Understanding Generic Drug Markets

Comparing Generic Drug Markets in Europe and the United States: Prices, Volumes, and Spending

The development of generic drug markets depends widely on an active regulator. This is the main reason of differences in consumption among countries. A new article highlights these differences and allows to understand better such market.

Substituting generic medicines for more expensive brand-name versions is likely among the most cost-effective interventions in health care systems.

There remain large differences in the usage and prices of generics in Europe and the United States. The barriers to market entry for generic companies vary between countries, as do pricing and reimbursement policies. Beyond such features of the market,
there are differences in whether, and to what extent, patients and health care professionals perceive generic and branded medicines to be bioequivalent.

Healthcare Quality Lessons

Caring for Quality in Health

An OECD report provides the lessons on caring for quality, quite general but of interest to dive into each one:

Lesson 1. High-performing health care systems offer primary care as a specialist service
that provides comprehensive care to patients with complex needs
Lesson 2. Patient-centred care requires more effective primary and secondary prevention
in primary care
Lesson 3. High-quality mental health care systems require strong health information systems
and mental health training in primary care
Lesson 4. New models of shared care are required to promote co-ordination across health
and social care systems
Lesson 5. A strong patient voice is a priority to keep health care systems focussed
on quality when financial pressures are acute
Lesson 6. Measuring what matters to people delivers the outcomes that patients expect
Lesson 7. Health literacy helps drive high-value care
Lesson 8. Continuous professional development and evolving practice maximise
the contribution of health professionals
Lesson 9. High-performing health care systems have strong information infrastructures
that are linked to quality-improvement tools
Lesson 10. Linking patient data is a pre-requisite for improving quality across pathways
of care
Lesson 11. External evaluation of health care organisation needs to be fed into continuous
quality-improvement cycles
Lesson 12. Improving patient safety requires greater effort to collect, analyse and learn
from adverse events 

It is like a check list, have you done your homework?

Searching for a book to read

Manel Castro

Precision medicine initivatives around the world

Human genomics projects and precision medicine

Governments and research funders in developed world have decided to support precision medicine with different initiatives. Its scope and strenght it is quite diverse. It is good to know what's going on, and this is explained in an article in Nature. A data driven medicine is raising with next generation sequencing (NGS) tools:

The tremendous amount of data that NGS technologies are producing and the difficulties to manage and analyze such quantity of data require the implementation of powerful data centers for storage and analysis. Nevertheless, recent improvements in cloud computing allow managing and analyzing these huge data amounts remotely. With this goal in mind, the main internet companies have taken positions to compete in this area of NGS (data storage and analysis).
As three main examples, Google Genomics, Microsoft Genomics and Amazon Web Services (AWS) Genomics In The Cloud allow researchers to store, process, explore, and share large and complex data sets. The idea behind is to provide userfriendly tools to the researchers.

But finally it is no only for researchers, there will be one day that will be applied by clinicians. The whole article worths to be read.

Lita Cabellut. Barcelona exhibition

Beyond precision medicine: high definition medicine

High-Definition Medicine

Some months ago I was posting on medicine as a data science. Now:

The foundation for a new era of data-driven medicine has been set by recent  technological advances that enable the assessment and management of human health at an unprecedented level of resolution—what we refer to as high-definition medicine. Our ability to assess human health in high definition is enabled, in part, by advances in DNA sequencing, physiological and environmental monitoring, advanced imaging, and behavioral tracking. Our ability to understand and act upon these observations at equally high precision is driven by advances in genome editing, celular reprogramming, tissue engineering, and information technologies, especially artificial intelligence.

This is what high definition medicine is about:

the dynamic assessment, management, and understanding of an individual’s health measured at (or near) its most basic units. It is the data-driven practice of medicine through the utilization of these highly detailed, longitudinal, and multi-parametric measures of the determinants of health to modify disease risk factors, detect disease processes early, drive precise and dynamically adjusted interventions, and determine preventative and therapeutic intervention efficacy from real-world outcomes

In this framework, precision medicine is only a small piece of the engine.

The article published in Cell by scholars from Scripps Translational Science Institute sheds light on the new perspectives of the practice of medicine, a milestone on the current knowledge of life sciences and its application.

***

Catalunya, 1 d'octubre de 2017 · .

Bloody Sunday

Bloody Sunday, Oct 1st, 2017

BBC
Le Monde

Rafael Subirachs 41 years ago - Els segadors - Anthem (1640)

One of the biggest financial scandals of all-time (and remains unsolved)

The LIBOR scandal involved the illegal fixing of this rate. Banks would over or under-report the rate so as to benefit them – making tons of cash in the process. Raise the rate a few basis points, and suddenly you’ve made an extra $200 million dollars in two minutes.
The size of fines for banks up to now is  €9 billion, and the most surprising thing is that it is still working as before. VoxEU explains

You might think that after this costly scandal, and knowing challenges of maintaining LIBOR, market participants and regulators would have quickly replaced LIBOR with a sustainable short-term interest rate benchmark that had little risk of manipulation. You’d be wrong. The current administrator (ICE Benchmark Administration), which replaced the BBA in 2014, estimates that this guide (now called ICE LIBOR) continues to serve as the reference interest rate for “an estimated $350 trillion of outstanding contracts in maturities ranging from overnight to more than 30 years"
In short, LIBOR is still the world’s leading benchmark for short-term interest rates

Sounds incredible but it is true. I'm reading the book: The spider network and it reports the worst professional financial practices that you can imagine. Where is the regulator? The european one is on vacation, for sure.

Public Health and behaviour change

Behavioral Epidemiology. Principles and Applications

It is quite surprising that a new book on Behavioral Epidemiology forgets Tversky and Kahneman, or Thaler. I couldn't find any reference to their works. After all these decades it seems that their works should be taken into account. Epidemiology and Public Health need to review its foundations, basically its rational decision making paradigm that has been their foundations.
I thought that this book could help, but finally I saw that only the first chapters are partially of interest. We'll have to wait.

Health in all policies narrative

Engagement of Sectors Other than Health in Integrated Health Governance, Policy, and Action

A good review on the topic is welcome. You'll find this article in Annual Reviews of Public Health. If health is created largely outside the health sector, engagement in health governance, policy, and intervention development and implementation by sectors other than health, is therefore important. I have reviewed this topic earlier, but I suggest a close look at it and its assumptions:

(a) Health is created largely outside the health care (or disease) sector; (b) the health care (or disease) sector, however, often carries social ownership of all health issues, even when they are beyond its control; (c) the health sector itself is a reproduction of (power) divisions in the public and private sectors and, while calling for integration, is itself fragmented; and (d) calls for broad social engagement with integrated research, policy, action, and governance for health may not align well with assumptions a–c.

The purpose of the article is to provide an evidence-based overview of how broad social engagement in health policy, action, and governance can be initiated, developed, and sustained.

 In Barcelona Caixaforum, right now.

Behavioral provider payment systems: the next step

Impact of Provider Incentives on Quality and Value of Health Care

Experimenting with incentives for quality is a risky task. The variable requires a precise measure and it must indicate the appropriate signal to the provider to have impact in decisions and behaviour. Usually, rational behaviour is assumed int the models. A recent review highlights this is issue:

Advocates of pay-for-performance in health care maintain that its early failures are the result of inadequate design, a failure to incorporate a more sophisticated understanding of provider motivation into program design (26). On the basis of evidence from early schemes and readings of economic and psychological theory, several researchers have produced blueprints for secondgeneration pay-for-performance frameworks. Their recommendations for designers include making rewards large enough to be meaningful; using penalties in addition to rewards; aligning incentives to professional priorities; using absolute rather than relative performance targets; providing frequent, discrete rewards or punishments; and making an explicit long-term commitment to incentives

But the authors admit that: " Some of these solutions are difficult to implement, are contradictory, or introduce further unintended consequences". And this paves the way to a pessimist view:

Programs are slowly becoming more sophisticated, but unless clear evidence for cost-effectiveness emerges soon, the incentive experiment may have to be abandoned. Many commentators see this abandonment as inevitable, believing incentive programs to be fundamentally flawed. Some concerns are technical in nature and relate to the difficulty of accurately defining and measuring the most important aspects of quality with the greatest impacts on patient outcomes

My impression is that the unit of analysis is usually wrong. Until we are not able to measure patient focused episodes of care properly, in a holistic way, will miss something. This should be the first concern. Of course, this is an overwhelming task, not an easy one.

Camille Pissarro in Sant Feliu de Guixols right now

Understanding The Value Of Innovations In Medicine

Video of the yesterday Health Affairs conference in Washington
Agenda and slides
Health Affairs site

Quite surprising the initial definition of value, quality over price?. It is not a ratio, it is the economic surplus, the worth created, one part for the producer and another for the consumer. But in healthcare the consumer is at the same time producer of surplus. This is unique. Maybe someday we should talk about how to split the value according to its contribution, and not only on value based payment.

How global health stands?

Measuring progress and projecting attainment on the basis of past trends of the health-related Sustainable Development Goals in 188 countries: an analysis from the Global Burden of Disease Study 2016

The Global Burden of Disease (GBD) report shows in an aggregated way how is the world population health. It tries to give an index, and the summary would be:

The median health-related SDG index was 56·7 (IQR 31·9–66·8) in 2016 and country-level performance markedly varied, with Singapore (86·8, 95% uncertainty interval 84·6–88·9), Iceland (86·0, 84·1–87·6), and Sweden (85·6, 81·8–87·8) having the highest levels in 2016 and Afghanistan (10·9, 9·6–11·9), the Central African Republic (11·0, 8·8–13·8), and Somalia (11·3, 9·5–13·1) recording the lowest.

Sustainable Development Goals (SDG) were set by UN   and there are specific indicators for health. However the study takes into account 37 of the 50 indicators. I have explained before some technicalities about the use of DALYs for such studies. And you may know that I am concerned about its use. Today I would add a new concern, it is the projection to 2030 for all these indicators. In my opinions it is a useless effort. Nobody knows, nad using the past to project the future, it is exactly a guarantee of a mistake. However, The Lancet will publish your article.
Let's have alook at the expenditure side:

By comparing performance on the health-related SDG index in 2016 with total health expenditure and DAH (Development Assistace for Health) per capita received from 2010 to 2014,insights might be gleaned regarding the association between overall health funding and performance on the health-related SDG index and whether DAH is being directed toward those countries with the greatest need. Generally, total health expenditure is positively correlated with performance on the health-related SDG index; however, considerable variation exists at the same level of expenditure. For example, among countries with a health-related SDG index of 30 to 70, the association between total health expenditure per capita and performance varied massively, spanning at least a 7 times difference in spending with similar levels of performance on the health-related SDG index.

That's a lot of variation, it would require a closer look. And a clear prescription:

For countries that received DAH between 2010–14, some of the most pronounced differences in cumulative DAH per capita received in the 2016 index were in sub-Saharan Africa, with several countries in southern sub-Saharan Africa posting nearly 3 times more cumulative DAH per capita than a number of countries in central and western sub-Saharan Africa. Most notably, some of the poorest performers on the health-related SDG index, such as the Central African Republic, South Sudan, Somalia, and Niger, received relatively little DAH.

All in all, GBD is what we have, it has limitations but it allows to understand the situation. It is unnecessary to project the future, in my opinion. We have to work for the improvement of current population health.

PS. By the way, there is a ranking. You'll see that Spain has fallen from 7th to 23rd. Forget it. It is still worse but useless. The health variations inside Spain are so huge that the unit of analysis is wrong.

Olga Sacharoff

The long and bumpy road to CRISPR

A Crack in Creation:The New Power to Control Evolution

I've read the same book than Diane Coyle this summer. If you want a clear understanding of what's going on in genomic editing, it should be your first choice. A crack in creation is a description and analysis by Jeniffer Doudna the main researcher on the topic. For those that are excited by genome editingit is good to read this statement:

It’s easy to get caught up in the excitement. The fact that gene editing might be able to reverse the course of a disease—permanently—by targeting its underlying genetic cause is thrilling enough. But even more so is the fact that CRISPR can be retooled to target new sequences of DNA and, hence, new diseases. Given CRISPR’s tremendous potential, I’ve grown accustomed over the past several years to being approached by established pharmaceutical companies asking for my help in learning about the CRISPR technology and about how it might be deployed in the quest for new therapeutics.
But therapeutic gene editing is still in its infancy—indeed, clinical trials have only just begun—and there are still big questions about how things will progress from here. The decades-long struggle to make good on the promise of gene therapy should serve as a reminder that medical advances are almost always more complicated than they might seem. For CRISPR, too, the road leading from the lab to the clinic will be long and bumpy.
Deciding what types of cells to target is one of the many dilemmas confronting researchers—should they edit somatic cells (from the Greek soma, for “body”) or germ cells (from the Latin germen, for “bud” or “sprout”)? The distinction between these two classes of cells cuts to the heart of one of the most heated and vital debates in the world of medicine today.
Germ cells are any cells whose genome can be inherited by subsequent generations, and thus they make up the germline of the organism—the stream of genetic material that is passed from one generation to the next. While eggs and sperm are the most obvious germ cells in humans, the germline also encompasses the progenitors of these mature sex cells as well as stem cells from the very early stages of the developing human embryo.
Somatic cells are virtually all the other cells in an organism: heart, muscle, brain, skin, liver—any cell whose DNA cannot be transmitted to offspring.

Therefore, caution is required and ethical implications are huge as I've said before.
Highly recommended.

The priceless conundrum in healthcare

Pricing the Priceless: A Health Care Conundrum

Allocating resources in health care is a pivotal taks and three tools are used to solve it: market, government and professionalism. Briefly, in the market, prices paid would try to reflect information needed to take a decision for the supply side and demand side (hypotetically). Government allocates resources according to information of a benevolent ruler (biased and incomplete information). Professionals decide over the need of care according to "rules and guidelines" and specific patient situation (hypotetically).
As you may imagine, all these three approaches are used everyday in every health system in the world, and unfortunately they are imperfect, basically due to asymetric and incomplete information on one side, and incentives on the other.
Joseph Newhouse wrote a book fifteen years ago, that summarized many of these conundrums. The first is that we don't find prices, we find "administered prices" in health care, those set by insurers (private and public), and:

Setting administered prices is inevitably fraught with error, and because of lags in adapting to technological change, the extent of the error increases as pricing systems age.

This is reason why today we use the term payment systems instead of pricing. Payment systems try to combine different dimensions beyond price, sometimes volume, sometimes quality. Basically they want to correct the error of administered prices.
Unfortunately, the book finishes with a worrying  statement:

This is the conundrum of medical pricing; all arrangements that can be implemented have important drawbacks. Although variation in ideology plays a role in the payment methods that different countries use, the wide variation in institutional arrangements around the world as well as the ongoing efforts at attempting to reform and improve those arrangements in almost every country are consistent with that conundrum.

My impression differs a little bit, it is not and ideological issue. Payment methods differ because risk transfer may be possible or not. In a public system, finally the State assumes all the risk. In a private system, providers  market power may reduce the opportunities to transfer such risk.  Professionals in a public and private system don't assume financial risk, they decide but it is finally transferred to insurers and providers. Nowdays, the issue is still open for debate.

Pasimonious medicine

PRÁCTICAS CLÍNICAS EVITABLES: EL COSTE DEL DESPILFARRO

Tilburg and Cassel wrote in JAMA

Parsimonious medicine is not rationing; it means delivering appropriate health care that fits the needs and circumstances of patients and that actively avoids wasteful care—care that does not benefit patients

And Austin Frakt answered in his blog:

Perhaps the consequences of what they support with good intention will include rationing. Perhaps it’s hard to achieve parsimony with out at least a touch of it. If that’s the case, how much rationing will we tolerate to achieve some additional efficiency? Keep in mind, today we have a high level of rationing by ability to pay and a low level of parsimony. (in USA)

Unfortunately we don't now the level of parsimony in our health system. But if you want to know the size of the waste  in spanish health system, these are some figures for primary care:

El estudio APEAS cifraba en 10,1 por 1000 visitas los eventos adversos en atención primaria de los que un 7,3% graves y un 70,2% evitables (40), mientras que el ENEAS los cifraba en 9,3% por cada 100 hospitalizados, con un 16% graves y 42,8% evitables (41). Mientras que ambos estudios tendían a minimizar el impacto de estas cifras, los 300 millones de visitas no urgentes anuales en atención primaria resultarían en 3 millones de efectos adversos anuales, de los que casi 300.000 graves y al menos 2 millones evitables. En el caso de la hospitalización, los 5,2 millones de hospitalizaciones del año en que se realizó el ENEAS ofrecerían cifras de 450.000 efectos adversos anuales, de los que 90.000 serían graves y unos 200.000 evitables. Estas cifras situarían los eventos adversos derivados de la atención sanitaria como la probable tercera causa de morbi-mortalidad en nuestro país, tras las enfermedades cardiovasculares y el cáncer.

And regarding hospitalizations,

Diversos estudios publicados en la década del 2000 cifran en torno al 10-15% la cuota de este tipo de ingresos hospitalarios sobre el total de hospitalizaciones producidas en España en los años estudiados (42-46). Este porcentaje sería aún mayor para los ingresos por hospitalizaciones evitables en enfermedades crónicas estudiados más recientemente por el grupo Atlas de Variaciones en la Práctica Médica

And the figures for inappropriateness and low value care are more diffiuclt to estimate, though:

En España se han realizado numerosos estudios sobre utilización inapropiada de la hospitalización con cifras que sitúan este problema alrededor del 10% de las admisiones y el 30% del total de estancias hospitalarias

And only one example regarding pharmaceuticals

Añadir lapatinib a capecitabina en el tratamiento en segunda línea del cáncer de mama permite ganar, en promedio, 0,3 meses (10 días) de supervivencia con respecto al tratamiento previo con solo capecitabina, con un coste adicional de 18.298 € (60.996 € por mes de vida adicional) (59). Estas cifras implicarían que socialmente estamos dispuestos a pagar unos 732.000 euros por cada año de vida adicional ganado y, si se tiene en cuenta la baja calidad de vida de estos días ganados en la fase final de los procesos oncológicos, probablemente estaríamos hablando de cifras superiores a los 2 millones de euros por año de vida ajustado por calidad (AVAC o QALY) ganado con la incorporación de este tratamiento a este precio a la cartera de servicios.

If we as a society, we are not able to solve the rationing puzzle, then we could start by a more parsimonious medicine. You'll find more details in the chapter by S. Peiró in this book (p.273).
After reading this chapter, you'll be more concerned than before.

Garry Winogrand