Why Stating Hypotheses in Grant Applications Is Unnecessary.

This Viewpoint argues that a hypothesis-centric approach to writing grant applications is problematic and instead suggests that funding applications should be evaluated by their relevance and methodological quality rather than by qualitative assertions before the study is conducted.

The 'Netflix plus model': can subscription financing improve access to medicines in low- and middle-income countries?

At present, pay for prescription models are insufficient at containing costs and improving access to medicines. Subscription financing through tenders, licensing fees and unrestricted or fixed volumes can benefit stakeholders across the supply chain. Pharmaceutical manufacturers can reduce the need for marketing expenses and gain certainty in revenue. This will decrease costs, improve predictability in budget expenditure for payers and remove price as a barrier of access from patients. Inherently, low- and middle-income countries lack the purchasing power to leverage price discounts through typical price arrangements. These markets can realise substantial savings for branded and generic medicines through subscription financing. Procuring of on-patent and off-patent drugs requires separate analysis for competition effects, the length of contract and encouraging innovation in the medicine pipeline. Prices of competitive on-patent medicines and orphan drugs can be reduced through increased competition and volume. Furthermore, pooling expertise and resources through joint procurement has the potential for greater savings. Incentivising research and development within the pharmaceutical industry is essential for sustaining a competitive market, preventing monopolies and improving access to expensive treatments. However, technical capacity, forecasting demand and the quality of generic medicines present limitations which necessitate government support and international partnerships. Ultimately, improving access requires progressive financing mechanisms with patients and cost containment in mind.

Opportunities for Gene and Environment Research in Cancer: An Updated Review of NCI's Extramural Grant Portfolio.

BACKGROUND: The study of gene-environment (GxE) interactions is a research priority for the NCI. Previously, our group analyzed NCI's extramural grant portfolio from fiscal years (FY) 2007 to 2009 to determine the state of the science in GxE research. This study builds upon our previous effort and examines changes in the landscape of GxE cancer research funded by NCI. METHODS: The NCI grant portfolio was examined from FY 2010 to 2018 using the iSearch application. A time-trend analysis was conducted to explore changes over the study interval. RESULTS: A total of 107 grants met the search criteria and were abstracted. The most common cancer types studied were breast (19.6%) and colorectal (18.7%). Most grants focused on GxE using specific candidate genes (69.2%) compared with agnostic approaches using genome-wide (26.2%) or whole-exome/whole-genome next-generation sequencing (NGS) approaches (19.6%); some grants used more than one approach to assess genetic variation. More funded grants incorporated NGS technologies in FY 2016-2018 compared with prior FYs. Environmental exposures most commonly examined were energy balance (46.7%) and drugs/treatment (40.2%). Over the time interval, we observed a decrease in energy balance applications with a concurrent increase in drug/treatment applications. CONCLUSIONS: Research in GxE interactions has continued to concentrate on common cancers, while there have been some shifts in focus of genetic and environmental exposures. Opportunities exist to study less common cancers, apply new technologies, and increase racial/ethnic diversity. IMPACT: This analysis of NCI's extramural grant portfolio updates previous efforts and provides a review of NCI grant support for GxE research.

Health Literacy Research Funded by the NIH for Disease Prevention.

BACKGROUND: Advancing health literacy is a fundamental step toward achieving population health. To that end, the National Institutes of Health (NIH) funded research to increase scientific understanding of how health literacy can reduce disparities and enhance the health of the United States. OBJECTIVE: This study identified and evaluated NIH-funded health literacy research focusing on disease prevention. METHODS: New R01, R03, and R21 research project grants awarded from fiscal year (FY) 2004 to FY 2017 studying health literacy and disease prevention were identified. Study characteristics, including the role of health literacy, how health literacy was measured, populations studied, and study design, were coded for each grant. Administrative grant data were obtained from the NIH's internal database. Research impact was assessed using the relative citation ratio (RCR). KEY RESULTS: There were 192 grants studying health literacy and disease prevention awarded by 18 NIH institutes and centers from FY 2004 to FY 2017, covering a wide variety of health conditions including cancer (26.0%), infectious diseases (13.5%), nutrition (8.3%), drug/alcohol use (7.8%), and cardiovascular disease (6.3%). Most grants studied the health literacy skills of patients (88%), with a few studies assessing the health literacy practices of health care providers (2.1%) or systems (1%). There was good representation of populations with traditionally low levels of health literacy, including Black/African American participants (30.2%), Hispanic/Latinx participants (28.6%), older adults (37%), and people with low income (20.8%). The scientific articles generated by these grants were more than twice (RCR = 2.18) as influential on the field as similar articles. CONCLUSIONS: The NIH provided support for a wide array of prevention-focused health literacy research. The value of this research is highlighted by the number of funding institutes and centers, the diversity of populations and health conditions studied, and the effect these grants had on the field. Future research should move beyond patient-level health literacy to health literacy practices of health care systems and providers. [HLRP: Health Literacy Research and Practice. 2020, 4(4):e212-e223.] PLAIN LANGUAGE SUMMARY: This study describes health literacy research funded by the National Institutes of Health that focused on disease prevention. These grants sought to prevent a variety of health conditions, but health literacy research over the past 14 years continued to concentrate on the capacity of patients despite increased attention on the health literacy practices of health care providers and systems.

Mapping the coevolution, leadership and financing of research on viral vectors, RNAi, CRISPR/Cas9 and other genomic editing technologies.

Genomic editing technologies are developing rapidly, promising significant developments for biomedicine, agriculture and other fields. In the present investigation, we analyzed and compared the process of innovation for six genomic technologies: viral vectors, RNAi, TALENs, meganucleases, ZFNs and CRISPR/Cas including the profile of the main research institutions and their funders, to understand how innovation evolved and what institutions influenced research trajectories. A Web of Science search of papers on viral vectors RNAi, CRISPR/Cas, TALENs, ZFNs and meganucleases was used to build a citation network of 16,746 papers. An analysis of network clustering combined with text mining was performed. For viral vectors, a long-term process of incremental innovation was identified, which was largely publicly funded in the United States and the European Union. The trajectory of RNAi research included clusters related to the study of RNAi as a biological phenomenon and its use in functional genomics, biomedicine and pest control. A British philanthropic organization and a US pharmaceutical company played a key role in the development of basic RNAi research and clinical application respectively, in addition to government and academic institutions. In the case of CRISPR/Cas research, basic science discoveries led to the technical improvements, and these two in turn provided the information required for the development of biomedical, agricultural, livestock and industrial applications. The trajectory of CRISPR/Cas research exhibits a geopolitical division of the investigation efforts between the US, as the main producer and funder of basic research and technical improvements, and Chinese research institutions increasingly leading applied research. Our results reflect a change in the model for financing science, with reduced public financing for basic science and applied research on publicly funded technological developments in the US, and the emergence of China as a scientific superpower, with implications for the development of applications of genomic technologies.

Assessing health research grant applications: A retrospective comparative review of a one-stage versus a two-stage application assessment process.

BACKGROUND: Research funders use a wide variety of application assessment processes yet there is little evidence on their relative advantages and disadvantages. A broad distinction can be made between processes with a single stage assessment of full proposals and those that first invite an outline, with full proposals invited at a second stage only for those which are shortlisted. This paper examines the effects of changing from a one-stage to a two-stage process within the UK's National Institute for Health Research's (NIHR) Research for Patient Benefit (RfPB) Programme which made this change in 2015. METHODS: A retrospective comparative design was used to compare eight one-stage funding competitions (912 applications) with eight two-stage funding competitions (1090 applications). Comparisons were made between the number of applications submitted, number of peer and lay reviews required, the duration of the funding round, average external peer review scores, and the total costs involved. RESULTS: There was a mean number of 114 applications per funding round for the one-stage process and 136 for the two-stage process. The one-stage process took a mean of 274 days and the two-stage process 348 days to complete, although those who were not funded (i.e. the majority) were informed at a mean of 195 days (mean 79 days earlier) under the two-stage process. The mean peer review score for full applications using the one-stage process was 6.46 and for the two-stage process 6.82 (5.6% difference using a 1-10 scale (with 10 being the highest), but there was no significant difference between the lay reviewer scores. The one-stage process required a mean of 423 peer reviews and 102 lay reviewers and the two-stage process required a mean of 208 peer reviews and 50 lay reviews (mean difference of 215 peer reviews and 52 lay reviews) per funding round. Overall cost per funding round changed from £148,908 for the one-stage process to £105,342 for the two-stage process saving approximately £43,566 per round. CONCLUSION: We conclude that a two-stage application process increases the number of applications submitted to a funding round, is less burdensome and more efficient for all those involved with the process, is cost effective and has a small increase in peer reviewer scores. For the addition of fewer than 11 weeks to the process substantial efficiencies are gained which benefit funders, applicants and science. Funding agencies should consider adopting a two-stage application assessment process.

Distributing Local Resources for Public Health Preparedness Grants: A Data-Driven Approach.

OBJECTIVES: To simulate allocations of Public Health Emergency Preparedness funds to counties using alternative metrics of need, minimum allocation amounts, and the proportion earmarked for discretionary considerations. DESIGN: We developed a county-level community resilience index of 57 New York State counties using publicly available indicators, which we incorporated into an interactive spreadsheet of 8 hypothetical allocation formulas with different combinations of population size, the index and its 5 domains, and population density. Simulations were compared with the 2013-2014 fiscal year grant allocation. RESULTS: New York allocated $6.27 million to counties outside New York City, with a median allocation of $78 038, ranging from $50 825 to $556 789. These allocations would vary under different strategies, with the largest changes among sparsely populated counties that currently receive a minimum allocation of $50 825. Allocations were sensitive to changes in minimum allocation, amount earmarked for discretionary allocation, and need indicator. CONCLUSIONS: Population-based approaches are commonly used but ignore important dimensions of need. It is feasible to include robust local community resilience measures in formulas, and interactive spreadsheet models can help stakeholders evaluate the consequences of alternative funding strategies.

Multidisciplinary Team Reviews of Drug Overdose Deaths and the Use of Minigrants to Advance Recommendations: A Statewide Pilot in Rhode Island.

CONTEXT: Rhode Island has been significantly impacted by the opioid epidemic, ranking 11th in unintentional drug overdose rates in the United States in 2017. Illicit fentanyl was involved in the majority of these deaths. PROGRAM: To enhance surveillance of this epidemic, the RI Department of Health piloted in-depth, multidisciplinary, and multiagency team reviews of drug overdose deaths. The goals were to identify gaps in policies and programming and develop recommendations to prevent future deaths. Time-sensitive minigrants were offered to nonprofit organizations as a novel way to further the recommendations put forth from these reviews. IMPLEMENTATION: Legal agreements between select state agencies and institutions enabled broad team representation and the sharing of information during each meeting. Reviews, revolving around a common theme, were conducted for up to 10 deaths each quarter. Recommendations for prevention were generated by the team and summarized in a report to the Governor's Overdose Prevention and Intervention Task Force and the public within 1 month of each meeting. Announcements of minigrant opportunities and funding to advance the community-specific recommendations were paired with each meeting. EVALUATION: From November 2016 through May 2018, the pilot team convened 7 times, generated 78 recommendations, and distributed 31 minigrants. Early process evaluations of these grants have shown positive impact within local environments. Following the pilot phase, state legislation for these reviews was passed in June 2018. DISCUSSION: The RI Department of Health was able to successfully pilot a multidisciplinary review process for overdose deaths and has recently institutionalized this process through legislation. The successful implementation of many of the team's community-oriented recommendations, supported through a minigrant process, highlights the impact that small financial investments can have to address the opioid epidemic and may be a model for other jurisdictions seeking to advance recommendations from these types of reviews.

Financing Global Common Goods for Health: When the World is a Country.

"Global functions" of health cooperation refer to those activities that go beyond the boundaries of individual nations to address transnational issues. This paper begins by presenting a taxonomy of global functions and laying out the key value propositions of investing in such functions. Next, it examines the current funding flows to global functions and the estimated price tag, which is large. Given that existing financing mechanisms have not closed the gap, it then proposes a suite of options for directing additional funding to global functions and discusses the governance of this additional funding. These options are organized into resource mobilization mechanisms, pooling approaches, and strategic purchasing of global functions. Given its legitimacy, convening power, and role in setting global norms and standards, the World Health Organization (WHO) is uniquely placed among global health organizations to provide the overarching governance of global functions. Therefore, the paper includes an assessment of WHO's financial situation. Finally, the paper concludes with reflections on the future of aid for health and its role in supporting global functions. The concluding section also summarizes a set of key priorities in financing global functions for health.

Evolución e impacto bibliométrico de las becas de la Sociedad Española de Cardiología/Fundación Española del Corazón en el periodo 2007-2012 / Trends and bibliometric impact of research grants of the Spanish Society of Cardiology/Spanish Heart Foundation (2007-2012)

Introducción y objetivos: La Sociedad Española de Cardiología/Fundación Española del Corazón (SEC/FEC) realiza convocatorias anuales de becas para proyectos de investigación cardiovascular. El objetivo es analizar la evolución de estas inversiones y la producción científica derivada en el periodo 2007-2012. Métodos: Se ha realizado una búsqueda de las publicaciones financiadas por SEC/FEC, según los siguientes criterios de inclusión: publicación en revista indexada en MEDLINE o EMBASE, fecha de publicación posterior a la de la ayuda, estar firmadas por el investigador principal de la ayuda y reconocer la financiación SEC/FEC. Se analizó el factor impacto y las citas posteriores de los artículos (Web of Science). Resultados: Se han otorgado 235 becas (39/año) con una dotación de 3.854.300 euros (642.383 euros/año), el 37% a mujeres. Hay 122 publicaciones derivadas de 88 proyectos (37%) de investigación financiados SEC/FEC. Estas publicaciones han recibido hasta octubre de 2017 un total de 2.258 citas en estudios posteriores en la Web of Science, con una media de 18,5 y una mediana de 8 citas/estudio. Conclusiones: Las becas concedidas por la SEC/FEC han crecido en número y cuantía media en el periodo analizado, a pesar de la crisis económica. Las mujeres acceden a ellas en igualdad de condiciones que los varones. El impacto bibliométrico de los proyectos financiados es aceptable, aunque deben hacerse esfuerzos para mejorarlo

Introduction and objectives: The Spanish Society of Cardiology/Spanish Heart Foundation (SEC/FEC) annually awards grants for cardiovascular research projects. Our objective was to analyze the trend in these investments and their resulting scientific production from 2007 to 2012. Methods: A search of the publications funded by the SEC/FEC was carried out, according to the following inclusion criteria: publication in a journal indexed in MEDLINE or EMBASE, publication date after the grant, authorship by the principal investigator of the grant, and acknowledgment of SEC/FEC funding. The impact factor and subsequent citations of the articles were analyzed (Web of Science). Results: A total of 235 grants were awarded (39/y) with an allocation of €3 854 300 (€642 383/y), 37% of them to women. In all, 122 publications resulted from 88 research projects (37%) funded by the SEC/FEC. Up to October 2017, these publications had received 2258 citations in subsequent studies in the Web of Science, with a mean of 18.5 and a median of 8 citations/study. Conclusions: Despite the economic crisis, the mean number and size of the grants awarded by the SEC/FEC increased in the period analyzed. Grants were awarded on an equal opportunity basis to men and women. The bibliometric impact of the funded projects is acceptable, although efforts should be made to improve it

Optimal allocation of HIV resources among geographical regions.

BACKGROUND: Health resources are limited, which means spending should be focused on the people, places and programs that matter most. Choosing the mix of programs to maximize a health outcome is termed allocative efficiency. Here, we extend the methodology of allocative efficiency to answer the question of how resources should be distributed among different geographic regions. METHODS: We describe a novel geographical optimization algorithm, which has been implemented as an extension to the Optima HIV model. This algorithm identifies an optimal funding of services and programs across regions, such as multiple countries or multiple districts within a country. The algorithm consists of three steps: (1) calibrating the model to each region, (2) determining the optimal allocation for each region across a range of different budget levels, and (3) finding the budget level in each region that minimizes the outcome (such as reducing new HIV infections and/or HIV-related deaths), subject to the constraint of fixed total budget across all regions. As a case study, we applied this method to determine an illustrative allocation of HIV program funding across three representative oblasts (regions) in Ukraine (Mykolayiv, Poltava, and Zhytomyr) to minimize the number of new HIV infections. RESULTS: Geographical optimization was found to identify solutions with better outcomes than would be possible by considering region-specific allocations alone. In the case of Ukraine, prior to optimization (i.e. with status quo spending), a total of 244,000 HIV-related disability-adjusted life years (DALYs) were estimated to occur from 2016 to 2030 across the three oblasts. With optimization within (but not between) oblasts, this was estimated to be reduced to 181,000. With geographical optimization (i.e., allowing reallocation of funds between oblasts), this was estimated to be further reduced to 173,000. CONCLUSIONS: With the increasing availability of region- and even facility-level data, geographical optimization is likely to play an increasingly important role in health economic decision making. Although the largest gains are typically due to reallocating resources to the most effective interventions, especially treatment, further gains can be achieved by optimally reallocating resources between regions. Finally, the methods described here are not restricted to geographical optimization, and can be applied to other problems where competing resources need to be allocated with constraints, such as between diseases.

International Funding for Global Common Goods for Health: An Analysis Using the Creditor Reporting System and G-FINDER Databases.

West Africa's Ebola epidemic of 2014-2016 exposed, among other problems, the under-funding of transnational global health activities known as global common goods for health (CGH), global functions such as pandemic preparedness and research and development (R&D) for neglected diseases. To mobilize sustainable funding for global CGH, it is critical first to understand existing financing flowing to different types of global CGH. In this study, we estimate trends in international spending for global CGH in 2013, 2015, and 2017, encompassing the era before and after the Ebola epidemic. We use a measure of international funding that combines official development assistance (ODA) for health with additional international spending on R&D for diseases of poverty, a measure called ODA+. We classify ODA+ into funding for three global functions-provision of global public goods, management of cross-border externalities, and fostering of global health leadership and stewardship-and country-specific aid. International funding for global functions increased between 2013 and 2015 by $1.4 billion to a total of $7.3 billion in 2015. It then declined to $7.0 billion in 2017, accounting for 24% of all ODA+ in 2017. These findings provide empirical evidence of the reactive nature of international funders for global CGH. While international funders increased funding for global functions in response to the Ebola outbreak, they failed to sustain that funding. To meet future global health challenges proactively, international funders should allocate more funding for global functions.

The Potential of Pay-for-Success as a Financing Strategy for Evidence-Based Practices: An Illustration with Multisystemic Therapy.

There is a critical need to identify strategies for financing the implementation of evidence-based practices. We illustrate the potential of pay-for-success financing (PFS)-a strategy in which private investors fund implementation and receive a return on investment from a government payer-using multisystemic therapy as an example. We argue that standard multisystemic therapy (for serious juvenile offenders) and several of its adaptations (for other complex behavioral problems in youth) would be good candidates for PFS in the right contexts. Despite some challenges for policymakers and administrators, PFS has significant potential as a financing strategy for evidence-based practices.

Impact of in vitro fertilization-preimplantation genetic testing (IVF-PGT) funding policy on clinical outcome: An issue that stems beyond effectiveness of treatment.

OBJECTIVE(S): The aim of this study was to compare the patient characteristics, type of genetic disease and inheritance, volume of activity, practice patterns and pregnancy outcomes, in private versus publically funded IVF pre-implantation genetic testing (PGT) for translocation (IVF-PGT-SR) and aneuploidy (PGT-A) periods. STUDY DESIGN: This study retrospectively analyzed data during both privately funded period (PRP) and publically funded period (PUP) of assisted reproductive technology (ART) for a total of 275 patients. 83 patients underwent IVF-PGT-SR and 192 patients underwent IVF-PGT-A. Given that PGT-SR is a chromosomal abnormality hereditary in nature, whereas PGT-A is sporadic in addition to the contrasting funding policies, the two cohorts were analyzed separately. To achieve the proposed objective, the two groups under analysis were grouped in accordance with their respective coverage systems for infertility. RESULTS: Among translocation patients, 94 normal/balanced embryos were obtained from 47 IVF-PGT cycles in PRP whereas 145 embryos were obtained from 92 IVF-PGT cycles in PUP. The average number of embryos transferred per embryo transfer cycle was significantly lower in PUP in comparison to PRP (1.13 vs. 1.74, p < 0.0001). 13 singletons and 2 sets of twins were conceived in PRP. 14 singletons were conceived in PUP. Regardless of funding period, there were more reciprocal translocation carriers (79.4% in PRP and 76.4% in PUP) and more male carriers (82.4% in PRP and 60% in PUP), of which the majority had abnormal sperm parameters. Among aneuploidy patients, on average 2.5 embryos in PRP and 1.4 embryos in PUP were transferred per ET cycle (p = 0.05). There was a 13.3% increase in number of IVF-PGT-A attempts per patient in PRP compared to PUP. Live birth rate per IVF-PGT-A was higher in PRP (29.7% vs. 15%, P = 0.02), which consisted of 48 singletons and 18 multiparous pregnancies in PRP and 9 singletons in PUP. CONCLUSION(S): Public coverage of ART is associated with a greater utilization ART, as well as a reduced number in embryo transfer (ET) per cycle, a lower proportion of cycles resulting in successful pregnancy and a lower multiple birth rate. Our study ultimately shines light on the effect of providers' and patients' monetary conscious on pregnancy outcome.

CEO-CLER Innovation Grants Program: Empowering Residents as Clinical Learning Environment Change Agents.

BACKGROUND: Many efforts over the past decade have focused on developing quality improvement and safety curricula for residents. Sponsoring institutions have encountered challenges aligning resident projects with institutional quality and safety priorities, engaging faculty mentors, and securing support for resident initiatives from executive leadership. OBJECTIVE: We developed a small grants program to support resident-led change projects intended to improve the clinical learning environment. We assessed program acceptability to residents and faculty, impact of program structure in supporting successful change projects, and program feasibility and financial sustainability. METHODS: Program acceptability was assessed through a review of resident participation. Three aspects of resident change project success were considered: (1) accomplishment of stated aims; (2) institutional change beyond the end of grant funding; and (3) academic publication or presentation. The impact of program structure on project success was assessed through a review of submitted end-of-year narrative reports. RESULTS: The Award Selection Committee has given 41 awards to 44 residents over 4 years, engaging 21% (44 of 213) of residents. Seventy-one percent of projects (29 of 41) produced changes that continued beyond the grant year, and 46% (19 of 41) produced an academic publication or presentation. At the end of the grant period that funded the program's initial 3 years, the chief executive officer elected to continue program funding. CONCLUSIONS: A small grants program supporting resident-led change projects intended to improve the clinical learning environment is acceptable to residents and faculty, feasible to administer, and sustainable with support from institutional senior leaders.