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The Lancet. Healthy Longevity Dec 2023The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E7, the guidance for the conduct of clinical trials in... (Review)
Review
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E7, the guidance for the conduct of clinical trials in people older than age 65 years, dates from 1994. Since then, the inclusion of older people in clinical trials has hardly improved, particularly for the oldest old age group (individuals older than age 75 years), which is the fastest growing demographic bracket in the EU. Even though most medications are taken by this group, relevant endpoints and safety outcomes for this cohort are rarely included and reported, both in clinical trials and regulatory approval documents. To improve the critical appraisal and the regulatory review of medicines taken by frail older adults, eight recommendations are presented and discussed in this Health Policy. These recommendations are brought together from different perspectives and experience of the treatment of older patients. On one side, the perspective of medical practitioners from various clinical disciplines, with their direct experience of clinical decision making; on the other, the perspective of regulators assessing the data submitted in medicine registration dossiers, their relevance to the risk-benefit balance for older patients, and the communication of the findings in the product information. Efforts to improve the participation of older people in clinical trials have been in place for more than a decade, with little success. The recommendations presented here are relevant for stakeholders, authorities, pharmaceutical companies, and researchers alike, as the implementation of these measures is not under the capacity of a single entity. Improving the inclusion of frail older adults requires awareness, focus, and action on the part of those who can effect a much needed change.
Topics: Aged, 80 and over; Aged; Humans; Frailty; Frail Elderly; Communication
PubMed: 37977177
DOI: 10.1016/S2666-7568(23)00208-8 -
BMC Medical Education Aug 2023To compare the pediatric neurologists' knowledge, practice, and barriers to the pharmacovigilance (PV) process in Poland and Germany.
OBJECTIVES
To compare the pediatric neurologists' knowledge, practice, and barriers to the pharmacovigilance (PV) process in Poland and Germany.
METHODS
The research tool was an online anonymous questionnaire on Google Forms e-mailed to pediatric neurologists from Poland and Germany.
RESULTS
The questionnaires were handed out to 830 pediatric neurologists and 371 expressed their consent to participate in the study. Most of the neurologists were familiar with the definition of PV and adverse drug reactions (ADRs). Only 34.10% of pediatric neurologists from Poland, and 38.88% from Germany believe that many ADRs are preventable and almost most of them believe it is necessary to report ADRs from children with epilepsy. Unfortunately, in opposite to this knowledge, only 37.79% of respondents from Poland and 40.32% from Germany felt co-responsible for reporting ADRs. The main reason for the neurologists not to report ADRs was a conviction that reporting ADRs would be an additional burden generating extra work.
CONCLUSION
There is no big difference between the practice of PV by pediatric neurologists in Poland and Germany. System-regulated PV stabilization in the country translates into the practice of maintaining PV. Monitoring the safety of pharmacotherapy and knowledge of risks associated with ADRs should be included in the curricula of academic neurologics courses.
Topics: Child; Humans; Neurologists; Pharmacovigilance; Poland; Adverse Drug Reaction Reporting Systems; Health Knowledge, Attitudes, Practice; Drug-Related Side Effects and Adverse Reactions; Germany
PubMed: 37528387
DOI: 10.1186/s12909-023-04542-4 -
Healthcare (Basel, Switzerland) Feb 2024Is pharmacovigilance at a moment of prominence for science, and in relation to governments' responsibilities towards their nations, as the new coronavirus pandemic has... (Review)
Review
BACKGROUND
Is pharmacovigilance at a moment of prominence for science, and in relation to governments' responsibilities towards their nations, as the new coronavirus pandemic has surprised everyone in a negative and lethal way?
OBJECTIVE
Evaluate pharmacovigilance as a resource for controlling and understanding adverse events caused by vaccines in use.
METHODS
This is a narrative review of the literature. Scientific articles available in databases, government bulletins and similar bodies were used. The search was carried out using the descriptors: "Pharmacovigilance AND COVID-19 in Brazil", "Vaccine Development AND COVID-19", "Vaccination Hesitancy AND COVID-19", "Public Health Surveillance AND COVID-19". The period from May 2021 to June 2022 was covered.
RESULTS
The occurrence of some adverse events was observed, including cases of allergy, myocarditis and rheumatoid arthritis. It is important to highlight that these adverse events were identified as rare, occurring in a small percentage of the vaccinated population. Despite these adverse events, the benefits of vaccines proved to be essential for controlling the pandemic.
CONCLUSIONS
The information presented highlights the importance of pharmacovigilance to continuously monitor and evaluate the safety of vaccines, identifying any potential adverse events early. This balance between risk and benefit emphasizes the need for a careful and informed approach when making decisions about vaccination policies, prioritizing public health and population safety.
PubMed: 38338256
DOI: 10.3390/healthcare12030371 -
Drug Safety Dec 2023Biosimilars are additional treatment options that are approved based on robust analytical and clinical comparisons with their reference biologic. At the time of initial... (Review)
Review
Long-Term Real-World Post-approval Safety Data of Multiple Biosimilars from One Marketing-Authorization Holder After More than 18 Years Since Their First Biosimilar Launch.
BACKGROUND
Biosimilars are additional treatment options that are approved based on robust analytical and clinical comparisons with their reference biologic. At the time of initial approval, the full safety profile of a biosimilar is inferred from the reference biologic. Nonetheless, there are still lingering concerns related to the long-term safety of biosimilars. Therefore, we reviewed the post-approval pharmacovigilance data for eight marketed biosimilars from one Marketing Authorization Holder (MAH) to summarize their safety experience in a real-world setting for up to 18 years since their first biosimilar launch.
METHODS
Post-approval cumulative patient exposure and safety experience for eight Sandoz biosimilars [adalimumab (Hyrimoz), epoetin alfa (Binocrit), etanercept (Erelzi), filgrastim (Zarzio), infliximab (Zessly), pegfilgrastim (Ziextenzo), rituximab (Rixathon), and somatropin (Omnitrope)] was summarized based on the available pharmacovigilance data from Periodic Safety Update Reports (PSURs) and the corresponding health authority-authored PSUR assessment reports, where available, as of 31 January 2023. Exposure to all biosimilars was calculated in patient treatment days (PTD) except for rituximab, which was expressed in number of patient doses (PD).
RESULTS
The combined post-approval cumulative exposure to seven out of the eight marketed Sandoz biosimilars was more than 1.3 billion PTD and for rituximab more than 1.8 million PD. Overall, a critical analysis of the cumulative safety data of all eight Sandoz biosimilar PSURs concluded that the overall benefit-risk profile of each remains favorable and is consistent with the respective reference biologics.
CONCLUSIONS
This is one of the largest reviews of post-approval biosimilar pharmacovigilance data to date by one MAH. The real-world experience of all eight marketed Sandoz biosimilars for up to 18 years demonstrates that Sandoz biosimilars can be used as safely as their respective reference biologics. Therefore, patients and healthcare providers can be confident in the clinical benefit and safety of Sandoz biosimilars. It is reasonable to believe that similar conclusions about safety may be reached for other biosimilars developed and approved to the high standards as are already in place by major health authorities such as the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). The long-term safety of biosimilars demonstrated here provides strong support for the concept of biosimilarity.
Topics: Humans; Biosimilar Pharmaceuticals; Rituximab; Infliximab; Adalimumab; Epoetin Alfa; Marketing; Drug Approval
PubMed: 37902937
DOI: 10.1007/s40264-023-01371-8 -
Frontiers in Pharmacology 2024
PubMed: 38694914
DOI: 10.3389/fphar.2024.1397291 -
International Journal of Clinical... Jun 2024In the era of personalized medicine, pharmacovigilance faces new challenges and opportunities, demanding a shift from traditional approaches. This article delves into... (Review)
Review
In the era of personalized medicine, pharmacovigilance faces new challenges and opportunities, demanding a shift from traditional approaches. This article delves into the evolving landscape of drug safety monitoring in the context of personalized treatments. We aim to provide a succinct reflection on the intersection of tailored therapeutic strategies and vigilant pharmacovigilance practices. We discuss the integration of pharmacogenetics in enhancing drug safety, illustrating how genetic profiling aids in predicting drug responses and adverse reactions. Emphasizing the importance of phase IV-post-marketing surveillance, we explore the limitations of pre-marketing trials and the necessity for a comprehensive approach to drug safety. The article discusses the pivotal role of pharmacogenetics in pre-exposure risk management and the redefinition of pharmacoepidemiological methods for post-exposure surveillance. We highlight the significance of integrating patient-specific genetic profiles in creating personalized medication leaflets and the use of advanced computational methods in data analysis. Additionally, we examine the ethical, privacy, and data security challenges inherent in precision medicine, emphasizing their implications for patient consent and data management.
Topics: Precision Medicine; Humans; Pharmacovigilance; Drug-Related Side Effects and Adverse Reactions; Pharmacogenetics; Product Surveillance, Postmarketing
PubMed: 38416349
DOI: 10.1007/s11096-024-01709-x -
Therapeutic Innovation & Regulatory... Sep 2023The pharmacovigilance agreements (PVA) landscape has evolved over recent decades with rapid growth in the number and complexity of partnerships, mergers, and...
The pharmacovigilance agreements (PVA) landscape has evolved over recent decades with rapid growth in the number and complexity of partnerships, mergers, and acquisitions between pharmaceutical companies. Simultaneously there has been increasing scrutiny from regulatory authorities. Detailed regulations and guidance are lacking in this domain; hence companies have developed their own processes, templates, and tools, which have headed in different directions. Where feasible, marketing authorization holders (MAHs) have written contracts based on mutually understood requirements. Currently, MAHs are striving to find optimal solutions that safeguard patients, and in turn, support pharmacovigilance compliance. Through the TransCelerate BioPharma consortium MAHs are seeking simplification and efficiencies, to optimize the process of developing contractual agreements for pharmacovigilance. A survey of MAHs confirmed the perceptions above, and the need for efficient solutions to help navigate through the maze of complexity. The authors have led the development of tools and techniques to enable partnership between MAHs, and ultimately to support patient safety.
Topics: Humans; Negotiating; Pharmacovigilance; Patient Safety
PubMed: 37270450
DOI: 10.1007/s43441-023-00513-5 -
Frontiers in Pharmacology 2023To investigate and analyze the post-marketing adverse event (AE) data of multiple sclerosis (MS) therapeutic drug dalfampridine using the US Food and Drug...
To investigate and analyze the post-marketing adverse event (AE) data of multiple sclerosis (MS) therapeutic drug dalfampridine using the US Food and Drug Administration Adverse Event Reporting System (FAERS) for its clinical safety application. Use OpenVigil2.1 platform to obtain AE data of dalfampridine from FAERS from February 2010 to September 2022. Match "adverse drug reaction" with preferred term (PT) and system organ class (SOC) according to the Medical Dictionary for Regulatory Activities (MedDRA), then merge the same PT and delete non-AE PT. Positive signals were identified by the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) methods. When AE signals met the criteria of those three methods, they were identified as positive signals. A total of 44,092 dalfampridine-related AE reports were obtained, and 335 AE signals were identified, including 11,889 AE reports. AEs were more common in females and in the 45-65 age group, which is consistent with the epidemiological characteristics of MS. The 335 AE signals involved 21 SOCs, including investigations, infections and infestations, eye disorders, etc. Among the top 20 PTs in signal strength, 10 were associated with abnormal lymphocyte percentage and count, and 5 were associated with abnormal urine tests, some of which were not described in the instruction, such as spinal cord injury cauda equina, haemoglobin urine present, urinary sediment abnormal and so on. The most frequently reported AE signals were urinary tract infection, dizziness, condition aggravated. In addition, 23 AE signals with death outcomes were identified, with an incidence of less than 0.1%. Data mining of FAERS was conducted to analyze the AEs of dalfampridine, and new AE signals were found. This study provides a reference for the safe use of dalfampridine in the treatment of MS.
PubMed: 37781705
DOI: 10.3389/fphar.2023.1226086 -
BMC Cancer Aug 2023Rucaparib has been approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. However, the...
BACKGROUND
Rucaparib has been approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. However, the long-term safety of rucaparib in large sample population was unknown. The presented study aimed to evaluate rucaparib-associated adverse events (AEs) according to the real-world pharmacovigilance database.
METHODS
Disproportionality analysis was conducted to assess the association between rucaparib and its AEs. Data were collected from the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS) between January 2017 and June 2022. The characteristics of rucaparib-related AEs, and the onset time were further analyzed.
RESULTS
A total of 9,296,694 AE reports were recorded in the FAERS during the study period, among which 7,087 reports were associated with rucaparib. About 135 rucaparib-related AE signals in 15 system organ class (SOCs) were identified. The most common AEs included anaemia, thrombocytopenia, nausea, vomiting, fatigue, blood creatinine increase, alanine aminotransferase increase, and aspartate aminotransferase increase, which were listed in the label for rucaparib. Of note, 21 new and unexpected significant AEs that off-label were also found in our study, such as preferred term (PTs) of intestinal obstruction, gastrooesophageal reflux disease, blood iron decreased, dehydration, and hypersomnia. The median onset time of rucaparib-related AEs was 12 days (interquartile range [IQR] 1-62 days), and had early failure types.
CONCLUSION
Our study demonstrated potential new AEs of rucaparib, and further studies were expected to confirm the results.
Topics: Adult; Female; United States; Humans; Pharmacovigilance; Indoles; Databases, Factual; United States Food and Drug Administration
PubMed: 37568126
DOI: 10.1186/s12885-023-11201-w -
Cell Death Discovery Oct 2023PLK1 is a key serine/threonine kinase as well as a master mitotic regulator, but it has never been reported that PLK1 regulates DNA methylation. In the present study, we...
PLK1 is a key serine/threonine kinase as well as a master mitotic regulator, but it has never been reported that PLK1 regulates DNA methylation. In the present study, we for the first time found that PLK1 inhibition disrupted global DNA methylation and elevated the expression level of tumor suppressor genes. Mechanistically, we found that PLK1 interacts UHRF1 protein to induce its phosphorylation at serine 265. Phosphorylation is required for the maintenance of UHRF1 protein stability by recruiting a deubiquitinase USP7. Conversely, PLK1 inhibition decreases UHRF1 protein interaction with USP7 and activates the ubiquitin-proteasome pathway, thereby accelerating UHRF1 protein degradation. UHRF1 degradation decreases the recruitment of DNMT1 to chromatin, and decreases the level of genome-wide DNA methylation, thereby elevating the expression of tumor suppressor genes and decreasing cell viability. We here presented the first report on the novel role of PLK1 in DNA methylation maintenance through UHRF1-DNMT1 pathway, and revealed a novel anticancer mechanism of PLK1 inhibitors.
PubMed: 37788997
DOI: 10.1038/s41420-023-01667-9