Thesis Thursday: Matthew Quaife

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 Matthew Quaife who has a PhD from the London School of Hygiene and Tropical Medicine. If you would like to suggest a candidate for an upcoming Thesis Thursday, get in touch.

Title
Using stated preferences to estimate the impact and cost-effectiveness of new HIV prevention products in South Africa
Supervisors
Fern Terris-Prestholt, Peter Vickerman
Repository link
http://researchonline.lshtm.ac.uk/4646708

Stated preferences for what?

Our main study looked at preferences for new HIV prevention products in South Africa – estimating the uptake and cost-effectiveness of multi-purpose prevention products, which protect against HIV, pregnancy and STIs. You’ll notice that condoms do this, so why even bother? Condom use needs both partners to agree (for the duration of a given activity) and, whilst female partners tend to prefer condom-protected sex, there is lots of evidence that male partners – who also have greater bargaining power in many contexts – do not.

Oral pre-exposure prophylaxis (PrEP), microbicide gels, and vaginal rings are new products which prevent HIV infection. More importantly, they are female-initiated and can generally be used without a male partner’s knowledge. But trials and demonstration projects among women at high risk of HIV in sub-Saharan Africa have shown low levels of uptake and adherence. We used a DCE to inform the development of attractive and usable profiles for these products, and also estimate how much additional demand – and therefore protection – would be gained from adding contraceptive or STI-protective attributes.

We also elicited the stated preferences of female sex workers for client risk, condom use, and payments for sex. Sex workers can earn more for risky unprotected sex, and we used a repeated DCE to predict risk compensation (i.e. how much condom use would change) if they were to use HIV prevention products.

What did you find most influenced people’s preferences in your research?

Unsurprisingly for products, HIV protection was most important to people, followed by STI and then pregnancy protection. But digging below these averages with a latent class analysis, we found some interesting variation within female respondents: over a third were not concerned with HIV protection at all, instead strongly caring about pregnancy and STI protection. Worryingly, these were more likely to be respondents from high-incidence adolescent and sex worker groups. The remainder of the sample overwhelmingly chose based on HIV protection.

In the second sex worker DCE, we found that using a new HIV prevention product made condoms become less important and price more important. We predict that the price premium for unprotected sex would reduce by two thirds, and the amount of condomless sex would double. This is an interesting labour market/economic finding, but – if true – also has real public health implications. Since economic changes mean sex workers move from multi-purpose condoms to single-purpose products which need high levels of adherence, we thought this would be interesting to model.

How did you use information about people’s preferences to inform estimates of cost-effectiveness?

In two ways. First, we used simple uptake predictions from DCEs to parameterise an HIV transmission model, allowing for condom substitution uptake to vary by condom users and non-users (it was double in the latter). We were also able to model the potential uptake of multipurpose products which don’t exist yet – e.g. a pill protecting from HIV and pregnancy. We predict that this combination, in particular, would double uptake among high-risk young women.

Second, we predicted risk compensation among sex workers who chose new products instead of condoms. We were also able to calculate the price elasticity of supply of unprotected sex, which we built into a dynamic transmission model as a determinant of behaviour.

Can discrete choice experiments accurately predict the kinds of behaviours that you were looking at?

To be honest, when I started the PhD I was really sceptical – and I still am to an extent. But two things make me think DCEs can be useful in predicting behaviours.

First is the data. We published a meta-analysis of how well DCEs predict real-world health choices at an individual level. We only found six studies with individual-level data, but these showed DCEs predict with an 88% sensitivity but just a 34% specificity. If a DCE says you’ll do something, you more than likely will – which is important for modelling heterogeneity in uptake. We desperately need more studies following up DCE participants making real-world choices.

Second is the lack of alternative inputs. Where products are new and potential users are inexperienced, modellers pick an uptake number/range and hope for the best. Where we don’t know efficacy, we may assume that uptake and efficacy are linearly related – but they may not be (e.g. if proportionately more people use a 95% effective product than a 45% effective one). Instead, we might assume uptake and efficacy are independent, but that might sound even less realistic. I think that DCEs can tell us something about these behaviours that are useful for the parameters and structures of models, even if they are not perfect predictors.

Your tread the waters of infectious disease modelling in your research – was the incorporation of economic factors a challenge?

It was pretty tricky, though not as challenging as building the simple dynamic transmission model as a first exposure to R. In general, behaviours are pretty crudely modelled in transmission models, largely due to assumptions like random mixing and other population-level dynamics. We made a simple mechanistic model of sex work based on the supply elasticities estimated in the DCE, and ran a few scenarios, each time estimating the impact of prevention products. We simulated the price of unprotected sex falling and quantity rising as above, but also overlaid a few behavioural rules (e.g. Camerer’s constant income hypothesis) to simulate behavioural responses to a fall in overall income. Finally, we thought about competition between product users and non-users, and how much the latter may be affected by the market behaviours of the former. Look out for the paper at Bristol HESG!

How would you like to see research build on your work to improve HIV prevention?

I did a public engagement event last year based on one statistic: if you are a 16-year old girl living in Durban, you have an 80% lifetime risk of acquiring HIV. I find it unbelievable that, in 2018, when millions have been spent on HIV prevention and we have a range of interventions that can prevent HIV, incidence among some groups is still so dramatically and persistently high.

I think research has a really important role in understanding how people want to protect themselves from HIV, STIs, and pregnancy. In addition to highlighting the populations where interventions will be most cost-effective, we show that variation in preferences drives impact. I hope we can keep banging the drum to make attractive and effective options available to those at high risk.

Sam Watson’s journal round-up for 16th 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 impact of NHS expenditure on health outcomes in England: alternative approaches to identification in all‐cause and disease specific models of mortality. Health Economics [PubMedPublished 2nd April 2018

Studies looking at the relationship between health care expenditure and patient outcomes have exploded in popularity. A recent systematic review identified 65 studies by 2014 on the topic – and recent experience from these journal round-ups suggests this number has increased significantly since then. The relationship between national spending and health outcomes is important to inform policy and health care budgets, not least through the specification of a cost-effectiveness threshold. Karl Claxton and colleagues released a big study looking at all the programmes of care in the NHS in 2015 purporting to estimate exactly this. I wrote at the time that: (i) these estimates are only truly an opportunity cost if the health service is allocatively efficient, which it isn’t; and (ii) their statistical identification method, in which they used a range of socio-economic variables as instruments for expenditure, was flawed as the instruments were neither strong determinants of expenditure nor (conditionally) independent of population health. I also noted that their tests would be unlikely to be any good to detect this problem. In response to the first, Tony O’Hagan commented to say that that they did not assume NHS efficiency, nor even that it was assumed that the NHS is trying to maximise health. This may well have been the case, but I would still, perhaps pedantically, argue then that this is therefore not an opportunity cost. For the question of instrumental variables, an alternative method was proposed by Martyn Andrews and co-authors, using information that feeds into the budget allocation formula as instruments for expenditure. In this new article, Claxton, Lomas, and Martin adopt Andrews’s approach and apply it across four key programs of care in the NHS to try to derive cost-per-QALY thresholds. First off, many of my original criticisms I would also apply to this paper, to which I’d also add one: (Statistical significance being used inappropriately complaint alert!!!) The authors use what seems to be some form of stepwise regression by including and excluding regressors on the basis of statistical significance – this is a big no-no and just introduces large biases (see this article for a list of reasons why). Beyond that, the instruments issue – I think – is still a problem, as it’s hard to justify, for example, an input price index (which translates to larger budgets) as an instrument here. It is certainly correlated with higher expenditure – inputs are more expensive in higher price areas after all – but this instrument won’t be correlated with greater inputs for this same reason. Thus, it’s the ‘wrong kind’ of correlation for this study. Needless to say, perhaps I am letting the perfect be the enemy of the good. Is this evidence strong enough to warrant a change in a cost-effectiveness threshold? My inclination would be that it is not, but that is not to deny it’s relevance to the debate.

Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. The Lancet Published 14th April 2018

“Moderate drinkers live longer” is the adage of the casual drinker as if to justify a hedonistic pursuit as purely pragmatic. But where does this idea come from? Studies that have compared risk of cardiovascular disease to level of alcohol consumption have shown that disease risk is lower in those that drink moderately compared to those that don’t drink. But correlation does not imply causation – non-drinkers might differ from those that drink. They may be abstinent after experiencing health issues related to alcohol, or be otherwise advised to not drink to protect their health. If we truly believed moderate alcohol consumption was better for your health than no alcohol consumption we’d advise people who don’t drink to drink. Moreover, if this relationship were true then there would be an ‘optimal’ level of consumption where any protective effect were maximised before being outweighed by the adverse effects. This new study pools data from three large consortia each containing data from multiple studies or centres on individual alcohol consumption, cardiovascular disease (CVD), and all-cause mortality to look at these outcomes among drinkers, excluding non-drinkers for the aforementioned reasons. Reading the methods section, it’s not wholly clear, if replicability were the standard, what was done. I believe that for each different database a hazard ratio or odds ratio for the risk of CVD or mortality for eight groups of alcohol consumption was estimated, these ratios were then subsequently pooled in a random-effects meta-analysis. However, it’s not clear to me why you would need to do this in two steps when you could just estimate a hierarchical model that achieves the same thing while also propagating any uncertainty through all the levels. Anyway, a polynomial was then fitted through the pooled ratios – again, why not just do this in the main stage and estimate some kind of hierarchical semi-parametric model instead of a three-stage model to get the curve of interest? I don’t know. The key finding is that risk generally increases above around 100g/week alcohol (around 5-6 UK glasses of wine per week), below which it is fairly flat (although whether it is different to non-drinkers we don’t know). However, the picture the article paints is complicated, risk of stroke and heart failure go up with increased alcohol consumption, but myocardial infarction goes down. This would suggest some kind of competing risk: the mechanism by which alcohol works increases your overall risk of CVD and your proportional risk of non-myocardial infarction CVD given CVD.

Family ruptures, stress, and the mental health of the next generation [comment] [reply]. American Economic Review [RePEc] Published April 2018

I’m not sure I will write out the full blurb again about studies of in utero exposure to difficult or stressful conditions and later life outcomes. There are a lot of them and they continue to make the top journals. Admittedly, I continue to cover them in these round-ups – so much so that we could write a literature review on the topic on the basis of the content of this blog. Needless to say, exposure in the womb to stressors likely increases the risk of low birth weight birth, neonatal and childhood disease, poor educational outcomes, and worse labour market outcomes. So what does this new study (and the comments) contribute? Firstly, it uses a new type of stressor – maternal stress caused by a death in the family and apparently this has a dose-response as stronger ties to the deceased are more stressful, and secondly, it looks at mental health outcomes of the child, which are less common in these sorts of studies. The identification strategy compares the effect of the death on infants who are in the womb to those infants who experience it shortly after birth. Herein lies the interesting discussion raised in the above linked comment and reply papers: in this paper the sample contains all births up to one year post birth and to be in the ‘treatment’ group the death had to have occurred between conception and the expected date of birth, so those babies born preterm were less likely to end up in the control group than those born after the expected date. This spurious correlation could potentially lead to bias. In the authors’ reply, they re-estimate their models by redefining the control group on the basis of expected date of birth rather than actual. They find that their estimates for the effect of their stressor on physical outcomes, like low birth weight, are much smaller in magnitude, and I’m not sure they’re clinically significant. For mental health outcomes, again the estimates are qualitatively small in magnitude, but remain similar to the original paper but this choice phrase pops up (Statistical significance being used inappropriately complaint alert!!!): “We cannot reject the null hypothesis that the mental health coefficients presented in panel C of Table 3 are statistically the same as the corresponding coefficients in our original paper.” Statistically the same! I can see they’re different! Anyway, given all the other evidence on the topic I don’t need to explain the results in detail – the methods discussion is far more interesting.

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Brent Gibbons’s journal round-up for 9th 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 effect of Medicaid on management of depression: evidence from the Oregon Health Insurance Experiment. The Milbank Quarterly [PubMed] Published 5th March 2018

For the first journal article of this week’s AHE round-up, I selected a follow-up study on the Oregon health insurance experiment. The Oregon Health Insurance Experiment (OHIE) used a lottery system to expand Medicaid to low-income uninsured adults (and their associated households) who were previously ineligible for coverage. Those interested in being part of the study had to sign up. Individuals were then randomly selected through the lottery, after which individuals needed to take further action to complete enrollment in Medicaid, which included showing that enrollment criteria were satisfied (e.g. income below 100% of poverty line). These details are important because many who were selected for the lottery did not complete enrollment in Medicaid, though being selected through the lottery was associated with a 25 percentage point increase in the probability of having insurance (which the authors confirm was overwhelmingly due to Medicaid and not other insurance). More details on the study and data are publicly available. The OHIE is a seminal study in that it allows researchers to study the effects of having insurance in an experimental design – albeit in the U.S. health care system’s context. The other study that comes to mind is of course the famous RAND health insurance experiment that allowed researchers to study the effects of different levels of health insurance coverage. For the OHIE, the authors importantly point out that it is not necessarily obvious what the impact of having insurance is. While we would expect increases in health care utilization, it is possible that increases in primary care utilization could result in offsetting reductions in other settings (e.g. hospital or emergency department use). Also, while we would expect increases in health as a result of increases in health care use, it is possible that by reducing adverse financial consequences (e.g. of unhealthy behavior), health insurance could discourage investments in health. Medicaid has also been criticized by some as not very good insurance – though there are strong arguments to the contrary. First-year outcomes were detailed in another paper. These included increased health care utilization (across all settings), decreased out-of-pocket medical expenditures, decreased medical debt, improvements in self-reported physical and mental health, and decreased probability of screening positive for depression. In the follow-up paper on management of depression, the authors further explore the causal effect and causal pathway of having Medicaid on depression diagnosis, treatment, and symptoms. Outcomes of interest are the effect of having Medicaid on the prevalence of undiagnosed and untreated depression, the use of depression treatments including medication, and on self-reported depressive symptoms. Where possible, outcomes are examined for those with a prior depression diagnosis and those without. In order to examine the effect of Medicaid insurance (vs. being uninsured), the authors needed to control for the selection bias introduced from uncompleted enrollment into Medicaid. Instrumental variable 2SLS was used with lottery selection as the sole instrument. Local average treatment effects were reported with clustered standard errors on the household. The effect of Medicaid on the management of depression was overwhelmingly positive. For those with no prior depression diagnosis, it increased the chance of receiving a diagnosis and decreased the prevalence of undiagnosed depression (those who scored high on study survey depression instrument but with no official diagnosis). As far as treatment, Medicaid reduced the share of the population with untreated depression, virtually eliminating untreated depression among those with pre-lottery depression. There was a large reduction in unmet need for mental health treatment and an increased share who received specific mental health treatments (i.e. prescription drugs and talk therapy). For self-reported symptoms, Medicaid reduced the overall rate screened for depression symptoms in the post-lottery period. All effects were relatively strong in magnitude, giving an overall convincing picture that Medicaid increased access to treatment, which improved depression symptoms. The biggest limitation of this study is its generalizability. Much of the results were focused on the city of Portland, which may not represent more rural parts of the state. More importantly, this was limited to the state of Oregon for low-income adults who not only expressed interest in signing up, but who were able to follow through to complete enrollment. Other limitations were that the study only looked at the first two years of outcomes and that there was limited information on the types of treatments received.

Tobacco regulation and cost-benefit analysis: how should we value foregone consumer surplus? American Journal of Health Economics [PubMed] [RePEcPublished 23rd January 2018

This second article addresses a very interesting theoretical question in cost-benefit analysis, that has emerged in the context of tobacco regulation. The general question is how should foregone consumer surplus, in the form of reduced smoking, be valued? The history of this particular question in the context of recent FDA efforts to regulate smoking is quite fascinating. I highly recommend reading the article just for this background. In brief, the FDA issued proposed regulations to implement graphic warning labels on cigarettes in 2010 and more recently proposed that cigars and e-cigarettes should also be subject to FDA regulation. In both cases, an economic impact analysis was required and debates ensued on if, and how, foregone consumer surplus should be valued. Economists on both sides weighed-in, some arguing that the FDA should not consider foregone consumer surplus because smoking behavior is irrational, others arguing consumers are perfectly rational and informed and the full consumer surplus should be valued, and still others arguing that some consumer surplus should be counted but there is likely bounded rationality and that it is methodologically unclear how to perform a valuation in such a case. The authors helpfully break down the debate into the following questions: 1) if we assume consumers are fully informed and rational, what is the right approach? 2) are consumers fully informed and rational? and 3) if consumers are not fully informed and rational, what is the right approach? The reason the first question is important is that the FDA was conducting the economic impact analysis by examining health gains and foregone consumer surplus separately. However, if consumers are perfectly rational and informed, their preferences already account for health impacts, meaning that only changes in consumer surplus should be counted. On the second question, the authors explore the literature on smoking behavior to understand “whether consumers are rational in the sense of reflecting stable preferences that fully take into account the available information on current and expected future consequences of current choices.” In general, the literature shows that consumers are pretty well aware of the risks, though they may underestimate the difficulty of quitting. On whether consumers are rational is a much harder question. The authors explore different rational addiction models, including quasi-rational addiction models that take into account more recent developments in behavioral economics, but declare that the literature at this point provides no clear answer and that no empirical test exists to distinguish between rational and quasi-rational models. Without answering whether consumers are fully informed and rational, the authors suggest that welfare analysis – even in the face of bounded rationality – can still use a similar valuation approach to consumer surplus as was recommended for when consumers are fully informed and rational. A series of simple supply and demand curves are presented where there is a biased demand curve (demand under bounded rationality) and an unbiased demand curve (demand where fully informed and rational) and different regulations are illustrated. The implication is that rather than trying to estimate health gains as a result of regulations, what is needed is to understand the amount of demand bias as result of bounded rationality. Foregone consumer surplus can then be appropriately measured. Of course, more research is needed to estimate if, and how much, ‘demand bias’ or bounded rationality exists. The framework of the paper is extremely useful and it pushes health economists to consider advances that have been made in environmental economics to account for bounded rationality in cost-benefit analysis.

2SLS versus 2SRI: appropriate methods for rare outcomes and/or rare exposures. Health Economics [PubMed] Published 26th March 2018

This third paper I will touch on only briefly, but I wanted to include it as it addresses an important methodological topic. The paper explores several alternative instrumental variable estimation techniques for situations when the treatment (exposure) variable is binary, compared to the common 2SLS (two-stage least squares) estimation technique which was developed for a linear setting with continuous endogenous treatments and outcome measures. A more flexible approach, referred to as 2SRI (two-stage residual inclusion) allows for non-linear estimation methods in the first stage (and second stage), including logit or probit estimation methods. As the title suggests, these alternative estimation methods may be particularly useful when treatment (exposure) and/or outcomes are rare (e.g below 5%). Monte Carlo simulations are performed on what the authors term ‘the simplest case’ where the outcome, treatment, and instrument are binary variables and a range of results are considered as the treatment and/or outcome become rarer. Model bias and consistency are assessed in the ability to produce average treatment effects (ATEs) and local average treatment effects (LATEs), comparing the 2SLS, several forms of probit-probit 2SRI models, and a bivariate probit model. Results are that the 2SLS produced biased estimates of the ATE, especially as treatment and outcomes become rarer. The 2SRI models had substantially higher bias than the bivariate probit in producing ATEs (though the bivariate probit requires the assumption of bivariate normality). For LATE, 2SLS always produces consistent estimates, even if the linear probability model produces out of range predictions. Estimates for 2SRI models and the bivariate probit model were biased in producing LATEs. An empirical example was also tested with data on the impact of long-term care insurance on long-term care use. Conclusions are that 2SRI models do not dependably produce unbiased estimates of ATEs. Among the 2SRI models though, there were varying levels of bias and the 2SRI model with generalized residuals appeared to produce the least ATE bias. For more rare treatments and outcomes, the 2SRI model with Anscombe residuals generated the least ATE bias. Results were similar to another simulation study by Chapman and Brooks. The study enhances our understanding of how different instrumental variable estimation methods may function under conditions where treatment and outcome variables have nonlinear distributions and where those same treatments and outcomes are rare. In general, the authors give a cautionary note to say that there is not one perfect estimation method in these types of conditions and that researchers should be aware of the potential pitfalls of different estimation methods.

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