Challenges and methodologies in using progression free survival as a surrogate for overall survival In oncology

Objectives: A primary outcome in oncology trials is overall survival (OS). However, to estimate OS accurately requires a sufficient number of patients to have died, which may take a long time. If an alternative end point is sufficiently highly correlated with OS, it can be used as a surrogate. Progression-free survival (PFS) is the surrogate most often used in oncology, but does not always satisfy the correlation conditions for surrogacy. We analyze the methodologies used when extrapolating from PFS to OS. Methods: Davis et al. previously reviewed the use of surrogate end points in oncology, using papers published between 2001 and 2011. We extend this, reviewing papers published between 2012 and 2016. We also examine the reporting of statistical methods to assess the strength of surrogacy. Results: The findings from 2012 to 2016 do not differ substantially from those of 2001 to 2011: the same factors are shown to affect the relationship between PFS and OS. The proportion of papers reporting individual patient data (IPD), strongly recommended for full assessment of surrogacy, remains low: 33 percent. A wide range of methods has been used to determine the appropriateness of surrogates. While usually adhering to reporting standards, the standard of scholarship appears sometimes to be questionable and the reporting of results often haphazard. Conclusions: Standards of analysis and reporting PFS to OS surrogate studies should be improved by increasing the rigor of statistical reporting and by agreeing to a minimum set of reporting guidelines. Moreover, the use of IPD to assess surrogacy should increase

Economies of scale and scope in publicly funded biomedical and health research: evidence from the literature

BACKGROUND: Publicly funded biomedical and health research is expected to achieve the best return possible for taxpayers and for society generally. It is therefore important to know whether such research is more productive if concentrated into a small number of ‘research groups’ or dispersed across many. METHODS: We undertook a systematic rapid evidence assessment focused on the research question: do economies of scale and scope exist in biomedical and health research? In other words, is that research more productive per unit of cost if more of it, or a wider variety of it, is done in one location? We reviewed English language literature without date restriction to the end of 2014. To help us to classify and understand that literature, we first undertook a review of econometric literature discussing models for analysing economies of scale and/or scope in research generally (not limited to biomedical and health research). RESULTS: We found a large and disparate literature. We reviewed 60 empirical studies of (dis-)economies of scale and/or scope in biomedical and health research, or in categories of research including or overlapping with biomedical and health research. This literature is varied in methods and findings. At the level of universities or research institutes, studies more often point to positive economies of scale than to diseconomies of scale or constant returns to scale in biomedical and health research. However, all three findings exist in the literature, along with inverse U-shaped relationships. At the level of individual research units, laboratories or projects, the numbers of studies are smaller and evidence is mixed. Concerning economies of scope, the literature more often suggests positive economies of scope than diseconomies, but the picture is again mixed. The effect of varying the scope of activities by a research group was less often reported than the effect of scale and the results were more mixed. CONCLUSIONS: The absence of predominant findings for or against the existence of economies of scale or scope implies a continuing need for case by case decisions when distributing research funding, rather than a general policy either to concentrate funding in a few centres or to disperse it across many

Exploring the interdependencies of research funders in the UK

Investment in medical research is vital to the continuing improvement of the UK's health and wealth. It is through research that we expand our understanding of disease and develop new treatments for patients. Medical research charities currently contribute over £1 billion annually to medical research in the UK, of which over £350 million is provided by Cancer Research UK. Many charities, including Cancer Research UK, receive no government funding for their research activity. Cancer Research UK is engaged in a programme of work in order to better understand the medical research funding environment and demonstrate the importance of sustained investment. A key part of that is the Office of Health Economics‟ (OHE) 2011 report “Exploring the interdependency between public and charitable medical research”. This study found that there are substantial benefits, both financial and qualitative, from the existence of a variety of funders and that reductions in the level of government financial support for medical research are likely to have broader negative effects. This contributed to other evidence which found that the activities and funding of the charity, public and private sectors respectively are complementary, i.e. mutually reinforcing, rather than duplicative or merely substituting for one another. “Exploring the interdependencies of research funders in the UK” by the Office of Health Economics (OHE) and SPRU: Science and Technology Policy Research at the University of Sussex, represents a continued effort to build the evidence base around the funding of medical research. This report uncovers the extent to which funders of cancer research are interdependent, nationally and internationally. Key figures show that two thirds of publications acknowledging external support have relied on multiple funders, while just under half benefited from overseas funding, and almost a fifth are also supported by industry. In addition the analysis shows that the general public would not want tax funding of cancer research to be reduced, but would not donate enough to charities to compensate for any such reduction

Estimating health system opportunity costs: the role of non-linearities and inefficiency

BACKGROUND: Empirical estimates of health system opportunity costs have been suggested as a basis for the cost-effectiveness threshold to use in Health Technology Assessment. Econometric methods have been used to estimate these in several countries based on data on spending and mortality. This study examines empirical evidence on four issues: non-linearity of the relationship between spending and mortality; the inclusion of outcomes other than mortality; variation in the efficiency with which expenditures generate health outcomes; and the relationship among efficiency, mortality rates and outcome elasticities. METHODS: Quantile Regression is used to examine non-linearities in the relationship between mortality and health expenditures along the mortality distribution. Data Envelopment Analysis extends the approach, using multiple measures of health outcomes to measure efficiency. These are applied to health expenditure data from 151 geographical units (Primary Care Trusts) of the National Health Service in England, across eight different clinical areas (Programme Budget Categories), for 3 fiscal years from 2010/11 to 2012/13. RESULTS: The results suggest differences in efficiency levels across geographical units and clinical areas as to how health resources generate outcomes, which indicates the capacity to adjust to a decrease in health expenditure without affecting health outcomes. Moreover, efficient units have lower absolute levels of mortality elasticity to health expenditure than inefficient ones. CONCLUSIONS: The policy of adopting thresholds based on estimates of a single system-wide cost-effectiveness threshold assumes a relationship between expenditure and health outcomes that generates an opportunity cost estimate which applies to the whole system. Our evidence of variations in that relationship and therefore in opportunity costs suggests that adopting a single threshold may exacerbate the efficiency and equity concerns that such thresholds are designed to counter. In most health care systems, many decisions about provision are not made centrally. Our analytical approach to understanding variability in opportunity cost can help policy makers target efficiency improvements and set realistic targets for local and clinical area health improvements from increased expenditure. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12962-022-00391-y

The value of international volunteers experience to the NHS.

BACKGROUND: Global Engagement works with health partnerships to establish workforce and educational translation on a global scale to support the National Health Service (NHS). There is growing evidence on how international experiences (through volunteering, exchanges and placements) benefit the NHS through an innovative workforce that develops international best practice and promotes lifelong learning. Most of this evidence has been captured though surveys to returned international volunteers. However, there is limited evidence about how to quantify the value that returned international healthcare volunteers bring back to their country of residence. METHODS: This paper identifies the various benefits to the NHS from returned international healthcare volunteers. The outcomes from returned international volunteers, which have been identified as relevant form a NHS perspective, are linked to three key areas in a multisector analytical framework used by the World Bank to evaluate labour market programmes: (1) Investment climate and Infrastructure, (2) Labor market regulations and institutions, and (3) Education and skills development. The monetary value of these outcomes is quantified through productivity indices which capture the economic value that the achievement of these outcomes have on the quality of the NHS labor force. This model is applied to a dataset of international volunteers provided by the Global Engagement health partnerships. RESULTS: The results suggest that international volunteering generates average productivity gains of up to 37% for doctors and up to 62% for nurses. Average productivity gains estimated from health partnerships data vary depending on duration of volunteering periods and occupational category mix. CONCLUSIONS: Our analysis offers a value for money rationale for international volunteering programmes purely from a domestic and NHS perspective. The valuation method considers only one of the aims of international volunteering programmes: the development of the existing and future NHS workforce. Broader benefits for health system strengthening at a global level are acknowledged but not accounted for. Overall, we conclude that if the acquisition of volunteering outcomes is realised, the NHS can accrue a productivity increase of between 24 and 41% per volunteer, with a value ranging from £13,215 to £25,934 per volunteer.HEE and the Global Engagement directorat

Evidence-informed capacity building for setting health priorities in low- and middle-income countries: : A framework and recommendations for further research

Priority-setting in health is risky and challenging, particularly in resource-constrained settings. It is not simply a narrow technical exercise, and involves the mobilisation of a wide range of capacities among stakeholders – not only the technical capacity to “do” research in economic evaluations. Using the Individuals, Nodes, Networks and Environment (INNE) framework, we identify those stakeholders, whose capacity needs will vary along the evidence-to-policy continuum. Policymakers and healthcare managers require the capacity to commission and use relevant evidence (including evidence of clinical and cost-effectiveness, and of social values); academics need to understand and respond to decision-makers’ needs to produce relevant research. The health system at all levels will need institutional capacity building to incentivise routine generation and use of evidence. Knowledge brokers, including priority-setting agencies (such as England’s National Institute for Health and Care Excellence, and Health Interventions and Technology Assessment Program, Thailand) and the media can play an important role in facilitating engagement and knowledge transfer between the various actors. Especially at the outset but at every step, it is critical that patients and the public understand that trade-offs are inherent in priority-setting, and careful efforts should be made to engage them, and to hear their views throughout the process. There is thus no single approach to capacity building; rather a spectrum of activities that recognises the roles and skills of all stakeholders. A range of methods, including formal and informal training, networking and engagement, and support through collaboration on projects, should be flexibly employed (and tailored to specific needs of each country) to support institutionalisation of evidence-informed priority-setting. Finally, capacity building should be a two-way process; those who build capacity should also attend to their own capacity development in order to sustain and improve impact

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat