Therapeutic innovation & regulatory science最新文献

{"title":"Consideration for Assessing Data/Models/Tools Expiration Supporting Drug Development and Clinical Decision Making.","authors":"Jeffrey S Barrett, Mark A Turner","doi":"10.1007/s43441-025-00793-z","DOIUrl":"10.1007/s43441-025-00793-z","url":null,"abstract":"<p><p>Decision making of any kind is informed by data and often by models, tools or other solutions built from data. Data are evaluated for such purposes within a specific context of use (COU) but implicitly we often believe the data to be relevant, accurate and of high quality. In reality, this is not always the case. The status of data for various COUs must constantly be revisited for relevance and information value over time. Using drug development as an example, we postulate that there are indeed occasions where data value diminishes over time and consideration for data expiration with respect to its relevance for decision making should be entertained and at least identified with respect to a time-dependent change in status. Other situations exist which will also necessitate periodic review and condition reassessment. For example, considerations for patient privacy and consent along with compliance to regulatory standards must factor into future recommendations as well. Actions regarding data expiration are proposed as initial thoughts to be expanded upon but this assessment is primarily an attempt to explore factors which impact opinions about data information value for both drug development and clinical decision making.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"707-717"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality of Randomized Controlled Trials in the Association of Southeast Asian Nations (ASEAN) - A Systematic Review.","authors":"Marlinang Diarta Siburian, Sifa Marie-Joelle Muchanga, Antonio Villanueva, Asuka Nagatani, Takuma Kato, Koji Wada, Masamitsu Eitoku, Takeshi Murakami, Narufumi Suganuma","doi":"10.1007/s43441-025-00789-9","DOIUrl":"10.1007/s43441-025-00789-9","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to assess the quality and characteristics of RCTs in the ASEAN Member States (AMS) during a decade of harmonization efforts.</p><p><strong>Methods: </strong>This study is a systematic review to assess the quality of RCTs conducted in AMS. Studies were included if they were (1) reports of RCTs involving AMS from 2010 to 2021; (2) published in English; and (3) available in full text. Literature searches were conducted in MEDLINE and EMBASE. Study quality was assessed using the Cochrane's risk-of-bias tool and were classified as high- or low-quality. Multiple logistic regression analysis was used to identify characteristics associated with RCT quality.</p><p><strong>Results & discussions: </strong>A total of 51,177 articles were identified, among which 437 studies were eligible for quality assessment. Of the 437 studies, 41.6% were of high-quality. The use of blinding and a higher number of participants (100-1000 and > 1000) contributed positively to study quality (odds ratio (OR): 1.60 [95% confidence interval (CI): 1.05-2.41]; OR: 1.91 [95%CI: 1.24-2.94]; OR: 3.14 [95%CI: 1.22-8.10], respectively). Whereas the use of non-parallel assignment in the type of randomization contributed negatively to study quality (OR: 0.51 [95% CI: 0.26-1.03], P = 0.060). Among the six AMS with a high number of RCTs, two had high-quality studies > 50%, three had slightly more than 40% and one had less than 20%.</p><p><strong>Conclusions: </strong>In the decade of regulatory harmonization, less than half of RCTs in AMS were of high-quality. Large numbers of participants and the use of blinding were associated with high-quality RCTs, while the opposite was true for studies with non-parallel assignment. To improve the quality of RCTs, more training and capacity building of local researchers is needed, with particular attention to study design.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"718-727"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cross-sectional Study and Comparison between Japan and the United States on Special Regulatory Pathways for Expedited Drug Development and Approval.","authors":"Kojiro Kobayashi, Yuina Inaba, Mayu Hashimoto, Hideki Maeda","doi":"10.1007/s43441-025-00771-5","DOIUrl":"10.1007/s43441-025-00771-5","url":null,"abstract":"<p><strong>Background: </strong>Investigations on the relationship between the designated systems for drug development and regulatory processes in Japan and those in the United States over an extended period of time are limited.</p><p><strong>Objectives: </strong>We aimed to comprehensively investigate the special regulatory pathways for approved drugs in Japan focusing on the types of drugs receiving SRPs, the benefits of SRP in terms of review periods, a comparison between Japan and the United States, and the investigation of mutual influences in obtaining SRPs in both countries over 20 years.</p><p><strong>Methods: </strong>All drugs approved in Japan between September 1999 and December 2022, and those that underwent various special regulations based on publicly available information were investigated. A comparison between Japan and the United States was conducted using publicly available information.</p><p><strong>Results: </strong>In total, 2,309 drugs were approved in Japan between September1999 and December 2022, of which 819 drugs received special regulatory pathways. The number of drugs receiving special regulatory pathways increased annually, from 10 from September to December in 1999 to 90 in 2022. Anticancer drugs accounted for one-third of all drugs. Orphan drugs (432 drugs, 52.7%), expedited reviews (257 drugs, 31.4%), and priority reviews (135 drugs, 16.5%) were the most common regulatory pathways. For drugs receiving special regulatory pathways, 315 (38.5%) were approved within 6 months and 699 (85.3%) were approved within 12 months (the mean review period in Japan). Designations of priority review, expedited review, and orphan drug in Japan mutually influence the designation of these special regulatory pathways. In addition, designation of expedited review and orphan drug in Japan was influenced by designation of breakthrough therapy in the US, and expedited review in Japan was influenced by fast track in the US. In the US, special regulatory pathways are not significantly overlapped each other in the US.</p><p><strong>Conclusions: </strong>In the drugs approved in Japan, the Japanese specific special regulatory pathways are mutually influenced. Expedited review and orphan drug in Japan are significantly impacted by the specific special regulatory pathways of the US. Additionally, special regulatory pathways of the US did not influence each other.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"753-760"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Comprehensive Retrospective Analysis of Trends and Strategic Implications of 505(b)(2) Approvals (2019-2023).","authors":"Ramesh Joga, Kailas Vijay Gadekar, Kajal Gandhi, M Sowndharya, Sonali Waikar, Rajeev Singh Raghuvanshi, Saurabh Srivastava","doi":"10.1007/s43441-025-00775-1","DOIUrl":"10.1007/s43441-025-00775-1","url":null,"abstract":"<p><strong>Background: </strong>The 505(b)(2) pathway, established by the USFDA, enables faster approval of new drug applications (NDAs) by allowing partial reliance on existing clinical data. This regulatory mechanism fosters innovation by encouraging new formulations, combinations, and delivery systems, accelerating the availability of advanced therapeutics.</p><p><strong>Objective: </strong>This study provides a comprehensive analysis of 505(b)(2) NDA approvals from 2019 to 2023, with an emphasis on trends, major players, therapeutic targets, and dosage form diversity. Furthermore, the impact of regulatory exclusivity strategies on market dynamics and drug pricing is explored.</p><p><strong>Methods: </strong>Approval data was gathered from the USFDA database and further classified by reformulation type, therapeutic area, primary players, and dosage form. The study also analyzed the therapeutic equivalence codes and the influence of non-patent exclusivity strategies on market competition to identify trends and the prevalence of product types across therapeutic categories.</p><p><strong>Results: </strong>Our findings reveal a strong presence of reformulations, with new dosage forms (Type 3) and new formulations or other differences (Type 5) accounting for a substantial portion of approvals. Cancer (16.7%), CNS disorders (16.2%), and anti-infective treatments emerged as key therapeutic areas. Teva Pharmaceuticals USA Inc. was the leading entity by approval count. Parenteral dosage forms dominated at 40.3%, followed by tablets at 20.6%. Exclusivity strategies, notably three year's new clinical investigation exclusivity, impacted drug pricing and competitive positioning.</p><p><strong>Conclusion: </strong>The 505(b)(2) pathway proves instrumental in advancing pharmaceutical innovation and expediting access to therapies targeting unmet needs. These insights offer value for regulatory professionals, drug developers, and policymakers in optimizing development and market strategies to enhance drug accessibility. Companies must remain vigilant and proactive in anticipating potential blocking exclusivities to secure successful approvals.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"790-807"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient Experience Data (PED) in 2019-2023 US FDA NME Drug Approvals: Analysis and Recommendations.","authors":"Jewell D Martin, Darcy Frear, Samantha A Roberts, Victoria A Dohnal, Cameron Kieffer, Steve L Morin, Ian Lock, Aliyah Balogun, Nimi Chhina","doi":"10.1007/s43441-025-00788-w","DOIUrl":"10.1007/s43441-025-00788-w","url":null,"abstract":"<p><strong>Background: </strong>Since 2012, the United States Congress enacted several laws requiring the U.S. Food and Drug Administration (FDA) to consider the voice and perspective of patients in the regulatory review process. The goal of the paper is to evaluate the implementation and impact of this provision by assessing the inclusion of Patient Experience Data (PED) (i.e., in PED Tables and benefit-risk frameworks) in approval documents for FDA approved drugs from 2019 through 2023. It builds on previous analyses by providing a comprehensive assessment of the use of PED by sponsors and FDA.</p><p><strong>Methods: </strong>Authors assessed whether PED was submitted and reported in approval documents of 277 drugs or biologics approved by FDA's Center for Drug Evaluation and Research (CDER) and Center for Biologic Evaluation and Research (CBER). PED reported in drug approval documents and in product labels were analyzed for each indication.</p><p><strong>Results: </strong>Of the 277 approval documents analyzed, 252 included the PED Table in some form, where 179 tables were considered complete with PED. PED was included in the benefit risk framework for 85 (30%) applications and included in the label in 75 (27%) applications.</p><p><strong>Conclusions: </strong>Efforts to standardize and improve the systematic approach to collecting and utilizing PED has been ongoing for over 10 years. Our analysis has shown that both FDA and sponsors are increasingly considering patient voice to inform drug development and decision-making; however, more transparency is needed to ensure external stakeholders understand how FDA is reviewing and considering PED to inform regulatory decision-making.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"859-870"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporating Patient Input into the Target Product Profile.","authors":"Jean-Noel Talabardon, Janet E Church, Masanori Okuse, Michaela Dinboeck, Sheila Dickinson, Simon Messner, Michael Boisclair, Jean-Pierre Malkowski","doi":"10.1007/s43441-025-00783-1","DOIUrl":"10.1007/s43441-025-00783-1","url":null,"abstract":"<p><p>Target product profiles (TPP) are summaries of characteristics which drug developers expect to be necessary for a product to meet patients' needs, receive regulatory and payer approval, and differ from existing treatment options. As the experts on their own disease, patients bring invaluable perspectives to drug development, which cannot be obtained by other means. This communication reports on the development of a systematic guidance framework for a patient-focused, standardized TPP. The guidance was developed in a long-term iterative process, with crucial aspects reviewed and validated with the patient community. Five focus areas of a TPP were identified where patient perspectives are fundamental: target population, unmet need, dosage frequency and route of administration, efficacy endpoints, and acceptability of benefit/risk profile trade-offs. A guiding principle should be to incorporate patient perspectives in a systematic process starting as early as possible. A number of tools are available for obtaining patient perspectives, e.g., desk research, patient advisory boards/patient councils/online bulletin boards, focus groups with patients/caregivers, and/or in-depth interviews. When discussing the proposed process with patient representatives, they identified several key requirements for the interaction between R&D organizations and patient representatives. These include the use of clear language, respect for patients, engagement with patient experts, provision of adequate context and background information. We further discuss the relative importance of integrating patient perspectives into the different focus areas and touch upon the potential benefits to patient organizations from adapting these concepts and processes to enhance their voices in drug development.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"659-667"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Composite Index in Psychiatry Clinical Trial.","authors":"Haiqi Zhang, Shein-Chung Chow","doi":"10.1007/s43441-025-00772-4","DOIUrl":"10.1007/s43441-025-00772-4","url":null,"abstract":"<p><p>In psychiatry clinical trials, a validated instrument (or questionnaire) which consists of a number of questions (or items) is often used for evaluation of the safety and efficacy of a test treatment under investigation. This approach based on rating scales for evaluation of safety and efficacy of a test treatment under study, however, has been criticized of being subjective. To overcome the problem, the use of a composite index which combines the subjective rating scales and objective functional magnetic resonance imaging is proposed. For this purpose, statistical methods for development of composite index are derived. The proposed composite index is evaluated both theoretically and via extensive clinical simulation studies.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"761-768"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Inflation Reduction Act and Drug Development: Potential Early Signals of Impact on Post-Approval Clinical Trials.","authors":"Hanke Zheng, Julie A Patterson, Jonathan D Campbell","doi":"10.1007/s43441-025-00774-2","DOIUrl":"10.1007/s43441-025-00774-2","url":null,"abstract":"<p><strong>Background: </strong>The Inflation Reduction Act's (IRA) Drug Price Negotiation Program (DPNP) may reduce incentives for industry investments in post-approval clinical development. We aimed to explore the IRA's impact on the initiation of industry-sponsored, post-approval clinical trials.</p><p><strong>Methods: </strong>Using Citeline's Trialtrove database (7/2014-8/2024), we conducted an interrupted time series analysis (ITSA) to estimate the IRA's impact on the initiation of industry-sponsored Phase I-III trials in previously approved drugs, excluding all vaccines and COVID-19 treatments. We conducted an additional ITSA to examine post-IRA changes in government-funded trials, hypothesized to be unaffected by the IRA, and sensitivity analyses to explore potential exogenous confounding factors. Finally, we explored differences in the IRA's impact on post-approval industry-sponsored clinical trial initiation in small versus large molecule drugs.</p><p><strong>Results: </strong>Following the IRA's passage, the average monthly number of industry-sponsored trials on post-approval drugs decreased by 38.4%. The ITSA indicated that the IRA's passage was associated with an immediate drop of 11.1 industry-sponsored trials (p-value < 0.05) and an additional decrease by 0.9 trials per month (p-value < 0.01). The IRA's passage was not statistically associated with changes in government-funded trial initiation. Sensitivity analyses supported ITSA findings. Initiation of post-approval industry-sponsored trials decreased by 47.3% and 32.9% for small and large molecule drugs, respectively.</p><p><strong>Conclusions: </strong>The IRA's passage was associated with reductions in industry-sponsored, but not government-funded, post-approval trials, with larger reductions for small molecule drugs. These findings provide early evidence supporting concerns around IRA-related reductions in incentives for post-approval clinical development.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"781-789"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Companion Diagnostic FDA Review Flexibilities: An Assessment of CDx for NSCLC to Support Aligned Approaches for Validation.","authors":"Hillary S Andrews, Grace Collins, Bernat Navarro-Serer, Mark D Stewart, Jeff D Allen","doi":"10.1007/s43441-025-00799-7","DOIUrl":"10.1007/s43441-025-00799-7","url":null,"abstract":"<p><p>The U.S. Food and Drug Administration (FDA) recommends concurrent development of targeted therapies with an associated companion diagnostic (CDx) as the optimal approach to provide patient access to novel, safe, and effective treatments. However, CDx validation often relies on clinical samples from pivotal clinical trials for the drug, which can be challenging, particularly when there is limited sample availability. A review of Summary of Safety and Effectiveness Data (SSED) documents for CDx approved for non-small cell lung cancer (NSCLC) revealed that CDx for rare biomarkers often use alternative samples for validation. While the practice of using alternative samples for validation occurs, it is not always clear when these flexibilities are considered or how alternative samples should be used for validation. To address this, we propose the FDA establish guidance for the use of alternative sample sources for CDx validation, especially for rare biomarkers, to ensure timely and effective patient access to targeted therapies.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"676-679"},"PeriodicalIF":1.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Reimbursement Status: Availability of Advanced Therapy Medicinal Products Across the European Union.","authors":"Zora Čechová, Jana Kubátová, Adéla Bártová, Jakub Jamárik, Jiří Samek","doi":"10.1007/s43441-025-00769-z","DOIUrl":"10.1007/s43441-025-00769-z","url":null,"abstract":"<p><strong>Background: </strong>Advanced Therapy Medicinal Products (ATMPs) represent an innovative therapeutic approach with the potential to impact the treatment of rare diseases significantly. Although authorised centrally in the European Union, their market launch differs across Member States (MS). This study aimed to describe the ATMP market availability in MS and explore potential influencing factors, providing insights into specific barriers beyond pricing and reimbursement policies.</p><p><strong>Methods: </strong>ATMP availability was defined as the product launch in each MS. Data was collected through open governmental sources, databases, and communication with national competent authorities. Spearman's correlation coefficients were calculated to examine the relationship between ATMP availability and their characteristics (time since granting marketing authorisation, target patient population size, and cost).</p><p><strong>Results: </strong>We collected the availability data on 18 ATMPs from 23 EU MS. Market uptake varied significantly, with Germany (89%), France and Italy (61%) leading. Estonia and Latvia confirmed that no ATMP has been launched on their markets yet. Six ATMPs were available in more than one-third of the analysed MS. No significant correlation was observed between ATMP availability and analysed product characteristics except for time dependency for CAR T-cell therapies.</p><p><strong>Conclusion: </strong>Beyond pricing and reimbursement processes, the ATMP commercialisation in particular MS is influenced by the marketing authorisation holder's decision and capacity. ATMPs face product-specific challenges in achieving EU-wide availability, including complex manufacturing, distribution, and administration processes. To increase the accessibility of innovative ATMP-based treatments, implementing the cross-border access framework or individual ATMP production under the hospital exemption is essential, especially in underserved MS.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"728-736"},"PeriodicalIF":2.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}