Pharmaceutical Medicine最新文献

Background: The Japanese biosimilar guideline requires that the sponsors conduct clinical studies such as comparative pharmacokinetic (PK), pharmacodynamic (PD), or efficacy studies. In each biosimilar development, the sponsors consider the clinical data package, and thus clinical data packages vary among biosimilar developments.

Objectives: The aim of this study was to elucidate the clinical data packages for the biosimilars approved in Japan. The details of clinical data packages and sample size for the regulatory approvals of biosimilars in Japan was reported.

Methods: We surveyed the clinical data packages and sample size based on the Pharmaceuticals and Medical Devices Agency (PMDA) website review reports between 2009 and 2023.

Results: Twenty-four biosimilars have been approved based on the comparative PK and efficacy studies, 10 biosimilars have been approved based on the comparative PK/PD study, and one biosimilar has been approved based on the comparative efficacy study. Regarding the sample size, comparative PK studies were conducted in healthy volunteers or patients for up to 300 cases, although the majority enrolled only 1-100 cases (68.1%, 32/47). Comparative PD studies enrolling 1-30, 31-60, and 61-90 cases totaled 4, 7, and 4 cases, respectively. Finally, comparative efficacy studies enrolling 1-300, 301-600, and 601-900 totaled 6, 10, and 11 cases, respectively. In particular, the oncology and rheumatology areas were the first and second disease areas recruiting 601-900 patients.

Conclusion: Large numbers of patients were enrolled to conduct a comparative efficacy study. Efficient biosimilar development should be considered on the basis of the accumulation of scientific understanding of comparable features of biosimilars and their development.

Background: Following marketing authorization in Japan, for almost all new drugs or new indications, postmarketing studies (PMS) are a regulatory requirement. These PMS focus on accrual of a defined number of cases with data being collected for a predetermined period after approval to confirm efficacy/effectiveness, safety, and quality in the Japanese population. In contrast to other regions where PMS are only required to address a specific scientific uncertainty, in Japan, PMS are often required regardless of any specific scientific uncertainty, and therefore, their scientific value is unclear.

Objectives: To determine the contribution to the understanding of benefit/risk of PMS conducted by Pfizer in Japan over 2000-2020 for Pharmaceuticals and Medical Devices Agency (PMDA) reexamination.

Methods: A retrospective analysis of all Pfizer Japan postmarketing studies (PMS) during 2000-2020 was performed. Available Pfizer clinical study reports (CSRs) and PMDA reexamination reports (RERs) were reviewed for key safety findings. The primary analysis was conducted on the subset of PMS that had both an English CSR and a discussion of that PMS in the relevant RER issued by the PMDA, which was subsequently translated into English by a professional translation vendor. Reexamination outcome is included in each RER and served to demonstrate the impact of the study of the benefit/risk profile of the drug.

Results: A total of 79 PMS for 43 different drug products across therapy areas enrolled a total of 98,035 patients. The 79 PMS comprised 34 general drug use investigation (GDUI) studies and 45 special investigation (SI) studies. The primary analysis involved 37 PMS with a CSR and RER available in English (40,470 patients); all of which were observational in design. For 31 of 37 PMS, the RER concluded the overall adverse drug reaction (ADR) rate in the PMS was nominally lower than in the phase 3 program. Unlabeled ADRs were reported in 28 of 37 PMS; however, no new safety concerns requiring regulatory action arose from any PMS. The PMDA did not require additional risk minimization measures for any of the 43 drug products studied in any of the 79 PMS assessed. Japan PMS data were consistent with prior global data with no evidence of clinically meaningful differences in safety in Japanese patients. In all cases, the reexamination outcome was category 1 ("usefulness is confirmed").

Conclusions: The reexamination process did not result in regulatory changes for any of the examined drugs. The Japan new-drug application (J-NDA) review and approval process, including implementation of the initial Japan product label, assures acceptable benefit/risk at the time of approval such that mandatory GDUI or SI studies for all products should be reconsidered. In the case of genuine scientific uncertainty to the extent that the benefit/risk of the product is not cle

Introduction: Medical departments have evolved from a position of support to one of strategic leadership. The number of tasks and the complexity of interactions in which they are involved is increasing. However, the spectrum of their activity in the sector differs significantly from one company to another. Therefore, the aim of this study was to describe their situation within the pharmaceutical industry, analyzing the positions, functions, and profiles of their professionals.

Methods: This study consisted of an online survey containing 25 questions grouped into four blocks (structure, medical direction, training, and activities and responsibilities). Medical departments in the Spanish pharmaceutical industry of different sizes and scope were invited to participate. The survey took place in 2021, with a designated response period of three months. It is important to note that all responses collected during this time were treated as anonymous.

Results: Thirty companies participated. A total of 93.3% of respondents worked for an international laboratory, with a size of 0-5 or 11-20 people (20.7%). For 27.6% of the companies, the number of medical advisors per medical department was 1 or 4, with varying numbers of medical scientific liaisons (1, 6-10, and > 20). A total of 56.7%, 33.3%, and 6.7% indicated that the country manager, head of regional medical affairs, and head of global medical affairs, respectively, had a solid-line reporting relationship with the medical directorate. Medical directors were mostly graduates in medicine (86.2%) with a doctorate (34.5%), and medical managers were mainly graduates in medicine (77.8%) and pharmacy (66.7%).

Conclusions: This study reveals that respondents predominantly work in internationally focused laboratories, with professionals ranging from experienced medical directors to managers with 6-20 years of experience, each with distinct roles.

Introduction: Spontaneous reporting of adverse events (AEs) is a mainstay of pharmacovigilance, and an ongoing challenge is how to ensure that more high-quality reports are collected for comprehensive information provision. The Med Safety App, a smartphone-based application, was launched in Nigeria in November 2020 to provide an electronic platform for users to seamlessly report AEs. There has been a paucity of evidence on the use of this application or other mobile applications for reporting adverse drug reactions/AEs following immunization in the Nigerian environment.

Objective: The aim of this study was to evaluate the trends in adverse event reporting before and after the introduction of the Med Safety App in Nigeria.

Methods: This was a retrospective, observational study using data from the VigiFlow database to compare adverse event reporting in Nigeria before and after the deployment of the Med Safety App. The baseline period was 1st April 2019 to 30th October 2020 and the comparison period was 1st November 2020 to 31st May 2022. We used Vigilance Hub, the back-end system for the Med Safety App, to extract data on App downloads and de-identified user statistics. Data were summarized using descriptive statistics, frequencies and proportions. Quality was assessed by assigning a completeness score to each individual case safety report. The Kruskal-Wallis test was used to test for differences in medians between groups.

Results: Following deployment of the App, the Nigerian National Pharmacovigilance Centre recorded an increase in the total number of adverse event reports received in VigiFlow, from 2051 in the baseline period to 18,995 following deployment of the App, with 81.7% of those reported via the Med Safety App. There was a reduction in the proportion of paper-based reporting from 98.4 to 15.7% post-deployment, and direct reporting by consumers increased from 2.7 to 17.6%. Of the 15,526 reports submitted via the App, 15,111 (97.3%) had a completeness score above 70% and 6993 (45%) had a completeness score of 100%. The median completeness score of adverse event reports on the Med Safety App was 6 out of 7. On bivariate analysis using the Kruskal-Wallis test, there was an association between means of reporting and completeness score, and this association was significant, with a p value of 0.0001, which may reflect the validation rules that are applied within the App.

Conclusion: Deployment of the Med Safety App increased both the number and quality of adverse event reports; however, more awareness and capacity building are needed to strengthen and sustain reporting on the tool by all categories of healthcare professionals and consumers/patients.

Children were often referred to as "therapeutic orphans" in the past due to different reasons such as ethical, regulatory, economic, scientific, etc., ones. They were exposed to avoidable risks while missing out on therapeutic advances. Pediatric patients have suffered from a lack of scientific and regulatory standards (e.g., proper drug testing, authorization of medicines for their use, etc.), although the pharmaceutical legislative framework, which ensures the high standards of safety, quality, and efficacy of medicinal products for use in adults, was developed primarily in response to past "drug disasters," mainly involving children. The adoption of pediatric regulatory initiatives first in the USA and then in Europe and other countries and regions has significantly changed the worldwide frameworks and permanently changed pediatric drug research and development. This article tries to give various perspectives with historical context, a review of the different challenges and opportunities as well as important stakeholders in pediatric drug development. The pediatric trial networks are probably the most important stakeholder that enables efficient patient recruitment, access to better resource utilization, and global collaboration of different stakeholders necessary for performing quality and well-designed clinical trials.

Purpose: The Summary of Product Characteristics (SmPC) is required to provide unambiguous information on the authorized use of a medicinal product. Therefore, we performed a structured analysis of the information provided for pediatric patients in current SmPCs.

Methods: In the German SmPC of the medicinal products of 452 active substances, we analyzed for each of the listed indications whether information on pediatric use was available in Sects. 4.1-4.4 of the SmPC and, if so, whether it was unambiguous. Information was considered unambiguous if it indicated an exact age- or weight-related specification. The analysis also considered the type of marketing authorization and the date of marketing authorization, either before or after the Pediatric Regulation 2007 came into force.

Results: Among the 30,354 identified indications in 8464 SmPCs, unambiguous information was found for 72.4% (21,974/30,354) of the indications. Of these, 45.4% (9967/21,974) disclosed a contraindication for the entire population under 18 years of age. The proportion of unambiguous information was higher for medicinal products with centralized marketing authorization (86.5% [1449/1676]) than for those with a national one (71.6% [20,525/28,678]; p < 0.001). A higher proportion of unambiguous information was found for the marketing authorization period 2007-2021 compared with 1996-2006 (1996-2006: 63.8% [7466/11,694]; 2007-2021: 82.1% [12,349/15,040]; p < 0.001).

Conclusion: For about a quarter of all indications, no or only ambiguous information was available for pediatric patients. The measures initiated in recent years to increase pediatric-specific information in SmPCs should be intensified in order to improve drug safety in children and adolescents.

Background: The Sleep Diary Questionnaire (SDQ), a modified version of the Consensus Sleep Diary, is a 17-item sleep diary for assessing subjective total sleep time (sTST: total time spent asleep at night) and other sleep parameters in insomnia trials. sTST is a key parameter of efficacy in insomnia trials; however, the magnitude of improvement in this parameter that people with insomnia disorder consider clinically meaningful is unclear.

Objective: The aim of this study was to estimate meaningful within-patient change for sTST using clinical trial data.

Methods: Data were from an open-label trial of zolpidem and pooled data from a phase III placebo-controlled trial of daridorexant. In both trials, adults with moderate to severe insomnia completed the SDQ daily. Meaningful change in sTST was estimated in an anchor-based analysis using outcome measures that were correlated with change in weekly average sTST (Spearman correlation coefficient ≥ 0.30): the Insomnia Severity Index, patient global assessments and impressions of severity and change in daytime and night-time symptoms (PGA-S, PGI-S, PGI-C), and clinician global impressions of severity and change in patients' daytime symptoms (CGI-S, CGI-C). Meaningful within-patient change estimates were 'triangulated' to identify a value where they converged.

Results: In the open-label trial (N = 114), subjects with a 1-point or 1-step improvement on the anchors had mean increases in sTST of 60.1-83.2 min at day 8 and 55.5-68.2 min at day 15. For subjects with a 2-point or 2-step improvement on the anchors, mean increases in sTST were 79.6-81.4 min at day 8 and 80.1-93.5 min at day 15. In the phase III trial (N = 930), weekly average increases in sTST for subjects with a 1-point or 1-step improvement on the anchors were 39.3-46.7 min at month 1 and 47.3-58.3 min at month 3. For subjects with a 2-point or 2-step improvement on the anchors, mean increases in sTST were 60.7-76.2 min at month 1 and 70.1-87.7 min at month 3. Triangulation of these values supported a meaningful within-patient change threshold starting at 55 min.

Conclusion: Increasing sTST is an important treatment outcome for people with insomnia. An increase in sleep time of approximately 55 min is meaningful to patients.

Clinical trials registration: NCT03056053 (17 February 2017) and NCT03545191 (4 June 2018).

Decentralised clinical trials (DCTs) encompass various terms such as virtual, home-based, remote and siteless trials. The objectives of DCTs are to enhance the ease of participation for patients in clinical trials by minimising or removing the necessity for trial subjects to travel to the trial sites. This approach has been shown to reduce drop-out rates, increase study effectiveness and ultimately get life-altering drugs to market faster-saving sponsors billions. At the outset, DCTs deploy a wide range of digital technologies to collect safety and efficacy data from study participants, providing study treatments and performing investigations from the comfort of the patient's own home. The aim of decentralised trials includes patient centricity, enhanced efficacy in clinical trial conduct and generating real-world data. This is done by not only making it convenient for the patient to participate in the trial execution, but also involving them from the planning stage and taking their inputs during designing of trials and consenting documentation, understanding their treatment requirements and designing the studies accordingly. Various regulatory authorities have published guidelines governing DCT principles, especially after the coronavirus disease 2019 (COVID-19) experience of undertaking multicentric clinical trials. Both United States Food and Drug Administration (USFDA) and European Medicines Agency (EMA) have newer, recently updated guidelines to capture this growing reality to undertake clinical trials using patient technology or patient-centric technologies. Other regulatory agencies are accepting data generated using decentralised and patient-centric technologies and making an effort to include elements of decentralised trials in their regulatory guidelines. Decentralised trials follow a hybrid approach to have a balanced mix of remote and in-person data collection and trial procedures. Decentralised and patient-centric approaches are the future of any organisation for the conduct of clinical trials. Globally, all sponsor pharmaceutical companies must start undertaking drug development and clinical trials using a decentralised approach while keeping patient centricity in mind.