Chris Sampson’s journal round-up for 31st 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.

An exploratory study on using principal-component analysis and confirmatory factor analysis to identify bolt-on dimensions: the EQ-5D case study. Value in Health Published 14th July 2017

I’m not convinced by the idea of using bolt-on dimensions for multi-attribute utility instruments. A state description with a bolt-on refers to a different evaluative space, and therefore is not comparable with the progenitor, thus undermining its purpose. Maybe this study will persuade me otherwise. The authors analyse data from the Multi Instrument Comparison database, including responses to EQ-5D-5L, SF-6D, HUI3, AQoL 8D and 15D questionnaires, as well as the ICECAP and 3 measures of subjective well-being. Content analysis was used to allocate items from the measures to underlying constructs of health-related quality of life. The sample of 8022 was randomly split, with one half used for principal-component analysis and confirmatory factor analysis, and the other used for validation. This approach looks at the underlying constructs associated with health-related quality of life and the extent to which individual items from the questionnaires influence them. Candidate items for bolt-ons are those items from questionnaires other than the EQ-5D that are important and not otherwise captured by the EQ-5D questions. The principal-component analysis supported a 9-component model: physical functioning, psychological symptoms, satisfaction, pain, relationships, speech/cognition, hearing, energy/sleep and vision. The EQ-5D only covered physical functioning, psychological symptoms and pain. Therefore, items from measures that explain the other 6 components represent bolt-on candidates for the EQ-5D. This study succeeds in its aim. It demonstrates what appears to be a meaningful quantitative approach to identifying items not fully captured by the EQ-5D, which might be added as bolt-ons. But it doesn’t answer the question of which (if any) of these bolt-ons ought to be added, or in what circumstances. That would at least require pre-definition of the evaluative space, which might not correspond to the authors’ chosen model of health-related quality of life. If it does, then these findings would be more persuasive as a reason to do away with the EQ-5D altogether.

Endogenous information, adverse selection, and prevention: implications for genetic testing policy. Journal of Health Economics Published 13th July 2017

If you can afford it, there are all sorts of genetic tests available nowadays. Some of them could provide valuable information about the risk of particular health problems in the future. Therefore, they can be used to guide individuals’ decisions about preventive care. But if the individual’s health care is financed through insurance, that same information could prove costly. It could reinforce that classic asymmetry of information and adverse selection problem. So we need policy that deals with this. This study considers the incentives and insurance market outcomes associated with four policy options: i) mandatory disclosure of test results, ii) voluntary disclosure, iii) insurers knowing the test was taken, but not the results and iv) complete ban on the use of test information by insurers. The authors describe a utility model that incorporates the use of prevention technologies, and available insurance contracts, amongst people who are informed or uninformed (according to whether they have taken a test) and high or low risk (according to test results). This is used to estimate the value of taking a genetic test, which differs under the four different policy options. Under voluntary disclosure, the information from a genetic test always has non-negative value to the individual, who can choose to only tell their insurer if it’s favourable. The analysis shows that, in terms of social welfare, mandatory disclosure is expected to be optimal, while an information ban is dominated by all other options. These findings are in line with previous studies, which were less generalisable according to the authors. In the introduction, the authors state that “ethical issues are beyond the scope of this paper”. That’s kind of a problem. I doubt anybody who supports an information ban does so on the basis that they think it will maximise social welfare in the fashion described in this paper. More likely, they’re worried about the inequities in health that mandatory disclosure could reinforce, about which this study tells us nothing. Still, an information ban seems to be a popular policy, and studies like this indicate that such decisions should be reconsidered in light of their expected impact on social welfare.

Returns to scientific publications for pharmaceutical products in the United States. Health Economics [PubMedPublished 10th July 2017

Publication bias is a big problem. Part of the cause is that pharmaceutical companies have no incentive to publish negative findings for their own products. Though positive findings may be valuable in terms of sales. As usual, it isn’t quite that simple when you really think about it. This study looks at the effect of publications on revenue for 20 branded drugs in 3 markets – statins, rheumatoid arthritis and asthma – using an ‘event-study’ approach. The authors analyse a panel of quarterly US sales data from 2003-2013 alongside publications identified through literature searches and several drug- and market-specific covariates. Effects are estimated using first difference and difference in first difference models. The authors hypothesise that publications should have an important impact on sales in markets with high generic competition, and less in those without or with high branded competition. Essentially, this is what they find. For statins and asthma drugs, where there was some competition, clinical studies in high-impact journals increased sales to the tune of $8 million per publication. For statins, volume was not significantly affected, with mediation through price. In rhematoid arthritis, where competition is limited, the effect on sales was mediated by the effect on volume. Studies published in lower impact journals seemed to have a negative influence. Cost-effectiveness studies were only important in the market with high generic competition, increasing statin sales by $2.2 million on average. I’d imagine that these impacts are something with which firms already have a reasonable grasp. But this study provides value to public policy decision makers. It highlights those situations in which we might expect manufacturers to publish evidence and those in which it might be worthwhile increasing public investment to pick up the slack. It could also help identify where publication bias might be a bigger problem due to the incentives faced by pharmaceutical companies.



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.


Thesis Thursday: Raymond Oppong

On the third Thursday of every month, we speak to a recent graduate about their thesis and their studies. This month’s guest is Dr Raymond Oppong who graduated with a PhD from the University of Birmingham. If you would like to suggest a candidate for an upcoming Thesis Thursday, get in touch.

Economic analysis alongside multinational studies
Sue Jowett, Tracy Roberts
Repository link

What attracted you to studying economic evaluation in the context of multinational studies?

One of the first projects that I was involved in when I started work as a health economist was the Genomics to combat Resistance against Antibiotics in Community-acquired lower respiratory tract infections (LRTI) in Europe (GRACE) project. This was an EU-funded study aimed at integrating and coordinating the activities of physicians and scientists from institutions in 14 European countries to combat antibiotic resistance in community-acquired lower respiratory tract infections.

My first task on this project was to undertake a multinational costing study to estimate the costs of treating acute cough/LRTI in Europe. I faced quite a number of challenges including the lack of unit cost data across countries. Conducting a full economic evaluation alongside the interventional studies in GRACE also brought up a number of issues with respect to methods of analysis of multinational trials which needed to be resolved. The desire to understand and resolve some of these issues led me to undertake the PhD to investigate the implications of conducting economic evaluations alongside multinational studies.

Your thesis includes some case studies from a large multinational project. What were the main findings of your empirical work?

I used three main case studies for my empirical work. The first was an observational study aimed at describing the current presentation, investigation, treatment and outcomes of community-acquired lower respiratory tract infections and analysing the determinants of antibiotic use in Europe. The other 2 were RCTs. The first was aimed at studying the effectiveness of antibiotic therapy (amoxicillin) in community-acquired lower respiratory tract infections, whilst the second was aimed at assessing training interventions to improve antibiotic prescribing behaviour by general practitioners. The observational study was used to explore issues relating to costing and outcomes in multinational studies whilst the RCTs explored the various analytical approaches (pooled and split) to economic evaluation alongside multinational studies.

The results from the observational study revealed large variations in costs across Europe and showed that contacting researchers in individual countries was the most effective way of obtaining unit costs. Results from both RCTs showed that the choice of whether to pool or split data had an impact on the cost-effectiveness of the interventions.

What were the key analytical methods used in your analysis?

The overall aim of the thesis was to study the implications of conducting economic analysis alongside multinational studies. Specific objectives include: i) documenting challenges associated with economic evaluations alongside multinational studies, ii) exploring various approaches to obtaining and estimating unit costs, iii) exploring the impact of using different tariffs to value EQ-5D health state descriptions, iv) comparing methods that have been used to conduct economic evaluation alongside multinational studies and v) making recommendations to guide the design and conduct of future economic evaluations carried out alongside multinational studies.

A number of approaches were used to achieve each of the objectives. A systematic review of the literature identified challenges associated with economic evaluations alongside multinational studies. A four-stage approach to obtaining unit costs was assessed. The UK, European and country-specific EQ-5D value sets were compared to determine which is the most appropriate to use in the context of multinational studies. Four analytical approaches – fully pooled one country costing, fully pooled multicountry costing, fully split one country costing and fully split multicountry costing – were compared in terms of resource use, costs, health outcomes and cost-effectiveness. Finally, based on the findings of the study, a set of recommendations were developed.

You completed your PhD part-time while working as a researcher. Did you find this a help or a hindrance to your studies?

I must say that it was both a help and a hindrance. Working in a research environment was really helpful. There was a lot of support from supervisors and colleagues which kept me motivated. I might have not gotten this support if I was not working in a research/academic environment. However, even though some time during the week was allocated to the PhD, I had to completely put it on hold for long periods of time in order to deal with the pressures of work/research. Consequently, I always had to struggle to find my bearings when I got back to the PhD. I also spent most weekends working on the PhD especially when I was nearing submission.

On the whole, it should be noted that a part-time PhD requires a lot of time management skills. I personally had to go on time management courses which were really helpful.

What advice would you give to a health economist conducting an economic evaluation alongside a multinational study?

For a health economist conducting an economic evaluation alongside a multinational trial, it is important to plan ahead and understand the challenges that are associated with economic evaluations alongside multinational studies. A lot of the problems such as those related to the identification of unit costs can be avoided by ensuring adequate measures are put in place at the design stage of the study. An understanding of the various health systems of the countries involved in the study is important in order to make a judgement about the differences and similarities in resource use across countries. Decision makers are interested in results that can be applied to their jurisdiction; therefore it is important to adopt transparent methods e.g. state the countries that participated in the study, state the sources of unit costs and make it clear whether data from all countries (pooling) or from a subset (splitting) were used. To ensure that the results of the study are generalisable to a number of countries it may be advisable to present country-specific results and probably conduct the analysis from different perspectives.