Paul Mitchell’s journal round-up for 6th November 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.

A longitudinal study to assess the frequency and cost of antivascular endothelial therapy, and inequalities in access, in England between 2005 and 2015. BMJ Open [PubMed] Published 22nd October 2017

I am breaking one of my unwritten rules in a journal paper round-up by talking about colleagues’ work, but I feel it is too important not to provide a summary for a number of reasons. The study highlights the problems faced by regional healthcare purchasers in England when implementing national guideline recommendations on the cost-effectiveness of new treatments. The paper focuses on anti-vascular endothelial growth factor (anti-VEGF) medicines in particular, with two drugs, ranibizumab and aflibercept, offered to patients with a range of eye conditions, costing £550-800 per injection. Another drug, bevacizumab, that is closely related to ranibizumab and performs similarly in trials, could be provided at a fraction of the cost (£50-100 per injection), but it is currently unlicensed for eye conditions in the UK. This study investigates how the regional areas in England have coped with trying to provide the recommended drugs using administrative data from Hospital Episode Statistics in England between 2005-2015 by tracking their use since they have been recommended for a number of different eye conditions over the past decade. In 2014/15 the cost of these two new drugs for treating eye conditions alone was estimated at £447 million nationally. The distribution of where these drugs are provided is not equal, varying widely across regions after controlling for socio-demographics, suggesting an inequality of access associated with the introduction of these high-cost drugs over the past decade at a time of relatively low growth in national health spending. Although there are limitations associated with using data not intended for research purposes, the study shows how the most can be made from data routinely collected for non-research purposes. On a public policy level, it raises questions over the provision of such high-cost drugs, for which the authors state the NHS are currently paying more for than US insurers. Although it is important to be careful when comparing to unlicensed drugs, the authors point to clear evidence in the paper as to why their comparison is a reasonable one in this scenario, with a large opportunity cost associated with not including this option in national guidelines. If national recommendations continue to insist that such drugs be provided, clearer guidance is also required on how to disinvest from existing services at a regional level to reduce further examples of inequality in access in the future.

In search of a common currency: a comparison of seven EQ-5D-5L value sets. Health Economics [PubMed] Published 24th October 2017

For those of us out there who like a good valuation study, you will need to set yourself aside a good piece of time to work your way through this one. The new EQ-5D-5L measure of health status, with a primary purpose of generating quality-adjusted life years (QALYs) for economic evaluations, is now starting to have valuation studies emerging from different countries, whereby the relative importance of each of the measure dimensions and levels are quantified based on general population preferences. This study offers the first comparison of value sets across seven countries: 3 Western European (England, Netherlands, Spain), 1 North American (Canada), 1 South American (Uruguay), and two East Asian (Japan and South Korea). The authors in this paper aim to describe methodological differences between the seven value sets, compare the relative importance of dimensions, level decrements and scale length (i.e. quality/quantity trade-offs for QALYs), as well as developing a common (Western) currency across four of the value sets. In brief summary, there does appear to be similar trends across the three Western European countries: level decrements from levels 3 to 4 have the largest value, followed by levels 1 to 2. There is also a pattern in these three countries’ dimensions, whereby the two “symptom” dimensions (i.e. pain/discomfort, anxiety/depression) have equal importance to the other three “functioning” dimensions (i.e. mobility, self-care and usual activities). There are also clear differences with the other four value sets. Canada, although it also has the highest level decrements between levels 3 and 4 (49%), unusually has equal decrements for the remainder (17% x 3). For the other three countries, greater weight is attached to the three functioning dimensions relative to the two symptom dimensions. Although South Korea also has the greatest level decrements between level 3 and 4, it was greatest between level 4 and level 5 in Uruguay and levels 1 and 2 in Japan. Although the authors give a number of plausible reasons as to why these differences may occur, less justification is given in the choice of the four value sets they offer as a common currency, beyond the need to have a value set for countries that do not have one already. The most in-common value sets were the three Western European countries, so a Western European value set may have been more appropriate if the criterion was to have comparable values across countries. If the aim was really for a more international common currency, there are issues with the exclusion of non-Western countries’ value sets from their common currency version. Surely differences across cultures should be reflected in a common currency if they are apparent in different cultures and settings. A common currency should also have a better spread of regions geographically, with no country from Africa, the Middle East, Central and South Asia represented in this study, as well as no lower- and middle-income countries. Though this final criticism is out of the control of the authors based on current data availability.

Quantifying the relationship between capability and health in older people: can’t map, won’t map. Medical Decision Making [PubMed] Published 23rd October 2017

The EQ-5D is one of many ways quality of life can be measured within economic evaluations. A more recent way based on Amartya Sen’s capability approach has attempted to develop outcome measures that move beyond health-related aspects of quality of life captured by EQ-5D and similar measures used in the generation of QALYs. This study examines the relationship between the EQ-5D and the ICECAP-O capability measure in three different patient populations included in the Medical Crises in Older People programme in England. The authors propose a reasonable hypothesis that health could be considered a conversion factor for a person’s broader capability set, and so it is plausible to test how well the EQ-5D-3L dimension values and overall score can map onto the ICECAP-O overall score. Through numerous regressions performed, the strongest relationship between the two measures in this sample was an R-squared of 0.35. Interestingly, the dimensions on the EQ-5D that had a significant relationship with the ICECAP-O score were a mix of dimensions with a focus on functioning (i.e. self-care, usual activities) and symptoms (anxiety/depression), so overall capability on ICECAP-O appears to be related, at least to a small degree, to both health components of EQ-5D discussed in this round-up’s previous paper. The authors suggest it provides further evidence of the complementary data provided by EQ-5D and ICECAP-O, but the causal relationship, as the authors suggest, between both measures remains under-researched. Longitudinal data analysis would provide a more definitive answer to the question of how much interaction there is between these two measures and their dimensions as health and capability changes over time in response to different treatments and care provision.

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Alastair Canaway’s journal round-up for 28th August 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.

Valuing health-related quality of life: an EQ-5D-5L value set for England. Health Economics [PubMed] Published 22nd August 2017

With much anticipation, the new EQ-5D-5L value set was officially published. For over 18 months we’ve had access to values via the OHE’s discussion paper but the formal peer-reviewed paper has (I imagine) been in publication purgatory. This paper presents the results of the value-set for the new (ish) EQ-5D-5L measure. The study used the internationally agreed hybrid model combining TTO and DCE data to generate the values for the 3125 health states. It’s worth noting that the official values are marginally different to those in the discussion paper, although in practice this is likely to have little impact on results. Important results of the new value set include fewer health states worse than death (5.1% vs over 33%), and a higher minimum value (-0.285 vs -0.594). I’d always been a bit suspect of the values for worse than death states for the 3L measure, so this if anything is encouraging. This does, however, have important implications, primarily for interventions seeking to improve those in the worst health, where potential gains may be reduced. Many of us are actively using the EQ-5D-5L within trials and have been eagerly awaiting this value set. Perhaps naively, I always anticipated that with more levels and an improved algorithm it would naturally supersede the 3L and the outdated 3L value set upon publication. Unfortunately, to mark the release of the new value set, NICE released a ‘position statement’ [PDF] regarding the choice of measure and value sets for the NICE reference case. NICE specifies that i) the 5L value set is not recommended for use, ii) the EQ-5D-3L with the original UK TTO value set is recommended and if both measures are included then the 3L should be preferred, iii) if the 5L measure is included, then scores should be mapped to the EQ-5D-3L using the van Hout et al algorithm, iv) NICE supports the use of the EQ-5D-5L generally to collect data on quality of life, and v) NICE will review this decision in August 2018 in light of future evidence. So, unfortunately, for the next year at least, we will be either sticking to the original 3L measure or mapping from the 5L. I suspect NICE is buying some time as transitioning to the 5L is going to raise lots of interesting issues e.g. if a measure is cost-effective according to the 3L, but not the 5L, or vice-versa, and comparability of 5L results to old 3L results. Interesting times lie ahead. As a final note, it’s worth reading the OHE blog post outlining the position statement and OHE’s plans to satisfy NICE.

Long-term QALY-weights among spouses of dependent and independent midlife stroke survivors. Quality of Life Research [PubMed] Published 29th June 2017

For many years, spillover impacts were largely being ignored within economic evaluation. There is increased interest in capturing wider impacts, indeed, the NICE reference case recommends including carer impacts where relevant, whilst the US Panel on Cost-Effectiveness in Health and Medicine now advocates the inclusion of other affected parties. This study sought to examine whether the dependency of midlife stroke survivors impacted on their spouses’ HRQL as measured using the SF-6D. An OLS approach was used whilst controlling for covariates (age, sex and education, amongst others). Spouses of dependent stroke survivors had a lower utility (0.69) than those whose spouses were independent (0.77). This has interesting implications for economic evaluation. For example, if a treatment were to prevent dependence, then there could potentially be large QALY gains to spouses. Spillover impacts are clearly important. If we are to broaden the evaluative scope as suggested by NICE and the US Panel to include spillover impacts, then work is vital in terms of identifying relevant contexts, measuring spillover impacts, and understanding the implications of spillover impacts within economic evaluation. This remains an important area for future research.

Conducting a discrete choice experiment study following recommendations for good research practices: an application for eliciting patient preferences for diabetes treatments. Value in Health Published 7th August 2017

To finish this week’s round-up I thought it’d be helpful to signpost this article on conducting DCEs, which I feel may be helpful for researchers embarking on their first DCE. The article hasn’t done anything particularly radical or made ground-breaking discoveries. What it does however do is give you a practical guide to walk you through each step of the DCE process following the ISPOR guidelines/checklist. Furthermore, it expands upon the ISPOR checklist to provide researchers with a further resource to consider when conducting DCEs. The case study used relates to measuring patient preferences for type 2 diabetes mellitus medications. For every item on the ISPOR checklist, it explains how they made the choices that they did, and what influenced them. The paper goes through the entire process from identifying the research question all the way through to presenting results and discussion (for those interested in diabetes – it turns out people have a preference for immediate consequences and have a high discount rate for future benefits). For people who are keen to conduct a DCE and find a worked example easier to follow, this paper alongside the ISPOR guidelines is definitely one to add to your reference manager.

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Paul Mitchell’s journal round-up for 17th July 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.

What goes wrong with the allocation of domestic and international resources for HIV? Health Economics [PubMedPublished 7th July 2017

Investment in foreign aid is coming under considered scrutiny as a number of leading western economies re-evaluate their role in the world and their obligations to countries with developing economies. Therefore, it is important for those who believe in the benefits of such investments to show that they are being done efficiently. This paper looks at how funding for HIV is distributed both domestically and internationally across countries, using multivariate regression analysis with instruments to control for reverse causality between financing and HIV prevalence, and domestic and international financing. The author is also concerned about countries free riding on international aid and estimates how countries ought to be allocating national resources to HIV using quintile regression to estimate what countries have fiscal space for expanding their current spending domestically. The results of the study show that domestic expenditure relative to GDP per capita is almost unit elastic, whereas it is inelastic with regards to HIV prevalence. Government effectiveness (as defined by the World Bank indices) has a statistically significant effect on domestic expenditure, although it is nonlinear, with gains more likely when moving up from a lower level of government effectiveness. International expenditure is inversely related to GDP per capita and HIV prevalence, and positively with government effectiveness, albeit the regression models for international expenditure had poor explanatory power. Countries with higher GDP per capita tended to dedicate more money towards HIV, however, the author reckons there is $3bn of fiscal space in countries such as South Africa and Nigeria to contribute more to HIV, freeing up international aid for other countries such as Cameroon, Ghana, Thailand, Pakistan and Columbia. The author is concerned that countries with higher GDP should be able to allocate more to HIV, but feels there are improvements to be made in how international aid is distributed too. Although there is plenty of food for thought in this paper, I was left wondering how this analysis can help in aiding a better allocation of resources. The normative model of what funding for HIV ought to be is from the viewpoint that this is the sole objective of countries of allocating resources, which is clearly contestable (the author even casts doubt as to whether this is true for international funding of HIV). Perhaps the other demands faced by national governments (e.g. funding for other diseases, education etc.) can be better reflected in future research in this area.

Can pay-for-performance to primary care providers stimulate appropriate use of antibiotics? Health Economics [PubMed] [RePEcPublished 7th July 2017

Antibiotic resistance is one of the largest challenges facing global health this century. This study from Sweden looks to see whether pay for performance (P4P) can have a role in the prescription practices of GPs when it comes to treating children with respiratory tract infection. P4P was introduced on a staggered basis across a number of regions in Sweden to incentivise primary care to use narrow spectrum penicillin as a first line treatment, as it is said to have a smaller impact on resistance. Taking advantage of data from the Swedish Prescribed Drug Register between 2006-2013, the authors conducted a difference in difference regression analysis to show the effect P4P had on the share of the incentivised antibiotic. They find a positive main effect of P4P on drug prescribing of 1.1 percentage points, that is also statistically significant. Of interest, the P4P in Sweden under analysis here was not directly linked to salaries of GPs but the health care centre. Although there are a number of limitations with the study that the authors clearly highlight in the discussion, it is a good example of how to make the most of routinely available data. It also highlights that although the share of the less resistant antibiotic went up, the national picture of usage of antibiotics did not reduce in line with a national policy aimed at doing so during the same time period. Even though Sweden is reported to be one of the lower users of antibiotics in Europe, it highlights the need to carefully think through how targets are achieved and where incentives might help in some areas to meet such targets.

Econometric modelling of multiple self-reports of health states: the switch from EQ-5D-3L to EQ-5D-5L in evaluating drug therapies for rheumatoid arthritis. Journal of Health Economics Published 4th July 2017

The EQ-5D is the most frequently used health state descriptive system for the generation of utility values for quality-adjusted life years (QALYs) in economic evaluation. To improve sensitivity and reduce floor and ceiling effects, the EuroQol team developed a five level version (5L) compared to the previous three level (3L) version. This study adds to recent evidence in this area of the unforeseen consequences of making this change to the descriptive system and also the valuation system used for the 5L. Using data from the National Data Bank for Rheumatic Diseases, where both 3L and 5L versions were completed simultaneously alongside other clinical measures, the authors construct a mapping between both versions of EQ-5D, informed by the response levels and the valuation systems that have been developed in the UK for the measures. They also test their mapping estimates on a previous economic evaluation for rheumatoid arthritis treatments. The descriptive results show that although there is a high correlation between both versions, and the 5L version achieves its aim of greater sensitivity, there is a systematic difference in utility scores generated using both versions, with an average 87% of the score of the 3L recorded compared to the 5L. Not only are there differences highlighted between value sets for the 3L and 5L but also the responses to dimensions across measures, where the mobility and pain dimensions do not align as one would expect. The new mapping developed in this paper highlights some of the issues with previous mapping methods used in practice, including the assumption of independence of dimension levels from one another that was used while the new valuation for the 5L was being developed. Although the case study they use to demonstrate the effect of using the different approaches in practice did not result in a different cost-effectiveness result, the study does manage to highlight that the assumption of 3L and 5L versions being substitutes for one another, both in terms of descriptive systems and value sets, does not hold. Although the authors are keen to highlight the benefits of their new mapping that produces a smooth distribution from actual to predicted 5L, decision makers will need to be clear about what descriptive system they now want for the generation of QALYs, given the discrepancies between 3L and 5L versions of EQ-5D, so that consistent results are obtained from economic evaluations.

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