Public's perspective on COVID-19 adenovirus vector vaccines after thrombosis with thrombocytopenia syndrome (TTS) reports and associated regulatory actions - A cross-sectional study in six EU member states.

OBJECTIVE: In 2021, thrombosis with thrombocytopenia syndrome (TTS) was confirmed by the European Medicines Agency (EMA) as a rare side effect of the COVID-19 adenovirus vector vaccines Vaxzevria® and Jcovden®. This study aimed to describe the public's knowledge of TTS and how it affected the willingness to be vaccinated with COVID-19 vaccines and other vaccines in six European countries. METHODS: From June to October of 2022, a multi-country cross-sectional online survey was conducted in Denmark, Greece, Latvia, Netherlands, Portugal, and Slovenia. The minimum target of participants to be recruited was based on the size of the country's population. The results were analysed descriptively. RESULTS: In total, 3794 respondents were included in the analysis; across the six countries, 33.3 %-68.3 % reported being familiar with signs and symptoms of TTS, although 3.1-61.4 % of those were able to identify the symptoms correctly. The reported changes in willingness to be vaccinated against COVID-19 and with other vaccines varied per country. The largest reported change in the willingness to be vaccinated with Vaxzevria® and Jcovden® was observed in Denmark (61.2 %), while the willingness to be vaccinated with other COVID-19 vaccines changed most in Slovenia (30.4 %). The smallest decrease in willingness towards future vaccination against COVID-19 was reported in the Netherlands (20.9 %) contrasting with the largest decrease observed in Latvia (69.1 %). CONCLUSION: Knowledge about TTS seemed to have influenced the public's opinion in Europe resulting in less willingness to be vaccinated with Vaxzevria® and Jcovden®. Willingness for vaccination against COVID-19 with other vaccines and widespread use of vaccines to prevent other diseases also differed and seemed to be determined by the approaches taken by national health authorities when reacting to and communicating about COVID-19 vaccination risks. Further investigation of optimal risk communication strategies is warranted.

Regulatory aspects of a nanomaterial for imaging therapeutic cells.

The ability to track therapeutic cells upon administration to the patient is of interest to both regulators and developers of cell therapy. The European Commission Horizon2020 project nTRACK from 2017-2022 aimed to develop a multi-modal nano-imaging agent to track therapeutic cells during development of a cell therapy. As part of this project, we investigated the regulatory pathway involved for such a product if marketed as a stand-alone product. An important regulatory hurdle appeared to be the appropriate regulatory classification of the nTRACK nano-imaging agent, as neither the definition for medicinal product nor the definition for medical device appeared to be a good fit for the purpose of the product and we were confronted with diverging views of competent authorities on the classification. As a consequence, the information requirements to fulfill before conducting a First in Human trial are not evident and can only be decided upon by closely collaborating and communicating with the relevant authorities throughout the development of the product. Moreover, standard test methods for demonstrating the quality and safety of a medicinal product or medical device are not always suitable for nanomaterials such as the nTRACK nano-imaging agent. Regulatory agility is therefore a great need to prevent delay of promising medical innovations, although regulatory guidance on these products will likely improve with more experience. In this article, we outline the lessons learnt related to the regulatory process of the nTRACK nano-imaging agent for tracking therapeutic cells and offer recommendations to both regulators and developers of similar products.

Magistral Compounding with 3D Printing: A Promising Way to Achieve Personalized Medicine.

BACKGROUND: Magistral compounding has always been an integral part of pharmacy practice. The increasing demand worldwide for personalized drug treatments might be accommodated by an increase in magistral compounding. The new, flexible technology of 3D medicine printing could advance this process even further. However, the issue of how 3D medicine printing can be implemented within the existing magistral compounding infrastructure has not been explored. AIMS: To investigate how 3D printing can be integrated into the existing compounding system by taking regulatory, economic, and profession-oriented aspects into account. METHODS: Semi-structured interviews were conducted with relevant Dutch stakeholders representing various health institutions, such as health ministries and boards, professional bodies, and different types of pharmacies. Participants were identified through purposeful sampling. Content analysis was applied to identify the main themes. RESULTS: A total of 15 Dutch stakeholders were interviewed. It was found that the prevalence of compounding in community pharmacies in the Netherlands has decreased as a result of the practice shifting to specialized compounding pharmacies due to higher costs, lack of space, and the need to fulfill quality requirements. All interviewees considered 3D printing to be a promising compounding technique for community pharmacies, as it offers an automated approach with high digital flexibility and enables adapted formulations, including 'polypills.' Regulatory and quality assurance challenges were considered comparable to those of normal magistral products; however, there remain pending regulatory issues regarding quality control, particularly for Active Pharmaceutical Ingredients containing intermediate feedstock materials (e.g., prefilled cartridges) in 3D printing. 3D printing was believed to become cost effective over time. CONCLUSION: In the Netherlands, specialized compounding pharmacies have largely taken over compounding activities. 3D printing could be introduced within this system; however, challenges regarding how to regulate prefilled cartridges have yet to be addressed. Compounding using 3D printing in regular community pharmacies could enhance patients' individualized treatment; however, this activity would require incentives to stimulate the return of compounding to normal pharmacy practice.

Awareness, use and perceptions of cigarillos, heated tobacco products and nicotine pouches: A survey among Dutch adolescents and adults.

OBJECTIVES: Many tobacco and related products (TRPs) are less strictly regulated and marketed as less harmful than cigarettes. Little is known about their awareness, use, user profile, use behavior, reasons for use and risk perception, especially for the newest products. In an exploratory survey study among Dutch adolescents and adults, we have investigated three examples of non-cigarette TRPs available on the worldwide market. METHODS: In a two-step web-based design, data on cigarillos, heated tobacco products (HTPs) and nicotine pouches were collected. In the first step (N = 5805), a representative sample (≥13 years) was studied to quantify their awareness, ever and current use in the Dutch population. In the second step (N = 526), in-depth data regarding use behavior, reasons for use and risk perception were collected among users and non-users. RESULTS: Awareness (<50%) and use (<15% ever use and <2% current use) is relatively low for all three products, but overall higher among men, (e-)cigarette users and respondents with higher education and social economic status. Most participants became aware of the products through people they knew. Reasons for use were mainly curiosity, pleasant taste, flavour variety, and lower harmfulness. All products were perceived as (slightly) less harmful and addictive than cigarettes. CONCLUSIONS: This study is one of the first to investigate awareness and use of cigarillos, HTPs and nicotine pouches. To prevent increased use, we recommend regulators to extend flavour and smoking bans to these products. In addition, public information may discourage use by increasing awareness of health risks.

Scenarios for 3D printing of personalized medicines - A case study.

Background: 3D printing is a promising new technology for medicines' production. It employs additive manufacturing techniques, and is ideal for producing personalized medicines (e.g., patient-tailored dose, dosage form, drug release kinetics). Objective: To investigate how 3D printing technologies can be implemented in a European pharmaceutical system, by suggesting different scenarios and assessing aspects that could affect its implementation. Method: Qualitative, semi-structured interviews were conducted with key stakeholders (e.g., from ministry, authorities, research organizations, pharmacies) in the Netherlands to elicit perspectives on 3D printing of personalized medicines. The Netherlands were chosen since it has a strong tradition in compounding. Five general scenarios were investigated: placing the 3D printers in industry, community pharmacies, hospital pharmacies, compounding facilities, and in patients' homes. Content analysis was used, building on verbatim transcripts. Results: Fifteen stakeholders were interviewed. Regulatory, economic, ethical and organizational challenges were identified to varying degrees in the different scenarios. The industry and home scenarios were associated with the most challenges, hospital pharmacies and compounding facilities with the least. Other important aspects identified were the role of community pharmacies, and who should design the tablets to be printed. Conclusion: All potential scenarios for 3D printing of personalized medicines include challenges. These should be taken into account when pursuing the use of 3D printing of medicine.

A logic model for pharmaceutical care.

Objectives To develop a logic model for pharmaceutical care that can be used by stakeholders as a tool to support innovation and to monitor the performance of the pharmaceutical care system in the Netherlands and abroad. The ultimate aim of such a system is the responsible provision of drug therapy to improve patients' quality of life. Methods The logic model for pharmaceutical care was created following a process consisting of four steps: (1) a literature review to identify what pharmaceutical care is and what elements it consists of; (2) separate interviews with 10 stakeholder organizations to discuss the results of the literature review; (3) construction of the logic model based on the findings from steps 1 and 2; and (4) separate interviews with three stakeholder organizations to discuss and fine-tune the model. This project was carried out by the National Institute for Public Health and the Environment ( Rijksinstituut voor Volksgezondheid en Milieu) in the Netherlands. Results According to the proposed logic model, pharmaceutical care is care defined as: (1) patient-centred; (2) effective and safe; (3) efficient and affordable; (4) in physical, financial and timely ways; and (5) with minimal environmental impact. Conclusion The proposed logic model provides stakeholders with a common framework for the innovation or further development of pharmaceutical care.

Research for Policy (R4P): development of a reflection tool for researchers to improve knowledge utilization.

BACKGROUND: To improve knowledge utilization in policymaking, alignment between researchers and policymakers during knowledge production is essential, but difficult to maintain. In three previously reported case studies, we extensively evaluated complex research projects commissioned by policymakers to investigate how alignment is achieved in a research process and to discover ways to enhance knowledge contributions to health policy. In the present study, we investigated how the findings of these three research projects could be integrated into a practical tool for researchers to enhance their contribution to evidence-based policy. METHODS: A cross-case analysis was conducted to integrate the findings of the evaluation of the three research projects and to identify important alignment areas in these projects. By means of an iterative process, we prepared a tool that includes reflection questions for researchers. The "Research for Policy" tool was tested with input from the project managers of three new research projects. Based on the findings, the final version of the Research for Policy tool was prepared. RESULTS: By cross-case analysis of the three case studies, the following important alignment areas were identified: the goal, quality, relevance, timing, and presentation of research, the tasks and authorities of actors, the consultative structure and vertical alignment within organizations, and the organizational environment. The project managers regarded the Research for Policy tool as a useful checklist for addressing the important alignment areas in a research project. Based on their feedback, the illustrative examples from the case studies were added to the reflection questions. The project managers suggested making the tool accessible not only to researchers but also to policymakers. The format of the Research for Policy tool was further adjusted to users' needs by adding clickable links. CONCLUSIONS: Alignment between research and policymaking requires continuous efforts and a clear understanding of process issues in the research project. The Research for Policy tool offers practical alignment guidance and facilitates reflection on process issues, which supports researchers in aligning with policymakers and in acting in a context-sensitive way.

Contributions of knowledge products to health policy: a case study on the Public Health Status and Forecasts Report 2010.

BACKGROUND: The Dutch Public Health Status and Forecasts report (PHSF Report) integrates research data and identifies future trends affecting public health in the Netherlands. To investigate how PHSF contributions to health policy can be enhanced, we analysed the development process whereby the PHSF Report for 2010 was produced (PHSF-2010). METHOD: To collect data, a case study approach was used along the lines of Contribution Mapping including analysis of documents from the PHSF-2010 process and interviews with actors involved. All interviews were recorded and transcribed ad verbatim and coded using an inductive code list. RESULTS: The PHSF-2010 process included activities aimed at alignment between researchers and policy-makers, such as informal meetings. However, we identified three issues that are easily overlooked in knowledge development, but provide suggestions for enhancing contributions: awareness of divergent; continuously changing actor scenarios; vertical alignment within organizations involved and careful timing of draft products to create early adopters. CONCLUSION: To enhance the contributions made by an established public health report, such as the PHSF Report, it is insufficient to raise the awareness of potential users. The knowledge product must be geared to policy-makers' needs and must be introduced into the scenarios of actors who may be less familiar. The demand for knowledge product adaptations has to be considered. This requires continuous alignment efforts in all directions: horizontal and vertical, external and internal. The findings of this study may be useful to researchers who aim to enhance the contributions of their knowledge products to health policy.

Characterization of Apps and Other e-Tools for Medication Use: Insights Into Possible Benefits and Risks.

BACKGROUND: In the past years, an enormous increase in the number of available health-related applications (apps) has occurred, from approximately 5800 in 2011 to over 23,000 in 2013, in the iTunes store. However, little is still known regarding the use, possible effectiveness, and risks of these applications. In this study, we focused on apps and other e-tools related to medicine use. A large subset of the general population uses medicines and might benefit from tools that aid in the use of medicine. OBJECTIVE: The aim of the present study was to gain more insight into the characteristics, possible risks, and possible benefits of health apps and e-tools related to medication use. METHODS: We first made an inventory of apps and other e-tools for medication use (n=116). Tools were coded by two independent researchers, based on the information available in the app stores and websites. Subsequently, for one type of often downloaded apps (aimed at people with diabetes), we investigated users' experiences using an online questionnaire. RESULTS: Results of the inventory show that many apps for medication use are available and that they mainly offer simple functionalities. In line with this, the most experienced benefit by users of apps for regulating blood glucose levels in the online questionnaire was "information quick and conveniently available". Other often experienced benefits were improving health and self-reliance. Results of the inventory show that a minority of the apps for medication use has potentially high risks and for many of the apps it is unclear whether and how personal data are stored. In contrast, online questionnaire among users of apps for blood glucose regulation indicates that they hardly ever experience problems or doubts considering reliability and/or privacy. Although, respondents do mention to experience disadvantages of use due to incomplete apps and apps with poor ease of use. Respondents not using app(s) indicate that they might use them in the future if reliability of the apps and instructions on how to use them are more clear. CONCLUSIONS: This study shows that for apps and e-tools related to medicine use a small subset of tools might involve relatively high risks. For the large group of nonmedical devices apps, risks are lower, but risks lie in the enormous availability and low levels of regulation. In addition, both users and nonusers indicated that overall quality of apps (ease of use, completeness, good functionalities) is an issue. Considering that important benefits (eg, improving health and self-reliance) are experienced by many of the respondents using apps for regulating blood glucose levels, improving reliability and quality of apps is likely to have many profits. In addition, creating better awareness regarding the existence and how to use apps will likely improve proper use by more people, enhancing the profits of these tools.

Risk indicator taxonomy for supervision of clinical trials on medicinal products.

AIM: To facilitate a risk-based approach for the supervision of clinical trials on medicinal products, we identified and categorized indicators that may present an elevated safety and/or ethical risk for participants, and/or for data integrity. The indicators are relevant for all stakeholders including participants, regulatory bodies, health care inspectorates, sponsors and trial sites. METHODS: The sources of indicators included Medline (using the search terms risk-based/-triggered/-driven oversight/monitoring/inspection), relevant documents from websites of regulatory authorities in Europe, North America and Australia, and results of a brainstorm session organized for experts working in the field. Indicators were classified according to risk area (safety and ethical, data integrity, or both). RESULTS: In total, we identified 69 risk indicators that were categorized into six branch-levels of the taxonomy. We visualized the taxonomy in a tree structure to clearly distinguish individual indicators. In addition to readily detectable risk indicators, more context-related aspects determine the final impact of the trial and constitute further components in risk assessment. Context-related aspects include potential high media attention, consequences for the reputation of medical research, and the socioeconomic situation in the geographic region and have to be considered on a case-by-case basis. CONCLUSIONS: We identified a wide array of risk indicators for clinical trials on medicinal products and we used a tree structure to incorporate the indicators identified to clearly distinguish individual indicators and to enable efficient use of the indicators. The overview of indicators may facilitate multiple stakeholders in developing structured risk assessment (identification and analysis) for supervising clinical trials on medicinal products. Stakeholders can interpret and prioritize the indicators from their own perspective.

Operation resistance: A snapshot of falsified antibiotics and biopharmaceutical injectables in Europe.

Operation Pangea is an annual international week of action combating pharmaceutical crime. In this study, called Operation Resistance, we asked the national agencies in Europe to search for falsified antibiotics and biopharmaceutical injectables (peptides and proteins) amongst the medicines seized in Pangea 7 (2014). Reports were received from Belgium, Cyprus, Czech Republic, Denmark, France, the Netherlands, Portugal, Sweden, Spain, the United Kingdom, Norway, and Switzerland. The countries reported seizing about 21,000 dose units (e.g. tablets, capsules) of falsified antibiotics in total. Most of the antibiotics were unlicensed medicines with common antibiotic drugs. In this study week, very few falsified biopharmaceutical injectables were reported. Laboratories reported human growth hormone, sermorelin, melanotan II, and no active ingredients. The average shipment size seemed too large for personal use indicating that a substantial part was intended for resale. This study provides a snapshot of the falsified antibiotics and biopharmaceuticals that enter European countries. How much is actually reaching users during Pangea week - in on other weeks - remains unknown. The shipment sizes indicate falsified antibiotics and biopharmaceuticals are imported for both personal use and resale. The use of antibiotics from unreliable sources is a health risk, contributes to antimicrobial resistance, and may obscure a source of infection from health agencies. The falsified biopharmaceuticals are a health risk because they lack all labelling and may contain unlicensed drugs for injection. It seems important to raise awareness among health-care professionals that falsified medicines in Europe are not restricted to erectile dysfunction drugs. Copyright © 2015 John Wiley & Sons, Ltd.

Enhancing the contribution of research to health care policy-making: a case study of the Dutch Health Care Performance Report.

OBJECTIVES: The Dutch Health Care Performance Report, issued by the National Institute of Public Health and the Environment, aims to monitor health care performance in The Netherlands. Both the National Institute and the Ministry of Health wish to increase the contribution of the Report to health care policy-making. Our aim was to identify ways to achieve that. METHOD: We used contribution mapping as a theoretical framework that recognizes alignment of research as crucial to managing contributions to policy-making. To investigate which areas need alignment efforts by researchers and/or policy-makers, we interviewed National Institute researchers and policy-makers from the Ministry of Health and assessed the process for developing the 2010 Report. RESULTS: We identified six areas where alignment is specifically relevant for enhancing the contributions of future versions of the Dutch Health Care Performance Report: well-balanced information for different ministerial directorates; backstage work; double role actors; reports of other knowledge institutes; data collection/generation and presentation forms. CONCLUSION: The contribution of health care performance reporting to policy-making is complex and requires continuous alignment efforts between researchers and policy-makers. These efforts should form an inseparable part of health care performance reporting and although this demands considerable resources, it is worth considering since it may pay back in better contributions to policy-making.

Empowerment of patients in online discussions about medicine use.

BACKGROUND: Patient empowerment is crucial in the successful self-management of people with chronic diseases. In this study, we investigated whether discussions about medicine use taking place on online message boards contribute to patient empowerment and could subsequently result in the more effective use of medicines. We discuss the extent to which patient empowerment processes occur in discussions on online message boards, focusing on patients with three disorders with different characteristics: diabetes, Amyotrophic Lateral Sclerosis (ALS) and Attention Deficit / Hyperactivity Disorder (ADHD). Because information is an important factor in both patient empowerment and self-management, we also evaluate the quality of the information being exchanged. METHODS: We used a deductive thematic analysis method based on pre-existing categories. We gathered and analysed 5532 posts related to the conditions ADHD, ALS and diabetes from seven message boards (three for ADHD, three for diabetes, and one for ALS). We coded the posts for empowerment processes and the quality of the information exchanged. RESULTS: We identified patient empowerment processes in posts related to all three disorders. There is some variation in the frequency of these processes, but they show a similar order in the results: patients used the online message boards to exchange information, share personal experiences and for empathy or support. The type of information shared in these processes could contribute to the patient's self-efficacy when it comes to medicine use. The exchanged information was either correct or largely harmless. We also observed a tendency whereby participants correct previously posted incorrect information, and refer people to a healthcare professional following a request for medical advice, e.g. concerning the choice of medicines or dosage. CONCLUSIONS: Our findings show that patient empowerment processes occur in posts related to all three disorders. The type of information shared in these processes can contribute to the patient's self-efficacy when it comes to medicine use. The tendency to refer people to a healthcare professional shows that patients still reserve an important role for healthcare professionals in the care process, despite the development towards more self-management.

Analyzing the contributions of a government-commissioned research project: a case study.

BACKGROUND: It often remains unclear to investigators how their research contributes to the work of the commissioner. We initiated the 'Risk Model' case study to gain insight into how a Dutch National Institute for Public Health and the Environment (RIVM) project and its knowledge products contribute to the commissioner's work, the commissioner being the Health Care Inspectorate. We aimed to identify the alignment efforts that influenced the research project contributions. Based on the literature, we expected interaction between investigators and key users to be the most determining factor for the contributions of a research project. METHODS: In this qualitative case study, we analyzed the alignment efforts and contributions in the Risk Model project by means of document analysis and interviews according to the evaluation method Contribution Mapping. Furthermore, a map of the research process was drafted and a feedback session was organized. After the feedback session with stakeholders discussing the findings, we completed the case study report. RESULTS: Both organizations had divergent views on the ownership of the research product and the relationship between RIVM and the Inspectorate, which resulted in different expectations. The RIVM considered the use of the risk models to be problematic, but the inspectors had a positive opinion about its contributions. Investigators, inspectors, and managers were not aware of these remarkably different perceptions. In this research project, we identified six relevant categories of both horizontal alignment efforts (between investigators and key users) as well as vertical alignment efforts (within own organization) that influenced the contributions to the Inspectorate's work. CONCLUSIONS: Relevant alignment efforts influencing the contributions of the project became manifest at three levels: the first level directly relates to the project, the second to the organizational environment, and the third to the formal and historical relationship between the organizations. Both external and internal alignments influence the contributions of a research project. Based on the findings, we recommend that research institutes invest in a reflective attitude towards the social aspects of research projects at all levels of the organization and develop alignment strategies to enhance the contributions of research.