Comparing the prognostic performance of iBOX and biopsy-proven acute rejection for long-term kidney graft survival.

Biopsy-proven acute rejection (BPAR) occurs in approximately 10% of kidney transplant recipients in the first year, making superiority trials unfeasible. iBOX, a quantitative composite of estimated glomerular filtration rate, proteinuria, antihuman leukocyte antigen donor-specific antibody, and + full/- abbreviated kidney histopathology, is a new proposed surrogate endpoint. BPAR's prognostic ability was compared with iBOX in a pooled cohort of 1534 kidney transplant recipients from 4 data sets, including 2 prospective randomized controlled trials. Discrimination analyses showed mean c-statistic differences between both iBOX compared with BPAR of 0.25 (95% confidence interval: 0.17-0.32) for full iBOX and 0.24 (95% confidence interval: 0.16-0.32) for abbreviated iBOX, indicating statistically significantly higher c-statistic values for the iBOX prognosis of death-censored graft survival. Mean (± standard error) c-statistics were 0.81 ± 0.03 for full iBOX, 0.80 ± 0.03 for abbreviated iBOX, and 0.57 ± 0.03 for BPAR. In calibration analyses, predicted graft loss events from both iBOX models were not significantly different from those observed. However, for BPAR, the predicted events were significantly (P < .01) different (observed: 64; predicted: 70; full iBOX: 76; abbreviated iBOX: 173 BPAR). IBOX at 1-year posttransplant is superior to BPAR in the first year posttransplant in graft loss prognostic performance, providing valuable additional information and facilitating the demonstration of superiority of novel immunosuppressive regimens.

Ensuring universal access to quality care for persons with presumed tuberculosis reaching the private sector: lessons from Kerala.

BACKGROUND: More than half of the people with Tuberculosis (TB) symptoms in India seek care from the private sector. People with TB getting treatment from private sector in India are considered to be at a higher risk for receiving suboptimal quality of care in terms of incorrect diagnosis and treatment, lack of treatment adherence support with a high loss to follow-up rate that could eventually increase their risk of drug resistance. The current study aims at documenting the approach and efforts taken by the Kerala state to partner with the private health care delivery providers for ensuring quality TB care to the people with presumed TB reaching them. METHODS: A case study approach was adopted with review of all available literature followed by five Key Informant Interviews to understand the case through a primary descriptive exploration. Grounded theory approach was used to generating the single theory of the case itself that explains it. RESULTS: Kerala state has taken a variety of interventions to ensure universal access to TB care for citizens reaching the private sector with documented improvement in the quality of TB care. Key learnings from these initiatives were (i) patients need to be at the centre of partnerships, (ii) good governance is essential for ensuring Universal Health Coverage in a mixed health system, (iii) data intelligence is required to guide partnerships, (iv) identification of the correct 'problems' is crucial for effective design of partnerships and (v) a platform for meaningful dialogue of key stakeholders is needed. CONCLUSION: Kerala experience demonstrated that if governments take a proactive role in engaging the private sector, in an informed and evidence-based way, they can leverage the advantages of the private sector while protecting the public health interest.

Project-Based Public-Private Collaborations.

Project-based collaborations between a single academic group and a single pharmaceutical company arguably are the most frequent form of public-private partnership in preclinical research and development of new drugs. This chapter discusses the benefits of such collaborations for both sides and potential challenges that can arise before and during the conduct of a project. This is largely based on a survey of expectations and experience by 134 academic investigators with a history of engagement in a project-based collaboration with a pharmaceutical company as well as unstructured experience directly, and learned through discussions with colleagues, from the authors. Obviously, a key benefit for both sides is achieving goals that neither could easily achieve by itself. Scientific discovery, and publications, may be a shared benefit, while for academics, funding and access to compounds, and for industry, access to assay technology and reputational factors may be important. Major hurdles can be freedom to publish and assignment of intellectual property rights. On pragmatic grounds, reaching a contract can be cumbersome, which is largely attributable to the legal expectations and needs of both parties. However, overall satisfaction with project-based collaborations appears very high for academic investigators.

The Alliance Between the German Cancer Research Center and Bayer: A Retrospective of an Innovative Collaboration Model.

In 2009, the German Cancer Research Center (DKFZ) and the biopharmaceutical company Bayer AG initiated an academic-industry co-discovery collaboration. The partners combined their expertise in tumor biology and drug discovery to identify and validate novel targets for cancer treatment. In the early phase of the Alliance, the focus was on target identification and validation projects. Over time, both partners realized that they could also successfully collaborate on later stages of drug discovery. As a result over the past few years, and following several contract extensions, the two partners have collaborated on several late-stage drug discovery projects. This has resulted in the achievement of several drug discovery milestones and the initiation of early clinical trials, the most recent in 2022. This success has been possible thanks to both partners' understanding of each other's needs and challenges. They jointly developed solutions to issues such as the intrinsic potential conflict of early publishing versus patent protection. Both partners also appreciated the risks involved in some of the experiments, such as starting a joint laboratory for immune-therapy with scientists from both parties working bench-to-bench. Recently, despite these successes the partners decided to terminate the Alliance, as Bayer AG wants to focus its activities on the development of its late pipeline.

Novel and Proven Models of Public, Private, and Public-Private Partnerships in Healthcare: An Update.

Initiatives to share assets in the life science sector through dedicated partnerships had and still have a multitude of different aspects in the past few decades. The range goes from industry partners, small and big companies, in bilateral agreements with academic institutions up to large privately and publicly funded consortia. In general, the term public-private partnership (PPP) is used when at least one public (non-profit, academic, and/or government) part and one or more private for-profit partners are involved. A Public-Private Partnership is often driven by a public body, i.e. a ministry or a public agency. Their synergism has been described 10 years ago (Dearing, Science 315(19):344-347, 2007; Casty and Wieman, Ther Innov Regul Sci 47(3):375-383, 2013; Stevens et al., Biotechnol Law Rep 34(4):153-165, 2015). So why view this synergism again today? It will be shown that the situation in life science has changed: novel partners acting digital, data expertise being involved on many levels and novel partnering models arising. Success and challenges will be described in this chapter.

Comparison of the market share of public and private hospitals under different Medical Alliances: an interrupted time-series analysis in rural China.

BACKGROUND: China initiated the Medical Alliances (MAs) reform to enhance resource allocation efficiency and ensure equitable healthcare. In response to challenges posed by the predominance of public hospitals, the reform explores public-private partnerships within the MAs. Notably, private hospitals can now participate as either leading or member institutions. This study aims to evaluate the dynamic shifts in market share between public and private hospitals across diverse MAs models. METHODS: Data spanning April 2017 to March 2019 for Dangyang County's MA and January 2018 to December 2019 for Qianjiang County's MA were analyzed. Interrupted periods occurred in April 2018 and January 2019. Using independent sample t-tests, chi-square tests, and interrupted time series analysis (ITSA), we compared the proportion of hospital revenue, the proportion of visits for treatment, and the average hospitalization days of discharged patients between leading public hospitals and leading private hospitals, as well as between member public hospitals and member private hospitals before and after the reform. RESULTS: After the MAs reform, the revenue proportion decreased for leading public and private hospitals, while member hospitals saw an increase. However, ITSA revealed a notable rise trend in revenue proportion for leading private hospitals (p < 0.001), with a slope of 0.279% per month. Member public and private hospitals experienced decreasing revenue proportions, with outpatient visits proportions declining in member public hospitals by 0.089% per month (p < 0.05) and inpatient admissions proportions dropping in member private hospitals by 0.752% per month (p < 0.001). The average length of stay in member private hospitals increased by 0.321 days per month after the reform (p < 0.01). CONCLUSIONS: This study underscores the imperative to reinforce oversight and constraints on leading hospitals, especially private leading hospitals, to curb the trend of diverting patients from member hospitals. At the same time, for private hospitals that are at a disadvantage in competition and may lead to unreasonable prolongation of hospital stay, this kind of behavior can be avoided by strengthening supervision or granting leadership.

Collaborative governance in a primary health care partnership in Papua New Guinea.

INTRODUCTION: Collaboration in primary health care is recommended to achieve global health goals. Public-private partnerships (PPP) are one means of collaboration. Our study examined collaboration in a case study PPP for primary health care in Western Province, Papua New Guinea (PNG). METHODS: Interviews with key informants involved in the PPP were conducted and key programme documents were reviewed. Data were coded and deductively analysed using the collaborative governance model developed by Emerson, Nabatchi and Balogh. RESULTS: The key features of the case study PPP that were highlighted by the collaborative governance model were: identification of partners, trust, procedural arrangements, and leadership. DISCUSSION: We identified four lessons of significance in the practical establishment and implementation of a partnership in a complex and challenging setting such as PNG: the need to (i) prioritise in-person collaboration and communication, (ii) engage dynamic individuals to lead the partnership, (iii) encourage relationships across all sectors and actors, and (iv) remain flexible and adapt to local cultural and context. CONCLUSION: Collaborative governance offers a practical framework to understand, assess and strengthen collaboration in multi-stakeholder partnerships in the health sector.

[Financial aspects of healthcare development].

The topic of financial support for the development of healthcare is especially relevant today due to the fact that public health is the key to the successful functioning of the state system. The article examines the key areas of health care development and analyzes the expenditures of the budgets of the budgetary system of the Russian Federation on health care. The transformations in the healthcare system are aimed at optimizing the work of medical organizations providing primary health care, forming a system of continuous training of medical personnel and forming criteria for assessing the quality and accessibility of medical care.

[The characteristics of medical technical task working out as a factor of successful implementation of project of public-private partnership in health care].

The application of mathematical modeling approaches based on factual demand of the population of territories in setting of medical and technical tasks makes it possible to significantly optimize costs of construction and equipping primary health care objects. This is confirmed by both corresponding calculations and results of analysis. This operation is oriented both on structural divisions of regional executive authorities responsible for setting of medical and technical tasks, and on investment companies implementing projects in health care.

Qualifying a novel clinical trial endpoint (iBOX) predictive of long-term kidney transplant outcomes.

New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute's Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency's qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials. Although the current efficacy failure endpoint has typically shown the noninferiority of therapeutic regimens, the iBOX Scoring System can be used to demonstrate the superiority of a new immunosuppressive therapy compared to the standard of care from 6 months to 24 months posttransplant in pivotal or exploratory drug therapeutic studies.

Mobilizing Patient and Public Involvement in the Development of Real-World Digital Technology Solutions: Tutorial.

Although the value of patient and public involvement and engagement (PPIE) activities in the development of new interventions and tools is well known, little guidance exists on how to perform these activities in a meaningful way. This is particularly true within large research consortia that target multiple objectives, include multiple patient groups, and work across many countries. Without clear guidance, there is a risk that PPIE may not capture patient opinions and needs correctly, thereby reducing the usefulness and effectiveness of new tools. Mobilise-D is an example of a large research consortium that aims to develop new digital outcome measures for real-world walking in 4 patient cohorts. Mobility is an important indicator of physical health. As such, there is potential clinical value in being able to accurately measure a person's mobility in their daily life environment to help researchers and clinicians better track changes and patterns in a person's daily life and activities. To achieve this, there is a need to create new ways of measuring walking. Recent advancements in digital technology help researchers meet this need. However, before any new measure can be used, researchers, health care professionals, and regulators need to know that the digital method is accurate and both accepted by and produces meaningful outcomes for patients and clinicians. Therefore, this paper outlines how PPIE structures were developed in the Mobilise-D consortium, providing details about the steps taken to implement PPIE, the experiences PPIE contributors had within this process, the lessons learned from the experiences, and recommendations for others who may want to do similar work in the future. The work outlined in this paper provided the Mobilise-D consortium with a foundation from which future PPIE tasks can be created and managed with clearly defined collaboration between researchers and patient representatives across Europe. This paper provides guidance on the work required to set up PPIE structures within a large consortium to promote and support the creation of meaningful and efficient PPIE related to the development of digital mobility outcomes.

Addressing immediate public health needs as part of Afghan evacuees' resettlement to the United States during the COVID-19 pandemic.

OBJECTIVES: Since the removal of US troops from Afghanistan in 2021, the United States welcomed Afghan evacuees through Operation Allies Welcome. Using cell phone accessibility, the CDC Foundation worked with public-private partners to protect evacuees from the spread of COVID-19 and provide accessibility to resources. STUDY DESIGN: This was a mixed methods study. METHODS: The CDC Foundation activated its Emergency Response Fund to accelerate public health components of Operation Allies Welcome, including testing, vaccination, and COVID-19 mitigation and prevention. The CDC Foundation began the provision of cell phones to evacuees to ensure access to public health and resettlement resources. RESULTS: The provision of cell phones provided connections between individuals and access to public health resources. Cell phones provided means to supplement in-person health education sessions, capture and store medical records, maintain official resettlement documents, and assist in registration for state-administered benefits. CONCLUSIONS: Phones provided necessary connectivity to friends and family for displaced Afghan evacuees and higher accessibility to public health and resettlement resources. As many evacuees did not have access to US-based phone services upon entry, provision of cell phones and plans for a fixed amount of service time provided a helpful start in resettlement while also being a mechanism to easily share resources. Such connectivity solutions helped to minimize disparities among Afghan evacuees seeking asylum in the United States. Provision of cell phones by public health or governmental agencies can help to provide equitable resources to evacuees entering the United States for social connection, healthcare resources, and resources to assist in the process of resettlement. Further research is needed to understand the generalizability of these findings to other displaced populations.

An intra-action review conducted by the CDC Foundation during COVID-19 to evaluate emergency response procedures.

OBJECTIVES: During times of emergency response, the CDC Foundation leverages partnerships and relationships to better understand the situation and respond rapidly to save lives. As the COVID-19 pandemic began to unfold, an opportunity became clear to improve our work in emergency response through documentation of lessons learned and incorporating them into best practices. STUDY DESIGN: This was a mixed methods study. METHODS: The CDC Foundation Response, Crisis and Preparedness Unit conducted an internal evaluation via an intra-action review to evaluate and rapidly improve emergency response activities to provide effective and efficient response-related program management. RESULTS: The processes developed during the COVID-19 response to conduct timely and actionable reviews of the CDC Foundation's operations led to the identification of gaps in the work and management processes and to creation of subsequent actions to address these issues. Such solutions include surge hiring, establishing standard operating procedures for processes not yet documented, and creating tools and templates to streamline emergency response operations. CONCLUSIONS: The creation of manuals and handbooks, intra-action reviews, and impact sharing for emergency response projects led to actionable items meant to improve processes and procedures and the ability of the Response, Crisis and Preparedness Unit to quickly mobilize resources directed toward saving lives. These products are now open-source resources that can be used by other organizations to improve their own emergency response management systems.

Effects of public-private partnership on diet-related obesity risk factors among school-aged children: A systematic literature review.

Background: Childhood obesity is a major public health challenge. Public-private partnerships (PPPs) have been proposed as a solution; however, valid concerns exist as to whether commercial interest can be balanced with public health goals. Aims: This study describes the effects of interventions carried out through PPPs on diet-related obesity risk factors, namely fruit and vegetable (F&V), sugar-sweetened beverage (SSB), and energy-dense food consumption, among school-aged children. Methods: A systematic literature review was conducted from January 1990 to December 2021 across three databases. Out of the 276 articles initially identified, 8 were included. Data were extracted from each article on study characteristics, partners involved, partnership descriptions, and partnership outcomes. A descriptive analysis included frequency counts for specific study attributes. Results: All studies took place in the United States and were published between 2010 and 2017. Most were cohort studies (75%) and involved structured, healthy lifestyle interventions (75%). Nearly all interventions included components targeting F&V consumption (88%), followed by energy-dense food consumption (50%), and SSB consumption (38%). Business sector partners were largely food producers, food retailers, and private healthcare providers; however, few studies provided details on their partnering arrangements. No studies reported harmful changes in diet-related obesity risk factors. Conclusion: Collaboration across sectors is needed to address drivers of obesity where children live, learn, and play. The small sample size and heterogeneity in this review prohibits definitive conclusions pertaining to the effect of PPPs on childhood obesity. Future research efforts are needed to develop a taxonomy for better classifying and examining PPPs.

A selectivity index for public-private partnership projects in the urban water and sanitation sector in Latin America and the caribbean.

The rapid urban development, the Agenda 2030, the climate change adaptation and the COVID 19 crisis highlight the need to increase investment in public infrastructure and improve water supply and sanitation services. For this, an alternative to traditional public procurement is the participation of the private sector under the public-private partnership (PPP) model. The objective of this article is to develop a tool based on critical success factors (CSFs) that allows for evaluation during early stages of the convenience of developing a PPP project for W&S in urban areas of Latin America and the Caribbean. The index was developed based on literature review (779 variables), review of cases (20 variables) and expert opinion to assign them an estimated value of importance. The results were analysed by exploratory and confirmatory factor analysis, selecting 17 main variables grouped into 6 CSFs, the most relevant of which are Convenience, Certainty, Leadership, Attraction, Performance and Reliability. The application of this index allows an early assessment of the feasibility of a PPP project and/or the selection of the alternatives with the best chances of success. On the other hand, this study contributes to the international discussion on the most relevant elements related to the success of PPP in W&S projects.

The possibilities and limits of insurance as governance in insuring pandemics.

Insurance can, as has clearly been indicated in the literature, play an important role in dealing with catastrophe risks, not only as a compensation mechanism but also as a mechanism to influence the behaviour of the insured. It is the concept known as 'insurance as governance'. However, we argue that there are limited possibilities for this role as far as the insurance of pandemics is concerned. The traditional technical tools, such as risk-based pricing, are difficult to apply. In addition, there may, ab initio, be serious problems in insuring pandemics within one of the main conditions of insurability (controlling moral hazard through an effective risk differentiation). One remedy that is traditionally applied, more particularly for natural catastrophes, is mandatory coverage. Furthermore, the capacity problem might potentially be solved through a multilayered approach in which, in addition to insurance and reinsurance, the government could also take up a role as reinsurer of last resort. That would also have the major advantage of stimulating market solution (and potentially providing incentives for the mitigation of damages), which clearly fails in a model where the government simply bails out operators. Finally, one important regulatory intervention is that insurers should be better informed than was apparently the case during the last pandemic about exactly which type of risks are covered and which are not.

[The modern mechanisms of integration of medical organizations in health care system].

The article considers mechanisms of cooperation of medical organizations of various forms of property, intersectoral interaction with purpose to unify resources of organizations to resolve established tasks, to form large medical clusters and to organize interaction of medical organizations with recreation structures. The actuality of issue is conditioned by the fact that population health is the most important value of society. This value is ultimate condition of prosperity and well-being of any state and depends on quality of medical care and efficiency of functioning of medical care system. In many countries occurs search for new mechanisms permitting to increase quality of medical care and its accessibility. The issues of interaction private sector with state system of financing of health care and state medical organizations, including development of integration mechanisms in health care system with private medicine potentials to update health care system is agenda priority. The purpose of the study is to consider modern mechanisms of integration of organizations in health care system and practical involvement into action.

[MODERN TRENDS IN IMMUNOPROPHYLAXIS (ANALYSIS OF FOREIGN EXPERIENCE)].

Currently, immunoporphylaxis reaches the population through information support, mass vaccination sites and the system of monitoring warning. The capabilities of information technologies have made it possible to monitor the patient's health at all stages of life, regardless of the place of medical care delivery (including vaccination). The use of mathematical modeling technologies coupled with the queueing theory made it possible to develop an optimum location scheme of vaccination sites. Organization of the work of vaccination centers considered the need to optimize travel arrangements of the recipients and operating costs. The integration with geographic information systems contributes to the adequate distribution of vaccination centers in densely populated areas. The availability of information support made it possible to create the following innovative vaccination solutions: "get a vaccine without ever leaving your car" (with prior registration on the website), vaccination at pharmacies (with the subsequent data transfer to the cloud storage), deployment of vaccination sites at sports and religious facilities. Compact mobile vaccination sites have proven their effectiveness in both sparsely populated areas and in places with a high throughput. Effective performance of mass vaccination centers is impossible without the use of effective information and communication technologies. The systems ensure interaction between the patient, medical professionals and software that allows you to write, read or update in real time the database located in the data storage center. The information technologies of vaccination have made it possible to create a system for continuous support of immunoprophylaxis.

Postauthorization safety study of betaine anhydrous.

Patient registries for rare diseases enable systematic data collection and can also be used to facilitate postauthorization safety studies (PASS) for orphan drugs. This study evaluates the PASS for betaine anhydrous (Cystadane), conducted as public private partnership (PPP) between the European network and registry for homocystinurias and methylation defects and the marketing authorization holder (MAH). Data were prospectively collected, 2013-2016, in a noninterventional, international, multicenter, registry study. Putative adverse and severe adverse events were reported to the MAH's pharmacovigilance. In total, 130 individuals with vitamin B6 nonresponsive (N = 54) and partially responsive (N = 7) cystathionine beta-synthase (CBS) deficiency, as well as 5,10-methylenetetrahydrofolate reductase (MTHFR; N = 21) deficiency and cobalamin C (N = 48) disease were included. Median (range) duration of treatment with betaine anhydrous was 6.8 (0-9.8) years. The prescribed betaine dose exceeded the recommended maximum (6 g/day) in 49% of individuals older than 10 years because of continued dose adaptation to weight; however, with disease-specific differences (minimum: 31% in B6 nonresponsive CBS deficiency, maximum: 67% in MTHFR deficiency). Despite dose escalation no new or potential risk was identified. Combined disease-specific treatment decreased mean ± SD total plasma homocysteine concentrations from 203 ± 116 to 81 ± 51 µmol/L (p < 0.0001), except in MTHFR deficiency. Recommendations for betaine anhydrous dosage were revised for individuals ≥ 10 years. PPPs between MAH and international scientific consortia can be considered a reliable model for implementing a PASS, reutilizing well-established structures and avoiding data duplication and fragmentation.

COVAX, vaccine donations and the politics of global vaccine inequity.

BACKGROUND: In 2021, donor countries, the pharmaceutical industry, and the COVAX initiative promoted vaccine donation or "dose-sharing" as a main solution to the inequitable global distribution of Covid-19 vaccines. COVAX positioned itself as a global vaccine-sharing hub that promised to share doses "equitably, effectively and transparently," according to rational criteria overseen by independent scientists. This article provides a critical analysis of the principles and practice of "dose-sharing," showing how it reveals the politics at play within COVAX. RESULTS: Donated doses were an important source of COVAX's vaccine supply in 2021, accounting for 60% of the doses the initiative delivered (543 million out of 910 million). However, donations could not compensate fully for COVAX's persistent procurement struggles: it delivered less than half of the two billion doses it originally projected for 2021, a fraction of the 9.25 billion doses that were administered globally in 2021. Donor countries and vaccine manufacturers systematically broke COVAX's principles for maximizing the impact of dose-sharing, delivering doses late, in smaller quantities than promised, and in ad hoc ways that made roll-out in recipient countries difficult. Some donors even earmarked doses for specific recipients, complicating and potentially undermining COVAX's equitable allocation mechanism. CONCLUSIONS: COVAX's pivot from global vaccine procurement mechanism to dose-sharing hub can be seen as a "win-win-win" solution for COVAX itself (who could claim success by having access to more doses), for donor countries (who could rebrand themselves as charitable donors rather than "vaccine hoarders"), and for the pharmaceutical industry (maintaining the status quo on intellectual property rights and protecting their commercial interests). Although dose-sharing helped COVAX's vaccine delivery, its impact was undermined by donors' and industry's pursuit of national security, diplomatic and commercial interests, which COVAX largely accommodated. The lack of transparency and accountability mechanisms within COVAX's overly complex governance structure as a global public-private partnership enabled these practices.