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.


Alastair Canaway’s journal round-up for 29th 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.

Is “end of life” a special case? Connecting Q with survey methods to measure societal support for views on the value of life-extending treatments. Health Economics [PubMed] Published 19th January 2018

Should end-of-life care be treated differently? A question often asked and previously discussed on this blog: findings to date are equivocal. This question is important given NICE’s End-of-Life Guidance for increased QALY thresholds for life-extending interventions, and additionally the Cancer Drugs Fund (CDF). This week’s round-up sees Helen Mason and colleagues attempt to inform the debate around societal support for views of end-of-life care, by trying to determine the degree of support for different views on the value of life-extending treatment. It’s always a treat to see papers grounded in qualitative research in the big health economics journals and this month saw the use of a particularly novel mixed methods approach adding a quantitative element to their previous qualitative findings. They combined the novel (but increasingly recognisable thanks to the Glasgow team) Q methodology with survey techniques to examine the relative strength of views on end-of-life care that they had formulated in a previous Q methodology study. Their previous research had found that there are three prevalent viewpoints on the value of life-extending treatment: 1. ‘a population perspective: value for money, no special cases’, 2. ‘life is precious: valuing life-extension and patient choice’, 3. ‘valuing wider benefits and opportunity cost: the quality of life and death’. This paper used a large Q-based survey design (n=4902) to identify societal support for the three different viewpoints. Viewpoints 1 and 2 were found to be dominant, whilst there was little support for viewpoint 3. The two supported viewpoints are not complimentary: they represent the ethical divide between the utilitarian with a fixed budget (view 1), and the perspective based on entitlement to healthcare (view 2: which implies an expanding healthcare budget in practice). I suspect most health economists will fall into camp number one. In terms of informing decision making, this is very helpful, yet unhelpful: there is no clear answer. It is, however, useful for decision makers in providing evidence to balance the oft-repeated ‘end of life is special’ argument based solely on conjecture, and not evidence (disclosure: I have almost certainly made this argument before). Neither of the dominant viewpoints supports NICE’s End of Life Guidance nor the CDF. Viewpoint 1 suggests end of life interventions should be treated the same as others, whilst viewpoint 2 suggests that treatments should be provided if the patient chooses them; it does not make end of life a special case as this viewpoint believes all treatments should be available if people wish to have them (and we should expand budgets accordingly). Should end of life care be treated differently? Well, it depends on who you ask.

A systematic review and meta-analysis of childhood health utilities. Medical Decision Making [PubMed] Published 7th October 2017

If you’re working on an economic evaluation of an intervention targeting children then you are going to be thankful for this paper. The purpose of the paper was to create a compendium of utility values for childhood conditions. A systematic review was conducted which identified a whopping 26,634 papers after deduplication – sincere sympathy to those who had to do the abstract screening. Following abstract screening, data were extracted for the remaining 272 papers. In total, 3,414 utility values were included when all subgroups were considered – this covered all ICD-10 chapters relevant to child health. When considering only the ‘main study’ samples, 1,191 utility values were recorded and these are helpfully separated by health condition, and methodological characteristics. In short, the authors have successfully built a vast catalogue of child utility values (and distributions) for use in future economic evaluations. They didn’t, however, stop there, they then built on the systematic review results by conducting a meta-analysis to i) estimate health utility decrements for each condition category compared to general population health, and ii) to examine how methodological factors impact child utility values. Interestingly for those conducting research in children, they found that parental proxy values were associated with an overestimation of values. There is a lot to unpack in this paper and a lot of appendices and supplementary materials are included (including the excel database for all 3,414 subsamples of health utilities). I’m sure this will be a valuable resource in future for health economic researchers working in the childhood context. As far as MSc dissertation projects go, this is a very impressive contribution.

Estimating a cost-effectiveness threshold for the Spanish NHS. Health Economics [PubMed] [RePEc] Published 28th December 2017

In the UK, the cost-per-QALY threshold is long-established, although whether it is the ‘correct’ value is fiercely debated. Likewise in Spain, there is a commonly cited threshold value of €30,000 per QALY with a dearth of empirical justification. This paper sought to identify a cost-per-QALY threshold for the Spanish National Health Service (SNHS) by estimating the marginal cost per QALY at which the SNHS currently operates on average. This was achieved by exploiting data on 17 regional health services between the years 2008-2012 when the health budget experienced considerable cuts due to the global economic crisis. This paper uses econometric models based on the provoking work by Claxton et al in the UK (see the full paper if you’re interested in the model specification) to achieve this. Variations between Spanish regions over time allowed the authors to estimate the impact of health spending on outcomes (measured as quality-adjusted life expectancy); this was then translated into a cost-per-QALY value for the SNHS. The headline figures derived from the analysis give a threshold between €22,000 and €25,000 per QALY. This is substantially below the commonly cited threshold of €30,000 per QALY. There are, however (as to be expected) various limitations acknowledged by the authors, which means we should not take this threshold as set in stone. However, unlike the status quo, there is empirical evidence backing this threshold and it should stimulate further research and discussion about whether such a change should be implemented.


Paul Mitchell’s journal round-up for 25th 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.

Consensus-based cross-European recommendations for the identification, measurement and valuation of costs in health economic evaluations: a European Delphi study. European Journal of Health Economics [PubMedPublished 19th December 2017

The primary aim of this study was to develop guidelines for costing in economic evaluation studies conducted across more than one European country. The starting point of the societal perspective as the benchmark for costing was not entirely obvious from the abstract, where this broadest approach to costing is not recommended uniformly across all European countries. Recommendations following this starting point looked at the identification, measurement and valuation of resource use, discount rate and discounting of future costs. A three-step Delphi study was used to gain consensus on what should be included in an economic evaluation from a societal perspective, based initially on findings from a review of costing methodologies adopted across European country-specific guidelines. Consensus required at least two thirds (67%) agreement across those participating in the Delphi study at all 3 stages. Where no agreement was reached after the three stages, a panel of four of the co-authors made a final decision on what should be recommended. In total, 26 of the 110 invited to participate completed at least one Delphi round, with all Delphi rounds having at least 16 participants. It remains unclear to me if 16 for a Delphi round is sufficient to reach a European wide consensus on costing methodologies. There were a number of key areas where no consensus was reached (e.g. including costs unrelated to the intervention, measurement of resource use and absenteeism, and valuation of opportunity costs of patient time and informal care), so the four-strong author panel had a leading role on some of the main recommendations. Notwithstanding the limitations associated with the reference perspective taken and sample for the Delphi study and panel, the paper provides a useful illustration of the different approaches to costing across European countries. It also provides a good coverage of costing issues that need to be explained in detail in economic evaluations to allow for clear understanding of methods used and the underpinning rationale for those decisions where a choice is required on the costing methodology applied.

A (five-)level playing field for mental health conditions?: exploratory analysis of EQ-5D-5L derived utility values. Quality of Life Research [PubMedPublished 16th December 2017

The UK health economics community has been reeling from the decision made earlier this year by UK guidelines developer, the National Institute for Health and Care Excellence (NICE), who recommended to not adopt the new population values developed for the EQ-5D-5L version when calculating QALYs and instead rely on a crosswalk of the values developed over 20 years ago for the 3 level EQ-5D version. This paper provides a timely comparison of how these two value sets perform for the EQ-5D-5L descriptive system in patient groups with mental health conditions, groups often thought to be disadvantaged by the physical health functioning focus of the EQ-5D descriptive system. Using baseline data from three trials, the authors find that the new utility values produce a higher mean EQ-5D score of 0.08 compared to the old crosswalk values, with a 0.225 difference for those reporting extreme problems with the anxiety/depression dimension on EQ-5D. Although, the authors of this study highlight using these new values would increase cost per QALY results in this sample using scenario analysis, when improvements are in the depression/anxiety category only, such improvements are relatively better than across the whole EQ-5D-5L descriptive system due to the relative additional value placed on the anxiety/depression dimension in the new values. This paper makes for interesting reading and one that NICE should take into consideration when reviewing their decision on this issue next year. Although I would disagree with the authors when they state that this study would be a primary reason for revising the NICE cost-effectiveness threshold (more compelling arguments for this elsewhere in my view), it does clearly highlight the influence of the choice of descriptive system and the values used in the outcomes produced for economic analysis such as QALYs, even when the two descriptive systems in question (EQ-5D-3L and EQ-5D-5L) are roughly the same.

What characteristics of nursing homes are most valued by customers? A discrete choice experiment with residents and family members. Value in Health Published 1st December 2017

Our final paper for review in 2017 looks at the characteristics that are of most importance to individuals and their family members when it comes to nursing home provision. The authors conducted a valuation exercise using a discrete choice experiment (DCE) to calculate the relative importance of the attributes contained on the Consumer Choice Index-Six Dimension (CCI-6D), a measure developed to assess the quality of nursing home care across 3 levels on six domains: 1. level of time care staff spent with residents; 2. homeliness of shared spaces; 3. homeliness of room setup; 4. access to outside and garden; 5. frequency of meaningful activities; and 6. flexibility with care routines. Those who lived in a nursing home for at least a year with low levels of cognitive impairment completed the DCE themselves, whereas family members were asked to proxy for their close relative with more severe cognitive impairment. 126 residents and 416 family member proxies completed the DCE comparisons of nursing homes with different qualities in these six areas. The results of the DCE show differences in preferences across the two groups. Although similar importance is placed on some dimensions across both groups (i.e. “homeliness of room set up” ranked highly, whereas “frequency of meaningful activities” ranked lower), residents value access to outside and garden four times as much as the family proxies do (second most important dimension for residents, lowest for family proxies), family members value level of time care staff spent with residents twice as much as residents themselves (most important attribute for family proxies, third most important for residents). Although residents in both groups may have important differences in characteristics that might explain some of this difference, it is probably a good time of year to remember family preferences may be inconsistent with individuals within them, so make sure to take account of this variation when preparing those Christmas dinners.

Happy holidays all.