Chris Sampson’s journal round-up for 11th March 2019

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.

Identification, review, and use of health state utilities in cost-effectiveness models: an ISPOR Good Practices for Outcomes Research Task Force report. Value in Health [PubMed] Published 1st March 2019

When modellers select health state utility values to plug into their models, they often do it in an ad hoc and unsystematic way. This ISPOR Task Force report seeks to address that.

The authors discuss the process of searching, reviewing, and synthesising utility values. Searches need to use iterative techniques because evidence requirements develop as a model develops. Due to the scope of models, it may be necessary to develop multiple search strategies (for example, for different aspects of disease pathways). Searches needn’t be exhaustive, but they should be systematic and transparent. The authors provide a list of factors that should be considered in defining search criteria. In reviewing utility values, both quality and appropriateness should be considered. Quality is indicated by the precision of the evidence, the response rate, and missing data. Appropriateness relates to the extent to which the evidence being reviewed conforms to the context of the model in which it is to be used. This includes factors such as the characteristics of the study population, the measure used, value sets used, and the timing of data collection. When it comes to synthesis, the authors suggest it might not be meaningful in most cases, because of variation in methods. We can’t pool values if they aren’t (at least roughly) equivalent. Therefore, one approach is to employ strict inclusion criteria (e.g only EQ-5D, only a particular value set), but this isn’t likely to leave you with much. Meta-regression can be used to analyse more dissimilar utility values and provide insight into the impact of methodological differences. But the extent to which this can provide pooled values for a model is questionable, and the authors concede that more research is needed.

This paper can inform that future research. Not least in its attempt to specify minimum reporting standards. We have another checklist, with another acronym (SpRUCE). The idea isn’t so much that this will guide publications of systematic reviews of utility values, but rather that modellers (and model reviewers) can use it to assess whether the selection of utility values was adequate. The authors then go on to offer methodological recommendations for using utility values in cost-effectiveness models, considering issues such as modelling technique, comorbidities, adverse events, and sensitivity analysis. It’s early days, so the recommendations in this report ought to be changed as methods develop. Still, it’s a first step away from the ad hoc selection of utility values that (no doubt) drives the results of many cost-effectiveness models.

Estimating the marginal cost of a life year in Sweden’s public healthcare sector. The European Journal of Health Economics [PubMed] Published 22nd February 2019

It’s only recently that health economists have gained access to data that enables the estimation of the opportunity cost of health care expenditure on a national level; what is sometimes referred to as a supply-side threshold. We’ve seen studies in the UK, Spain, Australia, and here we have one from Sweden.

The authors use data on health care expenditure at the national (1970-2016) and regional (2003-2016) level, alongside estimates of remaining life expectancy by age and gender (1970-2016). First, they try a time series analysis, testing the nature of causality. Finding an apparently causal relationship between longevity and expenditure, the authors don’t take it any further. Instead, the results are based on a panel data analysis, employing similar methods to estimates generated in other countries. The authors propose a conceptual model to support their analysis, which distinguishes it from other studies. In particular, the authors assert that the majority of the impact of expenditure on mortality operates through morbidity, which changes how the model should be specified. The number of newly graduated nurses is used as an instrument indicative of a supply-shift at the national rather than regional level. The models control for socioeconomic and demographic factors and morbidity not amenable to health care.

The authors estimate the marginal cost of a life year by dividing health care expenditure by the expenditure elasticity of life expectancy, finding an opportunity cost of €38,812 (with a massive 95% confidence interval). Using Swedish population norms for utility values, this would translate into around €45,000/QALY.

The analysis is considered and makes plain the difficulty of estimating the marginal productivity of health care expenditure. It looks like a nail in the coffin for the idea of estimating opportunity costs using time series. For now, at least, estimates of opportunity cost will be based on variation according to geography, rather than time. In their excellent discussion, the authors are candid about the limitations of their model. Their instrument wasn’t perfect and it looks like there may have been important confounding variables that they couldn’t control for.

Frequentist and Bayesian meta‐regression of health state utilities for multiple myeloma incorporating systematic review and analysis of individual patient data. Health Economics [PubMed] Published 20th February 2019

The first paper in this round-up was about improving practice in the systematic review of health state utility values, and it indicated the need for more research on the synthesis of values. Here, we have some. In this study, the authors conduct a meta-analysis of utility values alongside an analysis of registry and clinical study data for multiple myeloma patients.

A literature search identified 13 ‘methodologically appropriate’ papers, providing 27 health state utility values. The EMMOS registry included data for 2,445 patients in 22 counties and the APEX clinical study included 669 patients, all with EQ-5D-3L data. The authors implement both a frequentist meta-regression and a Bayesian model. In both cases, the models were run including all values and then with a limited set of only EQ-5D values. These models predicted utility values based on the number of treatment classes received and the rate of stem cell transplant in the sample. The priors used in the Bayesian model were based on studies that reported general utility values for the presence of disease (rather than according to treatment).

The frequentist models showed that utility was low at diagnosis, higher at first treatment, and lower at each subsequent treatment. Stem cell transplant had a positive impact on utility values independent of the number of previous treatments. The results of the Bayesian analysis were very similar, which the authors suggest is due to weak priors. An additional Bayesian model was run with preferred data but vague priors, to assess the sensitivity of the model to the priors. At later stages of disease (for which data were more sparse), there was greater uncertainty. The authors provide predicted values from each of the five models, according to the number of treatment classes received. The models provide slightly different results, except in the case of newly diagnosed patients (where the difference was 0.001). For example, the ‘EQ-5D only’ frequentist model gave a value of 0.659 for one treatment, while the Bayesian model gave a value of 0.620.

I’m not sure that the study satisfies the recommendations outlined in the ISPOR Task Force report described above (though that would be an unfair challenge, given the timing of publication). We’re told very little about the nature of the studies that are included, so it’s difficult to judge whether they should have been combined in this way. However, the authors state that they have made their data extraction and source code available online, which means I could check that out (though, having had a look, I can’t find the material that the authors refer to, reinforcing my hatred for the shambolic ‘supplementary material’ ecosystem). The main purpose of this paper is to progress the methods used to synthesise health state utility values, and it does that well. Predictably, the future is Bayesian.

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Chris Sampson’s journal round-up for 14th May 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 practical guide to conducting a systematic review and meta-analysis of health state utility values. PharmacoEconomics [PubMed] Published 10th May 2018

I love articles that outline the practical application of a particular method to solve a particular problem, especially when the article shares analysis code that can be copied and adapted. This paper does just that for the case of synthesising health state utility values. Decision modellers use utility values as parameters. Most of the time these are drawn from a single source which almost certainly introduces some kind of bias to the resulting cost-effectiveness estimates. So it’s better to combine all of the relevant available information. But that’s easier said than done, as numerous researchers (myself included) have discovered. This paper outlines the various approaches and some of the merits and limitations of each. There are some standard stages, for which advice is provided, relating to the identification, selection, and extraction of data. Those are by no means simple tasks, but the really tricky bit comes when you try and pool the utility values that you’ve found. The authors outline three strategies: i) fixed effect meta-analysis, ii) random effects meta-analysis, and iii) mixed effects meta-regression. Each is illustrated with a hypothetical example, with Stata and R commands provided. Broadly speaking, the authors favour mixed effects meta-regression because of its ability to identify the extent of similarity between sources and to help explain heterogeneity. The authors insist that comparability between sources is a precondition for pooling. But the thing about health state utility values is that they are – almost by definition – never comparable. Different population? Not comparable. Different treatment pathway? No chance. Different utility measure? Ha! They may or may not appear to be similar statistically, but that’s totally irrelevant. What matters is whether the decision-maker ‘believes’ the values. If they believe them then they should be included and pooled. If decision-makers have reason to believe one source more or less than another then this should be accounted for in the weighting. If they don’t believe them at all then they should be excluded. Comparability is framed as a statistical question, when in reality it is a conceptual one. For now, researchers will have to tackle that themselves. This paper doesn’t solve all of the problems around meta-analysis of health state utility values, but it does a good job of outlining methodological developments to date and provides recommendations in accordance with them.

Unemployment, unemployment duration, and health: selection or causation? The European Journal of Health Economics [PubMed] Published 3rd May 2018

One of the major socioeconomic correlates of poor health is unemployment. It appears not to be very good for you. But there’s an obvious challenge here – does unemployment cause ill-health, or are unhealthy people just more likely to be unemployed? Both, probably, but that answer doesn’t make for clear policy solutions. This paper – following a large body of literature – attempts to explain what’s going on. Its novelty comes in the way the author considers timing and distinguishes between mental and physical health. The basis for the analysis is that selection into unemployment by the unhealthy ought to imply time-constant effects of unemployment on health. On the other hand, the negative effect of unemployment on health ought to grow over time. Using seven waves of data from the German Socio-economic Panel, a sample of 17,000 people (chopped from 48,000) is analysed, of which around 3,000 experienced unemployment. The basis for measuring mental and physical health is summary scores from the SF-12. A fixed-effects model is constructed based on the dependence of health on the duration and timing of unemployment, rather than just the occurrence of unemployment per se. The author finds a cumulative effect of unemployment on physical ill-health over time, implying causation. This is particularly pronounced for people unemployed in later life, and there was essentially no impact on physical health for younger people. The longer people spent unemployed, the more their health deteriorated. This was accompanied by a strong long-term selection effect of less physically healthy people being more likely to become unemployed. In contrast, for mental health, the findings suggest a short-term selection effect of people who experience a decline in mental health being more likely to become unemployed. But then, following unemployment, mental health declines further, so the balance of selection and causation effects is less clear. In contrast to physical health, people’s mental health is more badly affected by unemployment at younger ages. By no means does this study prove the balance between selection and causality. It can’t account for people’s anticipation of unemployment or future ill-health. But it does provide inspiration for better-targeted policies to limit the impact of unemployment on health.

Different domains – different time preferences? Social Science & Medicine [PubMed] Published 30th April 2018

Economists are often criticised by non-economists. Usually, the criticisms are unfounded, but one of the ways in which I think some (micro)economists can have tunnel vision is in thinking that preferences elicited with respect to money exhibit the same characteristics as preferences about things other than money. My instinct tells me that – for most people – that isn’t true. This study looks at one of those characteristics of preferences – namely, time preferences. Unfortunately for me, it suggests that my instincts aren’t correct. The authors outline a quasi-hyperbolic discounting model, incorporating both short-term present bias and long-term impatience, to explain gym members’ time preferences in the health and monetary domains. A survey was conducted with members of a chain of fitness centres in Denmark, of which 1,687 responded. Half were allocated to money-related questions and half to health-related questions. Respondents were asked to match an amount of future gains with an amount of immediate gains to provide a point of indifference. Health problems were formulated as back pain, with an EQ-5D-3L level 2 for usual activities and a level 2 for pain or discomfort. The findings were that estimates for discount rates and present bias in the two domains are different, but not by very much. On average, discount rates are slightly higher in the health domain – a finding driven by female respondents and people with more education. Present bias is the same – on average – in each domain, though retired people are more present biased for health. The authors conclude by focussing on the similarity between health and monetary time preferences, suggesting that time preferences in the monetary domain can safely be applied in the health domain. But I’d still be wary of this. For starters, one would expect a group of gym members – who have all decided to join the gym – to be relatively homogenous in their time preferences. Findings are similar on average, and there are only small differences in subgroups, but when it comes to health care (even public health) we’re never dealing with average people. Targeted interventions are increasingly needed, which means that differential discount rates in the health domain – of the kind identified in this study – should be brought into focus.

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Alastair Canaway’s journal round-up for 29th January 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.

Is “end of life” a special case? Connecting Q with survey methods to measure societal support for views on the value of life-extending treatments. Health Economics [PubMed] Published 19th January 2018

Should end-of-life care be treated differently? A question often asked and previously discussed on this blog: findings to date are equivocal. This question is important given NICE’s End-of-Life Guidance for increased QALY thresholds for life-extending interventions, and additionally the Cancer Drugs Fund (CDF). This week’s round-up sees Helen Mason and colleagues attempt to inform the debate around societal support for views of end-of-life care, by trying to determine the degree of support for different views on the value of life-extending treatment. It’s always a treat to see papers grounded in qualitative research in the big health economics journals and this month saw the use of a particularly novel mixed methods approach adding a quantitative element to their previous qualitative findings. They combined the novel (but increasingly recognisable thanks to the Glasgow team) Q methodology with survey techniques to examine the relative strength of views on end-of-life care that they had formulated in a previous Q methodology study. Their previous research had found that there are three prevalent viewpoints on the value of life-extending treatment: 1. ‘a population perspective: value for money, no special cases’, 2. ‘life is precious: valuing life-extension and patient choice’, 3. ‘valuing wider benefits and opportunity cost: the quality of life and death’. This paper used a large Q-based survey design (n=4902) to identify societal support for the three different viewpoints. Viewpoints 1 and 2 were found to be dominant, whilst there was little support for viewpoint 3. The two supported viewpoints are not complimentary: they represent the ethical divide between the utilitarian with a fixed budget (view 1), and the perspective based on entitlement to healthcare (view 2: which implies an expanding healthcare budget in practice). I suspect most health economists will fall into camp number one. In terms of informing decision making, this is very helpful, yet unhelpful: there is no clear answer. It is, however, useful for decision makers in providing evidence to balance the oft-repeated ‘end of life is special’ argument based solely on conjecture, and not evidence (disclosure: I have almost certainly made this argument before). Neither of the dominant viewpoints supports NICE’s End of Life Guidance nor the CDF. Viewpoint 1 suggests end of life interventions should be treated the same as others, whilst viewpoint 2 suggests that treatments should be provided if the patient chooses them; it does not make end of life a special case as this viewpoint believes all treatments should be available if people wish to have them (and we should expand budgets accordingly). Should end of life care be treated differently? Well, it depends on who you ask.

A systematic review and meta-analysis of childhood health utilities. Medical Decision Making [PubMed] Published 7th October 2017

If you’re working on an economic evaluation of an intervention targeting children then you are going to be thankful for this paper. The purpose of the paper was to create a compendium of utility values for childhood conditions. A systematic review was conducted which identified a whopping 26,634 papers after deduplication – sincere sympathy to those who had to do the abstract screening. Following abstract screening, data were extracted for the remaining 272 papers. In total, 3,414 utility values were included when all subgroups were considered – this covered all ICD-10 chapters relevant to child health. When considering only the ‘main study’ samples, 1,191 utility values were recorded and these are helpfully separated by health condition, and methodological characteristics. In short, the authors have successfully built a vast catalogue of child utility values (and distributions) for use in future economic evaluations. They didn’t, however, stop there, they then built on the systematic review results by conducting a meta-analysis to i) estimate health utility decrements for each condition category compared to general population health, and ii) to examine how methodological factors impact child utility values. Interestingly for those conducting research in children, they found that parental proxy values were associated with an overestimation of values. There is a lot to unpack in this paper and a lot of appendices and supplementary materials are included (including the excel database for all 3,414 subsamples of health utilities). I’m sure this will be a valuable resource in future for health economic researchers working in the childhood context. As far as MSc dissertation projects go, this is a very impressive contribution.

Estimating a cost-effectiveness threshold for the Spanish NHS. Health Economics [PubMed] [RePEc] Published 28th December 2017

In the UK, the cost-per-QALY threshold is long-established, although whether it is the ‘correct’ value is fiercely debated. Likewise in Spain, there is a commonly cited threshold value of €30,000 per QALY with a dearth of empirical justification. This paper sought to identify a cost-per-QALY threshold for the Spanish National Health Service (SNHS) by estimating the marginal cost per QALY at which the SNHS currently operates on average. This was achieved by exploiting data on 17 regional health services between the years 2008-2012 when the health budget experienced considerable cuts due to the global economic crisis. This paper uses econometric models based on the provoking work by Claxton et al in the UK (see the full paper if you’re interested in the model specification) to achieve this. Variations between Spanish regions over time allowed the authors to estimate the impact of health spending on outcomes (measured as quality-adjusted life expectancy); this was then translated into a cost-per-QALY value for the SNHS. The headline figures derived from the analysis give a threshold between €22,000 and €25,000 per QALY. This is substantially below the commonly cited threshold of €30,000 per QALY. There are, however (as to be expected) various limitations acknowledged by the authors, which means we should not take this threshold as set in stone. However, unlike the status quo, there is empirical evidence backing this threshold and it should stimulate further research and discussion about whether such a change should be implemented.

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