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JAMA Internal Medicine Apr 2023Drug expenditures in the US are higher than in any other country and are projected to continue increasing, so US health systems may benefit from evaluating international...
IMPORTANCE
Drug expenditures in the US are higher than in any other country and are projected to continue increasing, so US health systems may benefit from evaluating international regulatory and reimbursement decision-making of new drugs.
OBJECTIVE
To evaluate regulatory decisions and health technology assessments (HTAs) in Australia, Canada, and the UK regarding new drugs approved by the US Food and Drug Administration (FDA) in 2017 through 2020, as well as to estimate the US cost per patient per year for drugs receiving negative recommendations.
DESIGN AND SETTING
In this cross-sectional study, recommendations issued by agencies in Australia, Canada, and the UK were collected for new drugs approved by the FDA in 2017 through 2020. All data were current as of May 31, 2022.
EXPOSURES
Authorizations and HTAs in selected countries.
MAIN OUTCOMES AND MEASURES
All FDA-approved drugs were matched by active ingredient to decision summary reports published by drug regulators and HTA agencies in Australia, Canada, and the UK. Regulatory approval concordance and reasons for negative recommendations were assessed using descriptive statistics. For drugs not recommended by an international agency, the annual US drug cost per patient was estimated from FDA labeling and wholesale acquisition costs.
RESULTS
The FDA approved 206 new drugs in 2017 through 2020, of which 162 (78.6%) were granted marketing authorization by at least 1 other regulatory agency at a median (IQR) delay of 12.1 (17.7) months following US approval. Conversely, 5 FDA-approved drugs were refused marketing authorization by an international regulatory agency due to unfavorable benefit-to-risk assessments. An additional 42 FDA-approved drugs received negative reimbursement recommendations from HTA agencies in Australia, Canada, or the UK due to uncertainty of clinical benefits or unacceptably high prices. The median (IQR) US cost of the 47 drugs refused authorization or not recommended for reimbursement by an international agency was $115 281 ($166 690) per patient per year. Twenty drugs were for oncology indications, and 36 were approved by the FDA through expedited regulatory pathways or the Orphan Drug Act.
CONCLUSIONS AND RELEVANCE
This cross-sectional study assessed reasons for which drugs recently approved by the FDA were refused marketing authorization or not recommended for public reimbursement in other countries. Drugs with limited international market presence may require close examination by US health care professionals and health systems.
Topics: Humans; Cross-Sectional Studies; Pharmaceutical Preparations; Orphan Drug Production; Australia; Canada; Drug Approval
PubMed: 36780147
DOI: 10.1001/jamainternmed.2022.6787 -
Vaccine Feb 2024The development of vaccines for COVID-19 occurred at an unprecedented pace, and 32 vaccines using a broad range of technologies had received authorization for use on an... (Review)
Review
The development of vaccines for COVID-19 occurred at an unprecedented pace, and 32 vaccines using a broad range of technologies had received authorization for use on an emergency basis by the end of 2021, from either a national regulatory authority or the World Health Organization. However, 27 of those 32 vaccines had little impact on the global course of the pandemic. Only five vaccines, from AstraZeneca, Pfizer/BioNTech, Sinovac, Moderna, and Sinopharm, were manufactured, authorized, and distributed in time to significantly impact the number of deaths worldwide. Together, these five vaccines averted an estimated 17 million deaths in the first year of the vaccination campaign. The shared characteristic of these five manufacturers was their ability to rapidly develop and scale up vaccine production to deliver the large manufacturing volumes required to immunize large segments of the global population. Because the development and manufacturing of these vaccines was generally on the critical path to authorization and supply, the technical activities involved with development, scale-up, testing, technology transfer, and full-scale manufacturing, as well as aspects of the Chemistry, Manufacturing, and Controls (CMC) regulatory interactions, are examined for each vaccine and technology for which information is available in the public domain to provide lessons learned and recommendations on proactive actions to better prepare us for a future pandemic response. The critical success factors include prior experience with commercialization and approval, robust quality systems, rigorous process development strategies, flexible manufacturing facilities with a skilled workforce, collaboration, access to consumables, reagents, and adjuvants (if relevant), and an equitable distribution of the global vaccine manufacturing network.
Topics: Humans; Influenza Vaccines; COVID-19 Vaccines; COVID-19; World Health Organization; Commerce
PubMed: 38228438
DOI: 10.1016/j.vaccine.2023.12.031 -
Cell Proliferation Aug 2022Clinical researches of stem cell-based therapies are highly active in China, while it was arduous to determine the most effective way of clinical translation of those... (Review)
Review
BACKGROUND
Clinical researches of stem cell-based therapies are highly active in China, while it was arduous to determine the most effective way of clinical translation of those advanced therapies.
METHODS
This article briefly introduced the regulatory framework development, the progress in stem cell clinical researches and clinical trials of commercially developed stem cell-based products, as well as the clinical review concerns of stem cell-based products in China.
MAIN FINDINGS
The current regulatory framework of stem cell clinical researches in China was launched in 2015, when regulatory authorities issued "Administrative Measures on Stem Cell Clinical Research" (AMSCCR) detailing the rules of stem cell clinical research. Thereafter, the rapidly growing stem cell clinical researches were rigorously managed and clinical use of stem cell therapy was halted. Meanwhile, commercially developed stem cell-based products are supervised by Drug Administration Law (DAL).
CONCLUSION
The regulatory framework of stem cell-based therapy in China has progressed in the last few decades, which is currently regulated according to AMSCCR and DAL. Well-designed and patient-focused clinical trial is required for commercially developed stem cell-based products, and definite clinical benefit evidence is crucial to obtain marketing authorization.
Topics: China; Humans; Stem Cell Transplantation
PubMed: 35419811
DOI: 10.1111/cpr.13217 -
EFSA Journal. European Food Safety... Jul 2017The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the... (Review)
Review
The conclusions of the European Food Safety Authority (EFSA) following the peer review of the initial risk assessments carried out by the competent authorities of the rapporteur Member State, the Netherlands, and co-rapporteur Member State, Spain, for the pesticide active substance chlorpropham and the assessment of applications for maximum residue levels (MRLs) are reported. The context of the peer review was that required by Commission Implementing Regulation (EU) No 844/2012. The conclusions were reached on the basis of the evaluation of the representative uses of chlorpropham as a plant growth regulator on potatoes and as a herbicide on glasshouse and field lettuce, field onion and field flower bulbs. MRLs were assessed in potato and animal commodities. The reliable end points, appropriate for use in regulatory risk assessment and the proposed MRLs, are presented. Missing information identified as being required by the regulatory framework is listed. Concerns are identified.
PubMed: 32625564
DOI: 10.2903/j.efsa.2017.4903 -
Chinese Medicine Feb 2021The National Medical Products Administration (NMPA) in China has set to advance the regulatory capacity of traditional Chinese medicines (TCMs) with the adoption of... (Review)
Review
Applying regulatory science in traditional chinese medicines for improving public safety and facilitating innovation in China: a scoping review and regulatory implications.
BACKGROUND
The National Medical Products Administration (NMPA) in China has set to advance the regulatory capacity of traditional Chinese medicines (TCMs) with the adoption of regulatory science (RS). However, the priority of actions at the interface of RS and TCMs were yet to be defined. This research aims to identify the priority areas and summarize core actions for advancing RS for traditional medicines in China.
METHODS
A mixed approach of documentary analysis of government policies, regulations and official information about TCMs regulation in China, and a scoping review of literature using 4 databases (PubMed, ScienceDirect, Scopus and CNKI) on major concerns in TCMs regulation was employed.
RESULTS
Ten priority areas in the development of TCM-related regulatory science in China have been identified, including: (1) modernizing the regulatory system with a holistic approach; (2) advancing the methodology for the quality control of TCMs; (3) fostering the control mechanism of TCMs manufacturing process; (4) improving clinical evaluation of TCMs and leveraging real world data; (5) re-evaluation of TCMs injection; (6) developing evaluation standards for classic TCMs formula; (7) harnessing diverse data to improve pharmacovigilance of TCMs; (8) evaluating the value of integrative medicine in clinical practice with scientific research; (9) advancing the regulatory capacity to encourage innovation in TCMs; and (10) advancing a vision of collaboration for RS development in TCMs.
CONCLUSIONS
RS for TCMs in China encompasses revolution of operational procedures, advancement in science and technology, and cross-disciplinary collaborations. Such experiences could be integrated in the communications among drug regulatory authorities to promote standardized and scientific regulation of traditional medicines.
PubMed: 33593397
DOI: 10.1186/s13020-021-00433-2 -
Bulletin de L'Academie Nationale de... Oct 2020The concept of biosimilar medicine was launched by 2001 and 2004 European Directives. First European marketing authorizations were delivered in 2006. They are "copies"... (Review)
Review
The concept of biosimilar medicine was launched by 2001 and 2004 European Directives. First European marketing authorizations were delivered in 2006. They are "copies" of biologically manufactured medicines, mostly proteins. Taking into account the intrinsic variability related to the biological manufacture process, some variation of the chemical structure of the finished compound may be observed. They impact especially the glycosylation residues but not the amino-acid sequence (for proteins). For this reason, the marketing authorization application dossier has to involve, as opposed to the generic medicine procedure, the demonstration of the therapeutic equivalence in at least one clinical indication of the princeps medicine. Introduction of biosimilar medicines of monoclonal antibodies has represented a remarkable event in the domain of rheumatology, gastroenterology and dermatology with infliximab, etanercept and adalimumab biosimilars and in cancerology domains with rituximab, trastuzumab and bevacizumab biosimilars. Biosimilar medicines availability reduces the risk of drug supply rupture of princeps but their main impact is the economic one allowing cost reduction of costly princeps biological medicines. With the acquired clinical experience, the initial fears concerning switch form princeps to a biosimilar for a given patient has progressively disappeared.
PubMed: 32836292
DOI: 10.1016/j.banm.2020.07.050 -
Journal of Clinical Oncology : Official... Jan 2023Cancer predictive or diagnostic assays, offered as Laboratory-Developed Tests (LDTs), have been subject to regulatory authority and enforcement discretion by the US Food... (Review)
Review
Cancer predictive or diagnostic assays, offered as Laboratory-Developed Tests (LDTs), have been subject to regulatory authority and enforcement discretion by the US Food and Drug Administration. Many LDTs enter the market without US Food and Drug Administration or any regulatory review. The Centers for Medicare & Medicaid Services under the Clinical Laboratory Improvement Amendments focuses on analytic performance, but has limited oversight of the quality or utility of LDTs, including whether patients have been harmed as a result of their use. Increasingly, LDTs for cancer risk or early detection have been marketed directly to consumers, with many LDT developers depicting these tests, requested by patients but ordered by personal or company-associated physicians, as procedures falling under the practice of medicine. This patchwork of regulation and enforcement uncertainty regarding LDTs and public concerns about accuracy of tests given emergency authorization during the COVID-19 pandemic led to the Verifying Accurate Leading-edge IVCT (in vitro clinical test) Development Act of 2021. This pending federal legislation represents an opportunity to harmonize regulatory policies and address growing concerns over quality, utility, and safety of LDTs for cancer genomics, including tests marketed directly to consumers. We review here questions regarding the potential benefits and harms of some cancer-related LDTs for cancer risk and presymptomatic molecular diagnosis, increasingly marketed to oncologists or directly to the worried well. We offer specific proposals to strengthen oversight of the accuracy and clinical utility of cancer genetic testing to ensure public safety.
Topics: Aged; Humans; United States; COVID-19; Pandemics; Medicare; Clinical Laboratory Services; Neoplasms
PubMed: 35944238
DOI: 10.1200/JCO.22.00995 -
Therapeutic Innovation & Regulatory... Mar 2024Limited evidence related to the safety or efficacy of medicines in pregnancy and during breastfeeding is available to inform patients and healthcare... (Review)
Review
Limited evidence related to the safety or efficacy of medicines in pregnancy and during breastfeeding is available to inform patients and healthcare professionals. Understanding the current regulatory landscape in the clinical trial and postmarketing settings is critical to facilitate the development of applicable processes and tools for studying medicine use during pregnancy and breastfeeding and comply with health authority expectations. This review summarizes key findings from a landscape assessment of regulations, guidelines, and guidance on the use of medicines in pregnancy and breastfeeding issued by health authorities in various territories (including the Americas, Europe, Africa, and Asia Pacific) and outlines relevant initiatives undertaken by health authorities, academic institutions, industry consortia, and public-private organizations. While global pharmacovigilance legislation regarding medication use during pregnancy and breastfeeding exists and continues to evolve, the landscape assessment revealed that there is a lack of global legislative harmonization in both the clinical trial and postmarketing surveillance settings and regulatory gaps still exist in many countries/regions. Despite ongoing efforts from health authorities and public and private organizations, intensive efforts for legislation harmonization and stakeholder collaboration are required to improve the current environment of medication safety in pregnancy and breastfeeding.
Topics: Humans; Female; Pregnancy; Infant, Newborn; Infant Health; Pharmacovigilance; Asia; Europe
PubMed: 38105314
DOI: 10.1007/s43441-023-00593-3 -
The Journal of Molecular Diagnostics :... Oct 2021The coronavirus disease 2019 (COVID-19) response necessitated innovations and a series of regulatory deviations that also affected laboratory-developed tests (LDTs). To... (Review)
Review
Temporary Regulatory Deviations and the Coronavirus Disease 2019 (COVID-19) PCR Labeling Update Study Indicate What Laboratory-Developed Test Regulation by the US Food and Drug Administration (FDA) Could Look Like.
The coronavirus disease 2019 (COVID-19) response necessitated innovations and a series of regulatory deviations that also affected laboratory-developed tests (LDTs). To examine real-world consequences and specify regulatory paradigm shifts, legislative proposals were aligned on a common timeline with Emergency Use Authorization (EUA) of LDTs and the US Food and Drug Administration (FDA)-orchestrated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) labeling update study. The initial EUA adoption by LDT developers shows that the FDA can have oversight over LDTs. We used efficiency-corrected microcosting of our EUA PCR assay to estimate the national cost of the labeling update study to $0.3 to $1.4 million US dollars. Labeling update study performance data showed lower average detection limits in commercial in vitro diagnostic (IVD) assays versus LDTs (32,000 ± 75,000 versus 71,000 ± 147,000 nucleic acid amplification tests/mL; P = 0.04); however, comparison also shows that FDA review of IVD assays and LDTs did not prevent differences between initial and labeling update performance (IVD assay, P < 0.0001; LDT, P = 0.003). The regulatory shifts re-emphasized that both commercial tests and LDTs rely heavily on laboratory competence and procedures; however, lack of performance data on authorized tests, when clinically implemented, precludes assessment of the benefit related to regulatory review. Temporary regulatory deviations during the pandemic and regulatory science tools (ie, reference material) have generated valuable real-world evidence to inform pending legislation regarding LDT regulation.
Topics: COVID-19 Nucleic Acid Testing; Humans; Laboratories; Limit of Detection; Polymerase Chain Reaction; Time Factors; United States; United States Food and Drug Administration
PubMed: 34538703
DOI: 10.1016/j.jmoldx.2021.07.011 -
BMJ Open Nov 2019There is a need to evaluate whether, and to what degree, labour inspections or other regulatory tools have the desired effects on psychosocial, organisational and...
Effectiveness of the Labour Inspection Authority's regulatory tools for work environment and employee health: study protocol for a cluster-randomised controlled trial among Norwegian home-care workers.
INTRODUCTION
There is a need to evaluate whether, and to what degree, labour inspections or other regulatory tools have the desired effects on psychosocial, organisational and mechanical work environment, and employee health. The Norwegian Labour Inspection Authority (NLIA) uses different tools and strategies to enforce compliance with occupational safety and health (OSH) legislation. The aim of the present study is to evaluate the effects of labour inspections and other regulatory tools employed by the NLIA. The home-care service is one of the fastest growing occupations and a prioritised area for the NLIA, hence the present study will investigate regulatory tools in this sector.
METHODS AND ANALYSIS
The research project has been designed as a longitudinal, cluster-randomised, controlled trial and will be conducted among Norwegian home-care workers. The objective of the research project is to evaluate the effects of the NLIA's regulatory tools (inspection and guidance) on: (1) compliance with OSH legislation and regulation; (2) psychosocial, organisational and mechanical work environment; (3) employee health in terms of musculoskeletal and mental health complaints; and (4) sickness absence. Public home-care services have been randomised to three intervention groups and one control group. Home-care services in the intervention groups will receive one of three intervention activities from the NLIA: (1) inspection from the Labour Inspection Authority; (2) guidance through an online interactive risk-assessment tool; and (3) guidance on psychosocial, organisational and mechanical work environment through workshops. The interventions will be performed at the organisational level (home-care service), and the effects of the interventions on the working environment and health complaints will be measured at the individual level (home-care employees).
ETHICS AND DISSEMINATION
This project has been approved by the Regional Committees for Medical and Health Research Ethics (REC) in Norway (REC South East) (2018/2003/REK sør-øst C), the Norwegian Center for Research Data (566128), and will be conducted in accordance with the World Medical Association Declaration of Helsinki. The results will be reported in international peer-reviewed journals.
TRIAL REGISTRATION NUMBER
NCT03855163.
Topics: Absenteeism; Government Agencies; Home Care Agencies; Home Care Services; Home Health Aides; Humans; Mental Disorders; Mental Health; Musculoskeletal Diseases; Norway; Occupational Health; Workplace; Randomized Controlled Trials as Topic
PubMed: 31772092
DOI: 10.1136/bmjopen-2019-031226