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.

Credits

Thesis Thursday: Ernest Law

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 Ernest Law who has a PhD from the University of Illinois at Chicago. If you would like to suggest a candidate for an upcoming Thesis Thursday, get in touch.

Title
Examining sources of variation in developing a societal health state value set
Supervisors
Simon Pickard, Todd Lee, Surrey Walton, Alan Schwartz, Feng Xie
Repository link
http://hdl.handle.net/10027/23037

How did you come to study EQ-5D valuation methods, and why are they important?

I came across health preferences research after beginning my studies at UIC with my thesis supervisor, Prof. Simon Pickard. Before this, I was a clinical pharmacist who spent a lot of time helping patients and their families navigate the trade-offs between the benefits and harms of pharmacotherapy. So, when I was introduced to a set of methods that seeks to quantify such trade-offs, I was quickly captivated and set on a path to understanding more. I continued on to expand my interests in valuation methods pertinent to health-system decision-making. Naturally, I collided with societal health state value sets – important tools developed from generic preference-based measures, such as the EQ-5D.

During my studies at UIC, our group received a grant (PI: Simon Pickard) from the EuroQol Research Foundation to develop the United States EQ-5D-5L value set. While developing the study protocol, we built in additional data elements (e.g., EQ-5D-3L valuation tasks, advance directive status) that would help answer important questions in explaining variation in value sets. By understanding these sources of variation, we could inform researchers and policymakers alike on the development and application of EQ-5D value sets.

What does your thesis add to the debate about EQ-5D-3L and -5L value sets?

As a self-reported measure, the literature appears reasonably clear regarding the 5L’s advantages over the 3L: reduced ceiling effects, more unique self-reported health states, and improved discriminatory power. However, less was known on how differences in descriptive systems impact direct valuations.

Previous comparisons focused on differences in index scores and QALYs generated from existing value sets. But these value sets differed in substantive ways: preferences from different respondents, in different time periods, from different geographic locations, using different study protocols. This makes it difficult to isolate the differences due to the descriptive system.

In our study, we asked respondents in the US EQ-5D valuation study to complete time trade-off tasks for 3L and 5L health states. By doing so, we were able to hold many of the aforementioned factors constant except the valued health state. From a research perspective, we provide strong evidence on how even small changes in the descriptive system can have a profound impact on the valuations. From a policy perspective, and an HTA agency deciding specifically between the 3L and 5L, we’ve provided critical insight into the kind of value set one might expect to obtain using either descriptive system.

Why are health state valuations by people with advance directives particularly interesting?

The interminable debate over “whose preferences” should be captured when obtaining preferences for the purposes of generating QALYs is well-known among health outcomes researchers and policy-makers. Two camps typically emerge, those that argue for capturing preferences from the general population and those that argue for patients to be the primary source. The supporting arguments for both sides have been well-documented. One additional approach has recently emerged which may reconcile some of the differences by using informed preferences. Guidance from influential groups in the US, such as the First and Second Panels of Cost-Effectiveness in Health and Medicine have also maintained that “the best articulation of a society’s preferences… would be gathered from a representative sample of fully informed members”.

We posited that individuals with advance directives may represent a group that had reflected substantially on their current health state, as well as the experience and consequences of a range of (future) health states. Individuals who complete an advance directive undergo a process that includes discussion and documentation of an individual’s preferences concerning their goals of care in the event they are unable to do so themselves. So we set out to examine this relationship between advance directives and stated preferences, and whether the completion of an advance directive was associated with differences in health state preferences (spoiler: it was).

Is there evidence that value sets should be updated over time?

We sought to address this literature gap by using respondent-level data from the US EQ-5D-3L study that collected TTO values in 2002 and from our EQ-5D-5L study, which also collected 3L TTO values in 2017. However there were inherent challenges with using these data collected so many years apart: demographics shift, new methods and modes of administration are implemented, etc.

So, we attempted to account for what was possible by controlling for respondent characteristics and restricting health state values to those obtained using the same preference elicitation technique (i.e., conventional TTO). We found that values in 2017 were modestly higher, implying that the average adult in the US in 2017 was less willing to trade time for quality of life than in 2002, i.e. 6 months over a 10-year time-horizon. Our research suggests that time-specific differences in societal preferences exist and that the time period in which values were elicited may be an important factor to consider when selecting or applying a value set.

Based on your research, do you have any recommendations for future valuation studies?

I would encourage researchers conducting future valuation studies, particularly societal value sets, to consider some of the following:

1) Consider building in small but powerful methodological sub-aims into your study. Of course, you must balance resource constraints, data quality, and respondent burden against such add-ons, but a balance can be struck!

2) Pay attention to important developments in the population being sampled; for example, we incorporated advance directives because it is becoming an important topic in the US healthcare debate, in addition to contributing to the discussion surrounding informed preferences.

3) Take a close look at the most commonly utilized health state values sets representing your health-system/target population. Is it possible that existing value sets are “outdated”? If so, a proposal to update this value set might fill a very important need. While you’re at it, consider an analysis to compare current and previous values. The evidence is scarce (and difficult to study!) so it’s important to continue building evidence that can inform the broader scientific and HTA community as to the role that time plays in changes to societal preferences.

Meeting round-up: ISPOR Europe 2018 (part 2)

Have you missed ISPOR Europe 2018 but are eager to know all about it? Time to continue reading! In yesterday’s post, I wrote about ISPOR’s outstanding short-course on causal inference and the superb sessions I had attended on day 1. This blog post is about day 2, Tuesday 13th, which was another big day.

The second plenary session was on fairness in pharmaceutical pricing. It was moderated by Sarah Garner, with presentations by many key stakeholders. The thought-provoking discussion highlighted the importance of pharmaceutical pricing policy and the large role that HTA can have in shaping it.

Communicating cost-effectiveness analysis was the next session, where myself, together with Rob Hettle, Gabriel Rogers and Mike Drummond, discussed the pitfalls and approaches to explaining cost-effectiveness models to non-health economists. This was a hugely popular session! We were delighted by the incredibly positive feedback we received, which reassured us that we are clearly not alone in finding it difficult to communicate cost-effectiveness analysis to a lay audience. We certainly feel incentivised to continue working on this topic. The slides are available here, and for the audience’s feedback, search on twitter #communicateCEA.

The lunch was followed by the open meeting of ISPOR Women in HEOR Initiative with Shelby Reed, Olivia Wu and Louise Timlin. It is really encouraging to see ISPOR taking a proactive stance to gender balance!

The most popular session in the afternoon was Valuing a cure: Are new approaches needed, with Steve Pearson, Jens Grueger, Sarah Garner and Mark Sculpher. The panel showed the various perspectives on the pricing of curative therapies. Payers call for a sustainable pricing model, whilst pharma warns that pricing policy is necessarily linked to the incentives for investment in research. I agree with Mark in that these challenges are not unique to curative therapies. As pharmaceutical therapies have greater health benefits but at large costs, it is pressing that cost-effectiveness assessments are also able to consider the opportunity cost of funding more costly treatments. See here for a roundup of the estimates already available.

I then attended the excellent session on Drug disinvestment: is it needed and how could it work, moderated by Richard Macaulay. Andrew Walker explained that HTA agencies’ advice does not always go down well with local payers, highlighting this with an amusing imaginary dialogue between NICE and a hospital. Detlev Parow argued that payers find that prices are often unaffordable, hence payment schemes should consider other options, such as treatment success, risk-sharing agreements and payment by instalments. Bettina Ryll made an impressive case from the patients’ perspective, for whom these decisions have a real impact.

The conference continued late into the evening and, I suspect, long into the early hours of Wednesday, with the ever-popular conference dinner. Wednesday was another day full of fascinating sessions. The plenary was titled Budget Impact and Expenditure Caps: Potential or Pitfall, moderated by Guillem López-Casasnovas. It was followed by inspiring sessions that explored a wide range of topics, presented by the top experts in the relevant fields. These really delved into the nitty-gritty on subjects, such as using R to build decision models, the value of diagnostic information, and expert elicitation, just to name a few.

I don’t think I’m just speaking personally when I say that ISPOR Barcelona was an absolutely brilliant conference! I’ve mentioned here a few of the most outstanding sessions, but there were many, many more. There were so many sessions at the same time that it was physically impossible to attend all of those with a direct relevance to my research. But fortunately, we can access all the presentations by downloading them from the ISPOR website. I’ll leave the suggestion to ISPOR here, that they should think about filming some of the key sessions and broadcasting them as webinars after the conference. This could create a further key resource for our sector.

As in previous editions, ISPOR Barcelona truly confirms ISPOR Europe in the top HTA conferences in Europe, if not the world. It expertly combines cutting-edge methodological research with outstanding applied work, all with the view to better inform decision making. As I’m sure you can guess, I’m already looking forward to the next ISPOR Europe in Copenhagen on the 2nd-6th November 2019, and the amazing sessions which will indubitably be featured!

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