The effect of medication nonadherence on progression-free survival among patients with renal cell carcinoma

Jason Shafrin,1 Jeffrey Sullivan,1 Jacquelyn W Chou,1 Michael N Neely,2 Justin F Doan,3 J Ross Maclean1 1Precision Health Economics, Los Angeles, CA, USA; 2Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 3Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, USA Objective: To examine how observed medication nonadherence to 2 second-line, oral anticancer medications (axitinib and everolimus) affects progression-free survival (PFS) among patients with renal cell carcinoma. Methods: We used an adherence–exposure–outcome model to simulate the impact of adherence on PFS. Using a pharmacokinetic/pharmacodynamic (PK/PD) population model, we simulated drug exposure measured by area under the plasma concentration–time curve (AUC) and minimum blood or trough concentration (Cmin) under 2 scenarios: 1) optimal adherence and 2) real-world adherence. Real-world adherence was measured using the medication possession ratios as calculated from health insurance claims data. A population PK/PD model was simulated on individuals drawn from the Medical Expenditure Panel Survey (MEPS), a large survey broadly representative of the US population. Finally, we used previously published PK/PD models to estimate the effect of drug exposure (i.e., Cmin and AUC) on PFS outcomes under optimal and real-world adherence scenarios. Results: Average adherence measured using medication possession ratios was 76%. After applying our simulation model to 2164 individuals in MEPS, drug exposure was significantly higher among adherent patients compared with nonadherent patients for axitinib (AUC: 249.5 vs. 159.8 ng×h/mL, P<0.001) and everolimus (AUC: 185.4 vs. 118.0 µg×h/L, P<0.001). Patient nonadherence in the real world decreased the expected PFS from an optimally adherent population by 29% for axitinib (8.4 months with optimal adherence vs. 6.0 months using real-world adherence, P<0.001) and by 5% (5.5 vs. 5.2 months, P<0.001) for everolimus. Conclusion: Nonadherence by renal cell carcinoma patients to second-line oral therapies significantly decreased the expected PFS. Keywords: adherence, axitinib, everolimus, outcomes, pharmacokinetics/pharmacodynamics, progression-free survival, renal cell carcinoma, second-lin

Does knowledge of patient non-compliance change prescribing behavior in the real world? A claims-based analysis of patients with serious mental illness

Jason Shafrin,1 Katalin Bognar,1 Katie Everson,1 Michelle Brauer,2 Darius N Lakdawalla,3 Felicia M Forma4 1Policy and Economics, Precision Health Economics, Los Angeles, CA, USA; 2Policy and Economics, Precision Health Economics, Boston, MA, USA; 3School of Pharmacy, Sol Price School of Public Policy, Leonard D. Schaeffer Center for Health Policy and Economics, University of Southern California, Los Angeles, CA, USA; 4Health Economics and Outcomes Management, Otsuka Pharmaceutical Development & Commercialization, Inc., Princeton, NJ, USA Background: New digital technologies offer providers the promise of more accurately tracking patients’ medication adherence. It is unclear, however, whether access to such information will affect provider treatment decisions in the real world.Methods: Using prescriber-reported information on patient non-compliance from health insurance claims data between 2008 and 2014, we examined whether prescribers’ knowledge of non-compliance was associated with different prescribing patterns for patients with serious mental illness (SMI). We examined patients who initiated an oral atypical antipsychotic, but were later objectively non-adherent to this treatment, defined as proportion of days covered (PDC) <0.8. We examined how a physician’s awareness of patient non-compliance (ICD-9 diagnosis code: V15.81) was correlated with the physician’s real-world treatment decisions for that patient. Treatment decisions studied included the share of patients who increased antipsychotic dose, augmented treatment, switched their antipsychotic, or used a long-acting injectable (LAI).Results: Among the 286,249 patients with SMI who initiated an antipsychotic and had PDC <0.8, 4,033 (1.4%) had documented non-compliance. When prescribers documented non-compliance, patients were more likely to be switched to another antipsychotic (32.8% vs 24.7%, P<0.001), have their dose increased (24.4% vs 22.1%, P=0.004), or receive an LAI (0.09% vs 0.04%, P=0.008), but were less likely to have augmented therapy with another antipsychotic (1.1% vs 1.3%, P=0.035) than patients without documented non-compliance.Conclusion: Among SMI patients with documented non-compliance, the frequency of dose, medication switches, and LAI use were higher and augmentation was lower compared to patients without documented non-compliance. Access to adherence information may help prescribers more rapidly switch ineffective medications as well as avoid unnecessary medication augmentation. Keywords: adherence, prescribing patterns, serious mental illnes

A diverse community of jute (Corchorus spp.) endophytes reveals mutualistic host–microbe interactions

Endophytes are plant-associated microbes that live within plants as an integral part of the host metabolism and function. This study aimed to identify the molecular and physiological characteristics of both culturable and non-culturable endophytic bacteria and fungi present in different parts of the jute (Corchorus olitorius) plant. Using universal primers used to amplify hypervariable bacterial 16S rDNA and fungal internal transcribed spacer (ITS) regions of 18S rDNA, we identified five different culturable and 20 non-culturable endophytic bacteria as well as 14 different fungal endophytes from various parts of jute. Biochemical and physiological tests suggest that these microbes may bring a wide range of benefits to their hosts. For example, all five culturable endophytic bacteria were positive for auxin and catalase activity, which may lead to improved root elongation and stress resistance, respectively. These bacteria also have metal uptake, haemolytic and hydrolytic activities that could be useful in medical, environmental and industrial applications. The fungal endophytes were positive for lignin peroxidase, cellulase and xylanase activities, all of which may influence jute physiology. Another important finding was the antifungal activity of one of the fungi against a devastating pernicious fungus that affects hundreds of plant species.Rifat Ara Najnin, Farhana Shafrin, Ahsan Habib Polash, Aubhishek Zaman, Amzad Hossain ... Jannatul Ferdoush Tuli ... et al