Fulfilling the Promise of Breathomics: Considerations for the Discovery and Validation of Exhaled Volatile Biomarkers.

The exhaled breath represents an ideal matrix for non-invasive biomarker discovery, and exhaled metabolomics have the potential to be clinically useful in the era of precision medicine. In this concise translational review we will specifically address volatile organic compounds in the breath, with a view towards fulfilling the promise of these as actionable biomarkers, in particular for lung diseases. We review the literature paying attention to seminal work linked to key milestones in breath research; discuss potential applications for breath biomarkers across disease areas and healthcare systems, including the perspectives of industry; and outline critical aspects of study design that will need to be considered for any pivotal research going forward, if breath analysis is to provide robust validated biomarkers that meet the requirements for future clinical implementation.

Toolkit for emerging technologies in laboratory medicine.

An emerging technology (ET) for laboratory medicine can be defined as an analytical method (including biomarkers) or device (software, applications, and algorithms) that by its stage of development, translation into broad routine clinical practice, or geographical adoption and implementation has the potential to add value to clinical diagnostics. Considering the laboratory medicine-specific definition, this document examines eight key tools, encompassing clinical, analytical, operational, and financial aspects, used throughout the life cycle of ET implementation. The tools provide a systematic approach starting with identifying the unmet need or identifying opportunities for improvement (Tool 1), forecasting (Tool 2), technology readiness assessment (Tool 3), health technology assessment (Tool 4), organizational impact map (Tool 5), change management (Tool 6), total pathway to method evaluation checklist (Tool 7), and green procurement (Tool 8). Whilst there are differences in clinical priorities between different settings, the use of this set of tools will help support the overall quality and sustainability of the emerging technology implementation.

Mobile Manipulators in Industry 4.0: A Review of Developments for Industrial Applications.

In the realm of Industry 4.0, diverse technologies such as AI, Cyber-Physical Systems, IoT, and advanced sensors converge to shape smarter future factories. Mobile manipulators (MMs) are pivotal, fostering flexibility, adaptability, and collaboration in industrial processes. On one hand, MMs offer a remarkable level of flexibility, adaptability, and collaboration in industrial processes, facilitating swift production line changes and efficiency enhancements. On the other hand, their integration into real manufacturing environments requires meticulous considerations, such as safety, human-robot interaction, and cybersecurity. This article delves into MMs' essential role in achieving Industry 4.0's automation and adaptability by integrating mobility with manipulation capabilities. The study reviews MMs' industrial applications and integration into manufacturing systems. The most observed applications are logistics (49%) and manufacturing (33%). As Industry 4.0 advances, the paper emphasizes updating and aligning MMs with the smart factory concept by networks of sensors and the real-time analysis of them, especially for an enhanced human-robot interaction. Another objective is categorizing considerations for MMs' utilization in Industry 4.0-aligned manufacturing. This review methodically covers a wide range of considerations and evaluates existing solutions. It shows a more comprehensive approach to understanding MMs in Industry 4.0 than previous works. Key focus areas encompass perception, data analysis, connectivity, human-robot interaction, safety, virtualization, and cybersecurity. By bringing together different aspects, this research emphasizes a more integrated view of the role and challenges of MMs in the Industry 4.0 paradigm and provides insights into aspects often overlooked. A detailed and synthetic analysis of existing knowledge was performed, and insights into their future path in Industry 4.0 environments were provided as part of the contributions of this paper. The article also appraises initiatives in these domains, along with a succinct technology readiness analysis. To sum up, this study highlights MMs' pivotal role in Industry 4.0, encompassing their influence on adaptability, automation, and efficiency.

Biomanufacturing readiness levels [BRL]-A shared vocabulary for biopharmaceutical technology development and commercialization.

The Manufacturing Readiness Levels (MRLs) developed by the Department of Defense are well-established tools for describing the maturity of new technologies resulting from government-sponsored Research and Development programs, from the concept phase to commercial deployment. While MRLs are generally applicable to a wide range of industries and technologies, there is significant value in offering an industry-specific view on how the basic principles may be applied to biomanufacturing. This paper describes Biomanufacturing Readiness Levels (BRLs) developed by the National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL), a public/private partnership that is part of the Manufacturing USA network. NIIMBL brings together private, federal, nonprofit, and academic stakeholders to accelerate the deployment of innovative technologies for biopharmaceutical production and to educate and train a world-leading biomanufacturing workforce. We anticipate that these BRLs will lay the groundwork for a shared vocabulary for assessment of technology maturity and readiness for commercial biomanufacturing that effectively meets the needs of this critical, specialized, and highly regulated industry.

Current state of micro-robots/devices as substitutes for screening colonoscopy: assessment based on technology readiness levels.

BACKGROUND: Previous reports have described several candidates, which have the potential to replace colonoscopy, but to date, there is still no device capable of fully replacing flexible colonoscopy in the management of colonic disorders and for mass adult population screening for asymptomatic colorectal cancer. MATERIALS AND METHODS: NASA developed the TRL methodology to describe and define the stages of development before use and marketing of any device. The definitions of the TRLS used in the present review are those formulated by "The US Department of Defense Technology Readiness Assessment Guidance" but adapted to micro-robots for colonoscopy. All the devices included are reported in scientific literature. They were identified by a systematic search in Web of Science, PubMed and IEEE Xplore amongst other sources. Devices that clearly lack the potential for full replacement of flexible colonoscopy were excluded. ASSESSMENT OF THE CURRENT SITUATION: The technological salient features of all the devices included for assessment are described briefly, with particular focus on device propulsion. The devices are classified according to the TRL criteria based on the reported information. An analysis is next undertaken of the characteristics and salient features of the devices included in the review: wireless/tethered devices, data storage-transmission and navigation, additional functionality, residual technology challenges and clinical and socio-economical needs. CONCLUSIONS: Few devices currently possess the required functionality and performance to replace the conventional colonoscopy. The requirements, including functionalities which favour the development of a micro-robot platform to replace colonoscopy, are highlighted.

Transportable, portable, wearable and (partially) implantable haemodialysis systems: comparison of technologies and readiness levels.

Background: Dialysis modalities and their various treatment schedules result from complex compromises ('trade-offs') between medical, financial, technological, ergonomic, and ecological factors. This study targets summarizing the mutual influence of these trade-offs on (trans)portable, wearable, or even (partially) implantable haemodialysis (HD) systems, identify what systems are in development, and how they might improve quality of life (QoL) for patients with kidney failure. Methods: HD as defined by international standard IEC 60601-2-16 was applied on a PUBMED database query regarding (trans)portable, wearable, and (partly) implantable HD systems. Out of 159 search results, 24 were included and scanned for specific HD devices and/or HD systems in development. Additional information about weight, size, and development status was collected by the internet and/or contacting manufacturers. International airplane hand baggage criteria formed the boundary between transportable and portable. Technology readiness levels (TRLs) were assigned by combining TRL scales from the European Union and NATO medical staff. Results: The query revealed 13 devices/projects: seven transportable (six TRL9, one TRL5); two portable (one TRL6-7, one TRL4); two wearable (one TRL6, one frozen); and two partly implantable (one TRL4-5, one TRL2-3). Discussion: Three main categories of technical approaches were distinguished: single-pass, dialysate regenerating, and implantable HD filter with extracorporeal dialysate regeneration (in climbing order of mobility). Conclusions: Kidneys facilitate mobility by excreting strongly concentrated waste solutes with minimal water loss. Mimicking this kidney function can increase HD system mobility. Dialysate-regenerating HD systems are enablers for portability/wearability and, combined with durable implantable HD filters (once available), they may enable HD without needles or intravascular catheters. However, lack of funding severely hampers progress.

Why bioprinting in regenerative medicine should adopt a rational technology readiness assessment.

Bioprinting is an annex of additive manufacturing, as defined by the American Society for Testing and Materials (ASTM) and International Organization for Standardization (ISO) standards, characterized by the automated deposition of living cells and biomaterials. The tissue engineering and regenerative medicine (TE&RM) community has eagerly adopted bioprinting, while review articles regularly herald its imminent translation to the clinic as functional tissues and organs. Here we argue that such proclamations are premature and counterproductive; they place emphasis on technological progress while typically ignoring the critical stage-gates that must be passed through to bring a technology to market. We suggest the technology readiness level (TRL) scale as a valuable metric for gauging the relative maturity of a bioprinting technology in relation to how it has passed a series of key milestones. We suggest guidelines for a bioprinting-oriented scale and use this to discuss the state-of-the-art of bioprinting in regenerative medicine (BRM) today. Finally, we make corresponding recommendations for improvements to BRM research that would support its progression to clinical translation.

Adaptation of the technology readiness levels for impact assessment in implementation sciences: The TRL-IS checklist.

Background: Intervention development is a critical process in implementation research. There are key stages involved in the process to design, pilot, demonstrate and release a technology or an intervention. The Technology Readiness Level (TRL) is a globally accepted instrument for assessing the maturity of research development. However, the original levels do not fit all, and some adjustments are required for its applicability in implementation sciences. Aims: This study aimed to gather the prior knowledge base on TRL in public and population health research; to develop a standard definition of readiness, and to adapt and validate the TRL to an implementation science context (TRL-IS). Materials and methods: A Mixed methods approach has been followed in this study. A scoping review using the PRISMA extension (PRISMA-ScR) informed a nominal expert panel for developing a standard definition of readiness and to modify the TRL following an ontoterminology approach. Then the maturity of six practical case study examples were rated by ten researchers using the modified TRL to estimate inter-rater reliability, and a group of experts provided final content and face validity and feasibility.This mixed methods study included 1) a scoping review to examine the current literature and develop a knowledge base, identify knowledge gaps and to clarify concepts; 2) the development of a standard definition of 'Readiness' and related terms; and 3) adaptation of the TRL to implementation science and development of a checklist to rate the maturity of applications.A standard definition of readiness and related terms was produced by the core team, and an international nominal group (n = 30) was conducted to discuss and validate the definition and terms, and the location of 'Readiness' in the initiation and early development phases of implementation.Following feedback from the nominal group, the development of the TRL-IS was finalised and a TRL-IS rating checklist was developed to rate the maturity of applications. The TRL-IS checklist was tested using six cases based on real world studies on implementation research.The inter-rater reliability of the TRL-IS was evaluated by ten raters and finally six raters evaluated the content and face validity, and feasibility, of the TRL-IS checklist using the System Usability Scale (SUS). Results: Few papers (n = 11) utilised the TRL to evaluate the readiness of readiness of health and social science implementation research. The main changes in the adaption of the TRL-IS included the removal of laboratory testing, limiting the use of "operational" environment and a clearer distinction between level 6 (pilot in a relevant environment) and 7 (demonstration in the real world prior to release). The adapted version was considered relevant by the expert panel. The TRL-IS checklist showed evidence of good inter-rater reliability (ICC = 0.90 with 95 % confident interval = 0.74-0.98, p < .001) and provides a consistent metric. Conclusions: In spite of recommendations made by national and international research funding agencies, few health and social science implementation studies include the TRL as part of their evaluation protocol. The TRL-IS offers a high degree of conceptual clarity between scientific maturity phases or readiness levels, and good reliability among raters of varying experience. This study highlights that adoption of the TRL-IS framework in implementation sciences will bolster the scientific robustness and comparability of research maturity in this domain.

From bytes to bedside: a systematic review on the use and readiness of artificial intelligence in the neonatal and pediatric intensive care unit.

PURPOSE: Despite its promise to enhance patient outcomes and support clinical decision making, clinical use of artificial intelligence (AI) models at the bedside remains limited. Translation of advancements in AI research into tangible clinical benefits is necessary to improve neonatal and pediatric care for critically ill patients. This systematic review seeks to assess the maturity of AI models in neonatal and pediatric intensive care unit (NICU and PICU) treatment, and their risk of bias and objectives. METHODS: We conducted a systematic search in Medline ALL, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar. Studies using AI models during NICU or PICU stay were eligible for inclusion. Study design, objective, dataset size, level of validation, risk of bias, and technological readiness of the models were extracted. RESULTS: Out of the 1257 identified studies 262 were included. The majority of studies was conducted in the NICU (66%) and most had a high risk of bias (77%). An insufficient sample size was the main cause for this high risk of bias. No studies were identified that integrated an AI model in routine clinical practice and the majority of the studies remained in the prototyping and model development phase. CONCLUSION: The majority of AI models remain within the testing and prototyping phase and have a high risk of bias. Bridging the gap between designing and clinical implementation of AI models is needed to warrant safe and trustworthy AI models. Specific guidelines and approaches can help improve clinical outcome with usage of AI.

Technology Readiness Level Roadmap for Developing Innovative Herbal Medicinal Products.

Despite the vast global botanical diversity, the pharmaceutical development of herbal medicinal products (HMPs) remains underexploited. Of over 370,000 described plant species, only a few hundred are utilized in HMPs. Most of these have originated from traditional use, and only a minority come from megadiverse countries. Exploiting the pharmacological synergies of the hundreds of compounds found in poorly studied plant species may unlock new therapeutic possibilities, enhance megadiverse countries' scientific and socio-economic development, and help conserve biodiversity. However, extensive constraints in the development process of HMPs pose significant barriers to transforming this unsatisfactory socio-economic landscape. This paper proposes a roadmap to overcome these challenges, based on the technology readiness levels (TRLs) introduced by NASA to assess the maturity of technologies. It aims to assist research entities, manufacturers, and funding agencies from megadiverse countries in the discovery, development, and global market authorization of innovative HMPs that comply with regulatory standards from ANVISA, EMA, and FDA, as well as WHO and ICH guidelines.

Development and application of the Rapha® device for the treatment of diabetic foot ulcers.

INTRODUCTION: Transforming medical research into real-world healthcare solutions is a complex endeavor that may benefit from the synergy between academic research, governmental support, and industry innovation. OBJECTIVES: In this article we delve into the framework of Translational Medical Research (TMR) in Brazil, elucidating the possible interplay between public universities and other pivotal stakeholders in the translational journey. METHODS: Our focal point is the Rapha® device, an innovative medical technology, as we explore its ethical and regulatory journey. We seek to understand the environment that shapes healthcare technology development through a mixed-methods research design, combining policy analysis with stakeholder interviews. RESULTS: The research begins by examining public policies, aiming to carve out a socially inclusive and advantageous ecosystem. We then highlight the pivotal components-steps, milestones, stakeholders, and policies that underpin the TMR process. Our findings reveal that while TMR frequently culminates in patents and technology transfer agreements, specific regulatory and production challenges exist, particularly during transitioning from the T3 (clinical trials) to T4 (public health practice) phase. We provide insights into its translational progression by tracing the developmental stages from foundational research (T0) to clinical trials (T3) for the Rapha® device. CONCLUSION: Ultimately, this study underscores TMR's vital role in advancing healthcare access and posits that academic institutions can significantly influence the creation of ethically robust, regulated, and impactful medical innovations, contributing meaningfully to global healthcare.

Analysis of current state, gaps, and opportunities for technologies in the Malaysian oil palm estates and palm oil mills towards net-zero emissions.

Malaysia is the second largest producer and exporter of palm oil. Though several works have explored achieving emissions reduction in the palm oil sector, there existing gaps in analysing pathways for achieving net-zero emissions. Moreover, there are limited studies that evaluate the potential of palm oil biomass utilisation pathways based on emissions reduction capabilities, the cost of emissions reduction, and the technology readiness for implementation. Therefore, this study analysed decarbonisation pathways for the upstream and midstream segments of the palm oil sector in Malaysia, encompassing oil palm plantations and palm oil mills. Various sources of greenhouse gas emissions in oil palm plantations and palm oil mills were identified and estimates of emissions were determined as theoretical emissions. The current emissions were established based on the current best practice in the plantation and mill. Several biomass conversion technologies for the recovery of palm-based by-products and conversion into value-added products to decarbonise the palm oil sector and evaluated strategies to attain net-zero status are considered. In this work, the analysis considered both the existing technologies that are adopted by plantations and mills as well as the emerging technologies that have scope for implementation. With the proposed approach, the current emissions level for crude palm oil (CPO) production in Malaysia is estimated as 1121.49 kg CO2-eq/t CPO. In current industry practice, empty fruit bunch (EFB) is underutilised as mills are typically located at rural areas with lack of suitable transportation. Besides, the lack of accessibility to the grid also limits the potential of converting EFB into electricity as supply for national grid. This work examined various pathways for EFB utilisation under different scenarios evaluating their contribution potential towards net-zero target in an energy self-sustained CPO production. As shown in the results, converting EFB to briquettes and pellets are able to achieve the net-zero objective. Furthermore, EFB-biochar and EFB-syngas pathways also exhibit the potential to accomplish the net-zero target. Note that this work also assessed the technologies' readiness levels, identified challenges in implementation, and proposed several recommendations.

Technical-scientific production and knowledge networks about medicinal plants and herbal medicines in the Amazon.

Introduction: This paper explores the role of Brazilian research institutions in the global and national context of study of medicinal plants. Most of these plants have ethnopharmacological use and herbal medicines related to the Amazon. It highlights Brazil's position in scientific production and the importance of Amazonian resources in developing phytomedicines. The study aims to provide an overview of the technical-scientific production of medicinal plants and herbal medicines related to the Amazon, focusing on scientific impact, collaboration, Technology Readiness Level (TRL) of scientific production, and innovation system maturity. Methods: The study employs a comprehensive methodological approach, including data collection from Scopus covering the period from 2002 to 2022. The data was cleaned and analyzed using bibliometric and network analysis techniques. Advanced natural language processing techniques, such as Latent Dirichlet Allocation and Jaccard distance measure, were used for TRL classification. Results: The findings reveal a predominant contribution from Brazilian institutions and authors, with 1,850 publications analyzed. Key areas identified include Pharmacology, Toxicology, Pharmaceuticals, Medicine, and Biochemistry. The study also uncovers various collaborative networks and technological maturity levels, with a significant focus on early-stage development phases. Discussion: The research concludes that Brazilian institutions, particularly those in the Amazon region, play a significant role in the scientific exploration and development of medicinal plants and herbal medicines. Despite this, countries like the USA were proportionally more productive in clinical trial research. The study underscores the potential of Brazil's rich biodiversity and traditional knowledge in the pharmaceutical industry, particularly for neglected diseases. It suggests the need for stronger research systems and international collaboration to leverage these resources for global health benefits.

An overview of emerging smart capsules using other-than-light technologies for colonic disease detection.

Wireless capsule endoscopy (CE) has revolutionized gastrointestinal diagnostics, offering a non-invasive means to visualize and monitor the GI tract. This review traces the evolution of CE technology. Addressing the limitations of traditional white light (WL) CE, the paper explores non-WL technologies, integrating diverse sensing modalities and novel biomarkers to enhance diagnostic capabilities. Concluding with an assessment of Technology Readiness Levels, the paper emphasizes the transformative impact of non-WL colon CE devices on GI diagnostics, promising more precise, patient-centric, and accessible healthcare for GI disorders.

Methanol production and purification via membrane-based technology: Recent advancements, challenges and the way forward.

Industrial revolution on the back of fossil fuels has costed humanity higher temperatures on the planet due to ever-growing concentration of carbon dioxide emissions in Earth's atmosphere. To tackle global warming demand for renewable energy sources continues to increase. Along renewables, there has been a growing interest in converting carbon dioxide to methanol, which can be used as a fuel or a feedstock for producing chemicals. The current review study provides a comprehensive overview of the recent advancements, challenges and future prospects of methanol production and purification via membrane-based technology. Traditional downstream processes for methanol production such as distillation and absorption have several drawbacks, including high energy consumption and environmental concerns. In comparison to conventional technologies, membrane-based separation techniques have emerged as a promising alternative for producing and purifying methanol. The review highlights recent developments in membrane-based methanol production and purification technology, including using novel membrane materials such as ceramic, polymeric and mixed matrix membranes. Integrating photocatalytic processes with membrane separation has been investigated to improve the conversion of carbon dioxide to methanol. Despite the potential benefits of membrane-based systems, several challenges need to be addressed. Membrane fouling and scaling are significant issues that can reduce the efficiency and lifespan of the membranes. The cost-effectiveness of membrane-based systems compared to traditional methods is a critical consideration that must be evaluated. In conclusion, the review provides insights into the current state of membrane-based technology for methanol production and purification and identifies areas for future research. The development of high-performance membranes and the optimization of membrane-based processes are crucial for improving the efficiency and cost-effectiveness of this technology and for advancing the goal of sustainable energy production.

Liposome-based vaccines for minimally or noninvasive administration: an update on current advancements.

INTRODUCTION: Vaccination requires innovation to provide effective protection. Traditional vaccines have several drawbacks, which can be overcome with advanced technologies and different administration routes. Over the past 10 years, a significant amount of research has focussed on the delivery of antigens into liposomes due to their dual role as antigen-carrying systems and vaccine adjuvants able to increase the immunogenicity of the carried antigen. AREAS COVERED: This review encompasses the progress made over the last 10 years with liposome-based vaccines designed for minimally or noninvasive administration, filling the gaps in previous reviews and providing insights on composition, administration routes, results achieved, and Technology Readiness Level of the most recent formulations. EXPERT OPINION: Liposome-based vaccines administered through minimally or noninvasive routes are expected to improve efficacy and complacency of vaccination programs. However, the translation from lab-scale production to large-scale production and collaborations with hospitals, research centers, and companies are needed to allow new products to enter the market and improve the vaccination programs in the future.

Are integrated bioelectrochemical technologies feasible for wastewater management?

The need for sustainable technological solutions for wastewater management at different scales has led to the emergence of several promising integrated bioelectrochemical technologies in the past decade. A thorough assessment of these technologies is imperative to understand their practical implementation feasibility and to identify the key challenges to prioritise the research and development work. Our multicriteria-based assessment reveals that the integrated technologies are efficient for wastewater treatment in terms of normalised land footprint [(0.31-1.39 m2/population equivalent (PE))] - and energy consumption (0.18-1.49 kWH/m3) as compared to the conventional biotechnologies, and suggests that they have potential for real-world application. Specifying the boundaries according to their treatment capabilities and scale-up potential besides niche application sites or geographical locations is required to expedite their transition to the real-world wastewater management sector.

Photocatalytic Reforming of Biomass: What Role Will the Technology Play in Future Energy Systems.

Photocatalytic reforming of biomass has emerged as an area of significant interest within the last decade. The number of papers published in the literature has been steadily increasing with keywords such as 'hydrogen' and 'visible' becoming prominent research topics. There are likely two primary drivers behind this, the first of which is that biomass represents a more sustainable photocatalytic feedstock for reforming to value-added products and energy. The second is the transition towards achieving net zero emission targets, which has increased focus on the development of technologies that could play a role in future energy systems. Therefore, this review provides a perspective on not only the current state of the research but also a future outlook on the potential roadmap for photocatalytic reforming of biomass. Producing energy via photocatalytic biomass reforming is very desirable due to the ambient operating conditions and potential to utilise renewable energy (e.g., solar) with a wide variety of biomass resources. As both interest and development within this field continues to grow, however, there are challenges being identified that are paramount to further advancement. In reviewing both the literature and trajectory of the field, research priorities can be identified and utilised to facilitate fundamental research alongside whole systems evaluation. Moreover, this would underpin the enhancement of photocatalytic technology with a view towards improving the technology readiness level and promoting engagement between academia and industry.

Readiness levels of Industry 4.0 technologies applied to aircraft manufacturing-a review, challenges and trends.

The present paper provides an overview of the state-of-the-art research, outlining the applications of the Industry 4.0 (I4.0) technologies on the aircraft manufacturing sector and their maturity state based on the technology readiness level (TRL) scale. A literature review has been conducted for the identification, selection, and evaluation of the published research. A total of 57 papers extracted from the two most relevant scientific databases for the area (Web of Science and Scopus), from 2010 to March 2021, were analysed and summarized. The research, analysis, and evaluation of these papers has provided an outlook of how the aircraft manufacturing industry is inserted into the I4.0 context, based on a classification of the I4.0 technologies maturity for this industrial branch. Then, a survey was performed with 12 specialists from 5 different aircraft manufacturing companies aiming to report the practical point-of-view in this area. Thus, this paper highlights and discusses the gaps found in the literature related to the I4.0 technologies applied to aircraft manufacturing and their main useful implications not only from the academic point-of-view but also from competitive business aspects, providing recommendations for industrial managers, engineers, and stakeholders. Finally, this paper proposes new opportunities and challenges for future research.

Time to act mature-Gearing eHealth evaluations towards technology readiness levels.

It is challenging to design a proper eHealth evaluation. In our opinion, the evaluation of eHealth should be a continuous process, wherein increasingly mature versions of the technology are put to the test. In this article, we present a model for continuous eHealth evaluation, geared towards technology maturity. Technology maturity can be determined best via Technology Readiness Levels, of which there are nine, divided into three phases: the research, development, and deployment phases. For each phase, we list and discuss applicable activities and outcomes on the end-user, clinical, and societal front. Instead of focusing on a single perspective, we recommend to blend the end-user, health and societal perspective. With this article we aim to contribute to the methodological debate on how to create the optimal eHealth evaluation design.