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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Thesis Thursday: Raymond Oppong

On the third Thursday of every month, we speak to a recent graduate about their thesis and their studies. This month’s guest is Dr Raymond Oppong who graduated with a PhD from the University of Birmingham. If you would like to suggest a candidate for an upcoming Thesis Thursday, get in touch.

Title
Economic analysis alongside multinational studies
Supervisors
Sue Jowett, Tracy Roberts
Repository link
http://etheses.bham.ac.uk/7288/

What attracted you to studying economic evaluation in the context of multinational studies?

One of the first projects that I was involved in when I started work as a health economist was the Genomics to combat Resistance against Antibiotics in Community-acquired lower respiratory tract infections (LRTI) in Europe (GRACE) project. This was an EU-funded study aimed at integrating and coordinating the activities of physicians and scientists from institutions in 14 European countries to combat antibiotic resistance in community-acquired lower respiratory tract infections.

My first task on this project was to undertake a multinational costing study to estimate the costs of treating acute cough/LRTI in Europe. I faced quite a number of challenges including the lack of unit cost data across countries. Conducting a full economic evaluation alongside the interventional studies in GRACE also brought up a number of issues with respect to methods of analysis of multinational trials which needed to be resolved. The desire to understand and resolve some of these issues led me to undertake the PhD to investigate the implications of conducting economic evaluations alongside multinational studies.

Your thesis includes some case studies from a large multinational project. What were the main findings of your empirical work?

I used three main case studies for my empirical work. The first was an observational study aimed at describing the current presentation, investigation, treatment and outcomes of community-acquired lower respiratory tract infections and analysing the determinants of antibiotic use in Europe. The other 2 were RCTs. The first was aimed at studying the effectiveness of antibiotic therapy (amoxicillin) in community-acquired lower respiratory tract infections, whilst the second was aimed at assessing training interventions to improve antibiotic prescribing behaviour by general practitioners. The observational study was used to explore issues relating to costing and outcomes in multinational studies whilst the RCTs explored the various analytical approaches (pooled and split) to economic evaluation alongside multinational studies.

The results from the observational study revealed large variations in costs across Europe and showed that contacting researchers in individual countries was the most effective way of obtaining unit costs. Results from both RCTs showed that the choice of whether to pool or split data had an impact on the cost-effectiveness of the interventions.

What were the key analytical methods used in your analysis?

The overall aim of the thesis was to study the implications of conducting economic analysis alongside multinational studies. Specific objectives include: i) documenting challenges associated with economic evaluations alongside multinational studies, ii) exploring various approaches to obtaining and estimating unit costs, iii) exploring the impact of using different tariffs to value EQ-5D health state descriptions, iv) comparing methods that have been used to conduct economic evaluation alongside multinational studies and v) making recommendations to guide the design and conduct of future economic evaluations carried out alongside multinational studies.

A number of approaches were used to achieve each of the objectives. A systematic review of the literature identified challenges associated with economic evaluations alongside multinational studies. A four-stage approach to obtaining unit costs was assessed. The UK, European and country-specific EQ-5D value sets were compared to determine which is the most appropriate to use in the context of multinational studies. Four analytical approaches – fully pooled one country costing, fully pooled multicountry costing, fully split one country costing and fully split multicountry costing – were compared in terms of resource use, costs, health outcomes and cost-effectiveness. Finally, based on the findings of the study, a set of recommendations were developed.

You completed your PhD part-time while working as a researcher. Did you find this a help or a hindrance to your studies?

I must say that it was both a help and a hindrance. Working in a research environment was really helpful. There was a lot of support from supervisors and colleagues which kept me motivated. I might have not gotten this support if I was not working in a research/academic environment. However, even though some time during the week was allocated to the PhD, I had to completely put it on hold for long periods of time in order to deal with the pressures of work/research. Consequently, I always had to struggle to find my bearings when I got back to the PhD. I also spent most weekends working on the PhD especially when I was nearing submission.

On the whole, it should be noted that a part-time PhD requires a lot of time management skills. I personally had to go on time management courses which were really helpful.

What advice would you give to a health economist conducting an economic evaluation alongside a multinational study?

For a health economist conducting an economic evaluation alongside a multinational trial, it is important to plan ahead and understand the challenges that are associated with economic evaluations alongside multinational studies. A lot of the problems such as those related to the identification of unit costs can be avoided by ensuring adequate measures are put in place at the design stage of the study. An understanding of the various health systems of the countries involved in the study is important in order to make a judgement about the differences and similarities in resource use across countries. Decision makers are interested in results that can be applied to their jurisdiction; therefore it is important to adopt transparent methods e.g. state the countries that participated in the study, state the sources of unit costs and make it clear whether data from all countries (pooling) or from a subset (splitting) were used. To ensure that the results of the study are generalisable to a number of countries it may be advisable to present country-specific results and probably conduct the analysis from different perspectives.

Chris Sampson’s journal round-up for 27th February 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.

Does it pay to know prices in health care? American Economic Journal: Economic Policy Published February 2017

In the US, people in need of health care have to pay for it – or for insurance to cover it – without knowing in advance how much said health care actually costs. Weird, right? Instinctively, it feels as if people really ought to be able to find out. However, if knowing prices in advance doesn’t actually affect consumption, maybe we can say it really doesn’t matter. Well, we can’t. As this new study shows, having access to price information affects consumer choices. There’s plenty of price dispersion to make this potentially important: in this study’s dataset, a move from the 90th to the 50th percentile is on average associated with a price drop of 35%. The data relate to 387,774 procedures for 6,208 people working for a corporate client of a price information firm. Access to this service was staggered for different employees, creating the potential for experimental investigation. The principal strategy is difference-in-differences regression analysis. Access to the price information service was associated with prices around 1.6% lower on average. For primary care – which might be less price sensitive – and for complex cases where lots of procedures are taking place, the effect is weakened. The results seem robust to matching and other tests. The author is able to provide further insight by showing that access to price information increases the probability of seeing a new doctor by 14%. And when an instrumental variable approach is used to assess the price reduction specifically for people who searched for price information and then received a procedure within 30 days, the reduction in price reaches a whopping 17%. This suggests that the average impact of a 1.6% reduction could be a lot higher if people searched for price information more frequently. The fact that they don’t is likely due to a particular kind of moral hazard being at play. Moral hazard in search occurs when people have no incentive to search for cheaper services. The author goes on to show that in any given week an individual is around 90% less likely to search if they have already met their deductible, and that this translates into an elasticity of search propensity to the proportion out-of-pocket expense of approximately 1.8. We mustn’t forget the other side of the welfare coin here. What if people are choosing lower quality care in order to save money, or foregoing it altogether? Looking at the rate of follow-through after searches and bringing in hospital quality data seems to show that this isn’t a concern here. This group of people aren’t representative of the general population so it may be that access to prices is only valuable to certain groups. Nevertheless, this paper tells us a lot about the importance of price information and in particular the special kind of moral hazard that can arise in the presence of comprehensive insurance coverage.

Mitigating the consequences of a health condition: The role of intra- and interhousehold assistance. Journal of Health Economics Published 20th February 2017

There’s a lot of research around the effect that an individual’s health problem can have on their immediate family, both in terms of the overspill in quality of life impacts and the costs of satisfying need for health care. However, large panel data research can be limited because the data can’t connect non-coresident family members. This study considers informal insurance and consumption smoothing within families beyond the current household. The data come from the Panel Study of Income Dynamics, with 7,578 individuals and around 33,000 household years from 2001-2011. The panel follows offspring after they leave a household, facilitating the identification of genetically linked families. Participants are asked whether they suffer from 11 different health problems and, if they do, the extent to which it limits their daily activities. The data also include information on different categories of spending, including health. The analysis involves regression that accounts for individual fixed effects and looks at the impact of a change in health status on consumption. If a household is fully insured, changes in health status should not affect non-health expenditures. The analysis focuses on the impact of severe limitations, which are reported at some point by 1,321 people. Such a change in health status was associated with a reduction in annual working hours of around 20%, corresponding to $5000 for men and $2800 for women. Additionally, household health expenditures increased by $479 on average. The notion of complete insurance facilitating consumption smoothing appears to fail, with a decline in consumption of around 10%. Partial insurance smoothes roughly half the loss. Households with formal insurance exhibit a much smaller reduction in consumption. A key finding is that being married may facilitate consumption smoothing to the extent of full insurance, while unmarried couples take a bigger hit. Home equity seems to play an important role in this dynamic, with married couples more likely to remortgage in response to a health shock. Married couples also receive more in social security transfers. Unmarried couples, it seems, have to turn to non-coresident family members instead and are 50% more likely to use this channel than married couples. Male children are more likely to use their own home equity to support their parents, while female children tend to reduce their own consumption. This study identifies a lot of interesting relationships and divergent strategies for consumption smoothing that warrant further investigation.

Handling missing data in within-trial cost-effectiveness analysis: a review with future recommendations. PharmacoEconomics – Open Published 9th February 2017

If you conduct trial-based cost-effectiveness analyses then chances are that at some point you’ve had to go and figure out how to deal with all that missing data. There are a handful of quality papers out there that offer guidance. If we all followed their advice then we’d be doing a decent job of it. This new paper demonstrates that we aren’t all doing a good job of it and offers fresh guidance. The paper starts by outlining the ‘principled’ approach to handling missing data. Essentially it means being sensible with the data, considering the most appropriate statistical model and describing assumptions about the missing data mechanism. Imputation methods that can support this principled approach are briefly discussed. The authors present a quality evaluation scheme, which can be used to assess the appropriateness of methods adopted in a study and the completeness of reporting. It makes recommendations with respect to the description of missing data, the methods used to handle it and the limitations associated with the study. The quality evaluation scheme can be used to score and rank papers from A-E. This is what the authors go on to do, with a systematic review including 81 eligible papers. A previous review found complete case analysis to be the most popular base case method adopted. In 2009-2015, multiple imputation became the most frequently used base case method, though complete case analysis remains common and many studies are still unclear about the methods adopted. Most articles did not describe any robustness analysis, reporting only the base case approach to missing data. Many articles were classified as the lowest quality (E), though this has improved over time. The authors demonstrate that their proposed grading system is associated with the strength of the assumptions in the adopted methods. If you’re engaged in trial-based economic evaluation, you ought to read this paper.

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