Clinical Value of Timely Targeted Therapy for Patients With Advanced Non-Small Cell Lung Cancer With Actionable Driver Oncogenes.

BACKGROUND: A recent real-world study observed that 24% of patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADOs) initiated nontargeted therapies before biomarker test results became available. This study assessed the clinical impact of the timing of first-line (1L) targeted therapies (TTs) in aNSCLC. MATERIALS AND METHODS: This retrospective analysis of a nationwide electronic health record-derived deidentified database included patients aged ≥18 years diagnosed with aNSCLC with ADOs (ALK, BRAF, EGFR, RET, MET, ROS-1, and NTRK) from January 1, 2015, to October 18, 2022, by biomarker testing within 90 days after advanced diagnosis and received 1L treatment. Cohorts were defined by treatment patterns ≤42 days after test results: "Upfront TT" received 1L TT ≤42 days; "Switchers" initiated 1L non-TT before or after testing but switched to TT ≤42 days; and "Non-switchers" initiated non-TT before or after testing and did not switch at any time. Adjusted multivariate Cox regression evaluated real-world progression-free survival, real-world time to next treatment or death, and real-world overall survival. RESULTS: A total of 3540 patients met the study criteria; 78% were treated in a community setting, and 50% underwent next-generation sequencing (NGS). There was no significant difference in outcomes between Switchers and Upfront TT; inferior outcomes were observed in Non-switchers versus Upfront TT. CONCLUSION: Our findings demonstrated improved outcomes with upfront 1L TT versus non-TT in patients with aNSCLC with ADOs and observed timely switching to TT after biomarker test result had similar outcomes to Upfront TT. Opportunities remain to improve the use of NGS for early ADO identification and determination of 1L TT.

Pertuzumab plus high-dose trastuzumab for HER2-positive breast cancer with brain metastases: PATRICIA final efficacy data.

The PATRICIA study (NCT02536339) examined the efficacy and safety of pertuzumab plus high-dose trastuzumab in patients with HER2-positive metastatic breast cancer (MBC) with progressive central nervous system (CNS) metastases following radiotherapy. Primary analysis confirmed CNS objective response rate (ORR) was 11% (95% confidence interval [CI]: 3-25); clinical benefit rate (CBR) was 68% (4 months) and 51% (6 months). We report final efficacy data after a further 21-months of follow-up, updated safety, survival, and patient-reported outcomes (PROs). Patients received standard-dose pertuzumab plus high-dose trastuzumab (6 mg/kg weekly) until CNS or systemic disease progression or unacceptable toxicity. Primary endpoint: confirmed ORR (CNS) per Response Assessment in Neuro-Oncology Brain Metastases criteria. Secondary endpoints were response duration, CBR, progression-free survival (PFS), overall survival (OS), safety, and PROs. By clinical cut-off, 39 patients had completed or discontinued treatment. Confirmed ORR (CNS) was 11% (95% CI: 3.0-25.4). Median CNS-PFS was 4.6 months (95% CI: 4.0-8.9), as was median CNS-PFS or systemic PFS (95% CI: 4.0-8.9); median OS was 27.2 months (95% CI: 16.1-not reached). CBR in the CNS was 51% (19 patients, 95% CI: 34.4-68.1) at 6 months. Two patients remained on treatment until study closure, achieving stable disease for 4.1 and 4.8 years. Treatment-related grade 3/4 adverse events occurred in 7.7% of patients. Patients with confirmed partial response or stable disease (≥4 months) in the CNS had stable PROs over time. Pertuzumab plus high-dose trastuzumab represents a reasonable non-chemotherapeutic treatment option for selected patients with HER2-positive MBC with CNS metastases.

Impact of Pertuzumab and Ado-Trastuzumab Emtansine on Cumulative Avoidance of Recurrence Among Women Treated for Locally Advanced, Inflammatory, or Early-Stage Nonmetastatic HER2-Positive Breast Cancer in the United States.

INTRODUCTION: We assessed the impact of HER2-positive early breast cancer (EBC) treatment landscape changes following the introduction of pertuzumab and ado-trastuzumab emtansine (T-DM1) on cumulative population-level recurrences avoided since 2013 (first pertuzumab approval for EBC in the United States; US). METHODS: We constructed a multi-year epidemiologic population treatment-impact model to estimate annual recurrences between 2013 and 2031. Parameters were: BC incidence; stage I-III proportion; HER2-positive disease proportion; treatment proportions for neoadjuvant-only, adjuvant-only, and neoadjuvant-adjuvant continuation; and therapeutic agent proportions within each of those settings (chemotherapy only, trastuzumab ± chemotherapy, pertuzumab with trastuzumab ± chemotherapy, or T-DM1). The primary endpoint was cumulative recurrences, estimated by incorporating extrapolated clinical trial data for each regimen of interest into the model under four scenarios. RESULTS: Approximately 889,057 women were predicted to be diagnosed with stage I-III HER2-positive BC from 2006 to 2031 in the US and potentially indicated for HER2-targeted treatment. In steady-state equilibrium, the model estimated that real-world utilization of pertuzumab and T-DM1 will reduce the population-level number of recurrences by approximately 32%, with 7226 recurrences predicted in 2031 based on current utilization rates. In different modeled scenarios, use of neoadjuvant pertuzumab, continuation of pertuzumab in the adjuvant setting, and T-DM1 in the adjuvant setting in women with residual disease after neoadjuvant treatment were all predicted to reduce the number of recurrences. CONCLUSION: Given the improvement of HER2-targeted treatments, alongside increases in BC disease burden, we expect that the population-level impact of HER2-targeted treatments will accelerate over the next decade. Our results suggest that utilization of HER2-targeted treatments in the US has the potential to change the epidemiology of HER2-positive EBC by preventing a substantial number of women from experiencing disease recurrence. These improvements may help to inform our understanding of the future disease and economic burden of HER2-positive BC in the US.

We predicted whether two treatments for a type of breast cancer called "HER2-positive," that had not yet spread from the breast, could be used to avoid the cancer coming back in women in the United States (US), using computer modeling. The model estimated that approximately 889,057 women were predicted to be diagnosed with this type of breast cancer from 2006 to 2031, and that use of the treatments pertuzumab and ado-trastuzumab emtansine (T-DM1) would reduce the number of breast cancers that came back by around 32%. Treating with pertuzumab before surgery, continuing pertuzumab treatment after surgery, and giving T-DM1 after surgery (in the event that some of the breast cancer remained after being treated before surgery) were all predicted to reduce the number of breast cancers that come back. Overall, we expect use of pertuzumab and T-DM1 to keep lowering the number of breast cancers that come back over the next decade in the US.

ALK Inhibitor Treatment Patterns and Outcomes in Real-World Patients with ALK-Positive Non-Small-Cell Lung Cancer: A Retrospective Cohort Study.

BACKGROUND: Randomized trials have demonstrated that anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) can be safe and efficacious treatments for patients with ALK-positive advanced non-small-cell lung cancer (aNSCLC). However, their safety, tolerability, effectiveness, and patterns of use in real-world patients remain understudied. OBJECTIVE: We sought to assess the overall treatment pattern characteristics, safety, and effectiveness outcomes of real-world patients with ALK-positive aNSCLC receiving ALK TKIs. PATIENTS AND METHODS: This retrospective cohort study using electronic health record data included adult patients with ALK-positive aNSCLC receiving ALK TKIs between January 2012 and November 2021 at a large tertiary medical center, University of California, San Francisco (UCSF), with alectinib or crizotinib as the initial ALK TKI therapy. Our primary endpoints included the incidence of treatment changes (treatment dose adjustments, interruptions, and discontinuations) during the initial ALK TKI treatment, the count and type of subsequent treatments, rates of serious adverse events (sAEs), and major adverse events (mAEs) leading to any ALK TKI treatment changes. Secondary endpoints included the hazard ratios (HRs) for median mAE-free survival (mAEFS), real-world progression-free survival (rwPFS), and overall survival (OS) when comparing alectinib with crizotinib. RESULTS: The cohort consisted of 117 adult patients (70 alectinib and 47 crizotinib) with ALK-positive aNSCLC, with 24.8%, 17.9%, and 6.0% experiencing treatment dose adjustments, interruptions, and discontinuation, respectively. Of the 73 patients whose ALK TKI treatments were discontinued, 68 received subsequent treatments including newer generations of ALK TKIs, immune checkpoint inhibitors, and chemotherapies. The most common mAEs were rash (9.9%) and bradycardia (7.0%) for alectinib and liver toxicity (19.1%) for crizotinib. The most common sAEs were pericardial effusion (5.6%) and pleural effusion (5.6%) for alectinib and pulmonary embolism (6.4%) for crizotinib. Patients receiving alectinib versus crizotinib as their first ALK TKI treatment experienced significantly prolonged median rwPFS (29.3 versus 10.4 months) with an HR of 0.38 (95% CI 0.21-0.67), while prolonged median mAEFS (not reached versus 91.3 months) and OS (54.1 versus 45.8 months) were observed in patients receiving alectinib versus crizotinib but did not reach statistical significance. Yet, it is worth noting that there was a high degree of cross-over post-progression, which could significantly confound the overall survival measures. CONCLUSIONS: We found that ALK TKIs were highly tolerable, and alectinib was associated with favorable survival outcomes with longer time to adverse events (AE) requiring medical interventions, disease progression, and death, in the context of real-world use. Proactive monitoring for adverse events such as rash, bradycardia, and hepatotoxicity may help further promote the safe and optimal use of ALK TKIs in the treatment of patients with aNSCLC.

Ineligible, Unaware, or Uninterested? Associations Between Underrepresented Patient Populations and Retention in the Pathway to Cancer Clinical Trial Enrollment.

PURPOSE: Cancer clinical trials can benefit current and future patients; however, Black patients, rural residents, and patients living in disadvantaged areas are often underrepresented. Using an adapted version of Unger and colleagues' model of the process of clinical trial enrollment, we evaluated the relationship between underrepresented patient populations and trial end points. METHODS: This retrospective study included 512 patients with breast or ovarian cancer who were prescribed a therapeutic drug at the University of Alabama at Birmingham from January 2017 to February 2020. Patient eligibility was assessed using open clinical trials. We estimated odds ratios and 95% CIs using logistic regression models to examine the relationship between underrepresented patient populations and trial enrollment end points: eligibility, interest, offer, enrollment, and declining enrollment. RESULTS: Of the patients in our sample, 27% were Black, 18% were rural residents, and 19% lived in higher disadvantaged neighborhoods. In adjusted models, each comparison group had similar odds of being eligible for a clinical trial. Black versus White patients had 0.40 times the odds of interest in clinical trials and 0.56 times the odds of enrollment. Patients living in areas of higher versus lower disadvantage had 0.46 times the odds of enrolling and 3.40 times the odds of declining enrollment when offered. CONCLUSION: Eligibility did not drive clinical trial enrollment disparities in our sample; however, retention in the clinical trial enrollment process appears to vary by group. Additional work is needed to understand how interventions can be tailored to each population's specific needs.

Associations between geography, decision-making style, and interest in cancer clinical trial participation.

BACKGROUND: Clinical trials offer novel treatments, which are essential to high quality cancer care. Patients living in rural areas are often underrepresented in clinical trials due to several factors. This study evaluated the association between rurality and interest in clinical trial participation, change in interest, and treatment decision-making style preference. METHODS: This cohort study included patients with cancer receiving oncology care at the University of Alabama at Birmingham from 2017 to 2019. Associations between treatment decision-making preference and the interaction between rurality and area deprivation were analyzed using multinomial logistic regression. Initial interest in clinical trial participation and change in interest were analyzed using modified Poisson regressions with robust standard errors. Initial interest model was stratified by Area Deprivation Index (ADI; higher vs. lower disadvantaged). RESULTS: In adjusted models, patients in rural versus urban areas had similar initial interest in clinical trials, both those in higher (40% vs. 50%) and lower disadvantaged settings (54% vs. 62%). Additionally, rural versus urban patients had similar change of clinical trial interest for both those who changed from uninterested-to-interested (31% vs. 26%) and interested-to-uninterested (47% vs. 42%). CONCLUSION: This study compares the interest in clinical trial participation among patients living in rural and urban settings. Lack of interest may be secondary to barriers that patients in rural areas face (e.g., transportation, financial, access). Most rural patients prefer a shared treatment decision-making style, which should be considered when identifying interventions to increase enrollment of underserved rural patients in clinical trials.

Assessment of the Cost-Effectiveness of HER2-Targeted Treatment Pathways in the Neoadjuvant Treatment of High-Risk HER2-Positive Early-Stage Breast Cancer.

INTRODUCTION: This study aims to assess differences in costs and benefits of treatment strategies for high-risk human epidermal growth factor receptor 2 positive (HER2+) early-stage breast cancer (ESBC). METHODS: We used a hybrid decision-tree/Markov model to simulate costs and outcomes across six health states: Invasive disease-free, non-metastatic recurrence, remission, first-line and second-line metastatic cancer, and death. We considered several strategies, defined by four attributes: (1) Neoadjuvant targeted therapy (infused pertuzumab and trastuzumab (PH) versus subcutaneous fixed-dose combination (FDC) of pertuzumab and trastuzumab versus trastuzumab alone (H)); (2) adjuvant targeted therapy if pathological complete response (pCR) is achieved (PH, FDC, or H); (3) adjuvant targeted therapy (T-DM1 or H) in the case of residual disease (RD); and (4) use of branded or biosimilar H. Transition probabilities were derived from relevant clinical trials. We included drug costs and costs associated with adverse events and administration. Health state utilities were obtained from clinical trials and the literature. RESULTS: Strategies not containing T-DM1 were dominated (worse outcomes and greater costs) by strategies containing T-DM1. Among strategies with pertuzumab continuation in the case of pCR and T-DM1 in the case of RD, use of FDC was dominant (equivalent outcomes and lower costs), relative to strategies using infused therapies, regardless of biosimilar versus branded trastuzumab. Adjuvant continuation of FDC was also cost-effective (better outcomes at reasonable cost increases) relative to strategies which discontinued pertuzumab following pCR. CONCLUSION: Dual targeted therapy via FDC (with transition to T-DM1 in the case of RD) is a cost-effective treatment strategy in high-risk HER2+ ESBC.

Cost-effectiveness Analysis of Ado-trastuzumab Emtansine (T-DM1) for the Adjuvant Treatment of Patients With Residual Invasive HER2+ Early Breast Cancer in the United States.

OBJECTIVE: Ado-trastuzumab emtansine (T-DM1) was recently approved for patients with human epidermal growth factor receptor 2 positive (HER2+) early breast cancer (eBC) with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. Cost-effectiveness analysis was conducted to compare T-DM1 versus trastuzumab in the United States. MATERIALS AND METHODS: A Markov cohort-based model tracked clinical and economic outcomes over a lifetime horizon from a US payer perspective. The model included 6 health states: invasive disease-free, nonmetastatic (locoregional) recurrence, remission, first-line and second-line metastatic BC and death. Model state transitions were based on statistical extrapolation of the head-to-head KATHERINE study and published sources. Dosing and treatment duration reflected prescribing information and trials. Costs (2019 US dollars) associated with pharmaceutical treatment (wholesale acquisition costs), health state specific care, adverse events, and end-of-life care were included. Health state utilities were obtained from KATHERINE and published literature. RESULTS: T-DM1 dominated trastuzumab, yielding lower lifetime costs (-$40,271), and higher life-years (2.980) and quality-adjusted life-years (2.336). Results were driven by patients receiving T-DM1 spending less time in more costly downstream health states, as these patients are less likely to experience a recurrence overall, despite having a higher likelihood of metastatic disease (distant recurrence) in the subset of patients who experience recurrence. Probabilistic sensitivity analysis indicated robust results, with 96.7% of 5000 stochastic simulations producing dominance for T-DM1. The most influential variables were related to treatment costs, off treatment utilities, and health state costs. Additional scenario analyses tested a range of model inputs and assumptions, and produced consistent results. CONCLUSION: Relative to trastuzumab, T-DM1 treatment for patients with HER2+ eBC who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment is likely to reduce the overall financial burden of cancer, while simultaneously improving patient outcomes.

Recurrence rates in patients with HER2+ breast cancer who achieved a pathological complete response after neoadjuvant pertuzumab plus trastuzumab followed by adjuvant trastuzumab: a real-world evidence study.

PURPOSE: This study assessed real-world risk of invasive disease recurrence (IDR) and associated factors in patients with human epidermal growth factor receptor-2 positive (HER2+) early breast cancer (BC) with pathological complete responses (pCR) after neoadjuvant pertuzumab plus trastuzumab (nPT) plus chemotherapy, followed by adjuvant trastuzumab (aT). METHODS: Patients with HER2+ BC with pCR after nPT from 2013 to 2015 who received aT were identified in the US Oncology Network and followed until IDR or censoring. Kaplan-Meier and Cox regression methods were used to assess invasive disease-free survival (iDFS) and correlation between iDFS and patient characteristics. RESULTS: A total of 217 pCR patients' charts were reviewed; median age was 52 years. Most had stage IIA or IIB disease (62%), Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1 (84%), tumor size > 2 cm (75%), positive nodes (N+, 62%) and negative estrogen and progesterone receptor (ER- and PR-) expression (52%). Four-year iDFS rates were 90.0% overall (95% CI 84.6%, 93.6%), 86.2% for the N+ cohort and 96.0% for the N- cohort. Cox regression suggested that age, body mass index, ECOG PS, N+ status, stage T3 or T4, and ER+ or PR+ status were risk factors for IDR but were not statistically significant. CONCLUSIONS: Consistent with previous studies, this real-world study observed that patients with HER2+ BC showing pCR with nPT remain at risk for IDR, especially with node-positive disease at diagnosis. Alternatives to adjuvant trastuzumab alone, including combined trastuzumab and pertuzumab, should be considered to improve outcomes for initially N+ patients showing pCR with nPT.

Risk factors and costs associated with 30-day readmissions following alcohol-related hospitalizations in the United States from 2010 to 2015.

Patients with alcohol-related diagnoses at initial hospitalization are at high risk of 30-day readmission. Understanding risk factors for 30-day readmission among these patients may help to identify those who would benefit from efforts to reduce risk of readmission. The Nationwide Readmissions Database was used to estimate 30-day all-cause readmissions among United States patients with an alcohol-related index hospitalization and to evaluate risk factors and costs associated with these readmissions. Included patients were 18 years of age or older at initial hospitalization, had an alcohol-related primary diagnosis (based on ICD-9-CM codes), and were discharged between 2010 and 2015. They were followed for 30 days after initial hospitalization within the calendar year to identify all-cause readmissions. A logistic regression analysis assessed the association between risk factors and 30-day readmission. Average costs of initial admissions and readmissions were estimated. Among 113,931,723 adult index hospitalizations, 1,124,228 had alcohol-related diagnoses. Patients had a mean age of 49 years, 73% were male, and 45% had public insurance coverage. The annual rate of 30-day readmissions among patients with index alcohol-related hospitalizations increased from 119 readmissions per 1000 admissions in 2010 to 140 per 1000 in 2015, while the rate of readmissions among patients with all-cause hospitalizations declined from 103 to 98 per 1000. The regression analysis suggested that age, male sex, comorbid conditions, discharge against medical advice, admission to large and teaching hospitals, and Medicaid vs. non-Medicaid payment were all risk factors for 30-day readmission. Mean costs of initial alcohol-related hospitalizations were greater among those with a 30-day readmission than without a 30-day readmission, and the mean cost of 30-day readmission was even greater. Mitigating the upward trend in rates of readmission following alcohol-related initial hospitalizations may be addressed through better identification of high-risk patients who are admitted with an alcohol-related diagnosis and greater use of existing evidence-based psychosocial and pharmacotherapy treatment methods.

HER2-Positive Metastatic Breast Cancer: A Retrospective Cohort Study of Healthcare Costs in the Targeted-Therapy Age.

INTRODUCTION: Claims data (IBM MarketScan Commercial and MarketScan Medicare Supplemental databases) from June 30, 2011 to September 30, 2017 were used to evaluate the cost impact of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) in this retrospective cohort study. METHODS: The primary analysis compared short-term costs for patients diagnosed with HER2+ MBC at least 180 days after the end of first HER2-targeted treatment (MBC+ cohort) versus a propensity score matched cohort of patients with breast cancer who did not develop MBC (MBC- cohort). A pseudo-post period for patients in the HER2+ MBC- cohort was defined by indexing to the HER2+ treatment completion-MBC diagnosis time interval of the matched pair in the HER2+ MBC+ cohort; we then compared average monthly cost differences between these groups for the year preceding and following MBC diagnosis. In secondary analyses, we estimated medium-term aggregate and categorical healthcare costs for patients with HER2+ MBC up to 3 years post-diagnosis. RESULTS: In the short-term primary analysis, costs for the HER2+ MBC+ and HER2+ MBC- cohorts were largely comparable in the year preceding MBC diagnosis. Monthly direct costs were significantly higher for the HER2+ MBC+ cohort in the months immediately preceding MBC diagnosis, with differences in the range of $500-5000. Following diagnosis, total monthly costs were $13,000-34,000 higher for patients in the HER2+ MBC+ cohort vs. the HER2+ MBC- cohort. In the medium-term secondary analysis, mean per patient total costs were $218,171 [standard error (SE) $5450] in the first year following MBC diagnosis and $412,903 (SE $13,034) cumulatively over 3 years following diagnosis (among patients with complete follow-up). Primary cost contributors were outpatient visits ($195,162; SE $8043) and HER2-targeted therapy drug costs ($177,489; SE $8120). CONCLUSIONS: HER2+ MBC is associated with high short-term and medium-term direct healthcare costs. These could be alleviated with early diagnosis and optimal standard-of-care treatment for early breast cancer, which can significantly reduce the risk of recurrence.

Economic value of transcatheter valve replacement for inoperable aortic stenosis.

OBJECTIVES: To project the social value of transcatheter aortic valve replacement (TAVR) for inoperable patients with severe, symptomatic aortic stenosis (SSAS). STUDY DESIGN: This study used an economic model with parameters obtained from the literature and from US Census Bureau population projections. METHODS: Our model estimated the economic value that will accrue to inoperable patients with SSAS and to device manufacturers as a result of TAVR utilization. We estimated individual patient value as the monetized gain in quality-adjusted life-years as estimated in the cost-effectiveness literature, net of device costs and cost offsets. We estimated manufacturer value by applying an assumed profit margin to revenue from device sales. We created population-level estimates by combining these individual-level estimates with age-stratified Census Bureau population projections and estimates of the incidence of AS. We assessed model uncertainty through the use of probabilistic sensitivity analyses. RESULTS: Between 2018 and 2028, approximately 465,000 inoperable Americans with SSAS will be treated with TAVR. These procedures will yield a cumulative social benefit of up to $48 billion, with roughly 80% of that benefit accruing to patients and 20% accruing to device manufacturers. CONCLUSIONS: Policy makers and payers should take this social value into account when considering decisions related to the care of inoperable patients with SSAS.

The economic burden of kidney graft failure in the United States.

Despite improvements in outcomes for kidney transplant recipients in the past decade, graft failure continues to impose substantial burden on patients. However, the population-wide economic burden of graft failure has not been quantified. This study aims to fill that gap by comparing outcomes from a simulation model of kidney transplant patients in which patients are at risk for graft failure with an alternative simulation in which the risk of graft failure is assumed to be zero. Transitions through the model were estimated using Scientific Registry of Transplant Recipients data from 1987 to 2017. We estimated lifetime costs, overall survival, and quality-adjusted life-years (QALYs) for both scenarios and calculated the difference between them to obtain the burden of graft failure. We find that for the average patient, graft failure will impose additional medical costs of $78 079 (95% confidence interval [CI] $41 074, $112 409) and a loss of 1.66 QALYs (95% CI 1.15, 2.18). Given 17 644 kidney transplants in 2017, the total incremental lifetime medical costs associated with graft failure is $1.38B (95% CI $725M, $1.98B) and the total QALY loss is 29 289 (95% CI 20 291, 38 464). Efforts to reduce the incidence of graft failure or to mitigate its impact are urgently needed.

Understanding price growth in the market for targeted oncology therapies.

OBJECTIVES: The causes of oncology drug price growth remain unclear. Analyzing corresponding trends in revenue can help understand these causes. This study seeks to assess changes over time in prices, patient counts, and drug-level revenues in the US market for oncology therapies and to investigate whether price growth is driven by an increased ability by pharmaceutical firms to capture profits. STUDY DESIGN: Nineteen-year retrospective study (1997-2015). METHODS: We used panel regression to investigate trends in prices, patient counts, and revenues within a US national data set consisting of targeted oncology therapies launched in different eras. RESULTS: We find that prices have roughly tripled, whereas average patient counts per therapy have fallen by 85% to 90% over this period. However, the entire distribution of annual revenues has fallen: For instance, median revenues for drugs launched in the early 2010s are about half of what they were for drugs launched in the late 1990s. CONCLUSIONS: Future research on the causes of quantity decline can help inform pharmaceutical policy.

Challenges with Forecasting Budget Impact: A Case Study of Six ICER Reports.

BACKGROUND: Payers frequently rely on budget impact model (BIM) results to help determine drug coverage policy and its effect on their bottom line. It is unclear whether BIMs typically overestimate or underestimate real-world budget impact. OBJECTIVE: We examined how different modeling assumptions influenced the results of 6 BIMs from the Institute for Clinical and Economic Review (ICER). STUDY DESIGN: Retrospective analysis of pharmaceutical sales data. METHODS: From ICER reports issued before 2016, we collected estimates of 3 BIM outputs: aggregate therapy cost (ie, cost to treat the patient population with a particular therapy), therapy uptake, and price. We compared these against real-world estimates that we generated using drug sales data. We considered 2 classes of BIM estimates: those forecasting future uptake of new agents, which assumed "unmanaged uptake," and those describing the contemporaneous market state (ie, estimates of current, managed uptake and budget impact for compounds already on the market). RESULTS: Differences between ICER's estimates and our own were largest for forecasted studies. Here, ICER's uptake estimates exceeded real-world estimates by factors ranging from 7.4 (sacubitril/valsartan) to 54 (hepatitis C treatments). The "unmanaged uptake" assumption (removed from ICER's approach in 2017) yields large deviations between BIM estimates and real-world consumption. Nevertheless, in some cases, ICER's BIMs that relied on current market estimates also deviated substantially from real-world sales data. CONCLUSIONS: This study highlights challenges with forecasting budget impact. In particular, assumptions about uptake and data source selection can greatly influence the accuracy of results.

Value-Based Payments and Incentives to Improve Care: A Case Study of Patients with Type 2 Diabetes in Medicare Advantage.

OBJECTIVES: To estimate the impact of increased glycated hemoglobin (A1C) monitoring and treatment intensification for patients with type 2 diabetes (T2D) on quality measures and reimbursement within the Medicare Advantage Star (MA Star) program. METHODS: The primary endpoint was the share of patients with T2D with adequate A1C control (A1C ≤ 9%). We conducted a simulation of how increased A1C monitoring and treatment intensification affected this end point using data from the National Health and Nutrition Examination Survey and clinical trials. Using the estimated changes in measured A1C levels, we calculated corresponding changes in the plan-level A1C quality measure, overall star rating, and reimbursement. RESULTS: At baseline, 24.4% of patients with T2D in the average plan had poor A1C control. The share of plans receiving the highest A1C rating increased from 27% at baseline to 49.5% (increased monitoring), 36.2% (intensification), and 57.1% (joint implementation of both interventions). However, overall star ratings increased for only 3.6%, 1.3%, and 4.8% of plans, respectively, by intervention. Projected per-member per-year rebate increases under the MA Star program were $7.71 (monitoring), $2.66 (intensification), and $10.55 (joint implementation). CONCLUSIONS: The simulation showed that increased monitoring and treatment intensification would improve A1C levels; however, the resulting average increases in reimbursement would be small.

Reconsidering the economic value of multiple sclerosis therapies.

OBJECTIVES: To illustrate a more comprehensive view of value associated with medicines treating a highly severe illness and to apply these insights to estimate the costs and benefits of 3 treatments for multiple sclerosis (MS): Avonex, Tysabri, and Tecfidera. STUDY DESIGN: Retrospective study spanning 2002 to 2013. We used economic theory to derive the value of therapy to patients with MS and to individuals who face the risk of contracting MS in the future, under the alternative assumptions that therapies were fully insured or paid for out of pocket. METHODS: Models were parameterized through secondary data analysis and targeted literature review. Estimates of individual value were aggregated to the societal level using therapy-specific treatment prevalence rates. Aggregate consumer value was compared with manufacturer revenue. RESULTS: In the baseline model, Avonex, Tysabri, and Tecfidera generated $46.2 billion of total value to consumers, almost one-third of which accrued to those without MS. The total value to consumers was double manufacturer revenue. Results were qualitatively robust to the use of alternate epidemiological and economic parameters. We found that value to the healthy is positively related to disease severity, and that value to both the sick and the healthy are larger when costs are shared via health insurance. CONCLUSIONS: Theory predicts that treatments for severe disease provide "peace of mind" value to the healthy. Avonex, Tysabri, and Tecfidera have generated significant social value, a large majority of which accrues to consumers. Future economic valuations of medical technology should consider both the potential value to the healthy and the effects of insurance.

Using Respondent-Driven Sampling to Recruit Illegal Drug Purchasers to Evaluate a Drug Market Intervention.

BACKGROUND: Violent drug markets are not as prominent as they once were in the United States, but they still exist and are associated with significant crime and lower quality of life. The drug market intervention (DMI) is an innovative strategy that uses focused deterrence, community engagement, and incapacitation to reduce crime and disorder associated with these markets. Although studies show that DMI can reduce crime and overt drug activity, one perspective is prominently missing from these evaluations: those who purchase drugs. OBJECTIVES: This study explores the use of respondent-driven sampling (RDS)-a statistical sampling method-to approximate a representative sample of drug users who purchased drugs in a targeted DMI market to gain insight into the effect of a DMI on market dynamics. METHODS: Using RDS, we recruited individuals who reported hard drug use (crack or powder cocaine, heroin, methamphetamine, or illicit use of prescriptions opioids) in the last month to participate in a survey. The main survey asked about drug use, drug purchasing, and drug market activity before and after DMI; a secondary survey asked about network characteristics and recruitment. CONCLUSIONS: Our sample of 212 respondents met key RDS assumptions, suggesting that the characteristics of our weighted sample approximate the characteristics of the drug user network. The weighted estimates for market purchasers are generally valid for inferences about the aggregate population of customers, but a larger sample size is needed to make stronger inferences about the effects of a DMI on drug market activity.

How much of the cocaine market are we missing? Insights from respondent-driven sampling in a mid-sized American city.

BACKGROUND: Studying markets for illegal drugs is important, but difficult. Data usually come from a selected subset of consumers, such as arrestees, treatment clients, or household survey respondents. There are rarely opportunities to study how such groups may differ from other market participants or how much of total consumption they represent. METHODS: This paper uses respondent-driven sampling (RDS) of drug users in a mid-sized American city to estimate the shares of cocaine (powder and crack) users and expenditures that are attributable to different combinations of these groups. RESULTS: We find that those arrested in the last year accounted for 34% of past-month cocaine users and 40% of past-week cocaine spending in the RDS sample. Augmenting past-year arrestees with those who received treatment in the past year increases these values to 44% (users) and 55% (spending). CONCLUSIONS: Our results suggest that estimates based only on people who were arrested and/or treated in the past year would have to be inflated by 100-200% to capture the market totals. Adding those who own or rent their place of residence increased coverage in this study to 76% (users) and 81% (spending), suggesting that in theory the inflation factor could be reduced to 23-32% by supplementing data on arrestees and treatment populations with household data, although in practice rates of under-reporting by survey respondents may make coverage (sampling frame) a secondary concern for household surveys.