Chris Sampson’s journal round-up for 15th October 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.

Reliability and validity of the contingent valuation method for estimating willingness to pay: a case of in vitro fertilisation. Applied Health Economics and Health Policy [PubMed] Published 13th October 2018

In vitro fertilisation (IVF) is a challenge for standard models of valuation in health economics. Mostly, that’s because, despite it falling within the scope of health care, and despite infertility being a health problem, many of the benefits of IVF can’t be considered health-specific. QALYs can’t really do the job, so there’s arguably a role for cost-benefit analysis, and for using stated preference methods to determine the value of IVF. This study adds to an existing literature studying willingness to pay for IVF, but differs in that it tries to identify willingness to pay (WTP) from the general population. This study is set in Australia, where IVF is part-funded by universal health insurance, so asking the public is arguably the right thing to do.

Three contingent valuation surveys were conducted online with 1,870 people from the general public. The first survey used a starting point bid of $10,000, and then, 10 months later, two more surveys were conducted with starting point bids of $4,000 and $10,000. Each included questions for a 10%, 20%, and 50% success rate. Respondents were asked to adopt an ex-post perspective, assuming that they were infertile and could conceive by IVF. Individuals could respond to starting bids with ‘yes’, ‘no’, ‘not sure’, or ‘I am not willing to pay anything’. WTP for one IVF cycle with a 20% success rate ranged from $6,353 in the $4,000 survey to $11,750 in the first $10,000 survey. WTP for a year of treatment ranged from $18,433 to $28,117. The method was reliable insofar as there were no differences between the first and second $10,000 surveys. WTP values corresponded to the probability of success, providing support for the internal construct validity of the survey. However, the big difference between values derived using the alternative starting point bids indicates a strong anchoring bias. The authors also tested the external criterion validity by comparing the number of respondents willing to pay more than $4,000 for a cycle with a 20% success rate (roughly equivalent to the out of pocket cost in Australia) with the number of people who actually choose to pay for IVF in Australia. Around 63% of respondents were willing to pay at that price, which is close to the estimated 60% in Australia.

This study provides some support for the use of contingent valuation methods in the context of IVF, and for its use in general population samples. But the anchoring effect is worrying and justifies further research to identify appropriate methods to counteract this bias. The exclusion of the “not sure” and “I will not pay anything” responses from the analysis – as ‘non-demanders’ – arguably undermines the ‘societal valuation’ aspect of the estimates.

Pharmaceutical expenditure and gross domestic product: evidence of simultaneous effects using a two‐step instrumental variables strategy. Health Economics [PubMed] Published 10th October 2018

The question of how governments determine spending on medicines is pertinent in the UK right now, as the Pharmaceutical Price Regulation Scheme approaches its renewal date. The current agreement includes a cap on pharmaceutical expenditure. It should go without saying that GDP ought to have some influence on how much public spending is dedicated to medicines. But, when medicines expenditure might also influence GDP, the actual relationship is difficult to estimate. In this paper, the authors seek to identify both effects: the income elasticity of government spending on pharmaceuticals and the effect of that spending on income.

The authors use a variety of data sources from the World Health Organization, World Bank, and International Monetary Fund to construct an unbalanced panel for 136 countries from 1995 to 2006. To get around the challenge of two-way causality, the authors implement a two-step instrumental variable approach. In the first step of the procedure, a model estimates the impact of GDP per capita on government spending on pharmaceuticals. International tourist receipts are used as an instrument that is expected to correlate strongly with GDP per capita, but which is expected to be unrelated to medicines expenditure (except through its correlation with GDP). The model attempts to control for health care expenditure, life expectancy, and other important country-specific variables. In the second step, a reverse causality model is used to assess the impact of pharmaceutical expenditure on GDP per capita, with pharmaceutical expenditure adjusted to partial-out the response to GDP estimated in the first step.

The headline average results are that GDP increases pharmaceutical expenditure and that pharmaceutical expenditure reduces GDP. A 1% increase in GDP per capita increases public pharmaceutical expenditure per capita by 1.4%, suggesting that pharmaceuticals are a luxury good. A 1% increase in public pharmaceutical expenditure is associated with a 0.09% decrease in GDP per capita. But the results are more nuanced than that. The authors outline various sources of heterogeneity. The positive effect of GDP on pharmaceutical expenditure only holds for high-income countries and the negative effect of pharmaceutical expenditure on GDP only holds for low-income countries. Quantile regressions show that income elasticity decreases for higher quantiles of expenditure. GDP only influences pharmaceutical spending in countries classified as ‘free’ on the index of Economic Freedom of the World, and pharmaceutical expenditure only has a negative impact on GDP in countries that are ‘not free’.

I’ve never come across this kind of two-step approach before, so I’m still trying to get my head around whether the methods and the data are adequate. But a series of robustness checks provide some reassurance. In particular, an analysis of intertemporal effects using lagged GDP and lagged pharmaceutical expenditure demonstrates the robustness of the main findings. Arguably, the findings of this study are more important for policymaking in low- and middle-income countries, where pharmaceutical expenditures might have important consequences for GDP. In high-income (and ‘free’) economies that spend a lot on medicines, like the UK, there is probably less at stake. This could be because of effective price regulation and monitoring, and better adherence, ensuring that pharmaceutical expenditure is not wasteful.

Parental health spillover in cost-effectiveness analysis: evidence from self-harming adolescents in England. PharmacoEconomics [PubMed] [RePEc] Published 8th October 2018

Any intervention has the potential for spillover effects, whereby people other than the recipient of care are positively or negatively affected by the consequences of the intervention. Where a child is the recipient of care, it stands to reason that any intervention could affect the well-being of the parents and that these impacts should be considered in economic evaluation. But how should parental spillovers be incorporated? Are parental utilities additive to that of the child patient? Or should a multiplier effect be used with reference to the effect of an intervention on the child’s utility?

The study reports on a trial-based economic evaluation of family therapy for self-harming adolescents aged 11-17. Data collection included EQ-5D-3L for the adolescents and HUI2 for the main caregiver (86% mothers) at baseline, 6-month follow-up, and 12-month follow-up, collected from 731 patient-parent pairs. The authors outline six alternative methods for including parental health spillovers: i) relative health spillover, ii) relative health spillover per treatment arm, iii) absolute health spillover, iv) absolute global health spillover per treatment arm, v) additive accrued health benefits, and vi) household equivalence scales. These differ according to whether parental utility is counted as depending on adolescent’s utility, treatment allocation, the primary outcome of the study, or some combination thereof. But the authors’ primary focus (and the main contribution of this study) is the equivalence scale option. This involves adding together the spillover effects for other members of the household and using alternative weightings depending on the importance of parental utility compared with adolescent utility.

Using Tobit models, controlling for a variety of factors, the authors demonstrate that parental utility is associated with adolescent utility. Then, economic evaluations are conducted using each of the alternative spillover accounting methods. The base case of including only adolescents’ utility delivers an ICER of around £40,453. Employing the alternative methods gives quite different results, with the intervention dominated in two of the cases and an ICER below £30,000 per QALY in others. For the equivalence scale approach, the authors employ several elasticities for spillover utility, ranging from 0 (where parental utility is of equivalent value to adolescent utility and therefore additive) to 1 (where the average health spillover per household member is estimated for each patient). The ICER estimates using the equivalence scale approach ranged from £27,166 to £32,504. Higher elasticity implied lower cumulated QALYs.

The paper’s contribution is methodological, and I wouldn’t read too much into the magnitude of the results. For starters, the use of HUI2 (a measure for children) in adults and the use of EQ-5D-3L (a measure for adults) in the children is somewhat confusing. The authors argue that health gains should only be aggregated at the household level if the QALY gain for the patient is greater or equal to zero, because the purpose of treatment is to benefit the adolescents, not the parents. And they argue in favour of using an equivalence scale approach. By requiring an explicit judgement to set the elasticity within the estimation, the method provides a useful and transparent approach to including parental spillovers.

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Alastair Canaway’s journal round-up for 30th 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.

Is there an association between early weight status and utility-based health-related quality of life in young children? Quality of Life Research [PubMed] Published 10th July 2018

Childhood obesity is an issue which has risen to prominence in recent years. Concurrently, there has been an increased interest in measuring utility values in children for use in economic evaluation. In the obesity context, there are relatively few studies that have examined whether childhood weight status is associated with preference-based utility and, following, whether such measures are useful for the economic evaluation of childhood obesity interventions. This study sought to tackle this issue using the proxy version of the Health Utilities Index Mark 3 (HUI-3) and weight status data in 368 children aged five years. Associations between weight status and HUI-3 score were assessed using various regression techniques. No statistically significant differences were found between weight status and preference-based health-related quality of life (HRQL). This adds to several recent studies with similar findings which imply that young children may not experience any decrements in HRQL associated with weight status, or that the measures we have cannot capture these decrements. When considering trial-based economic evaluation of childhood obesity interventions, this highlights that we should not be solely relying on preference-based instruments.

Time is money: investigating the value of leisure time and unpaid work. Value in Health Published 14th July 2018

For those of us who work on trials, we almost always attempt to do some sort of ‘societal’ perspective incorporating benefits beyond health. When it comes to valuing leisure time and unpaid work there is a dearth of literature and numerous methodological challenges which has led to a bit of a scatter-gun approach to measuring and valuing (usually by ignoring) this time. The authors in the paper sought to value unpaid work (e.g. household chores and voluntary work) and leisure time (“non-productive” time to be spent on one’s likings, nb. this includes lunch breaks). They did this using online questionnaires which included contingent valuation exercises (WTP and WTA) in a sample of representative adults in the Netherlands. Regression techniques following best practice were used (two-part models with transformed data). Using WTA they found an additional hour of unpaid work and leisure time was valued at €16 Euros, whilst the WTP value was €9.50. These values fall into similar ranges to those used in other studies. There are many issues with stated preference studies, which the authors thoroughly acknowledge and address. These costs, so often omitted in economic evaluation, have the potential to be substantial and there remains a need to accurately value this time. Capturing and valuing these time costs remains an important issue, specifically, for those researchers working in countries where national guidelines for economic evaluation prefer a societal perspective.

The impact of depression on health-related quality of life and wellbeing: identifying important dimensions and assessing their inclusion in multi-attribute utility instruments. Quality of Life Research [PubMed] Published 13th July 2018

At the start of every trial, we ask “so what measures should we include?” In the UK, the EQ-5D is the default option, though this decision is not often straightforward. Mental health disorders have a huge burden of impact in terms of both costs (economic and healthcare) and health-related quality of life. How we currently measure the impact of such disorders in economic evaluation often receives scrutiny and there has been recent interest in broadening the evaluative space beyond health to include wellbeing, both subjective wellbeing (SWB) and capability wellbeing (CWB). This study sought to identify which dimensions of HRQL, SWB and CWB were most affected by depression (the most common mental health disorder) and to examine the sensitivity of existing multi-attribute utility instruments (MAUIs) to these dimensions. The study used data from the “Multi-Instrument Comparison” study – this includes lots of measures, including depression measures (Depression Anxiety Stress Scale, Kessler Psychological Distress Scale); SWB measures (Personal Wellbeing Index, Satisfaction with Life Scale, Integrated Household Survey); CWB (ICECAP-A); and multi-attribute utility instruments (15D, AQoL-4D, AQoL-8D, EQ-5D-5L, HUI-3, QWB-SA, and SF-6D). To identify dimensions that were important, the authors used the ‘Glass’s Delta effect size’ (the difference between the mean scores of healthy and self-reported groups divided by the standard deviation of the healthy group). To investigate the extent to which current MAUIs capture these dimensions, each MAUI was regressed on each dimension of HRQL, CWB and SWB. There were lots of interesting findings. Unsurprisingly, the most important dimensions were in the psychosocial dimensions of HRQL (e.g. the ‘coping’, ‘happiness’, and ‘self-worth’ dimensions of the AQoL-8D). Interestingly, the ICECAP-A proved to be the best measure for distinguishing between healthy individuals and those with depression. The SWB measures, on the other hand, were less impacted by depression. Of the MAUIs, the AQoL-8D was the most sensitive, whilst our beloved EQ-5D-5L and SF-6D were the least sensitive at distinguishing dimensions. There is a huge amount to unpack within this study, but it does raise interesting questions regarding measurement issues and the impact of broadening the evaluative space for decision makers. Finally, it’s worth noting that a new MAUI (ReQoL) for mental health has been recently developed – although further testing is needed, this is something to consider in future.

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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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