Real-world evidence for coverage determination of treatments for rare diseases.

Health technology assessment (HTA) decisions for pharmaceuticals are complex and evolving. New rare disease treatments are often approved more quickly through accelerated approval schemes, creating more uncertainties about clinical evidence and budget impact at the time of market entry. The use of real-world evidence (RWE), including early coverage with evidence development, has been suggested as a means to support HTA decisions for rare disease treatments. However, the collection and use of RWE poses substantial challenges. These challenges are compounded when considered in the context of treatments for rare diseases. In this paper, we describe the methodological challenges to developing and using prospective and retrospective RWE for HTA decisions, for rare diseases in particular. We focus attention on key elements of study design and analyses, including patient selection and recruitment, appropriate adjustment for confounding and other sources of bias, outcome selection, and data quality monitoring. We conclude by offering suggestions to help address some of the most vexing challenges. The role of RWE in coverage and pricing determination will grow. It is, therefore, necessary for researchers, manufacturers, HTA agencies, and payers to ensure that rigorous and appropriate scientific principles are followed when using RWE as part of decision-making.

Global Challenges in Access to and Implementation of Precision Oncology: The Health Care Manager and Health Economist Perspective.

Precision medicine changes the landscape of oncology practices by offering the opportunity to optimize care through a more targeted, personalized approach of managing cancer treatments. However, precision oncology is costly and does not benefit all patients with cancer, making it critically important to consider the tradeoff between costs and health benefits. Here, we discuss the global challenges in implementing precision oncology from the perspective of health care management and health economics and emphasize the different challenges for high-income compared with low- and middle-income countries. For health care managers making resource allocation decisions, the decision to adopt, implement, and finance precision oncology must consider opportunity costs, and the allocation must be proportional to the system's capacity. The standard approach of health technology assessment is inadequate because it fails to consider the capacity to pay. From an economic perspective, global implementation of precision oncology must confront the issues of accessibility, affordability, and system readiness. Low- and middle-income countries often have no or delayed access to novel targeted-therapy agents, find these drugs cost-prohibitive, and struggle to build the infrastructure with sufficient workforce and adequate testing and computing facilities to capitalize the benefit of precision oncology. Although high-income countries are better equipped to implement precision oncology, the challenges there lie in implementing strategies to maximize the value of precision oncology through promoting appropriate use while limiting inappropriate applications. The recent rollout of COVID-19 vaccines internationally highlights the importance of information uncertainty and offers valuable insights on global access to and implementation of precision oncology.

Cancer control in Latin America and the Caribbean: recent advances and opportunities to move forward.

The increasing burden of cancer represents a substantial problem for Latin America and the Caribbean. Two Lancet Oncology Commissions in 2013 and 2015 highlighted potential interventions that could advance cancer care in the region by overcoming existing challenges. Areas requiring improvement included insufficient investment in cancer control, non-universal health coverage, fragmented health systems, inequitable concentration of cancer services, inadequate registries, delays in diagnosis or treatment initiation, and insufficient palliative services. Progress has been made in key areas but remains uneven across the region. An unforeseen challenge, the COVID-19 pandemic, strained all resources, and its negative effect on cancer control is expected to continue for years. In this Series paper, we summarise progress in several aspects of cancer control since 2015, and identify persistent barriers requiring commitment of additional resources to reduce the cancer burden in Latin America and the Caribbean.

Brazil's struggles and strengths in biomedical sciences and healthcare: A conversation with the former minister of health Nelson Teich.

This commentary is a summary of two conversations among Brazilian former Minister of Health and oncologist Nelson Teich; Brazilian thoracic surgeon, Marcio Lucas; and anatomists Jeffrey Laitman and Daniella Curcio. We discuss a number of topics in Medical Education, Biomedical Science, and Healthcare, including the different stages of the Brazilian response to the COVID-19 pandemic. The discussions also explore: Brazil's and Brazilians strengths and struggles in the advancement of biomedicine; universal barriers to furthering advances; and problems specific to Brazil.

Patient-centered outcomes in non-small-cell lung cancer: a real-world perspective.

Aims: To assess non-small-cell lung cancer (NSCLC) patient-centered outcomes in the real world. Methods: This is a prospective study of NSCLC patients treated at a private cancer care institution in Brazil between 2014 and 2019. Results: The report comprises 337 patients. Advanced stage was associated with higher symptom burden - fatigue (p = 0.03), pain (p < 0.001) and arm pain (p = 0.022) - and worse global, social and physical functioning (all p < 0.001). In the first 2 years, most factors evolved to either improvement or stability: cough (p = 0.02), pain (p = 0.002), global functioning (p < 0.001) and emotional functioning (p < 0.001). Staging (p < 0.001), fatigue (p = 0.001) and gender (p = 0.004) were independently associated with overall survival. Conclusions: Our results demonstrate the feasibility of conducting real-world prospective analysis of patient-centered outcomes.

Lay abstract This study looked at patient-centered outcomes in lung cancer in a real-world setting. Standardized quality-of-life questionnaires were used to actively measure patients' perception of their functional well-being and health in a clinical setting. Three hundred thirty-seven patients were enrolled in a private cancer center in Brazil between 2014 and 2019. We demonstrated that patients diagnosed at advanced stages presented with more symptoms and lower capacity to perform daily activities. However, symptoms and functioning tended to improve during treatment. Our results show that it is possible to put patients at the heart of cancer care and use their experience to guide clinical approach.

Outcome of Patients With Breast Cancer Treated in a Private Health Care Institution in Brazil.

PURPOSE: Middle-income countries like Brazil often have a dichotomous health care system in which patients may be treated in either public or private institutions that differ substantially in terms of level of access to diagnostic and therapeutic procedures. PATIENTS AND METHODS: This was a prospective, observational study to assess real-world data in 1,230 female patients with breast cancer who were treated in a private health care institution between 2012 and 2016 in Brazil. RESULTS: Breast cancer in these patients mostly was diagnosed at early (79.0% stages I or II) or locally advanced (16.1% stage III) stages. The primary tumor was resected in 89.0% of cases, most often through breast-conserving surgery (55.1%). Patients with locally advanced disease received more aggressive therapy (eg, higher rates of mastectomy, axillary dissection and chemotherapy use) than patients with early-stage disease. The estimated 2-year overall survival (OS) was 95.3%. Survival was significantly longer among patients with stage I or II disease (2-year OS, 97.9% and 97.5%, respectively) than those with stage III or IV disease (89.4% and 69.5%, respectively; P < .01). Tumor grade was also correlated with OS in the overall cohort ( P = .05); triple-negative status was only prognostic for patients with stage III disease ( P < .01). CONCLUSION: The data provided aid understanding of the current scenario of breast cancer presentation and treatment in the Brazilian private health care system and may serve as a foundation to guide resource allocation. Our results reinforce the need to pursue adequate access to cancer care in low- and middle-income countries to optimize patient outcome.

Cost-effectiveness of low-level laser therapy (LLLT) in head and neck cancer patients receiving concurrent chemoradiation.

BACKGROUND: Oral mucositis is a major event increasing treatment costs of head and neck squamous cell carcinoma (HNSCC) patients treated with chemoradiation (CRT). This study was designed to estimate the cost-effectiveness of low-level laser therapy (LLLT) to prevent oral mucositis in HNSCC patients receiving CRT. METHODS: From June 2007 to December 2010, 94 patients with HNSCC of nasopharynx, oropharynx, and hypopharynx entered a prospective, randomized, double blind, placebo-controlled, phase III trial. CRT consisted of conventional radiotherapy (RT: 70.2 Gy, 1.8 Gy/d, 5 times/wk)+concurrent cisplatin (100mg/m2) every 3 weeks. An InGaAlP (660 nm-100 mW-4J/cm2) laser diode was used for LLLT. RESULTS: From the perspective of Brazil's public health care system (SUS), total costs were higher in Placebo Group (PG) than Laser Group (LG) for opioid use (LG=US$ 9.08, PG=US$ 44.28), gastrostomy feeding (LG=US$ 50.50, PG=US$ 129.86), and hospitalization (PG=US$ 77.03). In LG, the cost was higher for laser therapy only (US$ 1880.57). The total incremental cost associated with the use of LLLT was US$ 1689.00 per patient. The incremental cost-effectiveness ratio (ICER) was US$ 4961.37 per grade 3-4 OM case prevented compared to no treatment. CONCLUSIONS: Our results indicate that morbidity was lower in the Laser Group and that LLLT was more cost-effective than placebo up to a threshold of at least US$ 5000 per mucositis case prevented. CLINICAL TRIAL INFORMATION: NCT01439724.

Survival and prognostic factors in patients with Non-Small Cell Lung Cancer treated in private health care / Sobrevida e fatores prognósticos em pacientes com câncer de pulmão de células não pequenas assistidos na saúde suplementar

INTRODUCTION: Outcomes data on Non-Small Cell Lung Cancer (NSCLC) are scarce with regard to the private health care in Brazil. The aim of this study was to describe the characteristics, treatments performed, and the survival of patients with NSCLC in a Brazilian private oncologic institution. METHODS: Medical charts from patients treated between 1998 and 2010 were reviewed, and data were transferred to a clinical research form. Long-term follow-up and survival estimates were enabled through active surveillance. RESULTS: Five hundred sixty-six patients were included, and median age was 65 years. Most patients were diagnosed in advanced stages (79.6% III/IV). The overall survival was 19.0 months (95%CI 16.2 - 21.8). The median survival was 99.7, 32.5, 20.2, and 13.3 months for stages I, II, III, and IV, respectively (p < 0.0001). Among patients receiving palliative chemotherapy, the median survival was 12.2 months (95%CI 10.0 - 14.4). CONCLUSIONS: The outcomes described are favorably similar to the current literature from developed countries. Besides the better access to health care in the private insurance scenario, most patients are still diagnosed in late stages. .

INTRODUÇÃO: Dados de desfechos em câncer de pulmão de células não pequenas (CPCNP) são escassos no contexto da saúde suplementar no Brasil. O objetivo deste estudo foi descrever as características, tratamentos realizados e a sobrevida desses pacientes em uma instituição oncológica privada brasileira. MÉTODOS: Foram revisados os prontuários de pacientes atendidos entre 1998 e 2010 com diagnóstico de CPCNP. Os dados foram transferidos para uma ficha clínica individual e posteriormente analisados. Pacientes ou familiares foram contatados a fim de otimizar o seguimento e a estimativa da sobrevida. RESULTADOS: Foram incluídos 566 pacientes, com idade mediana de 65 anos. Predominaram os diagnósticos em estádios avançados (79,6% III/IV). A sobrevida mediana foi de 19,0 meses (IC95% 16,2 - 21,8), sendo de 99,7, 32,5, 20,2 e de 13,3 meses nos estádios I, II, III e IV, respectivamente (p < 0,0001). Entre os pacientes que receberam quimioterapia paliativa, a sobrevida mediana foi de 12,2 meses (IC95% 10,0 - 14.4). CONCLUSÕES: Os desfechos encontrados se assemelham aos de países desenvolvidos. Apesar do maior acesso médico em pacientes com cobertura de planos de saúde, a maioria dos diagnósticos ocorre tardiamente. .

Survival and prognostic factors in patients with non-small cell lung cancer treated in private health care.

INTRODUCTION: Outcomes data on Non-Small Cell Lung Cancer (NSCLC) are scarce with regard to the private health care in Brazil. The aim of this study was to describe the characteristics, treatments performed, and the survival of patients with NSCLC in a Brazilian private oncologic institution. METHODS: Medical charts from patients treated between 1998 and 2010 were reviewed, and data were transferred to a clinical research form. Long-term follow-up and survival estimates were enabled through active surveillance. RESULTS: Five hundred sixty-six patients were included, and median age was 65 years. Most patients were diagnosed in advanced stages (79.6% III/IV). The overall survival was 19.0 months (95%CI 16.2 - 21.8). The median survival was 99.7, 32.5, 20.2, and 13.3 months for stages I, II, III, and IV, respectively (p < 0.0001). Among patients receiving palliative chemotherapy, the median survival was 12.2 months (95%CI 10.0 - 14.4). CONCLUSIONS: The outcomes described are favorably similar to the current literature from developed countries. Besides the better access to health care in the private insurance scenario, most patients are still diagnosed in late stages.

Impacto do uso da pinça seladora ou do bisturi harmônico nos desfechos intra-hospitalares e no custo de procedimentos de tireoidectomia / Impact of the use of vessel sealing or harmonic scalpel on intra-hospital outcomes and the cost of thyroidectomy procedures

OBJETIVOS: Analisar tempo cirúrgico, tempo de internação, sangramento, escore de dor no período pós-operatório e custo referente aos procedimentos de tireoidectomia com utilização de pinça seladora ou bisturi harmônico, comparando-os à técnica convencional. MÉTODOS: Análise retrospectiva das tireoidectomias, realizadas entre 2007 e 2010, pela técnica convencional e com uso de pinça seladora ou bisturi harmônico. Foram analisados: gênero, idade, diagnóstico principal e tipo de procedimento. Os desfechos analisados foram: duração do procedimento, tempo de permanência hospitalar, necessidade de transfusão de hemoderivados, dor e custo da internação. As conclusões foram baseadas em um nível de significância de 5%, e as análises estatísticas foram realizadas utilizando o software R. RESULTADOS: Para o desfecho "duração da cirurgia", o uso da pinça seladora resultou em aumento médio de, aproximadamente, 47 minutos, quando comparado à técnica convencional (p<0,001) e o uso do bisturi harmônico levou à redução média de, aproximadamente, 32 minutos, quando comparado à técnica convencional (p<0,001). Não houve diferença estatisticamente significativa entre os grupos quanto ao uso de hemoderivados e escore de dor. Procedimentos que utilizaram pinça seladora ou bisturi harmônico apresentaram custo superior quando comparados àqueles com a técnica convencional. CONCLUSÃO: O uso do bisturi harmônico mostrou-se favorável na redução do tempo cirúrgico, porém não foi observada redução no tempo de hospitalização. O custo do procedimento foi mais alto em relação à técnica convencional. O uso da pinça seladora não trouxe vantagens com relação aos desfechos, e o custo do procedimento foi maior quando comparado à técnica convencional.

OBJECTIVES: To analyze the operative time, length of hospitalization and cost, as well as the bleeding and pain observed during the postoperative period, of thyroidectomy procedures using vessel sealing, harmonic scalpel or the conventional technique. METHODS: Retrospective analysis of thyroidectomies performed between 2007 and 2010 using either the conventional technique or minimally invasive techniques involving vessel sealing or a harmonic scalpel. Gender, age, primary diagnosis and procedure type were analyzed. The outcomes analyzed included the length of the procedure, length of hospital stay, need for blood product transfusions, pain and cost of hospitalization. The findings were based on a significance level of 5%, and statistical analyses were performed using the R software. RESULTS: The use of the vessel sealing increased the duration of the surgery by approximately 47 minutes compared to the conventional technique (p<0.001), and the use of the harmonic scalpel decreased the duration of the surgery by approximately 32 minutes compared to the conventional technique (p<0.001). No statistically significant difference was found between the groups regarding the use of blood products and pain score. Procedures involving vessel sealing or a harmonic scalpel cost more than those using the conventional technique. CONCLUSION: The use of harmonic scalpel was favorable in terms of reducing the surgical time, but there was no reduction in hospitalization time. The cost of the procedure was higher than that of the conventional technique. The use of vessel sealing offered no advantages in terms of the outcomes assessed, and the cost of the procedure was greater than that of the conventional technique.

Bloodstream Infection in the Intensive Care Unit: Preventable Adverse Events and Cost Savings.

OBJECTIVES: Central line associated bloodstream infections (CLABSIs) impose a significant economic burden for patients admitted to the intensive care unit for adults (AICU). The objectives of the study were to evaluate the excess length of stay and extra costs attributable to CLABSIs diagnosed in the AICU. METHODS: Cases were selected as patients admitted to AICU from 2006 through 2009, who developed a CLABSI episode. These were matched (1:1) with appropriate controls. Matching criteria were selected to exclude other factors that could influence cost and care practices. The length of stay and resources used between AICU admission and discharge and until hospital discharge or death were measured. Incremental costs and lengths of stay were calculated for each pair of patients. RESULTS: Thirty cases and 30 controls were included in the study. A CLABSI episode resulted in an additional 10.5 days in the AICU and 9.1 days after AICU discharge, totaling an additional 19.6 days. The incremental cost associated with a CLABSI episode was US $65,993 in the AICU and US $23,893 after AICU discharge, totaling an incremental cost of US $89,886. CONCLUSIONS: By avoiding CLABSI events, cost offsets would be expected for payers with revenue losses to providers. An approach of sharing the gains resulting from preventive measures could be used to incentivize providers to maintain those investments, benefiting patients who will have a reduced risk of CLABSI development.

Impact of the use of vessel sealing or harmonic scalpel on intra-hospital outcomes and the cost of thyroidectomy procedures.

OBJECTIVES: To analyze the operative time, length of hospitalization and cost, as well as the bleeding and pain observed during the postoperative period, of thyroidectomy procedures using vessel sealing, harmonic scalpel or the conventional technique. METHODS: Retrospective analysis of thyroidectomies performed between 2007 and 2010 using either the conventional technique or minimally invasive techniques involving vessel sealing or a harmonic scalpel. Gender, age, primary diagnosis and procedure type were analyzed. The outcomes analyzed included the length of the procedure, length of hospital stay, need for blood product transfusions, pain and cost of hospitalization. The findings were based on a significance level of 5%, and statistical analyses were performed using the R software. RESULTS: The use of the vessel sealing increased the duration of the surgery by approximately 47 minutes compared to the conventional technique (p<0.001), and the use of the harmonic scalpel decreased the duration of the surgery by approximately 32 minutes compared to the conventional technique (p<0.001). No statistically significant difference was found between the groups regarding the use of blood products and pain score. Procedures involving vessel sealing or a harmonic scalpel cost more than those using the conventional technique. CONCLUSION: The use of harmonic scalpel was favorable in terms of reducing the surgical time, but there was no reduction in hospitalization time. The cost of the procedure was higher than that of the conventional technique. The use of vessel sealing offered no advantages in terms of the outcomes assessed, and the cost of the procedure was greater than that of the conventional technique.