Pharmaceutical Medicine最新文献

{"title":"Rare Immune-Related Adverse Events (irAEs): Approach to Diagnosis and Management.","authors":"Anadil Javaid, Catherine Bennett, Aparna Rao, Lavinia Spain","doi":"10.1007/s40290-023-00508-5","DOIUrl":"10.1007/s40290-023-00508-5","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have revolutionised the treatment landscape across many solid organ malignancies and form part of routine clinical practice in many tumours. As indications for monotherapy, doublet therapy and combination approaches with chemotherapy and targeted agents expand, clinicians must be aware of the wide range of possible immune-related adverse events (irAEs). Common toxicities, including rash, colitis, hepatitis and pneumonitis are well described in the literature, and have established diagnostic and management algorithms. Rarer toxicities, often with an incidence of less than 1%, are less defined. These syndromes can be poorly recognised, may take on a fulminant course and do not have established or evidence-based diagnostic and management strategies. As such, patients may experience increased morbidity, mortality and poorer outcomes, related both to these irAEs as well as how the treatment of these may affect the management of their underlying malignancy. In this review, we aim to explore the incidence, potential biomarkers, pathogenesis, diagnostic work-up and clinical sequelae of a selection of uncommon irAEs, with a focus on myocarditis, neurological and haematologic syndromes. Further prospective research is required to accurately define the incidence and pathogenesis of these conditions, with the aim of increasing clinician awareness of rare irAEs and to assist with a more personalised and mechanism-based approach to these syndromes.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403934","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":"Medicinal Products and Environmental Pollution.","authors":"Noel Snell","doi":"10.1007/s40290-023-00502-x","DOIUrl":"10.1007/s40290-023-00502-x","url":null,"abstract":"","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413407","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":"Eliciting Exploratory Patient Preference Data: A Case Study in a Rare Disease.","authors":"Kerrie-Anne Ho, Anna Pierce, Meredin Stoltenberg, Thais Tarancon, Carol Mansfield","doi":"10.1007/s40290-023-00509-4","DOIUrl":"10.1007/s40290-023-00509-4","url":null,"abstract":"<p><strong>Introduction: </strong>Qualitative and quantitative methods provide different and complementary insights into patients' preferences for treatment.</p><p><strong>Objective: </strong>The aim of this study was to use a novel, mixed-methods approach employing qualitative and quantitative approaches to generate preliminary insights into patient preferences for the treatment of a rare disease-generalized myasthenia gravis (gMG).</p><p><strong>Methods: </strong>We conducted a mixed-methods study to collect exploratory qualitative and quantitative patient preference information and generate informative results within a condensed timeline (about 4 months). Recruitment was facilitated by an international health research firm. Study participants first reviewed a brief document describing six treatment attributes (to facilitate more efficient review of the material during the focus groups) and were then provided a link to complete an online quantitative survey with a single risk threshold task. They then participated in online focus groups, during which they discussed qualitative questions about their experience with gMG treatment and completed up to three quantitative threshold tasks, the first of which repeated the threshold task from the online survey.</p><p><strong>Results: </strong>The study elicited both quantitative data on 18 participants' risk tolerance and qualitative data on their treatment experience, additional treatment attributes of importance, the reasoning behind their preferences, and the trade-offs they were willing to make. Most participants (n = 15) chose the same hypothetical treatment in the first threshold task in the online survey and the focus groups. Focus group discussions provided insights into participants' choices in the threshold tasks, confirmed that all the attributes were relevant, and helped clarify what was important about the attributes.</p><p><strong>Conclusions: </strong>Patient preference information can be collected using a variety of approaches, both qualitative and quantitative, tailored to fit the research needs of a study. The novel mixed-methods approach employed in this study efficiently captured patient preference data that were informative for exploratory research, internal decision making, and future research.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138830892","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 Importance of Assessing Drug Exposure and Medication Adherence in Evaluating Investigational Medications: Ensuring Validity and Reliability of Clinical Trial Results.","authors":"Bernard Vrijens, Antoine Pironet, Eric Tousset","doi":"10.1007/s40290-023-00503-w","DOIUrl":"10.1007/s40290-023-00503-w","url":null,"abstract":"<p><p>The objective of this current opinion paper is to draw global attention to medication adherence, emphasizing its crucial role in drug trials. Frequently, trialists lean on traditional approaches to assess medication adherence, which, while comfortable, may only reveal what trialists desire rather than offering the essential insights needed for informed decision making in drug development. Understanding drug exposure and medication adherence is paramount when evaluating the effectiveness and safety of investigational medications. Without a comprehensive understanding of how patients adhere to their prescribed treatment regimens, the integrity and dependability of clinical trial results can be compromised. This paper emphasizes the need for measures that accurately and reliably assess medication intake behaviors, enabling the differentiation between minor dosing errors and significant deviations that may impact the drug's efficacy and safety. Accurate knowledge of drug exposure empowers researchers to make informed decisions, identify potential confounding factors, and appropriately interpret study outcomes, ultimately ensuring the validity and reliability of the research findings. By prioritizing drug exposure assessment and medication adherence measurement, clinical trials can enhance their scientific rigor, contribute to more accurate evaluations of investigational medications, and ultimately speed up the development process.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138885618","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":"A Review of the Current FDA-Approved Antibody-Drug Conjugates: Landmark Clinical Trials and Indications.","authors":"Meghana Kesireddy, Srikanth Reddy Kothapalli, Sai Giridhar Gundepalli, Samia Asif","doi":"10.1007/s40290-023-00505-8","DOIUrl":"10.1007/s40290-023-00505-8","url":null,"abstract":"<p><p>Despite considerable treatment progress, cancer remains among the leading causes of death worldwide. Antibody-drug conjugates (ADCs), a rapidly growing class of systemic therapy, show promise by combining the properties of conventional chemotherapy and targeted therapy. Antibody-drug conjugates have been shown to be more efficacious than traditional chemotherapy. To date, there are 13 ADCs approved by the United States Food and Drug Administration (FDA) for treating various hematological and solid organ cancers. There are several new promising ADCs that are being developed and are in clinical trials. This review provides an overview of the current FDA-approved ADCs, the landmark clinical trials that led to their approval, the common toxicities seen in the landmark trials, the challenges associated with ADCs, and the potential future directions.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138452079","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":"Evaluation of Physician Knowledge of Safety and Safe Use Information for Intravitreal Aflibercept Injection in Europe: A Second Survey of Physicians Following Dissemination of Updated Risk-Minimization Materials.","authors":"Laurie J Zografos, Elizabeth Andrews, Dan L Wolin, Brian Calingaert, Eric K Davenport, Alexander Michel, Margarete Latocha, Ursula Maria Schmidt-Ott, Nejra Lovic, Lynne R Brunck, Kristian T Johnson, Kiliana Suzart-Woischnik","doi":"10.1007/s40290-023-00506-7","DOIUrl":"10.1007/s40290-023-00506-7","url":null,"abstract":"<p><strong>Background: </strong>Materials have been distributed in the European Union to inform physicians on the safe use of intravitreal aflibercept (IVT-AFL) as part of the risk-minimization plan for IVT-AFL.</p><p><strong>Objective: </strong>We aimed to measure physician knowledge and understanding of key safety information for IVT-AFL.</p><p><strong>Methods: </strong>The current study was a follow-up cross-sectional survey ('wave 2') to an earlier survey ('wave 1') examining the effectiveness of the IVT-AFL educational materials by assessing physician knowledge of the key safety information. Based on wave 1 results, the educational materials were revised to focus more on items of key concern (e.g., use in women of childbearing potential, procedural information); physicians in France, Germany, Italy, Spain, and the UK completed a questionnaire to evaluate their knowledge of key safety information in the revised educational materials.</p><p><strong>Results: </strong>Among 454 physician respondents (of 4715 invited; response rate 9.6%), most reported having received the IVT-AFL Summary of Product Characteristics (SmPC; 89%) and Prescriber Guide (82%). More than half reported receiving the Injection Procedure Video (54%) and Patient Booklet (65%). The highest percentage of correct answers was observed for questions concerning procedural steps, the most important risks, and safe use as emphasized by the educational materials and the SmPC.</p><p><strong>Conclusion: </strong>Physician knowledge and understanding of safe use of IVT-AFL, including for questions that prompted revisions to the educational materials, suggests the need to reconsider methods for developing educational materials to follow best practices (e.g., focusing on only key messages and pretesting with end users).</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":3.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10824811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138482786","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":"“Regulatory Sandboxes” Could Solve the Regulatory Problems Encountered in Europe and Arising from Innovation in Biological Medicinal Products","authors":"Mathieu Guerriaud","doi":"10.1007/s40290-023-00507-6","DOIUrl":"https://doi.org/10.1007/s40290-023-00507-6","url":null,"abstract":"","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138585426","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 Pharmacokinetics of Drugs Delivered to the Upper Nasal Space.","authors":"Stephen B Shrewsbury","doi":"10.1007/s40290-023-00495-7","DOIUrl":"10.1007/s40290-023-00495-7","url":null,"abstract":"<p><p>Pharmacokinetics (PK) includes how a drug is absorbed, distributed, metabolized and eliminated. The compartment providing this information is usually the plasma. This is as close to the tissue of interest that we can get, although biopsies may be obtained to give \"tissue levels\" of drugs. Ultimately, the goal of PK is to understand how long the drug is actually engaged with the target in the tissue of interest after a dose has been administered. Most drugs at some point in their development will have been administered intravenously (IV), which acts as the standard for 100% bioavailability. By comparing various routes of administration to IV, the percentage of drug delivered to the plasma, on a dose-normalized basis, can be calculated and is referred to as the \"absolute bioavailability\". As pharmacology has advanced and more drugs have become available, many older products have been reformulated to be given by routes other than those originally intended (often oral). As the drawbacks of oral (or IV) administration have become better appreciated, non-oral, non-IV formulations and methods of administration have become more popular. Nasal administration is one route that has historically been overlooked as an alternative to oral administration-particularly for products needing rapid and non-invasive access to the target tissue-mostly via the blood stream. But attention is now focused on nasal administration for direct access to the brain, as that has the potential to bypass the blood-brain-barrier (BBB), which not even IV administration can always achieve. Assessing PK for these drugs targeting the brain may require serial sampling of the cerebrospinal fluid (CSF), making PK assessments of CNS drugs more invasive and complex, but still possible in future product development. However, we are now seeing more drugs reformulated for nasal delivery to gain faster systemic levels than oral administration (especially in patients with known or suspected gastrointestinal dysmotility), while avoiding the use of needles. For example, in recent years several different formulations and delivery methods for an old drug, dihydroergotamine (DHE), have been developed and these show very different characteristics, suggesting that delivery to different parts of the nose may have very different PK profiles. This review summarizes the systemic PK of different nasal DHE options that have been, or are being, developed and suggests that delivery of drugs to the upper nasal space (UNS) may represent an optimal target. Further research is required to ascertain if this route could also be utilized for direct administration to the CNS (as an attractive alternative to intrathecal delivery) via the olfactory or trigeminal nerves-but already preclinical data (and some human data) suggest this is entirely possible.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f4/1c/40290_2023_Article_495.PMC10587213.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9934849","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":"American Geriatrics Society Annual Scientific Meeting (AGS 2023).","authors":"Caroline Herdson","doi":"10.1007/s40290-023-00492-w","DOIUrl":"10.1007/s40290-023-00492-w","url":null,"abstract":"","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9758912","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":"Practical Considerations for the Implementation and Monitoring of Risk Minimisation Measures for High-Risk Teratogenic Medicines.","authors":"Marion Mueller,&nbsp;Joseph Peakin,&nbsp;David J Lewis","doi":"10.1007/s40290-023-00496-6","DOIUrl":"10.1007/s40290-023-00496-6","url":null,"abstract":"<p><p>There is considerable societal interest in making medicines more affordable. A critical factor often inadequately considered early in the process of adding drugs to a company's product portfolio is that some products may require additional monitoring and complex, demanding and expensive additional risk minimisation measures (aRMMs). These aRMMs may have a sizeable impact on a company's commitment to that medicinal product throughout the product's entire life cycle. The teratogenic phthalimides were selected as an example of medicines that are recently being genericised and require a substantial commitment in terms of additional monitoring and aRMMs, most notably in the form of pregnancy prevention programmes (PPPs) with controlled distribution systems (CDSs). Implementing PPPs with CDSs is complex and demanding and encompasses all routine activities, aRMMs, local/regional Health Authority (HA) requirements, and commercialisation strategies. Considerations have been summarised that can support decision-making during due diligence processes, implementation and monitoring. Proactive, effective pharmacovigilance requires innovative, sustainable and flexible solutions to maintain high standards across the board. In particular, generic marketing authorisation holders operate with limited resources and may benefit appreciably from the following proposed suggestions and solutions such as early planning and preparation, knowledge-sharing, utilisation of new technologies and implementation of measures beyond HA-mandated requirements.</p>","PeriodicalId":19778,"journal":{"name":"Pharmaceutical Medicine","volume":null,"pages":null},"PeriodicalIF":2.5,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10024616","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}