Decision Resources Group Research Articles

Real-world evidence study on the impact of SPECT MPI, PET MPI, cCTA and stress echocardiography on downstream healthcare utilisation in patients with coronary artery disease in the US.

Coronary artery disease (CAD) is associated with a large clinical and economic burden. However, consensus on the optimal approach to CAD diagnosis is lacking. This study sought to compare downstream healthcare resource utilisation following different cardiac imaging modalities, to inform test selection for CAD diagnosis. Claims and electronic health records data from the Decision Resources Group Real-World Evidence US Data Repository were analysed for 2.5 million US patients who underwent single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI), positron emission tomography myocardial perfusion imaging (PET MPI), coronary computed tomography angiography (cCTA), or stress echocardiography between January 2016 and March 2018. Patients were stratified into nine cohorts based on suspected or existing CAD diagnosis, pre-test risk, and prior events or interventions. Downstream healthcare utilisation, including additional diagnostic imaging, coronary angiography, and cardiac-related health system encounters, was compared by cohort and index imaging modality. Among patients with suspected CAD diagnosed within 3 months of the index test, PET MPI was associated with lower downstream utilisation; 25-37% of patients who underwent PET MPI required additional downstream healthcare resources compared with 40-49% of patients who received SPECT MPI, 35-41% of patients who underwent cCTA, and 44-47% of patients who received stress echocardiography. Patients who underwent PET MPI experienced fewer acute cardiac events (5.3-9.4%) and generally had lower rates of healthcare encounters (0.8-4.1%) and invasive coronary angiography (ICA, 15.4-24.2%) than those who underwent other modalities. SPECT MPI was associated with more downstream ICA (31.3-38.2%) and a higher rate of cardiac events (9.5-13.2%) compared with PET MPI (5.3-9.4%) and cCTA (6.9-9.9%). Across all cohorts, additional diagnostic imaging was 1.6 to 4.7 times more frequent with cCTA compared with PET MPI. Choice of imaging modality for CAD diagnosis impacts downstream healthcare utilisation. PET MPI was associated with lower utilisation across multiple metrics compared with other imaging modalities studied.

Real-world analyses of mortality risk after androgen deprivation therapy initiation in Black vs. White patients with prostate cancer.

84 Background: 2 studies found significantly longer overall survival in Black vs. White patients with metastatic castration-resistant prostate cancer (PCa): a 2019 meta-analysis of 9 phase III trials and a 2020 registry study. Our real-world data study compared all-cause mortality risk for Black vs. White PCa patients. Compared to the prior studies, our study encompasses a broader scope and is not exclusive to men with castration-resistant PCa. Methods: Data were collected from the Decision Resources Group Real World Evidence repository, which links medical and prescription claims, and US Electronic Healthcare Records. The analysis set included PCa patients who received ≥1 androgen deprivation therapy (ADT) injection between 1991-2020. Cox regression was used to compare all-cause mortality rates between White and Black patients. Multivariable regression model accounted for the following variables: baseline metastasis, BMI, oncology vs. urology setting, antagonist vs. agonist, personal major adverse cardiovascular event (MACE) history, tobacco history, baseline PSA (>4 vs. ≤4 ng/mL), race (White vs. Black), statin use, increasing age per year, ethnicity (non-Hispanic vs. Hispanic), increasing ADT exposure per year, diabetes, hypertension, and family MACE history. Results: 44,439 patients were included for the all-patient analyses. 34,762 patients were included in the Black vs White analyses: 5,817 and 28,945 were Black and White, respectively. Overall, mortality risk was 2.6% and 17% at 1 and 4 years after ADT initiation, respectively. Mortality risk after ADT initiation was 1.6% and 2.6% at 1 year and 11.7% and 18.1% at 4 years for Black and White patients, respectively. Both unadjusted (HR=1.66, 95% CI 1.53-1.80, p<0.05) and adjusted (HR=1.24, 95% CI 1.01-1.52, p<0.05) mortality risks were higher for White vs. Black patients. Conclusions: All-cause mortality incidence was higher in White vs. Black patients. Adding to the body of evidence, our research also reveals that Black race is associated with a protective effect on survival for all-cause mortality in men undergoing ADT. Potential hypotheses for higher mortality in White vs. Black patients include survival bias to MACE (i.e., Black patients may have died from PCa before having MACE), survival bias to be diagnosed with PCa (i.e., Black patients may have higher rate of CV death and kidney failure prior to PCa diagnosis), and protective effects of higher BMI in Black patients against cancer cachexia. The large size (~45,000 patients from a database with >300 million patients), long follow-up (10 years for some patients), recent clinical experience (99% from 2010-2020), and diversity of the dataset give weight to the results being an accurate representation of current clinical experience. Future studies should confirm our findings that White PCa patients have higher mortality risk and investigate the above hypotheses.

Patient Demographics and Major Adverse Cardiovascular Events after Androgen Deprivation Therapy for Prostate Cancer.

The association between patient demographics and CV events after ADT using real-world data was evaluated. In addition to encompassing >30 times more patients than all previous MACE studies, this is the first study, to the best of our knowledge, to include a comprehensive listing of many demographic factors from one large, recent US dataset over a long period of time. The retrospective analysis of data in the Decision Resources Group (now Clarivate) Real World Evidence repository, representing >300M US patients from 1991 to 2020 across all US regions, was performed. Patients with PCa receiving ≥1 ADT injection were included. MACE risk after ADT initiation was evaluated for demographic and potential PCa-related risk factors. Kaplan-Meier survival curves were constructed, and Cox regression was used to evaluate the association between MACE risk and demographic/PCa-related risk factors. Overall, MACE risk was slightly lower in the first year after ADT initiation (3.9%) vs. years 2-4 (∼5.2%). In a multivariate Cox model, MACE risk after ADT initiation was significantly higher for older vs. younger patients (adjusted HR per increasing year = 1.08, 95% CI: 1.07-1.09), men with a history of MACE vs. without (HR = 2.22, 95% CI: 1.72-2.88), men with very low BMI vs. normal or high BMI (HR for decreasing BMI per kg/m2 = 1.02, 95% CI: 1.01-1.03), White vs. Black patients (HR = 1.30, 95% CI: 1.08-1.55), and patients who did not use statins vs. those who did (HR = 1.13, 95% CI: 1.00-1.27). Of the PCa-related risk factors, MACE risk after ADT initiation was significantly higher for oncology vs. urology treatment setting (HR = 2.47, 95% CI: 2.12-2.88), patients with baseline metastasis vs. those without (HR = 2.30, 95% CI: 1.72-3.07), and patients treated with antagonists vs. agonists (HR = 1.62, 95% CI: 1.25-2.10). Demographic factors are important contributors to increased MACE risk for men with PCa on ADT. Clinicians should monitor risk factors and modify if possible.

Cardiovascular Risk in Prostate Cancer Patients Using Luteinizing Hormone-Releasing Hormone Agonists or a Gonadotropin-Releasing Hormone Antagonist.

Luteinizing hormone-releasing hormone (LHRH) agonists are believed to have higher cardiovascular risk relative to gonadotropin-releasing hormone (GnRH) antagonists. However, previous studies have not consistently demonstrated this. We used real-world clinical practice data to evaluate differences in major adverse cardiovascular events (MACE) risk between LHRH agonists compared to a GnRH antagonist following androgen deprivation therapy (ADT) initiation. We performed a retrospective analysis of data in the Decision Resources Group (now Clarivate) Real World Evidence repository, which represents >300 million US patients from 1991 to 2020 across all US regions. Patients with prostate cancer who received at least 1 injection of ADT were included. The risks of MACE and all-cause mortality as independent endpoints were evaluated, Kaplan-Meier curves were constructed, and associations between MACE and all available confounding risk factors were evaluated by Cox regression analysis using Statistical Package for the Social Sciences. A total of 45,059 men with prostate cancer treated with ADT were analyzed. Overall, the risks of MACE and all-cause mortality were slightly lower in the first year after ADT initiation compared to subsequent years. MACE risk was higher for the GnRH antagonist compared to LHRH agonists (HR=1.62; 95% CI 1.21-2.18, P = .001). The risk of all-cause mortality was also higher for the GnRH antagonist vs LHRH agonists (HR=1.87; 95% CI 1.39-2.51, P < .001). The adjusted incidence of MACE was higher for men treated with the GnRH antagonist compared to the LHRH agonists. The demographic and risk factors with the greatest impact on MACE risk were higher age, baseline metastasis, oncology (vs urology) setting, personal MACE history, antagonist (vs agonist), tobacco history, White (vs Black) race, and lower BMI.

Device use trends in neuroendovascular procedures in the United States from 2015 to 2020.

Neuroendovascular therapies involve an everchanging landscape of new technologies. Understanding the real-world timeframe of adaptation of such technologies can provide further guidance on mechanisms that could be employed to shorten the duration necessary for the widespread use of proven therapies. In this study, we aim to investigate the trends in the use of neuroendovascular technologies, utilizing the sales of neuroendovascular devices, as a proxy for procedural volume. Utilizing a device sales data registry from the Decision Resources Group, a healthcare research and consulting company, we examined trends in the sales of devices utilized in cerebrovascular thrombectomy, cerebral aneurysm treatment, and carotid stenting from the same 407 reporting hospitals in the United States between January 1, 2015, and January 1, 2020. Device sales per year were plotted as both the total number of devices sold per year as well as the percent of total device sales when compared against at least one other device. The Cochran-Armitage test for trend was performed when comparing at least two devices to each other. Analyses were performed using RStudio Version 1.1.456 (https://rstudio.com). Between 2015 and 2020, there was a significant increase in the use of flow-diverting stents as well as nondiverting stents utilized for coil assistance. However, the total number of coils utilized over the years has declined. In terms of stroke therapy, between 2015 and 2020, there was a trend of increased use of both aspiration catheters as well as stent retrievers, which plateaued in 2020. The number of stents used for carotid procedures has also been gradually increasing over time. Our study demonstrates an increase in the use of flow-diverting stents, nondiverting stents, carotid stents, and reperfusion devices for acute ischemic stroke intervention between 2015 and 2020. Coil use for aneurysmal treatment has declined.

Characteristics, Conditions, and Healthcare Service Utilization Patterns of Individuals Diagnosed with Rett Syndrome: An Analysis of Administrative Claims Data

Aim: To date, no studies have used a commercially available claims dataset to examine the characteristics, conditions, and healthcare service utilization of individuals with Rett syndrome. Objective: To improve understanding of the Rett population using data available to health insurance plans. Methods: Data were integrated medical and pharmacy claims from the Real-World Evidence data repository licensed from the Decision Resources Group. Individuals had claims for &gt;2 visits which included a diagnosis of Rett and were stratified into three age groups: 1 (&lt;5 years), 2 (&gt;5 and &lt;10 years) and 3 (&gt;10 years). Co-occurring conditions and healthcare service utilization were measured. Diagnoses prior to Rett were evaluated. Results: Most were female. Epilepsy, incontinence, and scoliosis were common co-occurring conditions. Individuals averaged 4.6 office and 2.5 outpatient visits, and 2.1 emergency and 2.9 inpatient admissions. Group 1 used more physical, occupational and speech therapy and averaged more inpatient days compared with others (p &lt; 0.05). Conclusion: This study improves understanding of Rett using data that is typically available to health insurance companies.

Characteristics and key differences between patient populations receiving imaging modalities for coronary artery disease diagnosis in the US

BackgroundThere are limited data on the impact of imaging modality selection for the assessment of coronary artery disease (CAD) risk on downstream resource utilisation. This study sought to identify differences between patient populations in the US undergoing stress echocardiography, single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), positron emission tomography (PET) MPI, and coronary computed tomography angiography (cCTA) for the assessment of CAD risk, and associated physician referral patterns.MethodsClaims and electronic health records data for 2.5 million US patients who received stress echocardiography, cCTA, SPECT MPI or PET MPI between January 2016 and March 2018, from the Decision Resources Group Real-World Evidence US Data Repository, were analysed. Patients were stratified into suspected and existing CAD cohorts, and further stratified by pre-test risk and presence and recency of interventions or acute cardiac events (within 1–2 years pre-index test). Linear and logistic regression were used to compare numeric and categorical variables.ResultsPhysicians were more likely to refer patients to standalone SPECT MPI (77%) and stress echocardiography (18%) than PET MPI (3%) and cCTA (2%). Overall, 43% of physicians referred more than 90% of their patients to standalone SPECT MPI. Just 3%, 1% and 1% of physicians referred more than 90% of their patients to stress echocardiography, PET MPI or cCTA. At the aggregated imaging level, patients who underwent stress echocardiography or cCTA had similar comorbidity profiles. Comorbidity profiles were also similar for patients who underwent SPECT MPI and PET MPI.ConclusionMost patients underwent SPECT MPI at the index date, with very few undergoing PET MPI or cCTA. Patients who underwent cCTA at the index date were more likely to undergo additional imaging tests compared with those who underwent other imaging modalities. Further evidence is needed to understand factors influencing imaging test selection across patient populations.

A Retrospective Real-World Evidence Evaluation of the Characteristics of Exocrine Pancreatic Insufficiency in Patients With Chronic Pancreatitis and Type 2 Diabetes Treated With Pancrelipase in the United States.

This retrospective real-world data analysis assessed clinical/health care professional characteristics of gastrointestinal symptom profiles in pancrelipase-treated patients with exocrine pancreatic insufficiency symptoms and chronic pancreatitis (CP) or type 2 diabetes (T2D). Data were from the Decision Resources Group Real-World Evidence Data Repository US database. Patients 18 years and older receiving pancrelipase (Zenpep) between index dates August 2015 and June 2020 were included. Gastrointestinal symptoms were assessed 6, 12, and 18 months post-index versus baseline. A total of 10,656 pancrelipase-treated patients with CP (n = 3215) or T2D (n = 7441) were identified. Significant/sustained reductions in gastrointestinal symptoms were observed in both cohorts after pancrelipase treatment (P < 0.001) versus baseline. Significantly fewer patients with CP compliant with treatment for more than 270 days (n = 1553) reported abdominal pain (P < 0.001) and nausea/vomiting (P < 0.05) versus those compliant for less than 90 days (n = 1115). Significantly fewer patients with T2D compliant with treatment for more than 270 days (n = 2964) reported abdominal pain (P < 0.001) and diarrhea/steatorrhea (P < 0.05) versus those compliant for less than 90 days (n = 2959). Pancrelipase reduced exocrine pancreatic insufficiency symptoms in patients with CP or T2D, with greater treatment compliance associated with improved gastrointestinal symptom profiles.

Persistence with macitentan versus other endothelin receptor antagonists in patients with pulmonary arterial hypertension: experience from a real-world data repository in the USA

Abstract Background Pulmonary arterial hypertension (PAH) is a progressive and fatal disease and as such, it is imperative that patients remain on therapy to delay progression and maintain functional status. Previous research has demonstrated differences in overall survival in the real-world by endothelin receptor antagonists (ERA) treatments with a lower risk of death with macitentan than ambrisentan and bosentan. However, real-world data on persistence to ERAs are limited. Purpose To compare persistence to macitentan versus ambrisentan and bosentan) in patients with PAH. Methods This retrospective, non-interventional, observational study identified patients between 10/21/2013–3/31/2021 (study period) from the Decision Resources Group (DRG) Real World Data Repository. The repository links medical and prescription claims from commercial, Medicaid, and Medicare plans with electronic health records (EHRs) to provide longitudinal patient-level data representative of over 300 million patients in the US. Patients selected must have been dispensed an ERA prescription from 4/14/14–3/31/20 AND 1) either an inpatient diagnosis of pulmonary hypertension (PH), or 2) a right heart catheterization with any PH diagnosis, or 3) were taking a phosphodiesterase 5 inhibitor (PDE5i). The primary outcome was persistence defined by time from index to drug discontinuation (90-day gap after the end of the last prescription's days of supply). Descriptive analysis comprised means, standard deviations, medians, and interquartile ranges for continuous variables and frequencies and percentages for categorical variables. Three-sample proportion tests were conducted at baseline to detect differences between the three cohorts and identify potentially confounding variables. Hazard ratios (HR) for pairwise comparisons (macitentan vs ambrisentan; macitentan vs bosentan) were calculated using an inverse probability of treatment weighting (IPTW)-adjusted Cox proportional regression model, to adjust for potential confounders (see Table 1) of the probability of receiving a specific ERA. Data were analyzed by Kaplan-Meier method. Results A total of 4,526 patients were included, of whom 1,205 received macitentan, 2,592 received ambrisentan and 729 received bosentan. Study population characteristics were representative of a general PAH population (Table 1). Unadjusted Kaplan-Meier analysis showed that median persistence was shortest for ambrisentan (12.6 months) followed by bosentan (13.6 months) and greatest for macitentan (15.8 months; overall log-rank p-value: 0.061). Compared to macitentan, patients on other ERAs had a greater risk of discontinuation: ambrisentan (10%) and bosentan (18%) (Table 2). Conclusions Persistence to therapy was significantly greater for macitentan-treated patients than in those receiving ambrisentan or bosentan. Further research examining variability in key sub-groups as well as the impact of improved persistence on long-term outcomes is warranted. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Janssen Scientific Affairs, LLC

Disease Progression Stages and Burden in Patients with Duchenne Muscular Dystrophy Using Administrative Claims Supplemented by Electronic Medical Records.

This study aims to identify stages of Duchenne muscular dystrophy (DMD) and assess the disease burden by progression stage using real-world administrative claims supplemented by relevant electronic medical record (EMR) data. Claims and EMR data from the Decision Resources Group's Real World Data Repository (2011-2020) were used to identify patients with DMD by diagnosis code and to stratify them into four disease stages by diagnosis and procedure markers reflective of DMD progression. Clinical and medical history data from the Cooperative International Neuromuscular Research Group (CINRG) were used to validate the developed claims-based staging algorithm. The distribution and drivers by disease stage, as well as disease burden, were examined. A total of 938 (94%) of patients with DMD identified in claims/EMR data had sufficient information for stage classification. Patients were classified by stage based on patient characteristics and the presence or absence of progression markers such as genetic testing, wheelchair usage, scoliosis treatment, or ventilation assistance. Average ages at stages1-4 are 7, 13, 18, and 23years, respectively. Using natural history data, the claims-based staging algorithm was validated with high sensitivity and specificity rates. Both healthcare resource utilization and medical charges increased by stage. For example, the average annualized total charges were $17,688 (stage1), $36,868 (stage2), $72,801 (stage3), and $167,285 (stage4). Large-scale claims data supplemented by EMR data can be used to characterize DMD progression and evaluate disease burden which may inform the design of future real-world studies about DMD.

Real-world assessment of the relationship between migraine-related disability and healthcare costs in the United States.

ObjectiveThe objective of this study was to determine the associations among migraine disability assessment scores, healthcare resource utilization (HCRU; medical visits and pharmacy use) and direct medical costs among people with episodic migraine in a real‐world setting.BackgroundMigraine is a public health concern associated with a substantial economic burden in the United States. However, the association between migraine disability and direct medical costs among people with migraine is unknown.MethodThis retrospective, cohort study used claims and electronic health record data from the Decision Resources Group database. Adults with migraine with or without aura, defined by International Classification of Disease Revision 9 (ICD‐9) or ICD Revision 10 (ICD‐10) codes, and a completed Migraine Disability Assessment Scale (MIDAS) questionnaire from January 2016 to December 2018 were included (chronic migraine codes not included). The associations of MIDAS score with the cost of HCRU for the 6 months after MIDAS assessment were explored. Results were stratified by treatment setting.ResultsAmong 7662 included patients, MIDAS scores were distributed as: 3348 (43.7%; I, little/none), 1107 (14.4%; II, mild), 1225 (16.0%; III, moderate), 893 (11.7%; IVa, severe), and 1089 (14.2%; IVb, very severe). Worsening disability was associated with higher medical costs (adjusted from a multivariable model). In the primary care setting, healthcare visit costs were $206 (95% confidence interval: $144–294) for grade I and $631 ($384–1036) for grade IVb patients; corresponding pharmacy costs were $203 (grade I; $136–301) and $719 (grade IVb; $410–1259). For specialty care (e.g., neurologist), healthcare visits cost $509 ($411–629) for grade I and $885 ($634–1236) for grade IVb patients; corresponding pharmacy costs were $494 (grade I; $378–645) and $1020 (grade IVb; $643–1620).ConclusionHigher levels of migraine‐related disability (MIDAS assessed) are associated with increased HCRU costs among Americans with episodic migraine. Migraine disability assessment could be useful in the development, testing, and prescription of cost‐effective treatments for people with high migraine‐related disability.

Real-World Analysis of Weight Gain and Body Mass Index Increase Among Patients with HIV-1 Using Antiretroviral Regimen Containing Tenofovir Alafenamide, Tenofovir Disoproxil Fumarate, or Neither in the United States.

Background: While some studies among patients with HIV-1 suggest that antiretroviral therapy (ART) regimens containing tenofovir alafenamide (TAF) may be associated with greater weight gain than those not containing TAF, no studies have assessed the relationship between TAF doses and weight change. Objectives: To evaluate weight-related outcomes among patients with HIV-1 in the United States initiating ART containing different nucleoside reverse transcriptase inhibitors and doses. Methods: A retrospective longitudinal study was conducted using Decision Resources Group’s electronic medical records (July 17, 2017-March 1, 2020). Adult patients with HIV-1 initiating ART (index date) containing TAF 25 mg, TAF 10 mg, tenofovir disoproxil fumarate (TDF), or neither TAF nor TDF on or after July 17, 2018, were included. Changes in weight and body mass index (BMI) from pre-index to 3, 6, 9, and 12 months post-index were compared between cohorts using mean differences obtained from ordinary least squares models adjusted for baseline characteristics. Time-to-weight and BMI increase ≥5% were compared using Cox models adjusted for baseline characteristics. Results: Among 1652 eligible patients (TAF 25 mg, n=710; TAF 10 mg, n=303; TDF, n=219; non-TAF/TDF, n=420), the majority (83.2%-99.5%) initiated an integrase strand transfer inhibitor, except for the TDF cohort (45.2%). Patients initiating TAF 25 mg had greater weight or BMI increase across all time points compared with patients initiating TAF 10 mg, TDF, or non-TAF/TDF regimens (mean differences in weight or BMI changes between cohorts at 12 months post-index ranged from 0.78 kg [1.72 lb] to 1.34 kg [2.95 lb] and from 0.77 kg/m2 to 1.95 kg/m2, respectively), although findings were not statistically significant for all comparisons. Compared with TAF 25 mg, time-to-weight and BMI increase ≥5% in the other treatment cohorts were longer (hazard ratios ranged from 0.77 to 0.94), although findings were generally not statistically significant. Conclusions: Among a population of patients predominantly initiating integrase strand transfer inhibitors, increases in weight and BMI post-ART initiation were common and appeared to be higher and occur more rapidly among patients receiving TAF 25 mg compared with lower TAF doses or other nucleosides. When considering long-term health consequences, weight gain is an important factor to consider when selecting an ART regimen.

Body mass index increase and weight gain among people living with HIV-1 initiated on single-tablet darunavir/cobicistat/emtricitabine/tenofovir alafenamide or bictegravir/emtricitabine/tenofovir alafenamide in the United States

Objective This study evaluated body mass index (BMI) and weight changes in people living with human immunodeficiency virus (HIV-1; PLWH) initiated on single-tablet darunavir/cobicistat/emtricitabine/tenofovir alafenamide (DRV/c/FTC/TAF) or bictegravir/FTC/TAF (BIC/FTC/TAF). Methods Electronic medical records (EMR) data for treatment-naïve or virologically suppressed adults with HIV-1 who initiated treatment with DRV/c/FTC/TAF or BIC/FTC/TAF (index date) were obtained from Decision Resources Group’s EMR (7/17/2017–3/1/2020). Inverse probability of treatment weighting was used to account for differences in baseline characteristics between the two cohorts. BMI and weight changes from pre-index to 3, 6, 9, and 12 months following the index date were compared using weighted mean differences (MDs). The time until an increase in BMI or weight ≥5% or ≥10% was compared using weighted hazard ratios (HRs). Results The weighted DRV/c/FTC/TAF and BIC/FTC/TAF cohorts comprised 1,116 and 1,134 PLWH, respectively (mean age=∼49 years, females: ∼28%). Larger increases in BMI and weight from pre-index to each post-index time points were observed in PLWH initiating BIC/FTC/TAF vs DRV/c/FTC/TAF (12 months: MD in BMI =1.23 kg/m2, p < 0.001; MD in weight =2.84 kg [6.26 lbs], p = 0.008). PLWH receiving BIC/FTC/TAF were significantly more likely to experience weight gain ≥5% (HR =1.76, p = 0.004) and ≥10% (HR =2.01, p = 0.020) and BMI increase ≥5% (HR =1.77, p = 0.004) and ≥10% (HR =1.76, p = 0.044) than those receiving DRV/c/FTC/TAF. Conclusions BIC/FTC/TAF was associated with greater BMI and weight increases compared to DRV/c/FTC/TAF. Weight gain and its sequelae may add to the clinical burden of PLWH and should be considered among other factors when selecting antiretroviral single-tablet regimens.

Real-World Patient Characteristics, Treatment Patterns and Outcomes for Patients with Atypical Hemolytic Uremic Syndrome Who Have Switched from Eculizumab to Ravulizumab in the USA

IntroductionAtypical hemolytic uremic syndrome (aHUS) is a rare disease that can cause irreversible organ damage or death. Ravulizumab is a long-acting complement C5 inhibitor approved in the USA, Europe, and Japan for the treatment of aHUS. Ravulizumab was engineered from eculizumab to leverage its clinical benefits and safety profile while reducing dosing frequency. This study assessed real-world patient characteristics, treatment patterns, and clinical outcomes for adult and pediatric patients with aHUS in the USA who switched from eculizumab to ravulizumab.MethodsThis retrospective, non-interventional study evaluated the period from January 1, 2012 to March 22, 2021, using US claims data from the Decision Resources Group Real World Data repository. Eligible patients had ≥ 1 medical claim with an aHUS-related International Classification of Diseases 9/10 diagnosis code and ≥ 1 medical or pharmacy claim for treatment with eculizumab or ravulizumab. Patients with evidence of paroxysmal nocturnal hemoglobinuria, myasthenia gravis, neuromyelitis optical spectrum disorder or Shiga toxin Escherichia coli-related hemolytic uremic syndrome in the 3 months prior to their first aHUS-related treatment were excluded. A patient was classified as ‘switched’ if they had ≥ 1 claim for eculizumab followed by an initial claim for ravulizumab from 14 to 30 days after the last eculizumab claim. Patients were required to have ≥ 3 months of continuous enrollment in the database prior to their first ravulizumab claim. Ravulizumab treatment was considered to be continuous if all treatment intervals were ≤ 63 days.Data extracted included: demographics and clinical characteristics at the time of switching to ravulizumab; treatment patterns (including service setting, treatment history before switching to ravulizumab, and subsequent adherence); and clinical outcomes (dialysis, plasma exchange [PE], kidney transplant, and utilization of other end-stage renal disease [ESRD] services) in the 6 months before and after switching to ravulizumab. Data were summarized using descriptive statistics.ResultsOverall, 2101 patients had ≥ 1 eculizumab or ravulizumab claim and an aHUS-related diagnosis. Of these patients, 227 had claims for both eculizumab and ravulizumab with ≥ 3 months of continuous enrollment data before the first ravulizumab claim. The median (lower quartile, upper quartile) treatment interval between the last eculizumab claim and the first ravulizumab claim was 15 (14, 41) days.In total, 131 patients met the ‘switched’ criteria. Table 1 presents patient characteristics at the time of switching from eculizumab to ravulizumab. Outpatient facilities were the most common places of service for initiation of switch to ravulizumab (n = 41/89 patients [46%]); private practice facilities were the most common sites for administration of ravulizumab maintenance treatment (n = 84/213 claims [39%]).Prior to switching to ravulizumab, the median (lower quartile, upper quartile) duration between the first and last eculizumab claim was 788 (252, 1719) days. Among the 95 patients with ≥ 6 months of continuous enrollment after switching to ravulizumab, 73 (77%) patients were treated with ravulizumab continuously for ≥ 6 months. Selected clinical outcomes in the 6 months before and after switching to ravulizumab treatment are presented in Table 2. Although no inferential statistical comparisons were made, data show that fewer switched patients underwent dialysis or utilized other ESRD services in the 6-month post-switch period (with no recorded cases of PE or kidney transplant) compared with the 6-month pre-switch period.Discussion and conclusionsThis study provides real-world data on clinical characteristics and treatment patterns for patients with aHUS who have switched from eculizumab to ravulizumab. The majority of patients switching to ravulizumab were treated continuously for ≥ 6 months according to the treatment schedule in the prescribing information. Ongoing analyses with longer follow-up time will provide inferential assessment of the clinical and economic impacts of switching to ravulizumab. [Display omitted] DisclosuresWang: Alexion: Current Employment; AstraZeneca: Current Employment. Al-Dakkak: Alexion: Current Employment; AstraZeneca: Current Employment. Garlo: Alexion: Current Employment; AstraZeneca: Current Employment. Ong: Alexion: Current Employment; AstraZeneca: Current Employment. Tomazos: Alexion, AstraZeneca Rare Disease: Current Employment. Mahajerin: Alexion: Consultancy; AstraZeneca: Current Employment.

PMH6 Healthcare Costs Increase Substantially Following Adjunctive Therapy Among MDD Patients on Antidepressant Monotherapy

BACKGROUND Among patients with major depressive disorder (MDD), inadequate response to antidepressant monotherapy (ADT) is often followed by adjunctive pharmacotherapy or psychotherapy. Little is known about changes in costs following adjunctive therapy. To estimate changes in MDD-specific and all-cause healthcare costs following adjunctive therapy. From a national sample of insurance claims licensed from Decision Resources Group, MDD patients on ADT and added adjunctive therapy between 7/1/2014 and 12/31/2018 were identified. Eligible patients were on ADT for 8+ weeks preceding and following initiation of adjunctive therapy (index); and were stratified by insurance (Medicaid, commercial) and type of adjunctive therapy: “pharmacotherapy,” “psychotherapy,” or both (“dual adjunctive”). Costs were calculated for the six months pre- and post-index, changes in cost were annualized (PPPY) and standardized to 2019$. Pre-post significance testing was based on non-overlapping 95% confidence intervals. Following adjunctive therapy, annual all-cause healthcare costs increased by 2,213, $2,002, and $6,171 for commercially-insured pharmacotherapy (n=129,650), psychotherapy (n=20,037), and dual adjunctive (n=6,229), respectively. Pharmacotherapy patients realized significant increases in pharmacy ($1,129) and outpatient services ($932) and modest decreases ($231) in inpatient costs. Psychotherapy patients realized significant increases in office visits ($1,832) and decreases ($756) in inpatient costs. Dual adjunctive patients realized no decline in acute care costs, and increases in office visits ($2,335), outpatient services ($2,612), and pharmacy ($1,302). Among pharmacotherapy patients, MDD-specific pharmacy costs increased $526 and among psychotherapy patients, MDD-specific office visit costs increased $1,037. Among the 62,166 Medicaid-insured individuals (50,713 pharmacotherapy, 8,097 psychotherapy, and 3,356 dual adjunctive), total healthcare costs increased significantly more: $3,017 (pharmacotherapy); $3,005 (psychotherapy); $8,690 (dual adjunctive). Following adjunctive therapy, costs associated with office visits, outpatient services, and pharmacy increase substantially, and acute care services decrease only modestly. Total healthcare costs increase substantially for all MDD patients but substantially more for Medicaid-insured.

Real-World Evidence of Clinical Outcomes in Patients With Assumed Classic Congenital Adrenal Hyperplasia in the United States

Background: Classic congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder, usually due to a deficiency in the 21-hydroxylase enzyme, that results in impaired cortisol synthesis and excess androgen production. Patients with classic CAH experience both disease-related features from excess androgens and treatment-related complications from the chronic, supraphysiologic use of glucocorticoids (GCs) often required for androgen control. This study was conducted to evaluate the demographics and clinical characteristics of adult and pediatric patients in the United States (US) with assumed classic CAH based on International Classification of Diseases (ICD) codes, GC prescriptions, and medical claims. Methods: Analyses were based on longitudinal patient-level data from the Decision Resources Group Real World Evidence repository, which links medical claims, prescription claims, and electronic health records from >300 million US patients. Data were analyzed for patients aged ≥18 years (adult) and <18 years (pediatric) with assumed classic CAH based on ICD 9/10 codes associated with “adrenogenital disorders” and whose proportion of days covered with a GC in 2018–2019 was >75%. These patients were matched 1:3 with a control cohort based on age, gender, geographic region, and insurance type. Both assumed CAH and control cohorts had continuous coverage with at least 1 medical claim and 1 pharmacy claim in each year, 2018–2019. Results: Of 1,111 patients with assumed classic CAH, 778 were ≥18 years old (65% female; mean age [±SD], 43±17 years) and 333 were <18 years old (51% female; mean age [±SD], 11±4.7 years). Both adult and pediatric patients with assumed classic CAH were more likely than matched controls (adult N=2334; pediatric N=999) to experience events that could be related to chronic GC use, including infection (adult: 49.9% vs 37.3% [control]; pediatric: 49.5% vs 40.0%), weight gain (adult: 5.9% vs 2.5%; pediatric: 9.0% vs 2.6%), and moon face (adult: 44.0% vs 0.1%; pediatric: 37.8% vs 0.1%); all P<0.01 vs control. Adult patients were more likely than matched controls to experience acne (6.0% vs 3.6%), hirsutism (8.1% [47/508] vs 5.5% [84/1524]), and infertility (1.7% vs 0.4%); all P<0.01. Pediatric patients were more likely to experience pubertal development issues (10.5% vs 1.8%), acne (8.4% vs 5.1%), and advanced bone age (1.2% vs 0.1%); all P<0.05. Conclusions: Compared to matched controls, both adult and pediatric patients with assumed classic CAH had significantly more disease-related comorbidities and potential GC treatment-related conditions, indicating the challenges with current GC treatments. This study was limited by the assumed nature of classic CAH due to lack of a specific ICD code, but the combination of chronic GC use (>75% days) with the diagnosis code most likely used in these patients (adrenogenital disorder) supports the validity of this analysis.

Economic and Clinical Burden of Virus-Associated Hemorrhagic Cystitis in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation in the United States

Hemorrhagic cystitis (HC) caused by viral infections such as BK virus, cytomegalovirus, and/or adenovirus after allogeneic hematopoietic stem cell transplantation (allo-HCT) causes morbidity and mortality, affects quality of life, and poses a substantial burden to the health care system. At present, HC management is purely supportive, as there are no approved or recommended antivirals for virus-associated HC. The objective of this retrospective observational study was to compare the economic burden, health resource utilization (HRU), and clinical outcomes among allo-HCT recipients with virus-associated HC to those without virus-associated HC using a large US claims database. Claims data obtained from the Decision Resources Group Real-World Evidence Data Repository were used to identify patients with first (index) allo-HCT procedure from January 1, 2012, through December 31, 2017. Outcomes were examined 1 year after allo-HCT and included total health care reimbursements, HRU, and clinical outcomes for allo-HCT patients with virus-associated HC versus those without. Further, a generalized linear model was used to determine adjusted reimbursements stratified by the presence or absence of any acute or chronic graft-versus-host disease (GVHD) after adjusting for age, health plan, underlying disease, stem cell source, number of comorbidities, baseline reimbursements, and follow-up time. Of 13,363 allo-HCT recipients, 759 (5.7%) patients met the prespecified criteria for virus-associated HC. Total unadjusted mean reimbursement was $632,870 for patients with virus-associated HC and $340,469 for patients without virus-associated HC. In a multivariable model, after adjusting for confounders, the adjusted reimbursements were significantly higher for virus-associated HC patients with and without GVHD compared to patients without virus-associated HC (P < .0001). Patients with virus-associated HC stayed 7.9 additional days in the hospital (P < .0001) and 6.1 additional days (P=.0009) in the intensive care unit (ICU) for the index hospitalization, as compared to patients without virus-associated HC. The hospital readmission rate was higher for allo-HCT patients with versus without virus-associated HC (P < .0001), resulting in 12.9 more days in the hospital (P < .0001) and 7.3 more days in the ICU (P < .0001) after the index hospitalization. Among patients with GVHD, those with virus-associated HC had significantly higher all-cause mortality as compared to those without virus-associated HC (23.2% versus 18.4%; P=.0035). In an adjusted analysis, patients with virus-associated HC had a significantly higher risk of mortality, regardless of the presence of GVHD. When stratified by GVHD, there were no significant differences in the baseline risk for renal impairment; virus-associated HC was associated with increased risk for renal impairment in the follow-up period in patients with or without GVHD (P < .0001 for both). After allo-HCT, patients with virus-associated HC have significantly higher health care reimbursements and HRU, with worse clinical outcomes, including renal impairment, irrespective of the presence of GVHD and significantly higher all-cause mortality in the presence of GVHD. Our results highlight the unmet clinical need for effective strategies to prevent and treat virus-associated HC in HCT recipients that may also reduce costs among these patients.

1089. Health Resource Utilization and Costs Associated with Multi-Virus Infection after Allogeneic Hematopoietic Cell Transplantation

BackgroundReactivation or infection with multiple double-stranded DNA (dsDNA) viruses after allogeneic hematopoietic cell transplant (allo-HCT) has been associated with increased morbidity in single center studies. We used a large US claims database to compare health care reimbursements and health resource utilization (HRU) between allo-HCT patients with no versus multiple infections due to CMV, BKV, EBV, JCV, AdV, and HHV-6.MethodsWe used the Decision Resources Group Real World Evidence Data Repository to identify allo-HCT recipients from 1/1/12-12/31/17. We grouped BKV, EBV and JCV due to lack of specific diagnosis codes and calculated reimbursements from submitted charges using a reimbursement to charge ratio of 0.425. We describe reimbursements and HRU in the 1-year post allo-HCT for patients with 1 vs. 2 vs. ≥ 3 vs. no dsDNA viral infections. We also used a generalized linear model to determine reimbursements stratified by the presence or absence of any acute or chronic graft-versus-host diseases (GVHD) after adjusting for age, health plan, underlying disease, stem cell source, baseline costs, and follow-up time.ResultsAmong the 13,363 allo-HCT patients, 3,878 (29%) were coded with CMV, 1,754 (13%) with BKV/EBV/JCV, 626 (5%) with AdV, and 561 (4%) with HHV-6. Further, 3,949 (30%) were coded with 1 virus, 1,069 (8%) with 2, 238 (2%) with ≥3, and 8,107 (61%) with none. The unadjusted mean reimbursements per patient group were: 1 virus, $431,614; 2, $639,097; ≥3, $964,378; none, $266,345 (Table 1). Adjusted reimbursements were significantly higher for each additional viral infection among patients with and without GVHD compared to patients with no viral infections (p< .0001) (Figure 1). HRU also increased as the number of viral infections increased. Patients with multiple viruses had longer lengths of stay (up to 2.5 weeks for index, 5 weeks for readmissions), ICU days (up to 1.5 weeks for index and readmissions) and higher readmission rates (up to 3 times) (Table 1).Table 1: Economic burden and health resource utilization in the first year after allo-HCT, stratified by number of dsDNA viral infections Figure 1: Adjusted total reimbursements in the first year after allo-HCT, stratified by number of dsDNA viral infections and GVHD ConclusionAllo-HCT patients with multiple dsDNA viral infections have significantly higher health care costs and HRU in the first year after allo-HCT, irrespective of the presence of GVHD. Improved dsDNA virus prevention strategies may reduce costs and improve outcomes.Disclosures Joshua A. Hill, MD, Allogene (Consultant)Allovir (Consultant)Gilead (Consultant)Karius (Grant/Research Support, Scientific Research Study Investigator)Takeda (Grant/Research Support, Scientific Research Study Investigator) Richard T. Maziarz, MD, AlloVir (Consultant)Artiva Biotherapeutics (Board Member)Athersys (Advisor or Review Panel member)BMS/ Celgene (Consultant, Grant/Research Support, Scientific Research Study Investigator)CRSPR (Consultant, Scientific Research Study Investigator)Fate Therapeutics (Scientific Research Study Investigator)Incyte (Consultant, Scientific Research Study Investigator)Kite Therapeutics (Consultant)Novartis (Consultant, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support)Omeros (Consultant, Grant/Research Support)PACT Pharma (Consultant) Seung Hyun Moon, MD, MPA, AlloVir (Employee, Shareholder) Aastha Chandak, PhD, AlloVir (Independent Contractor) Zhiji Zhang, MS, AlloVir (Independent Contractor) Michael Boeckh, MD PhD, AlloVir (Consultant)EvrysBio (Advisor or Review Panel member, Other Financial or Material Support, share options)Gilead (Consultant, Grant/Research Support)GSK (Consultant)Helocyte (Advisor or Review Panel member, Shareholder)Lophius (Grant/Research Support)Merck (Consultant, Grant/Research Support)SymBio (Consultant)VirBio (Consultant, Grant/Research Support)

195. Economic and Clinical Burden of Respiratory Virus Infections in Allogeneic Hematopoietic Cell Transplantation Recipients

BackgroundRespiratory viruses (RV), including respiratory syncytial virus (RSV), influenza, parainfluenza virus (PIV), and human metapneumovirus (HMPV), frequently lead to serious complications such as lower respiratory tract infections and death in allogeneic hematopoietic cell transplantation (HCT) recipients. We used a large US claims database to compare the total reimbursement (TR), health resource utilization (HRU) and clinical outcomes between HCT patients with and without RV infections (RVI).MethodsWe used the Decision Resources Group Real World Evidence Data Repository to identify HCT recipients with date of service for the procedure from 1/1/2012-12/31/2017. We estimated the reimbursements from submitted charges using a reimbursement to charge ratio of 0.425. We examined the study outcomes in the year following HCT in patients with and without RVI. We also used a generalized linear model to determine adjusted TR stratified by the presence or absence of any acute or chronic graft-versus-host diseases (GVHD) after adjusting for age, health plan, underlying disease, stem cell source, number of comorbidities, baseline costs, and follow-up time.ResultsThe study included 13,363 patients, representing 22% of HCTs reported to CIBMTR for the study period, of which 1,368 (10%) were coded with an RVI in the year following HCT: 578 (4%) RSV, 687 (5%) influenza, 166 (1%) PIV, and 181 (1%) HMPV. Unadjusted median TR were $132,395 higher for any RVI ($139,439 RSV, $101,963 influenza, $185,041 PIV and $248,029 HMPV) compared to those without RVI (Table 1). Adjusted TR were significantly higher for patients with any RVI compared to patients without that infection (p< .01) with or without GVHD (Figure 1). Patients with any RVI had significantly longer length of stay (LOS) for the HCT hospitalization, readmission rate and LOS after HCT hospitalization compared to patients without RVI (p< 0.05) (Table 2). A significantly higher proportion of patients with any RVI had pneumonia as compared to patients without that infection, irrespective of presence of GVHD (p< .0001).Table 1: Total healthcare reimbursement within one year of undergoing allogeneic HCT for patients with and without respiratory viral infections Figure 1: Adjusted total reimbursements within one year of undergoing allogeneic HCT for patients with and without respiratory viral infections Table 2: Health resource utilization within one year of undergoing allogeneic HCT for patients with and without respiratory viral infections ConclusionAllogeneic HCT patients with RVI have a significantly higher burden of TR, health resource utilization and worse clinical outcomes such as pneumonia during one year of undergoing HCT, regardless of the presence of GVHD.Disclosures Michael G. Ison, MD MS, AlloVir (Consultant) Francisco M. Marty, MD, Allovir (Consultant)Amplyx (Consultant)Ansun (Scientific Research Study Investigator)Avir (Consultant)Cidara (Scientific Research Study Investigator)F2G (Consultant, Scientific Research Study Investigator)Kyorin (Consultant)Merck (Consultant, Grant/Research Support, Scientific Research Study Investigator)New England Journal of Medicine (Other Financial or Material Support, Honorarium for Video)Regeneron (Consultant, Scientific Research Study Investigator)ReViral (Consultant)Scynexis (Scientific Research Study Investigator)Symbio (Consultant)Takeda (Scientific Research Study Investigator)United Medical (Consultant)WHISCON (Scientific Research Study Investigator) Seung Hyun Moon, MD, MPA, AlloVir (Employee, Shareholder) Zhiji Zhang, MS, AlloVir (Independent Contractor) Aastha Chandak, PhD, AlloVir (Independent Contractor)

Economic and Clinical Burden of Virus-Associated Hemorrhagic Cystitis in Patients Following Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Hemorrhagic cystitis (HC) due to viral infections, such as BK virus, cytomegalovirus and/or adenovirus, after Allogeneic Hematopoietic Cell Transplantation (allo-HCT) causes morbidity and mortality, impacts quality of life, and poses a substantial burden to the health care system. Virus-associated HC (V-HC) occurs in up to 25% and 54% of pediatric and adult allo-HCT recipients respectively. V-HC is associated with incapacitating pain, life-disturbing urinary symptoms, and in severe forms, severe hematuria requiring transfusion support, bladder obstruction, renal impairment and increased mortality. At present, management is purely supportive as there are no approved or recommended anti-virals for V-HC. The impact of V-HC on health resource utilization (HRU) and HCT outcomes has not been studied at a national level. The objective of this study was to compare the economic burden, HRU and clinical outcomes among allo-HCT recipients with V-HC to those without V-HC using a large US claims database. Methods: A US claims database obtained from the Decision Resources Group Real World Evidence Data Repository was used to identify patients with first (index) allo-HCT procedure from 1/1/2012-12/31/2017. The 1-year period prior to the index allo-HCT was considered as the baseline period. Although, there are diagnosis codes in the International Classification of Diseases (ICD-9 or ICD-10) coding system for HC, there are no specific diagnosis codes to identify V-HC. Hence, an algorithm was developed through clinical guidance to identify these patients among those with HC diagnosis codes (Figure 1). Outcomes were examined in the 1-year post allo-HCT and included total healthcare reimbursements, HRU and clinical outcomes for allo-HCT patients with vs. without V-HC. Total reimbursements were estimated from submitted charges using a reimbursement-to-charge ratio of 0.425 and were reported in 2019 US dollars, adjusted using the medical care component of the US Consumer Price Index. Further, a generalized linear model was used to determine adjusted reimbursements stratified by the presence or absence of any acute or chronic graft-versus-host diseases (GVHD) after adjusting for age, health plan, underlying disease, stem cell source, number of comorbidities, baseline costs, and follow-up time. Results: Of 13,363 allo-HCT recipients, 759 (5.7%) patients met the criteria for V-HC. Total unadjusted mean reimbursement was $632,870 (SD=$640,815) for patients with V-HC and $340,469 (SD=$377,591) for patients without V-HC (Table 1). In multivariable model after adjusting for confounders, the adjusted reimbursements were significantly higher for V-HC patients with and without GVHD compared to patients without V-HC (p&amp;lt;.0001) (Figure 2). V-HC was associated with increased hospital length of stay (LOS) and readmission rates. Patients with V-HC had 7.9 additional days in the hospital (35.5 vs 27.6 days; p&amp;lt;.0001) and 6.1 additional days (34.3 vs. 28.2 days; p=0.0009) in the intensive care unit (ICU) for the index hospitalization, as compared to patients without V-HC (Table 1). The hospital readmission rate was higher for allo-HCT patients with V-HC compared to those without V-HC (3.5 vs. 1.9 per person yr; p&amp;lt;.0001), resulting in 12.9 more days in the hospital (50.0 days vs. 37.1 days; p&amp;lt;.0001) and 7.3 more days in the ICU (25.8 days vs. 18.5 days; p&amp;lt;.0001) after the index hospitalization (Table 1). V-HC was associated with increased mortality in patients with GVHD and increased risk of renal impairment in all allo-HCT patients. Among patients with GVHD, those with V-HC had significantly higher all-cause mortality as compared to those without V-HC (23.2% vs. 18.4%; p=0.0035) (Table 2). When stratified by GVHD, there were no significant differences in the baseline risk for renal impairment; while V-HC was associated with increased risk for renal impairment in the follow-up period in patients with or without GVHD (p&amp;lt;.0001 for both) (Table 2). Conclusions: Allo-HCT patients with V-HC have significantly higher healthcare reimbursements, health resource utilization, and worse clinical outcomes including renal impairment, irrespective of the presence of GVHD; with significantly higher all-cause mortality in the presence of GVHD. Our results highlight the unmet clinical need for effective strategies to prevent and treat V-HC in HCT recipients that may also reduce costs among these patients. Disclosures McGuirk: Pluristem Ltd: Research Funding; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Astellas: Research Funding; Kite Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau; Fresenius Biotech: Research Funding; Novartis: Research Funding; Gamida Cell: Research Funding; Bellicum Pharmaceutical: Research Funding; Allo Vir: Consultancy, Honoraria, Research Funding. Moon:AlloVir, Inc.: Current Employment, Current equity holder in publicly-traded company. Chandak:AlloVir, Inc.: Other: Independent contractor. Zhang:AlloVir, Inc.: Other: Independent contractor. Papanicolaou:Chimerix: Other: Consulting and other fees, Research Funding; Astellas Pharma: Other: Consulting and other fees, Research Funding; Merck &amp; Co.: Other: Consulting and other fees, Research Funding; Octapharma: Other: Consulting and other fees; Partner Therapeutics: Other: Consulting and other fees; ADMA Biologics: Other: Consulting and other fees; Shionogi: Other: Consulting and other fees; Cidara: Other: Consulting and other fees; Amplyx: Other: Consulting and other fees; Siemens: Other; Takeda: Research Funding.