Clinical characteristics and treatment patterns of patients with NTRK fusion-positive solid tumors: A multisite cohort study at US academic cancer centers.

BACKGROUND: Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare oncogenic drivers prevalent in 0.3% of solid tumors. They are most common in salivary gland cancer (2.6%), thyroid cancer (1.6%), and soft-tissue sarcoma (1.5%). Currently, there are 2 US Food and Drug Administration-approved targeted therapies for NTRK gene fusions: larotrectinib, approved in 2018, and entrectinib, approved in 2019. To date, the real-world uptake of tyrosine receptor kinase inhibitor (TRKi) use for NTRK-positive solid tumors in academic cancer centers remains largely unknown. OBJECTIVE: To describe the demographics, clinical and genomic characteristics, and testing and treatment patterns of patients with NTRK-positive solid tumors treated at US academic cancer centers. METHODS: This was a retrospective chart review study conducted in academic cancer centers in the United States. All patients diagnosed with an NTRK fusion-positive (NTRK1, NTRK2, NTRK3) solid tumor (any stage) and who received cancer treatment at participating sites between January 1, 2012, and July 1, 2023, were included in this study. Patient demographics, clinical characteristics, genomic characteristics, NTRK testing data, and treatment patterns were collected from electronic medical records and analyzed using descriptive statistics as appropriate. RESULTS: In total, 6 centers contributed data for 55 patients with NTRK-positive tumors. The mean age was 49.3 (SD = 20.5) years, 51% patients were female, and the majority were White (78%). The median duration of time from cancer diagnosis to NTRK testing was 85 days (IQR = 44-978). At the time of NTRK testing, 64% of patients had stage IV disease, compared with 33% at cancer diagnosis. Prevalent cancer types in the overall cohort included head and neck (15%), thyroid (15%), brain (13%), lung (13%), and colorectal (11%). NTRK1 fusions were most common (45%), followed by NTRK3 (40%) and NTRK2 (15%). Across all lines of therapy, 51% of patients (n = 28) received a TRKi. Among TRKi-treated patients, 71% had stage IV disease at TRKi initiation. The median time from positive NTRK test to initiation of TRKi was 48 days (IQR = 9-207). TRKis were commonly given as first-line (30%) or second-line (48%) therapies. Median duration of therapy was 610 (IQR = 182-764) days for TRKi use and 207.5 (IQR = 42-539) days for all other first-line therapies. CONCLUSIONS: This study reports on contemporary real-world NTRK testing patterns and use of TRKis in solid tumors, including time between NTRK testing and initiation of TRKi therapy and duration of TRKi therapy.

Potential of pharmacogenetics in minimizing drug therapy problems in cystic fibrosis.

BACKGROUND: With advancements in CF drug development, people with cystic fibrosis (PwCF) now take a median of seven medications daily, increasing treatment complexity, risk of drug therapy problems (DTPs), and interference with treatment goals. Given that some of these DTPs can be prevented with preemptive pharmacogenetic testing, the overall goal of this study was to test the clinical utility of a multi-gene pharmacogenetics (PGx) panel in potentially reducing DTPs in PwCF. METHODS: A population based retrospective study of patients with CF was conducted at the University of Utah Health Care System. The patients were genotyped for CYP450 enzymes using a pharmacogenomic assay, and their drug utilization information was obtained retrospectively. This pharmacogenomic information was combined with clinical guidelines to predict the number of actionable PGx interventions in this patient cohort. RESULTS: A total of 52 patients were included in this study. In the patient sample, a minimum of one order of actionable PGx medication was observed in 75 % of the cases. Results revealed that 4.2 treatment modifications per 10 patients can be enabled with the help of a PGx intervention in this patient population. Additionally, our findings suggest that polymorphisms in CYP2D6 and CYP2C19 are most likely to be the primary contributors to DTP's within PwCF. CONCLUSION: This study provides evidence that the PGx panel has the potential to help alleviate the clinical burden of DTPs in PwCF and can assist in informing pharmacotherapy recommendations. Future research should validate these findings and evaluate which subgroups of PwCF would most benefit from pharmacogenetic testing.

Addressing the Burden of Multiple Daily Insulin Injections in Type 2 Diabetes with Insulin Pump Technology: A Narrative Review.

The growing prevalence of type 2 diabetes (T2D) remains a leading health concern in the US. Despite new medications and technologies, glycemic control in this population remains suboptimal, which increases the risk of poor outcomes, increased healthcare resource utilization, and associated costs. This article reviews the clinical and economic impacts of suboptimal glycemic control in patients on basal-bolus insulin or multiple daily injections (MDI) and discusses how new technologies, such as tubeless insulin delivery devices, referred to as "patch pumps", have the potential to improve outcomes in patients with T2D.

The Association of Retinal Disease with Vision Impairment and Functional Status in Medicare Patients.

Background: The association of neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) with functional status in the general Medicare population are not well established. Objectives: This study examined patient-reported survey data linked with Medicare claims to describe the burden of these vision-threatening retinal diseases (VTRDs) among Medicare beneficiaries. Methods: Medicare Current Beneficiary Survey data linked with Medicare Fee-for-Service claims data from 2006 to 2018 were used in a nationally representative retrospective pooled cross-sectional population-based comparison study. Outcomes between community-dwelling beneficiaries with nAMD (n = 1228), DME (n = 101), or RVO (n = 251) were compared with community-dwelling beneficiaries without any VTRDs (n = 104 088), controlling for baseline demographic and clinical differences. Beneficiaries with a diagnosis of nAMD, DME, or RVO during the data year were included; those with other VTRDs were excluded. Outcomes included vision function and loss, overall functioning as assessed by difficulties with activities of daily living (ADLs) and instrumental ADLs (iADLs), anxiety/depression, falls, and fractures. Results: In patient cohorts with nAMD, DME, and RVO, approximately one-third (34.2%-38.3%) reported "a little trouble seeing" (vs 28.3% for controls), and 26%, 17%, and 9%, respectively, reported "a lot of trouble seeing/blindness" (vs 5% of controls). Difficulty walking and doing heavy housework were the most reported ADLs and iADLs, respectively. Compared with those without VTRDs, beneficiaries with nAMD had higher odds of diagnosed vision loss (odds ratio [OR], 5.39; 95% confidence interval, 4.06-7.16; P < .001) and difficulties with iADLs (odds ratio, 1.41; 95% confidence interval, 1.11-1.80; P = .005); no differences were observed for DME or RVO vs control. After adjusting for age, sex, race/ethnicity, poverty status, comorbidities, and other relevant covariates, nAMD, DME, and RVO were not significantly associated with anxiety/depression, falls, or fractures. Discussion: Patients with nAMD or DME were more likely to report severe visual impairment than those without VTRDs, although only those with nAMD were more likely to be diagnosed with vision loss. Conclusions: Patients with nAMD continue to experience more vision impairment and worse functional status compared with a similar population of Medicare beneficiaries despite availability of therapies like antivascular endothelial growth factor to treat retinal disease.

Gastrointestinal adverse effects associated with the use of intravenous oliceridine compared with intravenous hydromorphone or fentanyl in acute pain management utilizing adjusted indirect treatment comparison methods.

Background: In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. Aim: To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioid-induced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. Methods: A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. Results: A total of six randomized controlled trials (oliceridine - 2; hydromorphone - 3; fentanyl - 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was compared with hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. Conclusion: In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.

The impact of a statewide insulin copay cap policy for insured patients with diabetes in Utah.

BACKGROUND: Insulin affordability is a huge concern for patients with diabetes in the United States. On March 30, 2020, Utah signed House Bill 207 into law, aimed at capping copayments for insulin at $30 for a 30-day supply. The bill was enacted on January 1, 2021. OBJECTIVE: To assess patient basal insulin adherence, out-of-pocket costs, health plan costs, total costs on insulin, and hemoglobin A1c (A1c) in prepolicy vs postpolicy periods. METHODS: This study is a retrospective analysis using data from a regional health plan in Utah from October 1, 2019, to September 30, 2021. Inclusion criteria were fully enrolled members of all ages, under commercial insurance, with at least 1 fill for any type of insulin in both the preperiod and the postperiod. Adherence was measured by proportion of days covered (PDC). Paired t-tests and Wilcoxon sign rank tests were conducted to compare the health and economic outcomes. RESULTS: Out of 24,150 commercially insured individuals, a total of 244 patients were included. Across all 244 patients, there was a significant decline in monthly median out-of-pocket costs of insulin by 58.5% (P < 0.001), whereas the monthly median health plan costs of insulin increased by 22.0% (P < 0.001). The total monthly costs of insulin (the sum of out-of-pocket and health plan costs) were unchanged (P = 0.115). Only 74 patients with enough basal insulin fills in both periods were included in the analysis for PDC changes. PDC change was not statistically significant (P = 0.43). Among the 74 patients with PDC calculations, 29 patients had A1c recorded in both periods. The change in A1c was not statistically significant (P = 0.23). CONCLUSIONS: An insulin copayment max of $30 in Utah demonstrated lower patient out-of-pocket costs, subsidized by the health plan. PDC did not change, and HbA1c did not improve. An assessment of a longer period and on a larger population is needed.

The Utah Pharmacy Summit: Collaborating to Optimize Patient Care.

Pharmacy has evolved significantly over the past 20 years, despite advances in pharmacotherapy and the expanding scope of pharmacy practice, pharmacists have struggled to collaborate across disciplines to create improved processes that enable the best outcomes from these innovations. A lack of innovation at any part of the healthcare system could inhibit the progress of practice innovations thereby leading to suboptimal patient medication and health outcomes. The Utah Pharmacy Summit was held in late 2022 with the goal of promoting pharmacist collaboration and a unified pharmacist voice within the state. The success of the Summit leads us to encourage collaborative forums across the Globe.

Real-world evidence in the use of Bevacizumab in age-related macular degeneration (ArMD): a scoping review.

PURPOSE: Pharmacological treatments for age-related macular degeneration (ArMD) include anti-vascular endothelial growth factor therapies. Bevacizumab is used off-label, as it has no indication for ArMD. This study aims to identify and describe literature on real-world evidence of bevacizumab (originator or biosimilars) use in ArMD. METHODS: A scoping review was conducted in Medline, CINAHL and Embase databases. Studies published in English after September 2017, conducted in USA, including adults (≥ 18 years old) with ArMD who received treatment with bevacizumab for ArMD were included. The review was further limited to peer-reviewed observational studies that quantitatively analyze either clinical or patient-reported outcomes among patients treated with bevacizumab for ArMD. RESULTS: The search strategy retrieved 543 studies. After title and abstract screening, a total of 142 studies were selected for full-text review leading to a total of 12 studies qualifying for data charting. All were retrospective studies. Five (41.6%) of the studies had less than 500 eyes included in the analysis, and the rest had over a thousand eyes. All except one study reported clinical outcomes (visual acuity was the main outcome in 8 (66.6%) studies). There were 3 (25%) studies reporting adverse events of bevacizumab intravitreal injections. None of the studies specified using biosimilars for bevacizumab and none mentioned patient-reported outcomes. CONCLUSION: The lack of studies aiming to study the patient-reported outcomes as well as the use of biosimilars of bevacizumab in ArMD makes this field a potential for future research. The different exposures and times to follow-up make it difficult to compare results among the selected studies.

The implementation of value-based frameworks, clinical care pathways, and alternative payment models for cancer care in the United States.

BACKGROUND: Cancer treatment is a significant driver of rising health care costs in the United States, where the annual cost of cancer care is estimated to reach $246 billion in 2030. As a result, cancer centers are considering moving away from fee-for-service models and transitioning to value-based care models, including value-based frameworks (VBFs), clinical care pathways (CCPs), and alternative payment models (APMs). OBJECTIVE: To assess the barriers and motivations for using value-based care models from the perspectives of physicians and quality officers (QOs) at US cancer centers. METHODS: Sites were recruited from cancer centers in the Midwest, Northeast, South, and West regions in a 15/15/20/10 relative distribution. Cancer centers were identified based on prior research relationships and known participation in the Oncology Care Model or other APMs. Based on a literature search, multiple choice and open-ended questions were developed for the survey. A link to the survey was emailed to hematologists/oncologists and QOs at academic and community cancer centers from August to November 2020. Results were summarized using descriptive statistics. RESULTS: A total of 136 sites were contacted; 28 (21%) centers returned completed surveys, which were included in the final analysis. 45 surveys (23 from community centers, 22 from academic centers) were completed: 59% (26/44), 76% (34/45), and 67% (30/45) of physicians/QOs respondents had used or implemented a VBF, CCP, and APM, respectively. The top motivator for VBF use was "producing real-world data for providers, payers, and patients" (50% [13/26]). Among those not using CCPs, the most common barrier was a "lack of consensus on pathway choices" (64% [7/11]). For APMs, the most common difficulty was that "innovations in health care services and therapies must be adopted at the site's own financial risk" (27% [8/30]). CONCLUSIONS: The ability to measure improvements in cancer health outcomes was a large motivator for implementing value-based models. However, heterogeneity in practice size, limited resources, and potential increase in costs were possible barriers to implementation. Payers need to be willing to negotiate with cancer centers and providers to implement the payment model that will most benefit patients. The future integration of VBFs, CCPs, and APMs will depend on reducing the complexity and burden of implementation. DISCLOSURES :Dr Panchal was affiliated with the University of Utah at the time this study was conducted and discloses current employment with ZS. Dr McBride discloses employment with Bristol Myers Squibb. Dr Huggar and Dr Copher report employment, stock, and other ownership interests in Bristol Myers Squibb. The other authors have no competing interests to disclose. This study was funded by an unrestricted research grant from Bristol Myers Squibb to the University of Utah.

Cost-effectiveness of the tubeless automated insulin delivery system vs standard of care in the management of type 1 diabetes in the United States.

BACKGROUND: A tubeless, on-body automated insulin delivery (AID) system (Omnipod 5 Automated Insulin Delivery System) demonstrated improved glycated hemoglobin A1c levels and increased time in range (70 mg/dL to 180 mg/dL) for both adults and children with type 1 diabetes in a 13-week multicenter, single-arm study. OBJECTIVE: To assess the cost-effectiveness of the tubeless AID system compared with standard of care (SoC) in the management of type 1 diabetes (T1D) in the United States. METHODS: Cost-effectiveness analyses were conducted from a US payer's perspective, using the IQVIA Core Diabetes Model (version 9.5), with a time horizon of 60 years and an annual discount of 3.0% on both costs and effects. Simulated patients received either tubeless AID or SoC, the latter being defined as either continuous subcutaneous insulin infusion (86% of patients) or multiple daily injections. Two cohorts (children: <18 years; adults: ≥18 years) of patients with T1D and 2 thresholds for nonsevere hypoglycemia (nonsevere hypoglycemia event [NSHE] <54 mg/dL and <70 mg/dL) were considered. Baseline cohort characteristics and treatment effects of different risk factors for tubeless AID were sourced from the clinical trial. Utilities and cost of diabetes-related complications were obtained from published sources. Treatment costs were derived from US national database sources. Scenario analyses and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: Treating children with T1D with tubeless AID, considering an NSHE threshold of less than 54 mg/dL, brings incremental life-years (1.375) and quality-adjusted life-years (QALYs) (1.521) at an incremental cost of $15,099 compared with SoC, resulting in an incremental cost-effectiveness ratio of $9,927 per QALY gained. Similar results were obtained for adults with T1D assuming an NSHE threshold of less than 54 mg/dL (incremental cost-effectiveness ratio = $10,310 per QALY gained). Furthermore, tubeless AID is a dominant treatment option for children and adults with T1D assuming an NSHE threshold of less than 70 mg/dL compared with SoC. The probabilistic sensitivity analyses results showed that compared with SoC, in both children and adults with T1D, tubeless AID was cost-effective in more than 90% of simulations, assuming a willingness-to-pay threshold of $100,000 per QALY gained. The key drivers of the model were the cost of ketoacidosis, duration of treatment effect, threshold of NSHE, and definition of severe hypoglycemia. CONCLUSIONS: The current analyses suggest that the tubeless AID system can be considered a cost-effective treatment compared with SoC in people with T1D from a US payer's perspective. DISCLOSURES: This research was funded by Insulet. Mr Hopley, Ms Boyd, and Mr Swift are full-time Insulet employees and own stock in Insulet Corporation. IQVIA, the employer of Ms Ramos and Dr Lamotte, received consulting fees for this work. Dr Biskupiak is receiving research support and consulting fees from Insulet. Dr Brixner has received consulting fees from Insulet. The University of Utah has received research funding from Insulet. Dr Levy is a consultant with Dexcom and Eli Lilly and has received grant/research support from Insulet, Tandem, Dexcom, and Abbott Diabetes. Dr Forlenza conducted research sponsored by Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly. He has been speaker/consultant/advisory board member for Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly.

Caregiver survey in glioblastoma focused on cognitive dysfunction: development and results from a multicenter study.

Aim: To develop a cognitive dysfunction (CD) focused questionnaire to evaluate caregiver burden in glioblastoma. Materials & methods: The survey was developed from stakeholder consultations and a pilot study, and disseminated at eight US academic cancer centers. Caregivers self-reported caring for an adult with glioblastoma and CD. Results: The 89-item survey covered demographics, CD symptoms and caregiver burden domains. Among 185 caregivers, most were white, educated females and reported memory problems as the most common CD symptom. An exposure-effect was observed, with increase in number of CD symptoms significantly associated with greater caregiver burden. Conclusion: This questionnaire could guide caregiver interventions and be adapted for use longitudinally, in community cancer settings, and in patients with brain metastases.

Glioblastoma (GBM) is a very aggressive brain cancer. People who have GBM have trouble remembering things and are unable to do things they used to do. These changes can be very hard. Researchers are trying to better understand what it is like for people who take care of people with GBM (or caregivers). In this study, researchers created a new survey for caregivers. The survey included questions about what caregivers see happening in their loved one with GBM. Caregivers said that memory problems were common. Also, when the patient had more problems the caregiver had a harder time, too. Researchers hope to improve the survey and use it in the future for more studies.

Patient Perspectives on the Use of Digital Technology to Help Manage Cystic Fibrosis.

Background: Digital health technologies (DHTs) have shown potential to improve health outcomes through improved medication adherence in different disease states. Cystic fibrosis (CF) requires care coordination across pharmacies, patients, and providers. DHTs can potentially support patients, providers, and pharmacists in diseases like CF, where high medication burden can negatively impact patient quality of life and outcomes. Methods: In this prospective cohort study, a CF-specific mobile application (Phlo) was distributed to adults with CF who received care at the University of Utah Cystic Fibrosis Center, used an iPhone, and filled prescriptions through the University of Utah Specialty Pharmacy services. Participants were asked to use Phlo for 90 days with an optional 90-day extension period. Participants completed four surveys at baseline and after 90 days. Changes in patient-reported outcomes, adherence, clinical outcomes, and healthcare resource utilization from baseline to 90 days were tracked. Results: Phlo allowed users to track daily regimen activities, contact their care team, receive medication delivery reminders, and share progress with their healthcare team. A web-based dashboard allowed the care team to review reported performance scores from the app. Most patients (67%) said the app improved confidence in and motivation for continuing their regimen. The most important reported benefit of Phlo was having a single location to manage their whole routine. Conclusions: Phlo is a mobile health technology designed to help patients with CF manage their treatment regimen and improve patient-provider communication.

Understanding patient cost-sharing thresholds for diabetes treatment attributes via a discrete choice experiment.

BACKGROUND: The process used to prefer certain products across drug classes for diabetes is generally focused on comparative effectiveness and cost. However, payers rarely tie patient preference for treatment attributes to formulary management resulting in a misalignment of value defined by providers, payers, and patients. OBJECTIVES: To explore patients' willingness to pay (WTP) for the predetermined high-value and low-value type 2 diabetes mellitus (T2DM) treatments within a health plan. METHODS: A cross-sectional discrete choice experiment (DCE) survey was used to determine patient preference for the benefit, risk, and cost attributes of T2DM treatments. A comprehensive literature review of patient preference studies in diabetes and a review of guidelines and medical literature identified study attributes. Patients and diabetes experts were interviewed and instructed to identify, prioritize, and comment on which attributes of diabetes treatments were most important to T2DM patients. The patients enrolled in a health plan were asked to respond to the survey. A multinomial logit model was developed to determine the relative importance and the patient's WTP of each attribute. The patients' relative values based on WTPs for T2DM treatments were calculated and compared with the treatments by a health plan. RESULTS: A total of 7 attributes were selected to develop a web-based DCE questionnaire survey. The responses from a total of 58 patients were analyzed. Almost half (48.3%) of the respondents took oral medications and injections for T2DM. The most prevalent side effects due to diabetes medications were gastrointestinal (43.1%), followed by weight gain (39.7%) and nausea (32.8%). Patients were willing to pay more for treatments with proven cardiovascular benefit and for the risk reduction of hospitalization from heart failure. On the other hand, they would pay less for treatments with higher gastrointestinal side effects. Patients were willing to pay the most for sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide 1 receptor agonist agents and the least for dipeptidyl peptidase-4 inhibitors and thiazolidinediones. CONCLUSIONS: This study provides information to better align patient, provider, and payer preferences in both benefit design and value-based formulary strategy for diabetes treatments. A preferred placement of treatments with cardiovascular benefits and lower adverse gastrointestinal side effects may lead to increased adherence to medications and improved clinical outcomes at a lower overall cost to both patients and their health plan. DISCLOSURES: This study was supported by a grant from the PhRMA Foundation.

Cancer incidence in immunocompromised patients: a single-center cohort study.

BACKGROUND: Diminished immune defense plays an important role in cancer development. Cancer risk in immunocompromised patients may differ. Identifying individuals with elevated cancer risk can inform strategies for routine cancer screening. This study aimed to understand and compare cancer incidence and risk in three patient groups: recipients of solid organ transplant (SOT) or hematopoietic stem cell transplant (HSCT); diagnosis of primary or secondary immunodeficiency disorder (PID/SID); and recipients of tumor necrosis factor inhibitor (TNF-i) therapy. METHODS: This retrospective cohort study used the University of Utah Health System database and Huntsman Cancer Institute tumor registry. Patients aged ≥18 years with SOT/HSCT, PID/SID or ≥ 3 months of TNF-i therapy were included. The date of transplant, diagnosis of PID/SID, or 1st TNF-i medication order date was defined as the index date. We calculated cumulative cancer incidence by Kaplan-Meier method. A Cox-proportional hazard regression model with a stepwise variable selection process was used to identify independent risk factors associated with the time to onset of a new primary cancer. RESULTS: In total, 13,887 patients were included which comprised of 2982 (21%) SOT/HSCT, 7542 (54%) PID/SID and 3363 (24%) patients receiving TNF-i. The mean (SD) age ranged from 46.8 (15) years - 50.4 (18.2) years. The proportion of white patients ranged from 72.3-84.8%. The estimated cumulative cancer incidence was 11.5% in the SOT/HSCT cohort, 14.3% in the PID/SID cohort, and 8.8% in the TNF-i cohort. The multivariable model adjusted for age, benign in-situ disease, Charlson Comorbidity Index, hypertension/cardiovascular disease/end stage renal disease, gender, race/ethnicity, and renal cyst as significant risk factors. The adjusted hazard ratios for cancer development in SOT/HSCT and PID/SID cohorts compared to the TNF-i cohort over the full follow-up period were 1.57 (95% CI: 1.16-2.13) and 2.14 (95% CI: 1.65-2.77), respectively. CONCLUSION: A significantly increased risk of cancer was observed in PID/SID patients and SOT/HSCT patients compared to TNF-i patients. Age ≥ 50 years, male gender, and clinical comorbidities were additional factors impacting cancer risk. PID/SID and SOT/HSCT patients may benefit from more intensive cancer screening.

The Rise of Prescription Digital Therapeutics in Behavioral Health.

Medicine is evolving to incorporate digital technologies of all kinds-technologies that may improve patient health, reduce clinician workload, lower costs, reduce health disparities, and expand access to needed treatments. Prescription digital therapeutics (PDTs) are an emerging technology with particular potential. These are software-based treatments delivered on mobile devices that address the behavioral dimensions of many diseases and conditions. Unlike health and wellness apps, PDTs are rigorously evaluated for safety and effectiveness and are authorized by the US Food and Drug Administration (FDA). Nine PDTs are currently authorized to treat conditions such as substance use disorders, attention-deficit disorder, and chronic insomnia. The findings reported in two recent research papers published by Advances in Therapy related to use of PDTs for substance use disorder and opioid use disorder provide real-world evidence of clinical and cost effectiveness, strengthening the evidence base for these technologies and suggesting a role for these technologies in the efforts to help patients recover from these often-chronic and deadly conditions.

Advancing a managed care pharmacy research agenda: Generating real-world evidence to support US Food and Drug Administration Accelerated Approvals and improving benefit design to address health inequities.

To advance their research agenda, the Academy of Managed Care Pharmacy (AMCP) and the AMCP Foundation (AMCPF) invited a sample of AMCP membership to participate in focus groups and tasked them with developing tangible research aims for each of the top 2 previously identified AMCP/AMCPF research priorities: generating real-world evidence (RWE) to support US Food and Drug Administration (FDA) Accelerated Approvals and improving benefit design to address health inequities. The resulting research aims, which were further refined per feedback from additional stakeholders, will serve to guide requests for proposals for funding of specific research projects to address these top managed care priorities. Research aims identified by focus group participants related to generating RWE for FDA Accelerated Approvals include (1) creating a data survey tool for managed care to make RWE more readily available, (2) linking surrogate endpoints to meaningful clinical outcomes for drug development, and (3) improving patient outcomes by determining the optimal sequence of clinical pathways. Research aims identified by focus group participants related to improving benefit design to address health inequities include (1) identifying how the ability to navigate managed care benefit designs may impact inequities, (2) understanding the connection between health inequities and medication adherence, and (3) evaluating the impact of social determinants of health on medication affordability. DISCLOSURES: These proceedings were supported by Bridget Flavin, PharmD, Founder, Connected Content, Ltd. Connected Content, Ltd. received payment from AMCP for the preparation of this manuscript. Flavin is also an adjunct associate professor at the University of Florida College of Pharmacy. Diana Brixner received AMCP Foundation support of sabbatical to conduct this work, support of a medical writer to assist in putting the manuscript together, consulting fees from Millcreek Outcomes Group, Elevar, Sage, Haymarket, and AMCP funding of one trip to Alexandria, VA. This research and the development of this manuscript were funded by AMCP and the AMCP Foundation.

Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. study.

BACKGROUND: Tumor mutational burden (TMB) is a potential biomarker to predict tumor response to immuno-oncology agents in patients with metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A multi-site cohort study evaluated patients diagnosed with stage IV NSCLC between 2012 and 2019 who had received comprehensive genomic profiling (CGP) and any NSCLC-related treatment at 9 U.S. cancer centers. Baseline characteristics and clinical outcomes were compared between patients with TMB <10 and TMB ≥10. RESULTS: Among the 667 patients with CGP results, most patients received CGP from Foundation Medicine (64%) or Caris (20%). Patients with TMB ≥10 (vs. TMB <10) were associated with a positive smoking history. TMB was associated with ALK (p = 0.01), EGFR (p < 0.01), and TP53 (p < 0.05) alterations. TMB >10 showed a significant association towards longer overall survival (OS) (HR: 0.43, 95% CI: 0.21-0.88, p = 0.02) and progression-free survival (PFS) (HR: 0.43, 95% CI: 0.21-0.85, p = 0.02) in patients treated with first-line immunotherapy and tested by Foundation Medicine or Caris at treatment initiation. CONCLUSIONS: TMB levels greater than or equal to 10 mut/Mb, when tested by Foundation Medicine or Caris at treatment initiation, were significantly associated with improved OS and PFS among patients treated with first-line immunotherapy-containing regimens. Additional prospective research is warranted to validate this biomarker along with PD-L1 expression.

Caregiver burden by treatment and clinical characteristics of patients with glioblastoma.

BACKGROUND: Glioblastoma is an incurable disease with a poor prognosis. For caregivers of people with glioblastoma, the burden of care can be high. Patients often present with different clinical characteristics, which may impact caregiver burden in different ways. This study aimed to evaluate associations between patient clinical characteristics and caregiver burden/quality of life (QoL). METHODS: Caregiver-patient dyads were enrolled at 7 academic cancer centers in the United States. Eligible caregiver participants were self-reported as the primary caregiver of an adult living with glioblastoma and completed a caregiver burden survey. Eligible patients were age ≥ 18 years at glioblastoma diagnosis and alive when their respective caregiver entered the study, with the presence of cognitive dysfunction confirmed by the caregiver. Data were analyzed with descriptive statistics and multivariable analyses. RESULTS: The final cohort included 167 dyads. Poor patient performance status resulted in patient difficulty with mental tasks, more caregiving tasks, and increased caregiving time. Language problems were reported in patients with left-sided lesions. Patient confusion was negatively associated with all caregiver domains: emotional health, social health, general health, ability to work, confidence in finances, and overall QoL. Better caregiver QoL was observed in patients with frontal lobe lesions versus non-frontal lobe lesions. CONCLUSION: This study reinforced that patient performance status is a critical clinical factor that significantly affects caregiver burden, caregiving tasks, and caregiver time. Additionally, patient confusion affects multiple facets of caregiver burden/QoL. These results could be used to support guided intervention for caregiver support, customized to the patient experience.