Geisinger (it is not any fiord)

A suggestion for weekend reading: excellent interview by Eric Topol with the Geisinger Health System CEO, in Medscape.

Regarding genetics in clinical practice:

Our approach is based on asking, "What if we did whole-exome sequencing on our entire population?" We started this to see whether we could find medically actionable genetic conditions that we could do something about. We are 200,000 patients into it—or I should say, research subjects, because we started with research—and we have found that 3.5%-4% of those people have something actionable: BRCA, malignant hyperthermia, Lynch syndrome, genes associated with cardiac arrhythmia.

They are unique.

And this is what happens at Sotheby's after the purchase for$1.4m

Banksy is a genius 

As time goes by

The order of time

I've just finished the book I started this summer: The order of time. It's quite difficult to enter in physicists territories, and time is the last frontier and a mystery. But Carlo Rovelli does a great job explaining in easy terms such complicated things.

This is the disconcerting conclusion that emerges from Boltzmann’s work: the difference between the past and the future refers only to our own blurred vision of the world. It’s a conclusion that leaves us flabbergasted: is it really possible that a perception so vivid, basic, existential—my perception of the passage of time—depends on the fact that I cannot apprehend the world in all of its minute detail? On a kind of distortion that’s produced by myopia? Is it true that, if I could see exactly and take into consideration the actual dance of millions of molecules, then the future would be “just like” the past? Is it possible that I have as much knowledge of the past—or ignorance of it—as I do of the future? Even allowing for the fact that our perceptions of the world are frequently wrong, can the world really be so profoundly different from our perception of it as this?

All this undermines the very basis of our usual way of understanding time. It provokes incredulity, just as much as the discovery of the movement of the Earth did. But just as with the movement of the Earth, the evidence is overwhelming: all the phenomena that characterize the flowing of time are reduced to a “particular” state in the world’s past, the “particularity” of which may be attributed to the blurring of our perspective.

 As The Guardian review says, the book is "an expression of the scientific desire to know and understand the world". Rovelli's message: time doesn't go by, time doesn't really exist as we imagine, it is only our construct.

La rumba del temps by Joan Miquel Oliver

Insuring biomarkers coverage

From the Past to the Present:Insurer Coverage Frameworks for Next-Generation Tumor Sequencing

Technology is one step ahead regulation and coverage. Sounds normal. However, the size of this step may be bigger than you think if we refer to next generation sequencing biomarkers. A new article in Value in Health journal covers this topic in detail.

One of the challenges of insurance coverage for next-generation sequencing is that it pushes the very boundaries of the underlined framework used by insurers in coverage decisions.  For example,to receive insurance coverage, a medical technology must be determined “medically necessary” and not “experimental/investigational.” Next-generation sequencing blurs the boundaries between these two concepts, making coverage decisions difficult.

Therefore some trade-offs are unavoidable. Inside the article you'll find them.

Anoro, Barnadas gallery

Healthcare services governance

The Firm Divided
Manager-Shareholder Conflict and the Fight for Control of the Modern Corporation

There is a unique feature of health services,- where public or non-profit organizations play a major role- it requires a deep understanding of the governance of the firms and its conflicts.
A new book provides a summary for private firms. In my opinion, most of the recommendations are applicable to public and not-for-profit organizations.

There are many partial solutions to manager–shareholder conflict, but none of them
work perfectly. In fact, even when they are all combined, the outcome is far from perfect. In some solutions, shareholders and directors play a hands-on role, taking responsibility themselves for keeping managers in line. In short, they monitor. Shareholders do some monitoring themselves; the rest they leave to a board of directors, which they elect—but everyone is involved in managing the managers. Directors play more of a hands-off role in the next set of solutions.

They set a few ground rules that executives must follow, create few incentives, and then step back and allow events to unfold. That is, they motivate. 

However, directors cannot do everything themselves, so in the third set of solutions they enlist outside parties to do some of the monitoring and motivating on their behalf. They delegate. These outsiders have their own selfish reasons for getting involved, but their presence can still benefit shareholders. 

As a last resort, and the last time that shareholders are even indirectly involved in the game, shareholders can sell, or threaten to sell, their shares to another firm. Selling is the ultimate hands-off policy. 

All of these approaches to corporate governance occur in a world of rules and regulations. That is why there is a final solution to manager–shareholder conflict, of which shareholders are entirely passive beneficiaries: the fight to change the rules of the game. These are the key steps to effective corporate governance: monitor, motivate, delegate, sell. The rules of the game matter as well.

Definitely, the last resort doesn't apply to publicly owned and nonprofit organizations. For private managers, this is a real threat, not replicable elsewhere. It is precisely for this reason that governance matters and an additional effort should be devoted.

Economics of ownership in healthcare

Private Provision of Publicly Funded Health Care: The Economics of Ownership

You'll find an interesting review of public private provision by Martin Chalkley in this brief. It says:

Viewed through the lens of economics, concern over ownership arises from the impossibility of complete contracts between purchasers of health care and providers of health care. Were complete contracts feasible they would render the question of ownership redundant. But contracts will always be incomplete: it is not possible to specify in advance all of the relevant circumstances around the care of every patient who is to be served, so as to ensure that they receive appropriate quality of care at a cost that reflects complete efficiency and does not leave the provider either with unsustainable losses or supernormal profits.

But the existence of the collective purchaser(s) for health care means that purchasers have power that individual consumers in other sectors do not have. NHS purchasing arrangements have the potential to ensure that private ownership does not lead either to a ‘race to the bottom’ – sacrificing quality in order to cut costs – or to supernormal profits being earned – which would siphon off NHS funds that could otherwise be used to deliver more health care.

And the final statement:

 We conclude overall that when considering the ownership of health care providers in a publicly funded health care system, statements such as “public good, private bad”, or the other way about, are misplaced. All health care providers require regulation. All health care providers require carefully thought out contractual arrangements that recognise the incentives and constraints they operate with – and these do differ between ownership types. The collective nature of health care purchasing provides the means for achieving this.

That's it. A clear message for any open-mind politician.

Are we paying too much for pharmaceutical innovation?

Economics of the Pharmaceutical Industry

The question of whether innovation is too high or too low is a first-order—perhaps the first- order—policy question in the economics of the pharmaceutical industry. Yet, economists have not produced a definitive answer. At best, we have suggestive analyses that point to the low rate of surplus capture by innovators, and modeled estimates suggesting that the social return to innovation is positive on the margin. While helpful, these findings each require a speculative leap in order to draw an inference about the social efficiency of innovation. Much rides on the answer to this question. If innovation is indeed excessive, then public and private payers are wasting money paying excessively high rewards to firms producing innovations. In contrast, if innovation is too low, lives are being lost prematurely due to a lack of medical progress.

This is the "answer" that Lackdawalla gives in an interesting article in Journal of Economic Literature (more details inside). If you want a review in 50 pages of the main issues surrounding the industry, this is the article you have to read.

Courtauld Impressionists exhibition at the National Gallery
Video

Lamarck returns

Lamarck's Revenge: How Epigenetics Is Revolutionizing Our Understanding of Evolution's Past and Present

I've just started to read this amazing book. Chapter 1 says:

Charles Darwin espoused evolution as driven by natural selection. However, an earlier theory, proposed more than a half century before the first publication of Darwin’s greatest work, came from a naturalist whose life and work were limned by the flames of the French Revolution.

Lamarck arrived at a three-step process in what was to be the first really rational explanation for what we now call “organic evolution.” First, an animal experienced a radical change of the environment around it. Second, the initial response to the environmental change was some new kind of behavior by that animal (or whole species). Third, the behavioral change was followed by morphological changes that were heritable in subsequent generations. This proposed process came to be named after its author. Today, a variant on what Lamarck proposed is sometimes called “neo-Lamarckism,” but more often “epigenetics,” or “heritable epigenetics.”

Jean-Baptiste-Pierre-Antoine de Monet, Chevalier de Lamarck, had a different view about heredity and why animals changed through time. His scientific beliefs were that things that happen to us during our lives can change what we pass on to our next generation, and perhaps into even further generations. Darwin knew well what Lamarck theorized. Darwin believed that his own theories about evolution could not coexist with any aspect of what Lamarck postulated. We now know this is no longer the case.
Lamarck’s Revenge looks anew at what are, perhaps, humanity’s most basic questions: the “where,” “when,” and “why” of getting to the present-day biota on this planet. But the vehicle to do this is by asking specifically about the “how.” What were the evolutionary mechanisms, the balance between Darwinian and neo-Lamarckian (aka heritable epigenetics), that produced not only our physical biology but some aspects of our heritable behavior as well?

Here are some possibilities. First, that the process known as epigenetics combined with periods of extraordinary environmental change has played a far greater role in what is called the “history of life” than is accepted by all but a small cadre of revolutionary biologists. This is perhaps most decisively shown through the epigenetic process of “lateral gene transfer,” where on a given day, in a given minute, some organism is invaded by another and a product of that invasion is the incorporation of vast numbers of new genes, making the invaded creature something else again, neither the invader nor the invaded. This is known.
Second, new evidence points to a probable role of epigenetics in producing rapid species transitions by mechanisms other than lateral gene transfer. Science has discovered that major evolutionary change of a species can happen a thousand times faster by epigenetics than by the process demanded by the Darwinian theory of single, random mutations along a creature’s genome or DNA (or, in some cases, RNA). This is most likely to occur during and immediately after rare, major environmental perturbations (such as mass extinctions and their aftermath).

Commercial determinants of health

Systems Thinking as a Framework for Analyzing Commercial Determinants of Health

Unhealthy commodity industries (UCIs) are defined as industries in which a significant share of their product portfolio comprises unhealthy products including tobacco, alcohol, energy‐dense and low‐nutrient foods and beverages, and gambling services.

Unhealthy commodity industries actively design and shape the NCD policy system, intervene at different levels of the system to gain agency over policy and politics, and legitimize their presence in public health policy decisions.

Reviewing health systems

Spain Health system review

The series Health systems in transition by WHO is a helful source to understand the current state of healthcare. Now you can red the updated version for Spain. Check p.68 and you'll have to reduce the number of members with private insurance by 1.5m, because income protection products have been added,, and they don't reflect health insurance, they are "income insurance". Anyway, in p.61 you'll find the size of administrative costs, 3%. This is one of the reasons why the spanish health system is so cheap. But if you split between private and public you get the following: private insurance premiums are 10% approx of public expenditure, and represent half of administrative costs.I know that the estimation is quite difficult, but anyway, this is what the table says.
A big effort and a very helpful text for anyone interested in understanding the health system.

Khan el-Khalili based drug pricing

When is it too expensive? Cost-effectiveness thresholds and health care decision-making

In one week of difference, the same technology: CAR T-cells has had two different options for drug pricing. Last week, under NICE review the answer was no to Gilead, and yesterday was yes to Novartis. The first paradigm applied to Yescarta is well known: marginal effectiveness should be acceptable at an affordable cost (NICE). The second one applied to Kymriah is based on preferences and willingness to pay under confidential prices. It is also a well known system specially at bazaars like Khan el-Khalili in Cairo.
This is an example of how two systems are applied in practice and nobody cares about it. I'm concerned about transparency, and that's why I can't understand why with public money the expenditure is confidential. I would agree if somebody explain the budget impact that have been agreed, otherwise with public money Kahn el-Khalili system is not acceptable. After more than four decades, Torrance would ask himself if all this effort on cost-effectiveness analysis has had any sense to arrive at this point.
Anyway, the remaining question is: when is too expensive? This is precisely what this editorial asks. And the and the answer (?) is:

For deciding whether something is too expensive, thresholds are crucial. Depending on which perspective is taken, the word ‘threshold’ may either refer to the consumption value of health or the marginal cost-effectiveness of current spending. 

This is a standard health economics perspective that no health politician nowadays will buy. Right now they are not buying the idea, and I think that they prefer confidential prices. It allows to reflect power,  discretionality, or even worse arbitrariness. Khan el-Khalili system has won.

A controversial view of epigenetic inheritance

A critical view on transgenerational epigenetic inheritance in humans

A new article in Nature suggest that more evidence is needed to ascertain the role of epigenetic inheritance.

Even if the molecular mechanisms exist to transmit epigenetic information across generations in humans, it is very likely that the transgenerational transmission of culture by communication, imitation, teaching and learning surpasses the effects of epigenetic inheritance and our ability to detect this phenomenon. Cultural inheritance has certainly had an adaptive role in the evolution of our species, but the evidence for transgenerational epigenetic inheritance, as laid out above, is not (yet) conclusive. 

Let's wait for new evidence...

Overturning conventional wisdom

Randomistas: How Radical Researchers Are Changing Our World

Clinical trials are the standard way to produce new evidence. A new book reminds us that this is quite new. It starts explaining the scurby case and how it took 50 years to apply its results (lemon) to avoid death among sailors. There is aplenty of details and experiments among medicine, social and policy domains. You'll find a reference to the Rand Health Insurance Experiment and nudge examples.
If you want a good review of the book, check this one or Diane Coyle.

The more we ask the question ‘What’s your evidence?’, the more likely we are to find out what works – and what does not. Scepticism isn’t the enemy of optimism: it’s the channel through which our desire to solve big problems translates into real results. If we let our curiosity roam free, we might be surprised how much we can learn about the world, one coin toss at a time.

Is there a room for autonomous medical diagnosis?

Pivotal trial of an autonomous AI-based diagnostic system for detection of diabetic retinopathy inprimary care offices

With an eye to AI and autonomous diagnosis

In Digital medicine you'll find the article on an artificial intelligence-based  diagnostic of diabetic retinopathy. It's the first AI system approved by FDA last April, and represents the begining of new aids for medical decision making. Therefore, there is a room for supporting decision making with AI, but maybe one day autonomous diagnosis could be the issue, who knows.

The prespecified sensitivity end point agreed with the FDA was 85.0% and this was met with a point estimate of primary sensitivity of 87.2%. However, the confidence intervals of this estimate were 81.8–91.2% (that is, spanned the superiority end point). The study also employed an intention-to-screen protocol; however, 40 participants successfully enrolled in the study were excluded from analysis as their images were subsequently found to be insufficient quality to be graded by the image reading center. The authors attempt to address this by considering a worst-case scenario where all such images are incorrectly graded and repeating the analysis. In this approach the sensitivity would
be 80.7% (76.7–84.2%).

 Although deep learning will not be a panacea, it has huge potential in many clinical areas where high dimensional data is mapped to a simple classification and for which datasets are potentially stable over extended periods. As such, it will be incumbent on healthcare professionals to become more familiar with this and other AI technologies in the coming years to ensure that they are used appropriately.

Alice Francis - Coco Baca Bum Bum

The uselessness of current hospital rankings

Personalized Hospital Ratings — Transparency for the Internet Age

Eric Topol said in a tweet: It's high time to transcend hospital ratings and move to indvidualized ratings of hospitals. He refers to an NEJM article that supports personalized hospital ratings like the Rand ones.

As currently constructed, the weighting systems that underlie overall hospital performance ratings are expressions of the values, preferences, and tastes of their creators. Why not ask patients what’s important to them instead?

It makes sense.

PS. FT life of a song