Jason Shafrin’s journal round-up for 15th July 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.

Understanding price growth in the market for targeted oncology therapies. American Journal of Managed Care [PubMed] Published 14th June 2019

In the media, you hear that drugs prices—particularly for oncology—are on the rise. With high prices, it makes it difficult for payers to afford effective treatments. For countries where patients bear significant cost, patients may even go without treatment. Are pharmaceutical firms making money hand over fist with these rising prices?

Recent research by Sussell et al. argues that, despite increased drug price costs, pharmaceutical manufacturers are actually making less money on every new cancer drug they produce. The reason? Precision medicine.

The authors use data from both the IQVIA National Sales Perspective (NSP) data set and the Medicare Current Beneficiary Survey (MCBS) to examine changes in the price, quantity, and total revenue over time. Price is measured as episode price (price over a fixed line of therapy) rather than the price per unit of drug. The time period for the core analysis covers 1997-2015.

The authors find that drug prices have roughly tripled between 1997-2015. Despite this price increase, pharmaceutical manufacturers are actually making less money. The number of eligible (i.e., indicated) patients per new oncology drug launch fell between 85% to 90% over this time period. On net, median pharmaceutical manufacturer revenues fell by about half over this time period.

Oncology may be the case where high cost drugs are a good thing; rather than identifying treatments indicated for a large number of people that are less effective on average per patient, develop more highly effective drugs targeted to small groups of people. Patients don’t get unnecessary treatments, and overall costs to payers fall. Of course, manufacturers still need to justify that these treatments represent high value, but some of my research has shown that quality-adjusted cost of care in oncology has remained flat or even fallen for some tumors despite rising drug prices.

Do cancer treatments have option value? Real‐world evidence from metastatic melanoma. Health Economics [PubMed] [RePEc] Published 24th June 2019

Cost effectiveness models done from a societal perspective aim to capture all benefits and costs of a given treatment relative to a comparator. Are standard CEA approaches really capturing all costs and benefits? A 2018 ISPOR Task Force examines some novel components of value that are not typically captured, such as real option value. The Task Force describes real option value as value that is “…generated when a health technology that extends life creates opportunities for the patient to benefit from other future advances in medicine.” Previous studies (here and here) have shown that patients who received treatments for chronic myeloid leukemia and non-small cell lung cancer lived longer than expected since they were able to live long enough to reach the next scientific advance.

A question remains, however, of whether individuals’ behaviors actually take into account this option value. A paper by Li et al. 2019 aims to answer this question by examining whether patients were more likely to get surgical resection after the advent of a novel immuno-oncology treatment (ipilimumab). Using claims data (Marketscan), the authors use an interrupted time series design to examine whether Phase II and Phase III clinical trail read-outs affected the likelihood of surgical resection. The model is a multinomial logit regression. Their preferred specification finds that

“Phase II result was associated with a nearly twofold immediate increase (SD: 0.61; p = .033) in the probability of undergoing surgical resection of metastasis relative to no treatment and a 2.5‐fold immediate increase (SD: 1.14; p = .049) in the probability of undergoing both surgical resection of metastasis and systemic therapy relative to no treatment.”

The finding is striking, but also could benefit from further testing. For instance, the impact of the Phase III results are (incrementally) small relative to the Phase II results. This may be reasonable if one believes that Phase II is a sufficiently reliable indicator of drug benefit, but many people focus on Phase III results. One test the authors could look at is to see whether physicians in academic medical centers are more likely to respond to this news. If one believes that physicians at academic medical centers are more up to speed on the literature, one would expect to see a larger option value for patients treated at academic compared to community medical centers. Further, the study would benefit from some falsification tests. If the authors could use data from other tumors, one would expect that the ipilimumab Phase II results would not have a material impact on surgical resection for other tumor types.

Overall, however, the study is worthwhile as it looks at treatment benefits not just in a static sense, but in a dynamically evolving innovation landscape.

Aggregate distributional cost-effectiveness analysis of health technologies. Value in Health [PubMed] Published 1st May 2019

In general, health economists would like to have health insurers cover treatments that are welfare improving in the Pareto sense. This means, if a treatment provides more expected benefits than costs and no one is worse off (in expectation), then this treatment should certainly be covered. It could be the case, however, that people care who gains these benefits. For instance, consider the case of a new technology that helped people with serious diseases move around more easily inside a mansion. Assume this technology had more benefits than cost. Some (many) people, however, may not like covering a treatment that only benefits people who are very well-off. This issue is especially relevant in single payer systems—like the United Kingdom’s National Health Service (NHS)—which are funded by taxpayers.

One option is to consider both the average net health benefits (i.e., benefits less cost) to a population as well as its effect on inequality. If a society doesn’t care at all about inequality, then this is reduced to just measuring net health benefit overall; if a society has a strong preference for equality, treatments that provide benefits to only the better-off will be considered less valuable.

A paper by Love-Koh et al. 2019 provides a nice quantitative way to estimate these tradeoffs. The approach uses both the Atkinson inequality index and the Kolm index to measure inequality. The authors then use these indices to calculate the equally distributed equivalent (EDE), which is the level of population health (in QALYs) in a completely equal distribution that yields the same amount of social welfare as the distribution under investigation.

Using this approach, the authors find the following:

“Twenty-seven interventions were evaluated. Fourteen interventions were estimated to increase population health and reduce health inequality, 8 to reduce population health and increase health inequality, and 5 to increase health and increase health inequality. Among the latter 5, social welfare analysis, using inequality aversion parameters reflecting high concern for inequality, indicated that the health gain outweighs the negative health inequality impact.”

Despite the attractive features of this approach analytically, there are issues related to how it would be implemented. In this case, inequality is based solely on quality-adjusted life expectancy. However, others could take a more holistic approach and look at socioeconomic status including other factors (e.g., income, employment, etc.). In theory, one could perform the same exercise measuring individual overall utility including these other aspects, but few (rightly) would want the government to assess individuals’ overall happiness to make treatment decisions. Second, the authors qualify expected life expectancy by patients’ sex, primary diagnosis and postcode. Thus, you could have a system that prioritizes treatments for men—since men’s life expectancy is generally less than women. Third, this model assumes disease is exogenous. In many cases this is true, but in some cases individual behavior could increase the likelihood of having a disease. For instance, would citizens want to discount treatments for diseases that are preventable (e.g., lung cancer due to smoking, diabetes due to poor eating habits/exercise), even if treatments for these diseases reduced inequality. Typically, there are no diseases that are fully exogenous or fully at fault of the individual, so this is a slippery slope.

What the Love-Koh paper contributes is an easy to implement method for quantifying how inequality preferences should affect the value of different treatments. What the paper does not answer is whether this approach should be implemented.

Credits

OHE Lunchtime Seminar: Incentives for R&D, Competition and Intertemporal Effects of Payment Rules for Cures

OHE Lunchtime Seminar with Pedro Pita Barros on ‘Incentives for R&D, Competition and Intertemporal Effects of Payment Rules for Cures’. To be held on 6 June 2019 from 12 p.m. to 2 p.m.

Current payment and pricing rules for pharmaceutical products do not account for intertemporal effects of cures for infectious diseases, producing a positive intertemporal externality for future generations. This intuitively suggests that some form of intertemporal payments should exist to account for the positive intertemporal externality. In addition, reduced future demand due to the infectious disease eradication, or the reduction of its prevalence and transmission rate, reduces the future commercial value of new products and may reduce incentives for R&D.

Decisions to invest in pharmaceutical R&D are guided by expected future returns. A dynamic approach is therefore required to allow for the arrival of a new breakthrough product to the market in the first period; a second period in which potentially competing products appear; and, a third period when generic competition emerges. Demand in each period depends on how many patients were treated in previous periods. Similarly, payment/pricing rules used will affect prices, the number of patients treated, company profits, R&D investment decisions, and government/third-party payer expenditure. Under some current frameworks for pharmaceutical pricing either excessive or insufficient R&D investment may result. In this seminar, Prof. Pedro Pita Barros will examine how enlarging the set of possible pricing rules to those that include an intertemporal perspective can incentivise efficient investment in pharmaceutical R&D.

Pedro Pita Barros is Professor of Economics at Universidade Nova de Lisboa, member, by government appointment, of the Portuguese National Ethics Council for the Life Sciences, member of the EC Expert Panel on Effective Ways of Investing in Health, and member of the Portuguese National Health Council. His research focuses on health economics and on regulation and competition policy and has appeared in many academic journals. Pedro Pita Barros has also contributed to several books and has published several books on health economics. He also collaborates in the editorial process of several scientific journals in the field.

View the full seminar invite here.

The seminar will be held in the Sir Alexander Fleming Room, Southside, 7th Floor, 105 Victoria Street, London SW1E 6QT. A buffet lunch will be available from 12 p.m. The seminar will start promptly at 12:30 p.m. and finish promptly at 2 p.m.

If you would like to attend this seminar, please reply to Kerry Sheppard.

OHE Lunchtime Seminar: The People’s Prescription – Re-imagining Health Innovation to Deliver Public Value

Health innovation would be futile and unjust if it does not address public health needs or ensure access to new treatments and cures by the people that need them. The current health innovation system risks becoming just that: beleaguered by increasing financialisation and the obligation to maximise shareholder value through profit, the pharmaceutical sector is increasingly under pressure to deliver short-term financial returns through raising drug prices and executing share buybacks at the expense of directing innovation towards public and long-term benefits.

Drawing on an upcoming Open Society Foundation-funded report prepared by the UCL Institute for Innovation and Public Purpose (IIPP), Global Justice Now, STOPAIDS and Just Treatment, Mariana Mazzucato (IIPP) will outline in this seminar the key problems of the current health innovation system and present, with examples, the principles that would underpin a mission-oriented approach to driving health innovation in the interest of the public. Transformative proposals that rethink value creation, distribution of labour and sharing of risks and rewards across public and private actors in health innovation are proposed in three areas: (1) delinking the cost of research and development from drug prices; (2) attaching conditions to the provision of public funding; (3) changing the rules of corporate governance.

Mariana Mazzucato (PhD) is Professor in the Economics of Innovation and Public Value at University College London (UCL), and is Founder and Director of the UCL Institute for Innovation & Public Purpose (IIPP).   She advises policy makers around the world on innovation-led inclusive growth, including a special advisory role to the EC.

She is winner of the 2014 New Statesman SPERI Prize in Political Economy, the 2015 Hans-Matthöfer-Preis, and the 2018 Leontief Prize for Advancing the Frontiers of Economic Thought. She was named as one of the ‘3 most important thinkers about innovation‘ by the New Republic.

Her highly acclaimed book The Entrepreneurial State: debunking public vs. private sector myths was on the 2013 Books of the Year list of the Financial Times. Her new book The Value of Everything: making and taking in the global economy has just been released.

If you would like to attend this seminar, please reply to ohegeneral@ohe.org.