How to set the drug market size in precision medicine

 EL SISTEMA NACIONAL DE SALUD ante la medicina de precisión

In this book you'll find my chapter with Carlos Campillo on "Los biomarcadores y la medicina de precisión", p.35

La medicina estratificada se caracteriza por la estrecha relación y dependencia entre el diagnóstico y la terapia farmacológica. La elección del punto de corte de un biomarcador (cut-off) determina la población sujeta a tratamiento y ello afecta a la rentabilidad del fármaco. La empresa farmacéutica anticipará la situación y decidirá si vale la pena situar en el mercado un medicamento estratificado o no. Además, según sea la perspectiva (pacientes o industria), las preferencias por un punto de corte diferirán y también según el tratamiento.

You'll find the details inside the chapter. 

 

Prioritizing population health or the economy

 Economics in the Age of COVID-19

Open access book by Joshua Gans. Must read. Controversial. Telling.

Forget false dilemmas, health vs economy.

The starting point is to understand that at any given point in time, there is only so much we can produce. Broadly speaking, if we want to have better public health outcomes, we need to take resources from elsewhere and so we can imagine that we get less of other stuff – which we would broadly call ‘the economy.’ What makes these trade-offs easy to grasp is that when we talk about producing some more public health, we can then think about how much less of the economy we get. Moreover, we are also confident that as we push for each extra bit of health, the more of the economy we have to give up each time. So, if our public health is poor, it is relatively ‘cheap’ (in terms of a reduction in the economy) to get more of it. When our public health is already prioritized, pushing the system further to gain even more health is relatively ”expensive” in terms of reductions to the economy. Thus, we do end up balancing and we don’t have the best imaginable public health outcomes because, frankly, we have decided not to pay the price. (In the technical interlude at the end of this chapter, I put all of this discussion in graphical terms that might be familiar to an Econ 101 student – the production possibilities frontier. You can delve into that or skip as you see fit.)

One reason a pandemic is awful is that it constrains even further what we can do with our scarce resources. We can neither sustain the level of the economy we had before without a decline in public health or vice versa. That in of itself would not pose an issue for our ability to fine-tune. Instead, there are two factors that fundamentally mean that we can no longer fine-tune and instead face a choice between prioritizing public health or the economy without the ability to balance those choices. Those two factors are (1) that a pandemic hollows out our ability to maintain the same balance between health and the economy and (2) that our choice of priority changes our options going forward; that is, they can drift.

Let’s begin with hollowing out. Recall that our ability to obtain our current balance of health and the economy is that we recognize that having a little more health or a little more economy is not worth the price in terms of what we give up for each. Absent other innovations – say a vaccine or, as I will discuss later, testing – the way to achieve our previous level of public health in the face of a pandemic is to socially distance. That means that we cannot physically interact with one another and, therefore, to a very large extent, we can no longer produce the economic outcomes we once could.

The problem is that the pandemic now changes the price of obtaining a little improvement in the economy. In order to do that, we must now give up a large degree of health. Being able to have slightly larger groups of people interact or have a few workplaces open poses a potentially high risk to public health because of the way a coronavirus might spread. Put simply, the option of sacrificing a little public health for having a little more economy is no longer open to us.

This also works on the flip side. One option with dealing with a pandemic is simply to ignore it and let life go on as usual. The hope from that plan would be to maintain the economy at its previous level, see the virus spread through much of the population, hope not too many people die and have a one to two-year large decline in public health. This was sometimes referred to as allowing the virus to ‘burn through’ the population. Even here the ability to fine-tune is compromised. You might want to achieve a slightly smaller loss of life from the pandemic but find now that the price of doing that, as even that would require a large amount of social distancing, has become very high.

Hollowing out means that you no longer want to maintain the same balance of the economy and health as you did previously. Instead, the ‘best’ choices are to prioritize one or the other. To be sure, there is a trade-off but no longer can you dial up a little bit more of this and a little bit less of that, you either prioritize the economy or you prioritize public health. You don’t want to try and do both.

  PS: update and subscribe alerts to the new twitter account @econsalut

The bioethics horizon

 What's on the horizon for bioethics?

The Nuffield Council of Bioethics released a short overview of current critical issues. It is really helpful.

Against Labor Tax funding for health

The Case Against Labor-Tax-Financed Social Health Insurance For Low- And Low-Middle-Income
Countries

Adam Wagstaff laid out a strong case against labor-tax financing for health insurance,

based on analyses of the potential revenue generation, the distributional implications, the impact on the labor market, and the potential for universality in service coverage

A key problem with labor-tax social health insurance is that it can actually redistribute resources toward the wealthy, not the poor. This occurs when general revenues subsidize labor-tax social health insurance institutions that predominantly serve upper-income groups instead of having those subsidies be used to extend coverage to the rest of the population. When expenditures on health care for the eligible workers in the formal sector—already higher than expenditures for the general population—exceed their contributions, the resulting subsidy is financed through taxes levied on the entire population (for example,value-added taxes), which is a form of upward redistribution.

 

Improving risk adjustment with reinsurance

 Very high and low residual spenders in private health insurance markets: Germany, The Netherlands and the U.S. Marketplaces

The high degree of persistence in membership in the extremes of the residual spending distribution in all three countries raises concerns that insurers might take steps to deter those who tend to be underpaid and attract those who tend to be overpaid. Attracting the healthy/deterring the sick among subsets of the populations with the disease indicators (such as diabetes) prevalent on both extremes of the residual spending distribution could be a highly profitable strategy, and potentially lead to distortions in the efficient care for these groups. In response to these findings, we proposed a form of reinsurance, based on residuals, and targeted to members of a “risk pool” defined on past-year very high undercompensation. Careful targeting (along with re-estimating the beta weights in risk adjustment to take into account the reinsurance payments) leads to very substantial improvements in overall fit of payments to spending, with especially large effects for the most extremely under- and overcompensated. The share of people affected by this form of risk sharing is very small, less than 3 in 1000 in all three countries. While our proposed policy seems effective in better tying payments to spending, there are alternative approaches to the same issue. One example would be to find ways to split groups like those with diabetes and other illnesses prevalent among the undercompensated into those likely to be on one or the other side of the residual spending distribution. Calling attention to the powerful effects members of the tails of the residual distribution have on the overall fit of the models is the first step in directing policy attention to these important groups.

 

Share of spending on drugs by residual spending groups

Compression of morbidity

Revisiting Compression of Morbidity and Health Disparities in the 21st Century

Age, Socioeconomic Status, and Health

Compression of morbidity:

an ideal population health dynamic in which people live long, healthy lives with declines in physical and cognitive health associated with senescence “compressed” into a short time period at the end of life.

 There are many ongoing debates in the compression of morbidity literature, including which measures of morbidity should be prioritized and the best methodological approaches for life course analyses that adequately address the thorny challenge of isolating age, period, and cohort effects. Even so, the extant research literature regarding compression of morbidity in the United States suggests that it is not happening at the population level.[3] However, much of the published research does not stratify analyses by socioeconomic position, as House and colleagues had recommended in 1990. House, Lantz, and Herd’s 2005 longitudinal analysis of ACL data affirmed that those in the highest income and education groups were significantly more likely to postpone physical functional impairments until much later in life

 

Good news

 Too Much Information. Understanding What You Dont Want to Know

NYT created a weekly bulletin for those that only want to read good news. This means that they are not interested in what's going on really. Does this make sense? Cass Sunstein would say yes and in the book explains why.

Person-centred healthcare

Achieving Person-Centred Health Systems

In contrast to the political and policy emphasis placed upon ‘person focus’, there is continuing debate about its actual meaning in the health care context vis-à-vis concepts such as ‘patient-centred’, ‘user-centred’, ‘family-centred’ or ‘people-centred’ care, or indeed ‘personalized’ health care, as well as the strategies that are available and effective to promote and implement ‘person focus’. There is no single definition of related concepts, and there are different views on the extent to which patient or person-centredness.

This book precisely tries to shed some light on the issue: 

Covid Economics

 ECONOMÍA DE LA SALUD (Y MÁS) DE LA COVID-19

A consensus over genome editing

 Heritable human genome editing

Key goal:

The International Commission on the Clinical Use of Human Germline Genome Editing,which was convened by the U.S. National Academy of Medicine, the U.S. National Academy of Sciences, and the U.K.’s Royal Society and includes members from 10 countries, was tasked with addressing the scientific considerations that would be needed to inform broader societal decision-making. This task involves considering technical, scientific, medical, and regulatoryrequirements, as well as those societal and ethical issues that are inextricably linked to theserequirements, such as the significance of uncertainties related to outcomes, and potential benefits and harms to participants in clinical uses of HHGE.This report does not make judgments about whether any clinical uses of a safe andeffective HHGE methodology, if established by pre-clinical research, should at some point bepermitted. The report instead seeks to determine whether the safety and efficacy of genome editing methodologies and associated assisted reproductive technologies are or could be sufficiently well developed to permit responsible clinical use of HHGE; identifies initial potential applications of HHGE for which a responsible clinical translational pathway can currently be defined; and delineates the necessary elements of such a translational pathway. It also elaborates national and international mechanisms necessary for appropriate scientificgovernance of HHGE, while recognizing that additional governance mechanisms may be needed to address societal considerations that lie beyond the Commission’s charge.

A crucial report, a must read with 11 recommendations, I highlight only 2 below:

 Recommendation 10: In order to proceed with applications of heritable human genome editing (HHGE) that go beyond the translational pathway defined for initial classes of use of HHGE, an international body with appropriate standing and diverse expertise and experience should evaluate and make recommendations concerning any proposed new class of use. This international body should:

• clearly define each proposed new class of use and its limitations;

• enable and convene ongoing transparent discussions on the societal issues surrounding the new class of use;

• make recommendations concerning whether it could be appropriate to cross the threshold of permitting the new class of use; and

• provide a responsible translational pathway for the new class of use.

Recommendation 11: An international mechanism should be established by which concerns about research or conduct of heritable human genome editing that deviates from established guidelines or recommended standards can be received, transmitted to relevant national authorities, and publicly disclosed.

Unfortunately Catalan government was not among the 10 countries in the meeting. Is there anybody concerned on this issue? 

 

Vaccine allocation (2)

 An ethical framework for global vaccine allocation

Ezequiel Emanuel et al. article:

Fairly distributing a COVID-19 vaccine among countries is a problem of distributive justice. Although governments will be the initial recipients of vaccine, fair distribution across countries must reflect a moral concern for the ultimate recipients: individuals. Three values are particularly relevant: benefiting people and limiting harm, prioritizing the disadvantaged, and equal moral concern.

Benefiting people and limiting harm is widely recognized as important across ethical theories. Realizing this value requires defining relevant benefits, measuring them, and assessing the relative urgency—the importance and time sensitivity—of countries’ needs. A successful vaccine produces direct benefits by protecting people against death and morbidity caused by infection. It also produces indirect benefits by reducing death and morbidity arising from health systems overstressed by the pandemic, and by reducing poverty and social hardship such as closed schools.

Prioritizing the disadvantaged is a fundamental value in ethics and global health (10, 11). Realizing this value requires that vaccine distribution reflect special concern for people who are disadvantaged. Fairly distributing a COVID-19 vaccine internationally therefore requires assessing different types of disadvantage. Are the worst-off countries those experiencing the greatest poverty? Those where people have the lowest life expectancies?

Equal moral concern requires treating similar individuals similarly and not discriminating on the basis of morally irrelevant differences, such as sex, race, and religion. Distributing different quantities of vaccine to different countries is not discriminatory if it effectively benefits people while prioritizing the disadvantaged.

And the allocation model: 

 The Fair Priority Model proceeds in three phases, preventing more urgent harms earlier (see the Table). Phase 1 aims at reducing premature deaths and other irreversible direct and indirect health impacts. Phase 2 continues to address enduring health harms but additionally aims at reducing serious economic and social deprivations such as the closure of nonessential businesses and schools. Restoring these activities will lower unemployment, reduce poverty, and improve health. Finally, phase 3 aims at reducing community transmission, which in turn reduces spread among countries and permits the restoration of prepandemic freedoms and economic and social activities.

 

Vaccine allocation

 Discussion Draft of the Preliminary Framework for Equitable Allocation of COVID-19 Vaccine

Guiding Principles from Allocation Frameworks Developed for the COVID-19 Pandemic:

• Ensure that allocation maximizes benefit to patients, mitigates inequities and disparities, and adheres to ethical principles.

• Promote the common good through fairness, transparency, accountability, and trustworthiness.

• Save the greatest number of lives possible—while respecting rights and fairness—to

maximize benefit to the community as a whole.

• Use the best available evidence to assess benefit to communities and address uncertainty.

• Allocate scarce resources responsibly to reduce risk while providing benefit.

• Provide clear and transparent criteria for prioritization strategies.

• Ensure that allocation policies are flexible, responsive to the concerns of the affected

population, and proportionate to the epidemiological situation and the vaccine supply relative to need.

How to proceed in practical terms? Who knows...

 Hockney

Vaccine nationalism

 The Optimal Allocation of Covid-19 Vaccines

Covid-19 vaccine prioritization is key if the initial supply of the vaccine is limited. A consensus is emerging to first prioritize populations facing a high risk of severe illness in high-exposure occupations. The challenge is assigning priorities next among high-risk populations in low-exposure occupations and those that are young and healthy but work in high-exposure occupations. We estimate occupation-based infection risks and use age-based infection fatality rates in a model to assign priorities over populations with different occupations and ages. Among others, we find that 50-year-old food-processing workers and 60-year-old financial advisors are equally prioritized. Our model suggests a vaccine distribution that emphasizes age-based mortality risk more than occupation-based exposure risk.

Today we can confirm that the probability of such proposal is low. After reading FT, WHO framework has suffered a setback.

Banksy

The Pandemic Century. A History of Global Contagion from the Spanish Flu to Covid

 The Pandemic Century_ A History of Global Contagion from the Spanish Flu to Covid