Stem cell biotech: seeking a piece of the action.

Venture capital groups and big pharma have largely held back from investing in biotech companies focused on regenerative medicine. Will it take a clinical bull's eye to bring venture capitalists and big pharma into the cell therapy arena?

Digital Health Technologies for Remote Monitoring and Management of Inflammatory Bowel Disease: A Systematic Review.

INTRODUCTION: Digital health technologies may be useful tools in the management of chronic diseases. We performed a systematic review of digital health interventions in the management of patients with inflammatory bowel diseases (IBD) and evaluated its impact on (i) disease activity monitoring, (ii) treatment adherence, (iii) quality of life (QoL) measures, and/or (iv) health care utilization. METHODS: Through a systematic review of multiple databases through August 31, 2020, we identified randomized controlled trials in patients with IBD comparing digital health technologies vs standard of care (SoC) for clinical management and monitoring and reporting impact on IBD disease activity, treatment adherence, QoL, and/or health care utilization or cost-effectiveness. We performed critical qualitative synthesis of the evidence supporting digital health interventions in patients with IBD and rated certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Overall, we included 14 randomized controlled trials (median, 98 patients; range 34-909 patients; follow-up <12 months) that compared web-based interventions, mobile applications, and different telemedicine platforms with SoC (clinic-based encounters). Although overall disease activity and risk of relapse were comparable between digital health technologies and SoC (very low certainty of evidence), digital health interventions were associated with lower rate of health care utilization and health care costs (low certainty of evidence). Digital health interventions did not significantly improve patients' QoL and treatment adherence compared with SoC (very low certainty of evidence). Trials may have intrinsic selection bias due to nature of digital interventions. DISCUSSION: Digital health technologies may be effective in decreasing health care utilization and costs, though may not offer advantage in reducing risk of relapse, QoL, and improving treatment adherence in patients with IBD. These techniques may offer value-based care for population health management.

Surface Modification of Bacterial Cellulose for Biomedical Applications.

Bacterial cellulose is a naturally occurring polysaccharide with numerous biomedical applications that range from drug delivery platforms to tissue engineering strategies. BC possesses remarkable biocompatibility, microstructure, and mechanical properties that resemble native human tissues, making it suitable for the replacement of damaged or injured tissues. In this review, we will discuss the structure and mechanical properties of the BC and summarize the techniques used to characterize these properties. We will also discuss the functionalization of BC to yield nanocomposites and the surface modification of BC by plasma and irradiation-based methods to fabricate materials with improved functionalities such as bactericidal capabilities.

Health Preference Research in Europe: A Review of Its Use in Marketing Authorization, Reimbursement, and Pricing Decisions-Report of the ISPOR Stated Preference Research Special Interest Group.

OBJECTIVE: This study examines European decision makers' consideration and use of quantitative preference data. METHODS: The study reviewed quantitative preference data usage in 31 European countries to support marketing authorization, reimbursement, or pricing decisions. Use was defined as: agency guidance on preference data use, sponsor submission of preference data, or decision-maker collection of preference data. The data could be collected from any stakeholder using any method that generated quantitative estimates of preferences. Data were collected through: (1) documentary evidence identified through a literature and regulatory websites review, and via key opinion leader outreach; and (2) a survey of staff working for agencies that support or make healthcare technology decisions. RESULTS: Preference data utilization was identified in 22 countries and at a European level. The most prevalent use (19 countries) was citizen preferences, collected using time-trade off or standard gamble methods to inform health state utility estimation. Preference data was also used to: (1) value other impact on patients, (2) incorporate non-health factors into reimbursement decisions, and (3) estimate opportunity cost. Pilot projects were identified (6 countries and at a European level), with a focus on multi-criteria decision analysis methods and choice-based methods to elicit patient preferences. CONCLUSION: While quantitative preference data support reimbursement and pricing decisions in most European countries, there was no utilization evidence in European-level marketing authorization decisions. While there are commonalities, a diversity of usage was identified between jurisdictions. Pilots suggest the potential for greater use of preference data, and for alignment between decision makers.

Managed Entry Agreements: Policy Analysis From the European Perspective.

BACKGROUND: Mounting pressures on the healthcare system, such as budget constraints and new, costly health technologies reaching the market, have pushed payers and manufacturers to engage in managed entry agreements (MEAs) to address uncertainty and facilitate market access. OBJECTIVES: This study was conducted to illustrate the current landscape of MEAs in Europe and to analyze the main hurdles they face in implementation, providing a policy perspective. METHODS: We conducted a health policy analysis based on a literature review and described the emergence, classification, current use, and implementation obstacles of MEAs in Europe. RESULTS: Throughout Europe, uncertainty and high prices of health technologies have pushed stakeholders towards MEAs. Two main types of MEAs were applied heavily, finance-based agreements (FBAs) and performance-based agreements, including individual performance-based agreements and coverage with evidence development (CED). Service-based agreements have not been as heavily considered so far, yet are increasingly used. Many European countries are turning to CEDs to address uncertainty and facilitate market access while negotiating the pricing and reimbursement rates of products. Despite the interest in CEDs, European countries have moved toward FBAs due to the complexities and burdens associated with PBAs. CONCLUSIONS: Ultimately, in Europe, with the exception of Italy, where MEAs have proven to be inefficient, MEAs are predominantly FBAs dedicated to addressing cost containment from payers' perspective and external reference pricing from the manufacturers' perspective. It has been speculated that MEAs will disappear in the medium-term as they are counterproductive for extending patient access and emergence of innovation. To inform value-based decision making and allow early access to innovative medicines, CEDs should be revisited.

Case-studies of displacement effects in Dutch hospital care.

BACKGROUND: Under a constrained health care budget, cost-increasing technologies may displace funds from existing health services. However, it is unknown what services are displaced and how such displacement takes place in practice. The aim of our study was to investigate how the Dutch hospital sector has dealt with the introduction of cost-increasing health technologies, and to present evidence of the relative importance of three main options to deal with cost-increases in health care: increased spending, increased efficiency, or displacement of other services. METHODS: We conducted six case-studies and interviewed 84 professionals with various roles and responsibilities (practitioners, heads of clinical department, board of directors, insurers, and others) to investigate how they experienced decision making in response to the cost pressure of cost-increasing health technologies. Transcripts were analyzed thematically in Atlas.ti on the basis of an item list. RESULTS: Direct displacement of high-value care due to the introduction of new technologies was not observed; respondents primarily pointed to increased spending and efficiency measures to accommodate the introduction of the cost-increasing technologies. Respondents found it difficult to identify the opportunity costs; partly due to limited transparency in the internal allocation of funds within a hospital. Furthermore, respondents experienced the entry of new technologies and cost-containment as two parallel processes that are generally not causally linked: cost containment was experienced as a permanent issue to level costs and revenues, independent from entry of new technologies. Furthermore, the way of financing was found important in displacement in the Netherlands, especially as there is a separate budget for expensive drugs. This budget pressure was found to be reallocated horizontally across departments, whereas the budget pressure of other services is primarily reallocated vertically within departments or divisions. Respondents noted that hospitals have reacted to budget pressures primarily through a narrowing in the portfolio of their services, and a range of (other) efficiency measures. The board of directors is central in these processes, insurers are involved only to a limited extent. CONCLUSIONS: Our findings indicate that new technologies were generally accommodated by greater efficiency and increased spending, and that hospitals sought savings or efficiency measures in response to cumulative cost pressures rather than in response to single cost-increasing technologies.

The design and development of technology platforms in a developing country healthcare context from an ecosystem perspective.

BACKGROUND: Research on the development and functioning of technology platforms specifically for health applications in sub-Saharan Africa (SSA), is limited. The healthcare sector has also been resistant to platform adoption due to characteristics such as sensitive data and high cost of failure. A framework for the design, development and implementation of technology platforms in the South African health context could therefore contribute to the gap in research as well as provide a practical tool that platform owners could use to potentially increase the adoption of platforms in this context. METHODS: The research design for this study was based on the Grounded Theory Conceptual Framework Analysis process. The process focused on mapping and investigating data sources, categorising and integrating concepts, synthesising these concepts into a framework and iteratively evaluating the framework. The first stage of the evaluation process was a preliminary evaluation exploring an existing Health platform in South Africa (MomConnect). The second evaluation stage included local and international interviews with nine experts to identify any missing concepts in the framework. Stage three included a case study and case study interviews which led to the formulation of the final framework and management tool. RESULTS: The developed and evaluated framework comprised three components, namely the pre-use component, which includes considerations the platform owner should be aware of prior to using the framework. The framework comprises of two dimensions, 1) an ecosystem dimension to guide the platform owner to consider different ecosystem actors before embarking on designing a platform 2) a platform development dimension that include typical platform development components and presents an interpretation of the viewpoints included in the ecosystem levels. CONCLUSIONS: The final framework can be used by platform owners as a management tool. A unique contribution of this study is that the framework draws from two platform perspectives, namely the engineering and the economic perspectives to provide a holistic understanding of platforms. Finally, a contribution of this article is the tailoring of the framework for the South African health context.

A Prototype Framework Design for Assisting the Detection of Atrial Fibrillation Using a Generic Low-Cost Biomedical Sensor.

Cardiovascular diseases are the leading cause of death around the world. As a result, low-cost biomedical sensors have been gaining importance in business and research over the last few decades. Their main benefits include their small size, light weight, portability and low power consumption. Despite these advantages, they are not generally used for clinical monitoring mainly because of their low accuracy in data acquisition. In this emerging technological context, this paper contributes by discussing a methodology to help practitioners build a prototype framework based on a low-cost commercial sensor. The resulting application consists of four modules; namely, a digitalization module whose input is an electrocardiograph signal in portable document format (PDF) or joint photographic expert group format (JPEG), a module to further process and filter the digitalized signal, a selectable data calibration module and, finally, a module implementing a classification algorithm to distinguish between individuals with normal sinus rhythms and those with atrial fibrillation. This last module employs our recently published symbolic recurrence quantification analysis (SRQA) algorithm on a time series of RR intervals. Moreover, we show that the algorithm applies to any biomedical low-cost sensor, achieving good results without requiring.

Divergence and Convergence of Royalty Determinations between Compulsory Licensing under the TRIPS Agreement and Ongoing Royalties as an Equitable Remedy.

Patent rights are recognized as a property asset with an attendant right to exclude. However, recent policy developments highlight that the right to exclude is not inviolable. This paper explores two rapidly evolving exceptions to patent exclusivity, both of which take the form of compulsory licenses. First, under the international Agreement on Trade-Related Aspects of Intellectual Property Rights ("TRIPS"), national governments can compel patent owners to out-license technology in service of greater good. These egalitarian compulsory licenses improve access to technology but undermine patent value. Second, compulsory licenses are increasingly relied upon as an equitable remedy in U.S. patent litigation. Typically referred to as "ongoing royalties," these court-mandated compulsory licenses are a modern alternative to injunctions against adjudged infringers. TRIPS compulsory licenses and ongoing royalties arise under independent legal frameworks, but necessarily invoke parallel economic considerations. While the wisdom of each has been discussed at length by others, this paper explores principles of royalty determination employed in each context. Considering both frameworks, an analysis of where each succeeds and fails is provided, together with an exploration of optimized royalty frameworks.

The Digital Revolution in Behavioral Health.

BACKGROUND: Technology is disrupting every modern industry, from supermarkets to car manufacturing, and is now entering the health care space. Technological innovations in psychiatry include the opportunity for conducting therapy via two-way video conferencing, providing electronic consultations, and telementoring and education of community health care providers. Use of mobile health applications is also an expanding area of interest and promise. OBJECTIVE: The purpose of this article is to review the evolution and pros and cons of technology-enabled health care since the digital movement in psychiatry began more than 50 years ago as well as describe the University of Rochester's innovative digital behavioral health care model. METHODS: A review of the literature and recent reports on innovations in digital behavioral health care was conducted, along with a review of the University of Rochester's model to describe the current state of digital behavioral health care. RESULTS: Given the lack of access to care and mental health professional shortages in many parts of the United States, particularly rural areas, digital behavioral health care will be an increasingly important strategy for managing mental health care needs. However, there are numerous hurdles to be overcome in adopting digital health care, including provider resistance and knowledge gaps, lack of reimbursement parity, restrictive credentialing and privileging, and overregulation at both the state and federal levels. CONCLUSIONS: Digital health innovations are transforming the delivery of mental health care services and psychiatric mental health nurses can be on the forefront of this important digital revolution.

Improving Access to High-Cost Technologies in the Asia Region.

OBJECTIVES: Discussions at the Health Technology Assessment International (HTAi) Asia Policy Forum (HAPF) aimed to understand the meaning of "high-cost technologies," and to explore mechanisms to increase access to these technologies in publicly funded health systems in the Asia region. METHODS: Discussions and presentations at the 2018 HAPF, informed by a literature review and a premeeting survey of HTA agencies and industry, form the basis of this paper. RESULTS: Challenges payers in the public health system face when investing in high-cost technologies include a lack of data, especially real-world data, affordability, and the budgetary impact of high-cost technologies. Managed entry schemes (MES) are one means to enable earlier access to high-cost technologies, or at reduced cost to the system. Most countries surveyed had used an MES to introduce a new health technology and most industry representatives had experience with financial-based MES, such as discounts or rebates, with most put in place to increase access to pharmaceuticals. Little experience of outcome-based or evidence-generation MES was reported. CONCLUSIONS: Although it is early days in the implementation of MES in Asia, they have the potential to play an important role enabling access to new, mainly pharmaceutical, health technologies. The development of a "road map" of MES in the region should outline the intent and need for a MES, articulating the "rules of engagement" for all stakeholders-patients, providers, payers, and industry-which will assist countries to clearly identify the problem trying to be solved, and how an MES can be part of the solution.

Patient willingness to contribute to the cost of novel implants in total joint arthroplasty: the Canadian experience

Background: In Canada, health care is covered by provincial health insurance programs; patients do not directly participate in paying for their acute care expenses. The aim of this study is to assess the willingness of Canadian patients to contribute to the costs of novel total joint arthroplasty implants. Methods: We administered a questionnaire to patients attending an outpatient arthroplasty clinic in Ontario. In the questionnaire, the longevity and risk of complications of a "standard" implant were described. We asked if participants would be willing to contribute to the cost of 3 novel implants that had differing longevities and risks of complications compared with the standard implant. Results: One hundred and fifteen patients completed our questionnaire. Up to 62% of patients were willing to contribute a copayment to get an implant with greater longevity. Willingness to pay decreased to 40% for an implant with greater longevity but an increased risk of complications. Forty percent of participants were willing to pay for an implant with the same longevity as the standard implant but a decreased risk of complications. Participants with a higher income were more willing than other participants to contribute to the cost of a novel implant with greater longevity or lower complication rates. Conclusion: This study demonstrated that up to 62% of our sample of patients in Ontario were willing to share the costs of a novel total joint replacement implant. Willingness to pay was associated with the proposed benefits of the implant and certain patient characteristics. Our study shows that a high proportion of Canadian patients may be willing to copay to have access to new technologies.

Contexte: Au Canada, les soins de santé sont assurés par les régimes provinciaux d'assurance maladie; les patients ne participent pas directement au paiement des soins de santé actifs. Le but de cette étude était de vérifier si les patients canadiens sont prêts à contribuer au paiement de prothèses d'un type nouveau pour les arthroplasties totales. Méthodes: Nous avons administré un questionnaire à des patients d'une clinique externe d'arthroplastie en Ontario. Dans le questionnaire, on décrivait la durée de vie et les risques de complications associés à une prothèse « standard ¼. Nous avons demandé aux participants s'ils étaient ouverts à l'idée de contribuer au paiement de 3 prothèses d'un nouveau type, comportant une durée de vie et des risques de complications différents de ceux de la prothèse standard. Résultats: Cent quinze patients ont répondu à notre questionnaire. Jusqu'à 62 % des patients se sont dits prêts à contribuer à une forme de copaiement pour obtenir une prothèse plus durable. La volonté de payer diminuait à 40 % pour une prothèse plus durable mais comportant plus de risques de complications. Quarante pour cent des participants se sont dits prêts à payer pour une prothèse de même durée de vie que la prothèse standard, mais comportant moins de risques de complications. Les participants ayant un revenu plus élevé étaient davantage disposés à contribuer au paiement d'une prothèse d'un nouveau type plus durable et comportant moins de risques de complications comparativement aux autres participants. Conclusion: Cette étude a démontré que jusqu'à 62 % de notre échantillon de patients ontariens étaient prêts à partager les coûts d'une nouvelle prothèse pour arthroplastie totale. La volonté de payer était associée aux avantages présumés de la prothèse et à certaines caractéristiques des patients. Notre étude montre qu'une forte proportion de patients canadiens seraient prêts à s'engager dans un copaiement pour avoir accès à de nouvelles technologies.

Hard choices: Reflections from the tomb of the unknown patient.

Health Technology Assessment (HTA) has always sought to incorporate the evidence of all patients affected in the decision-making process. While health system budgets could increase to cover costs of new technologies, the relevant patients are those benefitting from access to the technology being appraised. More recently, with health system budgets effectively fixed, costs of new technologies are covered by displacing other, currently funded care. This reallocation means the patients affected by the decision include those whose healthcare is displaced. These patients are typically unidentified, however, and so HTA in this instance involves choosing between identified and unidentified patients. We argue that HTA should take account of identifiability bias in this decision-making, to avoid promoting inequitable and inefficient access to healthcare.

Estimating the value of implementing reimbursement decisions: What can payers and manufacturers learn from economics?

Implementation of reimbursement decisions is important to payers and manufacturers, however, evidence shows that it is highly variable. An economic framework is available to assess its value that has been successfully applied and which has developed over time to produce a more realistic representation of the real world. The framework incorporates the value of information, technology diffusion, and the interaction between the two, to generate a value of implementation. While potentially complex to apply, simple analyses are possible and qualitative lessons identified from its associated literature. Six lessons are identified which highlight the importance of considering pricing, population size, technology diffusion, evidence generation, and cost-effectiveness. Consideration of these issues would help payers and manufacturers to work together in a combined effort to increase the implementation of new technologies and generate greater value to society.

The Use of Technology for Sexually Transmitted Disease Partner Services in the United States: A Structured Review.

BACKGROUND: Since the late 1990s, health departments and sexually transmitted disease (STD) programs throughout the United States have used technologies, such as the Internet and mobile phones, to provide services to persons with a sexually transmitted infection, including human immunodeficiency virus (HIV), and their sex partners, also known as partner services. This study reviewed the published literature to assess and compare partner services outcomes as a result of using technology and to calculate cost savings through cases averted. METHODS: We conducted a structured literature review of all US studies that examined the use of technology to notify persons exposed to an STD (syphilis, chlamydia, gonorrhea), including HIV, by health care professionals in the United States from 2000 to 2017. Outcome measures, including the number of partners notified, screened or tested; and new positives identified, were captured and cost savings were calculated, when data were available. RESULTS: Seven studies were identified. Methods used for partner services differed across studies, although email was the primary mode in 6 (83%) of the 7 studies. Only 2 of the 7 studies compared use of technology for partner services to traditional partner services. Between 10% and 97% of partners were successfully notified of their exposure through the use of technology and between 34% and 81% were screened or tested. Five studies reported on new infections identified, which ranged from 3 to 19. Use of technology for partner serves saved programs between US $22,795 and US $45,362 in direct and indirect medical costs. CONCLUSIONS: Use of technology for partner services increased the number of partners notified, screened or tested, and new infections found. Importantly, the use of technology allowed programs to reach partners who otherwise would not have been notified of their exposure to an STD or HIV. Improved response times and time to treatment were also seen as was re-engagement into care for previous HIV positive patients. Data and outcome measures across the studies were not standardized, making it difficult to generalize conclusions. Although not a replacement for traditional partner services, the use of technology enhances partner service outcomes.

Design and development of low cost polyurethane biopolymer based on castor oil and glycerol for biomedical applications.

In the current study, we present the synthesis of novel low cost bio-polyurethane compositions with variable mechanical properties based on castor oil and glycerol for biomedical applications. A detailed investigation of the physicochemical properties of the polymer was carried out by using mechanical testing, ATR-FTIR, and X-ray photoelectron spectroscopy (XPS). Polymers were also tested in short term in-vitro cell culture with human mesenchymal stem cells to evaluate their biocompatibility for potential applications as biomaterial. FTIR analysis confirmed the synthesis of castor oil and glycerol based PU polymers. FTIR also showed that the addition of glycerol as co-polyol increases crosslinking within the polymer backbone hence enhancing the bulk mechanical properties of the polymer. XPS data showed that glycerol incorporation leads to an enrichment of oxidized organic species on the surface of the polymers. Preliminary investigation into in vitro biocompatibility showed that serum protein adsorption can be controlled by varying the glycerol content with polymer backbone. An alamar blue assay looking at the metabolic activity of the cells indicated that castor oil based PU and its variants containing glycerol are non-toxic to the cells. This study opens an avenue for using low cost bio-polyurethane based on castor oil and glycerol for biomedical applications.