Regulatory Science Research Articles

Development and early qualitative evidence of two novel patient-reported outcome instruments to assess daily functioning in people with early-stage Parkinson’s

BackgroundPrevious research on concepts that are important to people living with early-stage Parkinson’s indicated that ‘functional’ slowness, fine motor skills, and subtle gait abnormalities are cardinal concepts that are not comprehensively captured by existing patient-reported outcome (PRO) instruments that are used in clinical practice and research to assess symptoms and daily functioning within this patient population. We sought to develop novel PRO instruments to address this unmet need.MethodsPRO instrument development was led by a multidisciplinary research group, including people living with Parkinson’s (termed ‘patient experts’), as well as patient engagement and involvement, regulatory science, clinical, and outcome measurement experts. A first set of PRO instruments, termed Early Parkinson’s Function Slowness (42 items) and Early Parkinson’s Mobility (26 items), were drafted to capture ‘functional’ slowness, fine motor skills, and subtle gait abnormalities. These PRO instruments were used in cognitive debriefing interviews with people living with early-stage Parkinson’s (who were not involved with the multidisciplinary research group) to identify issues with relevance, clarity, ease of completion, conceptual overlap, or missing concepts.ResultsSixty people living with early-stage Parkinson’s were interviewed, which led to refining the items to 45 for the Early Parkinson’s Functional Slowness and 23 for the Early Parkinson’s Mobility PRO instruments. Refinement included rewording items to address clarity issues, merging or splitting items to address overlap issues, and adding new items to address missing concepts. The Early Parkinson’s Function Slowness PRO instrument resulted in a multidimensional instrument covering upper limb, complex/whole body, general activity, and cognitive functional slowness. The Early Parkinson’s Mobility PRO instrument resulted in comprehensive coverage of everyday mobility tasks, with a focus on gait concepts, plus complex/whole body, balance, and lower limb mobility.ConclusionsThe Early Parkinson’s Function Slowness and Early Parkinson’s Mobility PRO instruments aim to address gaps in existing PRO instruments to measure meaningful symptoms and daily functioning in people living with early-stage Parkinson’s. Utilizing a meticulous study design led by a multidisciplinary research group that included patient experts helped to ensure that the PRO instruments were patient-centric, content valid, and meaningful from a clinical and measurement perspective.

Abstract CT100: A new therapeutic cancer vaccine inducing multifunctional immunity, artificial adjuvant vector cells

Abstract Background: Cancer immunotherapy is an effective way of battling cancer, and is based on artificial stimulation of the immune system to attack cancer cells. Although several strategies show successful results, it remains to prevent the subsequent cancer escape from the immune surveillance. The further success depends on a variety of functional effector cell types involved and their sustenance following activation. For this purpose, simultaneous induction of innate and adaptive immunity should be one of ideal strategies. We focus on DCs, which play a pivotal role in determining the quality and magnitude of innate and adaptive immunity. To effectively utilize the DC in situ, we have developed a system using allogeneic cells as artificial adjuvant vector cells (aAVCs), comprised of a CD1d-NKT ligand complex on the cell surface and containing tumor antigen inside of the cells. This approach induces adjuvant effects by combining NKT cell activation with delivery of tumor antigen to DCs in vivo. In addition to linking innate and adaptive immunity, aAVC therapy can lead to efficient trafficking of specific anti-tumor CD8+ T cells to the tumor site and also the formation of long-term memory T cells. This novel design of aAVC therapy is a platform and allows for a replacement of any cancer antigens as the therapeutic package. After completion of the regulatory science consultation for discussing the pharmaceutical quality and the design of a clinical study with PMDA in Japan, we developed the WT1-expressing aAVC (aAVC-WT1) for the clinical application. Methods: This first-in-human, open label, single-center trial involves a bifurcated 3+3 design with aAVC-WT1 dose escalations (1 × 106, 1 × 107, and 1 × 108 per body). The three patients in each cohort had not received any chemotherapy during more than 2 weeks before the therapy and had received aAVC-WT1 intravenously twice in a 4-week interval. Nine of the ten enrolled patients with relapsed and refractory AML underwent complete analysis per-protocol set and were evaluated in our phase I dose-escalation trial of aAVC-WT1. Results: No dose-limiting toxicities were observed, whereas activation of NKT and/or NK cells was observed in all patients. Five patients experienced objective leukemic regression, which correlated with WT1-specific T-cell responses. Paired single-cell RNA and TCR sequencing demonstrated effector CD8+ T cell clones in the bone marrow. Some bone marrow CD8+ T cells underwent transition from pre-existing precursor exhausted T cells to functional T cells or emerged as newly activated T cells, some of which were maintained long-term. These demonstrate the feasibility and safety of aAVC-WT1 therapy and the capacity of this platform to activate both innate and adaptive immunity in humans. Conclusion: aAVC-WT1 therapy showed an acceptable safety profile at doses tested and encouraging signs of clinical response. These data support further development of aAVC-WT1 for patients with AML. Clinical trial registry number: UMIN 000028083. Citation Format: Shin-ichiro Fujii, Toyotaka Kawamata, Kanako Shimizu, Jun Nakabayashi, Satoru Yamasaki, Tomonori Iyoda, Jun Jun Shinga, Michihiro Hidaka, Masanori Nojima, Fumitaka Nagamura, Arinobu Tojo. A new therapeutic cancer vaccine inducing multifunctional immunity, artificial adjuvant vector cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT100.

Learning From Experience and Finding the Right Balance in the Governance of Artificial Intelligence and Digital Health Technologies

Artificial intelligence (AI) and machine learning medical tools have the potential to be transformative in care delivery; however, this change will only be realized if accompanied by effective governance that ensures patient safety and public trust. Recent digital health initiatives have called for tighter governance of digital health. A correct balance must be found between ensuring product safety and performance while also enabling the innovation needed to deliver better approaches for patients and affordable efficient health care for society. This requires innovative, fit-for-purpose approaches to regulation. Digital health technologies, particularly AI-based tools, pose specific challenges to the development and implementation of functional regulation. The approaches of regulatory science and "better regulation" have a critical role in developing and evaluating solutions to these problems and ensuring effective implementation. We describe the divergent approaches of the European Union and the United States in the implementation of new regulatory approaches in digital health, and we consider the United Kingdom as a third example, which is in a unique position of developing a new post-Brexit regulatory framework.

Artificial intelligence and real-world data for drug and food safety – A regulatory science perspective

In 2013, the Global Coalition for Regulatory Science Research (GCRSR) was established with members from over ten countries (www.gcrsr.net). One of the main objectives of GCRSR is to facilitate communication among global regulators on the rise of new technologies with regulatory applications through the annual conference Global Summit on Regulatory Science (GSRS). The 11th annual GSRS conference (GSRS21) focused on “Regulatory Sciences for Food/Drug Safety with Real-World Data (RWD) and Artificial Intelligence (AI).” The conference discussed current advancements in both AI and RWD approaches with a specific emphasis on how they impact regulatory sciences and how regulatory agencies across the globe are pursuing the adaptation and oversight of these technologies. There were presentations from Brazil, Canada, India, Italy, Japan, Germany, Switzerland, Singapore, the United Kingdom, and the United States. These presentations highlighted how various agencies are moving forward with these technologies by either improving the agencies’ operation and/or preparing regulatory mechanisms to approve the products containing these innovations. To increase the content and discussion, the GSRS21 hosted two debate sessions on the question of “Is Regulatory Science Ready for AI?” and a workshop to showcase the analytical data tools that global regulatory agencies have been using and/or plan to apply to regulatory science. Several key topics were highlighted and discussed during the conference, such as the capabilities of AI and RWD to assist regulatory science policies for drug and food safety, the readiness of AI and data science to provide solutions for regulatory science. Discussions highlighted the need for a constant effort to evaluate emerging technologies for fit-for-purpose regulatory applications. The annual GSRS conferences offer a unique platform to facilitate discussion and collaboration across regulatory agencies, modernizing regulatory approaches, and harmonizing efforts.

Music Therapy: Scientific Perspectives and Clinical Prospects

Music and arts for healing purposes look back over a multifaceted evolution and a myriad of phenomena in various cultures. Interdisciplinary considerations suggest to distinguish five different, but partly overlapping stages. The first refers to historical roots and ethnological sources, which have also influenced modern meta-theoretical perspectives and practices. The next stage marks the heterogeneous origins of modern music therapy in the 20th century that mirror psychological positions and novel clinical ideas about the healing power of music and the arts. The following heyday of music therapeutic models and schools of thought yielded an enormous variety of concepts and methods such as Nordoff-Robbins MT, Orff MT, Analytic MT, Regulatory MT, GIM or Sound Work. As music and arts therapies gained in international importance, clinical applications required research about their therapeutic efficacy. According to standards of evidence based medicine and with regard to clearly defined diagnoses research on music therapeutic practice became the core of stage four. The present stage is characterised by an emerging epistemological dissatisfaction with the paradigmatic reductionism of evidence based medicine and the strong will to discover the ‘true healing nature’ of music. This trend has given birth to interdisciplinary hermeneutics for novel foundations of music and arts therapies. Epigenetics, neuroplasticity, regulatory and chronobiological sciences, quantum physical philosophies, universal harmonies, spiritual and religious views, and the cultural anthropological phenomenon of aesthetics and creativity have become guiding principles. The present paper relates to the author’s EASA-speech on the 2nd of December 2022 about landmarks in the evolution of modern music therapy and its interdisciplinary perspectives.

Music therapy: scientific perspectives and clinical prospects

Music and arts for healing purposes look back over a multifaceted evolution and a myriad of phenomena in various cultures. Interdisciplinary considerations suggest to distinguish five different, but partly overlapping stages. The first refers to historical roots and ethnological sources, which have also influenced modern meta-theoretical perspectives and practices. The next stage marks the heterogeneous origins of modern music therapy in the 20th century that mirror psychological positions and novel clinical ideas about the healing power of music and the arts. The following heyday of music therapeutic models and schools of thought yielded an enormous variety of concepts and methods such as Nordoff-Robbins MT, Orff MT, Analytic MT, Regulatory MT, GIM or Sound Work. As music and arts therapies gained in international importance, clinical applications required research about their therapeutic efficacy. According to standards of evidence based medicine and with regard to clearly defined diagnoses research on music therapeutic practice became the core of stage four. The present stage is characterised by an emerging epistemological dissatisfaction with the paradigmatic reductionism of evidence based medicine and the strong will to discover the ‘true healing nature’ of music. This trend has given birth to interdisciplinary hermeneutics for novel foundations of music and arts therapies. Epigenetics, neuroplasticity, regulatory and chronobiological sciences, quantum physical philosophies, universal harmonies, spiritual and religious views, and the cultural anthropological phenomenon of aesthetics and creativity have become guiding principles. The present paper relates to the author’s EASA-speech on the 2nd of December 2022 about landmarks in the evolution of modern music therapy and its interdisciplinary perspectives.

Examining Visual Attention to Tobacco Marketing Materials Among Young Adult Smokers: Protocol for a Remote Webcam-Based Eye-Tracking Experiment.

Eye tracking provides an objective way to measure attention, which can advance researchers' and policy makers' understanding of tobacco marketing influences. The development of remote webcam-based eye-tracking technology, integrated with web-based crowdsourcing studies, may be a cost-effective and time-efficient alternative to laboratory-based eye-tracking methods. However, research is needed to evaluate the utility of remote eye-tracking methods. This study aimed to detail the process of designing a remote webcam-based eye-tracking experiment and provide data on associations between participant characteristics and the outcomes of experiment completion. A total of 2023 young adult (aged 18-34 years) cigarette smokers in the United States were recruited to complete a web-based survey that included a 90-second remote eye-tracking experiment that examined attention to e-cigarette marketing materials. Primary outcome measures assessed the completion of the remote eye-tracking experiment-specifically, experiment initiated versus not initiated, experiment completed versus not completed, and usable versus nonusable eye-tracking data generated. Multivariable logistic regressions examined the associations between outcome measures and participants' sociodemographic backgrounds, tobacco use history, and electronic devices (mobile vs desktop) used during the experiment. Study recruitment began on April 14, 2022, and ended on May 3, 2022. Of the 2023 survey participants, 1887 (93.28%) initiated the experiment, and 777 (38.41%) completed the experiment. Of the 777 participants who completed the experiment, 381 (49%) generated usable data. Results from the full regression models show that non-Hispanic Black participants (adjusted odds ratio [AOR] 0.64, 95% CI 0.45-0.91) were less likely to complete the eye-tracking experiment than non-Hispanic White participants. In addition, female (vs male) participants (AOR 1.46, 95% CI 1.01-2.11), those currently using (vs not using) e-cigarettes (AOR 2.08, 95% CI 1.13-3.82), and those who used mobile (vs desktop) devices (AOR 5.10, 95% CI 3.05-8.52) were more likely to generate usable eye-tracking data. Young adult participants were willing to try remote eye-tracking technology, and nearly half of those who completed the experiment generated usable eye-tracking data (381/777, 49%). Thus, we believe that the use of remote eye-tracking tools, integrated with crowdsourcing recruitment, can be a useful approach for the tobacco regulatory science research community to collect high-quality, large-scale eye-tracking data in a timely fashion and thereby address research questions related to the ever-evolving tobacco marketing landscape. It would be useful to investigate techniques to enhance completion rates and data usability. RR1-10.2196/43512.

Summary of the ONE SOCIETY track > opportunities and challenges

This report summarises the main discussions, conclusions and recommendations of the ‘One Society’ track of the ‘ONE – Health, Environment & Society – Conference 2022’ (21st–24th June 2002; Brussels and online), which was organised by the European Food Safety Authority. The four themes in the One Society track focused on risk communication, social science, engagement, including collaboration, the EU research agenda, and open science: more specifically, their integration into our understanding of existing and emerging food safety risks within agri-food systems, and as part of the ‘One Health’ context. The conclusions suggested that understanding food safety risks within ‘One Health’ requires collaboration and co-production of risk assessment and research objectives, data, methodologies and translation into policy with all interested actors, including the general public. Furthermore, effective implementation of open science practices and inter-agency collaboration are key to ensuring that policy and governance conditions can be optimised within the context of the transdisciplinary research environment in which the ‘One Health’ concept is embedded. Among main outcomes, the ‘One Society’ track clearly highlighted the need to: i) realise the EU’s collaborative food safety knowledge ecosystem, as no single actor can master the level of complexity alone, ii) consistently apply an ‘audience-first’ approach and use participatory formats from science to policymaking; iii) dedicate resources to build bridges with research projects; and iv) make open science a reality and a ‘default’ principle for regulatory science.

FDA Oncology Center of Excellence Crowdsourcing Initiative: Outreach to the Scientific Community to Identify Research Questions for Pooled Analyses of Oncology Clinical Trial Data.

The FDA Oncology Center of Excellence recently launched a crowdsourcing pilot to request ideas from the scientific community for research questions that FDA could address with pooled analyses of clinical trial data submitted to the agency for regulatory purposes. This effort builds on FDA's track record of publishing pooled analyses to explore scientific questions that cannot be addressed in a single trial due to limited sample size. The research crowdsourcing pilot tested a new approach for obtaining external input on regulatory science activities, because FDA is generally unable to share patient-level data outside of the agency due to federal disclosure laws and regulations protecting different types of data submitted in regulatory applications. We received 29 submissions over the 28-day crowdsourcing campaign, including one research idea that we are exploring for possible follow-up. Based on our experience with this pilot, we learned that crowdsourcing is a promising new approach to gather external input and feedback. We identified opportunities to build understanding in the external oncology community about the types of data typically included in regulatory applications and expand the dissemination of published FDA pooled analyses to help inform future drug development and clinical practice.

Scientific literature review on group decision‐making models

EFSA commissioned a review of available scientific literature on group decision-making in regulatory science to inform future recommendations for EFSA's panel system. This final summary report presents the results from the literature review that has been performed based on a list of 30 articles, proposed and validated in the ‘methodological note’ in the kick-off phase of this work. The review covers the following topics: social science theories and models of group decision-making; research on group decision-making in risks assessment, specifically in food safety; research on group decision-making in regulatory science, and group decision-making models adopted by national/EU/international organisations. The findings describe the factors that contribute to effective and efficient decision-making in groups, specific factors to consider for expert panels, some potential shortcomings of group decision-making to take into account, and some final considerations to inform EFSA's evaluation of its panel system.

Regulation and regulatory science for biosynthetic science, technology and applications

Regulation and regulatory science for biosynthetic science, technology and applications

English

To some Cannabis is antisocial anathema, to others it is a harmless sedative-hypnotic, or narcotic analgesic and to others it occupies a cultural position as religious sacrament. Some fear its use leads to psychosis and addiction; to others still it is a legal anomaly and should be decriminalized. Whatever the case may be, in Africa where Cannabis is a recreational drug. It is caught in a bizarrely legal and regulatory maze. Regulations are changing internationally and the Cannabis industry is growing. African, National Medicines Regulatory Authorities, NMRs, have to catch up. But unfortunately some lack competent professionals who require to understand regulatory science, RS, in general, and in particular as it pertains to cannabis products with complex pharmacology. RS is “a range of scientific disciplines that are applied - intellectually and practically - to the quality, safety and efficacy assessment of medical products and that inform regulatory decision making, throughout the life cycle of a medical/health product”. RS helps to answer the following questions: Is there a pathway that will lead cannabis to mainstream medicine in Africa? Will cannabis as a botanical agent have to follow the same time-honoured process that any pharmaceutical must attain to receive regulatory approval? There is no doubt the cannabis and regulatory sciences are going to influence the future shaping and implementation of pharmaceutical medicine laws and regulations in Africa. The aim of the article is to highlight the key regulatory science challenges, in Africa, that belong to either a societal or a biomedical sphere regarding Cannabis for adult use or medicinal purposes or nutrition. Key words:  Cannabis, regulatory science, challenges, Africa.

High-Throughput Cardiotoxicity Screening Using Mature Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Monolayers.

Human induced stem cell-derived cardiomyocytes (hiPSC-CMs) are used to replace and reduce the dependence on animals and animal cells for preclinical cardiotoxicity testing. In two-dimensional monolayer formats, hiPSC-CMs recapitulate the structure and function of the adult human heart muscle cells when cultured on an optimal extracellular matrix (ECM). A human perinatal stem cell-derived ECM (maturation-inducing extracellular matrix-MECM) matures the hiPSC-CM structure, function, and metabolic state in 7 days after plating. Mature hiPSC-CM monolayers also respond as expected to clinically relevant medications, with a known risk of causing arrhythmias and cardiotoxicity. The maturation of hiPSC-CM monolayers was an obstacle to the widespread adoption of these valuable cells for regulatory science and safety screening, until now. This article presents validated methods for the plating, maturation, and high-throughput, functional phenotyping of hiPSC-CM electrophysiological and contractile function. These methods apply to commercially available purified cardiomyocytes, as well as stem cell-derived cardiomyocytes generated in-house using highly efficient, chamber-specific differentiation protocols. High-throughput electrophysiological function is measured using either voltage-sensitive dyes (VSDs; emission: 488 nm), calcium-sensitive fluorophores (CSFs), or genetically encoded calcium sensors (GCaMP6). A high-throughput optical mapping device is used for optical recordings of each functional parameter, and custom dedicated software is used for electrophysiological data analysis. MECM protocols are applied for medication screening using a positive inotrope (isoprenaline) and human Ether-a-go-go-related gene (hERG) channel-specific blockers. These resources will enable other investigators to successfully utilize mature hiPSC-CMs for high-throughput, preclinical cardiotoxicity screening, cardiac medication efficacy testing, and cardiovascular research.

The Vaping and Patterns of e-Cigarette Use Research Study: Protocol for a Web-Based Cohort Study.

In total, 3.2% of American adults report using e-cigarettes every day or some days. The Vaping and Patterns of E-cigarette Use Research (VAPER) Study is a web-based longitudinal survey designed to observe patterns in device and liquid use that suggest the benefits and unintended consequences of potential e-cigarette regulations. The heterogeneity of the e-cigarette devices and liquids on the market, the customizability of the devices and liquids, and the lack of standardized reporting requirements result in unique measurement challenges. Furthermore, bots and survey takers who submit falsified responses are threats to data integrity that require mitigation strategies. This paper aims to describe the protocols for 3 waves of the VAPER Study and discuss recruitment and data processing experiences and lessons learned, including the benefits and limitations of bot- and fraudulent survey taker-related strategies. American adults (aged ≥21 years) who use e-cigarettes ≥5 days per week are recruited from up to 404 Craigslist catchment areas covering all 50 states. The questionnaire measures and skip logic are designed to accommodate marketplace heterogeneity and user customization (eg, different skip logic pathways for different device types and customizations). To reduce reliance on self-report data, we also require participants to submit a photo of their device. All data are collected using REDCap (Research Electronic Data Capture; Vanderbilt University). Incentives are US $10 Amazon gift codes delivered by mail to new participants and electronically to returning participants. Those lost to follow-up are replaced. Several strategies are applied to maximize the odds that participants who receive incentives are not bots and are likely to possess an e-cigarette (eg, required identity check and photo of a device). In total, 3 waves of data were collected between 2020 and 2021 (wave 1: n=1209; wave 2: n=1218; wave 3: n=1254). Retention from waves 1 to 2 was 51.94% (628/1209), and 37.55% (454/1209) of the wave 1 sample completed all 3 waves. These data were mostly generalizable to daily e-cigarette users in the United States, and poststratification weights were generated for future analyses. Our data offer a detailed examination of users' device features and specifications, liquid characteristics, and key behaviors, which can provide more insights into the benefits and unintended consequences of potential regulations. Relative to existing e-cigarette cohort studies, this study methodology has some advantages, including efficient recruitment of a lower-prevalence population and collection of detailed data relevant to tobacco regulatory science (eg, device wattage). The web-based nature of the study requires several bot- and fraudulent survey taker-related risk-mitigation strategies, which can be time-intensive. When these risks are addressed, web-based cohort studies can be successful. We will continue to explore methods for maximizing recruitment efficiency, data quality, and participant retention in subsequent waves. DERR1-10.2196/38732.

Impact of National Institutes of Health and Food and Drug Administration Tobacco Research Funding: A Bibliometrics Analyses.

Conduct bibliometric analyses documenting the output of National Institutes of Health (NIH) tobacco-related and Food and Drug Administration (FDA) tobacco regulatory science (FDA-TRS) research portfolios. PubMed identifiers for publications between 2015 and 2020 citing tobacco funding by NIH and/or FDA were imported into NIH iCite generating measures of productivity and influence, including number of citations, journal, relative citation ratios (RCR), and comparison of research influence across Web of Science (WoS) disciplines. Coauthorship and measures of centrality among and between NIH and FDA-supported investigators gauged collaboration. Between FY 2015 and 2020, 8160 publications cited funding from NIH tobacco-related grants, 1776 cited FDA-TRS grants and 496 cited Common funding (ie, both NIH and FDA-TRS funding). The proportion of publications citing NIH grants declined while those citing FDA-TRS or Common funding rose significantly. Publications citing Common funding showed the highest influence (mean RCR = 2.52). Publications citing FDA-TRS funding displayed higher median RCRs than publications citing NIH funding in most WoS categories. Higher translational progress was estimated over time for FDA-TRS and Common publications compared to NIH publications. Authors citing Common funding scored highest across all collaboration measures. This study demonstrates the high bibliometric output of tobacco research overall. The rise in publications citing FDA-TRS and Common likely reflects increased funding for TRS research. Higher RCRs across WoS subject categories and trends towards human translation among FDA-TRS and Common publications indicate focus on research to inform regulation. This analysis suggests that FDA support for TRS has expanded the field of tobacco control resulting in sustained productivity, influence, and collaboration. This paper is the first effort to better describe the impact of tobacco research resulting from the addition of FDA funding for TRS in the past decade. The analysis provides impetus for further investigation into the publication topics and their focus which would offer insight into the specific evidence generated on tobacco control and regulation.

What you don’t know won’t hurt you – Agnotology in anti-doping

When studying the production of knowledge for policy, focus is typically on science that is being done and taken up. This paper looks at the other side of the coin: science that remains undone or unseen. We analyse sports policies through the prism of ‘agnotology’, using the case of anti-doping as a ‘regulatory science’ (Jasanoff, 2011). Theoretical framework Agnotology refers to social production of ignorance (Proctor, 2008). Science may be suppressed, or otherwise not undertaken, or remain invisible (Boudia & Henry, 2022). Ignorance can range from deliberate hindrance to structural impediments (power to put issues onto the research agenda; resource allocation). Framing matters in policy, since any problem representation manages complexity by simplifying, and leaving gaps (Bacchi, 2009). Undone science may reproduce social inequality structures (Boudia & Henry, 2022). Connections can be made with sociology frameworks, such as Bourdieu’s concepts of habitus and field theory (Bourdieu, 1976). Scientific habitus is an incarnated form of being a scientist, which shapes issue selection and treatment (Jeon, 2019). Scientists self-censor for their career; certain research areas, or methods, are frowned upon. Ignorance is intrinsic to the construction of science: some statements may never be fortified into facts, e.g. if no scientist takes them up or challenges them (Latour & Woolgar, 1976). Various typologies exist of how organisations react to ignorance (Boswell & Badenhoop, 2019: elucidation, denial, resignation), or keep uncomfortable knowledge at bay (Rayner, 2012: denial, dismissal, diversion and displacement). Research questions How is ignorance created or maintained in anti-doping science? Research emphasis and gaps: what is (not) researched? What issues/methods are favoured/considered invalid? Policy uptake: what research is made visible or kept invisible? What actors are influential in the process? Influence of structures and power: who is authorised to do science? What is the role of the the World Anti-Doping Agency (WADA) and its regulatory framework? What strategies are developed in the face of ignorance? Methods i.) Analysis of the regulatory framework and other documents (Minutes of WADA Committees 2000-2022); ii.) semi-structured interviews with scientists (researchers with a record in publishing on doping related science) & decision-makers (officials at WADA & anti-doping organisations). We perform a content and discourse analysis, combining an inductive approach based on our experience in the field and the above frameworks. Preliminary Results The document analysis shows that scientists congregate into a community in which WADA authorizes who provide valid science. The most obvious aspect is accreditation by WADA of laboratories to perform doping analyses. Science predominantly involves these laboratories, based on their specialised expertise, but also privileged access to samples. WADA issues yearly research grants, selected through its expert committees. What science is then brought to the decision-making table also depends on WADA’s expert groups and science department. Through control of access to resources (samples, funding), coupled with regulation, WADA has a strong hold on the science produced. Next we identify, through interviews, specific areas of science that were/are unexplored or invisible, and can be furthered as case studies.

3D Printing: A Promising Revolutionary Technology in Pharmaceutical Drug Development and Health Car

The three-dimensional (3D) printing technique is an emerging paradigm shift in the field of drug manufacturing. It also proved to be a promising technology with respect to the pharmaceutical, clinical medicine, and regulatory sciences. It is a modern additive manufacturing technology in which digital information is used to produce a physical model. Unlike other subtractive and formative manufacturing processes which involve removing sections of material by machining or by cutting it away, in 3D printing technology objects are prepared from 3D model data in the process of joining materials layer by layer. In drug therapy, 3D printing has abundant opportunities for rapid preparation of multifunctional customized drug delivery systems with improved drug release features, flexible and personalized dosage forms, implants matching specific patient anatomical needs as well as cell-based materials for regenerative drug therapy and prosthesis. The 3D printing methods have gained vast importance in the field of pharmaceutical and medical applications. It is an interdisciplinary approach with the aim of exploring newer drug-delivery systems. 3D printing could also become a part of the drug production line in the pharmaceutical industry which tends to move towards personalized medicine along with mass manufacture. Presently 3D printing technology is broadly investigated in the field of drug delivery after the approval of the first 3D printed tablet containing an antiepileptic drug, levetiracetam under the trade name of Spritam® by Aprecia Pharmaceuticals in 2015. The present review recapitulates the novel applications of 3D printing technology in the field of pharmaceutical drug development and health care. It also reviews the working principle of various techniques of 3D printing along with their advantages and disadvantages.

Role of innovation in pharmaceutical regulation: A proposal for principles to evaluate EU General Pharmaceutical Legislation from the innovator perspective

Because the EU General Pharmaceutical Legislation is under review, the EFPIA Innovation Board developed evaluation principles for the policy proposals and key considerations on how the regulatory framework can support innovation while ensuring only safe, efficacious and quality medicines are authorized. The evaluation principles are anchored on actions to promote: agile adoption of new methodologies with soft law tools; continued emphasis on regulatory science to inform policies; a cost/benefit assessment of the new regulation to ensure they have an overall positive impact; and mitigation of any negative externalities or unintended effects for any type of innovation or products. The evaluation principles are intended to guide the impact assessment of the pharmaceutical legislation in the EU but the principles can be applied globally.

Towards critical ethnographies of resource risks: Regulatory science on shale industry risks in the global North contexts of Brussels and California

By examining two instances of the production of scientific knowledge on the risks of shale rock exploration and extraction in the global North’s context of democratic governance and a great concern for transparency, this paper argues for a combination of ethnographic and critical geographic approaches to studying expert knowledge production on risk as different ontological realities with different political consequences. Analytically, the study distinguishes between risks related to the natural environment and human health. While the former were presented as data by the experts, the latter gained a status of local stories. Risks as data and stories co-produced different spaces of extraction risks as abstract and absolute. With this focus, I extend the call recently made in resource anthropology, i.e. by Richardson and Weszkalnys, to ethnographically study how resources become various things for various actors beyond their commodity form and address the questions about the political realities that become co-produced and the possibility to extract and govern them.

Risk communication regarding radiation exposure by experts using two concepts of regulatory science and ALARA

In the Tohoku region of Japan, risk communication programs on radiation exposure are of great importance, especially with respect to reducing the stress and anxiety among those affected by radiation exposure. Although the concepts of ‘as low as reasonably achievable’ (ALARA) and regulatory sciences (RS) were very important for the smooth operation of risk communication among a wide range of stakeholders, our previous research showed that only 23.5% and 16.5% of medical doctors in Japan had an accurate awareness of them, respectively. To make risk communication more effective, this study examined the levels of awareness of the concepts of ALARA and RS among academic experts in Japan and compared their level of awareness of technical terms regarding radiation to that of the expected level for a layperson. This study also showed that, even among faculty working at graduate schools in Japan, only 29.8% and 39.4% had an accurate knowledge of ALARA and RS. To improve the knowledge of laypeople and experts on these concepts, they should be added to the primary education curriculum. This study demonstrated that among experts in many academic fields, a significant range of estimates existed of lay knowledge of technical terms regarding radiation. The highest scores were assigned by faculty in the field of humanities. Thus, before conducting risk communications, experts from all fields should identify the expected level of awareness among laypeople on the topic. In addition, risk communications regarding radiation should be conducted by academic experts and healthcare professionals together with facilitators or lecturers.