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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Chris Sampson’s journal round-up for 2nd April 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.

Quality-adjusted life-years without constant proportionality. Value in Health Published 27th March 2018

The assumption of constant proportional trade-offs (CPTO) is at the heart of everything we do with QALYs. It assumes that duration has no impact on the value of a given health state, and so the value of a health state is constant regardless of its duration. This assumption has been repeatedly demonstrated to fail. This study looks for a non-constant alternative, which hasn’t been done before. The authors consider a quality-adjusted lifespan and four functional forms for the relationship between time and the value of life: constant, discount, logarithmic, and power. These relationships were tested in an online survey with more than 5,000 people, which involved the completion of 30-40 time trade-off pairs based on the EQ-5D-5L. Respondents traded off health states of varying severities and durations. Initially, a saturated model (making no assumptions about functional form) was estimated. This demonstrated that the marginal value of lifespan is decreasing. The authors provide a set of values attached to different health states at different durations. Then, the econometric model is adjusted to suit a power model, with the power estimated for duration expressed in days, weeks, months, or years. The power value for time is 0.415, but different expressions of time could introduce bias; time expressed in days (power=0.403) loses value faster than time expressed in years (power=0.654). There are also some anomalies that arise from the data that don’t fit the power function. For example, a single day of moderate problems can be worse than death, whereas 7 days or more is not. Using ‘power QALYs’ could be the future. But the big remaining question is whether decisionmakers ought to respond to people’s time preferences in this way.

A systematic review of studies comparing the measurement properties of the three-level and five-level versions of the EQ-5D. PharmacoEconomics [PubMed] Published 23rd March 2018

The debate about the EQ-5D-5L continues (on Twitter, at least). Conveniently, this paper addresses a concern held by some people – that we don’t understand the implications of using the 5L descriptive system. The authors systematically review papers comparing the measurement properties of the 3L and 5L, written in English or German. The review ended up including 24 studies. The measurement properties that were considered by the authors were: i) distributional properties, ii) informativity, iii) inconsistencies, iv) responsiveness, and v) test-retest reliability. The last property involves consideration of index values. Each study was also quality-assessed, with all being considered of good to excellent quality. The studies covered numerous countries and different respondent groups, with sample sizes from the tens to the thousands. For most measurement properties, the findings for the 3L and 5L were very similar. Floor effects were generally below 5% and tended to be slightly reduced for the 5L. In some cases, the 5L was associated with major reductions in the proportion of people responding as 11111 – a well-recognised ceiling effect associated with the 3L. Just over half of the studies reported on informativity using Shannon’s H’ and Shannon’s J’. The 5L provided consistently better results. Only three studies looked at responsiveness, with two slightly favouring the 5L and one favouring the 3L. The latter could be explained by the use of the 3L-5L crosswalk, which is inherently less responsive because it is a crosswalk. The overarching message is consistency. Business as usual. This is important because it means that the 3L and 5L descriptive systems provide comparable results (which is the basis for the argument I recently made that they are measuring the same thing). In some respects, this could be disappointing for 5L proponents because it suggests that the 5L descriptive system is not a lot better than the 3L. But it is a little better. This study demonstrates that there are still uncertainties about the differences between 3L and 5L assessments of health-related quality of life. More comparative studies, of the kind included in this review, should be conducted so that we can better understand the differences in results that are likely to arise now that we have moved (relatively assuredly) towards using the 5L instead of the 3L.

Preference-based measures to obtain health state utility values for use in economic evaluations with child-based populations: a review and UK-based focus group assessment of patient and parent choices. Quality of Life Research [PubMed] Published 21st March 2018

Calculating QALYs for kids continues to be a challenge. One of the challenges is the choice of which preference-based measure to use. Part of the problem here is that the EuroQol group – on which we rely for measuring adult health preferences – has been a bit slow. There’s the EQ-5D-Y, which has been around for a while, but it wasn’t developed with any serious thought about what kids value and there still isn’t a value set for the UK. So, if we use anything, we use a variety of measures. In this study, the authors review the use of generic preference-based measures. 45 papers are identified, including 5 different measures: HUI2, HUI3, CHU-9D, EQ-5D-Y, and AQOL-6D. No prizes for guessing that the EQ-5D (adult version) was the most commonly used measure for child-based populations. Unfortunately, the review is a bit of a disappointment. And I’m not just saying that because at least one study on which I’ve worked isn’t cited. The search strategy is likely to miss many (perhaps most) trial-based economic evaluations with children, for which cost-utility analyses don’t usually get a lot of airtime. It’s hard to see how a review of this kind is useful if it isn’t comprehensive. But the goal of the paper isn’t just to summarise the use of measures to date. The focus is on understanding when researchers should use self- or proxy-response, and when a parent-child dyad might be most useful. The literature review can’t do much to guide that question except to assert that the identified studies tended to use parent–proxy respondents. But the study also reports on some focus groups, which are potentially more useful. These were conducted as part of a wider study relating to the design of an RCT. In five focus groups, participants were presented with the EQ-5D-Y and the CHU-9D. It isn’t clear why these two measures were selected. The focus groups included parents and some children over the age of 11. Unfortunately, there’s no real (qualitative) analysis conducted, so the findings are limited. Parents expressed concern about a lack of sensitivity. Naturally, they thought that they knew best and should be the respondents. Of the young people reviewing the measures themselves, the EQ-5D-Y was perceived as more straightforward in referring to tangible experiences, whereas the CHU-9D’s severity levels were seen as more representative. Older adolescents tended to prefer the CHU-9D. The youths weren’t so sure of themselves as the adults and, though they expressed concern about their parents not understanding how they feel, they were generally neutral to who ought to respond. The older kids wanted to speak for themselves. The paper provides a good overview of the different measures, which could be useful for researchers planning data collection for child health utility measurement. But due to the limitations of the review and the lack of analysis of the focus groups, the paper isn’t able to provide any real guidance.

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Chris Sampson’s journal round-up for 5th February 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.

Cost-effectiveness analysis of germ-line BRCA testing in women with breast cancer and cascade testing in family members of mutation carriers. Genetics in Medicine [PubMed] Published 4th January 2018

The idea of testing women for BRCA mutations – faulty genes that can increase the probability and severity of breast and ovarian cancers – periodically makes it into the headlines. That’s not just because of Angelina Jolie. It’s also because it’s a challenging and active area of research with many uncertainties. This new cost-effectiveness analysis evaluates a programme that incorporates cascade testing; testing relatives of mutation carriers. The idea is that this could increase the effectiveness of the programme with a reduced cost-per-identification, as relatives of mutation carriers are more likely to also carry a mutation. The researchers use a cohort-based Markov-style decision analytic model. A programme with three test cohorts – i) women with unilateral breast cancer and a risk prediction score >10%, ii) first-degree relatives, and iii) second-degree relatives – was compared against no testing. A positive result in the original high-risk individual leads to testing in the first- and second-degree relatives, with the number of subsequent tests occurring in the model determined by assumptions about family size. Women who test positive can receive risk-reducing mastectomy and/or bilateral salpingo-oophorectomy (removal of the ovaries). The results are favourable to the BRCA testing programme, at $19,000 (Australian) per QALY for testing affected women only and $15,000 when the cascade testing of family members was included, with high probabilities of cost-effectiveness at $50,000 per QALY. I’m a little confused by the model. The model includes the states ‘BRCA positive’ and ‘Breast cancer’, which clearly are not mutually exclusive. And It isn’t clear how women entering the model with breast cancer go on to enjoy QALY benefits compared to the no-test group. I’m definitely not comfortable with the assumption that there is no disutility associated with risk-reducing surgery. I also can’t see where the cost of identifying the high-risk women in the first place was accounted for. But this is a model, after all. The findings appear to be robust to a variety of sensitivity analyses. Part of the value of testing lies in the information it provides about people beyond the individual patient. Clearly, if we want to evaluate the true value of testing then this needs to be taken into account.

Economic evaluation of direct-acting antivirals for hepatitis C in Norway. PharmacoEconomics Published 2nd February 2018

Direct-acting antivirals (DAAs) are those new drugs that gave NICE a headache a few years back because they were – despite being very effective and high-value – unaffordable. DAAs are essentially curative, which means that they can reduce resource use over a long time horizon. This makes cost-effectiveness analysis in this context challenging. In this new study, the authors conduct an economic evaluation of DAAs compared with the previous class of treatment, in the Norwegian context. Importantly, the researchers sought to take into account the rebates that have been agreed in Norway, which mean that the prices are effectively reduced by up to 50%. There are now lots of different DAAs available. Furthermore, hepatitis C infection corresponds to several different genotypes. This means that there is a need to identify which treatments are most (cost-)effective for which groups of patients; this isn’t simply a matter of A vs B. The authors use a previously developed model that incorporates projections of the disease up to 2030, though the authors extrapolate to a 100-year time horizon. The paper presents cost-effectiveness acceptability frontiers for each of genotypes 1, 2, and 3, clearly demonstrating which medicines are the most likely to be cost-effective at given willingness-to-pay thresholds. For all three genotypes, at least one of the DAA options is most likely to be cost-effective above a threshold of €70,000 per QALY (which is apparently recommended in Norway). The model predicts that if everyone received the most cost-effective strategy then Norway would expect to see around 180 hepatitis C patients in 2030 instead of the 300-400 seen in the last six years. The study also presents the price rebates that would be necessary to make currently sub-optimal medicines cost-effective. The model isn’t that generalisable. It’s very much Norway-specific as it reflects the country’s treatment guidelines. It also only looks at people who inject drugs – a sub-population whose importance can vary a lot from one country to the next. I expect this will be a valuable piece of work for Norway, but it strikes me as odd that “affordability” or “budget impact” aren’t even mentioned in the paper.

Cost-effectiveness of prostate cancer screening: a systematic review of decision-analytical models. BMC Cancer [PubMed] Published 18th January 2018

You may have seen prostate cancer in the headlines last week. Despite the number of people in the UK dying each year from prostate cancer now being greater than the number of people dying from breast cancer, prostate cancer screening remains controversial. This is because over-detection and over-treatment are common and harmful. Plenty of cost-effectiveness studies have been conducted in the context of detecting and treating prostate cancer. But there are various ways of modelling the problem and various specifications of screening programme that can be evaluated. So here we have a systematic review of cost-effectiveness models evaluating prostate-specific antigen (PSA) blood tests as a basis for screening. From a haul of 1010 studies, 10 made it into the review. The studies modelled lots of different scenarios, with alternative screening strategies, PSA thresholds, and treatment pathways. The results are not consistent. Many of the scenarios evaluated in the studies were more costly and less effective than current practice (which tended to be the lack of any formal screening programme). None of the UK-based cost-per-QALY estimates favoured screening. The authors summarise the methodological choices made in each study and consider the extent to which this relates to the pathways being modelled. They also specify the health state utility values used in the models. This will be a very useful reference point for anyone trying their hand at a prostate cancer screening model. Of the ten studies included in the review, four of them found at least one screening programme to be potentially cost-effective. ‘Adaptive screening’ – whereby individuals’ recall to screening was based on their risk – was considered in two studies using patient-level simulations. The authors suggest that cohort-level modelling could be sufficient where screening is not determined by individual risk level. There are also warnings against inappropriate definition of the comparator, which is likely to be opportunistic screening rather than a complete absence of screening. Generally speaking, a lack of good data seems to be part of the explanation for the inconsistency in the findings. It could be some time before we have a clearer understanding of how to implement a cost-effective screening programme for prostate cancer.

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