Chris Sampson’s journal round-up for 19th 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.

Value of information methods to design a clinical trial in a small population to optimise a health economic utility function. BMC Medical Research Methodology [PubMed] Published 8th February 2018

Statistical significance – whatever you think of it – and the ‘power’ of clinical trials to detect change, is an important decider in clinical decision-making. Trials are designed to be big enough to detect ‘statistically significant’ differences. But in the context of rare diseases, this can be nigh-on impossible. In theory, the required sample size could exceed the size of the whole population. This paper describes an alternative method for determining sample sizes for trials in this context, couched in a value of information framework. Generally speaking, power calculations ignore the ‘value’ or ‘cost’ associated with errors, while a value of information analysis would take this into account and allow accepted error rates to vary accordingly. The starting point for this study is the notion that sample sizes should take into account the size of the population to which the findings will be applicable. As such, sample sizes can be defined on the basis of maximising the expected (societal) utility associated with the conduct of the trial (whether the intervention is approved or not). The authors describe the basis for hypothesis testing within this framework and specify the utility function to be maximised. Honestly, I didn’t completely follow the stats notation in this paper, but that’s OK – the trial statisticians will get it. A case study application is presented from the context of treating children with severe haemophilia A, which demonstrates the potential to optimise utility according to sample size. The key point is that the power is much smaller than would be required by conventional methods and the sample size accordingly reduced. The authors also demonstrate the tendency for the optimal trial sample size to increase with the size of the population. This Bayesian approach at least partly undermines the frequentist basis on which ‘power’ is usually determined. So one issue is whether regulators will accept this as a basis for defining a trial that will determine clinical practice. But then regulators are increasingly willing to allow for special cases, and it seems that the context of rare diseases could be a way-in for Bayesian trial design of this sort.

EQ-5D-5L: smaller steps but a major step change? Health Economics [PubMed] Published 7th February 2018

This editorial was doing the rounds on Twitter last week. European (and Canadian) health economists love talking about the EQ-5D-5L. The editorial features in the edition of Health Economics that hosts the 5L value set for England, which – 2 years on – has finally satisfied the vagaries of academic publication. The authors provide a summary of what’s ‘new’ with the 5L, and why it matters. But we’ve probably all figured that out by now anyway. More interestingly, the editorial points out some remaining concerns with the use of the EQ-5D-5L in England (even if it is way better than the EQ-5D-3L and its 25-year old value set). For example, there is some clustering in the valuations that might reflect bias or problems with the technique and – even if they’re accurate – present difficulties for analysts. And there are also uncertain implications for decision-making that could systematically favour or disfavour particular treatments or groups of patients. On this basis, the authors support NICE’s decision to ‘pause’ and await independent review. I tend to disagree, for reasons that I can’t fit in this round-up, so come back tomorrow for a follow-up blog post.

Factors influencing health-related quality of life in patients with Type 1 diabetes. Health and Quality of Life Outcomes [PubMed] Published 2nd February 2018

Diabetes and its complications can impact upon almost every aspect of a person’s health. It isn’t clear what aspects of health-related quality of life might be amenable to improvement in people with Type 1 diabetes, or which characteristics should be targeted. This study looks at a cohort of trial participants (n=437) and uses regression analyses to determine which factors explain differences in health-related quality of life at baseline, as measured using the EQ-5D-3L. Age, HbA1c, disease duration and being obese all significantly influenced EQ-VAS values, while self-reported mental illness and unemployment status were negatively associated with EQ-5D index scores. People who were unemployed were more likely to report problems in the mobility, self-care, and pain/discomfort domains. There are some minor misinterpretations in the paper (divining a ‘reduction’ in scores from a cross-section, for example). And the use of standard linear regression models is questionable given the nature of EQ-5D-3L index values. But the findings demonstrate the importance of looking beyond the direct consequences of a disease in order to identify the causes of reduced health-related quality of life. Getting people back to work could be more effective than most health care as a means of improving health-related quality of life.

Financial incentives for chronic disease management: results and limitations of 2 randomized clinical trials with New York Medicaid patients. American Journal of Health Promotion [PubMed] Published 1st February 2018

Chronic diseases require (self-)management, but it isn’t always easy to ensure that patients adhere to the medication or lifestyle changes that could improve health outcomes. This study looks at the effectiveness of financial incentives in the context of diabetes and hypertension. The data are drawn from 2 RCTs (n=1879) which, together, considered 3 types of incentive – process-based, outcome-based, or a combination of the two – compared with no financial incentives. Process-based incentives rewarded participants for attending primary care or endocrinologist appointments and filling their prescriptions, up to a maximum of $250. Outcome-based incentives rewarded up to $250 for achieving target reductions in systolic blood pressure or blood glucose levels. The combined arms could receive both rewards up to the same maximum of $250. In short, none of the financial incentives made any real difference. But generally speaking, at 6-month follow-up, the movement was in the right direction, with average blood pressure and blood glucose levels tending to fall in all arms. It’s not often that authors include the word ‘limitations’ in the title of a paper, but it’s the limitations that are most interesting here. One key difficulty is that most of the participants had relatively acceptable levels of the target outcomes at baseline, meaning that they may already have been managing their disease well and there may not have been much room for improvement. It would be easy to interpret these findings as showing that – generally speaking – financial incentives aren’t effective. But the study is more useful as a way of demonstrating the circumstances in which we can expect financial incentives to be ineffective, and support a better-informed targeting for future programmes.

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Chris Sampson’s journal round-up for 8th 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.

An empirical comparison of the measurement properties of the EQ-5D-5L, DEMQOL-U and DEMQOL-Proxy-U for older people in residential care. Quality of Life Research [PubMed] Published 5th January 2018

There is now a condition-specific preference-based measure of health-related quality of life that can be used for people with cognitive impairment: the DEMQOL-U. Beyond the challenge of appropriately defining quality of life in this context, cognitive impairment presents the additional difficulty that individuals may not be able to self-complete a questionnaire. There’s some good evidence that proxy responses can be valid and reliable for people with cognitive impairment. The purpose of this study is to try out the new(ish) EQ-5D-5L in the context of cognitive impairment in a residential setting. Data were taken from an observational study in 17 residential care facilities in Australia. A variety of outcome measures were collected including the EQ-5D-5L (proxy where necessary), a cognitive bolt-on item for the EQ-5D, the DEMQOL-U and the DEMQOL-Proxy-U (from a family member or friend), the Modified Barthel Index, the cognitive impairment Psychogeriatric Assessment Scale (PAS-Cog), and the neuropsychiatric inventory questionnaire (NPI-Q). The researchers tested the correlation, convergent validity, and known-group validity for the various measures. 143 participants self-completed the EQ-5D-5L and DEMQOL-U, while 387 responses were available for the proxy versions. People with a diagnosis of dementia reported higher utility values on the EQ-5D-5L and DEMQOL-U than people without a diagnosis. Correlations between the measures were weak to moderate. Some people reported full health on the EQ-5D-5L despite identifying some impairment on the DEMQOL-U, and some vice versa. The EQ-5D-5L was more strongly correlated with clinical outcome measures than were the DEMQOL-U or DEMQOL-Proxy-U, though the associations were generally weak. The relationship between cognitive impairment and self-completed EQ-5D-5L and DEMQOL-U utilities was not in the expected direction; people with greater cognitive impairment reported higher utility values. There was quite a lot of disagreement between utility values derived from the different measures, so the EQ-5D-5L and DEMQOL-U should not be seen as substitutes. An EQ-QALY is not a DEM-QALY. This is all quite perplexing when it comes to measuring health-related quality of life in people with cognitive impairment. What does it mean if a condition-specific measure does not correlate with the condition? It could be that for people with cognitive impairment the key determinant of their quality of life is only indirectly related to their impairment, and more dependent on their living conditions.

Resolving the “cost-effective but unaffordable” paradox: estimating the health opportunity costs of nonmarginal budget impacts. Value in Health Published 4th January 2018

Back in 2015 (as discussed on this blog), NICE started appraising drugs that were cost-effective but implied such high costs for the NHS that they seemed unaffordable. This forced a consideration of how budget impact should be handled in technology appraisal. But the matter is far from settled and different countries have adopted different approaches. The challenge is to accurately estimate the opportunity cost of an investment, which will depend on the budget impact. A fixed cost-effectiveness threshold isn’t much use. This study builds on York’s earlier work that estimated cost-effectiveness thresholds based on health opportunity costs in the NHS. The researchers attempt to identify cost-effectiveness thresholds that are in accordance with different non-marginal (i.e. large) budget impacts. The idea is that a larger budget impact should imply a lower (i.e. more difficult to satisfy) cost-effectiveness threshold. NHS expenditure data were combined with mortality rates for different disease categories by geographical area. When primary care trusts’ (PCTs) budget allocations change, they transition gradually. This means that – for a period of time – some trusts receive a larger budget than they are expected to need while others receive a smaller budget. The researchers identify these as over-target and under-target accordingly. The expenditure and outcome elasticities associated with changes in the budget are estimated for the different disease groups (defined by programme budgeting categories; PBCs). Expenditure elasticity refers to the change in PBC expenditure given a change in overall NHS expenditure. Outcome elasticity refers to the change in PBC mortality given a change in PBC expenditure. Two econometric approaches are used; an interaction term approach, whereby a subgroup interaction term is used with the expenditure and outcome variables, and a subsample estimation approach, whereby subgroups are analysed separately. Despite the limitations associated with a reduced sample size, the subsample estimation approach is preferred on theoretical grounds. Using this method, under-target PCTs face a cost-per-QALY of £12,047 and over-target PCTs face a cost-per-QALY of £13,464, reflecting diminishing marginal returns. The estimates are used as the basis for identifying a health production function that can approximate the association between budget changes and health opportunity costs. Going back to the motivating example of hepatitis C drugs, a £772 million budget impact would ‘cost’ 61,997 QALYs, rather than the 59,667 that we would expect without accounting for the budget impact. This means that the threshold should be lower (at £12,452 instead of £12,936) for a budget impact of this size. The authors discuss a variety of approaches for ‘smoothing’ the budget impact of such investments. Whether or not you believe the absolute size of the quoted numbers depends on whether you believe the stack of (necessary) assumptions used to reach them. But regardless of that, the authors present an interesting and novel approach to establishing an empirical basis for estimating health opportunity costs when budget impacts are large.

First do no harm – the impact of financial incentives on dental x-rays. Journal of Health Economics [RePEc] Published 30th December 2017

If dentists move from fee-for-service to a salary, or if patients move from co-payment to full exemption, does it influence the frequency of x-rays? That’s the question that the researchers are trying to answer in this study. It’s important because x-rays always present some level of (carcinogenic) risk to patients and should therefore only be used when the benefits are expected to exceed the harms. Financial incentives shouldn’t come into it. If they do, then some dentists aren’t playing by the rules. And that seems to be the case. The authors start out by establishing a theoretical framework for the interaction between patient and dentist, which incorporates the harmful nature of x-rays, dentist remuneration, the patient’s payment arrangements, and the characteristics of each party. This model is used in conjunction with data from NHS Scotland, with 1.3 million treatment claims from 200,000 patients and 3,000 dentists. In 19% of treatments, an x-ray occurs. Some dentists are salaried and some are not, while some people pay charges for treatment and some are exempt. A series of fixed effects models are used to take advantage of these differences in arrangements by modelling the extent to which switches (between arrangements, for patients or dentists) influence the probability of receiving an x-ray. The authors’ preferred model shows that both the dentist’s remuneration arrangement and the patient’s financial status influences the number of x-rays in the direction predicted by the model. That is, fee-for-service and charge exemption results in more x-rays. The combination of these two factors results in a 9.4 percentage point increase in the probability of an x-ray during treatment, relative to salaried dentists with non-exempt patients. While the results do show that financial incentives influence this treatment decision (when they shouldn’t), the authors aren’t able to link the behaviour to patient harm. So we don’t know what percentage of treatments involving x-rays would correspond to the decision rule of benefits exceeding harms. Nevertheless, this is an important piece of work for informing the definition of dentist reimbursement and patient payment mechanisms.

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Sam Watson’s journal round-up for 11th December 2017

Every Monday our authors provide a round-up of some of the most recently published peer reviewed articles from the field. We don’t cover everything, or even what’s most important – just a few papers that have interested the author. Visit our Resources page for links to more journals or follow the HealthEconBot. If you’d like to write one of our weekly journal round-ups, get in touch.

Can incentives improve survey data quality in developing countries?: results from a field experiment in India. Journal of the Royal Statistical Society: Series A Published 17th November 2017

I must admit a keen interest in the topic of this paper. As part of a large project looking at the availability of health services in slums and informal settlements around the world, we are designing a household survey. Much like the Demographic and Health Surveys, which are perhaps the Gold standard of household surveys in low-income countries, interviewers will go door to door to sampled households to complete surveys. One of the issues with household surveys is that they take a long time, and so non-response can be an issue. A potential solution is to offer respondents incentives, cash or otherwise, either before the survey or conditionally on completing it. But any change in survey response as a result of an incentive might create suspicion around data quality. Work in high-income countries suggests incentives to participate have little or no effect on data quality. But there is little evidence about these effects in low-income countries. We might suspect the consequences of survey incentives to differ in poorer settings. For a start, many surveys are conducted on behalf of the government or an NGO, and respondents may misrepresent themselves if they believe further investment in their area might be forthcoming if they are sufficiently badly-off. There may also be larger differences between the interviewer and interviewee in terms of education or cultural background. And finally, incentives can affect the balance between a respondent’s so-called intrinsic and extrinsic motivations for doing something. This study presents the results of a randomised trial where the ‘treatment’ was a small conditional payment for completing a survey, and the ‘control’ was no incentive. In both arms, the response rate was very high (>96%), but it was higher in the treatment arm. More importantly, the authors compare responses to a broad range of socioeconomic and demographic questions between the study arms. Aside from the frequent criticism that statistical significance is interpreted here as the existence of a difference, there are some interesting results. The key observed difference is that in the incentive arm respondents reported having lower wealth consistently across a number of categories. This may result from any of the aforementioned effects of incentives, but may be evidence that incentives can affect data quality and should be used with caution.

Association of US state implementation of newborn screening policies for critical congenital heart disease with early infant cardiac deaths. JAMA [PubMedPublished 5th December 2017

Writing these journal round-ups obviously requires reading the papers that you choose. This can be quite an undertaking for papers published in economics journals, which are often very long, but they provide substantial detail allowing for a thorough appraisal. The opposite is true for articles in medical journals. They are pleasingly concise, but often at the expense of including detail or additional analyses. This paper falls into the latter camp. Using detailed panel data on infant deaths by cause by year and by state in the US, it estimates the effect of mandated screening policies for infant congenital heart defects on deaths from this condition. Given these data and more space, one might expect to see more flexible models than the differences in differences type analysis presented here, such as allowing for state-level correlated time trends. The results seem clear and robust – the policies were associated with a reduction in death from congenital heart conditions by around a third. Given this, one might ask: if it’s so effective, why weren’t doctors doing it anyway? Additional analyses reveal little to no association of the policies with death from other conditions, which may suggest that doctors didn’t have to reallocate their time from other beneficial functions. Perhaps then the screening bore other costs. In the discussion, the authors mention that a previous economic evaluation showed that universal screening was relatively costly (approximately $40,000 per life year saved), but that this may be an overestimate in light of these new results. Certainly then an updated economic evaluation is warranted. However, the models used in the paper may lead one to be cautious about causal interpretations and hence using the estimates in an evaluation. Given some more space the authors may have added additional analyses, but then I might not have read it…

Subsidies and structure: the lasting impact of the Hill-Burton program on the hospital industry. Review of Economics and Statistics [RePEcPublished 29th November 2017

As part of the Hospital Survey and Construction Act of 1946 in the United States, the Hill-Burton program was enacted. As a reaction to the perceived lack of health care services for workers during World War 2, the program provided subsidies of up to a third for building nonprofit and local hospitals. Poorer areas were prioritised. This article examines the consequences of this subsidy program on the structure of the hospital market and health care utilisation. The main result is that the program had the consequence of increasing hospital beds per capita and that this increase was lasting. More specific analyses are presented. Firstly, the increase in beds took a number of years to materialise and showed a dose-response; higher-funded counties had bigger increases. Secondly, the funding reduced private hospital bed capacity. The net effect on overall hospital beds was positive, so the program affected the composition of the hospital sector. Although this would be expected given that it substantially affected the relative costs of different types of hospital bed. And thirdly, hospital utilisation increased in line with the increases in capacity, indicating a previously unmet need for health care. Again, this was expected given the motivation for the program in the first place. It isn’t often that results turn out as neatly as this – the effects are exactly as one would expect and are large in magnitude. If only all research projects turned out this way.

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