Identifying symptomatic adverse events using the patient-reported outcomes version of the common terminology criteria for adverse events in patients with non-small cell lung cancer with epidermal growth factor receptor exon 20 insertion mutations.

OBJECTIVE: Tolerability and safety of treatments are important in oncology trials and should be informed by patient assessments. We identified the most relevant patient-reported symptomatic adverse events (AEs) to measure in patients with non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations. METHODS: This study selected relevant symptomatic AEs from 78 AEs available in the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) measurement system. Initially, symptomatic AEs were selected based on literature and product labeling reviews, and then core sets of symptomatic AEs were identified by patient and clinician interviews. Qualitative and descriptive analyses were performed using the data collected from three iterative rounds of patient interviews. RESULTS: During concept elicitation interviews involving 29 patients, 12 symptomatic AEs were identified and were then adapted into a 25-item PRO-CTCAE form for use in future clinical trials along with commonly used PRO measures. Cognitive interviews showed that the PRO-CTCAE items were easy to answer and appropriate for assessing the patients' experience with symptomatic AEs. This study also assessed disease symptoms, impacts, and overall patient experience. CONCLUSIONS: The 25-item PRO-CTCAE form captures the most relevant symptomatic AEs in this patient population, and it is available for future studies. Baseline characterization of AEs associated with this distinct patient group contributes to our broader knowledge about NSCLC and through platforms like Project Patient Voice will expand our understanding of treatment tolerability and safety for NSCLC. Ultimately, this data collection will help inform decision-making for patients, caregivers, healthcare providers, and regulators.

Measuring patient-reported physical functioning and fatigue in myelodysplastic syndromes using a modular approach based on EORTC QLQ-C30.

PURPOSE: Physical functioning and fatigue are key patient concerns in myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). The objective of this research was to generate supportive quantitative evidence for modular physical functioning and fatigue measures based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) and a customized selection of 10 supplemental items from the EORTC Item Library. METHODS: The 40 items were completed online cross-sectionally by 51 patients (higher risk [HR] MDS: 53%; CMML: 26%; AML: 10%). Psychometric analyses based on Rasch measurement theory (RMT) were conducted on the QLQ-C30 physical functioning and fatigue domains as well as measures combining QLQ-C30 and supplemental items. A measure of anemia-related symptoms composed of QLQ-C30 and supplemental items covering fatigue, dyspnea, and dizziness was also investigated. RESULTS: The QLQ-C30 physical functioning and fatigue domains showed good targeting to the sample and adequate reliability, with few conceptual gaps identified. Combining the QLQ-C30 and supplemental physical functioning and fatigue items improved the conceptual coverage and the reliability of the measures. The patient-reported anemia-related symptom measure showed good measurement performance, underpinned by a clinically meaningful characterization of severity of these symptoms over a spectrum, starting with fatigue, then dyspnea, and finally dizziness (most severe). CONCLUSION: The modular measurement approach of combining EORTC QLQ-C30 and Item Library offers a promising pragmatic solution to the measurement of physical functioning and fatigue, as well as anemia-related symptoms in clinical trials conducted in HR MDS, CMML, and AML.

Treatment Satisfaction and Burden of Illness in Patients with Newly Diagnosed Multiple Myeloma.

OBJECTIVES: This observational study identified attributes of patient-reported satisfaction with therapy for multiple myeloma (MM), described the treatment-related time burden and indirect costs, and investigated the effect of administration route (oral vs. injectable) on these outcomes among patients with newly diagnosed MM (NDMM) and among caregivers. METHODS: Patients residing in the USA with a self-reported diagnosis of NDMM were recruited from PatientsLikeMe, MyelomaCrowd, and Facebook (16 December 2016 and 6 July 2017) to complete an electronic survey including questions on treatment experience, economic burden, and standardized patient-reported outcome measures, including the Treatment Satisfaction Questionnaire for Medication with three domains (global satisfaction, effectiveness, and convenience) and the Work Productivity and Activity Impairment Questionnaire. Univariate and multivariate analyses identified predictors of patient-perceived treatment satisfaction. RESULTS: Among 188 patients, worse Eastern Cooperative Oncology Group performance status (ECOG PS) was correlated with lower patient-perceived effectiveness and convenience of their current treatment. White race and oral administration route were independently correlated with higher patient-perceived convenience of treatment. Injectable therapy use was associated with a trend towards increased activity impairment (43 vs. 34%; p = 0.05) and significantly higher time burden of treatment administration, with threefold higher adjusted indirect costs of MM therapy compared with solely orally administered therapies (monthly mean $US482 vs. 153; 2016 values; p < 0.0001). CONCLUSIONS: Factors associated with patient-perceived satisfaction with NDMM treatment-ECOG PS, race, administration route-warrant increased attention in shared treatment decision making to help identify patient needs and improve the patient's treatment experience. The use of orally administered therapies could improve patients' activity impairment and reduce the time burden associated with therapy.

Patient-Reported Factors in Treatment Satisfaction in Patients with Relapsed/Refractory Multiple Myeloma (RRMM).

BACKGROUND: Therapy choices in relapsed/refractory multiple myeloma (RRMM) should consider patient satisfaction with treatment, because it is associated with adherence to therapy, health outcomes, and medical safety. The primary objective of this pilot cross-sectional observational study was to ascertain factors associated with patient-reported treatment satisfaction in RRMM. PATIENTS AND METHODS: Patients with a self-reported diagnosis of RRMM recruited from PatientsLikeMe, MyelomaCrowd, and Facebook were administered an electronic survey that included questions on demographics and clinical history, treatment experience, economic burden, and standardized patient-reported outcome measures, including the Treatment Satisfaction Questionnaire for Medication, Eastern Cooperative Oncology Group performance status (ECOG PS) measure, and Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Univariable and multivariable analyses were used to identify predictors of patient-perceived treatment satisfaction. RESULTS: One hundred sixty patients with RRMM participated in the study, with a median of two prior relapses and 66.3% reporting the most recent relapse within the last 12 months. ECOG PS ≥2 was associated with lower patient-reported global satisfaction and perceived effectiveness of current treatment. In addition to shorter time spent receiving therapy, orally administered treatment was the strongest predictor of higher satisfaction with treatment convenience. For patients receiving an injectable drug-containing regimen versus an all-oral regimen, respectively, time spent receiving multiple myeloma-directed therapy was higher (12.6 vs. 4.0 hours per month), and total monthly indirect costs were $1,033 and $241. CONCLUSION: Poor ECOG PS was linked to reduced treatment satisfaction and perceived effectiveness of current therapy, whereas an all-oral regimen was associated with increased treatment convenience satisfaction. IMPLICATIONS FOR PRACTICE: This study suggests that attributes including better Eastern Cooperative Oncology Group performance status, less time spent receiving treatment, and oral route of treatment administration lead to higher patient-perceived satisfaction with relapsed/refractory multiple myeloma (RRMM) treatment. Oral route of administration was also associated with less time spent receiving treatment and reduced economic burden for patients. Increased attention to these factors in shared treatment decision making is warranted to help identify individual patient needs, preferences, and expectations for RRMM treatments, to resolve dissatisfaction issues, and to improve the experience of patients with RRMM.

A pragmatic patient-reported outcome strategy for rare disease clinical trials: application of the EORTC item library to myelodysplastic syndromes, chronic myelomonocytic leukemia, and acute myeloid leukemia.

BACKGROUND: Novel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument's ability to detect clinically meaningful treatment benefit for this context of use. METHODS: Our mixed methods approach comprised literature review, clinician consultation (n = 3), and qualitative and quantitative analysis of two stages of patient interview data (n = 14, n = 18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30. RESULTS: Unique symptom (n = 54) and impact (n = 72) concepts were organized into conceptual frameworks of treatment benefit, compared with EORTC QLQ-C30 items and conceptual gaps identified. Supplemental items (n = 13) addressing those gaps were selected from the EORTC Item Library and tested with patients. Supplemental item endorsement frequencies met World Health Organization Quality of Life criteria, suggesting good targeting and relevance for this sample. However, three supplemental items were confirmed as problematic based upon cognitive debriefing results, and expert clinical consultations. Ultimately, 10 supplemental items (n = 7 symptom; n = 3 impact) were selected for the MDS/AML/CMML context. CONCLUSION: Supplemental items were selected to enhance the conceptual coverage of the EORTC QLQ-C30 in the areas of fatigue, shortness of breath, and functioning.

Evaluation of treatment patterns and survival among patients with diffuse large B-cell lymphoma in the USA.

AIM: To evaluate treatment patterns of diffuse large B-cell lymphoma (DLBCL). PATIENTS & METHODS: First-line and relapsed/refractory treatment patterns and survival outcomes following first-line therapy in adult patients newly diagnosed with DLBCL were evaluated. RESULTS: A total of 1436 DLBCL patients initiated treatment and mainly received a combination regimen versus monotherapy (92.1 vs 7.9%). Patients who received monotherapy were older with more comorbidities and had shorter progression-free survival than patients receiving combination therapy (median: 31.3 vs 55.8 months). In the second-line setting (n = 164), rituximab-based combination regimens were most common; 25% underwent stem cell transplantation, and were younger with fewer comorbidities. CONCLUSION: These results illustrate the need for new treatment options for patients unable to tolerate initial combination therapy and transplant-ineligible patients who require salvage therapy.

A retrospective study evaluating treatment patterns and survival outcomes in elderly patients with acute myeloid leukemia treated in the United States with either 7+3 or a hypomethylating agent.

Intensive treatment for newly diagnosed acute myelogenous leukemia (ND-AML) patients are reserved for "fit" patients. While guidelines recommend evaluation of age, performance status and comorbidities, there is no consensus on the definition of "fitness" or optimal therapy for elderly AML patients. This retrospective study evaluated characteristics and survival outcomes of 274 patients (age ≥60 years) with ND-AML treated with 7 + 3 (cytarabine + an anthracycline) vs. hypomethylating agents (HMAs). Most patients received 7 + 3 (60.2%) vs. HMAs (39.8%) in first-line therapy (1 L T); more HMA patients were ≥75 years old and had more comorbidities. Median progression-free survival (PFS) following 1 L T was longer for patients who received 7 + 3 vs. HMAs (6.7 months [95% confidence interval (CI)]: 4.9, 11.1) vs. 4.1 months (95% CI: 2.8, 4.9, respectively). Median overall survival (OS) following 1 L T was also longer for patients who received 7 + 3 vs. HMAs (14.7 months [95% CI: 11.0, not estimated] vs. 4.3 months [95% CI: 3.2, 5.8], respectively). An age-adjusted Charlson Comorbidity Index score of ≥4 vs. < 4 negatively affected PFS and OS irrespective of treatment. Overall, choosing an HMA over 7 + 3 in elderly patients with ND-AML may be influenced by age and comorbidities; patients receiving 7 + 3 had longer survival than those on an HMA.

Treatment Patterns and Survival Outcomes in Patients With Follicular Lymphoma: A 2007 to 2015 Humedica Database Study.

BACKGROUND: Few studies have evaluated real-world treatment patterns and survival in follicular lymphoma (FL). This study evaluated these outcomes among newly diagnosed patients with FL in routine clinical care. PATIENTS AND METHODS: A retrospective study was conducted in newly diagnosed patients with FL from Humedica, a large United States electronic medical record database, from January 1, 2008 to July 31, 2015. Patients were followed from treatment initiation until death, loss to follow-up, or end of study (September 30, 2015). Treatment patterns were assessed in the follow-up period. Progression-free survival (PFS) and overall survival (OS) at 2 years were evaluated in the overall population using Kaplan-Meier analyses. OS was also compared between patients with and without evidence of disease progression within 2 years following first-line therapy (ie, early progressors vs. non-early progressors). RESULTS: A total of 1346 patients were included in the study, with most patients receiving rituximab-based regimens. Fewer early progressors received rituximab-based regimens. Across all lines, combination therapies predominated, particularly bendamustine + rituximab. Following first-line therapy, OS was 86.9% at 2 years, and median OS was not reached. Two-year PFS after first-line therapy was 64.6%, and median PFS was 48.1 months (95% confidence interval, 39.4-58.4 months). OS at 2 years was 76.8% among early progressors versus 90.4% among non-early progressors (P < .001); the median OS was not reached in both groups. CONCLUSION: In routine clinical practice, rituximab-based regimens predominated; however, utilization of these regimens differed among early and non-early progressors. The assessment of survival outcomes also highlights the negative impact of early progression on OS in the rituximab-era.

Transfusion-free interval is associated with improved survival in patients with higher-risk myelodysplastic syndromes engaged in routine care.

Most higher-risk myelodysplastic syndrome (HR-MDS) patients will become transfusion-dependent, leading to potential complications, including infections or end-organ dysfunction. Data correlating achievement of transfusion-free intervals (TFIs) during first-line therapy (1LT) with survival are sparse. We evaluated HR-MDS patients receiving 1LT diagnosed from 1/1/2008 to 7/31/2015 and the impact of a TFI (≥60-day interval without transfusions) on progression-free and overall survival (PFS, OS) using Cox proportional-hazard models. Two hundred and twenty-nine HR-MDS patients received 1LT; overall, median PFS/OS were 8.4 months and 14.7 months, respectively. Two-year PFS/OS were 22.3% and 34.6%, respectively. Median PFS/OS were longer for patients with vs. without a TFI (16.9 vs. 6.1 months and 26.1 vs. 11.8 months, respectively; p < .01 [both]). Two-year PFS (43.0% vs. 3.9%; p < .01) and 2-year OS (51.8% vs. 22.5%; p < .01) were also longer in patients with a TFI vs. not. Achievement of a TFI during 1LT appears to positively affect PFS and OS in HR-MDS patients.

Economic Burden of Patients Treated for Higher-Risk Myelodysplastic Syndromes (HR-MDS) in Routine Clinical Care in the United States.

BACKGROUND AND OBJECTIVE: Significant clinical burden is associated with higher-risk myelodysplastic syndromes (HR-MDS); however, the economic burden has not been fully examined. We examined cost of care and healthcare utilization (HCU) in HR-MDS patients engaged in routine care in the United States (US). METHODS: Adult US patients diagnosed with HR-MDS from 1/1/2008 to 10/31/2015 were identified from the Optum database. Patients were followed until death, progression to acute myeloid leukemia (AML), end of enrollment, or end of study (12/31/2015). Myelodysplastic syndrome (MDS)-related costs/HCU (including medical/pharmacy claims with a primary diagnosis of MDS, MDS-related treatment, or supportive care) and non-MDS-related costs/HCU were evaluated. Costs were calculated as per-patient per-month (PPPM) costs adjusted to 2015 US dollars. RESULTS: Of the 209 HR-MDS patients included, median follow-up was 9.9 months (interquartile range 4.6-17.9), and 69.4% had at least one inpatient admission, 56.9% had at least one emergency department visit, and nearly all patients had at least one outpatient visit. Average PPPM costs over follow-up were $17,361; year 1 versus year 2 costs were higher ($17,337 vs $12,976) following HR-MDS diagnosis. The majority of costs were for MDS-related medical services ($10,327 PPPM). MDS-related medical PPPM costs decreased from $10,557 (year 1) to $6530 (year 2). The main drivers of MDS-related medical costs and the decrease in year 2 were chemotherapy and supportive care costs. CONCLUSIONS: The economic burden of HR-MDS is considerable, particularly within the first year of diagnosis. Treatment/supportive care costs accounted for a significant portion of MDS-related costs. As HR-MDS treatment evolves, the economic impact and HCU need to be further investigated.

Gastrointestinal complications in patients treated with ipilimumab and nivolumab combination therapy or monotherapy.

Aim & methods: A retrospective study using the IBM Explorys Universe Database assessed the risk of gastrointestinal events (enterocolitis or diarrhea) among melanoma and lung cancer patients treated with ipilimumab and nivolumab combination or monotherapy. Results & conclusion: There were 904 melanoma patients (607 ipilimumab, 140 nivolumab and 157 combo) and 1641 lung cancer patients (68 ipilimumab, 1542 nivolumab and 31 combo). Approximately, 37% of lung patients and 46% of melanoma patients experienced at least one adverse event. After adjusting for covariates, patients receiving combination therapy were more likely to have a gastrointestinal event compared with ipilimumab monotherapy patients (melanoma hazard ratio: 1.54; 95% CI: 1.06-2.25; lung hazard ratio: 2.93; 95% CI: 1.09-7.89).

Gastrointestinal adverse events with combination of checkpoint inhibitors in advanced melanoma: a systematic review.

INTRODUCTION: Immunotherapies, including checkpoint inhibitors (CIs) such as cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed death-1 (PD-1) inhibitors, are revolutionizing the treatment of advanced melanoma. Combining CTLA-4 and PD-1 inhibitors provides additional clinical benefit compared with single agents alone. However, combination therapy can increase the incidence of gastrointestinal adverse events (GI AEs). This systematic review assessed the epidemiological, clinical, economic, and humanistic burden of GI AEs due to combination CIs in advanced melanoma. METHODS: MEDLINE, EMBASE, and the Cochrane Library were systematically searched (December 2011 to December 2016) to identify primary studies, systematic reviews, meta-analyses, and conference proceedings (2014-2016) evaluating adults treated with ≥2 CIs for advanced melanoma. RESULTS: Of the 3391 identified articles, 14 were included. Most studies examined the ipilimumab plus nivolumab combination. Any grade and grade 3-4 GI AEs occurred in more patients receiving ipilimumab plus nivolumab versus ipilimumab or nivolumab alone. The most common grade 3-4 GI AEs were diarrhea and colitis. Grade 3-4 colitis occurred in more patients receiving ipilimumab plus nivolumab. However, grade 3-4 diarrhea occurred at the same rate as ipilimumab alone. GI AEs developed with ipilimumab plus nivolumab approximately 6.6 weeks after initiating treatment. No studies assessing the economic or humanistic burden of GI AEs were identified. CONCLUSION: GI AEs occurred at a higher rate and greater severity in patients treated with ipilimumab plus nivolumab versus ipilimumab or nivolumab monotherapy. The lack of research on economic and humanistic burden of GI AEs with combination CIs for advanced melanoma represents an unmet need in the literature and should be explored in future studies.

Economic burden of elderly patients with acute myeloid leukemia treated in routine clinical care in the United States.

This retrospective claims database study examined healthcare utilization (HCU) and costs associated with acute myeloid leukemia (AML) in 237 elderly patients who received chemotherapy or a stem cell transplant (SCT) following AML diagnosis. Patients with secondary AML were excluded. Over the entire follow-up period, 92.0% of patients had ≥1 inpatient admission; 85.7% had ≥1 AML-related admission, and 42.6% had ≥1 non-AML-related admission. During inpatient admissions, 39.2% of patients had ≥1 intensive care unit (ICU) admission, with 20.7% having ≥1 AML-related ICU admission, and 27.8% having ≥1 non-AML-related ICU admission. Total mean per-patient per-month (PPPM) costs over the follow-up period were $25,243 (SD: $21,909), with costs from Year 1 ($27,756 [SD: $22,121]) more than double those in Year 2 ($12,953 [SD: $26,334]) following AML diagnosis. The majority of total costs were medical ($24,512 PPPM [SD: $21,704]), which included inpatient admissions ($6548 PPPM [SD: $10,777]), other outpatient visits ($5021 PPPM [SD: $7997]), supportive care ($3640 PPPM [SD: $5589], and chemotherapy administration ($2029 PPPM [SD: $2345]). Healthcare costs of treated elderly AML patients are substantial, particularly in the first year following diagnosis. Further research is needed to understand factors contributing to high costs in various settings of care for elderly AML patients.

Economic burden of patients with diffuse large B-cell and follicular lymphoma treated in the USA.

AIM: Evaluate healthcare costs and utilization of treated diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) patients. MATERIALS & METHODS: Adults with newly diagnosed DLBCL and FL between 1 January 2008 and 31 October 2015 were identified in the Optum™ claims database. Healthcare costs and utilization were assessed from diagnosis date until end of follow-up. RESULTS: A total of 1267 DLBCL- and 1595 FL-treated patients were identified. Mean per-patient, per-month cost during follow-up was US$11,890 for DLBCL and US$10,460 for FL. Healthcare costs and utilization decreased from year 1 to 2 following diagnosis, due to a decrease in chemotherapy services, inpatient admissions and other outpatient services. CONCLUSION: The economic burden of treated DLBCL and FL is considerable, especially in the first year following diagnosis.

Effectiveness and Safety of Therapeutic Regimens for Elderly Patients With Acute Myeloid Leukemia: A Systematic Literature Review.

Acute myeloid leukemia (AML) is the second most common leukemia among adults. Although the median age at diagnosis is 67 years, with approximately one third of patients aged 75 years or older, limited treatment options exist for the elderly, who have 5-year survival rates of only 5%. A systematic review was conducted to examine effectiveness and safety outcomes of treatment regimens in elderly (≥60 years old) patients with AML. Published literature on the topic was scant, and the review included only 22 articles examining outcomes. Twelve studies examined treatment-specific outcomes; most of these examined azacitidine or intensive chemotherapy (IC). An international randomized controlled trial found that azacitidine significantly improved overall survival relative to conventional regimens including IC and low-dose cytarabine in patients aged > 65 years. Similar results in favor of azacitidine were demonstrated in 2 other studies. IC was generally associated with longer survival versus lower-intensity therapy or best supportive care. Findings suggest that azacitidine is a viable option for elderly AML patients who are ineligible for IC, and emerging agents used in combination with azacitidine could have a major impact in this difficult-to-treat population.

Systematic Literature Review of Treatment Options and Clinical Outcomes for Patients With Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia.

High-dose chemotherapy with allogeneic hematopoietic stem cell transplantation (allo-HSCT) can produce long-term remission in patients with higher-risk myelodysplastic syndromes (HR-MDS) and chronic myelomonocytic leukemia (CMML). However, this treatment regimen is not appropriate for elderly and/or comorbid patients; in these cases, azacitidine is a standard treatment. This systematic review was conducted to evaluate real-world evidence of treatment options for patients with HR-MDS/CMML. Medline and Embase (January 2006 to May 2016) were searched, in addition to conference proceedings and treatment guideline reviews. Studies on clinical effectiveness/efficacy outcomes with a sample size ≥50 patients were included. From 1061 unique citations identified, 87 full-text articles were reviewed, of which 24 articles reported at least 1 outcome of interest. Studies showed that HR-MDS/CMML patients treated with a conventional chemotherapy regimen (CCR) have poorer overall survival (OS). Key findings from individual HR-MDS studies showed improved survival with azacitidine over CCRs and higher overall response rates with clofarabine relative to low-dose cytosine arabinoside (but no significant difference in 2-year OS favoring clofarabine). OS was highest for patients treated with allo-HSCT. Findings indicate limited real-world data on treatment strategies available for HR-MDS/CMML patients. Most studies address the effect of chemotherapy or allo-HSCT on clinical outcomes, so are not applicable to elderly/comorbid patients who are too frail for those treatments. In particular, our analysis revealed limited evidence on viable options after failure of treatment with azacitidine, identifying a significant unmet need in this patient population.

Use of the SF-36v2 Health Survey as a Screen for Risk of Major Depressive Disorder in a US Population-based Sample and Subgroup With Chronic Pain.

STUDY OBJECTIVES: To assess the feasibility of using the SF-36v2 mental health (MH) and mental component summary (MCS) scores for classification of risk for major depressive disorder (MDD), and to determine cut-off scores based on the sensitivity and specificity in a general US representative sample, and a chronic pain subpopulation. METHODS: Data were analyzed from the 2013 US National Health and Wellness Survey (adults 18 y old and above; N=75,000), and among a chronic pain subpopulation (n=6679). Risk of MDD was a score ≥10 on the Patient Health Questionnaire (PHQ-9). Logistic regression modeling was used to predict at risk for MDD and receiver operating characteristic curves were produced. RESULTS: The total sample had MH scores of 48.8 and MCS scores of 48.9, similar to the normative US population mean. Percent of respondents with a PHQ-9≥10 were 15.0% and 29.1% for the total sample and chronic pain subpopulation, respectively. Cut-off scores (PHQ-9≥10) in the total sample for the MH and MCS were 43.0 and 46.0, respectively. Specificities for the MH and MCS were 77.8% and 76.1%; sensitivities were 84.9% and 88.1%, respectively. Among the subpopulation with chronic pain, cut-off scores for the MH and MCS were 40.4 and 43.1, respectively. Corresponding specificities for the MH and MCS were 77.9% and 73.9%; sensitivities were 78.3% and 83.4%, respectively. CONCLUSIONS: The SF-36v2 was found to have sufficient specificity and sensitivity to categorize participants at risk for MDD. If no depression questionnaire is available, it is feasible to use the SF-36v2 to characterize the MH of populations.

Opioid Treatment Patterns Following Prescription of Immediate-Release Hydrocodone.

BACKGROUND: Immediate-release (IR) hydrocodone is the most widely prescribed opioid in the United States; however, little is known about the utilization patterns and duration of opioid use among patients prescribed IR hydrocodone. A better understanding of the use of IR hydrocodone would result in more appropriate prescribing patterns of extended-release opioids. OBJECTIVE: To assess downstream length of opioid therapy and utilization patterns of extended-release/long-acting (ER/LA) opioids among patients on IR hydrocodone to provide a better understanding of how IR and ER/LA opioids are used to manage pain. METHODS: Retrospective analysis using health care claims from the Truven MarketScan Commercial, Medicare Supplemental, and Medicaid databases was performed. Patients prescribed IR hydrocodone during the 6-month baseline period (July 2011-December 2011) and with continuous enrollment for a 12-month follow-up period (2012) post-index date (January 1, 2012) were selected. Downstream length of therapy, defined as number of days supplied with opioids, and downstream use of ER/LA opioids during follow-up were examined by average pills per month (≤ 60 vs. > 60 pills per month) and days supply (< 60 vs. ≥ 60 days supply) of IR hydrocodone during baseline to mimic intermittent and consistent IR users. RESULTS: At baseline, 1,743,933 commercial, 277,096 Medicare, and 157,922 Medicaid IR hydrocodone patients were identified. During follow-up, 1.7%, 2.9%, and 2.8% of patients initiated (i.e., converted to or newly started) ER/LA opioids for commercial, Medicare, and Medicaid groups, respectively. Approximately 90% of patients were prescribed IR hydrocodone for less than 2 months in the following year, while 10% were high utilizers, averaging nearly 8 months of prescribed opioid use during follow-up. Downstream initiation of ER/LA opioids was significantly higher among commercial patients prescribed IR hydrocodone for > 60 pills per month than with ≤ 60 pills per month (7.8% vs. 1.2%, respectively, P < 0.05) at baseline. For commercial patients initiating ER/LA opioids, length of ER/LA therapy during follow-up was significantly longer among patients with baseline IR hydrocodone > 60 pills per month than with ≤ 60 pills per month. All results were consistent when examined by levels of days supply. CONCLUSIONS: A majority of the population prescribed IR hydrocodone was not prescribed opioid therapy beyond 2 months on average in the 1-year follow-up period. Only a small subset of patients with increased pills per month or days supply of IR hydrocodone in the baseline period continued to be high utilizers in the following year, averaging nearly 8 months of prescribed opioid use. A limited proportion of patients prescribed IR hydrocodone converted to ER/LA opioids. This knowledge can assist policymakers and physicians, providing an opportunity to identify small subsets of patients to improve ER/LA opioid prescribing. DISCLOSURES: Funding and support for this study was provided by Purdue Pharma L.P. Consulting fees were paid to Evidera by Purdue Pharma L.P. for this study. Kansal, Chitnis, and Paramore are employees of Evidera and were paid consultants to Purdue Pharma for this research. Holly is an employee for Purdue Pharma, and Bell and Ben-Joseph were full-time employees of Purdue Pharma during the design, planning, and execution of the studies and during the preparation of this manuscript. Burgoyne and Brixner were consultants on this project. Study design was created by Ben-Joseph, Brixner, Paramore, and Burgoyne. Data were collected by Kansal, Chitnis, Bell, Ben-Joseph, and Holly and interpreted by Ben-Joseph, Bell, Kansal, and Holly, with assistance from Brixner, Paramore, Burgoyne, and Chitnis. The manuscript was written by Ben-Joseph, Bell, Paramore, Chitnis, and Holly, with assistance from Kansal, and revised by Bell and Holly, along with Ben-Joseph, Brixner, Kansal, Paramore, Burgoyne, and Chitnis.

Characterizing downstream healthcare resource utilization and costs based on prior utilization patterns of immediate-release hydrocodone.

OBJECTIVE: To assess downstream healthcare resource utilization (HRU) and costs among immediate release (IR) hydrocodone patients by days' supply and average doses/month in the prior 6 months. METHODS: Retrospective analysis using healthcare claims from Truven MarketScan commercial, Medicare supplemental, and Medicaid multistate databases was performed. Patients prescribed IR hydrocodone during the 6-month baseline (July-December 2011), and with continuous enrollment during baseline and the 12-month follow-up (2012) were selected. HRU and per-patient-per-month (PPPM) costs (2014 US dollars) were assessed at follow-up. Descriptive analyses and multivariate regressions were conducted to compare HRU and costs at follow-up by days' supply (<60 vs ≥60 days) and average doses per month (≤60 vs >60 doses/month) of IR hydrocodone at baseline. RESULTS: In total, 1,698,845 commercial, 264,038 Medicare, and 151,063 Medicaid IR hydrocodone patients were identified. During follow-up, commercial patients with prior ≥60 days' supply were more likely to have an inpatient admission (13.2% vs 7.5%), outpatient hospital visit (69.1% vs 57.0%), office visit (97.6% vs 91.0%), emergency room (ER) visit (28.1% vs 21.4%), and had higher PPPM total costs ($1494 vs $842) than the <60 days' supply sub-group (all p < 0.05). Among commercial patients the adjusted odds ratio for prior ≥60 days' supply of IR hydrocodone vs prior <60 days' supply was 1.62 (inpatient), 1.33 (outpatient), 2.58 (office visit) and 1.48 (ER) (all p-values <0.05). Adjusted all-cause total costs were higher ($1245 vs $851, p <0.05) among commercial patients with longer days' supply than those with shorter days' supply. Trends were similar with ≤60 vs >60 doses per month sub-groups and across all plan types. CONCLUSION: Increased days' supply and higher doses/month of IR hydrocodone in the prior 6 months may help to predict levels of HRU and costs in the following year, providing an opportunity to identify patients in order to implement interventions to improve their quality of care.

Illustrating the impact of mild/moderate and severe haemophilia on health-related quality of life: hypothesised conceptual models.

INTRODUCTION/AIMS: Haemophilia and its treatment have a significant impact on patients' lives. The study objectives were to understand the impacts of haemophilia and its treatment from the patient perspective and to inform the development of comprehensive health-related quality-of-life (HRQL) conceptual models to illustrate these impacts. METHODS: The study included two phases. Phase I involved a review of literature published from 1995 to 2010, qualitative analysis of six patient (N = 31) and three healthcare provider (N = 15) focus group transcripts, and interviews with two experts to inform draft conceptual models of mild/moderate and severe haemophilia. Phase II involved interviews with 20 haemophilia patients and qualitative analysis of transcripts to confirm the concepts and structure of the conceptual models. RESULTS: The literature search resulted in 66 publications assessing HRQL, four of which were qualitative studies on the impact of haemophilia from the patient perspective. Results from Phase I indicated that acute bleeding events result in pain, swelling, bruising and restricted joint movement; repeated joint bleeds result in chronic symptoms, such as pain and arthropathy. Acute bleeds cause interruptions in daily activities and interfere with work/school. Patients have fears about having bleeds, which can affect their participation in activities, such as sports or crowded events. Patients also expressed feelings of depression, frustration, isolation and embarrassment. Results of Phase II corroborated findings from Phase I. CONCLUSIONS: The conceptual models illustrate the substantial impact of haemophilia and its treatments on patients' lives and can help inform clinical study design and the selection of endpoints to assess treatment benefit.