Public-private partnerships in transplant drug development.

The Transplant Therapeutics Consortium (TTC), a public-private partnership (PPP) led by the Critical Path Institute (C-Path), recently published a whitepaper titled "The Importance of Drug Safety and Tolerability in the Development of New Immunosuppressive Therapy for Transplant Recipients" by Stegall et al in the American Journal of Transplantation. As staff members of the Food and Drug Administration's (FDA), Center for Drug Evaluation and Research (CDER), Office of New Drugs and Office of Translational Science, and the Oncology Center of Excellence, we would like to provide our perspective on the TTCs efforts and the whitepaper.

Meeting report: FDA public meeting on patient-focused drug development and medication adherence in solid organ transplant patients.

The Food and Drug Administration (FDA) held a public meeting and scientific workshop in September 2016 to obtain perspectives from solid organ transplant recipients, family caregivers, and other patient representatives. The morning sessions focused on the impact of organ transplantation on patients' daily lives and the spectrum of activities undertaken to maintain grafts. Participants described the physical, emotional, and social impacts of their transplant on daily life. They also discussed their posttransplant treatment regimens, including the most burdensome side effects and their hopes for future treatment. The afternoon scientific session consisted of presentations on prevalence and risk factors for medication nonadherence after transplantation in adults and children, and interventions to manage it. As new modalities of Immunosuppressive Drug Therapy are being developed, the patient perceptions and input must play larger roles if organ transplantation is to be truly successful.

Programa de intervención con la técnica de cloze: Elaboración y Significancia Clínica / Programa de intervenção com a técnica de cloze: elaboração e significância clínica / Intervention program with the cloze technique: elaboration and clinical significance

RESUMO A hipótese deste estudo está pautada no fato de que um programa de remediação com a Técnica de Cloze, nivelado por diferentes graus de dificuldades, pode contribuir para o desenvolvimento da compreensão leitora de escolares com dificuldades de compreensão leitora. Sendo assim, objetivou-se elaborar este programa e analisar a significância clínica. Para isto, elaborou-se um programa de intervenção por meio de uma revisão bibliográfica e após foi realizado um estudo piloto e aplicado em 28 escolares ensino fundamental I, divididos em Grupo I Estudo (escolares com dificuldade em texto narrativo submetidos à intervenção); Grupo I Controle (escolares com dificuldade em texto narrativo não submetidos à intervenção); Grupo II Estudo (escolares com dificuldade em texto expositivo submetidos à intervenção); Grupo II Controle (escolares com dificuldade em texto expositivo não submetidos à intervenção). Os resultados analisados pelo Método JT apontaram mudança confiável positiva e com significância clínica para escolares do Grupo I Estudo, e de forma significativa para escolares do Grupo II Estudo.

RESUMEN La hipótesis de este estudio está centrada en el hecho de que un programa de remediar con la Técnica de Cloze, nivelado por distintos grados de dificultades, puede contribuir para el desarrollo de la comprensión lectora de escolares con dificultades de comprensión lectora. Por eso, se tuvo por objetivo elaborar este programa y analizar la significancia clínica. Para ello, se elaboró un programa de intervención por intermedio de una revisión bibliográfica y después se realizó un estudio piloto y aplicado en 28 escolares enseñanza básica I, divididos en Grupo I Estudio (escolares con dificultad en texto narrativo sometidos a la intervención); Grupo I Control (escolares con dificultad en texto narrativo no sometidos a la intervención); Grupo II Estudio (escolares con dificultad en texto expositivo sometidos a la intervención); Grupo II Control (escolares con dificultad en texto expositivo no sometidos a la intervención). Los resultados analizados por el Método JT apuntaran cambio fiable positivo y con significancia clínica para escolares del Grupo I Estudio, y de forma significativa para escolares del Grupo II Estudio.

ABSTRACT The hypothesis of this study is based on the fact that a remediation program with the Cloze Technique, leveled by different degrees of difficulties, it can contribute to the development of reading comprehension of students with reading comprehension difficulties. Therefore, the objective was to develop this program and analyze the clinical significance. For this, an intervention program was developed through a bibliographic review and after that a pilot study was carried out and applied in 28 elementary school students, divided into Group I Experimental (students with difficulty in narrative text submitted to the intervention); Group I Control (students with difficulty in narrative text not submitted to the intervention); Group II Experimental (students with difficulty in expository text submitted to the intervention); Group II Control (students with difficulty in expository text not submitted to the intervention). The results analyzed by the JT Method showed a reliable positive change with clinical significance for students in Group I Study, and significantly for students in Group II Experimental.

Summary of 2017 FDA Public Workshop: Antibody-mediated Rejection in Kidney Transplantation.

Despite major advances in understanding the pathophysiology of antibody-mediated rejection (AMR); prevention, diagnosis and treatment remain unmet medical needs. It appears that early T cell-mediated rejection, de novo donor-specific antibody (dnDSA) formation and AMR result from patient or physician initiated suboptimal immunosuppression, and represent landmarks in an ongoing process rather than separate events. On April 12 and 13, 2017, the Food and Drug Administration sponsored a public workshop on AMR in kidney transplantation to discuss new advances, importance of immunosuppressive medication nonadherence in dnDSA formation, associations between AMR, cellular rejection, changes in glomerular filtration rate, and challenges of clinical trial design for the prevention and treatment of AMR. Key messages from the workshop are included in this summary. Distinction between type 1 (due to preexisting DSA) and type 2 (due to dnDSA) phenotypes of AMR needs to be considered in patient management and clinical trial design. Standardization and more widespread adoption of routine posttransplant DSA monitoring may permit timely diagnosis and understanding of the natural course of type 2 and chronic AMR. Clinical trial design, especially as related to type 2 and chronic AMR, has specific challenges, including the high prevalence of nonadherence in the population at risk, indolent nature of the process until the appearance of graft dysfunction, and the absence of accepted surrogate endpoints. Other challenges include sample size and study duration, which could be mitigated by enrichment strategies.

Intervenção com a fluência de leitura - scoping review / Reading fluency intervention - Scoping review

A fluência de leitura envolve acurácia, velocidade de leitura e prosódia, sendo seu papel relevante na compreensão de leitura. Estudos com a fluência de leitura são escassos no Brasil, principalmente quando se refere a intervenção. A fim de auxiliar estudos brasileiros futuros, este scoping review tem como objetivo apresentar os artigos de revisão existentes sobre intervenção em fluência de leitura, buscando analisar as implicações dos resultados destas pesquisas para a prática interventiva em fluência de leitura. Os resultados demonstram nove estudos de revisão em que a leitura repetida é a estratégia mais utilizada e mais eficaz quando associada a outras estratégias. Além disso, grande parte dos estudos mostram o impacto positivo na compreensão de leitura. Conclui-se, portanto, que foi possível rastrear e analisar os estudos de intervenções eficazes em fluência de leitura, para que assim sirvam de referência para novas pesquisas brasileiras voltadas ao tema, auxiliando os profissionais.

Reading fluency involves accuracy, reading speed and prosody, with its relevant role in reading comprehension. Studies with reading fluency are scarce in Brazil, especially when referring to the intervention. In order to assist future Brazilian studies, this scoping review aims to present the existing review articles on intervention in reading fluency, seeking to analyze the implications of the results of these research for the interventional practice in reading fluency. The results show 9 review studies in which repeated reading is the most used and most effective strategy when associated with other strategies. In addition, most studies show a positive impact on reading comprehension. It is concluded, therefore, that it was possible to track and analyze the studies of effective interventions in reading fluency, so that they thus serve as a reference for new Brazilian research focused on the theme, assisting professionals.

US Food and Drug Administration approval of ciprofloxacin hydrochloride for management of postexposure inhalational anthrax.

In August 2000, the US Food and Drug Administration (FDA) approved ciprofloxacin hydrochloride (Cipro; Bayer) for management of postexposure inhalational anthrax. This was the first antimicrobial drug approved by the FDA for use in treating an infection due to a biological agent used intentionally. The terrorist attacks of 2001 involving anthrax underscore the imperative that safe and effective drugs to manage such infections be readily available in the United States. The approval of ciprofloxacin hydrochloride, which was made on the basis of a surrogate human marker of efficacy, made extensive use of data from an animal model of disease. This represents a new direction in the development of efficacy data in support of drug approval and facilitates the availability of those drugs for which there is an urgent need. This article presents the scientific data and regulatory mechanism that supported the approval of ciprofloxacin hydrochloride for management of postexposure of inhalational anthrax.

FDA perspective: enrolment of elderly transplant recipients in clinical trials.

Since 1989, the U.S. Food and Drug Administration (FDA) has encouraged the study of new drug and therapeutic products in elderly patients. However, despite the aging population in the United States, elderly patients continue to be underrepresented in clinical trials across a variety of therapeutic areas, including transplantation. The currently available tools for the FDA to encourage and require the evaluation and reporting of safety and efficacy information in elderly patients are summarized. Clinicians, sponsors, and investigators are encouraged to work with the FDA to expand the enrolment of elderly patients in clinical trials of transplantation.