Pharmaceutical Medicine最新文献

{"title":"Somatic Gene Therapy Research in Pediatric Populations: Ethical Issues and Guidance for Operationalizing Early Phase Trials.","authors":"Alison Bateman-House,&nbsp;Lesha D Shah,&nbsp;Rafael Escandon,&nbsp;Andrew McFadyen,&nbsp;Cara Hunt","doi":"10.1007/s40290-022-00451-x","DOIUrl":"https://doi.org/10.1007/s40290-022-00451-x","url":null,"abstract":"<p><p>Currently, pediatric research involving investigational gene therapies (GT, used without intending to imply a therapeutic effect) targets a broad range of indications (including rare and ultra-rare diseases) that vary in severity and availability of approved disease-modifying therapies. Because of this diversity of circumstances, there is no one-size-fits-all list of ethical concerns relevant to all uses of investigational GTs in children. Here, we review the main ethical issues, specifically those surrounding the current state of knowledge about GT product-related immunogenicity, toxicity, duration, irreversibility, informed consent/assent, trial design (including the question of who 'goes first'), participant and caregiver burdens, and equity in diagnosis and access to research opportunities. Ethical issues that can be anticipated to arise in pediatric GT clinical trials, e.g., the uncertainty and risk of this research, the resultant preclusion of GT trial participants from other research, the length of follow-up monitoring, and the urgency often felt by caregivers dealing with dire, rapidly progressive conditions, should be proactively identified, addressed in accordance with existing best practices, and transparently discussed among all stakeholders.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":"37 1","pages":"17-24"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9360607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Evidence: A Primer.","authors":"Amit Dang","doi":"10.1007/s40290-022-00456-6","DOIUrl":"https://doi.org/10.1007/s40290-022-00456-6","url":null,"abstract":"<p><p>Real-world evidence (RWE) is clinical evidence on a medical product's safety and efficacy that is generated using real-world data (RWD) resulting from routine healthcare delivery. There are several sources of RWD, including electronic health records (EHRs), registries, claims/billing data, and patient-generated data, as well as those from mobile health applications and wearable devices. Real-world data from these sources can be collected and analysed through different study designs such as prospective and retrospective cohort studies, case-control studies, and pragmatic clinical trials. Real-world evidence in the form of post-marketing surveillance has been extensively used to generate pharmacovigilance data. Of late, it has been realised that, apart from safety, RWE has additional applications in different stages of the drug approval cycle, and can be used to optimize the design of randomised controlled trials (RCTs). There has been an increasing awareness and acceptance of RWE from different stakeholders, including physicians, pharmaceutical companies, payers, regulators, and patients. Several regulatory authorities have also created frameworks and guidelines for efficient harnessing of RWE while acknowledging several challenges in RWD collection and analysis. The purpose of this review is to offer an outline of the current information on RWE, its advantages and disadvantages, as well as the associated challenges and ways to overcome them, while also throwing some light on the future of RWE.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":"37 1","pages":"25-36"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9815890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10870297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major Pharmaceutical Conferences and Courses: April to May 2023.","authors":"","doi":"10.1007/s40290-023-00460-4","DOIUrl":"https://doi.org/10.1007/s40290-023-00460-4","url":null,"abstract":"","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":"37 1","pages":"93-96"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10675005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Future of Health and Science: Envisioning an Intelligent HealthScience System.","authors":"Martin S Kohn,&nbsp;Rebecca Kush,&nbsp;Matthew Whalen,&nbsp;Mary Tobin,&nbsp;Dov Dori,&nbsp;Greg Koski","doi":"10.1007/s40290-022-00455-7","DOIUrl":"https://doi.org/10.1007/s40290-022-00455-7","url":null,"abstract":"","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":"37 1","pages":"1-6"},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9653034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Role of Polyphenolic Flavonoids as Senotherapeutic Agents in Degenerative Diseases and Geroprotection.","authors":"Kingsley C Mbara,&nbsp;Nikita Devnarain,&nbsp;Peter M O Owira","doi":"10.1007/s40290-022-00444-w","DOIUrl":"https://doi.org/10.1007/s40290-022-00444-w","url":null,"abstract":"<p><p>Cellular senescence, a hallmark of ageing, contributes to tissue or organ dysfunction and the pathophysiology of diverse age-related diseases (ARD) by various mechanisms. Targeting it by selective elimination of senescent cells (SCs) or blocking senescence-associated secretory phenotypes (SASP) with natural or synthetic compounds has been suggested to improve lifespan. Dietary phytochemicals possess a broad spectrum of biochemical and pharmacological effects that are beneficial to human health. Flavonoids, which are widely consumed in fruits and vegetables worldwide, are emerging as potential therapeutic agents to mitigate senescence. Naringenin, hesperetin, hesperidin, quercetin, fisetin, kaempferol, rutin, apigenin, luteolin, nobiletin, tangeretin, genistein, wogonin, epigallocatechin gallate (EGCG), theaflavin-3-gallate (TF2A), and procyanidin C1 possess potent antisenescence effects. A single biochemical process may not explain their pleiotropic pharmacological impact. Flavonoids directly modulate underlying cellular senescence processes or interact with molecular targets that regulate ageing-related pathways. This review discusses the potential use of flavonoids to mitigate senescence and consequently delay the onset of ageing-related diseases. We also highlight the underlying mechanisms of action of flavonoids as potential senotherapeutics and reflect on future perspectives and possible strategies to optimize and increase the translatability from bench to bedside in senotherapy.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":"36 6","pages":"331-352"},"PeriodicalIF":2.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9470070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33465921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Major Pharmaceutical Conferences and Courses: February to March 2023","authors":"","doi":"10.1007/s40290-022-00449-5","DOIUrl":"https://doi.org/10.1007/s40290-022-00449-5","url":null,"abstract":"","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":"36 1","pages":"401 - 403"},"PeriodicalIF":2.5,"publicationDate":"2022-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44908741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Pharmaceutical Year That Was, 2022","authors":"A. Fox","doi":"10.1007/s40290-022-00448-6","DOIUrl":"https://doi.org/10.1007/s40290-022-00448-6","url":null,"abstract":"","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":"36 1","pages":"327 - 330"},"PeriodicalIF":2.5,"publicationDate":"2022-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44746687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are the Current Processes and Regulations Fit for Purpose to Deliver Novel Therapies During Pandemics? A Perspective on COVID-19 from the UK.","authors":"Rajmeet Jandu, Carl Naraynassamy, Nadarajah Sreeharan","doi":"10.1007/s40290-022-00439-7","DOIUrl":"10.1007/s40290-022-00439-7","url":null,"abstract":"<p><p>The COVID-19 pandemic was the first 'stress test' to assess whether the current regulations in the United Kingdom (UK) are fit for purpose to develop novel therapies during pandemics. It saw innovations and collaborations across the spectrum of the drug development and regulatory pathways, including extraordinary collaborations between the various stakeholders involved in the process, the repositioning of medicines, the deployment of multi-arm, multi-interventional adaptive trials, the institution of operational simplicity and flexibility across various trial activities, and regulatory innovations. The question arises whether the innovative flexibilities and the urgency that were instituted could have resulted in compromises to the integrity of the process. An assessment of the conduct of the RECOVERY trial and the speedy approval of dexamethasone by the UK Medicines and Healthcare products Regulatory Agency demonstrates that no compromises were made to the ethical and scientific integrity of the process. Lessons learnt could be applied for future pandemics and to enhance R&D productivity and contribute to global health by improving access to medicines, especially in low- and middle-income countries and for neglected or rare diseases. What is needed is not a major transformation in the process but the flexible adaptation of existing regulations to reduce bureaucracy and handover times. Arriving at an optimal balance between scientific standards, regulations and commercial conflicts of interest will pose considerable challenges but what the COVID-19 pandemic has shown is that where there is will, there is always a way.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":"36 5","pages":"275-278"},"PeriodicalIF":3.1,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40653595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing Deep Learning for Detecting Adverse Drug Events in Structured and Unstructured Regulatory Drug Data Sets.","authors":"Benjamin M Knisely,&nbsp;Qais Hatim,&nbsp;Monifa Vaughn-Cooke","doi":"10.1007/s40290-022-00434-y","DOIUrl":"https://doi.org/10.1007/s40290-022-00434-y","url":null,"abstract":"<p><strong>Background: </strong>The US Food and Drug Administration (FDA) collects and retains several data sets on post-market drugs and associated adverse events (AEs). The FDA Adverse Event Reporting System (FAERS) contains millions of AE reports submitted by the public when a medication is suspected to have caused an AE. The FDA monitors these reports to identify drug safety issues that were undetected during the premarket evaluation of these products. These reports contain patient narratives that provide information regarding the AE that needs to be coded using standardized terminology to enable aggregation of reports for further review. Additionally, the FDA collects structured drug product labels (SPLs) that facilitate standardized distribution of information regarding marketed medical products. Manufacturers are currently not required to code labels with associated AEs.</p><p><strong>Objectives: </strong>Approaches for automated classification of reports by preferred terminology could enhance regulatory efficiency. The goal of this work was to assess the suitability of manually annotated FDA FAERS and SPL data sets to be subjected to predictive modeling.</p><p><strong>Methods: </strong>A recurrent neural network (RNN) was proposed as a proof-of-concept model for automated extraction of preferred AE terminology. A separate RNN was fit and cross-validated on two regulatory data sets with varying properties. First, the researchers trained and cross-validated a model on 325 annotated FAERS patient narratives for a sample of AE terms. A model was then trained and validated on a data set of 100 SPLs.</p><p><strong>Results: </strong>Model cross-validation results for product labels demonstrated that the model performed at least as well as more conventional models for all but one of the terms selected based on F1-score. Model results for the FAERS data set were mixed.</p><p><strong>Conclusions: </strong>This work successfully demonstrated a proof-of-concept machine learning approach to automatically detect AEs in several textual regulatory data sets to support post-market regulatory activities. Limited instances of each AE class likely prohibited models from generalizing data effectively. Additional data may permit more robust validation.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":"36 5","pages":"307-317"},"PeriodicalIF":2.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40532063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pricing and Market Access Challenges in the Era of One-Time Administration Cell and Gene Therapies.","authors":"Marco T Sabatini,&nbsp;Tia Xia,&nbsp;Mark Chalmers","doi":"10.1007/s40290-022-00443-x","DOIUrl":"https://doi.org/10.1007/s40290-022-00443-x","url":null,"abstract":"<p><p>With a large number of one-time administration cell and gene therapies expected to come to the market in the coming years, there is a renewed need to understand the existing and future challenges that such modalities bring about, especially as it relates to their assessment of value, pricing and access. Payer, health technology assessment (HTA) bodies and manufacturers alike are faced with a number of unprecedented challenges stemming from the fact that such therapies are 'one-time' and/or have curative intent, but often lack sufficient evidence to support such claims at the time of launch (i.e., during pricing and access negotiations). There are a number of different approaches to assessing economic value for cell and gene therapies across regions (e.g., US vs Europe), which ultimately lead to further disconnect in pricing and reimbursement outcomes across countries; yet, in many cases, affordability concerns relating to high upfront costs are raised by providers. To that end, cell and gene therapies have been frequently criticized by payers for their 'high sticker price' based on relatively limited evidence to support durability claims. New contracting solutions are increasingly being employed to overcome concerns specifically relating to the durability of clinical benefit, the comparative effectiveness of a therapy and affordability (i.e., the one-time high cost of therapy). Indeed, recent launches of cell and gene therapies have often leveraged outcome-based agreements, instalments, coverage with evidence generation, subscription models, stop-loss and payer reinsurance, etc. to mitigate concerns from payers and providers and drive access. In this paper, we aim to review challenges for cell and gene therapies from a pricing and access perspective and explore the growing role of innovative contracting solutions to overcome aforementioned challenges.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":"36 5","pages":"265-274"},"PeriodicalIF":2.5,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40631620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}