Therapeutic innovation & regulatory science最新文献

This study systematically evaluated the impact of China's drug review system reform on pediatric drug approval efficiency using 310 pediatric drug registration records (2015-2024) from the CDE of China's NMPA supplemented with the YaoZhi Database, with comparative analysis of adult drug review patterns. Post-2019 amendments to the DAL significantly reduced pediatric review timelines from a median of 450 days (2015-2019) to 377 days (2020-2024; P < 0.0001), representing a 16.4% reduction versus adult drugs (451 days). The standard review pathway showed even greater pediatric acceleration (385 days vs. adult 497.5 days; 22.6% reduction, P < 0.0001), demonstrating targeted regulatory resource allocation. While biologics exhibited significant review advantages (342 days vs. chemical drugs' 403 days; P = 0.0085), structural imbalances persisted: high import dependency (73.9% imported vs. 26.1% domestic), inadequate child-appropriate formulations (< 10%), and critical therapeutic gaps (traditional Chinese medicines: 1.3%; rare disease drugs: < 5%). Efficiency gains were linked to expanded priority review adoption and optimized technical standards, yet unresolved deficits necessitate: establishing a dedicated pediatric review database with unified standards and conditional access; optimizing resource allocation for clinically urgent drugs; enhancing rare disease incentives; and accelerating age-appropriate formulation innovation-collectively enhancing regulatory science to address pediatric clinical needs.

Introduction: Early health technology assessment (HTA) advice provides value to pharmaceutical companies during drug development by identifying potential data gaps, refining study designs, and improving understanding of HTA agencies' evidentiary requirements. This study evaluated the landscape, benefits, and challenges of early HTA advice, with a focus on European agencies and global practices amid the transition to the EU HTA Regulation.

Methods: A perception survey involving 12 pharmaceutical companies explored engagement with HTA agencies, challenges, and strategic priorities. Additionally, a forum was conducted with 22 company representatives, discussing internal and external best practices. Key topics included the evolving role of Joint Scientific Consultations (JSCs), integration of real-world evidence (RWE), and incorporation of patient-reported outcomes (PROs) into advice processes.

Results: The findings highlighted active engagement with national agencies such as NICE and G-BA and European initiatives like EUnetHTA Joint Actions. NICE advice was valued for cost-effectiveness insights, but its post-Brexit absence reduced collaboration at the European level. JSCs under the EU HTA Regulation were seen as critical, but resource constraints and limited availability posed challenges. Companies prioritized topics such as comparator choices, outcome measures, and RWE but faced internal barriers like resource allocation and unclear decision criteria. Outside Europe, uptake of advice services, such as those from CDA-AMC, remained limited but underscored the potential of lifecycle approaches for iterative learning.

Conclusions: Early HTA advice is essential in pharmaceutical development. Enhancing JSC capacity, stakeholder engagement, and feedback mechanisms will strengthen alignment between companies and HTA agencies, fostering evidence-based decision-making and improved health outcomes.

Introduction: A Japanese risk management plan (RMP) is a proactive planning tool for managing safety concerns (important identified risk [IIR], important potential risk [IPR], and important missing information [IMI]) for each drug and is continuously updated. However, no studies have examined the dynamic changes of safety concerns in RMPs throughout the drug lifecycle.

Methods: We conducted a longitudinal descriptive analysis of safety concerns in RMPs of drugs approved for new active ingredients in 2014 in Japan. We compared safety concerns in RMPs between the first version at approval and the latest version 8 years after the approval date using the Sankey diagram. We also investigated the evidence for RMP changes.

Results: This analysis included 38 drugs, whose first version RMPs included 155 IIRs, 119 IPRs, and 59 IMIs. Among them, all IIRs and 88% of the IPRs and the IMIs remained in the latest version of the RMPs 8 years after the approval date. During follow-up, 29 IIRs, 20 IPRs, and 3 IMIs were newly added, 14 IPRs were upgraded to IIRs, and 7 IMIs were deleted; thus, the final numbers of IIRs, IPRs, IMIs were 198, 125, and 55, respectively. Evidence for RMP changes was more often obtained from pharmacovigilance activities than from clinical/non-clinical studies conducted for additional approvals.

Conclusions: Most of the safety concerns identified at the first approval remained over 8 years, and the number of IIRs and IPRs tended to increase after approval. Most of the RMP changes were based on pharmacovigilance activities.

Objectives: To identify and describe patient experience data (PED)-related guidance issued by regulatory and health technology assessment (HTA) agencies in North America, Europe, and Asia Pacific.

Methods: National agency websites were manually searched (October 2021, updated October-December 2023) to identify standalone PED guidance, and general submission/clinical trial or disease-specific guidance in four therapy areas, including PED-related recommendations. Identified documents were reviewed for requirements/expectations on types of PED; concepts of interest and instruments/tools; validation, analysis, and interpretation; study design, and endpoint definitions.

Results: A total of 34 regulatory and 21 HTA documents were reviewed across 7 and 11 agencies, respectively. Most regulatory agencies expected data collected via clinical outcome assessments; concepts of interest were similar; specific tools were not usually recommended, although the use of validated instruments was expected; and meaningful within-patient change was generally considered key to interpretation. HTA guidance on PED varied primarily based on country requirement for utility estimates to inform economic evaluation (little/no guidance beyond the concept of interest) versus interest in PED on signs, symptoms, or disease impact on functioning (generally more comprehensive details on PED expectations).

Conclusion: Through PED, patient voice is an increasingly important factor in regulatory, access, and reimbursement decision-making. Regulatory and HTA agencies in North America, Europe, and Asia Pacific have varying expectations regarding PED. This misalignment can necessitate the collection of multiple types of PED to meet all requirements (resulting in complex clinical trial protocols and significant patient burden), and lead to differences in data interpretation or gaps in the expected data. Therefore, PED measurement standards should be harmonized globally, and the collection of required PED should be ensured early during drug development to ensure decisions can be made based on valid and reliable data.

Due to great unmet medical needs, orphan drug development is a common issue of high priority for policymakers, industry leaders, researchers and patients worldwide. The establishment of a harmonized support system is the way forward to address the dilemma facing rare diseases (RDs). This study pioneers the proposal of a framework and dimensions of support systems affecting orphan drug development, covering legal (political and legal basis), technical (regulatory guidance and acceleration), motivational (economic incentives and innovation returns) and logistical (fundamental infrastructure) factors. This study, based on the framework, shows that the conditions for orphan drug development above are basically developed in the US, the EU and China. Additionally, China lags behind in terms of economic incentives and fundamental infrastructure. Continuous improvements in pricing and reimbursement, as well as the acceleration of real-world data (RWD) database and biobank repository integration, are expected in China. Based on these findings from the three study regions, action plans with three strategies (national plans and strategies, a patient-centered health system, global governance and collaborations) and eleven actions are suggested for strengthening synergies between initiatives and stakeholders to satisfy the medical needs of RD patients and families. This study can provide a reference not only for orphan drug development in the three study regions but also for all other countries worldwide, especially for those with a late start in addressing RDs.

Objective Participatory Patient Advocacy (OPPA) is an important evolution from traditional patient advocacy to a strategic, data-driven approach that significantly impacts the patient voice vis-a-vis both drug development and the regulatory processes, particularly within the realm of rare diseases. Focusing on the exemplar of Parent Project Muscular Dystrophy (PPMD) and its work in Duchenne muscular dystrophy (DMD), this article highlights how OPPA leverages scientific rigor, collaborative partnerships, and a patient-centered perspective to accelerate the development and approval of effective therapies. The era of anecdote-driven advocacy is waning, making way for a new paradigm where patient advocacy organizations act as pivotal stakeholders in the drug development ecosystem. OPPA is characterized by its use of data-driven tools such as surveys, preference studies, and real-world evidence to inform research priorities, clinical trial designs, and regulatory decision-making. By adopting this objective approach, patient advocacy groups can contribute valuable insights into patient needs, preferences, and risk tolerance, which can then be integrated into the drug development process to ensure that therapies are both effective and aligned with patient values. These initiatives encompass a wide range of activities, including investing in cutting-edge research, advocating for legislative support for intramural research, and fostering collaborative partnerships with researchers, industry stakeholders, and regulatory agencies. PPMD's efforts to identify and validate biomarkers, map proteins, and develop industry guidance demonstrate its commitment to building a solid scientific foundation for DMD drug development. A key focus of the article is the collaborative effort between the FDA, PPMD, care-givers, healthcare providers, scientists, and regulatory experts to and the FDA, culminating in the creation of patient-initiated draft guidance for industry developing DMD therapies. This achievement signifies a shift in the regulatory landscape, with the FDA recognizing patient perspectives that has led to more flexible and patient-centered regulatory pathways and the approval of promising new therapies. Objective Participatory Patient Advocacy calls for continued collaboration between advocacy groups, regulators, industry, and researchers. These partnerships are essential to sustaining progress and ensuring meaningful outcomes. The lessons learned from PPMD's experience offer a roadmap for other rare disease communities to emulate, paving the way for a future where patient voices are central to the development of innovative therapies and the improvement of patient care.

Background: Decentralized clinical trials (DCTs) are increasingly being used to enable greater participation of patients in clinical research and improve the patient experience. In 2021, the Chiesi research and development team established the Digital innovAtion for patieNt Centric hEalth (DANCE) initiative with the aim to enhance the clinical trial journey for participants by merging patient perspectives with modern technology. As part of this project, the concept of DCTs was explored with patients affected by respiratory or rare diseases and with healthcare professionals (HCPs) treating these patients in the USA and Europe.

Methods: The concept of the clinical trial journey and DCTs were initially explored through semi-structured interviews with 37 patients and HCPs. A follow-on web survey of 390 patients and HCP participants was then performed to gather opinions on the different components of DCTs and to identify elements to be incorporated in future DCTs. A final web survey with 135 patients and caregivers expanded on the DCT concept focusing on direct-to-patient delivery of investigational medications.

Results: Overall, both patients and HCPs liked and were open to the concept of DCTs. They believed this approach in clinical trials would avoid patients having to travel long distances for screening or study visits, and increase participation of diverse populations in trials. The main concerns for both patients and HCP participants were the reduction of face-to-face interactions and whether the technology would be easy to use.

Conclusions: This work highlights the benefits of DCTs and identifies potential challenges to be addressed to make DCTs more appealing to all participants. Responses also demonstrate the significance of integrating face-to-face contact with remote contact through user-friendly tools.

The expansion of the use of decentralised elements in clinical trials in the European Union is driven by the opportunities they offer, including their potential to enhance trial access and improve research outcomes. Despite these potential benefits, several regulatory, operational, and technological challenges impede their widespread adoption. This paper, developed by members of the European Federation of Pharmaceutical Industries and Associations, proposes strategies and policy recommendations to overcome these barriers. Through harmonised regulatory frameworks, improved data validation methods, and increased stakeholder collaboration, the use of decentralised elements could become a standard practice in clinical research as part of the clinical trial toolbox to be deployed as appropriate, thereby enabling innovation and allowing for equitable access to clinical trials for diverse populations.