Application For Approval Research Articles

Overall conclusions on the application for approval of Quassia amara L. wood as a basic substance to be used in plant protection as an insecticide and repellent in pome fruit, stone fruit, hop and ornamentals

Abstract The European Food Safety Authority (EFSA) was asked by the European Commission to provide scientific assistance with respect to the evaluation of applications received in accordance with Article 23 of Regulation (EC) No 1107/2009 concerning basic substances. This evaluation was requested by way of a specific mandate from the European Commission following the submission of an application for approval of Quassia amara L. wood as a basic substance to be used in plant protection as an insecticide and repellent in pome fruit, stone fruit, hop and ornamentals. This report summarises the outcome of the public and targeted consultations with Member States and EFSA, and presents EFSA's scientific views on the individual comments received including the overall conclusions with the main findings on the application.

Representation of Native Hawaiian and Pacific Islander Individuals in Clinical Trials

Having diverse participants in clinical trials ensures new drug products work well across different demographic groups, making health care safer and more effective for everyone. Information on the extent of Native Hawaiian and Pacific Islander participation in clinical trials is limited. To examine representation of Native Hawaiian and Pacific Islanders in clinical trials leading to the first US Food and Drug Administration (FDA) approvals for the 10 drug products with the top worldwide sales forecasts in 2024. Cross-sectional secondary analysis of existing data from clinical trials that took place from 2006 to 2021 in the US. All clinical trials that were included in the FDA first approval application for the 10 drug products were evaluated in this study. Data were analyzed from February to August 2024. Participation in a clinical drug trial. Comparison of the proportion of Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts in 2024 to the Native Hawaiian and Pacific Islander population proportion. In this cross-sectional study of 139 062 individuals, Native Hawaiian and Pacific Islander participation in clinical trials for the 10 drug products with top sales forecasts was either unknown or low. For 6 of the 10 drug products (60%), the number of Native Hawaiian and Pacific Islander participants was not documented. All trials that reported Native Hawaiian and Pacific Islander participation had fewer Native Hawaiian and Pacific Islander participants than would be expected based on their US population proportion, with 2 of the differences being statistically significant. Of the trials that disaggregated Native Hawaiian and Pacific Islander participants from other racial groups, the number of Native Hawaiian and Pacific Islander participants was 8 for risankizumab-rzaa (0.38% of participants vs 0.49% of the population; percentage point difference, -0.11%; 95% CI, -0.37% to -0.15%), 7 for bictegravir/emtricitabine/tenofovir alafenamide (0.38% of participants vs 0.49% of the population; percentage point difference, -0.10%; 95% CI, -0.39% to 0.18%), 27 for 4vHPV/9vHPV (0.15% of participants vs 0.46% of the population; percentage point difference, -0.31%; 95% CI, -0.37% to -0.26%), and 90 for BNT162B2 COVID-19 vaccine (0.20% of participants vs 0.52% of the population; percentage point difference, -0.32; 95% CI, -0.36% to -0.27%). In this cross-sectional study, limited documentation and participation of Native Hawaiian and Pacific Islander individuals in clinical trials for drug products with top sales forecasts was found. This is especially concerning because Native Hawaiian and Pacific Islander individuals have a higher risk than other racial groups for type 2 diabetes, cancer, and several other conditions the products examined in this study treat. Given the importance of enrolling Native Hawaiian and Pacific Islander participants in clinical trials, sites should be established in key geographic regions, such as Hawai'i, and postmarket studies should be conducted within Native Hawaiian and Pacific Islander populations.

Improving Academic Promotion Success via Implementation of Targeted Preparation Strategies and Coaching Processes

Abstract Problem Academic promotion is important for faculty career development and retention in academic medicine. However, the promotion process is time consuming, with little guidance offered to ensure successful outcomes. The authors describe their institution’s standardized approach to providing clear and reliable academic promotion support and share associated outcomes. Approach An academic promotion support process, comprising 4 targeted preparation strategies and 3 coaching processes, was implemented in 2020 at Children’s Mercy Kansas City to prepare faculty to submit promotion applications. Targeted preparation strategies include communication plans, an intent to apply process, how-to guides and templates, and institutional promotion committee review. Coaching processes include structured conversations with an immediate faculty leader, an Office of Faculty Development director, and, after committee review of applications, an institutional promotion committee reviewer. Descriptive statistics and promotion outcomes were compared pre (2012–2019) and post (2020–2023) implementation. Outcomes In 2012–2019 (8 promotion cycles), prior to implementation of the academic promotion support process, 247 faculty applied for academic promotion. After implementation, in 2020–2023 (4 cycles), 196 faculty applied. From pre to post implementation, the mean volume of applications per cycle significantly increased from 31 to 49 (P = .03), and the proportion of approved promotion applications significantly increased from 89.5% (221/247) to 99.0% (194/196) (P < .001). No significant differences were observed in the proportions of applicants who were female (P = .77) or non-White (P = .51). Next Steps Creation of an institutional academic promotion support process can be effective in increasing the volume of applications and the likelihood of successful outcomes. Future research should focus on increasing the proportions of non-White faculty and female faculty who apply for promotion and analyzing longer-term outcomes for faculty who are promoted, such as progression to leadership roles.

Assessing Immunogenicity in Drug Reviews and Prescribing Information in Japan.

Anti-drug antibodies (ADAs) generated in response to biopharmaceuticals can significantly impact pharmacokinetics (PK) and overall drug efficacy. Thus, the ICH M4 guidelines mandate summarizing immunogenicity data from clinical trials in drug approval applications. However, following the approval of the first antibody drug in Japan in 2001, no cross-sectional investigation has focused on immunogenicity during the regulatory review process. Therefore, this study aims to examine the review reports and prescribing information of antibody drugs approved in Japan to identify key points related to immunogenicity evaluation. We conducted a cross-sectional analysis of review reports for antibody drugs approved between June 2001 and July 2022 by the Japanese regulatory authority. Specifically, we evaluated the ADA positivity rate, presence of neutralizing antibodies, antibody titers, and effects of ADA on PK, efficacy, and safety. We also compared this information with that provided in the prescribing information. Our analysis revealed that the ADA positivity rate and its effects on PK, efficacy, and safety were critical aspects of the review process. The emphasis on these factors varied depending on the number of applications and disease area. The information presented in the prescribing information was largely consistent with that discussed in the review reports. Overall, this study provides the first cross-sectional evaluation of immunogenicity considerations in the regulatory review of antibody drugs in Japan. Our findings can contribute to the efficiency of clinical trial planning and preparation of approval applications, to potentially improve the overall drug development process and address the drug loss problem in Japan.

The regulatory status of health apps that employ gamification

Smartphone applications are one of the main delivery modalities in digital health. Many of these mHealth apps use gamification to engage users, improve user experience, and achieve better health outcomes. Yet, it remains unclear whether gamified approaches help to deliver effective, safe, and clinically beneficial products to users. This study examines the compliance of 69 gamified mHealth apps with the EU Medical Device Regulation and assesses the specific risks arising from the gamified nature of these apps. Of the identified apps, 32 (46.4%) were considered non-medical devices; seven (10.1%) were already cleared/approved by the regulatory authorities, and 31 (44.9%) apps were assessed as likely non-compliant or potentially non-compliant with regulatory requirements. These applications and one approved application were assessed as on the market without the required regulatory approvals. According to our analysis, a higher proportion of these apps would be classified as medical devices in the US. The level of risk posed by gamification remains ambiguous. While most apps showed only a weak link between the degree of gamification and potential risks, this link was stronger for those apps with a high degree of gamification or an immersive game experience.

GAIT CHANGES FOLLOWING CERAMIC-ON-CERAMIC HIP RESURFACING ARTHROPLASTY: A PROSPECTIVE STUDY

A ceramic-on-ceramic hip resurfacing implant (cHRA) was developed and introduced in an MHRA-approved clinical investigation to provide a non metallic alternative hip resurfacing product. This study aimed to examine function and physical activity levels of patients with a cHRA implant using subjective and objective measures both before and 12 months following surgery in comparison with age and gender matched healthy controls.Eighty-two unilateral cHRA patients consented to this study as part of a larger prospective, non-randomised, clinical investigation. In addition to their patient reported outcome measures (PROMs), self- reported measures of physical activity levels and gait analysis were undertaken both pre- operatively (1.5 weeks) and post operatively (52 weeks). This data was then compared to data from a group of 43 age gender and BMI matched group of healthy controls. Kinetics and kinematics were recorded using an instrumented treadmill and 3D Motion Capture. Statistical parametric mapping was used for analysis.cHRA improved the median Harris Hip Score from 63 to 100, Oxford Hip score from 27 to 48 and the MET from 5.7 to 10.3. cHRA improved top walking speed (5.75km vs 7.27km/hr), achieved a more symmetrical ground reaction force profile, (Symmetry Index value: 10.6% vs 0.9%) and increased hip range of motion (ROM) (31.7° vs 45.9°). Postoperative data was not statistically distinguishable from the healthy controls in any domain.This gait study sought to document the function of a novel ceramic hip resurfacing, using those features of gait commonly used to describe the shortcomings of hip arthroplasty. These features were captured before and 12 months following surgery. Preoperatively the gait patterns were typical for OA patients, while at 1 year postoperatively, this selected group of patients had gait patterns that were hard to distinguish from healthy controls despite an extended posterior approach. Applications for regulatory approval have been submitted.

Need for Data Standardization and Infrastructure of Research Data Management to Promote Using Real-world Data

Real-world data (RWD) have been increasingly used for regulatory decision-making and as a control group for new drug approval applications. RWD is also helpful in understanding information such as risk factors (e.g., pre-existing medical conditions, personal protective equipment, travel, contacts, smoking, and exposure to animals) and vaccination status for the coronavirus disease 2019 (COVID-19). The methodology of utilizing RWD is inconsistent across healthcare institutions. However, there are possible solutions to standardize RWD for clinical data use, which include the use of Clinical Data Interchange Standards Consortium (CDISC) standards, tools, and concepts. This study examines the availability of CDISC and other international standards for the utilization of RWD with concrete examples and presents the potential platform for implementation. We consider the solution currently available to temporarily convert clinical data-warehouse (DWH) data into the Fast Healthcare Interoperability Resources (FHIR) format to comply with the CDISC standard. This approach would allow for converting institution-level standards to national standards as an interim solution until FHIR is supported, mapping national standards to international standards. We believe that the ideal research environment is a data platform that complies with national and international regulations related to RWD applications. Within such a platform, users can share data freely, rather than rely on a specific facility or vendor. Data platform developments are progressing in Japan and globally. In Japan, initiatives to use research data on research data platforms are being conducted. We are experimenting with implementing tools and knowledge shared by CDISC.

Decisions of public authorities in the field of land relations

The article focuses on the grounds for decision-making by public authorities on refusal to grant ownership of land plots. The issues related to the concept of unauthorized construction under the civil legislation of the Russian Federation, the basis for the acquisition of property rights arising as a result of bona fide, open and continuous ownership and use, referred to as the acquisition prescription, are disclosed. The author reveals the specifics of the application of the “garage amnesty” when considering an application for preliminary approval of the provision of a land plot for the placement of a capital garage. Depending on this, an assessment is given of the need to apply to judicial authorities for recognition of ownership of previously issued land plots by public authorities. The article provides judicial practice related to the appeal of decisions of the executive authorities of the subject of the Russian Federation. In this connection, the author concludes that it is necessary to carry out regular monitoring of the development and decision-making of public authorities, as well as professional development of officials. This will help to avoid misinterpretation of the law when making decisions on granting land plots to citizens.

CERTIFICATION OF MAJOR CHANGES IN AVIATION TECHNOLOGY

Major change certification allows organizations to implement and control changes to designs, systems and equipment. This is a complex and responsible step that requires compliance with standards and safety requirements. The application for approval of a major change must contain all necessary documentation and information to demonstrate that the changes comply with safety and quality requirements. This approach guarantees the reliability of the changes being implemented. This article describes in detail the procedure for certification of major changes in aviation technology.

Bloodborne pathogens in beef herds – a Kansas practitioner’s perspective

Management options for bloodborne diseases depend on preva­lence (herd level and geographic), disease stage and production class. Opportunities to manage disease can be classified ac­cording to disease stage. Newer studies show that, in contrast to older studies, there is not currently a known legal way to clear animals of anaplasmosis. The only currently labeled products for treatment of acute clinical anaplasmosis are injectable oxy­tetracyclines. For a time, an enrofloxacin product (Baytril-CA) was marketed with a label for treatment of anaplasmosis, but the conditional approval application has been withdrawn. Op­portunities for leukosis management are limited to exposure control as there are no effective treatments for animals in the clinical stage and no effective methods to clear infected non-clinical animals. Due to the relatively high prevalence in beef herds, a strict test-and-cull strategy is not practical. Instead identifying animals with high pre-viral load who are most infectious provides an option to decrease disease levels with reasonable economics at the farm level. More research is neces­sary to fully quantify production effects for carrier animals of both bovine leukosis and anaplasmosis.

Utilization, Expenditure, and Treatment Patterns Associated With Calcitonin Gene-Related Peptide Monoclonal Antibodies Reimbursed Subject to a Managed Access Protocol in Ireland

ObjectivesCalcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) are novel high-cost treatments for the prevention of migraine. This study presents data on utilization, expenditure, and treatment patterns with CGRP mAbs available under a managed access protocol in Ireland, to a cohort of treatment refractory patients (failed 3 or more previous treatments) with chronic migraine. MethodsData were extracted from the Primary Care Reimbursement Service High Tech claims database and special drug request online system and analyzed using Microsoft Excel and SAS. Treatment persistence was evaluated by refill patterns, and adherence was evaluated using the proportion of days covered method. Expenditure data were extracted directly from the database. ResultsBetween September 1, 2021 and April 30, 2023, 1517 applications for reimbursement approval for a CGRP mAb were received; 1458 (96.1%) were approved for reimbursement. Total expenditure on CGRP mAbs in year 1 (September 1, 2021 to August 31, 2022) was €3.2 million. The majority of patients initiated treatment with fremanezumab (60.8%) or erenumab (37.1%). Almost 90% of patients were considered adherent, and treatment persistence was high, with more than 75% of patients receiving more than 12 months of treatment in our 18-month study time frame. ConclusionsThis study demonstrates the importance of active health technology management, after reimbursement, in enabling cost-effective use of high-cost treatments while providing budget certainty for the healthcare payer. High levels of adherence and persistence suggest that treatment is successfully targeted in situations which unmet clinical need is greatest.

Development and validation of bioanalytical methods to support clinical study of disitamab vedotin.

Disitamab vedotin (RC48), a humanized anti-HER2 antibody conjugated with monomethyl auristatin E (MMAE), is the first antibody-drug conjugate in China with an approved biological license application. A bioanalytical method was established for three analytes (total antibody, conjugate antibody and free payload) to help characterize their pharmacokinetic behavior in clinical settings. The bioanalytical methods were validated according to M10 guidance. Electrochemiluminescence assaymethods were used for thequantitative measurement of total antibody and conjugated antibody in human serum. A LC-MS/MSmethod was used to quantify the concentration of MMAE in human serum. The method had high specificity and sensitivity with a quantitative range of 19.531-1250.000ng/ml (total antibody), 39.063-5000.000ng/ml (conjugated antibody)and 0.04-10.0ng/ml (MMAE), respectively.

Abstract 4038: TU2218 (TGFβRI/VEGFR2 dual inhibitor) maximizes the benefit of cancer immunotherapies

Abstract Approved anti-PD-1 antibodies play a pivotal role in driving innovative clinical outcomes through combination with cytotoxic agents, targeted therapies, or other immune checkpoint inhibitors in various cancers. Anti-PD-1 antibody-based combination therapies have led to a paradigm shift in cancer treatment from cytotoxic agents or targeted therapy to immunotherapy. Considering this change in the regimen, the clinical development of TU2218 aims to accelerate approval and clinical application by improving the efficacy and safety of clinically proven combination therapies. TU2218 is characterized by the following four mechanisms of action: 1) improvement of T lymphocyte activity, 2) suppression of Treg, 3) improvement of costimulatory signal defects, and 4) overcoming endothelial cell anergy. Based on the mechanisms of action, TU2218 is expected to show significant clinical effects when combined with immune checkpoint inhibitors by lowering the intensity of immune evasion and changing more favorably to immune checkpoint inhibitors. To test the feasibility of various combination options based on TU2218, in vivo efficacy studies were conducted in 4T1, MC38, and CT26 syngeneic tumor models. In the 4T1 of TNBC type, a level of tumor reduction was significant to p<0.001 on TU2218 and anti-PD-1 antibody combination group compared to vehicle, whereas anti-PD-1 antibody alone or anti-PD-1 antibody and paclitaxel combination group was not significant. Combination therapy with anti-CTLA4 antibody and anti-PD-1 antibody has been approved for some cancers but has therapeutic limitations due to safety issues such as immune-related toxicity and needs improvement. In the MC38, the effectiveness of a dose-sparing strategy of anti-CTLA4 antibody was evaluated by adding TU2218 to the anti-CTLA4 antibody and anti-PD-1 antibody combination regimen to improve safety concerns. In the anti-CTLA4 antibody sparing group, co-administration of TU2218 maintained the anti-tumor activity despite reducing 90% or 60% of the original anti-CTLA4 antibody dose. In effect, the difference in anti-tumor activity between the group with a reduced dose of anti-CTLA4 antibody and the group without was not statistically significant. In CT26, the efficacy of Lenvatinib and anti-PD-1 antibody combination therapy was compared with the combination of Lenvatinib, anti-PD-1 antibody, and TU2218. The efficacy of the Lenvatinib anti-PD-1 antibody, and TU2218 combination group was superior to that of TGI 99% and CR 67% than the Lenvatinib and anti-PD-1 antibody combination group of TGI 76% and CR 17%. Moreover, a statistical difference in anti-tumor activity between the two groups was significant at p<0.001. Collectively, the combination therapies using TU2218 not only improved efficacy but also showed high safety profiles without weight loss or any toxicity signs, supporting the feasibility of the combination strategy of TU2218. Citation Format: Jihyun Lee, Nam-Hoon Kim, Jeong Su Park, Jihyun Noh, Sowon Bae, Hun-Taek Kim. TU2218 (TGFβRI/VEGFR2 dual inhibitor) maximizes the benefit of cancer immunotherapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4038.

Chemistry and Pharmacology of Delta-8-Tetrahydrocannabinol.

Cannabis sativa is one of the oldest plants utilized by humans for both economic and medical purposes. Although the use of cannabis started millennia ago in the Eastern hemisphere, its use has moved and flourished in the Western nations in more recent centuries. C. sativa is the source of psychoactive cannabinoids that are consumed as recreational drugs worldwide. The C21 aromatic hydrocarbons are restricted in their natural occurrence to cannabis (with a few exceptions). Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component in cannabis, with many pharmacological effects and various approved medical applications. However, a wide range of side effects are associated with the use of Δ9-THC, limiting its medical use. In 1966, another psychoactive cannabinoid, Delta-8-tetrahydrocannabinol (Δ8-THC) was isolated from marijuana grown in Maryland but in very low yield. Δ8-THC is gaining increased popularity due to its better stability and easier synthetic manufacturing procedures compared to Δ9-THC. The passing of the U.S. Farm Bill in 2018 led to an increase in the sale of Δ8-THC in the United States. The marketed products contain Δ8-THC from synthetic sources. In this review, methods of extraction, purification, and structure elucidation of Δ8-THC will be presented. The issue of whether Δ8-THC is a natural compound or an artifact will be discussed, and the different strategies for its chemical synthesis will be presented. Δ8-THC of synthetic origin is expected to contain some impurities due to residual amounts of starting materials and reagents, as well as side products of the reactions. The various methods of analysis and detection of impurities present in the marketed products will be discussed. The pharmacological effects of Δ8-THC, including its interaction with CB1 and CB2 cannabinoid receptors in comparison with Δ9-THC, will be reviewed.

How can primary care benefit from digital health applications? – a quantitative, explorative survey on attitudes and experiences of general practitioners in Germany

BackgroundSince 2020, physicians in Germany have the possibility of prescribing approved digital health applications (DHAs) with the costs covered by the health system – a step that was unique in the world at that time and still is. So far, there have been hardly any studies that shed light on the possible applications of DHAs in the context of primary care and take stock of the benefits and potential for optimization. In 2022, a quantitative survey was carried out. The aim was to determine what attitudes, experiences and expectations GPs have with regard to the use of DHAs, under what conditions they are willing to integrate them into health care, and what experience they have already gained.MethodsThe focus was on a large-scale survey of GPs. Between spring and summer 2022, all 18,914 GPs in the federal states of Baden-Württemberg, Hesse, Lower Saxony, Rhineland-Palatinate and Saarland were invited to an online survey. 5,868 questionnaires were included in the evaluation (response rate: 31%). A t-test on independent samples was used to determine significant differences between two groups.Results68% of those surveyed are positive about DHAs and consider them to be reliable (69%) and safe (63%) applications that can generate efficiency benefits for the doctor-patient relationship. 24% trust themselves to competently advise patients on DHAs. 14% have already prescribed DHAs, 13% plan to do so. 85% of doctors with DHA experience rate the prescribed applications as (very) useful. Observed health care effects relate primarily to the improvement in compliance (94%), mobility (93%), and education (93%), as well as weight reduction (83%). Among other things, a further optimization of usability (59%), systematic further training of doctors on DHAs (53%) and the expansion of gamification elements (49%) are suggested. GPs lack well-founded information with regard to DHAs (52%).ConclusionFor GPs, DHAs can be effective tools to encourage patients in their personal responsibility, compliance and motivation to behave in a health-conscious manner and to strengthen prevention in the primary care setting. Where DHAs have been used in a practical context so far, widespread positive health care effects are noticeable. Most respondents do not dare to give patients competent advice on available applications. Comprehensive training courses that provide information about the framework conditions, strategies and advantages of using DHAs appear to be important. There is also a need for more well-founded sources of information and research for doctors to select suitable applications in a targeted manner. GPs see significant added value in DHAs compared to conventional health apps. In order for DHAs to be effectively implemented in primary care, it is important to better inform GPs about the legal basis and possible applications as well as to address their concerns.

Optimize The Authority To Judicial Review By The Supreme Court

Determined of Supreme Court Regulation Number 1 of 2011 about the Right to Test Material, where one of the substances remove strained period the submission deadline Applications for approval were previously limited to 180 days after regulation laws and regulations determined as previously regulated in the Regulations Supreme Court Number 1 of 2004 should be welcomed as a positive step in in order to make the authority to review statutory regulations effective by Supreme Court. In the future, in order to further optimize authority Therefore, the Supreme Court Regulations Concerning the Right to Judicial Review need to be revised through the establishment of Supreme Court Regulations regarding regulatory review regulations that include the right to material review and the right to formal review, because However, the Supreme Court does not only have the authority to carry out material tests also formal testing where the two understanding authorities are better known as the term judicial review authority.

Outgoing Letter Approval System at Class I Climatology Stations in North Sumatra Using the Prototype Method

The mechanism for outgoing correspondence at the North Sumatra Class I Climatology Station is through the approval of the Verifier and Kasklim. The system runs in approving outgoing letters, still going through the traditional process where the Verifier and Kasklim must go through directly in the room. This research aims to develop the intended outgoing letter approval application, to increase the effectiveness and efficiency of outgoing letter approval. This research is development research using the System Development Life Cycle (SDLC) approach and the prototype method which refers to data obtained from interviews with several letter operators at the North Sumatra Class I Climatology Station. Based on testing the system using a black box and evaluating the application by the staff concerned, it was concluded that the application was relevant to needs and could be implemented. This study also provides a basis for further research in optimizing similar systems in the context of climatology stations or other fields that require effective management of outgoing mail approvals.

Characteristics and use of patient-reported outcomes of clinical trials for high-risk neurological medical devices that received FDA premarket approval from 2001 to 2022

Neurological medical devices have revolutionized the management of neurological disorders, providing diagnostic, therapeutic, and monitoring solutions. High-risk neurological devices, such as deep brain stimulation and neurostimulators, offer groundbreaking treatments, emphasizing patient benefits while considering risks. To gain FDA approval, high-risk Class III devices necessitate premarket approval (PMA) applications with pivotal clinical trials, often assessing patient-reported outcomes (PROs). This article analyzes FDA-approved high-risk neurological devices from 2001 to 2022 via the PMA pathway. It explores device characteristics and pivotal clinical trials, and PRO incorporation. Of the 23 identified devices, pain neurology devices (30.4 %) predominated. All devices were therapeutic, with varying study designs. Pain neurology devices notably emphasized PRO endpoints as expected. This study underscores the significance of PROs in assessing device efficacy and safety, offering insights into regulatory processes and patient-centered care in neurological disorder management.

Health technology assessment of medicinal products in Greece: a 5-year (2018-2023) review of timelines and productivity.

To assess the health technology assessment (HTA) process in Greece from its establishment in 2018 until 2023 in terms of timeliness and productivity. Data were collected from the HTA Committee's database and other publicly available sources. The overall study timeframe was divided into three periods: (i) July 2018-January 2020, (ii) January 2020-July 2021, and (iii) July 2021-February 2023. During the study period, a total of 1,157 applications for medicinal products (MPs) (including 219 new active substances (NAS) and orphans) were submitted to the HTA Committee. The number of HTA recommendations increased from 60 (first period) to 641 (third period), while the backlog of MPs pending HTA and price negotiations decreased from 89 and 106 (January 2020) to 8 and 44 (February 2023), respectively. The median time intervals for all application types decreased significantly over time. In February 2023, the median time for clinical data assessment of NAS (excluding orphans) almost halved from 207days in the first period to 114days; median times for NAS and orphans from regulatory approval to HTA application were 420 and 457days, and from HTA application to reimbursement 228 and 417days, respectively. The performance of the HTA process in Greece improved significantly over time, with increased MP appraisals, backlog reduction, and decreased timelines. Delays in reimbursement of NAS were mainly caused by the long gap between regulatory approval and HTA application. Overall, HTA review times in Greece are now on par with that of well-established European HTA systems.

Platform trial for off-label oncology drugs using comprehensive genomic profiling under the universal public healthcare system: the BELIEVE trial

BackgroundPrecision medicine has transformed cancer treatment by focusing on personalized approaches based on genomic abnormalities. However, comprehensive genomic profiling (CGP) and access to targeted therapies are limited in Japan. This study investigates the BELIEVE trial, which aims to improve drug accessibility for patients with actionable genetic abnormalities through off-label drug administration.MethodsThe BELIEVE trial is a platform trial with a single master protocol, conducted under the Clinical Trials Act and the patient-proposed health services (PPHS) scheme. Eligible patients with solid tumors exhibiting actionable alterations were enrolled, and CGP tests covered by national health insurance were employed. Treatment selection, study drugs from collaborating pharmaceutical companies, and treatment schedules adhered to predefined protocols. Primary and secondary endpoints were evaluated, and statistical analysis was conducted based on patient response rates.ResultsThe BELIEVE trial offered treatment opportunities for patients with relapse/refractory disease who lacked standard therapies or clinical trial options. This study addresses unmet medical needs and contributes to the establishment of precision medicine systems. Similar trials like NCI-MATCH and TAPUR are being conducted globally. The BELIEVE trial provides a platform for off-label drug administration, collects essential clinical data, and contributes to drug approval applications.ConclusionThe BELIEVE trial provides hope for patients with actionable genetic abnormalities by facilitating access to targeted therapies through off-label drug administration. It establishes a regulatory framework and promotes collaboration between industry and academia by expanding organ-specific and cross-organ biomarker-based treatments.