Cost-Effectiveness of Molecularly Guided Treatment in Diffuse Large B-Cell Lymphoma (DLBCL) in Patients under 60.

BACKGROUND: Classifying diffuse large B-cell lymphoma (DLBCL) into cell-of-origin (COO) subtypes could allow for personalized cancer control. Evidence suggests that subtype-guided treatment may be beneficial in the activated B-cell (ABC) subtype of DLBCL, among patients under the age of 60. METHODS: We estimated the cost-effectiveness of age- and subtype-specific treatment guided by gene expression profiling (GEP). A probabilistic Markov model examined costs and quality-adjusted life-years gained (QALY) accrued to patients under GEP-classified COO treatment over a 10-year time horizon. The model was calibrated to evaluate the adoption of ibrutinib as a first line treatment among patients under 60 years with ABC subtype DLBCL. The primary data source for efficacy was derived from published estimates of the PHOENIX trial. These inputs were supplemented with patient-level, real-world data from BC Cancer, which provides comprehensive cancer services to the population of British Columbia. RESULTS: We found the cost-effectiveness of GEP-guided treatment vs. standard care was $77,806 per QALY (24.3% probability of cost-effectiveness at a willingness-to-pay (WTP) of $50,000/QALY; 53.7% probability at a WTP of $100,000/QALY) for first-line treatment. Cost-effectiveness was dependent on assumptions around decision-makers' WTP and the cost of the assay. CONCLUSIONS: We encourage further clinical trials to reduce uncertainty around the implementation of GEP-classified COO personalized treatment in this patient population.

Stakeholder Perspectives on Navigating Evidentiary and Decision Uncertainty in Precision Oncology.

(1) Background: Precision oncology has the potential to improve patient health and wellbeing through targeted prevention and treatment. Owing to uncertain clinical and economic outcomes, reimbursement has been limited. The objective of this pan-Canadian qualitative study was to investigate barriers to precision oncology implementation from the perspectives of health system stakeholders. (2) Methods: We conducted 32 semi-structured interviews with health technology decision makers (n = 14) and clinicians (n = 18) experienced with precision oncology. Participants were recruited using a purposive sampling technique. Interviews were analyzed using thematic analysis. Recruitment continued until two qualitative analysts reached agreement that thematic saturation was reached. (3) Results: While cautiously optimistic about the potential for enhanced therapeutic alignment, participants identified multiple decisional challenges under conditions of evidentiary uncertainty. Decision makers voiced concern over resource requirements alongside small benefitting patient populations and limited evidence supporting patient and health system impacts. Clinicians were comparatively tolerant of evidentiary uncertainty guiding clinical decision-making practices. Clinicians applied a broader definition of patient benefit, focusing on the ability to assist patients making informed clinical decisions. (4) Conclusions: Sustainable precision oncology must balance demand with evidence demonstrating benefit. We show that clinicians and decision makers vary in their tolerance for evolving knowledge, suggesting a need to establish evidentiary standards supporting precision oncology reimbursement decisions.

Clinical impact of low coverage in whole-exome genetic testing in the assessment of familial arrhythmogenic right ventricular cardiomyopathy: a case report.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited condition, with approximately 60% of patients carrying a possibly disease-causing genetic variant. Known desmosomal genes account for about 50% of those variants. We herein report a family with ARVC in which a pathogenic desmosomal variant was missed because of the initial genetic testing method. Case summary: A 54-year-old man diagnosed with ARVC underwent genetic cascade screening for a heterozygous titin variant (TTN: c.26542C>T), detected in his phenotypically affected sister. He did not harbour this TTN variant. Moreover, reclassification of this variant based on the American College of Medical Genetics (ACMG) 2015 criteria showed it to be likely benign. Upon genetic re-screening with a dedicated cardiomyopathy panel a heterozygous missense variant in desmoglein-2 (DSG2: c.152G>C) was found. His sister's DNA was re-analysed and the same DSG2 variant was detected, and classified as LP (likely pathogenic) by current literature. Discussion: The initial genetic screening tool used in the patient's sister (whole-exome sequencing, WES) failed to detect the likely causative desmosomal variant in our family. While WES represents a good tool in searching for novel genes in Trio Analysis, it has a low DNA coverage in important regions (mean 10×) of known ARVC-associated genes. We therefore propose using smaller panels with better coverage in the clinical setting, such as Trusight-cardio (mean DNA coverage 100-300×) as an initial genetic screening method.

Genomic Testing for Relapsed and Refractory Lymphoid Cancers: Understanding Patient Values.

BACKGROUND: New clinical genomic assays for lymphoid cancers allow for improved disease stratification and prognostication. At present, clinical implementation has been appropriately limited, owing to a paucity of evidence to support clinical and cost effectiveness. Understanding patients' values for precision oncology under conditions of uncertainty can be used to inform priority-setting decisions. OBJECTIVES: Our objective was to ascertain patients' qualitative preferences and attitudes for prognostic-based genomic testing. METHODS: Individuals who were diagnosed with lymphoid cancer between 2000 and 2018 in British Columbia, Canada, were recruited to participate in one of three focus groups. A maximum variation sampling technique was used to capture a diversity of perspectives. A patient partner was involved in the development of the focus group topic guide and presentation materials. All sessions were audio recorded and analyzed using NVivo qualitative analysis software, version 12. RESULTS: In total, 26 participants took part in focus groups held between November 2018 and February 2019. Results illustrate qualitative preference heterogeneity for situations under which individuals would be willing to undergo genomic testing for relapsed lymphoid cancers. Preferences were highly contextualized within personal experiences with disease and treatment protocols. Hypothetical willingness to pay for testing was contingent on invasiveness, the potential for treatment de-escalation, and personal health benefit. CONCLUSIONS: Patients are supportive and accepting of evidentiary uncertainty up until the point at which they are required to trade-off the potential for improved quality and length of life. Demand for precision medicine is contingent on expectations for benefit alongside an acknowledgment of the opportunity cost required for implementation. The clinical implementation of precision medicine will be required to address evidentiary uncertainty surrounding personal benefit while ensuring equitable access to emerging innovations.

Public perspectives on disinvestments in drug funding: results from a Canadian deliberative public engagement event on cancer drugs.

BACKGROUND: Decisions relating to the funding of new drugs are becoming increasingly challenging due to a combination of aging populations, rapidly increasing list prices, and greater numbers of drug-indication pairs being brought to market. This is especially true in cancer, where rapid list price inflation is coupled with steeply rising numbers of incident cancer cases. Within a publicly funded health care system, there is increasing recognition that resource allocation decisions should consider the reassessment of, and potential disinvestment from, currently funded interventions alongside new investments. Public input into the decision-making process can help legitimize the outcomes and ensure priority-setting processes are aligned with public priorities. METHODS: In September 2014, a public deliberation event was held in Vancouver, Canada, to obtain public input on the topic of cancer drug funding. Twenty-four members of the general public were tasked with making collective recommendations for policy-makers about the principles that should guide funding decisions for cancer drugs in the province of British Columbia. Deliberative questions and decision aids were used to elicit individuals' willingness to make trade-offs between expenditures and health outcomes. RESULTS: Participants discussed the implications of disinvestment decisions from cancer drugs in terms of its impact on patient choice, fairness and quality of life. Their discussions indicate that in order for a decision to disinvest from currently-funded cancer drugs to be acceptable, it must align with three main principles: the decision must be accompanied by significant gains, described both in terms of cost savings and opportunities to re-invest elsewhere in the health care system; those who are currently prescribed a cancer drug should be allowed to continue their course of treatment (referred to as a continuance clause, or "grandfathering" approach); and it must consider how access to care for specialized populations is impacted. CONCLUSIONS: The results from this deliberation event provide insight into what is acceptable to British Columbians with respect to disinvestment decisions for cancer drugs. These recommendations can be considered within wider health system decision-making frameworks for funding decisions relating to all drugs, as well as for cancer drugs.

Trade-offs, fairness, and funding for cancer drugs: key findings from a deliberative public engagement event in British Columbia, Canada.

BACKGROUND: Spending on cancer drugs has risen dramatically in recent years compared to other areas of health care, due in part to higher prices associated with newly approved drugs and increased demand for these drugs. Addressing this situation requires making difficult trade-offs between cost, harms, and ability to benefit when using public resources, making it important for policy makers to have input from many people affected by the issue, including citizens. METHODS: In September 2014, a deliberative public engagement event was conducted in Vancouver, British Columbia (BC), on the topic of priority setting and costly cancer drugs. The aim of the study was to gain citizens' input on the topic and have them generate recommendations that could inform cancer drug funding decisions in BC. A market research company was engaged to recruit members of the BC general public to deliberate over two weekends (four days) on how best to allocate resources for expensive cancer treatments. Participants were stratified based on the 2006 census data for BC. Participants were asked to discuss disinvestment, intravenous versus oral chemotherapy delivery, and decision governance. All sessions were audio recorded and transcribed. Transcripts were analyzed using NVivo 11 software. RESULTS: Twenty-four individuals participated in the event and generated 30 recommendations. Participants accepted the principle of resource scarcity and the need of governments to make difficult trade-offs when allocating health-care resources. They supported the view that cost-benefit thresholds must be set for high-cost drugs. They also expected reasonable health benefits in return for large expenditures, and supported the view that some drugs do not merit funding. Participants also wanted drug funding decisions to be made in a non-partisan and transparent way. CONCLUSION: The recommendations from the Vancouver deliberation can provide guidance to policy makers in BC and may be useful in challenging pricing by pharmaceutical companies.

Depression in dialysis patients and its association with nutritional markers and quality of life.

BACKGROUND: Depression is the most widely prevalent psychiatric disorder in dialysis and can result in a lower quality of life (QoL) and probably a worse nutritional status. The aim of this study was to evaluate the associations among depression, QoL and nutritional status in hemodialysis. METHODS: This study included 104 patients on dialysis longer than 3 months, aged 18-65 years. Their nutritional status was assessed according to body mass index (BMI), serum albumin and phase angle; QoL was assessed using the SF-36 questionnaire, and their risk of depression was measured using the Beck Depression Inventory (BDI). Associations among depression, QoL and nutritional status were assessed using Fisher's exact test, and correlations between continuous variables were examined by Pearson's coefficient. RESULTS: Depression was detected in 65.3% of patients, and all of the dimensions of QoL were compromised, with the worst values observed for role-functioning physical (RP) and general health (GH). A negative correlation between the dimensions of QoL and BDI score was observed. Serum albumin was significantly correlated with general health (GH), and phase angle with physical functioning (PF). CONCLUSION: A high prevalence of depression was detected, as well as reduced mean scores for QoL. BDI score was significantly correlated with both physical and mental components of QoL. Phase angle was associated with physical functioning (PF) and physical component summary scales (PCS), whereas no nutritional marker was associated with the BDI score. The periodic monitoring of depression should be implemented in hemodialysis, in addition to monitoring QoL and nutritional status. A better understanding of these relationships could result in a better efficiency of dialysis treatment.

The use of registered nurses to perform flexible sigmoidoscopy procedures in ontario: a cost minimization analysis.

RATIONALE: Rates of colorectal cancer (CRC) are on the rise in Canada. Flexible sigmoidoscopy (FS) is an initial screening test for CRC primarily used in adults aged 50 years and older at average risk for the disease. Physicians and registered nurses have been shown to have the same effectiveness in performing a FS procedure. This paper presents an analysis of the use of registered nurses (RN) compared to physicians in Ontario to assess costs to the healthcare system. OBJECTIVES: To evaluate whether FS performed by RNs is a less costly alternative to increase access to CRC screening capacity in Ontario. METHODOLOGY: A cost minimization analysis was conducted from a health system perspective. DISCUSSION: RN-performed FS is a viable alternative for increasing CRC screening capacity in Ontario. Remuneration schedules for on-call physicians must be taken into consideration if policies are developed for the implementation of RN screening procedures. RESULTS: The findings suggest that the use of RNs may be cost saving compared to physician-performed FS procedures, depending on physician remuneration.

CONTEXTE : Au Canada, les taux de cancer colorectal (CCR) sont à la hausse. La sigmoïdoscopie flexible (SF) est un test initial de dépistage du CCR principalement utilisé chez les adultes de 50 ans et plus qui présentent un risque moyen de développer la maladie. Il a été démontré que les médecins et les infirmières autorisées présentent la même efficacité pour effectuer les procédés de FS. Cet article présente une analyse de comparaison entre les infirmière autorisées et les médecins en Ontario afin d'en évaluer les coûts pour le système de santé. OBJECTIFS : Évaluer dans quelle mesure la SF effectuée par les infirmières autorisées est un choix moins coûteux pour accroître l'accès au dépistage du CCR en Ontario. MÉTHODOLOGIE : Une analyse de minimisation des coûts a été effectuée selon l'angle du système de santé. DISCUSSION : La FS effectuée par les infirmières autorisées afin d'accroître les capacités de dépistage du CCR en Ontario est une option viable. Les barèmes de rémunération des médecins sur appel doivent être reconsidérés si on souhaite élaborer des politiques de mise en place de procédés de dépistage par les infirmières autorisées. RÉSULTATS : Les résultats font voir que, par rapport aux médecins, l'utilisation des infirmières autorisées pour effectuer les procédés de SF peut permettre des économies, dépendamment de la rémunération des médecins.

Aborto induzido em mulheres de baixa renda: dimensão de um problema

Enfoca a prática de aborto, principalmente aborto induzido entre mulheres de baixa renda. A análise é baseada em dados de pesquisa coletados entre 1984 e 1985 em sete favelas localizadas na área metropolitana do Rio de Janeiro, Brasil. Apesar da legislação severa existente, a prática do aborto induzido é muito frequente. Entre as mulheres casadas, 21,4 declararam terem praticado aborto induzuzido. Embora grande parte dos abortos terem sidos feitos por médicos, a qualidade dos cuidados nestes procedimentos é questinável, devido ao fato de que, sendo ilegal, na maioria dos casos não há possibilidade de supervisão por parte das autoridades de saúde. A incidência de complicaçoes pós-aborto é muito alta, principalmente nos casos em que é praticado por curiosas ou pela própria mulher. Mais de 60 das mulheres não faziam uso de métodos contraceptivos ao engravidar. Cerca de 21 declararam que estavam usando pílula anticopcional. Claro está que uma taxa de falha tão elevada é inaceitável e deve-se ao seu uso incorreto. Tudo isso revela a necessidade urgente de um melhor acesso ao planejamento familiar oferecido pelos serviços de saúde dentro da concepção de atenção integral. São discutidas, também, as consequencias das leis restritivas em matéria de aborto no Brasil, restriçoes que, na prática, provam ser ineficazes para prevenir a prática do aborto induzido, mas podem ser muito efetivas para ampliar ainda mais as desigualdades sociais já existentes

A prática de planejamento familiar em mulheres de baixa renda no município do Rio de Janeiro / Family planning practice in low income women in the metropolitan area of Rio de Janeiro

Este trabalho examina a prática contraceptiva e os problemas que as mulheres de baixa renda enfrentam no controle de sua fecundade. A discussäo é baseada nos dados de uma pesquisa coletados entre 1984 e 1985 em sete favelas situada na Regiäo Metropolitana do Rio de Janeiro. Apesar da ausência de um programa de planejamento familiar na área do estudo, foi encontrada uma alta prevalência de uso de contraceptivos entre as mulheres em uniäo (67%). A análise revela porém, que a alta prevalência foi resultado quase que exclusivamente do uso de dois métodos femininos altamente eficazes - contracepçäo oral e esterilizaçäo feminina. A forma como estes métodos vêm sendo utilizados está associada a altos riscos desnecessarios à saúde da mulher. Foi concluído que é necessario que os cuidados de planejamento familiar façam parte de um programa integral à saúde da mulher, um programa que ofereça um amplo leque de métodos contraceptivos reversíveis e que dê ênfase às atividades de praticas educativas. De fato, esses princípios estäo contidos no PAISM, mas a sua emplementaçäo efetiva depende näo só de mudanças no setor saúde, mas principalmente de transformaçöes amplas dentro da sociedade brasileira