Chris Sampson’s journal round-up for 22nd May 2017

Every Monday our authors provide a round-up of some of the most recently published peer reviewed articles from the field. We don’t cover everything, or even what’s most important – just a few papers that have interested the author. Visit our Resources page for links to more journals or follow the HealthEconBot. If you’d like to write one of our weekly journal round-ups, get in touch.

The effect of health care expenditure on patient outcomes: evidence from English neonatal care. Health Economics [PubMed] Published 12th May 2017

Recently, people have started trying to identify opportunity cost in the NHS, by assessing the health gains associated with current spending. Studies have thrown up a wide range of values in different clinical areas, including in neonatal care. This study uses individual-level data for infants treated in 32 neonatal intensive care units from 2009-2013, along with the NHS Reference Cost for an intensive care cot day. A model is constructed to assess the impact of changes in expenditure, controlling for a variety of variables available in the National Neonatal Research Database. Two outcomes are considered: the in-hospital mortality rate and morbidity-free survival. The main finding is that a £100 increase in the cost per cot day is associated with a reduction in the mortality rate of 0.36 percentage points. This translates into a marginal cost per infant life saved of around £420,000. Assuming an average life expectancy of 81 years, this equates to a present value cost per life year gained of £15,200. Reductions in the mortality rate are associated with similar increases in morbidity. The estimated cost contradicts a much higher estimate presented in the Claxton et al modern classic on searching for the threshold.

A comparison of four software programs for implementing decision analytic cost-effectiveness models. PharmacoEconomics [PubMed] Published 9th May 2017

Markov models: TreeAge vs Excel vs R vs MATLAB. This paper compares the alternative programs in terms of transparency and validation, the associated learning curve, capability, processing speed and cost. A benchmarking assessment is conducted using a previously published model (originally developed in TreeAge). Excel is rightly identified as the ‘ubiquitous workhorse’ of cost-effectiveness modelling. It’s transparent in theory, but in practice can include cell relations that are difficult to disentangle. TreeAge, on the other hand, includes valuable features to aid model transparency and validation, though the workings of the software itself are not always clear. Being based on programming languages, MATLAB and R may be entirely transparent but challenging to validate. The authors assert that TreeAge is the easiest to learn due to its graphical nature and the availability of training options. Save for complex VBA, Excel is also simple to learn. R and MATLAB are equivalently more difficult to learn, but clearly worth the time saving for anybody expecting to work on multiple complex modelling studies. R and MATLAB both come top in terms of capability, with Excel falling behind due to having fewer statistical facilities. TreeAge has clearly defined capabilities limited to the features that the company chooses to support. MATLAB and R were both able to complete 10,000 simulations in a matter of seconds, while Excel took 15 minutes and TreeAge took over 4 hours. For a value of information analysis requiring 1000 runs, this could translate into 6 months for TreeAge! MATLAB has some advantage over R in processing time that might make its cost ($500 for academics) worthwhile to some. Excel and TreeAge are both identified as particularly useful as educational tools for people getting to grips with the concepts of decision modelling. Though the take-home message for me is that I really need to learn R.

Economic evaluation of factorial randomised controlled trials: challenges, methods and recommendations. Statistics in Medicine [PubMed] Published 3rd May 2017

Factorial trials randomise participants to at least 2 alternative levels (for example, different doses) of at least 2 alternative treatments (possibly in combination). Very little has been written about how economic evaluations ought to be conducted alongside such trials. This study starts by outlining some key challenges for economic evaluation in this context. First, there may be interactions between combined therapies, which might exist for costs and QALYs even if not for the primary clinical endpoint. Second, transformation of the data may not be straightforward, for example, it may not be possible to disaggregate a net benefit estimation with its components using alternative transformations. Third, regression analysis of factorial trials may be tricky for the purpose of constructing CEACs and conducting value of information analysis. Finally, defining the study question may not be simple. The authors simulate a 2×2 factorial trial (0 vs A vs B vs A+B) to demonstrate these challenges. The first analysis compares A and B against placebo separately in what’s known as an ‘at-the-margins’ approach. Both A and B are shown to be cost-effective, with the implication that A+B should be provided. The next analysis uses regression, with interaction terms demonstrating the unlikelihood of being statistically significant for costs or net benefit. ‘Inside-the-table’ analysis is used to separately evaluate the 4 alternative treatments, with an associated loss in statistical power. The findings of this analysis contradict the findings of the at-the-margins analysis. A variety of regression-based analyses is presented, with the discussion focussed on the variability in the estimated standard errors and the implications of this for value of information analysis. The authors then go on to present their conception of the ‘opportunity cost of ignoring interactions’ as a new basis for value of information analysis. A set of 14 recommendations is provided for people conducting economic evaluations alongside factorial trials, which could be used as a bolt-on to CHEERS and CONSORT guidelines.

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Paul Mitchell’s journal round-up for 17th April 2017

Every Monday our authors provide a round-up of some of the most recently published peer reviewed articles from the field. We don’t cover everything, or even what’s most important – just a few papers that have interested the author. Visit our Resources page for links to more journals or follow the HealthEconBot. If you’d like to write one of our weekly journal round-ups, get in touch.

Is foreign direct investment good for health in low and middle income countries? An instrumental variable approach. Social Science & Medicine [PubMed] Published 28th March 2017

Foreign direct investment (FDI) is considered a key benefit of globalisation in the economic development of countries with developing economies. The effect FDI has on the population health of countries is less well understood. In this paper, the authors draw from a large panel of data, primarily World Bank and UN sources, for 85 low and middle income countries between 1974 and 2012 to assess the relationship between FDI and population health, proxied by life expectancy at birth, as well as child and adult mortality data. They explain clearly the problem of using basic regression analysis in trying to explain this relationship, given the problem of endogeneity between FDI and health outcomes. By introducing two instrumental variables, using grossed fixed capital formation and volatility of exchange rates in FDI origin countries, as well as controlling for GDP per capita, education, quality of institutions and urban population, the study shows that FDI is weakly statistically associated with life expectancy, estimated to amount to 4.15 year increase in life expectancy during the study period. FDI also appears to have an effect on reducing adult mortality, but a negligible effect on child mortality. They also produce some evidence that FDI linked to manufacturing could lead to reductions in life expectancy, although these findings are not as robust as the other findings using instrumental variables, so they recommend this relationship between FDI type and population health to be explored further. The paper also clearly shows the benefit of robust analysis using instrumental variables, as the results without the introduction of these variables to the regression would have led to misleading inferences, where no relationship between life expectancy and FDI would have been found if the analysis did not adjust for the underlying endogeneity bias.

Uncovering waste in US healthcare: evidence from ambulance referral patterns. Journal of Health Economics [PubMed] Published 22nd March 2017

This study looks to unpick some of the reasons behind the estimated waste in US healthcare spending, by focusing on mortality rates across the country following an emergency admission to hospital through ambulances. The authors argue that patients admitted to hospital for emergency care using ambulances act as a good instrument to assess hospital quality given the nature of emergency admissions limiting the selection bias of what type of patients end up in different hospitals. Using linear regressions, the study primarily measures the relationship between patients assigned to certain hospitals and the 90-day spending on these patients compared to mortality. They also consider one-year mortality and the downstream payments post-acute care (excluding pharmaceuticals outside the hospital setting) has on this outcome. Through a lengthy data cleaning process, the study looks at over 1.5 million admissions between 2002-2011, with a high average age of patients of 82 who are predominantly female and white. Approximately $27,500 per patient was spent in the first 90 days post-admission, with inpatient spending accounting for the majority of this amount (≈$16,000). The authors argue initially that the higher 90-day spending in some hospitals only produces modestly lower mortality rates. Spending over 1 year is estimated to cost more than $300,000 per life year, which the authors use to argue that current spending levels do not lead to improved outcomes. But when the authors dig deeper, it seems clear there is an association between hospitals who have higher spending on inpatient care and reduced mortality, approximately 10% lower. This leads to the authors turning their attention to post-acute care as their main target of reducing waste and they find an association between mortality and patients receiving specialised nursing care. However, this target seems somewhat strange to me, as post-acute care is not controlled for in the same way as their initial, insightful approach to randomising based on ambulatory care. I imagine those in such care are likely to be a different mix from those receiving other types of care post 90 days after the initial event. I feel there really is not enough to go on to make recommendations about specialist nursing care being the key waste driver from their analysis as it says nothing, beyond mortality, about the quality of care these elderly patients are receiving in the specialist nurse facilities. After reading this paper, one way I would suggest in reducing inefficiency related to their primary analysis could be to send patients to the most appropriate hospital for what the patient needs in the first place, which seems difficult given the complexity of the private and hospital provided mix of ambulatory care offered in the US currently.

Population health and the economy: mortality and the Great Recession in Europe. Health Economics [PubMed] Published 27th March 2017

Understanding how economic recessions affect population health is of great research interest given the recent global financial crisis that led to the worst downturn in economic performance in the West since the 1930s. This study uses data from 27 European countries between 2004 and 2010 collected by WHO and the World Bank to study the relationship between economic performance and population health by comparing national unemployment and mortality rates before and after 2007. Regression analyses appropriate for time-series data are applied with a number of different specifications applied. The authors find that the more severe the economic downturn, the greater the increase in life expectancy at birth. Additional specific health mortality rates follow a similar trend in their analysis, with largest improvements observed in countries where the severity of the recession was the highest. The only exception the authors note is data on suicide, where they argue the relationship is less clear, but points towards higher rates of suicide with greater unemployment. The message the authors were trying to get across in this study was not very clear throughout most of the paper and some lay readers of the abstract alone could easily be misled in thinking recessions themselves were responsible for better population health. Mortality rates fell across all six years, but at a faster rate in the recession years. Although the results appeared consistent across all models, question marks remain for me in terms of their initial variable selection. Although the discussion mentions evidence that suggests health care may not have a short-term effect on mortality, they did not consider any potential lagged effect record investment in healthcare as a proportion of GDP up until 2007 may have had on the initial recession years. The authors rule out earlier comparisons with countries in the post-Soviet era but do not consider the effect of recent EU accession for many of the countries and more regulated national policies as a consequence. Another issue is the potential of countries’ mortality rates to improve, where countries with existing lower life expectancy have more room for moving in the right direction. However, one interesting discussion point raised by the authors in trying to explain their findings is the potential impact of economic activity on pollution levels and knock-on health impacts from this (and to a lesser extent occupational health levels), that may have some plausibility in better mortality rates linked to physical health during recessions.

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Alastair Canaway’s journal round-up for 20th March 2017

Every Monday our authors provide a round-up of some of the most recently published peer reviewed articles from the field. We don’t cover everything, or even what’s most important – just a few papers that have interested the author. Visit our Resources page for links to more journals or follow the HealthEconBot. If you’d like to write one of our weekly journal round-ups, get in touch.

The use of quality-adjusted life years in cost-effectiveness analyses in palliative care: mapping the debate through an integrative review. Palliative Medicine [PubMed] Published 13th February 2017

February saw a health economics special within the journal Palliative Medicine – the editorials are very much worth a read to get a quick idea of how health economics has (and hasn’t) developed within the end of life care context. One of the most commonly encountered debates when discussing end of life care within health economics circles relates to the use of QALYs, and whether they’re appropriate. This paper aimed to map out the pros and cons of using the QALY framework to inform health economic decisions in the palliative care context. Being a review, there were no ground-breaking findings, more a refresher on what the issues are with the QALY at end of life: i) restrictions in life years gained, ii) conceptualisation of quality of life and its measurement, and iii) valuation and additivity of time. The review acknowledges the criticisms of the QALY but concludes that it is still of use for informing decision making. A key finding, and one which should be common sense, is that the EQ-5D should not be relied on as the sole measure within this context: the dimensions important to those at end of life are not adequately captured by the EQ-5D, and other measures should be considered. A limitation for me was that the review did not include Round’s (2016) book Care at the End of Life: An Economic Perspective (disclaimer: I’m a co-author on a chapter), which has significant overlap and builds on a number of the issues relevant to the paper. That aside, this is a useful paper for those new to the pitfalls of economic evaluation at the end of life and provides an excellent summary of many of the key issues.

The causal effect of retirement on mortality: evidence from targeted incentives to retire early. Health Economics [PubMed] [RePEc] Published 23rd February 2017

It’s been said that those who retire earlier die earlier, and a quick google search suggests there are many statistics supporting this. However, I’m unsure how robust the causality is in such studies. For example, the sick may choose to leave the workforce early. Previous academic literature had been inconclusive regarding the effects, and in which direction they occurred. This paper sought to elucidate this by taking advantage of pension reforms within the Netherlands which meant certain cohorts of Dutch civil servants could qualify for early retirement at a younger age. This change led to a steep increase in retirement and provided an opportunity to examine causal impacts by instrumenting retirement with the early retirement window. Administrative data from the entire population was used to examine the probability of dying resulting from earlier retirement. Contrary to preconceptions, the probability of men dying within five years dropped by 2.6% in those who took early retirement: a large and significant impact. The biggest impact was found within the first year of retirement. An explanation for this is that the reduction of stress and lifestyle change upon retiring may postpone death for the civil servants which were in poor health. The paper is an excellent example of harnessing a natural experiment for research purposes. It provides a valuable contribution to the evidence base whilst also being reassuring for those of us who plan to retire in the next few years (lottery win pending).

Mapping to estimate health-state utility from non–preference-based outcome measures: an ISPOR Good Practices for Outcomes Research Task Force report. Value in Health [PubMed] Published 16th February 2017

Finally, I just wanted to signpost this new good practice guide. If you ever attend HESG, ISPOR, or IHEA, you’ll nearly always encounter a paper on mapping (cross-walking). Given the ethical issues surrounding research waste and the increasing pressure to publish, mapping provides an excellent opportunity to maximise the value of your data. Of course, mapping also serves a purpose for the health economics community: it facilitates the estimation of QALYs in studies where no preference based measure exists. There are many iffy mapping functions out there so it’s good to see ISPOR have taken action by producing a report on best practice for mapping. As with most ISPOR guidelines the paper covers all the main areas you’d expect and guides you through the key considerations to undertaking a mapping exercise, this includes: pre-modelling considerations, data requirements, selection of statistical models, selection of covariates, reporting of results, and validation. Additionally there is also a short section for those who are keen to use a mapping function to generate QALYs but are unsure which to pick. As with any set of guidelines, it’s not exactly a thriller, it is however extremely useful for anyone seeking to conduct mapping.

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