospitalization, skilled nursing facility (SNF) admission, and hospice care with treatment regimen, controlling for patient demographic and clinical characteristics. RESULTS: Of the 4,310 study patients with both CKD and anemia, 2,913 (67.6%) received neither IV iron nor ESA; 984 (22.8%) received ESA without IV iron; 277 (6.4%) received IV iron and ESA; and 136 (3.2%) received IV iron without ESA in the index quarter. Logistic regression analyses showed that patients receiving neither IV iron nor ESA (reference group) were at increased risk of death compared with patients receiving both IV iron and ESA (OR = 0.62, 95% CI = 0.42-0.90). Additionally, patients receiving neither IV iron nor ESA were more likely to be hospitalized compared with patients receiving both IV iron and ESA (OR = 0.66, 95% CI = 0.50-0.87), IV iron without ESA (OR = 0.55, 95% CI = 0.38-0.79), and ESA without IV iron (OR = 0.73, 95% CI = 0.62-0.87). Further, patients not receiving IV iron or ESA were more likely to be admitted to an SNF than patients receiving both IV iron and ESA (OR = 0.44, 95% CI = 0.32-0.61), IV iron without ESA (OR = 0.57, 95% CI = 0.36-0.88), and ESA without IV iron (OR = 0.56, 95% CI = 0.47-0.67). Patients receiving neither IV iron nor ESA in the index quarter had the highest mean [SD] total Medicare reimbursement per patient in the subsequent year ($42,353 [$52,887]) compared with patients receiving IV iron without ESA ($28,654 [$32,068]), IV iron and ESA ($34,152 [$30,506]), or ESA without IV iron ($38,172 [$35,591], P = 0.001). CONCLUSIONS: Use rates of IV iron and ESA in a sample of Medicare enrollees with CKD and anemia in 2006 suggest that anemia management therapies may be underutilized; however, oral iron therapy use was not measurable with the study database, and therapies initiated after the index quarter were not measured. Patients not treated with IV iron or ESA had significantly higher rates of hospitalization and SNF admission than patients treated with either IV iron or ESA. Further, mortality was significantly higher in patients receiving neither IV iron nor ESA than in patients who received IV iron and ESA. Additionally, total all-cause health care costs were higher among patients receiving neither IV iron nor ESA treatment compared with patients treated with IV iron and/or ESA.

The burden of neuropathic pain: results from a cross-sectional survey.

BACKGROUND: There are few published data on the treatment patterns and burden of neuropathic pain. We have investigated this in a large, observational, cross-sectional survey. METHODS: We surveyed 602 patients with neuropathic pain recruited from general practitioners in six European countries. Physicians recorded demographic and treatment information, including prescription medications. Patients completed Brief Pain Inventory (BPI) severity and interference questions, the EuroQol (EQ-5D), and questions about their productivity, non-prescription treatments, and frequency of physician visits. The BPI Pain Severity score (range: 0-10) is the mean of worst, least, average, and current pain ratings, with scores of 4-6 and 7-10 considered moderate and severe, respectively. We evaluated the impact of pain severity on functioning using analysis of variance models and chi2 tests. RESULTS: Mean (SD) age was 62.9 (14.4) years (50% female). Most patients reported moderate (54%) or severe (25%) pain. Nearly all patients (93%) were prescribed medications for their neuropathic pain: analgesics (71%); anti-epileptics (51%); antidepressants (29%); sedatives/hypnotics (15%). Seventy-six percent visited their physician at least once in the past month. Employment status was affected in 43% of patients; those employed missed a mean (SD) of 5.5 (9.8) workdays during the past month. Pain severity was associated significantly (P<0.001) with poorer EQ-5D scores (mild=0.67, moderate=0.46, severe=0.16), greater disruption of employment status (mild=24%, moderate=48%, severe=54%), and more frequent physician visits (% with one or more visits: mild=66%, moderate=79%, severe=83%). CONCLUSIONS: Patients with neuropathic pain visit their physician frequently and report substantial pain that interferes with daily functioning despite receiving treatment.