RESUMO
BACKGROUND: Oral mucositis (OM) is an oral toxicity caused by cancer treatment, found often in patients with head and neck cancer. Low-intensity laser therapy for OM has anti-inflammatory, analgesic, and tissue reparative properties. OBJECTIVE: The objective of this work is to perform a systematic review and meta-analysis of the randomized clinical trials of OM laser therapy in patients undergoing treatment for head and neck cancers, followed by a cost-effectiveness analysis of the therapy. METHOD: The search terms, mucositis and phototherapy, laser therapy and mucositis, photobiomodulation and mucositis, and low-level laser therapy and mucositis, were used to search the databases of PubMed, Web of Science, and MEDLINE. Randomized clinical trials were divided into two groups: one treated with laser therapy and the other given a placebo. Only 13 studies were included in the systematic review, and 6 studies in the meta-analysis. RESULTS: The results of the systematic review and meta-analysis show that the laser therapy presented good results in clinical improvement and pain reduction, decreasing the patients' likelihood of developing OM, with degrees of debilitating lesions, to 64% (RR = 0.36 [95% CI = 0.29-0.44]). The cost-effectiveness analysis revealed an incremental cost of R$ 3687.53 for the laser group, with an incremental effectiveness of 132.2. The incremental cost-effectiveness ratio (ICER) was 27.89, for the severe OM cases that were avoided. CONCLUSION: It was concluded, therefore, that photobiomodulation for OM in patients receiving head and neck cancer treatment was clinically effective and cost-effective.
Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Terapia a Laser/métodos , Fototerapia/métodos , Estomatite/terapia , Análise Custo-Benefício , Neoplasias de Cabeça e Pescoço/economia , Humanos , Terapia a Laser/economia , Fototerapia/economia , Lesões por Radiação/economia , Lesões por Radiação/etiologia , Lesões por Radiação/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Estomatite/induzido quimicamente , Estomatite/economia , Estomatite/etiologiaRESUMO
BACKGROUND: Clinical trials often report intervention efficacy in terms of the reduction in all-cause mortality between the treatment and control arms (i.e., an overall hazard ratio [oHR]) instead of the reduction in disease-specific mortality (i.e., a disease-specific hazard ratio [dsHR]). Using oHR to reduce all-cause mortality beyond the time horizon of the trial may introduce bias if the relative proportion of other-cause mortality increases with age. We sought to quantify this oHR extrapolation bias and propose a new approach to overcome this bias. METHODS: We simulated a hypothetical cohort of patients with a generic disease that increased background mortality by a constant additive disease-specific rate. We quantified the bias in terms of the percentage change in life expectancy gains with the intervention under an oHR compared with a dsHR approach as a function of the cohort start age, the disease-specific mortality rate, dsHR, and the duration of the intervention's effect. We then quantified the bias in a cost-effectiveness analysis (CEA) of implantable cardioverter-defibrillators based on efficacy estimates from a clinical trial. RESULTS: For a cohort of 50-year-old patients with a disease-specific mortality of 0.05, a dsHR of 0.5, a calculated oHR of 0.55, and a lifetime duration of effect, the bias was 28%. We varied these key parameters over wide ranges and the resulting bias ranged between 3 and 140%. In the CEA, the use of oHR as the intervention's effectiveness overestimated quality-adjusted life expectancy by 9% and costs by 3%, biasing the incremental cost-effectiveness ratio by - 6%. CONCLUSIONS: The use of an oHR approach to model the intervention's effectiveness beyond the time horizon of the trial overestimates its benefits. In CEAs, this bias could decrease the cost of a QALY, overestimating interventions' cost effectiveness.
Assuntos
Desfibriladores Implantáveis/economia , Modelos Econômicos , Mortalidade/tendências , Infarto do Miocárdio/economia , Avaliação de Resultados em Cuidados de Saúde/economia , Viés , Análise Custo-Benefício , Tomada de Decisões , Humanos , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Anos de Vida Ajustados por Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto/economiaRESUMO
BACKGROUND: Stepped-wedge cluster randomized trials (SW-CRTs) are increasingly popular in health-related research in both high- and low-resource settings. There may be specific ethical issues that researchers face when designing and conducting SW-CRTs in low-resource settings. Knowledge of these issues can help to improve the ethical conduct of SW-CRTs in a global health context. METHODS: We performed an ethical analysis of two studies using SW-CRT designs in low-resource settings: the Que Vivan Las Madres study conducted from 2014 to 2017 in Guatemala and the Atmiyata study conducted from 2017 to 2018 in rural parts of India. For both case studies, we identified and evaluated the classification of the study as research or nonresearch and the ethical issues regarding the justification of the design, including the delayed rollout of an intervention that had a promising effect. RESULTS: In our case studies, some minor ethical issues surfaced about the registration and stakeholder pressure on the order of randomization, but both included good justification for the design and delayed rollout. Our analysis did, however, demonstrate that careful consideration of the role of randomization and registration of the trials is important. DISCUSSION: SW-CRTs can provide an opportunity for rigorous evaluation of interventions destined to be rolled out on the basis of limited evidence. Furthermore, in SW-CRTs, the underlying objective is often to provide a robust evaluation of the effectiveness for generalized dissemination, and this makes the SW-CRT no less a research study than any other form of cluster randomized trial. CONCLUSION: The design and conduct of stepped-wedge cluster randomized trials raises at least two ethical issues that need special consideration in both high- and low-resource settings: the justification for using the design, specifically the delayed rollout of the intervention to the control group, and the classification of the study as research or nonresearch. In our case studies, these issues did not seem to raise special ethical scrutiny in low-resource settings. Further ethical evaluation will hopefully result in specific ethical guidelines for the use of SW-CRTs in both high- and low-resource settings to contribute to responsible functioning of these trials and adequate protection of participants.
Assuntos
Grupos Controle , Países em Desenvolvimento/economia , Recursos em Saúde/ética , Ensaios Clínicos Controlados Aleatórios como Assunto/ética , Projetos de Pesquisa , Análise por Conglomerados , Guatemala , Humanos , Índia , Ensaios Clínicos Controlados Aleatórios como Assunto/economiaRESUMO
Background: The purpose of inflammatory bowel disease (IBD) treatment is to achieve resolution of symptoms and remission of disease with a minimum of adverse events (AE). Aim: To report AE of different prescriptions used for the treatment of IBD. Material and Methods: Analysis of a registry of patients with IBD held at a private clinic from 1976 to 2013. All used medications, the occurrence and severity of AE were recorded. Results: The records of 346 patients aged 16 to 86 years, 74% with ulcerative colitis, were analyzed. The most commonly type of medications prescribed were 5-aminosalicylates (5-ASAs) in 329 patients (92%), followed by adrenal steroids in 218 (61%). Forty nine AE were recorded in the same number of patents (14%). These were more common in patients with Crohn disease (n = 19, 21%). An univariate analysis, demonstrated that extra-intestinal manifestations, hospitalizations secondary to IBD crisis, requirement of surgery and treatment with steroids, immunosuppressants or biologic agents were significantly associated with the presence of AE. AEs were more common with immunosuppressants, followed by 5-ASAs and steroids. Discontinuation of therapy was required in 79, 100 and 43% of patients taking these medications, respectively. Twenty percent of AEs were severe. Leukopenia and pancytopenia along with alopecia were the most common AEs attributable to azathioprine. Conclusions: The occurrence of AEs in patients with IBD is uncommon. Even inmunosuppressants or biologic agents have a low rate of AE and most of them mild.
Assuntos
Humanos , Pesquisa Biomédica/organização & administração , Dermatologia/organização & administração , Estudos Multicêntricos como Assunto , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Apoio à Pesquisa como Assunto/organização & administração , Antibacterianos/administração & dosagem , Pesquisa Biomédica/economia , Celulite (Flegmão)/prevenção & controle , Comportamento Cooperativo , Dermatologia/economia , Eczema/prevenção & controle , Reino Unido , Relações Interinstitucionais , Perna (Membro) , Estudos Multicêntricos como Assunto/economia , Objetivos Organizacionais , Avaliação de Programas e Projetos de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Pesquisadores/economia , Pesquisadores/organização & administração , Abrandamento da ÁguaRESUMO
The problem of standard of care in clinical research concerns the level of treatment that investigators must provide to subjects in clinical trials. Commentators often formulate answers to this problem by appealing to two distinct types of obligations: professional obligations and natural duties. In this article, I investigate whether investigators also possess institutional obligations that are directly relevant to the problem of standard of care, that is, those obligations a person has because she occupies a particular institutional role. I examine two types of institutional contexts: (1) public research agencies - agencies or departments of states that fund or conduct clinical research in the public interest; and (2) private-for-profit corporations. I argue that investigators who are employed or have their research sponsored by the former have a distinctive institutional obligation to conduct their research in a way that is consistent with the state's duty of distributive justice to provide its citizens with access to basic health care, and its duty to aid citizens of lower income countries. By contrast, I argue that investigators who are employed or have their research sponsored by private-for-profit corporations do not possess this obligation nor any other institutional obligation that is directly relevant to the ethics of RCTs. My account of the institutional obligations of investigators aims to contribute to the development of a reasonable, distributive justice-based account of standard of care.
Assuntos
Setor Privado , Setor Público , Ensaios Clínicos Controlados Aleatórios como Assunto/economia , Ensaios Clínicos Controlados Aleatórios como Assunto/ética , Justiça Social , Responsabilidade Social , Padrão de Cuidado/ética , Pesquisa Biomédica/economia , Pesquisa Biomédica/ética , Bolívia , Combinação de Medicamentos , Ética Institucional , Ética em Pesquisa , Álcoois Graxos/administração & dosagem , Álcoois Graxos/economia , Humanos , Cooperação Internacional , Fosfatidilgliceróis/administração & dosagem , Fosfatidilgliceróis/economia , Proteínas/administração & dosagem , Proteínas/economia , Surfactantes Pulmonares/administração & dosagem , Surfactantes Pulmonares/economia , Pesquisadores/economia , Pesquisadores/ética , Apoio à Pesquisa como Assunto , Estados UnidosRESUMO
OBJECTIVES: Several methodological problems arise when health outcomes and resource utilization are collected at different sites. To avoid misleading conclusions in multi-center economic evaluations the center effect needs to be taken into adequate consideration. The aim of this article is to compare several models, which make use of a different amount of information about the enrolling center. METHODS: To model the association of total medical costs with the levels of two sets of covariates, one at patient and one at center level, we considered four statistical models, based on the Gamma model in the class of the Generalized Linear Models with a log link, which use different amount of information on the enrolling centers. Models were applied to Cost of Strategies after Myocardial Infarction data, an international randomized trial on costs of uncomplicated acute myocardial infarction (AMI). RESULTS: The simple center effect adjustment based on a single random effect results in a more conservative estimation of the parameters as compared with approaches which make use of deeper information on the centers characteristics. CONCLUSIONS: This study shows, with reference to a real multicenter trial, that center information cannot be neglected and should be collected and inserted in the analysis, better in combination with one or more random effect, taking into account in this way also the heterogeneity among centers because of unobserved centers characteristics.