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This study explores the evaluation of research pathways of self-management health innovations from discovery to implementation in the context of practice-based research. The aim is to understand how a new process model for evaluating practice-based research provides insights into the implementation success of innovations. Data were collected from nine research projects in the Netherlands. Through document analysis and semi-structured interviews, we analysed how the projects start, evolve, and contribute to the healthcare practice. Building on previous research evaluation approaches to monitor knowledge utilization, we developed a Research Pathway Model. The model's process character enables us to include and evaluate the incremental work required throughout the lifespan of an innovation project and it helps to foreground that innovation continues during implementation in real-life settings. We found that in each research project, pathways are followed that include activities to explore a new solution, deliver a prototype and contribute to theory. Only three projects explored the solution in real life and included activities to create the necessary changes for the solutions to be adopted. These three projects were associated with successful implementation. The exploration of the solution in a real-life environment in which users test a prototype in their own context seems to be a necessary research activity for the successful implementation of self-management health innovations. [ABSTRACT FROM AUTHOR]

The true cost of implementing SP 177 sp Lu-PSMA depends upon the final costs of the overall therapy (an important part of which, as with most novel oncology drugs, will be determined by the price setting by the manufacturer) as well as the location of therapy delivery. In May 2018, the first phase III study, so-called VISION (ClinicalTrials.gov: NCT03511664), started, investigating SP 177 sp Lu-PSMA treatment safety and effectiveness against the current standard treatments for patients with progressive PSMA-positive, castration-resistant, post-chemotherapy metastatic prostate cancer [[3], [6], [10]]. In the Netherlands alone, with an estimated number of 4500 eligible patients per year and an anticipated 4-6 SP 177 sp Lu-PSMA treatment cycles per patient, this means that a number of 18,000-27,000 SP 177 sp Lu-PSMA treatments need to be accommodated per year. The interest in Lutetium-177 labeled, prostate specific membrane antigen ( SP 177 sp Lu-PSMA) targeted radioligand therapy for the treatment of advanced prostate cancer is growing: it generally appears well-tolerated and has a potential low toxicity as well as a beneficial efficacy profile [[4]-[8]]. [Extracted from the article]

National and international laws and regulations exist to protect animals used for scientific purposes in translational and applied research, which includes drug development. However, multiple animal models are available for each disease. We evaluated the argumentation behind the selection of a specific animal model using thematic content analysis in project applications issued in 2017-2019 in the Netherlands. In total, 125 animal models for translational and applied research from 110 project applications were assessed. Explanations to select a specific model included: the model's availability (79%); the availability of expertise (62%); and the model showing similar disease pathology/symptoms (59%) to humans. Therefore, current selection of a specific animal model seems to be based on tradition rather than its potential predictive value for clinical outcome. The applicants' explanations for the implementation of the 3R principles (replacement, reduction and refinement) as to the animal model were unspecific. Replacement was achieved by using data from prior in vitro studies, reduction by optimal experimental design and statistics, and refinement by reducing discomfort. Additionally, due to the stated need for a test model with high complexity (47%) and intactness (30%), the full replacement of animal models with alternative (non-live animal) approaches was thought unachievable. Without a clear, systematic and transparent justification for the selection of a specific animal model, the likelihood of poorly translatable research remains. It is not only up to the researcher to demonstrate this, as ethical committees and funding bodies can provide positive stimuli to drive this change. [ABSTRACT FROM AUTHOR]

The most pressing environmental problems of post-mining base metals production are solid waste production, gaseous emissions, and a high energy use. Most of the present solutions to clean up the post-mining base metals production can be characterised as incremental, end-of-pipe technologies. More sophisticated, radical solutions are scarcely implemented.The purpose of this study is to identify the barriers that impede the implementation of more radical solutions, with the aim to design strategies towards cleaner production in the base metals producing industry. The paper conceptualises the radicalness of a technological innovation, and presents the current base metals production processes, their environmental impact, and cleaner technologies. The most important barriers for radical innovations appear to be the cost of investment, the high risk involved in committing capital to unproven technology, and the intertwinement of the current production system. The paper presents firm-internal, inter-firm and firm-external strategies to overcome these barriers. [Copyright &y& Elsevier]

Background: We determined whether the market exclusivity incentive of the European Orphan Drug Regulation results in a market monopoly or that absence of another Orphan Medicinal Product (OMP) for the same rare disorder, a so-called follow-on OMP, is a matter of time or market size. In the interest of rare disorder patients better understanding of the effect of the market exclusivity incentive on follow-on OMP development is warranted.Methods: First, the impact of various market-, product- and disease-related characteristics on follow-on OMP development in the EU was determined by comparing rare disorders with an approved OMP and at least one follow-on OMP (N = 26), with rare disorders with an approved OMP and no follow-on OMP (N = 18). Next, we determined whether manufacturers continued development of a follow-on OMP upon approval of the first OMP for the intended rare disorder. Since in the EU significant benefit of an OMP has to be established, we determined for each follow-on OMP for which development was continued on what grounds significant benefit was assumed by the sponsor. Data were collected from the public domain only.Results: The likelihood of a rare disorder with an approved OMP to obtain at least one follow-on OMP development was strongly associated with disease prevalence, turnover of the first OMP, disease class, disease-specific scientific output and age of onset. Out of a total of 120 follow-on OMPs only one follow-on OMP could be identified for which development was discontinued upon approval of the first OMP for the same rare disorder. Only a substantial level of discontinuation of follow-on OMP development would have indicated the existence of a market monopoly. Moreover, sponsors that continued development of a follow-on OMP predominantly assumed that their product had an improved efficacy compared to the first approved OMP.Conclusions: This study provides evidence that absence of follow-on OMP development is a matter of time or market size, rather than that the market exclusivity incentive of the European Orphan Drug Regulation creates a market monopoly. [ABSTRACT FROM AUTHOR]

Background: Emerging technologies such as artificial intelligence (AI) require an early-stage assessment of potential societal and ethical implications to increase their acceptability, desirability, and sustainability. This paper explores and compares 2 of these assessment approaches: the responsible innovation (RI) framework originating from technology studies and the co-design approach originating from design studies. While the RI framework has been introduced to guide early-stage technology assessment through anticipation, inclusion, reflexivity, and responsiveness, co-design is a commonly accepted approach in the development of technologies to support the care for older adults with frailty. However, there is limited understanding about how co-design contributes to the anticipation of implications., Objective: This paper empirically explores how the co-design process of an AI-based decision support system (DSS) for dementia caregivers is complemented by explicit anticipation of implications., Methods: This case study investigated an international collaborative project that focused on the co-design, development, testing, and commercialization of a DSS that is intended to provide actionable information to formal caregivers of people with dementia. In parallel to the co-design process, an RI exploration took place, which involved examining project members' viewpoints on both positive and negative implications of using the DSS, along with strategies to address these implications. Results from the co-design process and RI exploration were analyzed and compared. In addition, retrospective interviews were held with project members to reflect on the co-design process and RI exploration., Results: Our results indicate that, when involved in exploring requirements for the DSS, co-design participants naturally raised various implications and conditions for responsible design and deployment: protecting privacy, preventing cognitive overload, providing transparency, empowering caregivers to be in control, safeguarding accuracy, and training users. However, when comparing the co-design results with insights from the RI exploration, we found limitations to the co-design results, for instance, regarding the specification, interrelatedness, and context dependency of implications and strategies to address implications., Conclusions: This case study shows that a co-design process that focuses on opportunities for innovation rather than balancing attention for both positive and negative implications may result in knowledge gaps related to social and ethical implications and how they can be addressed. In the pursuit of responsible outcomes, co-design facilitators could broaden their scope and reconsider the specific implementation of the process-oriented RI principles of anticipation and inclusion., (©Dirk R M Lukkien, Sima Ipakchian Askari, Nathalie E Stolwijk, Bob M Hofstede, Henk Herman Nap, Wouter P C Boon, Alexander Peine, Ellen H M Moors, Mirella M N Minkman. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 31.07.2024.)

Background: Although the use of artificial intelligence (AI)-based technologies, such as AI-based decision support systems (AI-DSSs), can help sustain and improve the quality and efficiency of care, their deployment creates ethical and social challenges. In recent years, a growing prevalence of high-level guidelines and frameworks for responsible AI innovation has been observed. However, few studies have specified the responsible embedding of AI-based technologies, such as AI-DSSs, in specific contexts, such as the nursing process in long-term care (LTC) for older adults., Objective: Prerequisites for responsible AI-assisted decision-making in nursing practice were explored from the perspectives of nurses and other professional stakeholders in LTC., Methods: Semistructured interviews were conducted with 24 care professionals in Dutch LTC, including nurses, care coordinators, data specialists, and care centralists. A total of 2 imaginary scenarios about AI-DSSs were developed beforehand and used to enable participants articulate their expectations regarding the opportunities and risks of AI-assisted decision-making. In addition, 6 high-level principles for responsible AI were used as probing themes to evoke further consideration of the risks associated with using AI-DSSs in LTC. Furthermore, the participants were asked to brainstorm possible strategies and actions in the design, implementation, and use of AI-DSSs to address or mitigate these risks. A thematic analysis was performed to identify the opportunities and risks of AI-assisted decision-making in nursing practice and the associated prerequisites for responsible innovation in this area., Results: The stance of care professionals on the use of AI-DSSs is not a matter of purely positive or negative expectations but rather a nuanced interplay of positive and negative elements that lead to a weighed perception of the prerequisites for responsible AI-assisted decision-making. Both opportunities and risks were identified in relation to the early identification of care needs, guidance in devising care strategies, shared decision-making, and the workload of and work experience of caregivers. To optimally balance the opportunities and risks of AI-assisted decision-making, seven categories of prerequisites for responsible AI-assisted decision-making in nursing practice were identified: (1) regular deliberation on data collection; (2) a balanced proactive nature of AI-DSSs; (3) incremental advancements aligned with trust and experience; (4) customization for all user groups, including clients and caregivers; (5) measures to counteract bias and narrow perspectives; (6) human-centric learning loops; and (7) the routinization of using AI-DSSs., Conclusions: The opportunities of AI-assisted decision-making in nursing practice could turn into drawbacks depending on the specific shaping of the design and deployment of AI-DSSs. Therefore, we recommend considering the responsible use of AI-DSSs as a balancing act. Moreover, considering the interrelatedness of the identified prerequisites, we call for various actors, including developers and users of AI-DSSs, to cohesively address the different factors important to the responsible embedding of AI-DSSs in practice., (©Dirk R M Lukkien, Nathalie E Stolwijk, Sima Ipakchian Askari, Bob M Hofstede, Henk Herman Nap, Wouter P C Boon, Alexander Peine, Ellen H M Moors, Mirella M N Minkman. Originally published in JMIR Nursing (https://nursing.jmir.org), 25.07.2024.)

The protein transition is one of today's major societal challenges to mitigate climate change. To support lasting consumer engagement, it has been suggested to look into consumers' understanding of the protein transition to identify barriers that go beyond the practical issues of changing one's diet. The current study explored consumers' mental models of how the transition unfolds to examine which factors consumers perceive as important drivers of the transition. With a fixed set of factors and actors identified with a questionnaire, Dutch consumers (N = 214) mapped their mental models. The content and structure of the mental models were analyzed with a focus on how consumers perceive their own role. Animal well-being and environmental concerns were most often included as important drivers. The findings showed a lack of consensus about which actor(s) drive the transition (i.e., none of the actors were included by a majority of the participants). This diffusion of responsibility may be a barrier for consumers to act. Moreover, the relative simplicity of the observed mental models suggests that consumers do not yet employ systems thinking. A systems thinking mindset may help consumers understand how the system behind the transition works and how their individual contributions matter. Two avenues to encourage consumer engagement were identified: 1) emphasizing the responsibility of different actors and what consumers can contribute, and 2) encouraging a systems thinking mindset., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Magnetic resonance image (MRI)-guided radiation therapy with the 1.5 Tesla magnetic resonance linear accelerator (MR-Linac) is a rapidly evolving and emerging treatment. The MR-Linac literature mainly focused on clinical and technological factors in technology implementation, but it is relatively silent on health care system-related factors. Consequently, there is a lack of understanding of opportunities and barriers in implementing the MR-Linac from a health care system perspective. This study addresses this gap with a case study of the US health care system., Methods and Materials: An exploratory, qualitative research design was used. Data collection consisted of 23 semistructured interviews ranging from clinical experts at the radiation therapy and radiology department to insurance commissioners in 7 US hospitals. Analysis of opportunities and barriers was guided by the Nonadoption, Abandonment, Scale-up, Spread and Sustainability framework for new medical technologies in health care organizations., Results: Opportunities included high-precision MR-guidance during radiation therapy with potential continued technical advances and better patient outcomes. MR-Linac also offers opportunities for research, professional, and economic development. Barriers included the lack of empirical evidence of clinical effectiveness, technological complexity, and large staffing and structural investments. Furthermore, the presence of patients with disadvantaged socioeconomic background, and the lack of appropriate reimbursement as well as regulatory conditions can hinder technology implementation., Conclusions: Our study confirms the current literature on implementing the MR-Linac, but also reveals additional challenges for the US health care system. Alongside the well-known clinical and technical factors, also professional, socioeconomic, market, and governing influences affect technology implementation. These findings highlight new connections to facilitate technology uptake and provide a richer start to understanding its long-term effect., (© 2022 The Authors.)

Transition studies have started to focus on market formation in innovation systems. This article investigates market formation in a global health transition that was instigated by drug-resistant malaria. We explore how markets for Artemisinin-based Combination Therapies (ACT) in the Greater Mekong Subregion (GMS) were formed at multiple geographical scales and locations. The study reveals the role of public institutes, academia and partnerships in early innovation system development. It demonstrates how transnational organizations created a supportive global landscape for ACT development and deployment. It then reveals how these advancements led to the formation of public-sector and private-sector ACT markets in the GMS. We illustrate how market formation activities took place on global, national and local scales and how structural couplings enabled the functioning of this global innovation system. The lessons learned are particularly relevant now that drug-resistant malaria has once more emerged in the GMS, urgently calling for new therapies and associated end-user markets., Competing Interests: Declaration of Competing Interest None.

Introduction:  According to the World Malaria Report 2019, Africa accounts for 94% of the global malaria deaths. While malaria prevalence and mortality have declined over the years, recent reports suggest that these gains may stand the risk of being reversed if resistance to Artemisinin Combination Therapies (ACTs) spreads from Southeast Asia to Africa. Efforts are being made to develop new treatments that will address the looming threat of ACT resistance, including the development of triple artemisinin combination therapies (TACTs). The proposed study seeks to explore the views of stakeholders on the key ethical, regulatory and market-related issues that should be considered in the potential introduction of triple artemisinin combination therapies (TACTs) in Africa. Methods:  The study employed qualitative research methods involving in-depth interviews and focus group discussions (FGDs) with stakeholders, who will be directly affected by the potential deployment of triple artemisinin combination treatments, as regulators, suppliers and end-users. Participants will be purposively selected and will include national regulatory authorities, national malaria control programs, clinicians, distributors and retailers as well as community members in selected districts in Burkina Faso and Nigeria. Discussion:  The proposed study is unique in being one of the first studies that seeks to understand the ethical, social, regulatory and market position issues prior to the development of a prospective antimalarial medicine., Competing Interests: No competing interests were disclosed., (Copyright: © 2021 Tindana P et al.)

Previous qualitative research has suggested there are only minor differences between the db/db mouse and the Zucker Diabetic Fatty (ZDF) rat, both animal models of type 2 diabetes. However, it is not known whether these models are also comparable regarding drug response in quantitative terms (effect size). To investigate the extent of these differences, we conducted a systematic review and meta-analysis of approved drugs in these models. We searched on PubMed and Embase on July 3, 2019 for studies including either model, a monotherapy arm with an EMA/FDA approved drug for the treatment of type 2 diabetes, HbA1c assessment and a control group. Studies aimed at diabetes prevention or with surgical interventions were excluded. We calculated the Standardised Mean Difference (SMD) to compare effect sizes (HbA1c reduction) per drug and drug class across models. We included a risk of bias assessment for all included publications. A total of 121 publications met our inclusion criteria. For drugs with more than two comparisons, both models predicted the direction of the effect regarding HbA1c levels. There were no differences between the db/db mouse and ZDF rat, except for exenatide (P = 0.02) and GLP-1 agonists (P = 0.03) in which a larger effect size was calculated in the ZDF rat. Our results indicate the differences between the db/db mouse and ZDF rat are not relevant for preliminary efficacy testing. This methodology can be used to further differentiate between animal models used for the same indication, facilitating the selection of models more likely to predict human response., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Clinical trial failures (>99%) in Alzheimer's disease are in stark contrast to positive efficacy data in animals. We evaluated the correlation between animal and clinical efficacy outcomes (cognition) in Alzheimer's disease using data from registered drugs as well as interventions tested in phase II or III clinical trials for Alzheimer's disease. We identified 20 interventions, which were tested in 208 animal studies in 63 different animal models. Clinical outcome was correlated with animal results in 58% of cases. But, individual animal models showed divergent results across interventions, individual interventions showed divergent results across animal models, and animal model outcomes were determined with 16 different methods. This result is unsurprising due to poor external validity (what do we model) of the animal models. Although the animal models all share Alzheimer's disease symptoms, none represents the whole syndrome. Investigators did not motivate why one model was chosen over another, and did not consider the ways the disease phenomena were generated (spontaneous, (experimentally) induced or by genetic modification), or the species characteristics, which determine the outcomes. The explanation for the lack of correlation between animal and human outcomes can be manifold: the pathogenesis of Alzheimer's disease is not reflected in the animal model or the outcomes are not comparable. Our conclusion is that currently no animal models exist which are predictive for the efficacy of interventions for Alzheimer's disease., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

The European Union (EU) was the first region to establish a regulatory framework for biosimilars, in which animal studies are required to confirm similarity to a reference product. However, animal studies described in European public assessment reports (EPARs) or marketing authorization applications (MAAs) did not identify clinically or toxicologically relevant differences despite differences in quality, suggesting that animal studies lack the sensitivity to confirm biosimilarity. Scientific advice provided learning opportunities to evolve existing guidance. Altogether, the data support a step-wise approach to develop biosimilars that focuses on quality and clinical efficacy of biosimilar. This approach might be more effective and does not necessarily require animal studies, which is also reflected in new EU draft guidance., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Drug development has become the exclusive activity of large pharmaceutical companies. However, the output of new drugs has been decreasing for the past decade and the prices of new drugs have risen steadily, leading to access problems for many patients. By analyzing the history of drug development and the pharmaceutical industry, we identified the main factors causing this system failure. Although many solutions have been suggested to fix the drug development system, we believe that a combination of reforms of the regulatory and patent systems is necessary to make drug development sustainable. These reforms must be combined with a larger, open-access role for public research institutes in the discovery, clinical evaluation and safety evaluation of new drugs., (Copyright © 2014 Elsevier Ltd. All rights reserved.)