Chris Sampson’s journal round-up for 5th November 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.

Stratified treatment recommendation or one-size-fits-all? A health economic insight based on graphical exploration. The European Journal of Health Economics [PubMed] Published 29th October 2018

Health care is increasingly personalised. This creates the need to evaluate interventions for smaller and smaller subgroups as patient heterogeneity is taken into account. And this usually means we lack the statistical power to have confidence in our findings. The purpose of this paper is to consider the usefulness of a tool that hasn’t previously been employed in economic evaluation – the subpopulation treatment effect pattern plot (STEPP). STEPP works by assessing the interaction between treatments and covariates in different subgroups, which can then be presented graphically. Imagine your X-axis with the values defining the subgroups and your Y-axis showing the treatment outcome. This information can then be used to determine which subgroups exhibit positive outcomes.

This study uses data from a trial-based economic evaluation in heart failure, where patients’ 18-month all-cause mortality risk was estimated at baseline before allocation to one of three treatment strategies. For the STEPP procedure, the authors use baseline risk to define subgroups and adopt net monetary benefit at the patient level as the outcome. The study makes two comparisons (between three alternative strategies) and therefore presents two STEPP figures. The STEPP figures are used to identify subgroups, which the authors apply in a stratified cost-effectiveness analysis, estimating net benefit in each defined risk subgroup.

Interpretation of the STEPPs is a bit loose, with no hard decision rules. The authors suggest that one of the STEPPs shows no clear relationship between net benefit and baseline risk in terms of the cost-effectiveness of the intervention (care as usual vs basic support). The other STEPP shows that, on average, people with baseline risk below 0.16 have a positive net benefit from the intervention (intensive support vs basic support), while those with higher risk do not. The authors evaluate this stratification strategy against an alternative stratification strategy (based on the patient’s New York Heart Association class) and find that the STEPP-based approach is expected to be more cost-effective. So the key message seems to be that STEPP can be used as a basis for defining subgroups as cost-effectively as possible.

I’m unsure about the extent to which this is a method that deserves to have its own name, insofar as it is used in this study. I’ve seen plenty of studies present a graph with net benefit on the Y-axis and some patient characteristic on the X-axis. But my main concern is about defining subgroups on the basis of net monetary benefit rather than some patient characteristic. Is it OK to deny treatment to subgroup A because treatment costs are higher than in subgroup B, even if treatment is cost-effective for the entire population of A+B? Maybe, but I think that creates more challenges than stratification on the basis of treatment outcome.

Using post-market utilisation analysis to support medicines pricing policy: an Australian case study of aflibercept and ranibizumab use. Applied Health Economics and Health Policy [PubMed] Published 25th October 2018

The use of ranibizumab and aflibercept has been a hot topic in the UK, where NHS providers feel that they’ve been bureaucratically strong-armed into using an incredibly expensive drug to treat certain eye conditions when a cheaper and just-as-effective alternative is available. Seeing how other countries have managed prices in this context could, therefore, be valuable to the NHS and other health services internationally. This study uses data from Australia, where decisions about subsidising medicines are informed by research into how drugs are used after they come to market. Both ranibizumab (in 2007) and aflibercept (in 2012) were supported for the treatment of age-related macular degeneration. These decisions were based on clinical trials and modelling studies, which also showed that the benefit of ~6 aflibercept prescriptions equated to the benefit of ~12 ranibizumab prescriptions, justifying a higher price-per-injection for aflibercept.

In the UK and US, aflibercept attracts a higher price. The authors assume that this is because of the aforementioned trial data relating to the number of doses. However, in Australia, the same price is paid for aflibercept and ranibizumab. This is because a post-market analysis showed that, in practice, ranibizumab and aflibercept had a similar dose frequency. The purpose of this study is to see whether this is because different groups of patients are being prescribed the two drugs. If they are, then we might anticipate heterogenous treatment outcomes and thus a justification for differential pricing. Data were drawn from an administrative claims database for 208,000 Australian veterans for 2007-2017. The monthly number of aflibercept and ranibizumab prescriptions was estimated for each person, showing that total prescriptions increased steadily over the period, with aflibercept taking around half the market within a year of its approval. Ranibizumab initiators were slightly older in the post-aflibercept era but, aside from that, there were no real differences identified. When it comes to the prescription of ranibizumab or aflibercept, gender, being in residential care, remoteness of location, and co-morbidities don’t seem to be important. Dispensing rates were similar, at around 3 prescriptions during the first 90 days and around 9 prescriptions during the following 12 months.

The findings seem to support Australia’s decision to treat ranibizumab and aflibercept as substitutes at the same price. More generally, they support the idea that post-market utilisation assessments can (and perhaps should) be used as part of the health technology assessment and reimbursement process.

Do political factors influence public health expenditures? Evidence pre- and post-great recession. The European Journal of Health Economics [PubMed] Published 24th October 2018

There is mixed evidence about the importance of partisanship in public spending, and very little relating specifically to health care. I’d be worried if political factors didn’t influence public spending on health, given that that’s a definitively political issue. How the situation might be different before and after a recession is an interesting question.

The authors combined OECD data for 34 countries from 1970-2016 with the Database of Political Institutions. This allowed for the creation of variables relating to the ideology of the government and the proximity of elections. Stationary panel data models were identified as the most appropriate method for analysis of these data. A variety of political factors were included in the models, for which the authors present marginal effects. The more left-wing a government, the higher is public spending on health care, but this is only statistically significant in the period before the crisis of 2007. Before the crisis, coalition governments tended to spend more, while governments with more years in office tended to spend less. These effects also seem to disappear after 2007. Throughout the whole period, governing parties with a stronger majority tended to spend less on health care. Several of the non-political factors included in the models show the results that we would expect. GDP per capita is positively associated with health care expenditures, for example. The findings relating to the importance of political factors appear to be robust to the inclusion of other (non-political) variables and there are similar findings when the authors look at public health expenditure as a percentage of total health expenditure. In contradiction with some previous studies, proximity to elections does not appear to be important.

The most interesting finding here is that the effect of partisanship seems to have mostly disappeared – or, at least, reduced – since the crisis of 2007. Why did left-wing parties and right-wing parties converge? The authors suggest that it’s because adverse economic circumstances restrict the extent to which governments can make decisions on the basis of ideology. Though I dare say readers of this blog could come up with plenty of other (perhaps non-economic) explanations.

Credits

ICU triage: a challenge and an opportunity

In a well-publicized snapshot of the challenge of ICU triage, Chang and colleagues wrote:

Critical care services can be life-saving, but many patients admitted to intensive care units (ICUs) are too sick or, conversely, not sick enough to benefit. Intensive care unit overutilization can produce more costly and invasive care without improving outcomes.

Emphasis added. Hyder provides an interesting critique to which Chang and Shapiro respond. In this post, I shall consider over-utilization by those “not sick enough to benefit”: 23.4% of the 808 patients admitted to the UCLA Medical Center in the study by Chang et al. This over-utilization provides both a challenge and a win-win opportunity (better outcomes at lower cost) if we can meet the challenge.

In a forward-looking vision, which some may regard as optimistic, Anesi et al wrote:

In the year 2050 we will unambiguously reimburse healthcare based on value, and so there is good reason to suspect that we will have targeted and reduced many services that provide little or no benefit to patients…

It can be argued that ICU over-utilization, on average, provides no overall benefit, while significantly increasing costs. Gooch and Kahn observed that US spending on critical care represents nearly 3% of GDP, while:

In contrast, the United Kingdom spends only 0.1% of its gross domestic product on critical care services, with no evidence of worse patient outcomes and similar life expectancies as in the United States. Although there are many differences between these 2 countries, one significant difference is intensive care unit (ICU) bed supply. The United States has 25 ICU beds per 100 000 people, as compared with 5 per 100 000 in the United Kingdom. As a result, ICU case-mix differs substantially. In the United Kingdom, the majority of ICU patients are at high risk for death, whereas in the United States, many patients are admitted to the ICU for observation.

As observed by Halpern, these differences come at a significant cost in the US:

The number of intensive care unit (ICU) beds in the United States has continued to increase over the last 3 decades, as have ICU utilization rates and costs, and this despite the lack of any federal, regional, or critical care society mandates to justify these increases. Some experts believe that the increase in the number of ICU beds has led to inappropriate use of these beds by patients who are either too healthy or too sick to benefit from intensive care. This may in part explain the stable national ICU occupancy rate of approximately 68% between 1985 and 2010 and suggests that ICU utilization has simply risen to meet the increased number of beds.

Emphasis added. I shall consider here only ICU usage by patients too healthy to benefit. Although the economics behind reducing ICU over-utilization by “those not sick enough to benefit” appears simple, the underlying cause is in fact likely complex.

icu-costs-fig-1

This one appears easy: lower costs and potentially better outcomes

At the same time, I recall several caveats, well known to health economists, but important in planning and communication:

  1. We expect ICUs to be available when needed, including for emergencies and disasters,
  2. ICUs have high fixed costs,
  3. Decision-making is critical: incremental costs of adding capacity become fixed costs in the future.

Chris Sampson recently reviewed a study aimed at overconsumption or misconsumption (a consequence of over-utilization). The authors of that paper suggest that “cultural change might be required to achieve significant shifts in clinical behaviour.” Chris laments that this study did not ‘dig deeper’; here we aim to dig deeper in one specific area: ICU triage for patients “not sick enough to benefit.” More questions than answers at this stage, but hopefully the questions will ultimately lead to answers.

I begin by stepping back: economic decisions frequently involve compromises in allocating scarce resources. Decisions in health economics are frequently no different. How scarce are ICU resources? What happens if they are less scarce? What are the costs? Increasing availability can frequently lead to increased utilization, a phenomenon called “demand elasticity”. For example, increasing expressway/motorway capacity “can lead to increased traffic as new drivers seize the opportunity to travel on the larger road”, and thus no reduction in travel time. Gooch and Kahn further note that:

The presence of demand elasticity in decisions regarding ICU care has major implications for health care delivery and financing. Primarily, this indicates it is possible to reduce the costs of US hospital care by constraining ICU bed supply, perhaps through certificate of need laws or other legislation.

I offer a highly simplified sketch of how ICU over-utilization by those “not sick enough to benefit” is one driver of a vicious cycle in ICU cost growth.

icu-costs-fig-2

ICU over-utilization by patients “not sick enough to benefit” as a driver for ICU demand elasticity

Who (if anyone) is at fault for this ICU vicious cycle? Chang and Shapiro offer one suggestion:

For medical conditions where ICU care is frequently provided, but may not always be necessary, institutions that utilize ICUs more frequently are more likely to perform invasive procedures and have higher costs but have no improvement in hospital mortality. Hospitals had similar ICU utilization patterns across the 4 medical conditions, suggesting that systematic institutional factors may influence decisions to potentially overutilize ICU care.

Emphasis added. I note that demand elasticity is not in itself bad; it must simply be recognized, controlled and used appropriately. As part of a discussion in print on the role of cost considerations in medical decisions, Du and Kahn write:

Although we argue that costs should not be factored into medical decision-making in the ICU, this does not mean that we should not strive toward healthcare cost reduction in other ways. One strategy is to devise systems of care that prevent unnecessary or unwanted ICU admissions—given the small amount of ICU care that is due to discretionary spending, the only real way to reduce ICU costs is to prevent ICU admissions in the first place.

Du and Kahn also argue for careful cost-effectiveness analyses, such as that supported by NICE in the UK:

These programs limit use of treatments that are not cost-effective, taking cost decisions out of the hands of physicians and putting them where they belong: in the hands of society at large… We will achieve real ICU savings only by encouraging a society committed to system-based reforms.

Emphasis added. One can debate “taking cost decisions out of the hands of physicians”, though Guidet & Beale‘s and Capuzzo & Rhodes‘s argument for more physician awareness of cost might provide a good intermediate position in this debate.

Finally, increasing ICU supply (that is, ICU beds) in response to well-conceived increases in ICU demand is not in itself bad; ICU supply must be able to respond to demands imposed by disasters or other emergencies. We need to seek out novel ways to provide this capacity without incurring potentially unnecessary fixed costs, perhaps from region-wide stockpiling of supplies and equipment, and region-wide pools of on-call physicians and other ICU personnel. In summary, current health-related literature offers a wide-ranging discussion of the growing costs of intensive care; in my opinion: more questions than answers at this stage, but hopefully the questions will ultimately lead to answers.

Credits