Rita Faria’s journal round-up for 2nd September 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.

RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ [PubMed] Published 28th August 2019

RCTs are the gold standard primary study to estimate the effect of treatments but are often far from perfect. The question is the extent to which their flaws make a difference to the results. Well, RoB 2 is your new best friend to help answer this question.

Developed by a star-studded team, the RoB 2 is the update to the original risk of bias tool by the Cochrane Collaboration. Bias is assessed by outcome, rather than for the whole RCT. For me, this makes sense.  For example, the primary outcome may be well reported, yet the secondary outcome, which may be the outcome of interest for a cost-effectiveness model, much less so.

Bias is considered in terms of 5 domains, with the overall risk of bias usually corresponding to the worst risk of bias in any of the domains. This overall risk of bias is then reflected in the evidence synthesis, with, for example, a stratified meta-analysis.

The paper is a great read! Jonathan Sterne and colleagues explain the reasons for the update and the process that was followed. Clearly, there was quite a lot of thought given to the types of bias and to develop questions to help reviewers assess it. The only downside is that it may require more time to apply, given that it needs to be done by outcome. Still, I think that’s a price worth paying for more reliable results. Looking forward to seeing it in use!

Characteristics and methods of incorporating randomised and nonrandomised evidence in network meta-analyses: a scoping review. Journal of Clinical Epidemiology [PubMed] Published 3rd May 2019

In keeping with the evidence synthesis theme, this paper by Kathryn Zhang and colleagues reviews how the applied literature has been combining randomised and non-randomised evidence. The headline findings are that combining these two types of study designs is rare and, when it does happen, naïve pooling is the most common method.

I imagine that the limited use of non-randomised evidence is due to its risk of bias. After all, it is difficult to ensure that the measure of association from a non-randomised study is an estimate of a causal effect. Hence, it is worrying that the majority of network meta-analyses that did combine non-randomised studies did so with naïve pooling.

This scoping review may kick start some discussions in the evidence synthesis world. When should we combine randomised and non-randomised evidence? How best to do so? And how to make sure that the right methods are used in practice? As a cost-effectiveness modeller, with limited knowledge of evidence synthesis, I’ve grappled with these questions myself. Do get in touch if you have any thoughts.

A cost-effectiveness analysis of shortened direct-acting antiviral treatment in genotype 1 noncirrhotic treatment-naive patients with chronic hepatitis C virus. Value in Health [PubMed] Published 17th May 2019

Rarely we see a cost-effectiveness paper where the proposed intervention is less costly and less effective, that is, in the controversial southwest quadrant. This exceptional paper by Christopher Fawsitt and colleagues is a welcome exception!

Christopher and colleagues looked at the cost-effectiveness of shorter treatment durations for chronic hepatitis C. Compared with the standard duration, the shorter treatment is not as effective, hence results in fewer QALYs. But it is much cheaper to treat patients over a shorter duration and re-treat those patients who were not cured, rather than treat everyone with the standard duration. Hence, for the base-case and for most scenarios, the shorter treatment is cost-effective.

I’m sure that labelling a less effective and less costly option as cost-effective may have been controversial in some quarters. Some may argue that it is unethical to offer a worse treatment than the standard even if it saves a lot of money. In my view, it is no different from funding better and more costlier treatments, given that the savings will be borne by other patients who will necessarily have access to fewer resources.

The paper is beautifully written and is another example of an outstanding cost-effectiveness analysis with important implications for policy and practice. The extensive sensitivity analysis should provide reassurance to the sceptics. And the discussion is clever in arguing for the value of a shorter duration in resource-constrained settings and for hard to reach populations. A must read!

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Rita Faria’s journal round-up for 26th August 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.

Vaccine hesitancy and (fake) news: quasi‐experimental evidence from Italy. Health Economics [PubMed] [RePEc] Published 20th August 2019

Has fake news led to fewer children being vaccinated? At least in Italy, the answer seems to be yes.

It’s shocking to read that the WHO has included the reluctance or refusal to vaccinate as one of the 10 threats to global health today. And many of us are asking: why has this happened and what can we do to address it? Vincenzo Carrieri, Leonardo Madio and Francesco Principe help answer this first question. They looked at how fake news affects the take-up of vaccines, assuming that exposure to fake news is proxied by access to broadband and within a difference-in-differences framework. They found that a 10% increase in broadband coverage is associated with a 1.2-1.6% reduction in vaccination rates.

The differences-in-differences method hinges on a court ruling in 2012 that accepted that the MMR vaccine causes autism. Following the ruling, fake news about vaccines spread across the internet. In parallel, broadband coverage increased over time due to a government programme, but it varied by region, depending on the existing infrastructure and geographical conditions. Broadband coverage, by itself, cannot lead to lower vaccination rates. So it makes sense to assume that broadband coverage leads to greater exposure to fake news about vaccines, which in turn leads to lower vaccination rates.

On the other hand, it may be that greater broadband coverage and lower vaccination rates are both caused by something else. The authors wrote a good introduction to justify the model assumptions and show a few robustness checks. Had they had more space, I would have like to read a bit more about the uncertainties around the model assumptions. This is a fantastic paper and good food for thought on the consequences of fake news. Great read!

The cost-effectiveness of one-time birth cohort screening for hepatitis C as part of the National Health Service Health Check programme in England. Value in Health Published 19th August 2019

Jack Williams and colleagues looked at the cost-effectiveness of one-time birth cohort screening for hepatitis C. As hepatitis C is usually asymptomatic before reaching its more advanced stages, people may not be aware that they are infected. Therefore, they may not get tested and treated, even though treatment is effective and cost-effective.

At the level of the individual eligible for testing, the ICERs were between £8k-£31k/QALY, with lower ICERs for younger birth cohorts. The ICERs also depended on the transition probabilities for the progression of the disease, with lower ICERs if progression is faster. Extensive sensitivity and value of information analyses indicate that the key cost-effectiveness drivers are the transition probabilities, probabilities of referral and of treatment post-referral, and the quality of life benefits of being cured.

This is a great example of a good quality applied cost-effectiveness analysis. The model is well justified, the results are thoroughly tested, and the discussion is meticulous. Well done!

NICE, in confidence: an assessment of redaction to obscure confidential information in Single Technology Appraisals by the National Institute for Health and Care Excellence. PharmacoEconomics [PubMed] Published 27th June 2019

NICE walks a fine line between making decisions transparent and protecting confidential information. Confidential information includes commercially sensitive information (e.g. discounts to the price paid by the NHS) and academic-in-confidence information, such as unpublished results of clinical trials. The problem is that the redacted information may preclude readers from understanding NICE decisions.

Ash Bullement and colleagues reviewed NICE appraisals of technologies with an approved price discount. Their goal was to understand the extent of redactions and their consequences on the transparency of NICE decisions. Of the 171 NICE appraisals, 118 had an approved commercial arrangement and 110 had a simple price discount. The type of redacted information varied. Some did not present the ICER, others presented ICERs but not the components of the ICERs, and others did not even present the estimates of life expectancy from the model. Remarkably, the confidential discount could be back-calculated in seven NICE appraisals! The authors also looked at the academic-in-confidence redactions. They found that 68 out of 86 appraisals published before 2018 still had academic-in-confidence information redacted. This made me wonder if NICE has a process to review these redactions and disclose them once the information is in the public domain.

As Ash and colleagues rightly conclude, this review shows that there does not seem to be a consistent process for redaction and disclosure. This is a compelling paper on the practicalities of the NICE process, and with useful reflections for HTA agencies around the world. The message for NICE is that it may be time to review the process to handle sensitive information.

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Meeting round-up: iHEA Congress 2019

Missed iHEA 2019? Or were you there but could not make it to all of the amazing sessions? Stay tuned for my conference highlights!

iHEA started on Saturday 13th with pre-congress sessions on fascinating research as well as more prosaic topics, such as early-career networking sessions with senior health economists. All attendees got a super useful plastic bottle – great idea iHEA team!

The conference proper launched on Sunday evening with the brilliant plenary session by Raj Chetty from Harvard University.

Monday morning started bright and early with the thought-provoking session on validation of CE models. It was chaired and discussed by Stefan Lhachimi and featured presentations by Isaac Corro Ramos, Talitha Feenstra and Salah Ghabri. I’m pleased to see that validation is coming to the forefront of current topics! Clearly, we need to do better in validating our models and documenting code, but we’re on the right track and engaged in making this happen.

Next up, the superb session on the societal perspective for cost-effectiveness analysis. It was an all-star cast with Mark Sculpher, Simon Walker, Susan Griffin, Peter Neumann, Lisa Robinson, and Werner Brouwer. I’ve live-tweeted it here.

The case was expertly made that taking a single sector perspective can be misleading when evaluating policies with cross-sectoral effects, hence the impact inventory by Simon and colleagues is a useful tool to guide the choice of sectors to include. At the same time, we should be mindful of the requirements of the decision-maker for whom CEA is intended. This was a compelling session, which will definitely set the scene for much more research to come.

After a tasty lunch (well done catering team!), I headed to the session on evaluations using non-randomised data. The presenters included Maninie Molatseli, Fernando Antonio Postali, James Love-Koh and Taufik Hidayat, on case studies from South Africa, Brazil and Indonesia. Marc Suhrcke chaired. I really enjoyed hearing about the practicalities of applying econometric methods to estimate treatment effects of system wide policies. And James’s presentation was a great application of distributional cost-effectiveness analysis.

I was on the presenter’s chair next, discussing the challenges in implementing policies in the southwest quadrant of the CE plane. This session was chaired by Anna Vassall and discussed by Gesine Meyer-Rath. Jack Dowie started by convincingly arguing that the decision rule should be the same regardless of where in the CE plane the policy falls. David Bath and Sergio Torres-Rueda presented fascinating case studies of south west policies. And I argued that the barrier was essentially a problem of communication (presentation available here). An energetic discussion followed and showed that, even in our field, the matter is far from settled.

The day finished with the memorial session for the wonderful Alan Maynard and Uwe Reinhardt, both of whom did so much for health economics. It was a beautiful session, where people got together to share incredible stories from these health economics heroes. And if you’d like to know more, both Alan and Uwe have published books here and here.

Tuesday started with the session on precision medicine, chaired by Dean Regier, and featuring Rosalie Viney, Chris McCabe and Stuart Peacock. Rather than slides, the screen was filled with a video of a cosy fireplace, inviting the audience to take part in the discussion.

Under debate was whether precision medicine is a completely different type of technology, with added benefits over and above improvement to health, and needing a different CE framework. The panellists were absolutely outstanding in debating the issues! Although I understand the benefits beyond health that these technologies can offer, I side with the view that, like with other technologies, value is about whether the added benefits are worth the losses given the opportunity cost.

My final session of the day was by the great Mike Drummond, comparing how HTA has influenced the uptake of new anticancer drugs in Spain versus England (summary in thread below). Mike and colleagues found that positive recommendations do increase utilisation, but the magnitude of change differs by country and region. The work is ongoing in checking that utilisation has been picked up accurately in the routine data sources.

The conference dinner was at the Markthalle, with plenty of drinks and loads of international food to choose from. I had to have an early night given that I was presenting at 8:30 the next morning. Others, though, enjoyed the party until the early hours!

Indeed, Wednesday started with my session on cost-effectiveness analysis of diagnostic tests. Alison Smith presented on her remarkable work on measurement uncertainty while Hayley Jones gave a masterclass on her new method for meta-analysis of test accuracy across multiple thresholds. I presented on the CEA of test sequences (available here). Simon Walker and James Buchanan added insightful points as discussants. We had a fantastically engaged audience, with great questions and comments. It shows that the CEA of diagnostic tests is becoming a hugely important topic.

Sadly, some other morning sessions were not as well attended. One session, also on CEA, was even cancelled due to lack of audience! For future conferences, I’d suggest scheduling the sessions on the day after the conference dinner a bit later, as well as having fewer sessions to choose from.

Next up on my agenda was the exceptional session on equity, chaired by Paula Lorgelly, and with presentations by Richard Cookson, Susan Griffin and Ijeoma Edoka. I was unable to attend, but I have watched it at home via YouTube (from 1:57:10)! That’s right, some sessions were live streamed and are still available via the iHEA website. Do have a look!

My last session of the conference was on end-of-life care, with Charles Normand chairing, discussed by Helen Mason, Eric Finkelstein, and Mendwas Dzingina, and presentations by Koonal Shah, Bridget Johnson and Nikki McCaffrey. It was a really thought-provoking session, raising questions on the value of interventions at the end-of-life compared to at other stages of the life course.

Lastly, the outstanding plenary session by Lise Rochaix and Joseph Kutzin on how to translate health economics research into policy. Lise and Joseph had pragmatic suggestions and insightful comments on the communication of health economics research to policy makers. Superb! Also available on the live stream here (from 06:09:44).

iHEA 2019 was truly an amazing conference. Expertly organised, well thought-out and with lots of interesting sessions to choose from. iHEA 2021 in Cape Town is firmly in my diary!