Children’s drug research and development incentives and market pricing optimization based on medical imaging

This series of monographs covers the latest in paediatric drug development and areas of clinical research. It also gives the reader a background to the enormous strides being made globally by agencies such as the European Medicines Agency, and the impact that the Food and Drugs Administration (FDA) Modernisation Act exclusivity incentive have had in encouraging paediatric drug research and development. As the introduction to this book suggests, children in the developed world have never had it so good as far as modern medical care and longevity are concerned. It is noteworthy that more than half of babies born in any G8 country today will live to 100 years based on current life expectancy trends. However (and embarrassingly so for the developed world), the monograph examining global access to essential medicines for children reminds us that although children in the developing world are increasingly enjoying the fruits of better healthcare, the morbidity and mortality rates for treatable medical conditions remain disturbingly high. The WHO Better Medicines for Children programme is clearly committed to narrowing this ever increasing global disparity in children's health and welfare, nevertheless the challenges faced by this organization will mean that at least one third of the world's population will remain ‘therapeutic orphans.’ The use of unlicensed and ‘off label’ medicines in children is widespread and yet drug toxicity remains a significant issue. The majority of drugs prescribed for children have not been adequately or properly tested in paediatric populations and without sufficient information and adequate data arising from further studies, children will remain the poor relations to their adult counterparts in the area of paediatric drug research and development. It is estimated that one in 10 children in hospital are likely to experience an adverse drug reaction. To address this and other concerns, governments, European regulation and the pharmaceutical industry are all applying a concerted approach in the area of paediatric drug development and clinical research, and there are several useful monographs in this book dealing with the regulatory and practical aspects of such developments. No guide to paediatric research can ignore the ethical and practical issues that have to be addressed when embarking on a paediatric pharmacological study and the book's monograph on this topic deals with these issues both adequately and succinctly. The last few chapters of this book deal with the practicalities of drug research trials in paediatric infections and vaccinations, paediatric obesity, hypertension and familial dyslipidaemias and attempt to deal with the thorny issue of using placebo therapy in children enrolled in randomized controlled trials. In conclusion, the editors of this book have brought together a diverse array of opinion in paediatric drug development. Any individual or organization embarking upon clinical research and paediatric drug development would be well placed in having read and considered some of the chapters in this book which identify the ethical, economic, logistical and technical issues currently hindering paediatric drug development. The ultimate expectation from carefully considered and conducted clinical trials is that children worldwide will benefit from the strides being made in this important area of children's health.

Pediatric Ontogeny: Moving From Translational Science to Drug Development.

This paper constructs theoretical game models to explore the joint effects of tax rate disparity and consumers’ strategic purchasing behavior on brand’s foreign market encroachment strategy and the downstream enterprises’ pricing strategy, as well as supply chain members’ profit. Results show that (1) Under selling subsidiary encroachment, uniform pricing strategy is only adopted when strategic consumers’ patience level is relatively high and the tax rate disparity is sufficiently low. Under retail encroachment, the retailer prefers dynamic pricing strategy when strategic consumers’ patience level is relatively low, and uniform pricing strategy otherwise. (2) When dynamic pricing strategy is chosen, a larger tax rate disparity can benefit the selling subsidiary and higher strategic consumers’ patience level may benefit both the brand and the selling subsidiary. (3) When strategic consumers’ patience level is relatively low, with sufficiently large tax rate disparity, the brand would always choose retail encroachment strategy. With relatively small tax rate disparity, the brand may choose the selling subsidiary encroachment if the establishing cost is not so high, and retail encroachment otherwise. However, when strategic consumers’ patience level is relatively high, the brand may also choose selling subsidiary encroachment strategy even if the tax rate disparity is not that high, regardless of what the establishing cost is. This is probably due to retailer’s dynamic pricing strategy can bring more demand than the selling subsidiary’s uniform pricing strategy does.

Pediatric drug development is a challenging process due to the rarity of the population, the need to meet regulatory requirements across the globe, the associated uncertainty in extrapolating data from adults, the paucity of validated biomarkers, and the lack of systematic testing of drugs in pediatric patients. In oncology, pediatric drug development has additional challenges that have historically delayed availability of safe and effective medicines for children. In particular, the traditional approach to pediatric oncology drug development involves conducting phase 1 studies in children once the drug has been characterized and in some cases approved for use in adults. The objective of this article is to describe clinical pharmacology factors that influence pediatric oncology trial design and execution and to highlight efficient approaches for designing and expediting oncology drug development in children. The topics highlighted in this article include (1) study design considerations, (2) updated dosing approaches, (3) ways to overcome the significant biopharmaceutical challenges unique to the oncology pediatric population, and (4) use of data analysis strategies for extrapolating data from adults, with case studies. Finally, suggestions for ways to use clinical pharmacology approaches to accelerate pediatric oncology drug development are provided.

Implementation of mechanism of action biology-driven early drug development for children with cancer

This study presents a novel approach to understanding the complex dynamics of the electric vehicle (EV) market through the lens of differential game theory. We developed a comprehensive model that captures the strategic interactions between EV manufacturers and charging network operators, while incorporating the effects of consumer behavior, market uncertainties, and reference price effects. Using differential game theory, we examined the impact of reference price effects and the charging network’s influence on pricing strategies, focusing on three distinct approaches: basic pricing, static pricing considering reference price effects, and dynamic pricing strategies. Our model offers new insights into consumer behavior and price expectations in the rapidly evolving EV market. The key findings reveal that under static or dynamic pricing strategies, the optimal pricing for EV manufacturers is positively correlated with the initial reference price. When the initial reference price is high (low), the optimal pricing strategy resembles skimming pricing (penetration pricing). As the effort level of charging network operators increases and their influence on consumers’ purchase decisions grows stronger, EV manufacturers tend to set higher prices. Notably, while dynamic pricing strategies can optimize EV manufacturers’ profits, the profits of charging network operators may decrease compared with static pricing strategies. This integrated approach significantly contributes to the field by bridging gaps among market dynamics, pricing strategies, and the infrastructure’s development in the context of electric mobility, providing a comprehensive framework for understanding and optimizing the EV ecosystem. Ultimately, this study advances sustainable business models that balance profitability, consumer behavior, and the infrastructure’s growth in the rapidly evolving EV market.

Improving Therapeutics to Better Care for Older Adults and the Young: Report From the American College of Clinical Pharmacology Workshop.

The literature thoroughly describes the challenges of pediatric drug development for rare diseases. This includes (1) generating interest from sponsors, (2) small numbers of children affected by a particular disease, (3) difficulties with study design, (4) lack of definitive outcome measures and assessment tools, (5) the need for additional safeguards for children as a vulnerable population, and (6) logistical hurdles to completing trials, especially with the need for longer term follow-up to establish safety and efficacy. There has also been an increasing awareness of the need to engage patients and their families in drug development processes and to address inequities in access to pediatric clinical trials. The year 2020 ushered in yet another challenge—the COVID-19 pandemic. The pediatric drug development ecosystem continues to evolve to meet these challenges. This article will focus on several key factors including recent regulatory approaches and public health policies to facilitate pediatric rare disease drug development, emerging trends in product development (biologics, molecularly targeted therapies), innovations in trial design/endpoints and data collection, and current efforts to increase patient engagement and promote equity. Finally, lessons learned from COVID-19 about building adaptable pediatric rare disease drug development processes will be discussed.

For more than two decades, regulatory agencies throughout the world released guidelines, rules and laws to stimulate and assist in paediatric drug development. In 2014, the National Health and Family Planning Commission (now known as the National Health Commission, NHC) and five other departments in China jointly issued 'Several Opinions on Safeguarding Medication for Children', after which several policies and regulations were issued to implement the priority review and approval of paediatric medicinal products and support the development of new drugs, including new dosage forms and strengths, for children. A total of 172 special medicinal products for children were approved from 2018 to 2022. Since 2016, the NHC, together with relevant administrative departments, has formulated and issued four paediatric drug lists containing 129 medicinal products to encourage research and development. At present, approximately 25 of these drugs (at exactly the same dosage forms and strengths as on the lists) have been approved for marketing, including antitumour drugs and immunomodulators, nervous system drugs, drugs for mental disorders and drugs for rare diseases. In this review, we analysed the regulations issued for promoting paediatric drug development in China, including the priority review and approval system, technical guidelines, data protection and financial support policies and general profiles of paediatric drug approval, clinical trials and the addition of information for children in the labels of marketed medicinal products. Finally, we discussed the challenges and possible strategies in the research and development of paediatric drugs in China.

The Pediatric Pharmacy Association and Members Threaded Through a Career and the Impact on Pediatric Drug Development.

Taxi journeys are usually priced according to the distance covered and time taken for the trip. Such a fixed cost strategy is simple to understand, but does not take into account the likelihood that a taxi can pick up additional passengers at the original passenger's destination. In this paper we investigate dynamic taxi pricing strategies. By using domain knowledge, such strategies discount trips to locations containing many potential passengers, and increase fares to those areas with few potential passengers. Identifying a closed form optimal dynamic pricing strategy is difficult, and by representing the domain as an MDP, we can identify an optimal strategy for specific domains. We empirically compare such dynamic pricing strategies with fixed cost strategies, and suggest future extensions to this work.

The needs and advances in pediatric drug development have burgeoned since Shirkey initially referred to children as ‘therapeutic orphans’ [1]. Owing to requirements and incentives to investigate and develop therapeutic classes of molecules in children, drug development involving pediatric patients has risen steadily. The requirements are the result of the Pediatric Research Equity Act and the incentives are from the Best Pharmaceuticals for Children Act, two pieces of legislation that are set to expire in 2012 [101]. Pediatric Research Equity Act and Best Pharmaceuticals for Children Act have resulted in a total of 335 written requests issued (1998–July 2011), 323 marketing applications approved with postmarketing requirements (through May 2011) and 415 labels changed (1998–July 2011). From a global development perspective, ongoing collaborations between the US FDA and the other regulatory agencies, including the European Medicines Agency, facilitate these advances in pediatric product development. The significant role of personnel exchanges (short-term), working groups between both agencies, European Medicines Agency Non-clinical and Formulations Working Groups and expert meetings and workshops (including FDA representatives) and WHO initiatives, are helping to facilitate critical involvement and participation. Other collaborative networks between global regulatory partners include the Pediatric Regulators Network and Essential Medicines for Children Activities, Japan’s Pharmaceuticals & Medical Devices Agency as observers in the FDA’s and European Medicines Agency’s pediatric collaboration and the FDA and NIH collaboration to develop a publicly available framework on pediatric formulations. One important area for further development is the understanding of biomarkers and surrogate markers and their applications to pediatric clinical trials and drug development. The lack of appropriate parameters for pediatric clinical trials in children with gastrointestinal disease has resulted in the lack of appropriate end point identification and delays in pediatric product development. This is an area that would benefit from earlier attention in the overall development process. A renewed commitment to identify appropriate drug candidates and plan a process for approval for children is needed. Of the total products studied and labeled under US pediatric legislation, drugs with pediatric gastroenterology labeling account for only 8.6% (n = 11). Drug classes studied included treatment of hyper cholesterolemia, inflammatory bowel disease, vomiting, obesity and hepatitis B and C and acid blockade

El impacto de la fijación dinámica de precios en las percepciones de los clientes de restaurantes y en el sentimiento hacia los preciosResumenPropósitoEste estudio examina cómo la fijación dinámica de precios impacta en las percepciones de los clientes de los restaurantes y en el sentimiento hacia los precios a través de métricas de reputación en línea. Además, para profundizar en el debate sobre la fijación dinámica de precios, se propone una definición novedosa explorando las formas específicas de discriminación que pueden manifestarse en diferentes industrias.Diseño/metodología/enfoqueUtilizando un conjunto de datos exhaustivo de reseñas de restaurantes obtenidas de TripAdvisor, el estudio se centra en los restaurantes afiliados a uno de los mayores grupos de restaurantes en España. Empleamos un método cuasiexperimental (diferencias en diferencias) para estudiar cómo las estrategias de precios dinámicos influyen en las percepciones de valor de los clientes basándonos en las calificaciones numéricas. Mientras tanto, empleamos un modelo BERT en el componente textual de las reseñas para desentrañar los matices emocionales de la fijación dinámica de precios.HallazgosLos resultados no revelaron un impacto causal de las estrategias de precios dinámicos en las percepciones de los clientes. Además, el análisis de sentimiento no muestra una visión negativa aumentada después de introducir la fijación dinámica de precios en los restaurantes en comparación con el grupo de control. Contrariamente a lo que sugiere la literatura previa, nuestros hallazgos indican que la implementación de precios dinámicos no afecta negativamente las percepciones o los sentimientos de los clientes respecto a los precios en los restaurantes.Limitaciones/implicaciones de la investigaciónLa configuración cuasiexperimental del estudio presenta desafíos inherentes para establecer la causalidad que requieren una investigación más profunda utilizando entornos experimentales controlados. Sin embargo, nuestro estudio revela que los clientes de restaurantes no perciben la fijación de precios dinámica como injusta. Este hallazgo es crítico para los gerentes de restaurantes al considerar la implementación de la fijación de precios dinámica y estrategias de gestión de ingresos. Además, nuestro estudio resalta la importancia de considerar no solo las calificaciones numéricas sino también el análisis del sentimiento del cliente. Este enfoque más holístico para evaluar el impacto de las estrategias de precios puede dar a los gerentes de restaurantes una comprensión más profunda de las reacciones de los clientes. Además, se proporciona una definición de fijación de precios dinámica más rigurosa, aclarando su naturaleza y su distinción en el uso de diferentes discriminaciones de precios.Originalidad/valorEste estudio contribuye a la comprensión en evolución del impacto de las estrategias de fijación de precios dinámicos en las percepciones y sentimientos de los clientes en la industria restaurantera. Su objetivo es llenar el vacío en la comprensión de las reacciones de los clientes a los precios determinados algorítmicamente (a través de sistemas de gestión de ingresos (RMS) como DynamEat) en esta industria. La combinación de inferencia causal y análisis de sentimientos ofrece una perspectiva novedosa, arrojando luz sobre las conexiones matizadas entre la implementación de la fijación de precios dinámicos y las emociones de los clientes.

ICH E11 : développement d’un médicament pédiatrique : comparaison entre les États-Unis, l’Union Européenne et le Japon

Peak reduction in decentralised electricity systems : Markets and prices for flexible planning