Rachel Houten’s journal round-up for 22nd April 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.

To HTA or not to HTA: identifying the factors influencing the rapid review outcome in Ireland. Value in Health [PubMed] Published 6th March 2019

National health services are constantly under pressure to provide access to new medicines as soon as marketing authorisation is granted. The NCPE in the Republic of Ireland has a rapid review process for selecting medicines that require a full health technology assessment (HTA), and the rest, approximately 45%, are able to be reimbursed without such an in-depth analysis.

Formal criteria do not exist. However, it has previously been suggested that the robustness of clinical evidence of at least equivalence; a drug that costs the same or less; an annual (or estimated) budget impact of less than €0.75 million to €1 million; and the ability of the current health systems to restrict usage are some of what is considered when making the decision.

The authors of this paper used the allocation over the past eight years to explore the factors that drive the decision to embark on a full HTA. They found, unsurprisingly, that first-in-class medicines are more likely to require an HTA as too are those with orphan status. Interestingly, the clinical area influenced the requirement for a full HTA, but the authors consider all of these factors to indicate that high-cost drugs are more likely to require a full assessment. Drug cost information is not publicly available and so the authors used the data available on the Scottish Medicine Consortium website as a surrogate for costs in Ireland. In doing so, they were able to establish a relationship between the cost per person for each drug and the likelihood of the drug having a full HTA, further supporting the idea that more expensive drugs are more likely to require HTA. On the face of it, this seems eminently sensible. However, my concern is that, in a system that is designed to deliberately measure cost per unit of health care (usually QALYs), there is the potential for lower-cost but ineffective drugs to become commonplace while more expensive medicines are subject to more rigor.

The paper provides some insight into what drives a decision to undertake a full HTA in Ireland. The NICE fast-track appraisal system operates as an opt-in system where manufacturers can ask to follow this shorter appraisal route if their drug is likely to produce an ICER of £10,000 or less. As my day job is for an Evidence Review Group (opinions my own), how things are done elsewhere – unsurprisingly – captured my attention. The desire to speed up the HTA process is obvious but the most appropriate mechanisms in which to do so are far from it. Whether or not the same decision is ultimately made is what concerns me.

NHS joint working with industry is out of public sight. BMJ [PubMed] Published 27th March 2019

This paper suggests that ‘joint working arrangements’ – a government-supported initiative between pharmaceutical companies and the NHS – are not being implemented according to guidelines on transparency. These arrangements are designed to promote collaborative research between the NHS and industry and help advance NHS provision of services.

The authors used freedom of information requests to obtain details on how many trusts were involved in joint working arrangements in 2016 and 2017. The declarations of payments made by drug companies are disclosed but the corresponding information from trusts is less readily accessible, and in some cases access to any details was prevented. Theoretically, the joint working arrangements are supposed to be void of any commercial influence on what is prescribed, but my thoughts are echoed in this paper when it asks “what’s in it for the private sector?” The sheer fact that some NHS trusts were unwilling to provide the BMJ with the information requested due to ‘commercial interest’ rings huge alarm bells.

I’m not completely cynical of these arrangements in principle, though, and the paper cites a couple of projects that involved building new facilities for age-related macular generation, which likely offer benefits to patients, and possibly much faster than could have been achieved with NHS funding alone. Some of the arrangements intend to push the implementation of national guidance, which, as a small cog in the guidance generation machine, I unashamedly (and predictably) think is a good thing.

Does it matter to us? As economists, it means that any work based on national practice and costs is likely to be unrepresentative of what actually happens. This, however, has always been the case to some extent, with variations in local service provision and the negotiation power of trusts with large volumes of patients. A national register of the arrangements would have the potential to feed into economic analysis, even if just as a statement of awareness.

Can the NHS survive without getting into bed with industry? Probably not. I think the paper does a good job of presenting the arguments on all sides and pushing for increasing availability of what is happening.

Estimating joint health condition utility values. Value in Health [PubMed] Published 22nd February 2019

I’m really interested in how this area is developing. Multi-morbidity is the norm, especially as we age. Single condition models are criticised for their lack of representation of patients in the real world. Appropriately estimating the quality of life of people with several chronic conditions, when only individual condition data are available, is incredibly difficult.

In this paper, parametric and non-parametric methods were tested on a dataset from a large primary care patient survey in the UK. The multiplicative approach was the best performing for two conditions. When more than two conditions were considered, the linear index (which incorporates additive, multiplicative, and minimum models with the use of linear regression and parameter weights derived from the underlying data) achieved the best results.

Including long-term mental health within the co-morbidities for which utility was estimated produced biased estimates. The authors discuss some possible explanations for this, including the fact that the anxiety and depression question in the EQ-5D is the only one which directly maps to an individual condition, and that mental health may have a causal effect on physical health. This is a fascinating finding, which has left me somewhat scratching my head as to how this oddity could be addressed and if separate methods of estimation will need to be used for any population with multi-morbidity including mental health conditions.

It did make me wonder if more precise EQ-5D data could be helpful to uncover the true interrelationships between joint health conditions and quality of life. The EQ-5D asks patients to think about their health state ‘today’. Although the primary care dataset used includes 16 chronic health conditions, it doesn’t, as far as I know, contain any information on the symptoms apparent on the day of quality of life assessment, which could be flaring or absent at any given time. This is a common problem with the EQ-5D and I don’t think a readily available data source of this type exists, so it’s a thought on ideals. Unsurprisingly, the more joint health conditions to be considered, the larger the error in terms of estimation from individual conditions. This may be due to the increasing likelihood of overlap in the symptoms experienced across conditions and thus a violation of the assumption that quality of life for an individual condition is independent of any other condition.

Whether the methodology remains robust for populations outside of the UK or for other measures of utility would need to be tested, and the authors are keen to highlight the need for caution before running away and using the methods verbatim. The paper does present a nice summary of the evidence to date in this area, what the authors did, and what it adds to the topic, so worth a read.


Chris Sampson’s journal round-up for 1st April 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.

Toward a centralized, systematic approach to the identification, appraisal, and use of health state utility values for reimbursement decision making: introducing the Health Utility Book (HUB). Medical Decision Making [PubMed] Published 22nd March 2019

Every data point reported in research should be readily available to us all in a structured knowledge base. Most of us waste most of our time retreading old ground, meaning that we don’t have the time to do the best research possible. One instance of this is in the identification of health state utility values to plug into decision models. Everyone who builds a model in a particular context goes searching for utility values – there is no central source. The authors of this paper are hoping to put an end to that.

The paper starts with an introduction to the importance of health state utility values in cost-effectiveness analysis, which most of us don’t need to read. Of course, the choice of utility values in a model is very important and can dramatically alter estimates of cost-effectiveness. The authors also discuss issues around the identification of utility values and the assessment of their quality and applicability. Then we get into the objectives of the ‘Health Utility Book’, which is designed to tackle these issues.

The Health Utility Book will consist of a registry (I like registries), backed by a systematic approach to the identification and inclusion (registration?) of utility values. The authors plan to develop a quality assessment tool for studies that report utility values, using a Delphi panel method to identify appropriate indicators of quality to be included. The quality assessment tool will be complemented by a tool to assess applicability, which will be developed through interviews with stakeholders involved in the reimbursement process.

In the first place, the Health Utility Book will only compile utility values for cancer, and some of the funding for the project is cancer specific. To survive, the project will need more money from more sources. To be sustainable, the project will need to attract funding indefinitely. Or perhaps it could morph into a crowd-sourced platform. Either way, the Health Utility Book has my support.

A review of attitudes towards the reuse of health data among people in the European Union: the primacy of purpose and the common good. Health Policy Published 21st March 2019

We all agree that data protection is important. We all love the GDPR. Organisations such as the European Council and the OECD are committed to facilitating the availability of health data as a means of improving population health. And yet, there often seem to be barriers to accessing health data, and we occasionally hear stories of patients opposing data sharing (e.g. care.data). Maybe people don’t want researchers to be using their data, and we just need to respect that. Or, more likely, we need to figure out what it is that people are opposed to, and design systems that recognise this.

This study reviews research on attitudes towards the sharing of health data for purposes other than treatment, among people living in the EU, employing a ‘configurative literature synthesis’ (a new one for me). From 5,691 abstracts, 29 studies were included. Most related to the use of health data in research in general, while some focused on registries. A few studies looked at other uses, such as for planning and policy purposes. And most were from the UK.

An overarching theme was a low awareness among the population about the reuse of health data. However, in some studies, a desire to be better informed was observed. In general, views towards the use of health data were positive. But this was conditional on the data being used to serve the common good. This includes such purposes as achieving a better understanding of diseases, improving treatments, or achieving more efficient health care. Participants weren’t so happy with health data reuse if it was seen to conflict with the interests of patients providing the data. Commercialisation is a big concern, including the sale of data and private companies profiting from the data. Employers and insurance companies were also considered a threat to patients’ interests. There were conflicting views about whether it is positive for pharmaceutical companies to have access to health data. A minority of people were against sharing data altogether. Certain types of data are seen as being particularly sensitive, including those relating to mental health or sexual health. In general, people expressed concern about data security and the potential for leaks. The studies also looked at the basis for consent that people would prefer. A majority accepted that their data could be used without consent so long as the data were anonymised. But there were no clear tendencies of preference for the various consent models.

It’s important to remember that – on the whole – patients want their data to be used to further the common good. But support can go awry if the data are used to generate profits for private firms or used in a way that might be perceived to negatively affect patients.

Health-related quality of life in injury patients: the added value of extending the EQ-5D-3L with a cognitive dimension. Quality of Life Research [PubMed] Published 18th March 2019

I’m currently working on a project to develop a cognition ‘bolt-on’ for the EQ-5D. Previous research has demonstrated that a cognition bolt-on could provide additional information to distinguish meaningful differences between health states, and that cognition might be a more important candidate than other bolt-ons. Injury – especially traumatic brain injury – can be associated with cognitive impairments. This study explores the value of a cognition bolt-on in this context.

The authors sought to find out whether cognition is sufficiently independent of other dimensions, whether the impact of cognitive problems is reflected in the EuroQol visual analogue scale (EQ VAS), and how a cognition bolt-on affects the overall explanatory power of the EQ-5D-3L. The data used are from the Dutch Injury Surveillance System, which surveys people who have attended an emergency department with an injury, including EQ-5D-3L. The survey adds a cognitive bolt-on relating to memory and concentration.

Data were available for 16,624 people at baseline, with 5,346 complete responses at 2.5-month follow-up. The cognition item was the least affected, with around 20% reporting any problems (though it’s worth noting that the majority of the cohort had injuries to parts of the body other than the head). The frequency of different responses suggests that cognition is dominant over other dimensions in the sense that severe cognitive problems tend to be observed alongside problems in other dimensions, but not vice versa. The mean EQ VAS for people reporting severe cognitive impairment was 41, compared with a mean of 75 for those reporting no problems. Regression analysis showed that moderate and severe cognitive impairment explained 8.7% and 6.2% of the variance of the EQ VAS. Multivariate analysis suggested that the cognitive dimension added roughly the same explanatory power as any other dimension. This was across the whole sample. Interestingly (or, perhaps, worryingly) when the authors looked at the subset of people with traumatic brain injury, the explanatory power of the cognitive dimension was slightly lower than overall.

There’s enough in this paper to justify further research into the advantages and disadvantages of using a cognition bolt-on. But I would say that. Whether or not the bolt-on descriptors used in this study are meaningful to patients remains an open question.

Developing the role of electronic health records in economic evaluation. The European Journal of Health Economics [PubMed] Published 14th March 2019

One way that we can use patients’ routinely collected data is to support the conduct of economic evaluations. In this commentary, the authors set out some of the ways to make the most of these data and discuss some of the methodological challenges. Large datasets have the advantage of being large. When this is combined with the collection of sociodemographic data, estimates for sub-groups can be produced. The data can also facilitate the capture of outcomes not otherwise available. For example, the impact of bariatric surgery on depression outcomes could be identified beyond the timeframe of a trial. The datasets also have the advantage of being representative, where trials are not. This could mean more accurate estimates of costs and outcomes. But there are things to bear in mind when using the data, such as the fact that coding might not always be very accurate, and coding practices could vary between observations. Missing data are likely to be missing for a reason (i.e. not at random), which creates challenges for the analyst. I had hoped that this paper would discuss novel uses of routinely collected data systems, such as the embedding of economic evaluations within them, rather than simply their use to estimate parameters for a model. But if you’re just getting started with using routine data, I suppose you could do worse than start with this paper.


Chris Sampson’s journal round-up for 11th March 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.

Identification, review, and use of health state utilities in cost-effectiveness models: an ISPOR Good Practices for Outcomes Research Task Force report. Value in Health [PubMed] Published 1st March 2019

When modellers select health state utility values to plug into their models, they often do it in an ad hoc and unsystematic way. This ISPOR Task Force report seeks to address that.

The authors discuss the process of searching, reviewing, and synthesising utility values. Searches need to use iterative techniques because evidence requirements develop as a model develops. Due to the scope of models, it may be necessary to develop multiple search strategies (for example, for different aspects of disease pathways). Searches needn’t be exhaustive, but they should be systematic and transparent. The authors provide a list of factors that should be considered in defining search criteria. In reviewing utility values, both quality and appropriateness should be considered. Quality is indicated by the precision of the evidence, the response rate, and missing data. Appropriateness relates to the extent to which the evidence being reviewed conforms to the context of the model in which it is to be used. This includes factors such as the characteristics of the study population, the measure used, value sets used, and the timing of data collection. When it comes to synthesis, the authors suggest it might not be meaningful in most cases, because of variation in methods. We can’t pool values if they aren’t (at least roughly) equivalent. Therefore, one approach is to employ strict inclusion criteria (e.g only EQ-5D, only a particular value set), but this isn’t likely to leave you with much. Meta-regression can be used to analyse more dissimilar utility values and provide insight into the impact of methodological differences. But the extent to which this can provide pooled values for a model is questionable, and the authors concede that more research is needed.

This paper can inform that future research. Not least in its attempt to specify minimum reporting standards. We have another checklist, with another acronym (SpRUCE). The idea isn’t so much that this will guide publications of systematic reviews of utility values, but rather that modellers (and model reviewers) can use it to assess whether the selection of utility values was adequate. The authors then go on to offer methodological recommendations for using utility values in cost-effectiveness models, considering issues such as modelling technique, comorbidities, adverse events, and sensitivity analysis. It’s early days, so the recommendations in this report ought to be changed as methods develop. Still, it’s a first step away from the ad hoc selection of utility values that (no doubt) drives the results of many cost-effectiveness models.

Estimating the marginal cost of a life year in Sweden’s public healthcare sector. The European Journal of Health Economics [PubMed] Published 22nd February 2019

It’s only recently that health economists have gained access to data that enables the estimation of the opportunity cost of health care expenditure on a national level; what is sometimes referred to as a supply-side threshold. We’ve seen studies in the UK, Spain, Australia, and here we have one from Sweden.

The authors use data on health care expenditure at the national (1970-2016) and regional (2003-2016) level, alongside estimates of remaining life expectancy by age and gender (1970-2016). First, they try a time series analysis, testing the nature of causality. Finding an apparently causal relationship between longevity and expenditure, the authors don’t take it any further. Instead, the results are based on a panel data analysis, employing similar methods to estimates generated in other countries. The authors propose a conceptual model to support their analysis, which distinguishes it from other studies. In particular, the authors assert that the majority of the impact of expenditure on mortality operates through morbidity, which changes how the model should be specified. The number of newly graduated nurses is used as an instrument indicative of a supply-shift at the national rather than regional level. The models control for socioeconomic and demographic factors and morbidity not amenable to health care.

The authors estimate the marginal cost of a life year by dividing health care expenditure by the expenditure elasticity of life expectancy, finding an opportunity cost of €38,812 (with a massive 95% confidence interval). Using Swedish population norms for utility values, this would translate into around €45,000/QALY.

The analysis is considered and makes plain the difficulty of estimating the marginal productivity of health care expenditure. It looks like a nail in the coffin for the idea of estimating opportunity costs using time series. For now, at least, estimates of opportunity cost will be based on variation according to geography, rather than time. In their excellent discussion, the authors are candid about the limitations of their model. Their instrument wasn’t perfect and it looks like there may have been important confounding variables that they couldn’t control for.

Frequentist and Bayesian meta‐regression of health state utilities for multiple myeloma incorporating systematic review and analysis of individual patient data. Health Economics [PubMed] Published 20th February 2019

The first paper in this round-up was about improving practice in the systematic review of health state utility values, and it indicated the need for more research on the synthesis of values. Here, we have some. In this study, the authors conduct a meta-analysis of utility values alongside an analysis of registry and clinical study data for multiple myeloma patients.

A literature search identified 13 ‘methodologically appropriate’ papers, providing 27 health state utility values. The EMMOS registry included data for 2,445 patients in 22 counties and the APEX clinical study included 669 patients, all with EQ-5D-3L data. The authors implement both a frequentist meta-regression and a Bayesian model. In both cases, the models were run including all values and then with a limited set of only EQ-5D values. These models predicted utility values based on the number of treatment classes received and the rate of stem cell transplant in the sample. The priors used in the Bayesian model were based on studies that reported general utility values for the presence of disease (rather than according to treatment).

The frequentist models showed that utility was low at diagnosis, higher at first treatment, and lower at each subsequent treatment. Stem cell transplant had a positive impact on utility values independent of the number of previous treatments. The results of the Bayesian analysis were very similar, which the authors suggest is due to weak priors. An additional Bayesian model was run with preferred data but vague priors, to assess the sensitivity of the model to the priors. At later stages of disease (for which data were more sparse), there was greater uncertainty. The authors provide predicted values from each of the five models, according to the number of treatment classes received. The models provide slightly different results, except in the case of newly diagnosed patients (where the difference was 0.001). For example, the ‘EQ-5D only’ frequentist model gave a value of 0.659 for one treatment, while the Bayesian model gave a value of 0.620.

I’m not sure that the study satisfies the recommendations outlined in the ISPOR Task Force report described above (though that would be an unfair challenge, given the timing of publication). We’re told very little about the nature of the studies that are included, so it’s difficult to judge whether they should have been combined in this way. However, the authors state that they have made their data extraction and source code available online, which means I could check that out (though, having had a look, I can’t find the material that the authors refer to, reinforcing my hatred for the shambolic ‘supplementary material’ ecosystem). The main purpose of this paper is to progress the methods used to synthesise health state utility values, and it does that well. Predictably, the future is Bayesian.