Challenges in Cost-Effectiveness Analysis of genomic tests

From: Cost-effectiveness analyses of genetic and genomic diagnostic tests (Must read)

Type of challenge	Example of challenge	Description of challenge
Methodological	Selecting the appropriate evaluative framework	Is the standard extra-welfarist view and use of CEA appropriate, or should the distinct theoretical approach reflecting the welfarist view and use of CBA be adopted to allow consequences other than health gain, such as the value of diagnostic information from the genomic-targeted diagnostic test, to be valued?
	Relevant study perspective	Is the standard recommendation to focus on the use of health-care services appropriate when the genomic-targeted diagnostic test may provide information that affects the use of other services, such as education or employment?
	Relevant time horizon	Is a lifetime sufficient when the impact of a genomic-targeted diagnostic test may extend to infinite time horizons that are not limited by the lifespan of one individual?
	Defining the relevant study population	Is the standard definition of a patient (the person receiving the technology) appropriate when there could be spillover effects to family members (currently alive or to be born) as a result of information from a genomic-targeted diagnostic test?
	Valuing consequences	Is identifying and measuring the impact on health status alone sufficient to capture the (good and bad) consequences of a genomic-targeted diagnostic test?
Technical	Variation in the individual characteristics of the relevant study population	The use of cohort state transition Markov models, sometimes combined with decision trees, cannot easily capture the impact of individual patient variation within a population with different genotypes and phenotypes
	Number of diagnostic and, if appropriate, subsequent treatment pathways	The use of cohort state transition Markov models, sometimes combined with decision trees, cannot easily account for multiple comparators often needed when evaluating a new genomic-targeted diagnostic test
	Capturing impact of reduced time to diagnosis	The use of cohort state transition Markov models, sometimes combined with decision trees, cannot account for the impact of reduced time to achieve a diagnosis, which is often a proposed benefit of a genomic-targeted diagnostic test
	Capturing impact of capacity constraints	Decision analytic model-based CEA currently assumes limitless capacity within health-care systems, which is often not a reasonable assumption when introducing a genomic-targeted diagnostic test to populations for whom a diagnosis was not previously available
Practical	Availability of data	There is often a lack of data available to populate decision analytic model-based CEA
	National tariff of test cost	No national tariff for genomic-targeted tests exist
Organizational	Complex health-care systems	Decision analytic model-based CEA assumes that money saved and benefits accrued are transferable, but this is often challenging in complex health-care systems that comprise an overarching funding mechanism (public, private, insurance), a service and staffing model for providing care for different sectors (community, general practice, hospital, specialist) and a means of allocating funding to these different sectors
	Generalizability of results	Decision analytic model-based CEA is relevant only to the defined decision problem, and decision-makers who want to use the results must decide whether the focus of the analysis is relevant to their own jurisdiction
	Expensive nature of health technology assessment	Decision analytic model-based CEA conducted within national health technology assessment processes requires considerable funding and expertise that are not available to all, which may contribute to the inequity in access to new genomic-targeted diagnostic tests across the world

1. CBA, cost-benefits analysis; CEA, cost-effectiveness analysis.

 

Payment systems vs. prices in health care

Payment Methods: How They Work

The problem in health care is not that prices play a role—that is unavoidable. The problem is that prices are distorted in ways that result in inefficient allocation of health care resources. Patients and physicians use too much of health care services that are of low value and not enough of services that are of high value.

This statement refers to US private health care. It may refer to any private health system. The JAMA article reflects an interesting and forgotten issue: The Importance of Relative Prices in Health Care Spending. Data is usually unavailable, and few studies are able to show the implications of relative prices on outcomes.
My impression is that we should review the role of prices in health care and understand better that we do need payment systems, that beyond the standard Hayek signal for producers and consumers, there is a signal of appropriate acces that sends the regulator. This is what some health systems try to apply in public settings, and what we did in Catalonia long ago.
Therefore, the key issue is not to define the method as this report does, though it is necessary. The most important focus should be devoted to the environment and the process that finally will guarantee access and quality of outcomes.

PS. By the way, does anybody know where current payment system in Catalonia stands? Glups!

Paying for high intensity inpatient activities

How should hospital reimbursement be refined to support concentration of complex care services?

Concentration of certain inpatient activities is absolutely necessary to guarantee the right efficiency and outcomes that can only be achieved under a large scale. However, how to pay for this is a different and difficult issue. Usually these activities result from a blending of costs of care, teaching costs, and sometimes with research costs. Therefore, the first step is to try to split them as far as possible.
A new paper tries to disentangle in part the issue of how to pay for complex services, and says:

There is no universally agreed definition of what constitutes complex care hospital care, but in England attempts have been made to define complex care according to the  presence of specific diagnoses and procedures in each patient’s medical record. We have applied these complex care definitions to determine whether the receipt of complex care is associated with higher costs relative to patients allocated to the same HRG who did not receive complex care. To do this, we estimate random effects models using patient-level activity and cost data for all patients admitted to English hospitals during the 2013/14 financial year. Compared to otherwise equivalent patients allocated to the same HRG, costs were more than 10% higher for patients receiving 26 (out of 69) types of complex care delivered in hospitals.

And the reason behind these higher costs, maybe severity within the classification or ...

 Irving Penn, maintenant au Grand Palais

Pharmaceutical research, Wall Street and financial crime

 Black Edge_ Inside Information, Dirty Money, and the Quest to Bring Down the Most Wanted Man on Wall Street

Today I would like to recommend a book on finance, on one of the largest financial crimes up to now. It is the case of insider trading at SAC, where they plead guilty and a settlement was achieved after paying $1.8 billion. In Black Edge you'll understand better how some hedge funds have been trading on private information rather than with stocks. You'll know how research-physicians received more money from Wall Street rather than from their own salary. And specially you'll understand how the case of bapi by Elan-Wyeth evolved with plenty of details.
I have insisted in this blog that short selling strategies should be banned. This book provides an excellent argument for it. The incentive for insider trading in pharmaceutical research is huge, and those that are able to get short earlier when there are bad news, get the most!
Some statements from the epilogue:

The financial industry has evolved to be so complex that large parts of it are almost  completely beyond the reach of regulators and law enforcement. Wall Street’s most  successful enterprises are constantly pushing into the frontier; every time the law looks like it’s catching up, they move farther away. There is a perception that in the years after the Milken era, and especially since the financial crisis of 2008, it has become almost impossible, due to a lack of will or expertise, to prosecute corporate criminals who operate at the highest levels. The fear of suffering embarrassing losses after long,  expensive trials has led to a kind of paralysis in law enforcement. The Justice Department was unable, or unwilling, to bring any senior Wall Street figures to face criminal charges for the widespread fraud that swept the financial system prior to 2008. Instead, it extracted billions of dollars in fines from the world’s largest banks.

The hedge fund industry created unprecedented fortunes for a new generation of Wall Street traders whose primary innovation was to find ways to make more aggressive bets in the stock market. Cohen was a pioneer, the creator of a trading empire designed to gain an edge over less sophisticated investors. Years later, after paying the largest fines in the history of financial crime—and seeing a dozen of his employees implicated in insider trading—Cohen emerged from the crisis that engulfed his company as one of the world’s wealthiest men.

 

October 1st, in Catalonia, a documentary

Alcohol regulation as a public policy issue

Alcohol, Power and Public Health: A Comparative Study of Alcohol Policy

Nowadays, I would say that Alcohol Policy this is one of the most difficult and curcial issues in public health. Our societies have internalised its consumption without addressing its risks and the power between industry and regulators is absolutely unbalanced.
A new book that compares the situation in 5 countries is really welcome. Our country is leaving this policy for tomorrow. I would suggest a close look, just for inspiration. Maybe someday it will be the right time.

In particular, change to the alcohol policy status quo requires the convergence of various factors:

1. For alcohol harm to emerge as a significant, and visible, social problem. This means not only a raised public and political awareness of alcohol harms, but a degree of consensus in framing those harms as a particular type of problem. This, as we have seen, is often driven by concrete social change – especially increases in the amount of alcohol consumed in a given society. However, it also implies the successful framing of a problem by advocacy coalitions, often relying on the development of a more or less compelling body of scientific evidence, as well as external sociopolitical factors (such as, for instance, the crisis of the First World War in Europe) that force the political issue and place the public spotlight on alcohol as a social problem in need of tailored political solutions.
2. For proponents of change to convince sufficient relevant stakeholders of the validity of their solutions to the putative problem. These include the scientific community, key policymaking networks, influential sections of the media, and so on. As we have seen, for alcohol policy advocates, this means not only winning the argument that alcohol harms exists on a continuum, but also that the line of justifiable intervention is some distance below that commonly understood as ‘dependency’ or limited to those who behave badly when drunk.
3. For the proposed policy actions to chime sufficiently with the prevailing political context. That is, for policymakers not only to accept the diagnostic and political arguments but, crucially, to decide that implementation of the proposed solutions is politically viable, realistic, consonant with both the ‘national mood’ and internal party politics, and – of course – capable of withstanding resistance from opposing interest groups.

Sounds obvious, but first steps should be well grounded. Current hypocritical attitude should be overcome.

Marc Figueras

Regulatory uncertainty in "home-brew" lab testing

Laboratory-Developed Tests: A Legislative and Regulatory Review

In vitro diagnostics regulation requires continuous adaptation to technologic innovation. Unfortunately, there is a lack of understanding that such a crucial task should be performed efficiently. Europe has waited 23 years for a new regulation!. Anyway, US is under the same trend. Laboratory developed tests were initially regulated 25 years ago and there are still pending issues in the new draft legislation. If you want to know the details, an article in Clinical Chemistry explains the whole issue.

A quarter of a century after the FDA first asserted regulatory authority over LDTs in a draft guidance document, rules and/or guidance regarding LDT oversight have not been implemented. As such, legal questions regarding MDA authority over LDTs and the FDA draft guidance approach have neither been escalated to nor resolved by the judiciary. In addition, many questions central to this debate have not been answered. Are clinical laboratories manufacturers? Should laboratory devices and procedures be regulated similarly? Are there always clear limits between laboratory operations and the practice of laboratory medicine? Any future LDTregulatory or legislative efforts will need to balance and address these concerns if they are to be successful. It is unlikely that interpretation of current statutes and regulations can fully resolve these issues.

 Josep Moscardó, Barcelona landscape

The cost of a year of life gained

Four years ago in my post: How much does healthcare cost during your life? I said  that it was 111.936 € for women and 81.566 € for men (on average and without any additional assumption about changes in unit costs or quality of life). Now you can find in Health Economics, an estimation of the cost of one additional year of life adjusted by quality.

 The mean cost of an additional Quality-Adjusted Life Year (QALY) within a National Health Service (NHS) reveals how much health is lost, on average, when services currently provided by the NHS are displaced. This value has been suggested as a proxy of the average opportunity cost required to set a cost-effectiveness threshold when facing fixed budget constraints. The aim of this paper is to generate information on the marginal cost per QALY in the Spanish NHS that can be used to inform a cost-effectiveness threshold

And the answer is:

A cost per QALY of between 21,000€ and 24,000€ in Spain, depending on whether we take an average across different age groups or the value derived from the whole population model, respectively.

Conclusion: A cost-effectiveness threshold based on the estimated opportunity cost derived from this study is below the figure of 30,000€ commonly cited in Spain. Further work on societal values of health gains is needed to provide decision makers with the relevant information required in different decision-making contexts.

Interesting result, though expenditures are not necessary "social preferences". Cost-effectiveness threshold literature sometimes try to focus on a normative decision for the society society from a technical point of view. I'm interested in the political one.

Au Grand Palais, maintenant

Evidence of what

Evidence-Based Health Policy

Evidence as a topic suggests a common shared framework of values. We all know that this is far from current health policy across countries and within countries. Evidence is difficult to assess without taking into account the underlying values of a community. However, health economists and epidemiologists insist on it. In my opinion we have to know better what works according to social expectations. However we have to avoid the confusion between any descriptive and normative framework. Evidence sounds that any desparture from it may sound unacceptable.
Anyway, NEJM provides a perspective on the issue, and these are key statements in a figure:

The constraints to genomic editing

CRISPR… ¿debemos poner límites a la edición genética?

A new publication by Fundació Grifols highlights the potential constraints to genomic editing. It is a good moment to have a look at it. Savador Macip says:

Los peligros, pues, son muchos, tantos como las cosas buenas que la edición genética nos puede aportar. De alguna forma, recuerda la energía nuclear. Descubrir los secretos del átomo nos ha permitido acceder a una cantidad inimaginable de energía, que usamos diariamente, pero que se debe regular de una forma muy precisa para evitar accidentes terribles y contaminaciones no deseadas. Y, lo que es más peligroso aún, la misma información sirve para fabricar una de las armas más mortíferas que conocemos, capaz incluso de destruir el planeta. A otra escala, CRISPR/Cas9 podría tener efectos parecidos.

La ciencia no se detiene, siempre continúa avanzando, y la sociedad corre el peligro de quedarse atrás. Por ello es importante que los debates sobre hacia dónde queremos ir empiecen cuanto antes mejor y que en ellos participe una muestra amplia de la población, no solo los científicos. Para conseguirlo es necesario que el máximo número posible de gente esté bien informada acerca de los avances más recientes, que entienda su alcance y sus implicaciones y que haga el esfuerzo de contribuir en los debates. A la vez, los científicos deben salir a explicar qué está pasando en sus laboratorios y los políticos deben proporcionar plataformas necesarias para estas discusiones. Solo así nos aseguraremos de que estos descubrimientos son usados

A must read.

Side effects, a good film to watch

Diagnostic testing and outcomes

When diagnostic testing leads to harm: a new outcomes-based approach for laboratory medicine

There are five causes of testing-related diagnostic error:

• An inappropriate test is ordered
• An appropriate test is not ordered
• An appropriate test result is misapplied
• An appropriate test is ordered, but a delay occurs somewhere in the total testing process
• The result of an appropriately ordered test is inaccurate

If we know that that these are the causes, are there any measures available?

In Lundberg’s model, the value of laboratory results is influenced by events
that occur before the sample reaches the laboratory and after the results are released
from it. His model encompasses the physician’s cognitive involvement at the start of
the process and at the end.

The weirdest financing of a health system in the world

Alternative Financing Strategies for Universal Health Coverage

This article from WHO by Joe Kutzin provides a deep analysis of the implications of financing universal coverage. Today I would like to highlight this statement:

There is a general trend toward greater diversification of revenue sources, including a diminishing role for payroll tax funding. This is a practical consequence of the “ideology” of UHC. With the move toward UHC, entitlement to health coverage is being delinked from employment, and from direct contributions more generally. On the practical side, wage-linked contributions cannot generate a sufficient revenue base, both in high-income countries (because of aging populations and macroeconomic concerns regarding increasing wage-based taxation) and also in low- and middle-income countries (LMICs) (because of low participation rates in formal sector employment).

Spain has decided exactly the opposite. Coverage entitlement comes from social security membership, while funds come from taxes. The weirdest financing of a health system in the world.

La capsa entròpica

Now is the time for artificial intelligence in healthcare

Artificial intelligence in health care: within touching distance

Medical practice has so far been largely unchanged by the digital revolution that has disrupted so many other industries, but perhaps artificial intelligence (AI) will provide the improvements in medical care and research promised for so long.

A short editorial in Lancet highlights the importance of deep learning in healthcare.

In 2017, successful use of deep neural networks was reported for the analysis of skin cancer images with greater accuracy than a dermatologist and the diagnosis of diabetic retinopathy from retinal images. The inherent requirement for large-scale, high-quality, well structured data might ultimately limit the areas in which AI can bring benefits to health care.

 Jordi Parramon exhibition

The urgent need to define delivery models for genetic testing

Identification of Delivery Models for the Provision of Predictive Genetic testing in Europe: Protocol for a Multicentre Qualitative study and a systematic review of the literature

The increasing role of genomics in medical decision making requires a review on how services should be organised. Unless this effort is taken promptly, it will be much more difficult to adapt the messy organization to an efficient model for the delivery of services. This issues are explained in a recent article. The ten questions:

 The transfer of genomic technologies from research to clinical application is influenced not only by several factors inherent to research goals and delivery of healthcare but also by external and commercial interests that may cause the premature introduction of genetic tests in the public or private sector (i.e., introduction of a test despite insufficient evidence regarding its analytical validity, clinical validity, and utility). Furthermore, current genetic services are delivered without a standardized set of process and outcome measures, which are essential for the evaluation of healthcare services. It is important that only genetic/genomic applications with proven efficacy and effectiveness are delivered to populations, and particularly that technologies have favorable cost-effectiveness ratios

Why we must not let the tech and drug industry forge the future alone

On the tech industry by Martin Wolf in FT

Selected statements on 7 reasons

What are the economics of these extraordinary valuations? The answer must be monopoly. As of September 30, the book value of Apple’s equity was $134bn, while its market valuation was close to $900bn. The difference has to reflect the expectation of enduring “super-normal” profits. This may not be the product of malign behaviour, but of innovation and economies of scale and scope, including the network externalities that lock in customers. Yet only monopoly could deliver such super-normal profits

How should we think about competition policy for businesses that benefit from such powerful monopoly positions? A question is whether these positions are temporary — as the great Austrian economist, Joseph Schumpeter, with his idea of “creative destruction”, would argue — or lasting. This suggests a host of responses, but one at least seems straightforward. Schumpeter would argue that new entries are a necessary condition for eroding such temporary monopolies. If so, the technology giants should be strongly deterred from buying up their potential competitors. That must be anti-competitive

Yet these enormously profitable businesses are parasitic on the investments in collecting information made by others. At the limit, they will become highly efficient disseminators of non-information. This links to a further point: they can, as we now know, be used by people of ill will for the deliberate dissemination of dangerous falsehoods. These facts raise huge issues.

Finally, the activities in which the technology industry is now engaged — what Andrew McAfee and Erik Brynjolfsson call “machine, platform, crowd” — are going to have a huge impact on our labour markets and, if artificial intelligence continues to advance, on our very place in the world.

What are the implications? They are that our futures are too important to be left to the mercies of the technology industry alone. It has done magical things. Yet nobody elected it master of the universe. Policymakers must get an intellectual grip on what is happening. The time to begin such an effort is now

On a particular drug company, in Project Syndicate:  The Opiate of the Bosses

Business ethics are again making headlines. This time, the focus is on the rapidly escalating opioid crisis that is destroying lives across the United States. While there is plenty of blame to go around, the largest share of the guilt belongs squarely on the shoulders of the major drug companies – Big Pharma.

The cynicism with which pharmaceutical firms have encouraged opioid drug use is appalling. Providing far too little analysis and oversight, they distribute opiates widely, alongside misinformation about how addictive the drugs truly are. Then they entice doctors with inducements and giveaways – including trips, toys, fishing hats, and, in one case, a music CD called “Get in the Swing with OxyContin” (one of the most popular opioids) – to prescribe them.

In 2007, several executives of the parent company of Purdue Pharma, which markets OxyContin, pleaded guilty to misleading doctors, regulators, and patients about the risk of addiction associated with the drug. The company was hit with some $600 million in fines and penalties.

Estimating individual life expectancy for alzheimer patients

Personalized predictive modeling for patients with Alzheimer's disease using an extension of Sullivan’s life table model

Alzheimer's disease is the most common type of dementia. Ageing is boosting its spread over populations. Eric Stallard et al. asked wether it was posible to estimate the residual total life expectancy (TLE) and its decomposition into disability-free life expectancy (DFLE) and disabled life
expectancy (DLE) for individual patients. It sounds really of interest, though it may seem unattainable.
Fortunately you may find succesful results in this article, it says:

Methods: We estimated a new SLT/L-GoM model of the natural history of AD over 10 years in the Predictors 2 Study cohort: N = 229 with 6 fixed and 73 time-varying covariates over 21 examinations covering 11 measurement domains including cognitive, functional, behavioral, psychiatric, and other symptoms/signs. Total remaining life
expectancy was censored at 10 years. Disability was defined as need for full-time care (FTC), the outcome most strongly associated with AD progression. All parameters were estimated via weighted maximum likelihood using data-dependent weights designed to ensure that the estimates of the prognostic subtypes were of high quality.
Goodness of fit was tested/confirmed for survival and FTC disability for five relatively homogeneous subgroups defined to cover the range of patient outcomes over the 21 examinations.

Results: The substantial heterogeneity in initial patient presentation and AD progression was captured using three clinically meaningful prognostic subtypes and one terminal subtype exhibiting highly differentiated symptom severity on 7 of the 11 measurement domains. Comparisons of the observed and estimated survival and FTC disability probabilities demonstrated that the estimates were accurate for all five subgroups, supporting their use in AD life expectancy calculations. Mean 10-year TLE differed widely across subgroups: range 3.6–8.0 years, average 6.1 years. Mean 10-year DFLE differed relatively even more widely across subgroups: range 1.2–6.5 years, average 4.0 years. Mean 10-year DLE was relatively much closer: range 1.5–2.3 years, average 2.1 years.

Excellent, good job from Duke University, where I did part of my PhD, using the same methodology Grade of Membership.

PS. My speech at the Economist's day.

Anders Zorn au Petit Palais



Improving health in OECD countries

Health at a Glance 2017

Let me highlight toady one figure: 54% of adults in OECD countries today are overweight, including 19% who are obese. Obesity rates are higher than 30% in Hungary, New Zealand, Mexico and the United States.
Many indicators about current state of health in OECD and partner countries can be found in the report. And the public health message is:

While smoking rates continue to decline, there has been little success in tackling obesity and harmful alcohol use, and air pollution is often neglected

These are the new epidemics and prescriptions are not easy to find to curb the current trend.
The report shows many positive messages and this should be a reason for trust in our future, however the uncertainties regarding new risks and how to tackle remain.

Gramophone All Stars Jazz Band. Maraca Soul album. Iko Iko

Uncertainty and regret in medicine

The Power of Regret

While reading NEJM I find an article on regret:

As physicians, we are acutely aware of the element of uncertainty in medicine, but we less often recognize its close companion, regret. Regret in all its forms can be a powerful undercurrent, moving patients to act in ways that may baffle us.

Kahneman and Tversky said  that bad outcomes from recent action are more regretted than similar outcomes from inertia. There two types of bias that affect regret. Omission bias is the tendency toward inaction or inertia — reflects anticipated regret. Commission bias is the tendency to believe that action is better than inaction, and can result in regret arriving later when a bad outcome occurs.

When we’re in pain or acutely anxious, we are “hot” and apt to make choices that we imagine will rapidly remedy our condition, which predisposes us to commission bias. In a hot state, patients may discount too deeply the risks posed by a treatment and overestimate its likelihood for success, paving the way for later regret if the outcome is poor. Patients who choose elective procedures while in a hot
state and end up with a bad outcome may be at particular risk for regret due to commission bias.

Georges Seurat. Two Sailboats at Grandcamp (Deux voiliers à Grandcamp), c. 1885.
Oil on panel, BF1153. Public Domain. Barnes Foundation

The apocalypse and our true fate, who knows?

THE FIVE HORSEMEN OF THE MODERN WORLD: Climate, Food, Water, Disease, and Obesity

In the book of Revelation or Apocalypse of John, you'll find the seven bowls. Seven angels are thus given seven bowls of God's wrath, each consisting of judgements full of the wrath of God poured onto Earth:

First Bowl: A "foul and malignant sore" afflicts the followers of the Beast. (16:1–2)
Second Bowl: The Sea turns to blood and everything within it dies. (16:3)
Third Bowl: All fresh water turns to blood. (16:4–7)
Fourth Bowl: The Sun scorches the Earth with intense heat and even burns some people with fire. (16:8–9)
Fifth Bowl: There is total darkness and great pain in the Beast's kingdom. (16:10–11)
Sixth Bowl: The Great River Euphrates is dried up and preparations are made for the kings of the East and the final battle at Armageddon between the forces of good and evil. (16:12–16)
Seventh Bowl: A great earthquake and heavy hailstorm: "every island fled away and the mountains were not found." (16:17–21)

As you may notice Apocalypse is just that, a book. Daniel Callahan set a title of five horsemen of the modern world as a metaphor of current evils. Global warming, food shortages, water shortages and quality, chronic illness, and obesity could be the key ingredients of our fate?.
At the end, Daniel Callahan calls for a diplomatic model:

to persuade the research, academic, and policy communities to accept what I will call the diplomatic model of relationships, typically now seen between and among nations, and to open a serious dialogue with the business community

Agree.

Obesity: a multifaceted approach

The Current State of Obesity Solutions in the United States

We all agree that we need to face the obesity epidemic. But, when talking about solutions, difficulties and uncertainties  arise. US National Academies held a worksop on 2014 that described interventions designed to prevent and treat obesity in seven settings:
• early care and education,
• schools,
• worksites,
• health care institutions,
• communities and states,
• the federal government, and
• businesses and industry
The book is only a first approach to these experiences, though more evidence is needed in my opinion. They say in the book:

"Much of what needs to be done is clear, he said. The challenge now is to figure out how to do what needs to be done."

 DocField 2017

Now in Barcelona

How to change individual letters of your DNA?

Gene editing has made another step forward. And maybe a complementary to the former one, the CRISPR-Cas9,  that was proved viable by Jennifer Doudna and I explained some months ago in this post. No it is indeed more interesting. Two different approaches, base editing and CRISPR-Cas13, have been described in Science and Nature. Adenine base editing allows to correct mutations, it doesn't cut the gene to insert a new one. It is a sharp pencil rather than scisors. With CRISP-Cas13 it is possible to edit RNA, which converts genetic information into proteins. An exciting approach, you correct a book with temporary ink that disappears, rather than making a permanent mark (like in CRISPR-Cas9).
These are exciting times for genetic research, though we'll have to wait for specific clinical applications

Modigliani, now at Tate Gallery

Voluntary health insurance: fulfilling expectations

Memòria entitats d'assegurança lliure 2015
Regulació de l'assegurança voluntària de salut

Let's take one country that has a mandatory social security system for the whole population, though its funding comes from taxes (?). If 25% of the population in this country voluntarily buy  duplicate coverage for the roughly the same benefits, what would you say?. The potential answer is that the public system is not fulfilling people expectations and has a big problem. Unfortunately, politicians don't recognise the situation. Imagine that in the capital more than one third of the population hold private insurance, you would say indeed that the problem is larger. This is the case of Barcelona.
Somebody should review the situation. Both public and private systems have their drawbacks. If public mandatory funding is not providing an efficient system, than a prescription is needed. If voluntary health insurance solves the unfulfilled expectations, then a close relationship should be established, and this is not an option by now.
I wrote a paper some time ago on the required new regulation for voluntary health insurance. My impression is that nobody read it. Maybe now it's the time.

PS. Right now 735.997 patients are waiting for a surgery, a visit or a diagnostic procedure.

 

 

Richard Estes. Galeria Marlborough

The end of marginal revolution

Richard Thaler was awarded with the Nobel Prize some days ago. If you follow this blog you'll know his works on behavioral economics and nudging. Since many years I've been interested in this perspective, though it has still more to deliver.
Today I would suggest you to read JM Colomer blog. He has written an excellent post on him and its impact on economic science. Selected statements:

Marginalist microeconomics held that we could understand collective outcomes by assuming that they derive from free interactions among homines economici.
A first big counter-revolution was the reintroduction of institutions in the basic analysis, especially since the 1980 and 1990s (including by Nobel laureates related to the social choice and public choice schools such as Kenneth Arrow, James Buchanan, Ronald Coase, Douglass North, Amartya Sen, Thomas Schelling, Leonid Hurwicz, Roger Myerson, political scientist Elinor Ostrom, Oliver Williamson, and others).

The second is the reintroduction of realistic observations about people’s motivations and behavior, including emotions. This has been based on psychology, on the background of huge progress in neuroscience (while pioneers include political scientist Herbert Simon and psychologist Daniel Kahneman). That Richard Thaler professes at the University of Chicago, once the temple of the neoclassical school, shows the depth of the change.

Now we know again that the three pillars of social analysis are, together with people’s calculated self-interested choices, emotions and institutions, as Hume and Smith masterfully had already established.

And this is the return to the roots of economics with a new toolkit.

Parov Stelar

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

Responsible corporate governance

A Skeptical View of Financialized Corporate Governance

Corporate governance practices need to improve, though the approach to fix it is still a work in progress. The last recession gave us multiple examples of irresponsible corporate governance, but few actions have been taken to reverse the trend. A recent article shows how this misallocation of risk and resources should be addressed:

Effective governance requires that those in control are accountable for actions they take. However, those who control and benefit most from corporations' success are often able to avoid accountability. The history of corporate governance includes a parade of scandals and crises that have caused significant harm. After each, most key individuals tend to minimize their own culpability. Common claims from executives, boards of directors, auditors, rating agencies, politicians, and regulators include "we just didn't know," "we couldn't have predicted," or "it was just a few bad apples." Economists, as well, may react to corporate scandals and crises with their own version of "we just didn't know," as their models had ruled out certain possibilities. Effective governance of institutions in the private and public sectors should make it much more difficult for individuals in these institutions to get away with claiming that harm was out of their control when in reality they had encouraged or enabled harmful misconduct, and ought to have taken action to prevent it.

 Public and private organizations are affected and these are the author's "skeptical" suggestions:

The key to improving corporate governance is to increase transparency, create better internal and external control and accountability, and address distortions and inefficiencies through effective laws and regulations.

Society should demand such change, though laws in regulations are not enough. As Foucault reminds us from roman culture, infamia is a crucial measure. Nowadays,  power and money through the media are able to stop infamia too often.

Bjork digital now in Barcelona

Health care priorities in practice

Implementation of the 2013 amended Patients’ Rights Act in
Norway: Clinical priority guidelines and access to specialised
health care

Norway decided to update their system to set health care priorities. In 2013, the Patient Rights Act was amended to simplify the priority setting process for specialized elective health care and to improve access to care. And now, this is what they have:

Priority for treatment is now determined by only two criteria: 1) clinical effectiveness; and 2) cost-effectiveness of the intervention. There are 33 clinical priority setting guidelines organised by medical specialty, which help hospitals evaluate whether individual patients have a right to access care.
The revised guidelines define and score a total of 556 condition-intervention pairs, and will give all patients who are evaluated as having a need for specialist elective healthcare the right to access these services

Health policy must define priorities, it is not only a professional issue. Unfortunately by now, in our country are quite far from Norway, geographically and politically.

People on the waiting list? In Catalonia there are 736.000 citizens (10% of population) waiting for an appointment, test or hospitalization. SOMEBODY SHOULD SOMETHING

Weegee by Weegee in Barcelona