Rachel Houten’s journal round-up for 11th November 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.

A comparison of national guidelines for network meta-analysis. Value in Health [PubMed] Published October 2019

The evolving treatment landscape results in a greater dependence on indirect treatment comparisons to generate estimates of clinical effectiveness, where the current practice has not been compared to the proposed new intervention in a head-to-head trial. This paper is a review of the guidelines of reimbursement bodies for conducting network meta-analyses. Reassuringly, the authors find that it is possible to meet the needs of multiple agencies with one analysis.

The authors assign three categories to the criteria; “assessment and analysis to test assumptions required for a network meta-analysis, presentation and reporting of results, and justification of modelling choices”, with heterogeneity of the included studies highlighted as one of the key elements to be sure to include if prioritisation of the criteria is necessary. I think this is a simple way of thinking about what needs to be presented but the ‘justification’ category, in my experience, is often given less weight than the other two.

This paper is a useful resource for companies submitting to multiple HTA agencies with the requirements of each national body displayed in tables that are easy to navigate. It meets a practical need but doesn’t really go far enough for me. They do signpost to the PRISMA criteria, but I think it would have been really good to think about the purpose of the submission guidelines; to encourage a logical and coherent summary of the approaches taken so the evidence can be evaluated by decision-makers.

Variation in responsiveness to warranted behaviour change among NHS clinicians: novel implementation of change detection methods in longitudinal prescribing data. BMJ [PubMed] Published 2nd October 2019

I really like this paper. Such a lot of work, from all sectors, is devoted to the production of relevant and timely evidence to inform practice, but if the guidance does not become embedded into the real world then its usefulness is limited.

The authors have managed to utilize a HUGE amount of data to identify the real reaction to two pieces of guidance recommending a change in practice in England. The authors used “trend indicator saturation”, which I’m not ashamed to admit I knew nothing about beforehand, but it is explained nicely. Their thoughtful use of the information available to them results in three indicators of response (in this case the deprescribing of two drugs) around when the change occurs, how quickly it occurs, and how much change occurs.

The authors discover variation in response to the recommendations but suggest an application of their methods could be used to generate feedback to clinicians and therefore drive further response. As some primary care practices took a while to embed the guidance change into their prescribing, the paper raises interesting questions as to where the barriers to the adoption of guidance have occurred.

What is next for patient preferences in health technology assessment? A systematic review of the challenges. Value in Health Published November 2019

It may be that patient preferences have a role to play in the uptake of guideline recommendations, as proposed by the authors of my final paper this week. This systematic review, of the literature around embedding patient preferences into HTA decision-making, groups the discussion in the academic literature into five broad areas; conceptual, normative, procedural, methodological, and practical. The authors state that their purpose was not to formulate their own views, merely to present the available literature, but they do a good job of indicating where to find more opinionated literature on this topic.

Methodological issues were the biggest group, with aspects such as the sample selection, internal and external validity of the preferences generated, and the generalisability of the preferences collected from a sample to the entire population. However, in general, the number of topics covered in the literature is vast and varied.

It’s a great summary of the challenges that are faced, and a ranking based on frequency of topic being mentioned in the literature drives the authors proposed next steps. They recommend further research into the incorporation of preferences within or beyond the QALY and the use of multiple-criteria decision analysis as a method of integrating patient preferences into decision-making. I support the need for “a scientifically and valid manner” to integrate patient preferences into HTA decision-making but wonder if we can first learn of what works well and hasn’t worked so well from the attempts of HTA agencies thus far.

Credits

Sam Watson’s journal round-up for 30th April 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.

The Millennium Villages Project: a retrospective, observational, endline evaluation. The Lancet Global Health [PubMedPublished May 2018

There are some clinical researchers who would have you believe observational studies are completely useless. The clinical trial is king, they might say, observation studies are just too biased. And while it’s true that observational studies are difficult to do well and convincingly, they can be a reliable and powerful source of evidence. Similarly, randomised trials are frequently flawed, for example there’s often missing data that hasn’t been dealt with, or a lack of allocation concealment, and many researchers forget that randomisation does not guarantee a balance of covariates, it merely increases the probability of it. I bring this up, as this study is a particularly carefully designed observational data study that I think serves as a good example to other researchers. The paper is an evaluation of the Millennium Villages Project, an integrated intervention program designed to help rural villages across sub-Saharan Africa meet the Millennium Development Goals over ten years between 2005 and 2015. Initial before-after evaluations of the project were criticised for inferring causal “impacts” from before and after data (for example, this Lancet paper had to be corrected after some criticism). To address these concerns, this new paper is incredibly careful about choosing appropriate control villages against which to evaluate the intervention. Their method is too long to summarise here, but in essence they match intervention villages to other villages on the basis of district, agroecological zone, and a range of variables from the DHS – matches were they reviewed for face validity and revised until a satisfactory matching was complete. The wide range of outcomes are all scaled to a standard normal and made to “point” in the same direction, i.e. so an increase indicated economic development. Then, to avoid multiple comparisons problems, a Bayesian hierarchical model is used to pool data across countries and outcomes. Costs data were also reported. Even better, “statistical significance” is barely mentioned at all! All in all, a neat and convincing evaluation.

Reconsidering the income‐health relationship using distributional regression. Health Economics [PubMed] [RePEcPublished 19th April 2018

The relationship between health and income has long been of interest to health economists. But it is a complex relationship. Increases in income may change consumption behaviours and a change in the use of time, promoting health, while improvements to health may lead to increases in income. Similarly, people who are more likely to make higher incomes may also be those who look after themselves, or maybe not. Disentangling these various factors has generated a pretty sizeable literature, but almost all of the empirical papers in this area (and indeed all empirical papers in general) use modelling techniques to estimate the effect of something on the expected value, i.e. mean, of some outcome. But the rest of the distribution is of interest – the mean effect of income may not be very large, but a small increase in income for poorer individuals may have a relatively large effect on the risk of very poor health. This article looks at the relationship between income and the conditional distribution of health using something called “structured additive distribution regression” (SADR). My interpretation of SADR is that, one would model the outcome y ~ g(a,b) as being distributed according to some distribution g(.) indexed by parameters a and b, for example, a normal or Gamma distribution has two parameters. One would then specify a generalised linear model for a and b, e.g. a = f(X’B). I’m not sure this is a completely novel method, as people use the approach to, for example, model heteroscedasticity. But that’s not to detract from the paper itself. The findings are very interesting – increases to income have a much greater effect on health at the lower end of the spectrum.

Ask your doctor whether this product is right for you: a Bayesian joint model for patient drug requests and physician prescriptions. Journal of the Royal Statistical Society: Series C Published April 2018.

When I used to take econometrics tutorials for undergraduates, one of the sessions involved going through coursework about the role of advertising. To set the scene, I would talk about the work of Alfred Marshall, the influential economist from the late 1800s/early 1900s. He described two roles for advertising: constructive and combative. The former is when advertising grows the market as a whole, increasing everyone’s revenues, and the latter is when ads just steal market share from rivals without changing the size of the market. Later economists would go on to thoroughly develop theories around advertising, exploring such things as the power of ads to distort preferences, the supply of ads and their complementarity with the product they’re selling, or seeing ads as a source of consumer information. Nevertheless, Marshall’s distinction is still a key consideration, although often phrased in different terms. This study examines a lot of things, but one of its key objectives is to explore the role of direct to consumer advertising on prescriptions of brands of drugs. The system is clearly complex: drug companies advertise both to consumers and physicians, consumers may request the drug from the physician, and the physician may or may not prescribe it. Further, there may be correlated unobservable differences between physicians and patients, and the choice to advertise to particular patients may not be exogenous. The paper does a pretty good job of dealing with each of these issues, but it is dense and took me a couple of reads to work out what was going on, especially with the mix of Bayesian and Frequentist terms. Examining the erectile dysfunction drug market, the authors reckon that direct to consumer advertising reduces drug requests across the category, while increasing the proportion of requests for the advertised drug – potentially suggesting a “combative” role. However, it’s more complex than that patient requests and doctor’s prescriptions seem to be influenced by a multitude of factors.

Credits

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.

Credits