Bioethical conflicts arising out of access to orphan drugs in Brazil: the example of laronidase for treating mucopolysaccharidosis type I

Submitted by Gilvan Almeida ([email protected]) on 2016-08-10T18:30:49Z No. of bitstreams: 2 891.pdf: 5555282 bytes, checksum: 4967cf80e2f0f12e343be4ff4e9e02f8 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Maria Arruda ([email protected]) on 2018-02-08T12:21:29Z (GMT) No. of bitstreams: 2 891.pdf: 5555282 bytes, checksum: 4967cf80e2f0f12e343be4ff4e9e02f8 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2018-02-08T12:21:29Z (GMT). No. of bitstreams: 2 891.pdf: 5555282 bytes, checksum: 4967cf80e2f0f12e343be4ff4e9e02f8 (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2011Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Rio de Janeiro, RJ, Brasil.Esta pesquisa busca, como seu objetivo principal, discutir conflitos morais decorrentes do acesso e da alocação de recursos públicos, a medicamentos órfãos, tomando como exemplo a laronidase, medicamento pleiteado para o tratamento de uma doença órfã denominada mucopolissacaridose tipo I. A partir da obtenção de dados empíricos para análise, realizamos uma elaboração teórica acerca dos conflitos morais que permearam a prescrição, o acesso ou a negativa ao medicamento órfão pleiteado, em reflexões que se distribuíram em três artigos distintos:No primeiro artigo, ao caracterizarmos o acesso à laronidase, ponderamos acerca da judicialização da assistência farmacêutica. A necessidade de políticas focalizadoras que contemplem a necessidade de minorias versus a crescente preocupação com o financiameno público de medicamentos órfãos, em que pese os princípios do SUS, foram colocados, utilizando-se como base de discussão pensadores que lidam com a bioética principialista e teorias da justiça no contexto das instituições de saúde. No segundo artigo, ao caracterizarmos os argumentos processuais, discutimos os conflitos associados nas suas diversas esferas. Observamos a necessidade de trazer à tona a questão da transparência acerca das tomadas de decisões alocativas em saúde, visto que o critério de publicidade é uma dimensão ética do processo político, de acordo com um dos critérios definidos como accountability for reasonableness . No terceiro artigo, ao caracterizarmos as justificativas médicas para a prescrição da laronidase contidas nos laudos obtidos dos processos judiciais refletimos sobre os argumentos morais observados. Estes foram discutidos à luz dos princípios de beneficência e não maleficência e das ponderações de pensadores acerca das decisões alocativas em saúde e suas formas de racionamento.The main objective of this research project was to discuss the moral conflicts associated with public resource allocation and access to orphan drugs, based on the example of laronidase, a medication used in the treatment of the orphan disease mucopolysaccharidosis type I. After collecting empirical data for analysis, we constructed a theoretical framework of the moral conflicts that permeated prescription of and granting or denial of access to the requested drug, with reflections spanning three distinct article: In the first article, we sought to characterize access to laronidase and reflect on the judicialization of pharmaceutical assistance. We discuss the need for focal policies that take into account the needs of minorities versus a growing concern with public funding for orphan drugs, considering the principles of the Brazilian Unified Health System, using the work of principlist bioethicists and several theories of justice in the context of health care as a foundation. In the second article, we characterize arguments advanced in lawsuits and discuss the associated conflicts at various levels. We note the need to address the issue of transparency in resource allocation decisions in health care, as publicity is an ethical dimension of the political process, according to one of the criteria defined as “accountability for reasonableness”. In the third article, we characterize physicians’ rationales for prescribing laronidase, as contained in medical reports filed in support of lawsuits, and reflect on the moral arguments contained in these rationales, which are then discussed from the standpoint of the principles of beneficence and nonmaleficence and in light of the reflections of several thinkers as to resource allocation decisions and forms of rationing in health care

Luteoma Recorrente da Gravidez com Virilização Materna e Fetal Recurrent Luteoma of Pregnancy with Maternal and Fetal Virilization

Os luteomas da gravidez são pseudotumores ovarianos diagnosticados pelo exame ultra-sonográfico ou durante realização de cesariana e laqueadura pós-parto. Determinam, na segunda metade da prenhez, sinais de virilização materna em um quarto dos casos, o mesmo ocorrendo com a metade dos fetos femininos destas gestantes virilizadas nos quais se observa hipertrofia clitoridiana ou fusão labial. As dosagens séricas maternas dos hormônios androgênicos durante a prenhez e do sangue umbilical por ocasião do parto revelam taxas significativamente aumentadas. No exame ultra-sonográfico apresentam-se como estruturas sólidas ou cístico-sólidas, que após o parto tendem a regredir com o ovário readquirindo as dimensões normais em poucas semanas. Os autores apresentam uma paciente que em duas gestações sucessivas apresentou virilização materna e fetal. Ao exame ultra-sonográfico foram evidenciadas imagem ovariana nodular e dosagens elevadas dos androgênios plasmáticos.<br>Luteomas of pregnancy are ovarian pseudotumors diagnosed by ultrasound, during cesarean section or at postdelivery tubal ligation. Twenty-five per cent of the cases appear around the second half of pregnancy. Usually there are signs of maternal virilization and 50% are detected because female newborns show clitorimegaly and/or labial fusion. The concentrations of androgenic steroids in the maternal blood during pregnancy and in the cord blood at child-birth show significantly increased rates. The ultrasound shows solid or cystic-solid structures and few weeks after the delivery they decrease and the ovary size returns to normal. The authors report a case of a patient who exhibited virilization signs in two consecutive pregnancies as well as in the two female fetuses. At adnexal sonographic examination a solid tumoral image was found in both pregnancies. Serum androgen levels were increased

Dandy-Walker Malformation and Down Syndrome Association: Good Developmental Outcome and Successful Endoscopic Treatment of Hydrocephalus

The association of Down syndrome (DS) with Dandy Walker malformation (DWM) is extremely rare, with only 3 cases reported to date. All cases reported have shown a bad life expectancy and a bad developmental outcome. The present case reveals the possibility of a good prognosis. A 19-month-old male patient had successful endoscopic hydrocephalus treatment and a good developmental outcome. He probably had a better outcome because of good DS and DWM prognostic parameters. Our patient suffered from a DWM with vermis identification of 2 fissures and 3 lobes and a DS with a well-preserved tonus, which was not associated with other congenital systemic defects. We may conclude that the prognosis of DS-DWM association may separately depend on the degree of clinical and neurological involvement of each malformation

Molecular analysis of TSC1 and TSC2 genes and phenotypic correlations in Brazilian families with tuberous sclerosis

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by the development of multiple hamartomas in many organs and tissues. It occurs due to inactivating mutations in either of the two genes, TSC1 and TSC2, following a second hit in a tumor suppressor gene in most hamartomas. Comprehensive screening for mutations in both the TSC1 and TSC2 loci has been performed in several cohorts of patients and a broad spectrum of pathogenic mutations have been described. In Brazil, there is no data regarding incidence and prevalence of tuberous sclerosis and mutations in TSC1 and TSC2. We analyzed both genes in 53 patients with high suspicion of tuberous sclerosis using multiplex-ligation dependent probe amplification and a customized next generation sequencing panel. Confirmation of all variants was done by the Sanger method. We identified 50 distinct variants in 47 (89%) of the patients. Five were large rearrangements and 45 were point mutations. The symptoms presented by our series of patients were not different between male and female individuals, except for the more common occurrence of shagreen patch in women (p = 0.028). In our series, consistent with other studies, TSC2 mutations were associated with a more severe phenotypic spectrum than TSC1 mutations. This is the first study that sought to characterize the molecular spectrum of Brazilian individuals with tuberous sclerosis1210CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFundo de Incentivo a Pesquisa e Eventos (FIPE) of Hospital de Clinicas de Porto Alegre; Institute do Cancer Infantil (ICI

Families with a likely benign or variant of uncertain significance in <i>TSC1</i> and <i>TSC</i>.

<p>Families with a likely benign or variant of uncertain significance in <i>TSC1</i> and <i>TSC</i>.</p

Molecular analysis of <i>TSC1</i> and <i>TSC2</i> genes and phenotypic correlations in Brazilian families with tuberous sclerosis

<div><p>Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by the development of multiple hamartomas in many organs and tissues. It occurs due to inactivating mutations in either of the two genes, <i>TSC1</i> and <i>TSC2</i>, following a second hit in a tumor suppressor gene in most hamartomas. Comprehensive screening for mutations in both the <i>TSC1</i> and <i>TSC2</i> loci has been performed in several cohorts of patients and a broad spectrum of pathogenic mutations have been described. In Brazil, there is no data regarding incidence and prevalence of tuberous sclerosis and mutations in <i>TSC1</i> and <i>TSC2</i>. We analyzed both genes in 53 patients with high suspicion of tuberous sclerosis using multiplex-ligation dependent probe amplification and a customized next generation sequencing panel. Confirmation of all variants was done by the Sanger method. We identified 50 distinct variants in 47 (89%) of the patients. Five were large rearrangements and 45 were point mutations. The symptoms presented by our series of patients were not different between male and female individuals, except for the more common occurrence of shagreen patch in women (p = 0.028). In our series, consistent with other studies, <i>TSC2</i> mutations were associated with a more severe phenotypic spectrum than <i>TSC1</i> mutations. This is the first study that sought to characterize the molecular spectrum of Brazilian individuals with tuberous sclerosis.</p></div

Phenotypic comparison between male and female individuals with TSC.

<p>Phenotypic comparison between male and female individuals with TSC.</p