Stage III melanoma incidence and impact of transitioning to the 8th AJCC staging system: a US population-based study.

AIM: To estimate incidence of stage III melanoma using the American Joint Committee on Cancer (AJCC) staging, 7th and 8th edition. PATIENTS & METHODS: The SEER US cancer registry was analyzed (2010-2014). AJCC7 stages were recorded in the data; AJCC8 stages were inferred. RESULTS: Of 106,195 melanoma patients, 7669 and 7342 had stage III melanoma by AJCC7 and AJCC8, respectively (95% overlap). Nearly 30% of patients with AJCC7 stage III melanoma were reclassified in a higher stage III group by AJCC8 versus 7% in lower stage group. Regardless of the AJCC edition, incidence of stage III melanoma has increased from 2010 to 2014 both overall and within each stage III group. CONCLUSION: Providing appropriate management to this growing population of high-risk patients is a priority.

A cluster-randomized trial to reduce cesarean delivery rates in Quebec.

BACKGROUND: In Canada, cesarean delivery rates have increased substantially over the past decade. Effective, safe strategies are needed to reduce these rates. METHODS: We conducted a cluster-randomized, controlled trial of a multifaceted 1.5-year intervention at 32 hospitals in Quebec. The intervention involved audits of indications for cesarean delivery, provision of feedback to health professionals, and implementation of best practices. The primary outcome was the cesarean delivery rate in the 1-year postintervention period. RESULTS: Among the 184,952 participants, 53,086 women delivered in the year before the intervention and 52,265 women delivered in the year following the intervention. There was a significant but small reduction in the rate of cesarean delivery from the preintervention period to the postintervention period in the intervention group as compared with the control group (change, 22.5% to 21.8% in the intervention group and 23.2% to 23.5% in the control group; odds ratio for incremental change over time, adjusted for hospital and patient characteristics, 0.90; 95% confidence interval [CI], 0.80 to 0.99; P=0.04; adjusted risk difference, -1.8%; 95% CI, -3.8 to -0.2). The cesarean delivery rate was significantly reduced among women with low-risk pregnancies (adjusted risk difference, -1.7%; 95% CI, -3.0 to -0.3; P=0.03) but not among those with high-risk pregnancies (P=0.35; P = 0.03 for interaction). The intervention group also had a reduction in major neonatal morbidity as compared with the control group (adjusted risk difference, -0.7%; 95% CI, -1.3 to -0.1; P=0.03) and a smaller increase in minor neonatal morbidity (adjusted risk difference, -1.7%; 95% CI, -2.6 to -0.9; P<0.001). Changes in minor and major maternal morbidity did not differ significantly between the groups. CONCLUSIONS: Audits of indications for cesarean delivery, feedback for health professionals, and implementation of best practices, as compared with usual care, resulted in a significant but small reduction in the rate of cesarean delivery, without adverse effects on maternal or neonatal outcomes. The benefit was driven by the effect of the intervention in low-risk pregnancies. (Funded by the Canadian Institutes of Health Research; QUARISMA Current Controlled Trials number, ISRCTN95086407.).

Martingale residual-based method to control for confounders measured only in a validation sample in time-to-event analysis.

Unmeasured confounding remains an important problem in observational studies, including pharmacoepidemiological studies of large administrative databases. Several recently developed methods utilize smaller validation samples, with information on additional confounders, to control for confounders unmeasured in the main, larger database. However, up-to-date applications of these methods to survival analyses seem to be limited to propensity score calibration, which relies on a strong surrogacy assumption. We propose a new method, specifically designed for time-to-event analyses, which uses martingale residuals, in addition to measured covariates, to enhance imputation of the unmeasured confounders in the main database. The method is applicable for analyses with both time-invariant data and time-varying exposure/confounders. In simulations, our method consistently eliminated bias because of unmeasured confounding, regardless of surrogacy violation and other relevant design parameters, and almost always yielded lower mean squared errors than other methods applicable for survival analyses, outperforming propensity score calibration in several scenarios. We apply the method to a real-life pharmacoepidemiological database study of the association between glucocorticoid therapy and risk of type II diabetes mellitus in patients with rheumatoid arthritis, with additional potential confounders available in an external validation sample. Compared with conventional analyses, which adjust only for confounders measured in the main database, our estimates suggest a considerably weaker association. Copyright © 2016 John Wiley & Sons, Ltd.

The missing cause approach to unmeasured confounding in pharmacoepidemiology.

Unmeasured confounding is a major threat to the validity of pharmacoepidemiological studies of medication safety and effectiveness. We propose a new method for detecting and reducing the impact of unobserved confounding in large observational database studies. The method uses assumptions similar to the prescribing preference-based instrumental variable (IV) approach. Our method relies on the new 'missing cause' principle, according to which the impact of unmeasured confounding by (contra-)indication may be detected by assessing discrepancies between the following: (i) treatment actually received by individual patients and (ii) treatment that they would be expected to receive based on the observed data. Specifically, we use the treatment-by-discrepancy interaction to test for the presence of unmeasured confounding and correct the treatment effect estimate for the resulting bias. Under standard IV assumptions, we first proved that unmeasured confounding induces a spurious treatment-by-discrepancy interaction in risk difference models for binary outcomes and then simulated large pharmacoepidemiological studies with unmeasured confounding. In simulations, our estimates had four to six times smaller bias than conventional treatment effect estimates, adjusted only for measured confounders, and much smaller variance inflation than unbiased but very unstable IV estimates, resulting in uniformly lowest root mean square errors. The much lower variance of our estimates, relative to IV estimates, was also observed in an application comparing gastrointestinal safety of two classes of anti-inflammatory drugs. In conclusion, our missing cause-based method may complement other methods and enhance accuracy of analyses of large pharmacoepidemiological studies.

Treatment Discontinuation Patterns for Patients With Chronic Lymphocytic Leukemia in Real-World Settings: Results From a Multi-Center International Study.

INTRODUCTION: This study assessed treatment discontinuation patterns and reasons among chronic lymphocytic leukemia (CLL) patients initiating first-line (1L) and second-line (2L) treatments in real-world settings. MATERIALS AND METHODS: Using deidentified electronic medical records from the CLL Collaborative Study of Real-World Evidence, premature treatment discontinuation was assessed among FCR, BR, BTKi-based, and BCL-2-based regimen cohorts. RESULTS: Of 1364 1L patients (initiated in 1997-2021), 190/13.9% received FCR (23.7% discontinued prematurely); 255/18.7% received BR (34.5% discontinued prematurely); 473/34.7% received BTKi-based regimens, of whom 28.1% discontinued prematurely; and 43/3.2% received venetoclax-based regimens, of whom 16.3% discontinued prematurely (venetoclax monotherapy: 7/0.5%, of whom 42.9% discontinued; VG/VR: 36/2.6%, of whom 11.1% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 25/13.2%; BR: 36/14.1%; BTKi-based regimens: 75/15.9%) and disease progression (venetoclax-based: 3/7.0%). Of 626 2L patients, 20/3.2% received FCR (50.0% discontinued); 62/9.9% received BR (35.5% discontinued); 303/48.4% received BTKi-based regimens, of whom 38.0% discontinued; and 73/11.7% received venetoclax-based regimens, of whom 30.1% discontinued (venetoclax monotherapy: 27/4.3%, of whom 29.6% discontinued; VG/VR: 43/6.9%, of whom 27.9% discontinued). The most common reasons for treatment discontinuation were adverse events (FCR: 6/30.0%; BR: 11/17.7%; BTKi-based regimens: 60/19.8%; venetoclax-based: 6/8.2%). CONCLUSION: The findings of this study highlight the continued need for tolerable therapies in CLL, with finite therapy offering a better tolerated option for patients who are newly diagnosed or relapsed/refractory to prior treatments.

Comparison of healthcare resource utilization and costs of patients with HR+/HER2- advanced breast cancer treated with ribociclib versus other CDK4/6 inhibitors.

AIMS: To assess healthcare resource utilization (HRU) and healthcare costs among women with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- aBC) treated with cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors. METHODS: Women with HR+/HER2- aBC, initiating CDK4/6 inhibitor treatment were identified using IBM MarketScan Commercial and Medicare Supplemental databases (Q1/2000-Q3/2018). Based on the first CDK4/6 inhibitor patients received (index therapy), three cohorts were identified: abemaciclib, palbociclib, and ribociclib. The baseline period (six months preceding treatment initiation) was used to describe patient characteristics. All-cause HRU and direct total healthcare costs (medical and pharmacy) from treatment initiation until the earliest of the end of index therapy, continuous health plan enrollment, or data availability, were compared for the ribociclib cohort versus the abemaciclib and palbociclib cohorts, separately, using weighted regression analyses balanced on baseline covariates. RESULTS: Average age at treatment initiation was ∼60 years and the majority of patients were postmenopausal (abemaciclib: 92%; palbociclib: 92%; ribociclib: 79%). Average follow-up duration was 3.9, 8.8, and 5.9 months for the abemaciclib, palbociclib, and ribociclib cohorts, respectively. After reweighting, HRU was not statistically different between the ribociclib and abemaciclib cohorts, however, the ribociclib cohort incurred significantly lower total healthcare costs (-$5,452; 95% CI: -$8,726; -$1,139, p = .01). Medical costs (driven by outpatient costs) and pharmacy costs (driven by CDK4/6 inhibitor costs) were significantly lower for the ribociclib cohort. Among the reweighted ribociclib and palbociclib cohorts, HRU and total healthcare costs were not statistically different, although the ribociclib cohort had lower outpatient costs per-patient-per-month (-$1,245, 95% CI: -$2,349; -$37, p = .04). LIMITATIONS: Due to the retrospective, observational design, treatment cohorts were not randomly assigned. CONCLUSIONS: During CDK4/6 inhibitor therapy, ribociclib patients tended to incur lower medical and pharmacy costs than abemaciclib patients. Among ribociclib and palbociclib patients, HRU and healthcare costs were similar.

Hospitalizations and healthcare costs associated with rifaximin versus lactulose treatment among commercially insured patients with hepatic encephalopathy in the United States.

AIMS: To assess healthcare costs and hospitalization rates associated with rifaximin therapy versus lactulose alone among patients at risk for hepatic encephalopathy (HE). METHODS AND MATERIALS: IBM Marketscan Commercial and Optum's de-identified Clinformatics Data Mart databases were used separately to identify commercially insured HE patients treated with rifaximin or lactulose alone, using an algorithm developed with clinical experts. HE-related hospitalizations were defined based on an algorithm using diagnosis codes and diagnosis-related group codes. HE-related/all-cause hospital admissions/days and healthcare costs were compared between rifaximin and lactulose episodes using incidence rate ratios and adjusted cost differences. RESULTS: In Marketscan, there were 13,515 [Optum: 5,217] rifaximin episodes and 9,946 [4,897] lactulose alone episodes included. Yearly rates of HE-related hospital admissions decreased by 33% [34%] when treated with rifaximin versus lactulose alone, and rates of HE-related hospital days similarly decreased by 43% [57%]. Yearly rates of all-cause hospital admissions decreased by 27% [27%]; rates of all-cause hospital days decreased by 33% [37%] during rifaximin episodes versus lactulose alone. This translated to $2,417 [$2,301] and $173 [$397] lower total mean medical costs and HE-related hospital costs per-patient-per-month, respectively (p < .05). Despite increased pharmacy costs associated with rifaximin, there was no change in total healthcare costs. Patients adherent to rifaximin incurred $2,891 [$2,340] lower total healthcare costs than non-adherent patients. In a simulated plan of 1 million lives, if 50% of HE patients treated with lactulose alone had rifaximin added on and were adherent to rifaximin therapy, the total cost savings would be $7.5 [$6.1] million per year ($0.62 [$0.50] per-member-per-month). CONCLUSIONS: Patients incurred significantly lower rates of HE-related and all-cause hospitalizations during rifaximin versus lactulose episodes, resulting in lower facility and professional costs. Cost savings may be possible if rifaximin adherence is improved in HE patients. LIMITATIONS: The study is subject to limitations common to claims-based analyses.

In-Hospital Therapy for Heart Failure With Reduced Ejection Fraction in the United States.

OBJECTIVES: This study sought to characterize in-hospital treatment patterns and associated patient outcomes among patients hospitalized for heart failure (HF) in U.S. clinical practice. BACKGROUND: Hospitalizations for HF are common and associated with poor patient outcomes. Real-world patterns of in-hospital treatment, including diuretic therapy, in contemporary U.S. practice are unknown. METHODS: Using Optum de-identified Electronic Health Record data from 2007 through 2018, patients hospitalized for a primary diagnosis of HF (ejection fraction ≤40%) and who were hemodynamically stable at admission, without concurrent acute coronary syndrome or end-stage renal disease, and treated with intravenous (IV) diuretic agents within 48 h of admission were identified. Patients were categorized into 1 of 4 mutually exclusive hierarchical treatment groups defined by complexity of treatment during hospitalization (intensified treatment with mechanical support or IV vasoactive therapy, IV diuretic therapy reinitiated after discontinuation for ≥1 day without intensified treatment, IV diuretic dose increase/combination diuretic treatment without intensified treatment or IV diuretic reinitiation, or uncomplicated). RESULTS: Of 22,677 patients hospitalized for HF with reduced ejection fraction (HFrEF), 66% had uncomplicated hospitalizations without escalation of treatment beyond initial IV diuretic therapy. Among 7,809 remaining patients, the highest level of therapy received was IV diuretic dose increase/combination diuretic treatment in 25%, IV diuretic reinitiation in 36%, and intensified therapy in 39%. Overall, 19% of all patients had reinitiation of IV diuretic agents (26% of such patients had multiple instances), 12% were simultaneously treated with multiple diuretics, and 61% were transitioned to oral diuretic agents before discharge. Compared with uncomplicated treatment, IV diuretic reinitiation and intensified treatment were associated with significantly longer median length of stay (uncomplicated: 4 days; IV diuretic reinitiation: 8 days; intensified: 10 days) and higher rates of in-hospital (uncomplicated: 1.6%; IV diuretic reinitiation: 4.2%; intensified: 13.2%) and 30-day post-discharge mortality (uncomplicated: 5.2%; IV diuretic reinitiation: 9.7%; intensified: 12.7%). CONCLUSIONS: In this contemporary real-world population of U.S. patients hospitalized for HFrEF, one-third of patients had in-hospital treatment escalated beyond initial IV diuretic therapy. These more complex treatment patterns were associated with highly variable patterns of diuretic use, longer hospital lengths of stay, and higher mortality. Standardized and evidence-based approaches are needed to improve the efficiency and effectiveness of in-hospital HFrEF care.

Adjustment for time-dependent unmeasured confounders in marginal structural Cox models using validation sample data.

Large databases used in observational studies of drug safety often lack information on important confounders. The resulting unmeasured confounding bias may be avoided by using additional confounder information, frequently available in smaller clinical "validation samples". Yet, no existing method that uses such validation samples is able to deal with unmeasured time-varying variables acting as both confounders and possible mediators of the treatment effect. We propose and compare alternative methods which control for confounders measured only in a validation sample within marginal structural Cox models. Each method corrects the time-varying inverse probability of treatment weights for all subject-by-time observations using either regression calibration of the propensity score, or multiple imputation of unmeasured confounders. Two proposed methods rely on martingale residuals from a Cox model that includes only confounders fully measured in the large database, to correct inverse probability of treatment weight for imputed values of unmeasured confounders. Simulation demonstrates that martingale residual-based methods systematically reduce confounding bias over naïve methods, with multiple imputation including the martingale residual yielding, on average, the best overall accuracy. We apply martingale residual-based imputation to re-assess the potential risk of drug-induced hypoglycemia in diabetic patients, where an important laboratory test is repeatedly measured only in a small sub-cohort.

Patterns of treatment and BRAF testing with immune checkpoint inhibitors and targeted therapy in patients with metastatic melanoma presumed to be BRAF positive.

Patients with BRAF V600 (BRAF) mutated metastatic melanoma are eligible for therapy with both immune checkpoint inhibitors and targeted therapies, making treatment choice a complex decision. The present study aimed to describe patterns of treatment with immunotherapy and targeted therapy and BRAF testing in patients with metastatic melanoma presumed to have BRAF mutations (BRAF+) in the years following the approval of the newer generation of immune checkpoint inhibitors and targeted therapies (2014-2016). Two large US commercial claims databases [Truven Health Analytics MarketScan and IQVIA Real-World Data Adjudicated Claims - USA (IQVIA RWD Adjudicated Claims - USA)] were used. Patients were presumed BRAF+ if they received at least 2 lines of therapy of which at least 1 included targeted therapy. Sequence of lines of therapy and regimens used in first (1L), second (2L), and third (3L), as well as timing of BRAF testing by sequence of therapy were described. In the Truven sample (n=162), targeted therapy was used by 66% in 1L and by 54% in 2L, and 62% had a BRAF test; in the IQVIA RWD Adjudicated Claims - USA sample (n=247), targeted therapy was used by 62% in 1L and by 50% in 2L, and 68% had a BRAF test. Among those with a claim for a BRAF test prior to 1L, over two-thirds were initiated on targeted therapy. These findings suggest that the rate of BRAF testing remained low in the years following the approval of BRAF-targeted regimens for metastatic disease. Given the recently approved adjuvant treatment options for stage III melanoma, improving the rates of BRAF testing becomes increasingly important.

Adjuvant therapy versus watch-and-wait post surgery for stage III melanoma: a multicountry retrospective chart review.

AIM: To describe treatment patterns among patients with stage III melanoma who underwent surgical excision in years 2011-2016, and assess outcomes among patients who subsequently received systemic adjuvant therapy versus watch-and-wait. METHODS: Chart review of 380 patients from 17 melanoma centers in North America, South America and Europe. RESULTS: Of 129 (34%) patients treated with adjuvant therapy, 85% received interferon α-2b and 56% discontinued treatment (mostly due to adverse events). Relapse-free survival was significantly longer for patients treated with adjuvant therapy versus watch-and-wait (hazard ratio = 0.63; p < 0.05). There was considerable heterogeneity in adjuvant treatment schedules and doses. Similar results were found in patients who received interferon-based adjuvant therapy. CONCLUSION: Adjuvant therapies with better safety/efficacy profiles will improve clinical outcomes in patients with stage III melanoma.

Healthcare resource utilization in patients with metastatic melanoma receiving first-line therapy with dabrafenib + trametinib versus nivolumab or pembrolizumab monotherapy.

OBJECTIVE: To compare healthcare resource utilization (HRU) between patients with metastatic melanoma (MM) initiated on first-line (1L) combination therapy with the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib (D + T; oral) and those initiated on 1 L monotherapy with the anti-PD1 monoclonal antibodies nivolumab or pembrolizumab (N/P; intravenous). METHODS: Patients with melanoma initiated on D + T or N/P from Q1/2014 to Q2/2016 (defined as 1 L treatment for MM) were identified in the Truven MarketScan database. Entropy balancing was used to reweight the N/P cohort in order to make it comparable to the D + T cohort with respect to the mean and variance of baseline covariates. HRU outcomes during 1 L therapy, reported per patient-year (PPY), were described and compared between the two cohorts post-weighting (i.e. independently of baseline covariates). RESULTS: Of the 445 patients included, 202 and 243 were initiated on D + T and N/P, respectively. After weighting, patients initiated on N/P had more outpatient visits for drug administration during 1 L therapy than those initiated on D + T (difference = 18.6 visits PPY [95% CI = 16.0-21.1]). Patients initiated on N/P also had more outpatient office visits for reasons other than drug administration (difference = 8.1 visits PPY [95% CI = 1.9-13.7]). No significant differences were observed for other HRU parameters (i.e. inpatient admissions, inpatient days, and emergency department visits during 1 L therapy). CONCLUSIONS: HRU during 1 L therapy was generally similar between patients initiated on D + T and N/P. Nonetheless, patients initiated on N/P had more outpatient visits, including more outpatient visits for reasons unrelated to drug administration.

Economic Burden of HR+/HER2- Metastatic Breast Cancer Among Adult Premenopausal Women.

INTRODUCTION: Premenopausal women with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC) have complex treatment needs and may receive sequential combinations of endocrine therapy (ET) or chemotherapy. This study describes healthcare utilization (HRU) and costs among premenopausal women with HR+/HER2- mBC in real-world settings from a payer's perspective. METHODS: In this retrospective cohort study, premenopausal women with HR+/HER2- mBC who received ET or chemotherapy were identified from the Truven Health Analytics MarketScan database (1 January 2006-31 December 2015). The main HRU outcomes per patient per 6 months (PPP6 M) were measured during each line of therapy and included number of days in inpatient (IP) and outpatient (OP) services. Healthcare costs per patient per month (PPPM) included medical and pharmacy costs. RESULTS: A total of 3203 patients received first-line, 2194 received second-line, and 1242 received third-line therapy for mBC. Mean number of IP days PPP6 M were 1.6, 1.3, and 1.5 days in the first, second, and third lines, respectively. Mean number of days with OP services PPP6 M was 31.4, 30.9, and 23.3 in the first, second, and third lines, respectively. Among patients receiving ET, mean total healthcare costs were $6521, $4440, and $4555 PPPM in the first, second, and third line, respectively. Among patients receiving chemotherapy, mean total healthcare costs were $16,842, $12,868, and $16,129 PPPM in the first, second, and third line, respectively. These costs were mainly driven by treatment and OP costs. CONCLUSION: Real-world HRU and costs among premenopausal women with HR+/HER2- mBC are extensive. Patients who received chemotherapy incurred approximately twice the costs of patients treated with ET. FUNDING: Novartis Pharmaceutical Corp.

Treatment and Monitoring Patterns Among Premenopausal Women with HR+/HER2- Advanced Breast Cancer.

INTRODUCTION: Premenopausal women with hormone receptor positive (HR+) and human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (aBC) often present with aggressive tumor types that lead to poor prognosis, high rates of recurrence, and mortality. Although clinical guidelines provide evidence-based recommendations for optimal treatment and monitoring, there is a dearth of information regarding treatment and monitoring patterns in clinical practice. In this study, we describe treatment and monitoring patterns among premenopausal women with HR+/HER2- aBC in real-world practice. METHODS: A large US claims database was used to describe treatment patterns for patients in first, second, and third lines of therapy. Treatment monitoring included complete blood count (CBC), liver function test (LFT), and electrocardiogram (EKG) monitoring, described for the first three lines of therapy, and separately for patients receiving endocrine monotherapy (ET) and chemotherapy. RESULTS: Among 3203 patients, chemotherapy was the most common treatment used in first-line (63.6%) and second-line therapy (66.9%). ET was used in 34.4, 30.1, and 73.6% of patients in first, second, and third lines of therapy, respectively. The two most common treatment sequences were a single line of ET (27.3%), and two consecutive lines of chemotherapy followed by a line of ET (19.3%). Patients receiving chemotherapy were monitored with CBC on average more than two times per month, and for LFT one to two times per month. Patients receiving ET were monitored with CBC and LFT on average once every 2-3 months. Overall, approximately 20% of patients were monitored with an EKG at some point during each line of therapy. CONCLUSION: A considerable proportion of premenopausal women with aBC received first- and second-line chemotherapy, which appears inconsistent with current clinical guidelines. The observed treatment heterogeneity points to a lack real-world consensus on the management of premenopausal women with HR+/HER2- aBC. FUNDING: Novartis Pharmaceuticals Corporation.

Dosing Patterns and Economic Burden of Palbociclib Drug Wastage in HR+/HER2- Metastatic Breast Cancer.

INTRODUCTION: Targeted therapies have revolutionized the treatment of hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (mBC). However, as for many oncology drugs, the dose of targeted therapies may need to be adjusted over time, leading to drug wastage when a dose modification is needed but the dose cannot be split or saved. This has been shown to be the case for palbociclib and has led to concerns among payers. This study described palbociclib dosing patterns and estimated the economic burden of the drug wastage associated with palbociclib dose modifications in postmenopausal women with HR+/HER2- mBC. METHODS: A large US claims database was used to identify postmenopausal women with HR+/HER2- mBC who received a palbociclib-based therapy during one of their first three lines of therapy for mBC between February 2015 (palbociclib approval) and December 2015. Dosing patterns (dosing modifications and sequences) were reported; a dose modification was defined as an increase/decrease of at least 25 mg daily compared to the preceding dose. Estimates of drug wastage costs were based on days with overlap in prescription fills for different palbociclib doses. RESULTS: A total of 473 postmenopausal palbociclib-treated women with HR+/HER2- mBC were included (first line 214; second line 157; third line 120). Over an average duration of line of therapy of approximately 4 months, dose modification was observed in 17.8%, 31.2%, and 35.0% of patients in first, second, and third line. Average overlap in prescription fills was 9.2, 9.9, and 5.4 days in first, second, and third line. This potential drug wastage resulted in an average cost of $4376, $4740, and $2592 per patient in first, second, and third line. CONCLUSIONS: This study showed that drug wastage due to palbociclib dose modification results in substantial costs. Treatment options with more flexible dosing may help reduce the costs of drug wastage. FUNDING: Novartis Pharmaceuticals Corporation.

Postsurgical treatment landscape and economic burden of locoregional and distant recurrence in patients with operable nonmetastatic melanoma.

Surgery is the mainstay treatment for operable nonmetastatic melanoma, but recurrences are common and limit patients' survival. This study aimed to describe real-world patterns of treatment and recurrence in patients with melanoma and to quantify healthcare resource utilization (HRU) and costs associated with episodes of locoregional/distant recurrences. Adults with nonmetastatic melanoma who underwent melanoma lymph node surgery were identified from the Truven Health MarketScan database (1 January 2008 to 31 July 2017). Locoregional and distant recurrence(s) were identified on the basis of postsurgery recurrence indicators (i.e. initiation of new melanoma pharmacotherapy, new radiotherapy, or new surgery; secondary malignancy diagnoses). Of 6400 eligible patients, 219 (3.4%) initiated adjuvant therapy within 3 months of surgery, mostly with interferon α-2b (n=206/219, 94.1%). A total of 1191/6400 (18.6%) patients developed recurrence(s) over a median follow-up of 23.1 months (102/6400, 1.6% distant recurrences). Among the 219 patients initiated on adjuvant therapy, 73 (33.3%) experienced recurrences (distant recurrences: 13/219, 5.9%). The mean total all-cause healthcare cost was $2645 per patient per month (PPPM) during locoregional recurrence episodes and $12 940 PPPM during distant recurrence episodes. In the year after recurrence, HRU was particularly higher in patients with distant recurrence versus recurrence-free matched controls: by 9.2 inpatient admissions, 54.4 inpatient days, 8.8 emergency department admissions, and 185.9 outpatient visits (per 100 person-months), whereas all-cause healthcare costs were higher by $14 953 PPPM. It remains to be determined whether the new generation of adjuvant therapies, such as immune checkpoint inhibitors and targeted agents, will increase the use of adjuvant therapies, and reduce the risk of recurrences and associated HRU/cost.

Asthma is not associated with the need for surgery in Crohn's disease when controlling for smoking status: a population-based cohort study.

PURPOSE: Growing evidence suggests asthma and Crohn's disease commonly cooccur. However, the impact of asthma on the prognosis of Crohn's disease is unknown. The aim of our study was to assess the effect of asthma on the need for intestinal resection in patients with Crohn's disease while adjusting for smoking status, imputed from a smaller, secondary data set. PATIENTS AND METHODS: Using health administrative data from a universally funded healthcare plan in Alberta, Canada, we conducted a cohort study to assess the effect of asthma on the need for surgery in patients with Crohn's disease diagnosed between 2002 and 2008 (N=2,113). Validated algorithms were used to identify incident cases of Crohn's disease, cooccurring asthma, and intestinal resection. The association between asthma and intestinal resection was estimated using multivariable Cox proportional hazards regression. Smoking status was imputed using a novel method using martingale residuals, derived from a data set of 485 patients enrolled in the Alberta Inflammatory Bowel Disease Consortium (2007 to 2014) who completed environmental questionnaires. All analyses were adjusted for age, sex, rural/urban status, and mean neighborhood income quintile. RESULTS: Asthma did not increase the risk of surgery in the health administrative data when not adjusting for smoking status (HR 1.03, 95% CI 0.81 to 1.29). The association remained nonsignificant after imputing smoking status in the health administrative data (HR 1.03, 95% CI 0.81 to 1.29). CONCLUSION: Although asthma is associated with an increased risk of Crohn's disease, co-occurring asthma is not associated with the risk of surgery in these patients. This null association persisted after adjusting for smoking status. This study described a novel method to adjust for confounding (smoking status) in time-to-event analyses, even when the confounding variable is unmeasured in health administrative data.