Sam Watson’s journal round-up for 13th November 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.

Scaling for economists: lessons from the non-adherence problem in the medical literature. Journal of Economic Perspectives [RePEcPublished November 2017

It has often been said that development economics has been at the vanguard of the use of randomised trials within economics. Other areas of economics have slowly caught up; the internal validity, and causal interpretation, offered by experimental randomised studies can provide reliable estimates for the effects of particular interventions. Health economics though has perhaps an even longer history with randomised controlled trials (RCTs), and now economic evaluation is often expected alongside clinical trials. RCTs of physician incentives and payments, investment programmes in child health, or treatment provision in schools all feature as other examples. However, even experimental studies can suffer from the same biases in the data analysis process as observational studies. The multiple decisions made in the data analysis and publication stages of research can lead to over-inflated estimates. Beyond that, the experimental conditions of the trial may not pertain in the real world – the study may lack external validity. The medical literature has long recognised this issue, as many as 50% of patients don’t take the medicines prescribed to them by a doctor. As a result, there has been considerable effort to develop an understanding of, and interventions to remedy, the lack of transferability between RCTs and real-world outcomes. This article summarises this literature and develops lessons for economists, who are only just starting to deal with, what they term, ‘the scaling problem’. For example, there are many reasons people don’t respond to incentives as expected: there are psychological costs to switching; people are hyperbolic discounters and often prefer small short-term gains for larger long-term costs; and, people can often fail to understand the implications of sets of complex options. We have also previously discussed the importance of social preferences in decision making. The key point is that, as policy is becoming more and more informed by randomised studies, we need to be careful about over-optimism of effect sizes and start to understand adherence to different policies in the real world. Only then are recommendations reliable.

Estimating the opportunity costs of bed-days. Health Economics [PubMedPublished 6th November 2017

The health economic evaluation of health service delivery interventions is becoming an important issue in health economics. We’ve discussed on many occasions questions surrounding the implementation of seven-day health services in England and Wales, for example. Other service delivery interventions might include changes to staffing levels more generally, medical IT technology, or an incentive to improve hand washing. Key to the evaluation of these interventions is that they are all generally targeted at improving quality of care – that is, to reduce preventable harm. The vast majority of patients who experience some sort of preventable harm do not die but are likely to experience longer lengths of stay in hospital. Consider a person suffering from bed sores or a fall in hospital. Therefore, we need to be able to value those extra bed days to be able to say what the value of improving hospital quality is. Typically we use reference costs or average accounting costs for the opportunity cost of a bed-day, mainly for pragmatic reasons, but also on the assumption that this is equivalent to the value of the second-best alternative foregone. This requires the assumption that health care markets operate properly, which they almost certainly do not. This paper explores the different ways economists have thought about opportunity costs and applies them to the question of the opportunity cost of a hospital bed-day. This includes definitions such as “Net health benefit forgone for the second-best patient‐equivalents”, “Net monetary benefit forgone for the second-best treatment-equivalents”, and “Expenditure incurred + highest net revenue forgone.” The key takeaway is that there is wide variation in the estimated opportunity costs using all the different methods and that, given the assumptions underpinning the most widely used methodologies are unlikely to hold, we may be routinely under- or over-valuing the effects of different interventions.

Universal investment in infants and long-run health: evidence from Denmark’s 1937 Home Visiting Program. American Economic Journal: Applied Economics [RePEcPublished October 2017

We have covered a raft of studies that look at the effects of in-utero health on later life outcomes, the so-called fetal origins hypothesis. A smaller, though by no means small, literature has considered what impact improving infant and childhood health has on later life adult outcomes. While many of these studies consider programmes that occurred decades ago in the US or Europe, their findings are still relevant today as many countries are grappling with high infant and childhood mortality. For many low-income countries, programmes with community health workers – lay-community members provided with some basic public health training – involving home visits, education, and referral services are being widely adopted. This article looks at the later life impacts of an infant health programme, the Home Visiting Program, implemented in Denmark in the 1930s and 40s. The aim of the programme was to provide home visits to every newborn in each district to provide education on feeding and hygiene practices and to monitor infant progress. The programme was implemented in a trial based fashion with different districts adopting the programme at different times and some districts remaining as control districts, although selection into treatment and control was not random. Data were obtained about the health outcomes in the period 1980-2012 of people born 1935-49. In short, the analyses suggest that the programme improved adult longevity and health outcomes, although the effects are small. For example, they estimate the programme reduced hospitalisations by half a day between the age of 45 and 64, and 2 to 6 more people per 1,000 survived past 60 years of age. However, these effect sizes may be large enough to justify what may be a reasonably low-cost programme when scaled across the population.

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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.