Thesis Thursday: Koh Jun Ong

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 Koh Jun Ong who has a PhD from the University of Groningen. If you would like to suggest a candidate for an upcoming Thesis Thursday, get in touch.

Title
Economic aspects of public health programmes for infectious disease control: studies on human immunodeficiency virus & human papillomavirus
Supervisors
Maarten Postma, Mark Jit
Repository link
http://hdl.handle.net/11370/0edbcfae-2a0c-4103-9722-fb8086d75cff

Which public health programmes did you consider in your research?

Three public health programmes were considered in the thesis: 1) HIV Pre-Exposure Prophylaxis (PrEP), 2) Human Papillomavirus (HPV) vaccination, and 3) HIV screening to reduce undiagnosed infections in the population.

The first two of the three involved primary infectious disease prevention among men who have sex with men (MSM), and both of these programmes were to be delivered via sexual health clinics in England (commonly known as genitourinary medicine, GUM, clinics).

The third public health infectious disease control programme involved secondary prevention of onward HIV transmission in the general population by encouraging routine HIV screening to reduce undiagnosed HIV, with a view of earlier diagnosis leading to antiretroviral treatment initiation, which will stop HIV transmission with viral suppression.

Was it necessary to develop complex mathematical models?

It depends on the policy research question. A dynamic model was used for the HPV vaccination research question, which captures the ecological externality that vaccination provides by reducing transmission to non-vaccinees. A dynamic model was used because this programme would likely reach a high proportion of MSM who attend GUM clinics in England, and therefore the subsequent knock-on impact of disease transmission in the population was likely to be substantial.

The policy research question was different for PrEP and a static model was more suitable since the objective was to advise NHS England on whether and how such a programme, with relatively small numbers of patients over an initial time-limited period, may represent value for money in England. We first considered a public health control programme, with promising new efficacy data from the 500-person PrEP pilot study (the UK-based PROUD trial) and additional information from per protocol participants in the earlier iPrEx study. The initial consideration was to maintain the preventative effect of a drug that needs to be taken on a daily basis (compared with near one-off HPV vaccination – three doses in total delivered within a year’s time). Regular monitoring of STI and patient’s renal function meant there were clinical service capacity issue to consider, which was likely to limit access initially. Thus, a static model that did not take into account transmission was used.

However, dynamic modelling would be useful to inform policy decisions as PrEP usage expands. Firstly, because it would then be important to capture the indirect effect on infection transmission. Secondly, because when the force of infection begins to fall as incidence declines, dynamic modelling will inform future delivery of a programme that maintains its value. These represent important areas for future research.

Finally, the model designed for the research question on HIV screening was quite straightforward as its aim is primarily to advise local commissioners on financial implications of offering routine screening in their local area, which is dependent on local clinical resources and local disease prevalence.

Did you draw any important conclusions from your literature reviews?

Two literature reviews were conducted: 1) a review on economic parameters i.e. cost and utility estimates for HPV-related outcomes, and 2) a review on published MSM HPV vaccination economic evaluations.

In relation to the first review, most economic models of HPV-related interventions selected economic parameters in a pretty ad hoc way, without reviewing the entirety of the literature. We found substantial variations in cost and utility estimates for all diseases considered in our systematic review, wherever there were more than one publication. These variations in value estimates could result from the differences in cancer site, disease stages, study population, treatment pathway/settings, treatment country and utility elicitation methods used. It would be important for future models to be transparent about parameter sources and assumptions, and to recognise that as patient disease management changes over time, there will be corresponding effects on both cost and utility, necessitating future updates to the estimates. These must be considered when applied to future economic evaluations, to ensure that assumptions are up-to-date and closely reflect the case mix of patients being evaluated.

In relation to the second review, despite limited models, different modelling approaches and assumptions, a general theme from these studies reveal modelling outcomes to be most sensitive to assumptions around vaccine efficacy and price. Future studies could consider synchronising parameter assumptions to test outputs generated by different models.

What can your research tell us about the ‘cost-effective but unaffordable’ paradox?

A key finding and concluding remark of this thesis was that “findings around cost-effectiveness should not be considered independently of budget impact and affordability considerations, as the two are interlinked”. Ultimately, cost-effectiveness is linked to the budget and, in an ideal world, a cost-effectiveness threshold should correspond to the opportunity cost of replacing least cost-effective care at the margin of the whole healthcare budget spend. This willingness to pay threshold should be linked to the amount of budgetary resources an intervention displaces. After all, the concept of opportunity cost in a fixed budget setting means that decisions to invest in something translates to funding being displaced elsewhere.

Since most health economies do not have unlimited resources, even if investment in a new intervention gives high returns and therefore is worthwhile from a value for money perspective, without the necessary resources it cannot always be afforded despite its high return on investment. Having a limited budget means that funding an expensive new intervention may mean moving funding away from existing services, which may be more cost-effective than the new intervention. Hence, the services from which funds are moved from will lose out, and this may leave society worse-off.

A simple analogy may be that buying a property that guarantees return over a defined period is worthwhile, but if I cannot afford it in the first place, is this still an option?

This was clearly demonstrated in the PrEP example, where despite potential to be cost-effective, the high cost of the intervention at list price carried with it a very high budget impact. The size of the population needed to be given PrEP to achieve substantial public health benefits is large, which meant that a public health programme could pose an affordability challenge to the national health care system.

Based on your findings, how might HIV and HPV prevention strategies be made more cost-effective?

Two strategies could influence cost effectiveness: optimizing the population covered and using an appropriate comparator price.

The most obvious way to improve cost-effectiveness is to optimise the population covered. For example, we know that HIV risk, as measured by HIV incidence, is higher among GUM-attending MSM. Therefore, delivering a PrEP programme to this population (at least in the initial phase until the intervention becomes more affordable) will likely result in a higher number of new HIV infections prevented. Similarly, HIV screening offered to areas with high local prevalence would likely give a higher number of new diagnoses.

The other important factor to consider around cost-effectiveness is the comparator price on which the technology appraisal is based. In the chapter on estimating HIV care cost in England, we demonstrated that with imminent availability of generic antiretrovirals, the lifetime care cost for a person living with HIV will reduce substantially. This reduced cost, representing cost of care with existing intervention, should be used as comparator for newer HIV interventions, as they would represent what society will be paying in the absence of the new interventions, allowing corresponding reduced price expectations for new interventions to ensure cost-effectiveness is maintained.

How did you find the experience of completing your thesis by publication?

It was brilliant! I must acknowledge all the contributions from my supervisors and co-authors in making this possible and for the very positive experience of this process. A major advantage of doing a PhD by publication is that the work conducted was regularly peer-reviewed, hence providing an extra check of the robustness of the analyses. And also the fact that these works are out for public consumption almost immediately, making the science available for other researchers to consider and to move the science to the next stage.

Chris Sampson’s journal round-up for 6th January 2020

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.

Child sleep and mother labour market outcomes. Journal of Health Economics [PubMed] [RePEc] Published January 2020

It’s pretty clear that sleep is important to almost all aspects of our lives and our well-being. So it is perhaps surprising that economists have paid relatively little attention to the ways in which the quality of sleep influences the ‘economic’ aspects of our lives. Part of the explanation might be that almost anything that you can imagine having an effect on your sleep is also likely to be affected by your sleep. Identifying causality is a challenge. This paper shows us how it’s done.

The study is focussed on the relationship between sleep and labour market outcomes in new mothers. There’s good reason to care about new mothers’ sleep because many new mothers report that lack of sleep is a problem and many suffer from mental and physical health problems that might relate to this. But the major benefit to this study is that the context provides a very nice instrument to help identify causality – children’s sleep. The study uses data from the Avon Longitudinal Study of Parents and Children (ALSPAC), which seems like an impressive data set. The study recruited 14,541 pregnant women with due dates between 1991 and 1993, collecting data on mothers’ and children’s sleep quality and mothers’ labour market activity. The authors demonstrate that children’s sleep (in terms of duration and disturbances) affects the amount of sleep that mothers get. No surprise there. They then demonstrate that the amount of sleep that mothers get affects their labour market outcomes, in terms of their likelihood of being in employment, the number of hours they work, and household income. The authors also demonstrate that children’s sleep quality does not have a direct impact on mothers’ labour market outcomes except through its effect on mothers’ sleep. The causal mechanism seems difficult to refute.

Using a two-stage least squares model with a child’s sleep as an instrument for their mother’s sleep, the authors estimate the effect of mothers’ sleep on labour market outcomes. On average, a 30-minute increase in a mother’s sleep duration increases the number of hours she works by 8.3% and increases household income by 3.1%. But the study goes further (much further) by identifying the potential mechanisms for this effect, with numerous exploratory analyses. Less sleep makes mothers more likely to self-report having problems at work. It also makes mothers less likely to work full-time. Going even further, the authors test the impact of the UK Employment Rights Act 1996, which gave mothers the right to request flexible working. The effect of the Act was to reduce the impact of mothers’ sleep duration on labour market outcomes, with a 6 percentage points lower probability that mothers drop out of the labour force.

My only criticism of this paper is that the copy-editing is pretty poor! There are so many things in this study that are interesting in their own right but also signal need for further research. Unsurprisingly, the study identifies gender inequalities. No wonder men’s wages increase while women’s plateau. Personally, I don’t much care about labour market outcomes except insofar as they affect individuals’ well-being. Thanks to the impressive data set, the study can also show that the impact on women’s labour market outcomes is not simply a response to changing priorities with respect to work, implying that it is actually a problem. The study provides a lot of food for thought for policy-makers.

Health years in total: a new health objective function for cost-effectiveness analysis. Value in Health Published 23rd December 2019

It’s common for me to complain about papers on this blog, usually in relation to one of my (many) pet peeves. This paper is in a different category. It’s dangerous. I’m angry.

The authors introduce the concept of ‘health years in total’. It’s a simple idea that involves separating the QA and the LY parts of the QALY in order to make quality of life and life years additive instead of multiplicative. This creates the possibility of attaching value to life years over and above their value in terms of the quality of life that is experienced in them. ‘Health years’ can be generated at a rate of two per year because each life year is worth 1 and that 1 is added to what the authors call a ‘modified QALY’. This ‘modified QALY’ is based on the supposition that the number of life years in its estimation corresponds to the maximum number of life years available under any treatment scenario being considered. So, if treatment A provides 2 life years and treatment B provides 3 life years, you multiply the quality of life value of treatment A by 3 years and then add the number of actual life years (i.e. 2). On the face of it, this is as stupid as it sounds.

So why do it? Well, some people don’t like QALYs. A cabal of organisations, supposedly representing patients, has sought to undermine the use of cost-effectiveness analysis. For whatever reason, they have decided to pursue the argument that the QALY discriminates against people with disabilities, or anybody else who happens to be unwell. Depending on the scenario this is either untrue or patently desirable. But the authors of this paper seem happy to entertain the cabal. The foundation for the development of the ‘health years in total’ framework is explicitly based in the equity arguments forwarded by these groups. It’s designed to be a more meaningful alternative to the ‘equal value of life’ measure; a measure that has been used in the US context, which adds a value of 1 to life years regardless of their quality.

The paper does a nice job of illustrating the ‘health years in total’ approach compared with the QALY approach and the ‘equal value of life’ approach. There’s merit in considering alternatives to the QALY model, and there may be value in an ‘additive’ approach that in some way separates the valuation of life years from the valuation of health states. There may even be some ethical justification for the ‘health years in total’ framework. But, if there is, it isn’t provided by this paper. To frame the QALY as discriminatory in the way that the authors do, describing this feature as a ‘limitation’ of the QALY approach, and to present an alternative with no basis in ethics is, at best, foolish. In practice, the ‘health years in total’ calculation would favour life-extending treatments over those that improve health. There are some organisations with vested interests in this. Expect to see ‘health years in total’ obscuring decision-making in the United States in the near future.

The causal effect of education on chronic health conditions in the UK. Journal of Health Economics Published 23rd December 2019

Since the dawn of health economics, researchers have been interested in the ways in which education and health outcomes depend on one another. People with more education tend to be healthier. But identifying causal relationships in this context is almost impossible. Some studies have claimed that education has a positive (causal) effect on both general and specific health outcomes. But there are just as many studies that show no impact. This study attempts to solve the problem by throwing a lot of data at it.

The authors analyse the impact of two sets of reforms in the UK. First, the raising of the school leaving age in 1972, from 15 to 16 years. Second, the broader set of reforms that were implemented in the 1990s that resulted in a major increase in the number of people entering higher education. The study’s weapon is the Quarterly Labour Force Survey (QLFS), which includes over 5 million observations from 1.5 million people. Part of the challenge of identifying the impact of education on health outcomes is that the effects can be expected to be observed over the long-term and can therefore be obscured by other long-term trends. To address this, the authors limit their analyses to people in narrow age ranges in correspondence with the times of the reforms. Thanks to the size of the data set, they still have more than 350,000 observations for each reform. The QLFS asks people to self-report having any of a set of 17 different chronic health conditions. These can be grouped in a variety of ways, or looked at individually. The analysis uses a regression discontinuity framework to test the impact of raising the school leaving age, with birth date acting as an instrument for the number of years spent in education. The analysis of the second reform is less precise, as there is no single discontinuity, so the model identifies variation between the relevant cohorts over the period. The models are used to test a variety of combinations of the chronic condition indicators.

In short, the study finds that education does not seem to have a causal effect on health, in terms of the number of chronic conditions or the probability of having any chronic condition. But, even with their massive data set, the authors cannot exclude the possibility that education does have an effect on health (whether positive or negative). This non-finding is consistent across both reforms and is robust to various specifications. There is one potentially important exception to this. Diabetes. Looking at the school leaving age reform, an additional year of schooling reduces the likelihood of having diabetes by 3.6 percentage points. Given the potential for diabetes to depend heavily on an individual’s behaviour and choices, this seems to make sense. Kids, stay in school. Just don’t do it for the good of your health.

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Rita Faria’s journal round-up for 30th December 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.

Value in hepatitis C virus treatment: a patient-centered cost-effectiveness analysis. PharmacoEconomics [PubMed] Published 2nd December 2019

There have been many economic evaluations of treatments for viral hepatitis C. The usual outcomes are costs and a measure of quality-adjusted survival, such as QALYs. But health-related quality of life and life expectancy may not be the only important outcomes for patients. This fascinating paper by Joe Mattingly II and colleagues fills in the gap by collaborating with patients in the development of an economic evaluation of treatments for viral hepatitis C.

Patient engagement was guided by a stakeholder advisory board including health care professionals, four patients and a representative of a national patient advocacy organisation. This board reviewed the model design, model inputs and presentation of results. To ensure that the economic evaluation included what is important to patients, the team conducted a Delphi process with patients who had received treatment or were considering treatment. This is reported in a separate paper.

The feedback from patients led to the inclusion of two outcomes beyond QALYs and costs: infected life-years, which relate to the patient’s fear of infecting others, and workdays missed, which relate to financial issues and impact on work and career.

I was impressed with the effort put into engaging with patients and stakeholders. For example, there were 11 meetings with the stakeholder advisory board. This shows that engaging with stakeholders takes time and energy to do right! The challenge with the patient-centric outcome measures is in using them to make decisions. From an individual or an employer’s perspective, it may be useful to have results in terms of costs per workday missed avoided, for example, if these can then be compared to a maximum acceptable cost. As suggested by the authors, an interesting next step would be to seek feedback from managed care organisations. Whether such measures would be useful to inform decisions in publicly funded healthcare services is less clear.

Patient engagement is all the rage at present, but there’s not much guidance on how to do it in practice. This paper is a great example of how to go about it.

TECH-VER: a verification checklist to reduce errors in models and improve their credibility. PharmacoEconomics [PubMed] [RePEc] Published 8th November 2019

Looking for help in checking your decision model? Fear not, there’s a new tool on the block! The TECH-VER checklist lists a set of steps to assess the internal validity of your model.

I have to admit that I’m getting a bit weary of checklists, but this one is truly useful. It’s divided into five areas: model inputs, event/state calculations, results, uncertainty analysis, and overall validation and other supplementary checks. Each area includes an assessment of the completeness of the calculations in the electronic model, their consistency with the technical report, and then steps to check their correctness.

Correctness is assessed with a series of black-box, white-box, and replication-based tests. Black-box tests involve changing parameters in the model and checking if the results change as expected. For example, if the HRQOL weights=1 and decrements=0, the QALYs should be the same as the life years. White-box testing involves checking the calculations one by one. Replication-based tests involve redoing calculations independently.

The authors’ handy tip is to apply the checks in ascending order of effort and time: starting first with black-box tests, then conducting white-box tests only for priority calculations or if there are unexpected results. I recommend this paper to all cost-effectiveness modellers. TECH-VER will definitely feature in my toolbox!

Proposals on Kaplan-Meier plots in medical research and a survey of stakeholder views: KMunicate. BMJ Open [PubMed] Published 30th September 2019

What’s your view of the Kaplan-Meier plot? I find it quite difficult to explain to non-specialist audiences, particularly the uncertainty in the differences in survival time between treatment groups. It seems that I’m not the only one!

Tim Morris and colleagues agree that Kaplan-Meier can be difficult to interpret. To address this, they proposed improvements to better show the status of patients over time and the uncertainty around those estimates. They then assessed the proposed improvements with a survey of researchers. Similar to my own views, the majority of respondents preferred having a table with the number of patients who had the events and who were censored to show the status of patients over time, and confidence intervals to show the uncertainty.

The Kaplan-Meier plot with confidence intervals and the table would definitely help me to interpret and explain Kaplan-Meier plots. Also, the proposed improvements seem to be straightforward to implement. One way to make it easy for researchers to implement these plots in practice would be to publish the code to replicate the preferred plots.

There is a broader question, outside the scope of this project, about how to convey survival times and their uncertainty to untrained audiences, from health care professionals and managers to patients. Would audience-specific tools be the answer? Or should we try to up-skill the audience to understand a Kaplan-Meier plot?

Better communication is surely key if we want to engage stakeholders with research and if our research is to have an impact on policy. I, for one, would be grateful for more guidance on how to communicate research. This study is an excellent first step in making a specialist tool – the Kaplan-Meier plot – easier to understand.

Cost-effectiveness of strategies preventing late-onset infection in preterm infants. Archives of Disease in Childhood [PubMed] Published 13th December 2019

And lastly, a plug for my own paper! This article reports the cost-effectiveness analysis conducted for a ‘negative’ trial. The PREVAIL trial found that the experimental intervention – anti-microbial impregnated peripherally inserted central catheters (AM-PICCs) – had no effect compared to the standard PICCS, which are used in the NHS. AM-PICCs are more costly than standard PICCs. Clearly, AM-PICCs are not cost-effective. So, you may ask, why conduct a cost-effectiveness analysis and develop a new model?

Developing a model to evaluate the cost-effectiveness of AM-PICCs was one of the project’s objectives. We started the economic work pretty early on. By the time that the trial reported, the model was already built, tested with data from the literature, and all ready to receive the trial data. Wasted effort? Not at all!

Thanks to this cost-effectiveness analysis, we have concluded that avoiding neurodevelopmental impairment in children born preterm is very beneficial; hence warranting a large investment by the NHS. If we believe the observational evidence that infection causes neurodevelopmental impairment, interventions that reduce the risk of infection can be cost-effective.

The linkage to Hospital Episode Statistics, National Neonatal Research Database and Paediatric Intensive Care Audit Network allowed us to get a good picture of the hospital care and costs of the babies in the PREVAIL trial. This informed some of the cost inputs in the cost-effectiveness model.

If you’re planning a cost-effectiveness analysis of strategies to prevent infections and/or neurodevelopmental impairment in preterm babies, do feel free to get in touch!

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