Variation in completeness of coding external cause of injuries under ICD-10-CM.

INTRODUCTION: Information about causes of injury is key for injury prevention efforts. Historically, cause-of-injury coding in clinical practice has been incomplete due to the need for extra diagnosis codes in the International Classification of Diseases-Ninth Revision-Clinical Modification (ICD-9-CM) coding. The transition to ICD-10-CM and increased use of clinical support software for diagnosis coding is expected to improve completeness of cause-of-injury coding. This paper assesses the recording of external cause-of-injury codes specifically for those diagnoses where an additional code is still required. METHODS: We used electronic health record and claims data from 10 health systems from October 2015 to December 2021 to identify all inpatient and emergency encounters with a primary diagnosis of injury. The proportion of encounters that also included a valid external cause-of-injury code is presented. RESULTS: Most health systems had high rates of cause-of-injury coding: over 85% in emergency departments and over 75% in inpatient encounters with primary injury diagnoses. However, several sites had lower rates in both settings. State mandates were associated with consistently high external cause recording. CONCLUSIONS: Completeness of cause-of-injury coding improved since the adoption of ICD-10-CM coding and increased slightly over the study period at most sites. However, significant variation remained, and completeness of cause-of-injury coding in any diagnosis data used for injury prevention planning should be empirically determined.

Benefits, harms, and costs of newborn genetic screening for hypertrophic cardiomyopathy: Estimates from the PreEMPT model.

PURPOSE: Population newborn genetic screening for hypertrophic cardiomyopathy (HCM) is feasible, however its benefits, harms, and cost-effectiveness are uncertain. METHODS: We developed a microsimulation model to simulate a US birth cohort of 3.7 million newborns. Those identified with pathogenic/likely pathogenic variants associated with increased risk of HCM underwent surveillance and recommended treatment, whereas in usual care, individuals with family histories of HCM underwent surveillance. RESULTS: In a cohort of 3.7 million newborns, newborn genetic screening would reduce HCM-related deaths through age 20 years by 44 (95% uncertainty interval [UI] = 10-103) however increase the numbers of children undergoing surveillance by 8127 (95% UI = 6308-9664). Compared with usual care, newborn genetic screening costs $267,000 per life year saved (95% UI, $106,000 to $919,000 per life year saved). CONCLUSION: Newborn genetic screening for HCM could prevent deaths but at a high cost and would require many healthy children to undergo surveillance. This study shows how modeling can provide insights into the tradeoffs between benefits and costs that will need to be considered as newborn genetic screening is more widely adopted.

Association Between Adverse Social Determinants of Health and Suicide Death.

OBJECTIVE: The aim of this study was to identify adverse social determinants of health (SDoH) International Statistical Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code prevalence among individuals who died by suicide and to examine associations between documented adverse SDoH and suicide. RESEARCH DESIGN: A case-control study using linked medical record, insurance claim, and mortality data from 2000 to 2015 obtained from 9 Mental Health Research Network-affiliated health systems. We included 3330 individuals who died by suicide and 333,000 randomly selected controls matched on index year and health system location. All individuals in the study (cases and controls) had at least 10 months of enrollment before the study index date. The index date for the study for each case and their matched controls was the suicide date for that given case. RESULTS: Adverse SDoH documentation was low; only 6.6% of cases had ≥1 documented adverse SDoH in the year before suicide. Any documented SDoH and several specific adverse SDoH categories were more frequent among cases than controls. Any documented adverse SDoH was associated with higher suicide odds [adjusted odds ratio (aOR)=2.76; 95% CI: 2.38-3.20], as was family alcoholism/drug addiction (aOR=18.23; 95% CI: 8.54-38.92), being an abuse victim/perpetrator (aOR=2.53; 95% CI: 1.99-3.21), other primary support group problems (aOR=1.91; 95% CI: 1.32-2.75), employment/occupational maladjustment problems (aOR=8.83; 95% CI: 5.62-13.87), housing/economic problems (aOR: 6.41; 95% CI: 4.47-9.19), legal problems (aOR=27.30; 95% CI: 12.35-60.33), and other psychosocial problems (aOR=2.58; 95% CI: 1.98-3.36). CONCLUSIONS: Although documented SDoH prevalence was low, several adverse SDoH were associated with increased suicide odds, supporting calls to increase SDoH documentation in medical records. This will improve understanding of SDoH prevalence and assist in identification and intervention among individuals at high suicide risk.

A new analytic tool for assessing the impact of the US Food and Drug Administration regulatory actions.

PURPOSE: Develop and test a flexible, scalable tool using interrupted time series (ITS) analysis to assess the impact of Food and Drug Administration (FDA) regulatory actions on drug use. METHODS: We applied the tool in the Sentinel Distributed Database to assess the impact of FDA's 2010 drug safety communications (DSC) concerning the safety of long-acting beta2-agonists (LABA) in adult asthma patients. We evaluated changes in LABA use by measuring the initiation of LABA alone and concomitant use of LABA and asthma controller medications (ACM) after the DSCs. The tool generated ITS graphs and used segmented regression to estimate baseline slope, level change, slope change, and absolute and relative changes at up to two user-specified time point (s) after the intervention. We tested the tool and compared our results against prior analyses that used similar measures. RESULTS: Initiation of LABA alone declined among asthma patients aged 18-45 years before FDA DSCs (-0.10% per quarter; 95%CI: -0.11% to -0.09%) and the downward trend continued after. Concomitant use of LABA and ACM was stable before FDA DSCs. After FDA DSCs, there was a small trend decrease of 0.006% per quarter (95% CI, -0.008% to -0.003%). We found similar results among those aged 46-64 years and patients with poorly-controlled asthma. Our results were consistent with previous studies, confirming the performance of the new tool. CONCLUSIONS: We developed and tested a reusable ITS tool in real-world databases formatted to the Sentinel Common Data Model that can assess the impact of regulatory actions on drug use.

"Go ahead and screen" - advice to healthcare systems for routine lynch syndrome screening from interviews with newly diagnosed colorectal cancer patients.

BACKGROUND: Lynch syndrome (LS) is the most common cause of inherited colorectal cancer (CRC). Universal tumor screening (UTS) of newly diagnosed CRC cases is recommended to aid in diagnosis of LS and reduce cancer-related morbidity and mortality. However, not all health systems have adopted UTS processes and implementation may be inconsistent due to system and patient-level complexities. METHODS: To identify barriers, facilitators, and suggestions for improvements of the UTS process from the patient perspective, we conducted in-depth, semi-structured interviews with patients recently diagnosed with CRC, but not screened for or aware of LS. Patients were recruited from eight regionally diverse US health systems. Interviews were conducted by telephone, 60-minutes, audio-recorded, and transcribed. An inductive, constant comparative analysis approach was employed.  RESULTS: We completed 75 interviews across the eight systems. Most participants were white (79%), about half (52%) were men, and the mean age was 60 years. Most self-reported either no (60%) or minimal (40%) prior awareness of LS. Overall, 96% of patients stated UTS should be a routine standard of care for CRC tumors, consistently citing four primary motivations for wanting to know their LS status and engage in the process for LS identification: "knowledge is power"; "family knowledge"; "prevention and detection"; and "treatment and surveillance." Common concerns pertaining to the process of screening for and identifying LS included: creating anticipatory worry for patients, the potential cost and the accuracy of the genetic test, and possibly having one's health insurance coverage impacted by the LS diagnosis. Patients suggested health systems communicate LS results in-person or by phone from a trained expert in LS; offer proactive verbal and written education about LS, the screening steps, and any follow-up surveillance recommendations; and support patients in communicating their LS screening to any of their blood relatives. CONCLUSION: Our qualitative findings demonstrate patients with CRC have a strong desire for healthcare systems to regularly implement and offer UTS. Patients offer key insights for health systems to guide future implementation and optimization of UTS and other LS screening programs and maximize diagnosis of individuals with LS and improve cancer-related surveillance and outcomes. TRIAL REGISTRATION: Not available: not a clinical trial.

An Assessment of Perspectives and Concerns Among Research Participants of Childbearing Age Regarding the Health-Relatedness of Data, Online Data Privacy, and Donating Data to Researchers: Survey Study.

BACKGROUND: The June 2022 US Supreme Court decision to ban abortion care in Dobbs v Jackson Women's Health Organization sparked ominous debate about the privacy and safety of women and families of childbearing age with digital footprints who actively engage in family planning, including abortion and miscarriage care. OBJECTIVE: To assess the perspectives of a subpopulation of research participants of childbearing age regarding the health-relatedness of their digital data, their concerns about the use and sharing of personal data online, and their concerns about donating data from various sources to researchers today or in the future. METHODS: An 18-item electronic survey was developed using Qualtrics and administered to adults (aged ≥18 years) registered in the ResearchMatch database in April 2021. Individuals were invited to participate in the survey regardless of health status, race, gender, or any other mutable or immutable characteristics. Descriptive statistical analyses were conducted using Microsoft Excel and manual queries (single layer, bottom-up topic modeling) and used to categorize illuminating quotes from free-text survey responses. RESULTS: A total of 470 participants initiated the survey and 402 completed and submitted the survey (for an 86% completion rate). Nearly half the participants (189/402, 47%) self-reported to be persons of childbearing age (18 to 50 years). Most participants of childbearing age agreed or strongly agreed that social media data, email data, text message data, Google search history data, online purchase history data, electronic medical record data, fitness tracker and wearable data, credit card statement data, and genetic data are health-related. Most participants disagreed or strongly disagreed that music streaming data, Yelp review and rating data, ride-sharing history data, tax records and other income history data, voting history data, and geolocation data are health-related. Most (164/189, 87%) participants were concerned about fraud or abuse based on their personal information, online companies and websites sharing information with other parties without consent, and online companies and websites using information for purposes that are not explicitly stated in their privacy policies. Free-text survey responses showed that participants were concerned about data use beyond scope of consent; exclusion from health care and insurance; government and corporate mistrust; and data confidentiality, security, and discretion. CONCLUSIONS: Our findings in light of Dobbs and other related events indicate there are opportunities to educate research participants about the health-relatedness of their digital data. Developing strategies and best privacy practices for discretion regarding digital-footprint data related to family planning should be a priority for companies, researchers, families, and other stakeholders.

Risk of suicide among stroke survivors in the United States.

BACKGROUND: Stroke is the largest cause of disability and the 5th leading cause of death in the United States. Suicide is the 12th leading cause of death in the United States. However, little is known about the risk of suicide among people with a prior stroke. OBJECTIVES: Using Multiple Cause of Death data (1999-2020) from the Centers for Disease Control and Prevention WONDER database, we examined via cross-sectional analysis the risk of suicide among survivors of stroke as compared to the general U.S. population and among subgroups within the United States. METHODS: We assessed disparities in suicide rate among patients with stroke stratified by sex, race, urbanization levels, and census regions using the CDC WONDER multiple cause of death database. Standardized mortality rates were calculated to compare the suicide rate of stroke patients with the rates among demographic-matched cohorts and the general United States population. RESULTS: As compared to the general population, stroke survivors had an elevated risk of suicide. Black stroke survivors had a lower rate of suicide as compared to the general population, while White stroke survivors and those in nonmetropolitan areas had an elevated risk compared to the general population. CONCLUSION: There was a slightly elevated risk of suicide among people with a prior stroke in the United States. This risk may be elevated among White people and among people living in nonmetropolitan areas.

Factors associated with suicide mortality among reproductive age women: a case-control study.

OBJECTIVE: Examine demographic, psychosocial, pregnancy-related, and healthcare utilisation factors associated with suicide mortality among reproductive age women. METHODS: Data from nine health care systems in the Mental Health Research Network were included. A case-control study design was used in which 290 reproductive age women who died by suicide (cases) from 2000 to 2015 were matched with 2,900 reproductive age women from the same healthcare system who did not die by suicide (controls). Conditional logistic regression was used to analyse associations between patient characteristics and suicide. RESULTS: Women of reproductive age who died by suicide were more likely to have mental health (aOR = 7.08, 95% CI: 5.17, 9.71) or substance use disorders (aOR = 3.16, 95% CI: 2.19, 4.56) and to have visited the emergency department in the year prior to index date (aOR = 3.47, 95% CI: 2.50, 4.80). Non-Hispanic White women (aOR = 0.70, 95% CI: 0.51, 0.97) and perinatal (pregnant or postpartum) women were less likely to have died by suicide (aOR = 0.27, 95% CI: 0.13, 0.58). CONCLUSIONS: Reproductive age women with mental health and/or substance use disorders, prior emergency department encounters, or who are of racial or ethnic minority status were at increased risk of suicide mortality and may benefit from routine screening and monitoring. Future research should further examine the relationship between pregnancy-related factors and suicide mortality.

Universal newborn genetic screening for pediatric cancer predisposition syndromes: model-based insights.

PURPOSE: Genetic testing for pediatric cancer predisposition syndromes (CPS) could augment newborn screening programs, but with uncertain benefits and costs. METHODS: We developed a simulation model to evaluate universal screening for a CPS panel. Cohorts of US newborns were simulated under universal screening versus usual care. Using data from clinical studies, ClinVar, and gnomAD, the presence of pathogenic/likely pathogenic (P/LP) variants in RET, RB1, TP53, DICER1, SUFU, PTCH1, SMARCB1, WT1, APC, ALK, and PHOX2B were assigned at birth. Newborns with identified variants underwent guideline surveillance. Survival benefit was modeled via reductions in advanced disease, cancer deaths, and treatment-related late mortality, assuming 100% adherence. RESULTS: Among 3.7 million newborns, under usual care, 1,803 developed a CPS malignancy before age 20. With universal screening, 13.3% were identified at birth as at-risk due to P/LP variant detection and underwent surveillance, resulting in a 53.5% decrease in cancer deaths in P/LP heterozygotes and a 7.8% decrease among the entire cohort before age 20. Given a test cost of $55, universal screening cost $244,860 per life-year gained; with a $20 test, the cost fell to $99,430 per life-year gained. CONCLUSION: Population-based genetic testing of newborns may reduce mortality associated with pediatric cancers and could be cost-effective as sequencing costs decline.

Randomized prospective evaluation of genome sequencing versus standard-of-care as a first molecular diagnostic test.

PURPOSE: To evaluate the diagnostic yield and clinical relevance of clinical genome sequencing (cGS) as a first genetic test for patients with suspected monogenic disorders. METHODS: We conducted a prospective randomized study with pediatric and adult patients recruited from genetics clinics at Massachusetts General Hospital who were undergoing planned genetic testing. Participants were randomized into two groups: standard-of-care genetic testing (SOC) only or SOC and cGS. RESULTS: Two hundred four participants were enrolled, 202 were randomized to one of the intervention arms, and 99 received cGS. In total, cGS returned 16 molecular diagnoses that fully or partially explained the indication for testing in 16 individuals (16.2% of the cohort, 95% confidence interval [CI] 8.9-23.4%), which was not significantly different from SOC (18.2%, 95% CI 10.6-25.8%, P = 0.71). An additional eight molecular diagnoses reported by cGS had uncertain relevance to the participant's phenotype. Nevertheless, referring providers considered 20/24 total cGS molecular diagnoses (83%) to be explanatory for clinical features or worthy of additional workup. CONCLUSION: cGS is technically suitable as a first genetic test. In our cohort, diagnostic yield was not significantly different from SOC. Further studies addressing other variant types and implementation challenges are needed to support feasibility and utility of broad-scale cGS adoption.

Integrating public preferences into national reimbursement decisions: a descriptive comparison of approaches in Belgium and New Zealand.

BACKGROUND: Public health care payer organizations face increasing pressures to make transparent and sustainable coverage decisions about ever more expensive prescription drugs, suggesting a need for public engagement in coverage decisions. However, little is known about countries' approaches to integrating public preferences in existing funding decisions. The aim of this study was to describe how Belgium and New Zealand used deliberative processes to engage the public and to identify lessons learned from these countries' approaches. METHODS: To describe two countries' deliberative processes, we first reviewed key country policy documents and then conducted semi-structured interviews with five leaders of the processes from Belgium and New Zealand. We assessed each country's rationales for and approaches to engaging the public in pharmaceutical coverage decisions and identified lessons learned. We used qualitative content analysis of the interviews to describe key themes and subthemes. RESULTS: In both countries, the national public payer organization initiated and led the process of integrating public preferences into national coverage decision making. Reimbursement criteria considered outdated and changing societal expectations prompted the change. Both countries chose a deliberative process of public engagement with a multi-year commitment of many stakeholders to develop new reimbursement processes. Both countries' new reimbursement processes put a stronger emphasis on quality of life, the separation of individual versus societal perspectives, and the importance of final reimbursement decisions being taken in context rather than based largely on cost-effectiveness thresholds. CONCLUSIONS: To face the growing financial pressure of sustainable funding of medicines, Belgium's and New Zealand's public payers have developed processes to engage the public in defining the reimbursement system's priorities. Although these countries differ in context and geographic location, they came up with overlapping lessons learnt which include the need for 1) political commitment to initiate change, 2) broad involvement of all stakeholders, and 3) commitment of all to engage in a long-term process. To evaluate these changes, further research is required to understand how coverage decisions in systems with and without public engagement differ.

Variation in patterns of health care before suicide: A population case-control study.

BACKGROUND: The United States has experienced a significant rise in suicide. As decision makers identify how to address this national concern, healthcare systems have been identified as an optimal location for prevention. OBJECTIVE: To compare variation in patterns of healthcare use, by health setting, between individuals who died by suicide and the general population. DESIGN: Case-Control Study. SETTING: Eight healthcare systems across the United States. PARTICIPANTS: 2674 individuals who died by suicide between 2000 and 2013 along with 267,400 individuals matched on time-period of health plan membership and health system affiliation. MEASUREMENTS: Healthcare use in the emergency room, inpatient hospital, primary care, and outpatient specialty setting measured using electronic health record data during the 7-, 30-, 60-, 90-, 180-, and 365-day time periods before suicide and matched index date for controls. RESULTS: Healthcare use was more common across all healthcare settings for individuals who died by suicide. Nearly 30% of individuals had a healthcare visit in the 7-days before suicide (6.5% emergency, 16.3% outpatient specialty, and 9.5% primary care), over half within 30 days, and >90% within 365 days. Those who died by suicide averaged 16.7 healthcare visits during the year. The relative risk of suicide was greatest for individuals who received care in the inpatient setting (aOR = 6.23). There was both a large relative risk (aOR = 3.08) and absolute utilization rate (43.8%) in the emergency room before suicide. LIMITATIONS: Participant race/ethnicity was not available. The sample did not include uninsured individuals. CONCLUSIONS: This study provides important data about how care utilization differs for those who die by suicide compared to the general population and can inform decision makers on targeting of suicide prevention activities within health systems.

The impact of the Orphan Drug Act on Food and Drug Administration-approved therapies for rare skin diseases and skin-related cancers.

The Orphan Drug Act of 1983 (ODA) put in place a set of financial and marketing incentives to stimulate the development of drugs to treat rare diseases, and since its passage, more than 600 orphan drug and biologic products have been brought to market in the United States. Rapid growth in orphan drug approvals in conjunction with high orphan drug prices have triggered concern that drug makers are exploiting certain aspects of the ODA for financial gain and that some pharmaceutical drugs are receiving orphan status where it is not warranted. The landscape of approved therapies for rare skin diseases has not been well described. In this article, we provide a descriptive analysis of the United States Food and Drug Administration-approved orphan drugs for the treatment of rare dermatologic conditions and skin-related cancers since the enactment of the ODA. We discuss policy issues that emerge from the analysis and suggest areas for future research. Next, we elucidate ODA loopholes using dermatologic drugs as examples and propose potential reforms. Finally, we consider future directions for orphan drug development in the field of dermatology.

High-Deductible Insurance and Delay in Care for the Macrovascular Complications of Diabetes.

Background: Little is known about the long-term effects of high-deductible insurance on care for chronic medical conditions. Objective: To determine whether a transition from low-deductible to high-deductible insurance is associated with delayed medical care for macrovascular complications of diabetes. Design: Observational longitudinal comparison of matched groups. Setting: A large national health insurer during 2003 to 2012. Participants: The intervention group comprised 33 957 persons with diabetes who were continuously enrolled in low-deductible (≤$500) insurance plans during a baseline year followed by up to 4 years in high-deductible (≥$1000) plans. The control group included 294 942 persons with diabetes who were enrolled in low-deductible plans contemporaneously with matched intervention group members. Intervention: Employer-mandated transition to a high-deductible plan. Measurements: The number of months it took for persons in each study group to seek care for their first major macrovascular symptom, have their first major diagnostic test for macrovascular disease, and have their first major procedure-based treatment was determined. Between-group differences in time to reach a midpoint event rate were then calculated. Results: No baseline differences were found between groups. During follow-up, the delay for the high-deductible group was 1.5 months (95% CI, 0.8 to 2.3 months) for seeking care for the first major symptom, 1.9 months (CI, 1.4 to 2.3 months) for the first diagnostic test, and 3.1 months (CI, 0.5 to 5.8 months) for the first procedure-based treatment. Limitation: Health outcomes were not examined. Conclusion: Among persons with diabetes, mandated enrollment in a high-deductible insurance plan was associated with delays in seeking care for the first major symptoms of macrovascular disease, the first diagnostic test, and the first procedure-based treatment. Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases.

The Mediating Effect of Sleep Disturbance on the Relationship Between Nonmalignant Chronic Pain and Suicide Death.

IMPORTANCE: Few studies have examined the relationship between nonmalignant chronic pain (NMCP) and suicide death, and even fewer have specifically explored what role sleep disturbance might play in the association between NMCP and suicide death. OBJECTIVE: To assess whether sleep disturbance mediates the relationship between NMCP and suicide death. DESIGN: This case-control study included 2,674 individuals who died by suicide between 2000 and 2013 (cases) and 267,400 matched individuals (controls). SETTING: Eight Mental Health Research Network (MHRN)-affiliated healthcare systems. PARTICIPANTS: All cases and matched controls were health plan members for at least 10 months during the year prior to the index date. MAIN OUTCOMES AND MEASURES: Sociodemographic data and diagnosis codes for NMCP and sleep disorders were extracted from the MHRN's Virtual Data Warehouse. Suicide mortality was identified using International Statistical Classification of Diseases and Related Health Problems (ICD)-10 codes from official government mortality records matched to health system records. RESULTS: After accounting for covariates, there was a significant relationship between NMCP and sleep disturbance; those who were diagnosed with NMCP were more likely to develop subsequent sleep disturbance. Similarly, sleep disturbance was significantly associated with suicide death. Finally, a significant indirect effect of NMCP on suicide death, through sleep disturbance, and a nonsignificant direct effect of NMCP on suicide death provide support for a fully mediated model. CONCLUSIONS AND RELEVANCE: There is a need for clinicians to screen for both sleep disturbance and suicidal ideation in NMCP patients and for health systems to implement more widespread behavioral treatments that address comorbid sleep problems and NMCP.

Survival outcomes for Australian women receiving trastuzumab for HER2-positive metastatic breast cancer following (neo)adjuvant trastuzumab: a national population-based observational study (2006-2014).

BACKGROUND: Patients treated with (neo)adjuvant trastuzumab who relapse and receive trastuzumab for metastatic breast cancer (MBC) are a growing population with little outcome data given their exclusion from most clinical trials. We aim to estimate survival outcomes for this trastuzumab 'pre-treated' population. METHODS: Population-based study of Australian women receiving trastuzumab for HER2-positive MBC between 2006 and 2014, who also received (neo)adjuvant trastuzumab. We used Kaplan-Meier methods to estimate the following: overall survival (OS) from initiation of trastuzumab for MBC; duration of trastuzumab for MBC; and time from last (neo)adjuvant trastuzumab to first trastuzumab for MBC. RESULTS: Of 3199 patients dispensed trastuzumab for MBC, 634 (20%) had received (neo)adjuvant traztuzumab. Pre-treated patients had a median (interquartile range) OS of 21.8 months (10.9-51.6), trastuzumab duration of 12.8 months (4.7-17.5), and time from last (neo)adjuvant trastuzumab to first trastuzumab for MBC of 15.6 months (6.5-28.6). Median OS for patients initiating trastuzumab <12 months and ⩾12 months from their last (neo)adjuvant trastuzumab were 17.1 months and 24.8 months, respectively. CONCLUSIONS: Patients starting trastuzumab for MBC following (neo)adjuvant trastuzumab had a median treatment duration of 1 year and OS of almost 2 years. These data help inform clinical practice and service planning for this under-researched population.

Long-term survival in trastuzumab-treated patients with HER2-positive metastatic breast cancer: real-world outcomes and treatment patterns in a whole-of-population Australian cohort (2001-2016).

PURPOSE: Patients treated with trastuzumab for HER2-positive metastatic breast cancer (HER2+MBC) are living longer, but there is little information on their outcomes and treatment experience beyond the median survival from clinical trials and real-world observational studies. We aim to describe the real-world treatment patterns and overall survival (OS) for women surviving five or more years from initiation of trastuzumab for HER2+MBC. METHODS: This is a retrospective, whole-of-population cohort study of women initiating trastuzumab for HER2+MBC between 2001 and 2011, followed to 2016. We defined long-term survivors (LTS) as those patients surviving ≥ 5 years from trastuzumab initiation. We used dispensing claims to describe timing of cancer treatments used by LTS and to estimate time on and off HER2-targeted therapies, and OS from trastuzumab initiation for HER2+MBC. RESULTS: Of 4177 women initiating trastuzumab for HER2+MBC, 1082 (26%) survived ≥ 5 years. Median age for LTS was 54 years (IQR 46-63). At a median follow-up of 9.4 years, 36% of LTS died; their conditional probability of surviving an additional 5 years was 55%. Median time on trastuzumab and all HER2-targeted therapy was 58.9 months (27.6-88.1) and 69.1 months (35.6-124.5), respectively. 85% of LTS had a period off HER2 therapy, lasting a median of 30.4 months (8.2-NR). CONCLUSIONS: LTS generally receive HER2-targeted therapies for periods of time longer than in clinical trials, but most LTS also had breaks in treatment. More research is needed to understand the effects of long-term treatment and to identify patients who may be able to safely discontinue HER2-targeted therapy.

Total and out-of-pocket expenditures among women with metastatic breast cancer in low-deductible versus high-deductible health plans.

PURPOSE: High-deductible health plan (HDHP) enrollment is expanding rapidly and might substantially increase out-of-pocket (OOP) payment burden. We examined trends in total and OOP health service expenditures overall and by insurance coverage type among women with metastatic breast cancer. METHODS: We used a longitudinal time series design to examine measures among 5364 women with metastatic breast cancer insured by a large US health insurer from 2004 to 2011. We measured outcomes during the 12 months after a first identified metastatic breast cancer diagnosis and required women to have at least 6 months of prior enrollment. We plotted enrollment measures and adjusted total and OOP spending. We fit trend lines using linear autoregressive models. RESULTS: Between 2004 and 2011, the percentage of women with metastatic breast cancer enrolled in employer-mandated HDHPs increased from 8 to 23% while the percentage enrolled in employer-mandated low-deductible plans (LDHPs) decreased from 69 to 37%. Over the same time period, estimated annual inflation-adjusted total health service spending among women with metastatic breast cancer whose employers only offered HDHPs or LDHPS increased from $96,899 to $104,688 (increase of $1197 per year; 95% confidence interval [CI]: $47,$2,348). Corresponding OOP spending values among these women with employer-mandated deductible levels were $4,496 and $5,151 ($91 per year trend; 95% CI -$13,$195). From 2004-2011, women in HDHPs and LDHPs had unchanged annual OOP spending, estimated at of $6642 (95% CI $6,268,$7016) and $4,247 (95% CI $3956,$4538), respectively. Thus, women in HDHPs experienced 55% (44%, 66%) more OOP spending than women in LDHP. CONCLUSIONS: OOP spending among women with metastatic breast cancer and employer-mandated deductible levels was 55% higher among HDHP than LDHP members, and employer-mandated HDHP enrollment increased substantially from 2004 to 2011. Stakeholders and policymakers should design health plans that protect financially vulnerable cancer patients from high OOP costs.

Impact of high-deductible insurance on adjuvant hormonal therapy use in breast cancer.

OBJECTIVE: High-deductible health plans (HDHPs) have become the predominant commercial health insurance arrangement in the US. HDHPs require substantial out-of-pocket (OOP) costs for most services but often exempt medications from high cost sharing. We examined effects of HDHPs on OOP costs and utilization of adjuvant hormonal therapy (AHT), which are fundamental care for patients with breast cancer. METHODS: This controlled quasi-experimental study used claims data (2003-2012) from a large national health insurer. We included 986 women with incident early-stage breast cancer, age 25-64 years, insured by employers that mandated a transition from low-deductible (≤ $500/year) to high-deductible (≥ $1000/year) coverage, and 3479 propensity score-matched controls whose employers offered only low-deductible plans. We examined AHT utilization and OOP costs per person-year before and after the HDHP switch. RESULTS: At baseline, the OOP costs for AHT were $40.41 and $36.55 per person-year among the HDHP and control groups. After the HDHP switch, the OOP costs for AHT were $91.76 and $72.98 per person-year among the HDHP and control groups, respectively. AHT OOP costs increased among HDHP members relative to controls but the change was not significant (relative change 13.72% [95% CI - 9.25, 36.70%]). AHT use among HDHP members did not change compared to controls (relative change of 2.73% [95% CI - 14.01, 19.48%]); the change in aromatase inhibitor use was - 11.94% (95% CI - 32.76, 8.88%) and the change in tamoxifen use was 20.65% (95% CI - 8.01, 49.32%). CONCLUSION: We did not detect significant changes in AHT use after the HDHP switch. Findings might be related to modest increases in overall AHT OOP costs, the availability of low-cost generic tamoxifen, and patient awareness that AHT can prolong life and health. Minimizing OOP cost increases for essential medications might represent a feasible approach for maintaining medication adherence among HDHP members with incident breast cancer.

A proposed approach to accelerate evidence generation for genomic-based technologies in the context of a learning health system.

Genomic technologies should demonstrate analytical and clinical validity and clinical utility prior to wider adoption in clinical practice. However, the question of clinical utility remains unanswered for many genomic technologies. In this paper, we propose three building blocks for rapid generation of evidence on clinical utility of promising genomic technologies that underpin clinical and policy decisions. We define promising genomic tests as those that have proven analytical and clinical validity. First, risk-sharing agreements could be implemented between payers and manufacturers to enable temporary coverage that would help incorporate promising technologies into routine clinical care. Second, existing data networks, such as the Sentinel Initiative and the National Patient-Centered Clinical Research Network (PCORnet) could be leveraged, augmented with genomic information to track the use of genomic technologies and monitor clinical outcomes in millions of people. Third, endorsement and engagement from key stakeholders will be needed to establish this collaborative model for rapid evidence generation; all stakeholders will benefit from better information regarding the clinical utility of these technologies. This collaborative model can create a multipurpose and reusable national resource that generates knowledge from data gathered as part of routine care to drive evidence-based clinical practice and health system changes.