Chris Sampson’s journal round-up for 16th 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.

MCDA-based deliberation to value health states: lessons learned from a pilot study. Health and Quality of Life Outcomes [PubMed] Published 1st July 2019

The rejection of the EQ-5D-5L value set for England indicates something of a crisis in health state valuation. Evidently, there is a lack of trust in the quantitative data and methods used. This is despite decades of methodological development. Perhaps we need a completely different approach. Could we instead develop a value set using qualitative methods?

A value set based on qualitative research aligns with an idea forwarded by Daniel Hausman, who has argued for the use of deliberative approaches. This could circumvent the problems associated with asking people to give instant (and possibly ill-thought-out) responses to preference elicitation surveys. The authors of this study report on the first ever (pilot) attempt to develop a consensus value set using methods of multi-criteria decision analysis (MCDA) and deliberation. The study attempts to identify a German value set for the SF-6D.

The study included 34 students in a one-day conference setting. A two-step process was followed for the MCDA using MACBETH (the Measuring Attractiveness by a Categorical Based Evaluation Technique), which uses pairwise comparisons to derive numerical scales without quantitative assessments. First, a scoring procedure was conducted for each of the six dimensions. Second, a weighting was identified for each dimension. After an introductory session, participants were allocated into groups of five or six and each group was tasked with scoring one SF-6D dimension. Within each group, consensus was achieved. After these group sessions, all participants were brought together to present and validate the results. In this deliberation process, consensus was achieved for all domains except pain. Then the weighting session took place, but resulted in no consensus. Subsequent to the one-day conference, a series of semi-structured interviews were conducted with moderators. All the sessions and interviews were recorded, transcribed, and analysed qualitatively.

In short, the study failed. A consensus value set could not be identified. Part of the problem was probably in the SF-6D descriptive system, particularly in relation to pain, which was interpreted differently by different people. But the main issue was that people had different opinions and didn’t seem willing to move towards consensus with a societal perspective in mind. Participants broadly fell into three groups – one in favour of prioritising pain and mental health, one opposed to trading-off SF-6D dimensions and favouring equal weights, and another group that was not willing to accept any trade-offs.

Despite its apparent failure, this seems like an extremely useful and important study. The authors provide a huge amount of detail regarding what they did, what went well, and what might be done differently next time. I’m not sure it will ever be possible to get a group of people to reach a consensus on a value set. The whole point of preference-based measures is surely that different people have different priorities, and they should be expected to disagree. But I think we should expect that the future of health state valuation lies in mixed methods. There might be more success in a qualitative and deliberative approach to scoring combined with a quantitative approach to weighting, or perhaps a qualitative approach informed by quantitative data that demands trade-offs. Whatever the future holds, this study will be a valuable guide.

Preference-based health-related quality of life outcomes associated with preterm birth: a systematic review and meta-analysis. PharmacoEconomics [PubMed] Published 9th December 2019

Premature and low birth weight babies can experience a whole host of negative health outcomes. Most studies in this context look at short-term biomedical assessments or behavioural and neurodevelopmental indicators. But some studies have sought to identify the long-term consequences on health-related quality of life by identifying health state utility values. This study provides us with a review and meta-analysis of such values.

The authors screened 2,139 articles from their search and included 20 in the review. Lots of data were extracted from the articles, which is helpfully tabulated in the paper. The majority of the studies included adolescents and focussed on children born very preterm or at very low birth weight.

For the meta-analysis, the authors employed a linear mixed-effects meta-regression, which is an increasingly routine approach in this context. The models were used to estimate the decrement in utility values associated with preterm birth or low birth weight, compared with matched controls. Conveniently, all but one of the studies used a measure other than the HUI2 or HUI3, so the analysis was restricted to these two measures. Preterm birth was associated with an average decrement of 0.066 and extremely low birth weight with a decrement of 0.068. The mean estimated utility scores for the study groups was 0.838, compared with 0.919 for the control groups.

Reviews of utility values are valuable as they provide modellers with a catalogue of potential parameters that can be selected in a meaningful and transparent way. Even though this is a thorough and well-reported study, it’s a bit harder to see how its findings will be used. Most reviews of utility values relate to a particular disease, which might be prevented or ameliorated by treatment, and the value of this treatment depends on the utility values selected. But how will these utility values be used? The avoidance of preterm or low-weight birth is not the subject of most evaluations in the neonatal setting. Even if it was, how valuable are estimates from a single point in adolescence? The authors suggest that future research should seek to identify a trajectory of utility values over the life course. But, even if we could achieve this, it’s not clear to me how this should complement utility values identified in relation to the specific health problems experienced by these people.

The new and non-transparent Cancer Drugs Fund. PharmacoEconomics [PubMed] Published 12th December 2019

Not many (any?) health economists liked the Cancer Drugs Fund (CDF). It was set-up to give special treatment to cancer drugs, which weren’t assessed on the same basis as other drugs being assessed by NICE. In 2016, the CDF was brought within NICE’s remit, with medicines available through the CDF requiring a managed access agreement. This includes agreements on data collection and on payments by the NHS during the period. In this article, the authors contend that the new CDF process is not sufficiently transparent.

Three main issued are raised: i) lack of transparency relating to the value of CDF drugs, ii) lack of transparency relating to the cost of CDF drugs, and iii) the amount of time that medicines remain on the CDF. The authors tabulate the reporting of ICERs according to the decisions made, showing that the majority of treatment comparisons do not report ICERs. Similarly, the time in the CDF is tabulated, with many indications being in the CDF for an unknown amount of time. In short, we don’t know much about medicines going through the CDF, except that they’re probably costing a lot.

I’m a fan of transparency, in almost all contexts. I think it is inherently valuable to share information widely. It seems that the authors of this paper do too. A lack of transparency in NICE decision-making is a broader problem that arises from the need to protect commercially sensitive pricing agreements. But what this paper doesn’t manage to do is to articulate why anybody who doesn’t support transparency in principle should care about the CDF in particular. Part of the authors’ argument is that the lack of transparency prevents independent scrutiny. But surely NICE is the independent scrutiny? The authors argue that it is a problem that commissioners and the public cannot assess the value of the medicines, but it isn’t clear why that should be a problem if they are not the arbiters of value. The CDF has quite rightly faced criticism over the years, but I’m not convinced that its lack of transparency is its main problem.


Meeting round-up: ISPOR Europe 2019

For many health economists, November is ISPOR Europe month, and this year was no exception! We gathered in the fantastic Bella Center in Copenhagen to debate, listen and breathe health economics and outcomes research from the 2nd to the 6th November. Missed it? Would like a recap? Stay tuned for the #ISPOREurope 2019 round-up!

Bella Center

My ISPOR week started with the fascinating course ‘Tools for reproducible real-world data analysis’ by Blythe Adamson and Rachael Sorg. My key take-home messages? Use an interface like R-markdown to produce a document with code and results automatically. Use a version control platform like Phabricator to make code review easy. Write a detailed protocol, write the code to follow the protocol, and then check the code side by side with the protocol.

Monday started with the impressive workshop on translating oncology clinical trial endpoints to real-world data (RWD) for decision making.

Keith Abrams set the scene. Electronic health records (EHRs) may be used to derive the overall survival (OS) benefit given the observed benefit on progression-free survival (PFS). Sylwia Bujkiewicz showed an example where a bivariate meta-analysis of RCTs was used to estimate the surrogate relationship between PFS and OS (paper here). Jessica Davies discussed some of the challenges, such as the lack of data on exposure to treatments in a way that matches the data recorded in trials. Federico Felizzi presented a method to determine the optimal treatment duration of a cancer drug (see here for the code).

Next up, the Women in HEOR session! Women in HEOR is an ISPOR initiative that aims to support the growth, development, and contribution of women. It included various initiatives at ISPOR Europe, such as dinners, receptions and, of course, this session.

Shelby Reed introduced, and Olivia Wu presented on the overwhelming evidence on the benefits of diversity and on how to foster it in our work environment. Nancy Berg presented on ISPOR’s commitment to diversity and equality. We then heard from Sabina Hutchison about how to network in a conference environment, how to develop a personal brand and present our pitch. Have a look at my twitter thread for the tips. For more information on the Women in HEOR activities at ISPOR Europe, search #WomenInHEOR on twitter. Loads of cool information!

My Monday afternoon started with the provocatively titled ‘Time for change? Has time come for the pharma industry to accept modest prices?’. Have a look here for my live twitter thread. Kate Dion started by noting that the pressure is on for the pharmaceutical industry to reduce drug prices. Sarah Garner argued that lower prices lead to more patients being able to access the drug, which in turn increases the company’s income. Michael Schröter argued that innovative products should have a premium price, such as with Hemlibra. Lastly, Jens Grueger supported the implementation of value-based price, given the cost-effectiveness threshold.

Keeping with the drug pricing theme, my next session was on indication-based pricing. Mireia Jofre Bonet tackled the question of whether a single price is stifling innovation. Adrian Towse was supportive of indication-based pricing because it allows for the price to depend on the value of each indication and expand access to the full licensed population. Andrew Briggs argued against indication-based pricing for three reasons. First, it would give companies the maximum value-based price across all indications. Second, it would lead to greater drug expenditure, leading to greater opportunity costs. Third, it would be difficult to enforce, given that it would require cooperation of all payers. Francis Arickx explained the pricing system in Belgium. Remarkably, prices can be renegotiated over time depending on new entrants to market and new evidence. Another excellent session at ISPOR Europe!

My final session on Monday was about the timely and important topic of approaches for OS extrapolation. Elisabeth Fenwick introduced the session by noting that innovations in oncology have given rise to different patterns of survival, with implications for extrapolation. Sven Klijn presented on the various available methods for survival extrapolation. John Whalen focused on mixture cure models for cost-effectiveness analysis. Steve Palmer argued that, although new methods, such as mixture cure models, may provide additional insight, the approach should be justified, evidence-based and alternatives explored. In sum, there is no single optimal method.

On Tuesday, my first session was the impressive workshop on estimating cost-effectiveness thresholds based on the opportunity cost (twitter thread). Nancy Devlin set the scene by explaining the importance of getting the cost-effectiveness threshold right. James Lomas explained how to estimate the opportunity cost to the health care system following the seminal work by Karl Claxton et al and also touching on some of James’s recent work. Martin Henriksson noted that, by itself, the opportunity cost is not sufficient to define the threshold if we wish to consider solidarity and need alongside cost-effectiveness. The advantage of knowing the opportunity cost is that we can make informed trade-offs between health maximisation and other elements of value. Danny Palnoch finished the panel by explaining the challenges when deciding what to pay for a new treatment.

Clearly there is a tension between the price that pharmaceutical companies feel is reasonable, the opportunity cost to the health care service, and the desire by stakeholders to use the drug. I feel this in every session of the NICE appraisal committee!

My next session was the compelling panel on the use of RWD to revisit the HTA decision (twitter thread). Craig Brooks-Rooney noted that, as regulators increasingly license technologies based on weaker evidence, HTA agencies are under pressure to adapt their methods to the available evidence. Adrian Towse proposed a conceptual framework to use RWD to revisit decisions based on value of information analysis. Jeanette Kusel went through examples where RWD has been used to inform NICE decisions, such as brentuximab vendotin. Anna Halliday discussed the many practical challenges to implement RWD collection to inform re-appraisals. Anna finished with the caution against prolonging negotiations and appraisals, which could lead to delays to patient access.

My Wednesday started with the stimulating panel on drugs with tumour agnostic indications. Clarissa Higuchi Zerbini introduced the panel and proposed some questions to be addressed. Rosa Giuliani contributed with the clinical perspective. Jacoline Bouvy discussed the challenges faced by NICE and ways forward in appraising tumour-agnostic drugs. Marc van den Bulcke finished the panel with an overview of how next generation sequencing has been implemented in Belgium.

My last session was the brilliant workshop on HTA methods for antibiotics.

Mark Sculpher introduced the topic. Antibiotic resistance is a major challenge for humanity, but the development of new antibiotics is declining. Beth Woods presented a new framework for HTA of antibiotics. The goal is to reflect the full value of antibiotics whilst accounting for the opportunity cost and uncertainties in the evidence (see this report for more details). Angela Blake offered the industry perspective. She argued that revenues should be delinked to volume, to be holistic in the value assessment, and to be mindful of the incentives faced by drug companies. Nick Crabb finished by introducing a new project, by NICE and NHS England, on the feasibility of innovative value assessments for antibiotics.

And this is the end of the absolutely outstanding ISPOR Europe 2019! If you’re eager for more, have a look at the video below with my conference highlights!

Rachel Houten’s journal round-up for 11th November 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.

A comparison of national guidelines for network meta-analysis. Value in Health [PubMed] Published October 2019

The evolving treatment landscape results in a greater dependence on indirect treatment comparisons to generate estimates of clinical effectiveness, where the current practice has not been compared to the proposed new intervention in a head-to-head trial. This paper is a review of the guidelines of reimbursement bodies for conducting network meta-analyses. Reassuringly, the authors find that it is possible to meet the needs of multiple agencies with one analysis.

The authors assign three categories to the criteria; “assessment and analysis to test assumptions required for a network meta-analysis, presentation and reporting of results, and justification of modelling choices”, with heterogeneity of the included studies highlighted as one of the key elements to be sure to include if prioritisation of the criteria is necessary. I think this is a simple way of thinking about what needs to be presented but the ‘justification’ category, in my experience, is often given less weight than the other two.

This paper is a useful resource for companies submitting to multiple HTA agencies with the requirements of each national body displayed in tables that are easy to navigate. It meets a practical need but doesn’t really go far enough for me. They do signpost to the PRISMA criteria, but I think it would have been really good to think about the purpose of the submission guidelines; to encourage a logical and coherent summary of the approaches taken so the evidence can be evaluated by decision-makers.

Variation in responsiveness to warranted behaviour change among NHS clinicians: novel implementation of change detection methods in longitudinal prescribing data. BMJ [PubMed] Published 2nd October 2019

I really like this paper. Such a lot of work, from all sectors, is devoted to the production of relevant and timely evidence to inform practice, but if the guidance does not become embedded into the real world then its usefulness is limited.

The authors have managed to utilize a HUGE amount of data to identify the real reaction to two pieces of guidance recommending a change in practice in England. The authors used “trend indicator saturation”, which I’m not ashamed to admit I knew nothing about beforehand, but it is explained nicely. Their thoughtful use of the information available to them results in three indicators of response (in this case the deprescribing of two drugs) around when the change occurs, how quickly it occurs, and how much change occurs.

The authors discover variation in response to the recommendations but suggest an application of their methods could be used to generate feedback to clinicians and therefore drive further response. As some primary care practices took a while to embed the guidance change into their prescribing, the paper raises interesting questions as to where the barriers to the adoption of guidance have occurred.

What is next for patient preferences in health technology assessment? A systematic review of the challenges. Value in Health Published November 2019

It may be that patient preferences have a role to play in the uptake of guideline recommendations, as proposed by the authors of my final paper this week. This systematic review, of the literature around embedding patient preferences into HTA decision-making, groups the discussion in the academic literature into five broad areas; conceptual, normative, procedural, methodological, and practical. The authors state that their purpose was not to formulate their own views, merely to present the available literature, but they do a good job of indicating where to find more opinionated literature on this topic.

Methodological issues were the biggest group, with aspects such as the sample selection, internal and external validity of the preferences generated, and the generalisability of the preferences collected from a sample to the entire population. However, in general, the number of topics covered in the literature is vast and varied.

It’s a great summary of the challenges that are faced, and a ranking based on frequency of topic being mentioned in the literature drives the authors proposed next steps. They recommend further research into the incorporation of preferences within or beyond the QALY and the use of multiple-criteria decision analysis as a method of integrating patient preferences into decision-making. I support the need for “a scientifically and valid manner” to integrate patient preferences into HTA decision-making but wonder if we can first learn of what works well and hasn’t worked so well from the attempts of HTA agencies thus far.