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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Rita Faria’s journal round-up for 24th September 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.

Methodological issues in assessing the economic value of next-generation sequencing tests: many challenges and not enough solutions. Value in Health [PubMed] Published 8th August 2018

This month’s issue of Value in Health includes a themed section on assessing the value of next-generation sequencing. Next-generation sequencing is sometimes hailed as the holy grail in medicine. The promise is that our individual genome can indicate how at-risk we are for many diseases. The question is whether the information obtained by these tests is worth their costs and potentially harmful consequences on well-being and health-related quality of life. This largely remains unexplored, so I expect seeing more economic evaluations of next-generation sequencing in the future.

This paper has caught my eye given an ongoing project on cascade testing protocols for familial hypercholesterolaemia. Next-generation sequencing can be used to identify the genetic cause of familial hypercholesterolaemia, thereby identifying patients suitable to have their relatives tested for the disease. I read this paper with the hope of finding inspiration for our economic evaluation.

This thought-provoking paper discusses the challenges in conducting economic evaluations of next-generation sequencing, such as complex model structure, inclusion of upstream and downstream costs, identifying comparators, identifying costs and outcomes that are related to the test, measuring costs and outcomes, evidence synthesis, data availability and quality.

I agree with the authors that these are important challenges, and it was useful to see them explained in a systematic way. Another valuable feature of this paper is the summary of applied studies which have encountered these challenges and their approaches to overcome them. It’s encouraging to read about how other studies have dealt with complex decision problems!

I’d argue that the challenges are applicable to economic evaluations of many other interventions. For example, identifying the relevant comparators can be a challenge in the evaluations of treatments: in an evaluation of hepatitis C drugs, we compared 633 treatment sequences in 14 subgroups. I view the challenges as the issues to think about when planning an economic evaluation of any intervention: what the comparators are, the scope of the evaluation, the model conceptualisation, data sources and their statistical analysis. Therefore, I’d recommend this paper as an addition to your library about the conceptualisation of economic evaluations.

Compliance with requirement to report results on the EU Clinical Trials Register: cohort study and web resource. BMJ [PubMed] Published 12th September 2018

You may be puzzled at the choice of the latest Ben Goldacre and colleagues’ paper, as it does not include an economic component. This study investigates compliance with the European Commission’s requirements that all trials on the EU Clinical Trials Register post results to the registry within 12 months of completion. At first sight, the economic implications may not be obvious, but they do exist and are quite important.

Clinical trials are a large investment of resources, not only financial but also in the health of patients who accept to take part in an experiment that may impact their health adversely. Therefore, clinical trials can have a huge sunk cost in both money and health. The payoff only realises if the trial is reported. If the trial is not reported, the benefits from the investment cannot be realised. In sum, an unreported trial is clearly a cost-ineffective use of resources.

The solution is simple: ensure that trial results are reported. This way we can all benefit from the information collected by the trial. The issue is, as Goldacre and colleagues have revealed, compliance is far from perfect.

Remarkably, around half of the 7,274 studies are due to publish results. The worst offenders are non-commercial sponsors, where only 11% of trials had their results reported (compared with 68% of trials by a commercial sponsor).

The authors provide a web tool to look up unreported trials by institution. I looked up my very own University of York. It was reassuring to know that my institution has no trials due to report results. Nonetheless, many others are less compliant.

This is an exciting study on the world of clinical trials. I’d suggest that a possible next step would be to estimate the health lost and costs from failing to report trial results.

Network meta-analysis of diagnostic test accuracy studies identifies and ranks the optimal diagnostic tests and thresholds for health care policy and decision-making. Journal of Clinical Epidemiology [PubMed] Published 13th March 2018

Diagnostic tests are an emerging area of methodological development. This timely paper by Rhiannon Owen and colleagues addresses the important topic of evidence synthesis of diagnostic test accuracy studies.

Diagnostic test studies cannot be meta-analysed with the standard techniques used for treatment effectiveness. This is because there are two quantities of interest (sensitivity and specificity), which are correlated, and vary depending on the test threshold (that is, the value at which we say the test result is positive or negative).

Owen and colleagues propose a new approach to synthesising diagnostic test accuracy studies using network meta-analysis methodology. This innovative method allows for comparing multiple tests, evaluated at various test threshold values.

I cannot comment on the method itself as evidence synthesis is not my area of expertise. My interest comes from my experience in the economic evaluation of diagnostic tests, where we often wish to combine evidence from various studies.

With this in mind, I recommend having a look at the NIHR Complex Reviews Support Unit website for more handy tools and the latest research on methods for evidence synthesis. For example, the CRSU has a web tool for meta-analysis of diagnostic tests and a web tool to conduct network meta-analysis for those of us who are not evidence synthesis experts. Providing web tools is a brilliant way of helping analysts using these methods so, hopefully, we’ll see greater use of evidence synthesis in the future.

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Method of the month: Distributional cost effectiveness analysis

Once a month we discuss a particular research method that may be of interest to people working in health economics. We’ll consider widely used key methodologies, as well as more novel approaches. Our reviews are not designed to be comprehensive but provide an introduction to the method, its underlying principles, some applied examples, and where to find out more. If you’d like to write a post for this series, get in touch. This month’s method is distributional cost effectiveness analysis.

Principles

Variation in population health outcomes, particularly when socially patterned by characteristics such as income and race, are often of concern to policymakers. For example, the fact that people born in the poorest tenth of neighbourhoods in England can expect to live 19 fewer years of healthy life than those living in the richest tenth of neighbourhoods in the country, or the fact that black Americans born today can expect to die 4 years earlier than white Americans, are often considered to be unfair and in need of policy attention. As policymakers look to implement health programmes to tackle such unfair health disparities, they need the tools to enable them to evaluate the likely impacts of alternative programmes available to them in terms of the programmes’ impact on reducing these undesirable health inequalities, as well as their impact on improving population health.

Traditional tools for prospectively evaluating health programmes – that is to say, estimating the likely impacts of health programmes prior to their implementation – are typically based on cost-effectiveness analysis (CEA). CEA selects those programmes that improve the health of the average recipient of the programme the most, taking into consideration the health opportunity costs involved in implementing the programme. When using CEA to select health programmes there is, therefore, a risk that the programmes selected will not necessarily reduce the health disparities of concern to policymakers as these disparities are not part of the evaluation process used when comparing programmes. Indeed, in some cases, the programmes chosen using CEA may even unintentionally exacerbate these health inequalities.

There has been recent methodological work to build upon the standard CEA methods explicitly incorporating concerns for reducing health disparities into them. This equity augmented form of CEA is called distributional cost effectiveness analysis (DCEA). DCEA estimates the impacts of health interventions on different groups within the population and evaluates the health distributions resulting from these interventions in term of both health inequality and population health. Where necessary, DCEA can then be used to guide the trade-off between these different dimensions to pick the most “socially beneficial” programme to implement.

Implementation

The six core steps in implementing a DCEA are outlined below – full details of how DCEA is conducted in practice and applied to evaluate alternative options in a real case study (the NHS Bowel Cancer Screening Programme in England) can be found in a published tutorial.

1. Identify policy-relevant subgroups in the population

The first step in the analysis is to decide which characteristics of the population are of policy concern when thinking about health inequalities. For example, in England, there is a lot of concern about the fact that people born in poor neighbourhoods expect to die earlier than those born in rich neighbourhoods but little concern about the fact that men have shorter life expectancies than women.

2. Construct the baseline distribution of health

The next step is to construct a baseline distribution of health for the population. This baseline distribution describes the health of the population, typically measured in quality-adjusted life expectancy at birth, to show the level of health and health inequality prior to implementing the proposed interventions. This distribution can be standardised (using methods of either direct or indirect standardisation) to remove any variation in health that is not associated with the characteristics of interest. For example, in England, we might standardise the health distribution to remove variation associated with gender but retain variation associated with neighbourhood deprivation. This then gives us a description of the population health distribution with a particular focus on the health disparities we are trying to reduce. An example of how to construct such a ‘social distribution of health’ for England is given in another published article.

3. Estimate post-intervention distributions of health

We next estimate the health impacts of the interventions we are comparing. In producing these estimates we need to take into account differences by each of the equity relevant subgroups identified in the:

  • prevalence and incidence of the diseases impacted by the intervention,
  • rates of uptake and adherence to the intervention,
  • efficacy of the intervention,
  • mortality and morbidity, and
  • health opportunity costs.

Standardising these health impacts and combining with the baseline distribution of health derived above gives us estimated post-intervention distributions of health for each intervention.

4. Compare post-intervention distributions using the health equity impact plane

Once post-intervention distributions of health have been estimated for each intervention we can compare them both in terms of their level of average health and in terms of their level of health inequality. Whilst calculating average levels of health in the distributions is straightforward, calculating levels of inequality requires some value judgements to be made. There is a wide range of alternative inequality measures that could be employed each of which captures different aspects of inequality. For example, relative inequality measures would conclude that a health distribution where half the population lives for 40 years and the other half lives for 50 years is just as unequal as a health distribution where half the population lives for 80 years and the other half lives for 100 years. An absolute inequality measure would instead conclude that the equivalence is with a population where half the population lives for 80 years and the other half lives for 90 years.

Two commonly used inequality measures are the Atkinson relative inequality measure and the Kolm absolute inequality measure. These both have the additional feature that they can be calibrated using an inequality aversion parameter to vary the level of priority given to those worst off in the distribution. We will see these inequality aversion parameters in action in the next step of the DCEA process.

Having selected a suitable inequality measure we can plot our post interventions distributions on a health equity impact plane. Let us assume we are comparing two interventions A and B, we can plot intervention A at the origin of the plane and plot intervention B relative to A on the plane.

 

 

If intervention B falls in the north-east quadrant of the health equity impact plane we know it both improves health overall and reduces health inequality relative to intervention A and so intervention B should be selected. If, however, intervention B falls in the south-west quadrant of the health equity impact plane we know it both reduces health and increases health inequality relative to intervention A and so intervention A should be selected. If intervention B falls either in the north-west or south-east quadrants of the health equity impact plane there is no obvious answer as to which intervention should be preferred as there is a trade-off to be made between health equity and total health.

5. Evaluate trade-offs between inequality and efficiency using social welfare functions

We use social welfare functions to trade-off between inequality reduction and average health improvement. These social welfare functions are constructed by combining our chosen measure of inequality with the average health in the distribution. This combination of inequality and average health is used to calculate what is known as an equally distributed equivalent (EDE) level of health. The EDE summarises the health distribution being analysed as one number representing the amount of health that each person in a hypothetically perfectly equal health distribution would need to have for us to be indifferent between the actual health distribution analysed and this perfectly equal health distribution. Where our social welfare function is built around an inequality measure with an inequality aversion parameter this EDE level of health will also be a function of the inequality aversion parameter. Where inequality aversion is set to zero there is no concern for inequality and the EDE simply reflects the average health in the distribution replicating results we would see under standard utilitarian CEA. As the inequality aversion level approaches infinity, our focus becomes increasingly on those worse off in the health distribution until at the limit we reflect the Rawlsian idea of focusing entirely on improving the lot of the worst-off in society.

 

Social welfare functions derived from the Atkinson relative inequality measure and the Kolm absolute inequality measure are given below, with the inequality aversion parameters circled. Research carried out with members of the public in England suggests that suitable values for the Atkinson and Kolm inequality aversion parameters are 10.95 and 0.15 respectively.

Atkinson Relative Social Welfare Function Kolm Absolute Social Welfare Function

When comparing interventions where one intervention does not simply dominate the others on the health equity impact plane we need to use our social welfare functions to calculate EDE levels of health associated with each of the interventions and then select the intervention that produces the highest EDE level of health.

In the example depicted in the figure above we can see that pursuing intervention A results in a health distribution which appears less unequal but has a lower average level of health than the health distribution resulting from intervention B. The choice of intervention, in this case, will be determined by the form of social welfare function selected and the level of inequality this social welfare function is parameterised to embody.

6. Conduct sensitivity analysis on forms of social welfare function and extent of inequality aversion

Given that the conclusions drawn from DCEA may be dependent on the social value judgments made around the inequality measure used and the level of inequality aversion embodied in it, we should present results for a range of alternative social welfare functions parameterised at a range of inequality aversion levels. This will allow decision makers to clearly understand how robust conclusions are to alternative social value judgements.

Applications

DCEA is of particular use when evaluating large-scale public health programmes that have an explicit goal of tackling health inequality. It has been applied to the NHS bowel cancer screening programme in England and to the rotavirus vaccination programme in Ethiopia.

Some key limitations of DCEA are that: (1) it currently only analyses programmes in terms of their health impacts whilst large public health programmes often have important impacts across a range of sectors beyond health; and (2) it requires a range of data beyond that required by standard CEA which may not be readily available in all contexts.

For low and middle-income settings an alternative augmented CEA methodology called extended cost effectiveness analysis (ECEA) has been developed to combine estimates of health impacts with estimates of impacts on financial risk protection. More information on ECEA can be found here.

There are ongoing efforts to generalise the DCEA methods to be applied to interventions having impacts across multiple sectors. Follow the latest developments on DCEA at the dedicated website based at the Centre for Health Economics, University of York.

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