Sam Watson’s journal round-up for Monday 20th August 2018

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.

A Randomized Trial of Epinephrine in Out-of-Hospital Cardiac Arrest. New England Journal of Medicine. Published July 2018.

Adrenaline (epinephrine) is often administered to patients in cardiac arrest in order to increase blood flow and improve heart rhythm. However, there had been some concern about the potential adverse effects of using adrenaline, and a placebo controlled trial was called for. This article presents the findings of this trial. While there is little economics in this article, it is an interesting example of what I believe to be erroneous causal thinking, especially in the way it was reported in the media. For example, The Guardian‘s headline was,

Routine treatment for cardiac arrest doubles risk of brain damage – study

while The Telegraph went for the even more inflammatory

Cardiac arrest resuscitation drug has needlessly brain-damaged thousands

But what did the study itself say about their findings:

the use of epinephrine during resuscitation for out-of-hospital cardiac arrest resulted in a significantly higher rate of survival at 30 days than the use of placebo. […] although the rate of survival was slightly better, the trial did not show evidence of a between-group difference in the rate of survival with a favorable neurologic outcome. This result was explained by a higher proportion of patients who survived with severe neurologic disability in the epinephrine group.

Clearly, a slightly more nuanced view, but nevertheless it leaves room for the implication that the adrenaline is causing the neurological damage. Indeed the authors go on to say that “the use of epinephrine did not improve neurologic outcome.” But a counterfactual view of causation should lead us to ask what would have happened to those who survived with brain damage had they not been given adrenaline.

We have a competing risks set up: (A) survival with favourable neurologic outcome, (B) survival with neurologic impairment, and (C) death. The proportion of patients with outcome (A) was slightly higher in the adrenaline group (although not statistically significant so apparently no effect eyes roll), the proportion of patients with outcome (B) was a lot higher in the adrenaline group, and the proportion of patients with outcome (C) was lower in the adrenaline group. This all suggests to me that the adrenaline caused patients who would have otherwise died to mostly survive with brain damage, and a few to survive impairment free, not that adrenaline caused those who would have otherwise been fine to have brain damage. So the question in response to the above quotes is then, is death a preferable neurologic outcome to brain damage? As trite as this may sound, it is a key health economics question – how do we value these health states?

Incentivizing Safer Sexual Behavior: Evidence from a Lottery Experiment on HIV Prevention. American Economic Review: Applied Economics. [RePEcPublished July 2018. 

This article presents a randomised trial testing an interesting idea. People who are at high risk of HIV and other sexually transmitted infections (STIs) and often those who engage in riskier sexual behaviour. A basic decision theoretic conception would be that those individuals don’t consider the costs to be high enough relative to the benefits (although there is clearly some divide between this explanation and how people actually think in terms of risky sexual behaviour, much like any other seemingly irrational behaviour). Conditional cash transfers can change the balance of the decision to incentivise people to act differently, what this study looks at is using a conditional lottery with the chance of high winnings instead, since this should be more attractive still to risk-seeking individuals. While the trial was designed to reduce HIV prevalance, entry into the lottery in the treatment arm was conditional on being free of two curable STIs at each round – this enabled people who fail to be eligible again, and also allowed the entry of HIV-positive individuals whose sexual behaviour is perhaps the most important to reducing HIV transmission. The lottery arm of the trial was found to have 20% lower incidence over the study period compared to the control arm – quite impressive. However, the cost-effectiveness of the program was estimated to be $882 per HIV infection averted on the basis of lottery payments alone, and around $3,300 per case averted all in. This seems quite high to me. Despite a plethora of non-comparable outcomes in cost-effectiveness studies of HIV public health interventions other studies have reported costs per cases averted an order of magnitude lower than this. The conclusions seems to be then that the idea works well – it’s just too costly to be of much use.

Monitoring equity in universal health coverage with essential services for neglected tropical diseases: an analysis of data reported for five diseases in 123 countries over 9 years. The Lancet: Global Health. [PubMedPublished July 2018. 

Universal health coverage (UHC) is one the key parts of Sustainable Development Goal (SDG) 3, good health and well-being. The text of the SDG identifies UHC as being about access to services – but this word “access” in the context of health care is often vague and nebulous. Many people mistakenly treat access to health services as synonymous with use of health services, but having access to something is not dependent on whether you actually use it or not. Barriers to a person’s ability to use health care for a given complaint are numerous: financial cost, time cost, lack of education, language barrier, and so forth. It is therefore difficult to quantify and measure access. Hogan and co-authors proposed an index to quantify and monitor UHC across the world that was derived from a number of proxies such as women with four or more antenatal visits, children with vaccines, blood pressure, and health worker density. Their work is useful but of course flawed – these proxies all capture something different, either access, use, or health outcomes – and it is unclear that they are all sensitive to the same underlying construct. Needless to say, we should still be able to diagnose access issues from some combination of these data. This article extends the work of Hogan et al to look at neglected tropical diseases, which affect over 1.5 billion, yet which are, obviously, neglected. The paper uses ‘preventative chemotherapy coverage’ as its key measure, which is the proportion of those needed the chemotherapy who actually receive it. This is a measure of use and not access (although they should be related), for example, there may be near universal availability of the chemotherapy, but various factors on the demand side limiting use. Needless to say, the measure should still be a useful diagnostic tool and it is interesting to see how much worse countries perform on this metric for neglected tropical diseases than general health care.

 

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Chris Sampson’s journal round-up for 2nd July 2018

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.

Choice in the presence of experts: the role of general practitioners in patients’ hospital choice. Journal of Health Economics [PubMed] [RePEc] Published 26th June 2018

In the UK, patients are in principle free to choose which hospital they use for elective procedures. However, as these choices operate through a GP referral, the extent to which the choice is ‘free’ is limited. The choice set is provided by the GP and thus there are two decision-makers. It’s a classic example of the principal-agent relationship. What’s best for the patient and what’s best for the local health care budget might not align. The focus of this study is on the applied importance of this dynamic and the idea that econometric studies that ignore it – by looking only at patient decision-making or only at GP decision-making – may give bias estimates. The author outlines a two-stage model for the choice process that takes place. Hospital characteristics can affect choices in three ways: i) by only influencing the choice set that the GP presents to the patient, e.g. hospital quality, ii) by only influencing the patient’s choice from the set, e.g. hospital amenities, and iii) by influencing both, e.g. waiting times. The study uses Hospital Episode Statistics for 30,000 hip replacements that took place in 2011/12, referred by 4,721 GPs to 168 hospitals, to examine revealed preferences. The choice set for each patient is not observed, so a key assumption is that all hospitals to which a GP made referrals in the period are included in the choice set presented to patients. The main findings are that both GPs and patients are influenced primarily by distance. GPs are influenced by hospital quality and the budget impact of referrals, while distance and waiting times explain patient choices. For patients, parking spaces seem to be more important than mortality ratios. The results support the notion that patients defer to GPs in assessing quality. In places, it’s difficult to follow what the author did and why they did it. But in essence, the author is looking for (and in most cases finding) reasons not to ignore GPs’ preselection of choice sets when conducting econometric analyses involving patient choice. Econometricians should take note. And policymakers should be asking whether freedom of choice is sensible when patients prioritise parking and when variable GP incentives could give rise to heterogeneous standards of care.

Using evidence from randomised controlled trials in economic models: what information is relevant and is there a minimum amount of sample data required to make decisions? PharmacoEconomics [PubMed] Published 20th June 2018

You’re probably aware of the classic ‘irrelevance of inference’ argument. Statistical significance is irrelevant in deciding whether or not to fund a health technology, because we ought to do whatever we expect to be best on average. This new paper argues the case for irrelevance in other domains, namely multiplicity (e.g. multiple testing) and sample size. With a primer on hypothesis testing, the author sets out the regulatory perspective. Multiplicity inflates the chance of a type I error, so regulators worry about it. That’s why triallists often obsess over primary outcomes (and avoiding multiplicity). But when we build decision models, we rely on all sorts of outcomes from all sorts of studies, and QALYs are never the primary outcome. So what does this mean for reimbursement decision-making? Reimbursement is based on expected net benefit as derived using decision models, which are Bayesian by definition. Within a Bayesian framework of probabilistic sensitivity analysis, data for relevant parameters should never be disregarded on the basis of the status of their collection in a trial, and it is up to the analyst to properly specify a model that properly accounts for the effects of multiplicity and other sources of uncertainty. The author outlines how this operates in three settings: i) estimating treatment effects for rare events, ii) the number of trials available for a meta-analysis, and iii) the estimation of population mean overall survival. It isn’t so much that multiplicity and sample size are irrelevant, as they could inform the analysis, but rather that no data is too weak for a Bayesian analyst.

Life satisfaction, QALYs, and the monetary value of health. Social Science & Medicine [PubMed] Published 18th June 2018

One of this blog’s first ever posts was on the subject of ‘the well-being valuation approach‘ but, to date, I don’t think we’ve ever covered a study in the round-up that uses this method. In essence, the method is about estimating trade-offs between (for example) income and some measure of subjective well-being, or some health condition, in order to estimate the income equivalence for that state. This study attempts to estimate the (Australian) dollar value of QALYs, as measured using the SF-6D. Thus, the study is a rival cousin to the Claxton-esque opportunity cost approach, and a rival sibling to stated preference ‘social value of a QALY’ approaches. The authors are trying to identify a threshold value on the basis of revealed preferences. The analysis is conducted using 14 waves of the Australian HILDA panel, with more than 200,000 person-year responses. A regression model estimates the impact on life satisfaction of income, SF-6D index scores, and the presence of long-term conditions. The authors adopt an instrumental variable approach to try and address the endogeneity of life satisfaction and income, using an indicator of ‘financial worsening’ to approximate an income shock. The estimated value of a QALY is found to be around A$42,000 (~£23,500) over a 2-year period. Over the long-term, it’s higher, at around A$67,000 (~£37,500), because individuals are found to discount money differently to health. The results also demonstrate that individuals are willing to pay around A$2,000 to avoid a long-term condition on top of the value of a QALY. The authors apply their approach to a few examples from the literature to demonstrate the implications of using well-being valuation in the economic evaluation of health care. As with all uses of experienced utility in the health domain, adaptation is a big concern. But a key advantage is that this approach can be easily applied to large sets of survey data, giving powerful results. However, I haven’t quite got my head around how meaningful the results are. SF-6D index values – as used in this study – are generated on the basis of stated preferences. So to what extent are we measuring revealed preferences? And if it’s some combination of stated and revealed preference, how should we interpret willingness to pay values?

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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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