Pharmaceutical Medicine最新文献

{"title":"Assessing Definitions and Incentives Adopted for Innovation for Pharmaceutical Products in Five High-Income Countries: A Systematic Literature Review.","authors":"Naohiko Wakutsu,&nbsp;Emi Hirose,&nbsp;Naohiro Yonemoto,&nbsp;Sven Demiya","doi":"10.1007/s40290-022-00457-5","DOIUrl":"https://doi.org/10.1007/s40290-022-00457-5","url":null,"abstract":"<p><strong>Background: </strong>The concept of health care innovation varies across organizations and countries. Harmonizing the definitions of innovation can augment the discovery of new therapies, minimize costs, and streamline drug development and approval processes. A systematic literature review (SLR) was conducted to gather insights surrounding different elements of innovation in the USA, the UK, France, Germany, and Japan. The SLR identified studies that have defined innovation and captured the types of incentives provided to promote innovation.</p><p><strong>Methods: </strong>The MEDLINE, Embase, and EconLit databases were searched via the OVID SP platform on October 22, 2020. A secondary desk search literature review was performed to identify additional information of interest in regional languages: French, German, and Japanese. All the relevant literature in English was screened using the Linguamatics natural language processing (NLP) tool, except for articles from EconLit, which were screened manually using structured search strategies. Articles that describe a definition of innovation or refer to a definition of innovation published were included. All full-text articles were reviewed manually, and two reviewers independently screened the full texts for eligibility.</p><p><strong>Results: </strong>After screening, 90 articles were considered to meet the SLR objectives. The most common dimension of innovation identified was therapeutic benefit as a measure of innovation, followed by newness and novelty aspects of innovations. Incentives around exclusivities were found to be the most prevalent in the data set, followed by rewards and premiums. Among the different therapy areas, the largest number of innovations was targeted at oncology.</p><p><strong>Conclusions: </strong>This SLR highlights the lack of a unified definition of innovation among regulatory authorities and health technology assessment bodies in five countries, and variation in the types of incentives associated with innovation. The targeted countries cover different dimensions of definition and incentives of innovation at varying levels, with a few focused on specific therapy areas. Harmonization and consensus for innovation would be needed across countries because drug development is a global undertaking. This SLR envisages a more holistic approach to evaluation, wherein the value provided to patients and health systems is accounted for. The results of this SLR will help to promote broader discussion among different stakeholders and decision makers across countries to identify gaps in policies and develop sustainable strategies to promote innovation for pharmaceutical products.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9f/fd/40290_2022_Article_457.PMC9843662.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10871160","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":"Evaluating Treatment Efficacy by Combining Multiple Measures in Clinical Trial Applications.","authors":"Abdullah Al Masud,&nbsp;Samaradasa Weerahandi,&nbsp;Ching-Ray Yu","doi":"10.1007/s40290-022-00454-8","DOIUrl":"https://doi.org/10.1007/s40290-022-00454-8","url":null,"abstract":"<p><p>A variety of clinical and laboratory measures can be used in clinical trials to assess the benefit of a new treatment over the standard of care. Data from clinical studies are often analyzed by combining individual outcomes into one primary outcome. That primary outcome is then referred to as a composite endpoint or a combined endpoint. We propose an analysis on the composite endpoint with Gehan's (1965) ranking approach where each subject in the treatment group is compared with each subject in the control group in a pair-wise manner. Our approach reduces computational time and complexity to construct a subject-level pairwise composite score. We develop a statistical testing procedure for the analysis of composite endpoints when using the hierarchical scores. In this article, we propose two tests (a parametric test and a non-parametric bootstrap procedure) for evaluating the effect of treatment. The proposed parametric test has an asymptotic F-distribution based on standard statistical assumptions. We conduct an extensive simulation study to assess the operating characteristics of the proposed methods and to compare them with an existing method. We illustrate the methods using publicly available data from two clinical studies.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10815490","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":"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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":"Correction to: The Impact of the Priority Review Voucher on Research and Development for Tropical Diseases.","authors":"Celine Aerts,&nbsp;Eliana Barrenho,&nbsp;Marisa Miraldo,&nbsp;Elisa Sicuri","doi":"10.1007/s40290-022-00440-0","DOIUrl":"https://doi.org/10.1007/s40290-022-00440-0","url":null,"abstract":"","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1c/07/40290_2022_Article_440.PMC9701173.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40450750","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":null,"pages":null},"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":"The Characteristics of Clinical Trials on Cannabis and Cannabinoids: A Review of Trials for Therapeutic or Drug Development Purposes.","authors":"Farhang Modaresi,&nbsp;Kaivan Talachian","doi":"10.1007/s40290-022-00447-7","DOIUrl":"https://doi.org/10.1007/s40290-022-00447-7","url":null,"abstract":"<p><strong>Introduction: </strong>Patients and healthcare practitioners are increasingly interested in using cannabis and cannabinoids to address unmet clinical needs. Although we have clinical evidence on the medical use of cannabinoids, a significant portion of the data is not based on randomized clinical trials, which are considered the gold standard in clinical research. We have reviewed the registered clinical trials on cannabis and cannabinoids for therapeutic or drug development purposes to underline the past and current attempts to generate robust clinical evidence and identify existing knowledge gaps.</p><p><strong>Methods: </strong>We reviewed four clinical trial registries (International Clinical Trials Registry Program [ICTRP], ClinicalTrials.gov, European Clinical Trial Registry [EUCTR], Australian New Zealand Clinical Trial Registry [ANZCTR]) to identify clinical trials on cannabinoids (phyto- or synthetic) or cannabis-based medications between January 1, 2000, and December 31, 2021. All interventional clinical trials on cannabinoids and other compounds interacting with the endocannabinoid system, regardless of the investigated medical condition, assessed health outcomes, or choice of comparator, were included, provided they had a therapeutic or drug development purpose. Data on the primary sponsor, type of sponsor, date of registration, recruitment status, number of participants, study design, the phase of the study, country, medical conditions, investigated cannabinoids, and the route of administration were extracted. The therapeutic area and class of cannabinoids were identified based on the details of each trial.</p><p><strong>Results: </strong>We included 834 out of 2966 reviewed clinical trials. The number of registered clinical trials has constantly increased from 30 in 2013 to 103 in 2021. More than 40% of registered clinical trials in 2021 were phase II and phase III clinical trials. The mean number of trial enrollments for completed, ongoing, and terminated studies were 128, 156, and 542, respectively. Clinical research on Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and the oral routes of administration dominate the field. Approximately two-thirds of clinical trials were conducted in five therapeutic areas (i.e., 'Chronic pain,' 'Mental, behavioral or neurodevelopmental disorders,' 'Nervous system diseases,' 'Endocrine, nutritional or metabolic diseases,' and 'Neoplasms'). Pharmaceutical companies sponsored 39% of all clinical trials. However, trial sponsorships vary noticeably in different jurisdictions, likely due to, in part, different regulatory frameworks.</p><p><strong>Conclusion: </strong>Our review highlights the diversification of clinical trials on cannabinoid-based medications in the past 21 years. This review underlines the increased interest in conducting clinical studies on new cannabinoid administration methods such as topical applications and on the investigation of emerging phyto- and synthetic canna","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40691800","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 Effectiveness and Safety of Cannabidiol in Non-seizure-related Indications: A Systematic Review of Published Randomized Clinical Trials.","authors":"Yuni Tang, Kolbi L Tonkovich, Toni Marie Rudisill","doi":"10.1007/s40290-022-00446-8","DOIUrl":"10.1007/s40290-022-00446-8","url":null,"abstract":"<p><strong>Background: </strong>Legislative changes have fueled the global availability of cannabis and cannabis-derived compounds, such as cannabidiol. Little is known about the effectiveness and safety of cannabidiol for treating health conditions other than seizure disorders.</p><p><strong>Objective: </strong>A systematic review of the literature was performed to investigate other health conditions, characteristics of the studied populations, and the effectiveness of cannabidiol in randomized clinical trials.</p><p><strong>Methods: </strong>Seven publication databases were searched from February to March 2021. The inclusion criteria for studies were: (1) utilized a randomized clinical trial design; (2) published in a peer-reviewed journal or thesis/dissertation; (3) published in English; (4) investigated either prescription (i.e., Epidiolex) or non-prescription CBD that was derived from the Cannabis sativa plant with < 3% ∆9-tetrahydrocannabinol; and (5) reported at least one outcome. This review excluded seizure-related disorders as several previous reviews have been done on this topic; it also excluded published protocols, other systematic reviews, or meta-analyses of randomized clinical trials that investigated cannabidiol. Independent reviewing, risk of bias assessment, and data abstraction were performed by two authors.</p><p><strong>Results: </strong>Fifty-eight studies from eight countries were included in this review. Twenty-seven studies (47%) were conducted in healthy populations, 14% were restricted to male individuals (n = 8), and 72% had sample sizes of fewer than 40 participants. Doses of cannabidiol used in these studies ranged from 400 µg to 6000 mg. The effect of cannabidiol on mental health was the most studied topic (53%), which focused mainly on anxiety, psychosis, schizophrenia, and substance use disorders. The remaining studies investigated neurological conditions (19%) and a myriad of other health conditions or outcomes. While cannabidiol appears to be anxiolytic, its effectiveness for other conditions was highly variable.</p><p><strong>Conclusions: </strong>This review highlights the inconsistencies of cannabidiol as a treatment for non-seizure-related health conditions or outcomes. Studies incorporating larger sample sizes in more diverse populations are encouraged. While cannabidiol was generally safe and well tolerated even in high doses among the included studies, clearer dosing guidelines and increased regulation of cannabidiol products are also needed.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9708636/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40564830","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}