David Mott’s journal round-up for 16th September 2019

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

Opening the ‘black box’: an overview of methods to investigate the decision‑making process in choice‑based surveys. The Patient [PubMed] Published 5th September 2019

Choice-based surveys using methods such as discrete choice experiments (DCEs) and best-worst scaling (BWS) exercises are increasingly being used in health to understand people’s preferences. A lot of time and energy is spent on analysing the data that come out from these surveys but increasingly there is an interest in better understanding respondents’ decision-making processes. Whilst many will be aware of ‘think aloud’ interviews (often used for piloting), other methods may be less familiar as they’re not applied frequently in health. That’s where this fascinating paper by Dan Rigby and colleagues comes in. It provides an overview of five different methods of what they call ‘pre-choice process analysis’ of decision-making, describing the application, state of knowledge, and future research opportunities.

Eye-tracking has been used in health recently. It’s intuitive and provides an insight into where the participants’ focus is (or isn’t). The authors explained that one of the ways it has been used is to explore attribute non-attendance (ANA), which essentially occurs when people are ignoring attributes either because they’re irrelevant to them, or simply because it makes the task easier. However, surprisingly, it has been suggested that ‘visual ANA’ (not looking at the attribute) doesn’t always align with ‘stated ANA’ (participants stating that they ignored the attribute) – which raises some interesting questions!

However, the real highlight for me was the overview of the use of brain imaging techniques to explore choices being made in DCEs. One study highlighted by the authors – which was a DCE about eggs and is now at least #2 on my list of the bizarre preference study topics after this oddly specific one on Iberian ham – predicted choices from an initial ‘passive viewing’ using functional magnetic resonance imaging (fMRI). They found that incorporating changes in blood flow (prompted by changes in attribute levels during ‘passive viewing’) into a random utility model accounted for a lot of the variation in willingness to pay for eggs – pretty amazing stuff.

Whilst I’ve highlighted the more unusual methods here, after reading this overview I have to admit that I’m an even bigger advocate for the ‘think aloud’ technique now. Although it may have some limitations, the amount of insight offered combined with its practicality is hard to beat. Though maybe I’m biased because I know that I won’t get my hands on any eye-tracking or brain imaging devices any time soon. In any case, I highly recommend that any researchers conducting preference studies give this paper a read as it’s really well written and will surely be of interest.

Disentangling public preferences for health gains at end-of-life: further evidence of no support of an end-of-life premium. Social Science & Medicine [PubMed] Published 21st June 2019

The end of life (EOL) policy introduced by NICE in 2009 [PDF] has proven controversial. The policy allows treatments that are not cost-effective within the usual range to be considered for approval, provided that certain criteria are met. Specifically, that the treatment targets patients with a short life expectancy (≤24 months), offers a life extension (of ≥3 months) and is for a ‘small patient population’. One of the biggest issues with this policy is that it is unclear whether the general population actually supports the idea of valuing health gains (specifically life extension) at EOL more than other health gains.

Numerous academic studies, usually involving some form of stated preference exercise, have been conducted to test whether the public might support this EOL premium. A recent review by Koonal Shah and colleagues summarised the existing published studies (up to October 2017), highlighting that evidence is extremely mixed. This recently published Danish study, by Lise Desireé Hansen and Trine Kjær, adds to this literature. The authors conducted an incredibly thorough stated preference exercise to test whether quality of life (QOL) gains and life extension (LE) at EOL are valued differently from other similarly sized health gains. Not only that, but the study also explored the effect of perspective on results (social vs individual), the effect of age (18-35 vs. 65+), and impact of initial severity (25% vs. 40% initial QOL) on results.

Overall, they did not find evidence of support for an EOL premium for QOL gains or for LEs (regardless of perspective) but their results do suggest that QOL gains are preferred over LE. In some scenarios, there was slightly more support for EOL in the social perspective variant, relative to the individual perspective – which seems quite intuitive. Both age and initial severity had an impact on results, with respondents preferring to treat the young and those with worse QOL at baseline. One of the most interesting results for me was within their subgroup analyses, which suggested that women and those with a relation to a terminally ill patient had a significantly positive preference for EOL – but only in the social perspective scenarios.

This is a really well-designed study, which covers a lot of different concepts. This probably doesn’t end the debate on NICE’s use of the EOL criteria – not least because the study wasn’t conducted in England and Wales – but it contributes a lot. I’d consider it a must-read for anyone interested in this area.

How should we capture health state utility in dementia? Comparisons of DEMQOL-Proxy-U and of self- and proxy-completed EQ-5D-5L. Value in Health Published 26th August 2019

Capturing quality of life (QOL) in dementia and obtaining health state utilities is incredibly challenging; which is something that I’ve started to really appreciate recently upon getting involved in a EuroQol-funded ‘bolt-ons’ project. The EQ-5D is not always able to detect meaningful changes in cognitive function and condition-specific preference-based measures (PBMs), such as the DEMQOL, may be preferred as a result. However, this isn’t the only challenge because in many cases patients are not in a position to complete the surveys themselves. This means that proxy-reporting is often required, which could be done by either a professional (formal) carer, or a friend or family member (informal carer). Researchers that want to use a PBM in this population therefore have a lot to consider.

This paper compares the performance of the EQ-5D-5L and the DEMQOL-Proxy when completed by care home residents (EQ-5D-5L only), formal carers and informal carers. The impressive dataset that the authors use contains 1,004 care home residents, across up to three waves, and includes a battery of different cognitive and QOL measures. The overall objective was to compare the performance of the EQ-5D-5L and DEMQOL-Proxy, across the three respondent groups, based on 1) construct validity, 2) criterion validity, and 3) responsiveness.

The authors found that self-reported EQ-5D-5L scores were larger and less responsive to changes in the cognitive measures, but better at capturing residents’ self-reported QOL (based on a non-PBM) relative to proxy-reported scores. It is unclear whether this is a case of adaptation as seen in many other patient groups, or if the residents’ cognitive impairments prevent them from reliably assessing their current status. The proxy-reported EQ-5D-5L scores were generally more responsive to changes in the cognitive measures relative to the DEMQOL-Proxy (irrespective of which type of proxy), which the authors note is probably due to the fact that the DEMQOL-Proxy focuses more on the emotional impact of dementia rather than functional impairment.

Overall, this is a really interesting paper, which highlights the challenges well and illustrates that there is value in collecting these data from both patients and proxies. In terms of the PBM comparison, whilst the authors do not explicitly state it, it does seem that the EQ-5D-5L may have a slight upper hand due to its responsiveness, as well as for pragmatic reasons (the DEMQOL-Proxy has >30 questions). Perhaps a cognition ‘bolt-on’ to the EQ-5D-5L might help to improve the situation in future?

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Sam Watson’s journal round-up for 3rd June 2019

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

Limits to human life span through extreme value theory. Journal of the American Statistical Association [RePEc] Published 2nd April 2019

The oldest verified person to have ever lived was Jeanne Calment who died in 1997 at the superlative age of 122. No-one else has ever been recorded as living longer than 120, but there have been perhaps a few hundred supercentarians over 110. Whenever someone reaches such a stupendous age, some budding reporter will ask them what the secret was. They will reply that they have stuck to a regimen of three boiled eggs and a glass of scotch every day for 80 years. And this information is of course completely meaningless due to survivorship bias. But as public health and health care improves and with it life expectancy, there remains the question of whether people will ever exceed these extreme ages or whether there is actually a limit to human longevity.

Some studies have attempted to address the question of maximum human longevity by looking at how key biological systems, like getting oxygen to the muscles or vasculature, degrade. They suggest that there would be an upper limit as key systems of the body just cannot last, which is not to say medicine might not find a way to fix or replace them in the future. Another way of addressing this question is to take a purely statistical approach and look at the distribution of the ages of the oldest people alive and try to make inferences about its upper limit. Such an analysis relies on extreme value theory.

There are two types of extreme value data. The first type consists of just the series of maximum values from the distribution. The Fisher-Tippett-Gnedenko theorem shows that these maxima can only be distributed according to one of three distributions. The second type of data are all of the most extreme observations above a certain threshold, and wonderfully there is another triple-barrelled theorem that shows that these data are distributed as a generalised Pareto distribution – the Pickand-Balkema-de Haan theorem. This article makes use of this latter type of data and theorem to estimate: (i) is there an upper limit to the distribution of human life spans? (ii) What is it, if so? And (iii) does it change over time?

The authors use a dataset of the ages of death in days of all Dutch residents who died over the age of 92 between 1986 and 2015. Using these data to estimate the parameters of the generalised Pareto distribution, they find strong evidence to suggest that, statistically at least, it has an upper limit and that this limit is probably around 117-124. Over the years of the study there did not appear to be any change in this limit. This is not to say that it couldn’t change in the future if some new miraculous treatment appeared, but for now, we humans must put up with a short and finite existence.

Infant health care and long-term outcomes. Review of Economics and Statistics [RePEc] Published 13th May 2019

I haven’t covered an article on infant health and economic conditions and longer term outcomes for a while. It used to be that there would be one in every round-up I wrote. I could barely keep up with the literature, which I tried to summarise in a different blog post. Given that it has been a while, I thought I would include a new one. This time we are looking at the effect of mother and child health centres in Norway in the 1930s on the outcomes of adults later in the 20th Century.

Fortunately the health centres were built in different municipalities at different times. The authors note that the “key identifying assumption” is that they were not built at a time related to the health of infants in those areas (well, this and that the model is linear and additive, time trends are linear, etc. etc. something that economists often forget). They don’t go into too much detail on this, but it seems plausible. Another gripe of mine with most empirical economic papers, and indeed in medical and public health fields, is that plotting the data is a secondary concern or doesn’t happen at all. It should be the most important thing. Indeed, in this article much of the discussion can be captured by the figure buried two thirds through. The figure shows that the centres likely led to a big reduction in diarrhoeal disease, probably due to increased rates of breast feeding, but on other outcomes effects are more ambiguous and probably quite small if they exist. Some evidence is provided to suggest that these differences were associated with very modest increases in educational attainment and adult wages. However, a cost-benefit calculation suggests that on the basis of these wage increases the intervention had a annualised rate of return of about 5%.

I should say that this study is well-conducted and fairly solid so any gripes with it are fairly minor. It certainly fits neatly into the wide literature on the topic, and I don’t think anyone would doubt that investing in childhood interventions is likely to have a number of short and long term benefits.

Relationship between poor olfaction and mortality among community-dwelling older adults: a cohort study. Annals of Internal Medicine [PubMed] Published 21st May 2019

I included this last study, not because of any ground-breaking economics or statistics, but because it is interesting. This is one of a number of studies to have looked at the relationship between smell ability and risk of death. These studies have generally found a strong direct relationship between poor olfaction and risk of death in the following years (summarised briefly in this editorial). This study examines a cohort of a couple of thousand older people whose smell was rigourously tested at baseline, among other things. If they died then their death was categorised by a medical examiner into one of four categories: dementia or Parkinson disease, cardiovascular disease, cancer, and respiratory illness.

There was a very strong relationship between poor ability to smell and all-cause death. They found that cumulative risk for death was 46% and 30% higher in persons with a loss of smelling ability at 10 and 13 years respectively. Delving into death by cause, they found that this relationship was most important among those who died of dementia or Parkinson disease, which makes sense as smell is one of the oldest limbic structures and linked to many parts of the brain. Some relationship was seen with cardiovascular disease but not cancer or respiratory illness. They then use a ‘mediation analysis’, i.e. conditioning on post-treatment variables to ‘block’ causal pathways, to identify how much variation is explained and conclude that dementia, Parkinson disease, and weight loss account for about 30% of the observed relationship. However, I am usually suspicious of mediation analyses, and standard arguments would suggest that model parameters would be biased.

Interestingly, olfaction is not normally used as a diagnostic test among the elderly despite sense of smell being one of the strongest predictors of mortality. People do not generally notice their sense of smell waning as it is gradual, so would not likely remark on it to a doctor. Perhaps it is time to start testing it routinely?

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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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