A Causality Assessment Framework for COVID-19 Vaccines and Adverse Events at the COVID-19 Vaccine Safety Research Center.

During the coronavirus disease 2019 (COVID-19) pandemic, conclusively evaluating possible associations between COVID-19 vaccines and potential adverse events was of critical importance. The National Academy of Medicine of Korea established the COVID-19 Vaccine Safety Research Center (CoVaSC) with support from the Korea Disease Control and Prevention Agency to investigate the scientific relationship between COVID-19 vaccines and suspected adverse events. Although determining whether the COVID-19 vaccine was responsible for any suspected adverse event necessitated a systematic approach, traditional causal inference theories, such as Hill's criteria, encountered certain limitations and criticisms. To facilitate a systematic and evidence-based evaluation, the United States Institute of Medicine, at the request of the Centers for Disease Control and Prevention, offered a detailed causality assessment framework in 2012, which was updated in the recent report by the National Academies of Sciences, Engineering, and Medicine (NASEM) in 2024. This framework, based on a weight-of-evidence approach, allows the independent evaluation of both epidemiological and mechanistic evidence, culminating in a comprehensive conclusion about causality. Epidemiological evidence derived from population studies is categorized into four levels-high, moderate, limited, or insufficient-while mechanistic evidence, primarily from biological and clinical studies in animals and individuals, is classified as strong, intermediate, weak, or lacking. The committee then synthesizes these two types of evidence to draw a conclusion about the causal relationship, which can be described as "convincingly supports" ("evidence established" in the 2024 NASEM report), "favors acceptance," "favors rejection," or "inadequate to accept or reject." The CoVaSC has established an independent committee to conduct causality assessments using the weight-of-evidence framework, specifically for evaluating the causality of adverse events associated with COVID-19 vaccines. The aim of this study is to provide an overview of the weight-of-evidence framework and to detail the considerations involved in its practical application in the CoVaSC.

Tell me what you want, what you really really want: Estimands in observational pharmacoepidemiologic comparative effectiveness and safety studies.

PURPOSE: Ideally, the objectives of a pharmacoepidemiologic comparative effectiveness or safety study should dictate its design and data analysis. This paper discusses how defining an estimand is instrumental to this process. METHODS: We applied the ICH-E9 (Statistical Principles for Clinical Trials) R1 addendum on estimands - which originally focused on randomized trials - to three examples of observational pharmacoepidemiologic comparative effectiveness and safety studies. Five key elements specify the estimand: the population, contrasted treatments, endpoint, intercurrent events, and population-level summary measure. RESULTS: Different estimands were defined for case studies representing three types of pharmacological treatments: (1) single-dose treatments using a case study about the effect of influenza vaccination versus no vaccination on mortality risk in an adult population of ≥60 years of age; (2) sustained-treatments using a case study about the effect of dipeptidyl peptidase 4 inhibitor versus glucagon-like peptide-1 agonist on hypoglycemia risk in treatment of uncontrolled diabetes; and (3) as needed treatments using a case study on the effect of nitroglycerin spray as-needed versus no nitroglycerin on syncope risk in treatment of stabile angina pectoris. CONCLUSIONS: The case studies illustrated that a seemingly clear research question can still be open to multiple interpretations. Defining an estimand ensures that the study targets a treatment effect that aligns with the treatment decision the study aims to inform. Estimand definitions further help to inform choices regarding study design and data-analysis and clarify how to interpret study findings.

The impact of "To Err Is Human" on patient safety in anesthesiology. A bibliometric analysis of 20 years of research.

Background: Patient safety gained public notoriety following the 1999 report of the Institute of Medicine: To Err is Human - Building a Safer Health System which summarized a culminated decades' worth of research that had so far been largely ignored. The aim of this study was to analyze the report's impact on patient safety research in anesthesiology. Methods: A bibliometric analysis was performed on all anesthesiologic publications from 2000 to 2019 that referenced To Err Is Human. In bibliometric literature, references are understood to represent an author's conscious decision to express a relationship between his own manuscript and the cited document. Results: The anesthesiologic data base contained 1.036 publications. The journal with the most references to the IOM report is Anesthesia & Analgesia. By analyzing author keywords and patterns of collaboration, changes in the patient safety debate and its core themes in anesthesiology over time could be visualized. The generic notion of "error," while initially a central topic in the scientific discourse, was subsequently replaced by terms representing a more granular, team-oriented, and educational approach. Patient safety research in anesthesia, while profiting from a certain intellectual and conceptual head start, showed a discursive shift toward more managerial, quality-management related topics as observed in the health care system as a whole. Conclusions: Over the last 20 years, the research context expanded from the initial focus set forth by the IOM report, which ultimately led to an underrepresentation of research on critical incident reporting and systemic approaches to safety. Important collaborations with safety researchers from outside of health care dating back to the 1990's were gradually reduced, while previous research within anesthesiology was aligned with a broader, more managerial patient safety agenda.

[Drones in medical care : A new member of the rescue chain?] / Drohnen in der medizinischen Versorgung : Ein neues Glied in der Rettungskette?

Do drones have the potential to become established as a new member of the rescue chain? This article attempts to provide answers to this important question. In addition to a brief historical review, the many possible applications are described. The contents of selected research projects are also presented. This shows how far developments have come today and which applications are conceivable in the near future. The associated challenges, such as compliance with legal requirements or training, are also addressed.

Micromagnetic Microstructure- and Stress-Independent Materials Characterization in Reactor Safety Research.

Reactor safety research aims at the safe operation of nuclear power plants during their service life. In this respect, Fraunhofer IZFP's micromagnetic multiparameter, microstructure, and stress analysis (3MA) has already made a significant contribution to the understanding of different aging mechanisms of component materials and their characterization. The basis of 3MA is the fact that microstructure and mechanical stress determine both the mechanical and magnetic material behavior. The correlation between features of magnetic and mechanical material behavior enables the micromagnetic prediction of mechanical properties and stress, both of which can decisively influence the service life. The Federal Ministry for Economic Affairs and Energy (BMWi) funded this research, handling the mutually superimposed microstructural and stress-dependent influences, a substantial challenge, especially under practical conditions. This superposition leads to ambiguities in the micromagnetic features. The 3MA testing system has been extended by more sophisticated evaluation methods being able to cope with more complex datasets. Investigations dealing with the expansion of the feature extraction and machine learning methods have led to a more precise distinction between microstructural and stress-dependent influences. This approach provides the basis for future applications in reactor safety.

Produção científica em saúde coletiva pós-implantação do Programa Nacional de Segurança do Paciente / Scientific production in public health after the implementation of the National Patient Safety Program / Producción científica en salud colectiva post implantación del Programa Nacional de Seguridad del Paciente

Objetivo: Caracterizar as dissertações e teses produzidas nos programas de pós-graduação da área da saúde coletiva relacionadas à segurança do paciente pós-implantação do Programa Nacional de Segurança do Paciente no Brasil. Métodos: Trata-se de pesquisa documental, de abordagem quantitativa, desenvolvida a partir da coleta de dados de dissertações e teses disponíveis no Catálogo de Teses e Dissertações da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, acessado por meio eletrônico. Os dados foram obtidos em março de 2019 e analisados por estatística descritiva simples. Resultados: A maioria das pesquisas foi desenvolvida nos cursos stricto sensu de mestrado profissional (73,02%) e acadêmico (23,81%). Em relação às instituições de ensino superior, o maior percentual se caracterizou como pública (85,72%) e da região Nordeste (50,17%). Dos estudos, 63,49% não estavam relacionados com nenhum dos protocolos básicos de segurança do paciente. Conclusão: Identificou-se maior investigação em nível de mestrado, bem como o desenvolvimento de pesquisas predominantemente em hospitais, e que abordam, com maior intensidade, a segurança no uso de medicamentos, a cultura de segurança nos serviços de saúde e os incidentes e eventos adversos nos serviços de saúde. Descritores: Segurança do Paciente; Pesquisa; Saúde Coletiva

Objective: To characterize the dissertations and theses produced in graduate programs in the public health field related to patient safety after the implementation of the National Patient Safety Program in Brazil. Methods: This is a quantitative documentary study of data collected from dissertations and theses available in the Catalog of Theses and Dissertations of the Coordination for the Improvement of Higher Education Personnel retrieved electronically. Data were collected in March 2019 and analyzed using simple descriptive statistics. Results: Most of the studies were carried out in the professional (73.02%) and academic (23.81%) stricto sensu programs. With regard to the higher education institutions, most of them were public (85.72%) and in the Northeast region (50.17%). In all, 63.49% of the studies were not related to any of the basic patient safety protocols. Conclusion: Most studies were developed in master's programs and predominantly conducted in hospitals. They addressed mainly safety in the use of medicines, safety culture in health services and incidents and adverse events in health services. Descriptors: Patient Safety; Research; Public Health

Objetivo: Caracterizar los trabajos de maestría y las tesis doctorales de los programas de posgrado del área de la salud colectiva relacionadas con la seguridad del paciente post implantación del Programa Nacional de Seguridad del Paciente en Brasil. Métodos: Se trata de una investigación documental de abordaje cuantitativo desarrollada a partir de la recogida de datos de trabajos de maestría y tesis doctorales disponibles en el Catalogo de Trabajos de Maestría y Tesis Doctorales de la Coordinación de Perfeccionamiento de Personal de Nivel Superior con acceso a través del correo electrónico. Se ha obtenido los datos en marzo de 2019 y se les ha analizado por la estadística descriptiva simple. Resultados: La mayoría de las investigaciones ha sido desarrollada en los cursos stricto sensu de maestría profesional (73,02%) y académico (23,81%). Respecto las instituciones de educación superior, el mayor porcentual se ha caracterizado como pública (85,72%) y de la región Noreste (50,17%). Entre los estudios, el 63,49% no se ha relacionado con ningún de los protocolos básicos para la seguridad del paciente. Conclusión: Se ha identificado más investigaciones de maestría así como el desarrollo de investigaciones predominantemente en los hospitales y que abordan con más intensidad la seguridad para el uso de medicamentos, la cultura de seguridad para los servicios de salud y los incidentes y eventos adversos de los servicios de salud. Descriptores: Seguridad del Paciente; Investigación; Salud Pública

Current States and Future Trends in Safety Research of Construction Personnel: A Quantitative Analysis Based on Social Network Approach.

The construction industry is recognized as a high-risk industry given that safety accidents and personnel injuries frequently occur. This study provided a systematic and quantitative review of existing research achievements by conducting social network approach to identify current states and future trends for the occupational safety of construction personnel. A total of 250 peer-reviewed articles were collected to examine the research on safety issues of workers in construction industry. Social network approach was applied to analyze the interrelationship among authors, keywords, and citations of these articles using VOS viewer and CitNetExplorer. A knowledge structure map was drawn using main path analysis (MPA) towards the collected papers, which was implemented by Pajek. In line with the findings of social network analysis, five research groups, and six keyword themes were identified in accordance with the times of cooperation of researchers and correlation among keywords of the papers. Core papers were identified by using main path analysis for each research domain to represent the key process and backbone for the corresponding area. Based on the finding of the research, significant implications and insights in terms of current research status and further research trends were provided for the scholars, thus helping generate a targeted development plan for occupational safety in construction industry.

Poly traditional Chinese medicine formulation prepared with skin moisturizing properties.

Many traditional Chinese medicine compositions can moisturize the skin and utilize in cosmetics. Using a combination of Chinese Medicine Materials and guided by Traditional Chinese Medicine principles, this study selected Echinacea purpurea to protect the skin barrier, Dendrobium nobile to clear heat and promote fluid production, Sophora flavescens to clear heat for diminished inflammation, and Aloe vera combined Lycium barbarum to nourish yin, to together form a "poly TCM moisturizing formulation." These poly plant extracts were investigated and optimized for the stability, safety, and moisturizing ability. The combination moisturizing effect was determined by measuring the expression of FLG mRNA, CLDN-1 mRNA, and AQP3 protein. Toxicological analysis included a red blood cell hemolysis test and a 3T3 phototoxicity test. It has been observed that by using polysaccharide yield as the evaluation criterion showed optimal extraction at a material-to-liquid ratio of 1:100, an extraction temperature of 100°C, and an extraction time of 3 hours. Moisturizing effect experiments showed that the expression of FLG mRNA, CLDN-1 mRNA, and AQP3 protein was significantly increased. Toxicological tests showed that the composition was safe and caused no irritating effects. Based on these results, this poly traditional Chinese medicine moisturizing formulation is safe within moisturizing effects and can be used as a moisturizing raw material in cosmetics.

Molecular Profiling of Human Induced Pluripotent Stem Cell-Derived Cells and their Application for Drug Safety Study.

Drug-induced toxicity remains one of the leading causes of discontinuation of the drug candidate and post-marketing withdrawal. Thus, early identification of the drug candidates with the potential for toxicity is crucial in the drug development process. With the recent discovery of human- Induced Pluripotent Stem Cells (iPSC) and the establishment of the differentiation protocol of human iPSC into the cell types of interest, the differentiated cells from human iPSC have garnered much attention because of their potential applicability in toxicity evaluation as well as drug screening, disease modeling and cell therapy. In this review, we expanded on current information regarding the feasibility of human iPSC-derived cells for the evaluation of drug-induced toxicity with a focus on human iPSCderived hepatocyte (iPSC-Hep), cardiomyocyte (iPSC-CMs) and neurons (iPSC-Neurons). Further, we CSAHi, Consortium for Safety Assessment using Human iPS Cells, reported our gene expression profiling data with DNA microarray using commercially available human iPSC-derived cells (iPSC-Hep, iPSC-CMs, iPSC-Neurons), their relevant human tissues and primary cultured human cells to discuss the future direction of the three types of human iPSC-derived cells.

Research implications of the FDA ECG warehouse and related resources.

The electrocardiogram is often used as an efficacy endpoint for comparing new drugs or as an indicator for cardiovascular safety in both studies of arrhythmic and non-arrhythmic novel drugs. The FDA ECG Warehouse data are owned by the submitting entities, generally pharmaceutical company manufacturers. However, a subset of these ECG data was released with permission from the data owners to the CSRC for access by investigators, equipment manufacturers and algorithm developers for CSRC-approved research and development studies. This article provides an overview of the Cardiac Safety Research Consortium (CSRC) ECG Warehouse, including data availability, completed and ongoing projects, as well as future growth potential amidst an ever expanding FDA ECG Warehouse. Given that current ICH E14 guidelines request that sponsors submitting new drug applications assess the effects on the QT interval using a thorough QT (TQT) or dose-ranging study with concentration-QT analysis during early clinical development to assess cardiac risk, developing novel methods to determine cardiovascular safety, as well as understanding current ECG collection and analysis methods are prudent. The ability to utilize previously collected ECG data for secondary analyses improves cardiovascular safety by multiplying the scientific contribution of the original research.

Patterns of Incident Reporting Across Clinical Sites in a Regionally Expanding Academic Radiation Oncology Department.

PURPOSE: We evaluated patterns of event reporting across five clinical locations within an academic radiation oncology department, with the goal of better understanding variability across sites. METHODS AND MATERIALS: We analyzed 1,351 events reported to a departmental incident learning system over 1 calendar year across the five locations with respect to volume of events, event type, process map location of origin and detection, and event reporter. RESULTS: We found marked variability in reporting patterns, including reporting rate, event type, event severity, event location of origin and detection within the departmental process map, and discipline of event reporters. These differences relate both to variability in process and workflow (reflected by frequency of specific workflow events at each site) and in reporting culture (reflected by volume or rate of event reporting, and discipline of event reporter). CONCLUSIONS: These data highlight the variability in reporting culture even within a single department, and therefore the need to tailor and individualize safety and quality programs to the unique clinical site, with the long-term goal of achieving a common culture of safety while supporting unique processes at individual locations. This work also raises concern about extrapolating single-institution incident learning system results without understanding the unique workflow and culture of clinical sites.

Cardiovascular (CV) Risk after Initiation of Abatacept versus TNF Inhibitors in Rheumatoid Arthritis Patients with and without Baseline CV Disease.

OBJECTIVE: To evaluate the cardiovascular safety of abatacept (ABA) versus tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA) patients with and without underlying cardiovascular disease (CVD). METHODS: We identified RA patients with and without baseline CVD who initiated ABA or TNFi by using data from 2 large US insurance claims databases: Medicare (2008-2013) and Truven MarketScan (2006-2015). After stratifying by baseline CVD, ABA initiators were 1:1 propensity score (PS) matched to TNFi initiators to control for > 60 baseline covariates. Cox proportional hazards regression estimated the HR and 95% CI for a composite endpoint of CVD including myocardial infarction, stroke/transient ischemic stroke, or coronary revascularization in the PS-matched cohorts. HR from 2 databases were combined through an inverse variance-weighted fixed-effects model. RESULTS: We included 6102 PS-matched pairs of ABA and TNFi initiators from Medicare and 6934 pairs from MarketScan. Of these, 35.3% in Medicare and 14.0% in MarketScan had baseline CVD. HR (95% CI) for composite CVD in the overall ABA group versus TNFi was 0.67 (0.55-0.81) in Medicare and 1.08 (0.83-1.41) in MarketScan with the combined HR of 0.79 (0.67-0.92). Among patients with baseline CVD, the HR (95% CI) was 0.71 (0.55-0.92) in Medicare and 1.02 (0.68-1.51) in MarketScan, with the combined HR of 0.79 (0.64-0.98). CONCLUSION: In this large cohort of publicly or privately insured patients with RA in the United States, ABA was associated with a 20% reduced risk of CVD versus TNFi. While this observational study is subject to potential residual confounding, our results were consistent in patients with baseline CVD.

Cardiovascular Risks of Probenecid Versus Allopurinol in Older Patients With Gout.

BACKGROUND: Patients with gout are at an increased risk of cardiovascular (CV) disease including myocardial infarction (MI), stroke, and heart failure (HF). OBJECTIVES: The authors conducted a cohort study to examine comparative CV safety of the 2 gout treatments-probenecid and allopurinol-in patients with gout. METHODS: Among gout patients ≥65 years of age and enrolled in Medicare (2008 to 2013), those who initiated probenecid or allopurinol were identified. The primary outcome was a composite CV endpoint of hospitalization for MI or stroke. MI, stroke, coronary revascularization, HF, and mortality were assessed separately as secondary outcomes. The authors estimated the incidence rate and hazard ratio of the primary and secondary outcomes in the 1:3 propensity score-matched cohort of probenecid and allopurinol initiators. RESULTS: A total of 9,722 probenecid initiators propensity score-matched to 29,166 allopurinol initiators with mean age of 76 ± 7 years, and 54% males were included. The incidence rate of the primary composite endpoint of MI or stroke per 100 person-years was 2.36 in probenecid and 2.83 in allopurinol initiators with a hazard ratio of 0.80 (95% confidence interval: 0.69 to 0.93). In the secondary analyses, probenecid was associated with a decreased risk of MI, stroke, HF exacerbation, and mortality versus allopurinol. These results were consistent in the subgroup analyses of patients without baseline CV disease or those without baseline chronic kidney disease. CONCLUSIONS: In this large cohort of 38,888 elderly gout patients, treatment with probenecid appears to be associated with a modestly decreased risk of CV events including MI, stroke, and HF exacerbation compared with allopurinol.

Radiology Research in Quality and Safety: Current Trends and Future Needs.

Promoting quality and safety research is now essential for radiology as reimbursement is increasingly tied to measures of quality, patient safety, efficiency, and appropriateness of imaging. This article provides an overview of key features necessary to promote successful quality improvement efforts in radiology. Emphasis is given to current trends and future opportunities for directing research. Establishing and maintaining a culture of safety is paramount to organizations wishing to improve patient care. The correct culture must be in place to support quality initiatives and create accountability for patient care. Focused educational curricula are necessary to teach quality and safety-related skills and behaviors to trainees, staff members, and physicians. The increasingly complex healthcare landscape requires that organizations build effective data infrastructures to support quality and safety research. Incident reporting systems designed specifically for medical imaging will benefit quality improvement initiatives by identifying and learning from system errors, enhancing knowledge about safety, and creating safer systems through the implementation of standardized practices and standards. Finally, validated performance measures must be developed to accurately reflect the value of the care we provide for our patients and referring providers. Common metrics used in radiology are reviewed with focus on current and future opportunities for investigation.

The minority report: Hazard reporting in an Australian University.

BACKGROUND: Understanding what influences reporting is critical to underpinning the knowledge base around reporting behaviour and assisting in developing effective strategies to increase reporting levels within an organisation. Universities should investigate reporting behaviour in their own organisation and investigate why differences exist between different job profiles. OBJECTIVE: The aim of this study was to investigate hazard reporting in an Australian University and to assess what factors (employment type, level of safety responsibility and prior injury) influence reporting behaviour. METHODS: A total of 256 university employees and postgraduate students completed a survey on their hazard reporting. RESULTS: The study indicated that demographic variables such as department type, role in the organisation, level of safety activity in role, and prior injury effected the reporting of hazards. Issues for non-reporting were also found to support findings in other studies. A unique finding was that while teaching-focused academics were not more likely to have been injured at work they were more likely to have reported a hazard, while researchers were less likely to report despite not being more or less likely to have received an injury. CONCLUSIONS: Although this study indicates there are differences in an organisations hazard reporting based on demographics and prior injury occurrence further research is required to evaluate the impact across other organisations and sectors.

To establish a body of evidence on safety for postmarketing Chinese medicine: A new research paradigm.

The issue of safety evaluation on postmarketing Chinese medicines has become a hot topic in mainland China recently. Researchers and decision-makers can obtain a variety of evidence resources about safety in order to evaluate the safety profile for postmarketing Chinese medicines. A registry study on ten Chinese medicine injections for postmarketing surveillance has come to the end. From such a study observing more than 300,000 patients for more than 4 years, a theoretical research question emerges, that is, how to identify and evaluate safety evidence systematically. We put forward a brand new research paradigm on the theory level, which is to establish a body of evidence on safety evaluation for postmarketing Chinese medicine. Therefore, multiple information sources were explored and extracted from preclinical experiments for toxicity, postmarketing clinical trials for effificacy and safety evaluation, registry study for surveillance, retrospective data analysis from hospital information system and spontaneous response system, and case reports and systematic review from literature. Greater efforts for this idea and cooperation with experts in this fifield both in China and abroad are urgently needed.

To establish a body of evidence on safety for postmarketing Chinese medicine: A new research paradigm / 中国结合医学杂志

The issue of safety evaluation on postmarketing Chinese medicines has become a hot topic in mainland China recently. Researchers and decision-makers can obtain a variety of evidence resources about safety in order to evaluate the safety profile for postmarketing Chinese medicines. A registry study on ten Chinese medicine injections for postmarketing surveillance has come to the end. From such a study observing more than 300,000 patients for more than 4 years, a theoretical research question emerges, that is, how to identify and evaluate safety evidence systematically. We put forward a brand new research paradigm on the theory level, which is to establish a body of evidence on safety evaluation for postmarketing Chinese medicine. Therefore, multiple information sources were explored and extracted from preclinical experiments for toxicity, postmarketing clinical trials for effificacy and safety evaluation, registry study for surveillance, retrospective data analysis from hospital information system and spontaneous response system, and case reports and systematic review from literature. Greater efforts for this idea and cooperation with experts in this fifield both in China and abroad are urgently needed.

[Jean-Jacques Lefrère: A miscarried ambition for blood safety in francophone Africa]. / Jean-Jacques Lefrère: une ambition fauchée pour la sécurité transfusionnelle en Afrique francophone.

The announcement of the death of Professor Jean-Jacques Lefrère caused considerable emotion and surprise within the francophone Africa blood transfusion research network. The group was created in 2007 in Paris. Each member that works within this group wanted to pay their last respects through dedicated publication for a brilliant researcher and writer. The tribute describes the creation of the group, its goals, its operations, its achievements and the prospects of its activities while emphasizing the essential role that Professor Lefrère played within the group.

Attendance at NHS mandatory training sessions.

AIM: To identify factors that affect NHS healthcare professionals' attendance at mandatory training sessions. METHOD: A quantitative approach was used, with a questionnaire sent to 400 randomly selected participants. A total of 122 responses were received, providing a mix of qualitative and quantitative data. Quantitative data were analysed using statistical methods. Open-ended responses were reviewed using thematic analysis. FINDINGS: Clinical staff value mandatory training sessions highly. They are aware of the requirement to keep practice up-to-date and ensure patient safety remains a priority. However, changes to the delivery format of mandatory training sessions are required to enable staff to participate more easily, as staff are often unable to attend. CONCLUSION: The delivery of mandatory training should move from classroom-based sessions into the clinical area to maximise participation. Delivery should be assisted by local 'experts' who are able to customise course content to meet local requirements and the requirements of different staff groups. Improved arrangements to provide staff cover, for those attending training, would enable more staff to attend training sessions.

Nanosafety research--are we on the right track?

The number of studies that have been published on the topic of nanosafety speaks for itself. We have seen an almost exponential rise over the past 15 years or so in the number of articles on nanotoxicology. Although only a couple of hundred papers had appeared on the topic of "Nanomaterials: environmental and health effects" before 2000, this number has exploded to over 10 000 since 2001. Most of these studies, however, do not offer any kind of clear statement on the safety of nanomaterials. On the contrary, most of them are either self-contradictory or arrive at completely erroneous conclusions. Three years ago in this Journal we underscored the deficiencies in the way these studies were designed and pointed out the sources of error in the methods used. Now, on the basis of a comprehensive review of the literature and with the help of selected toxicological end points, we attempt to indicate where the significant weaknesses of these studies lie and what we must improve in the future.