Regulating alcohol marketing

Policy Approaches for Regulating Alcohol Marketing in a Global Context: A Public Health Perspective

The article says:

The range of policy options for alcohol marketing restrictions includes four main categories: no restrictions, voluntary regulation or self-regulation, partial restrictions (e.g., on content, time and place, or particular audiences), and complete bans.

Unfortunately you'll not find a clear assessment of the impact of these policies. Only anecdotical facts. Therefore, no prescriptions can be made with sounding evidence. My impression is that somebody should care about the current advertising strategies that are very far from what WHO considered as comercials some years ago.

Conceptual framework on the growth of alcohol corporations, exposure to alcohol marketing, and alcohol-related public health problems.

Enabling Patients to Stick to their Medication

Investing in medication adherence improves health outcomes and health system efficiency

OECD provides some key figures on medication adherence:

Poor adherence is estimated to contribute to nearly 200 000 premature deaths in Europe per year. Patients with chronic diseases are particularly vulnerable to poor health outcomes if they do not adhere to their medications. Mortality rates for patients with diabetes and heart disease who don’t adhere are nearly twice as high as for those who do adhere.

It is estimated to cost EUR 125 billion in Europe and USD 105 billion in the United States per year in avoidable hospitalisations, emergency care, and outpatient visits.

The three most prevalent chronic conditions – diabetes, hypertension, and hyperlipidaemia – stand out as the diseases with the highest avoidable costs, for
which every extra USD spent on medications for patients who do adhere can generate between USD 3 to 13 in savings on avoidable emergency department visits and inpatient hospitalisations alone.

I'm dubious about the exact figures, anyway if you imagine that it is half ow what the say it would be a lot. Systematic reviews say that non-adherence is 15%. This is a hot topic and the ways to tackle are known.

Acknowledge: Medication non-adherence harms health and increases healthcare costs. The first step for the relevant stakeholders is to acknowledge that this problem exists and to adequately recognise its main drivers. Medication adherence needs to move up the policy agenda in order to raise awareness of the problem and mobilise adequate responses.

Inform: Few countries systematically monitor adherence. Routine adherence measures as well as adherence-related quality and performance indicators should be encouraged in order to improve health system effectiveness and efficiency.

Incentivise: Changes in financial incentives for providers and patients are essential. Shifting to payment systems that reward providers for the quality of patient outcomes would provide strong motivation to improve adherence. Medication adherence could also be considered as a measure for performance based contracts with pharmaceutical companies. Where patients’ co-payments for chronic medications exist, their reduction or removal should be considered to reduce financial barriers.

Steer and Support: The adherence process begins with a patient and a prescribing clinician and a dispensing pharmacist who should all be supported by other health system stakeholders. Payers/system designers can develop IT systems that facilitate optimal prescribing and patient-clinician communication or renewing prescriptions by patients. Educators have a role in equipping health professionals with skills in managing adherence such as person centred communication, shared decision-making, and socio-cultural competencies.

Clinical utility of genomic sequencing

The Path to Routine Genomic Screening in Health Care

Now that whole genome sequencing is knocking at the door of the clinician, it is the time to ask for clinical utility. The understanding of how such information will change diagnostic and therapy is paramount. There is still no need for cost-effectiveness, clinical utility comes first.
And the editorial at Annals explains exactly this issue, highly recommended:

There should be little doubt that individually tailored health care management plans based on DNA analysis are coming, but the timing of their introduction into routine clinical care is contingent on further demonstrations of clinical utility and proven implementation models.

My impression: let's wait for epigenetic biomarkers, beyond whole genome sequencing that provides less than 100 actionable genes out of 20.000. Though,

 The fact that only a small percentage of people would benefit from GS today is counterbalanced by growing evidence that the benefit could be significant, and perhaps even life saving

 

Pepe Castellanos at Barnadas Gallery

Who should get treatment?

Who should receive treatment? An empirical enquiry into the relationship between societal views and preferences concerning healthcare priority setting

The concern for an equitable and fair allocation of healthcare resources requires a prioritisation approach. Otherwise we are going to live in an arbitrary and opaque world.
An article from the Netherlands explains what people think about three perspectives:

The view “Equal right to healthcare” comprises an egalitarian view on health and healthcare. People with this view consider access to healthcare a basic human right. Everyone is equal, hence has an equal right to healthcare. According to people with this view, prioritisation should solely be based on the need for care and prioritisation based on patient, disease, and intervention characteristics, such as the effect of treatment, is opposed. What is considered to be “the right care” is a matter of personal concern for patients and, according to people with this view, patients should be supported in their treatment choices regardless of the costs.

The view “Limits to healthcare” comprises a view with a strong concern for providing “the right care” for patients. People with this view consider health-related quality of life to be an important outcome of treatment. According to people with this view, providing the right care may imply refraining from (life prolonging) treatment. People with this view do not consider cost-effectiveness to be an important criterion for priority setting, although they do consider it important to make good use of money. Hence, providing treatments that generate minimal benefits should be avoided. Priority setting based on patient characteristics is rejected, with an exception made for lifestyle. According to people with this view, patients who are culpable of their own disease should receive lower priority and prevention should receive higher priority in allocation decisions.

The view “Effective and efficient healthcare” comprises a utilitarian view on health and healthcare. People with this view consider it important to generate as much health for society as possible given the budget constraint, and consider a patient’s capacity to benefit from treatment important when setting priorities. Although people with this view focus on the cost-effectiveness of treatments, they do believe it is not possible to “put a [fixed] price on life”. The value of health benefits depends on circumstances and patient characteristics, such as age and culpability, and hence these should be taken into account in priority setting.

 And the result is:

 The majority of respondents was matched to the view “Equal right to healthcare” (64.5%), followed by “Limits to healthcare” (22.5%), and “Effective and efficient healthcare” (7.1%). A minority of respondents (5.9%) could not be matched

My impression is that we change such criteria according to the exact setting we are in a precise moment. That's why beyond societal criteria we do need professional criteria. Sounds too easy to solve the prioritisation exercise according to three principles.

PS. Still waiting for the book:Rationing and Resource Allocation in Healthcare: Essential Readings

 Juan Genovés exhibition at Marlborough gallery

Research and results

The Biomedical Bubble: Why UK research and innovation needs a greater diversity of priorities, politics, places and people

More resources for research are needed. This is the usual mantra. However, what about outcomes?. Since this is not so easy to measure it really lies in an uncertain land. A new report tries to put things clearer, at least for UK. It explains the mismatch about research funding and what is needed to improve health. This is exactly what I consider the right approach. It is useless to ask for more money unless we explain and focus on the priorities for achieveing better health.

A biomedical bubble has developed, which threatens to unbalance the UK’s research and
innovation system, by crowding out the space and funding for alternative priorities. This
is not a speculative bubble, as developed for tulips in the 1630s, or dotcoms in the early
2000s; there is far too much substance in the biomedical sciences for this. But it is a social, political and epistemic bubble (similar to the ‘Westminster bubble’, or the ‘filter bubble’), in which supporters of biomedical science create reinforcing networks, feedback loops and commitments beyond anything that can be rationalised through cost-benefit analysis.

The biomedical bubble represents a risky bet on the continued success of the pharmaceutical industry, despite mounting evidence that this sector faces a deepening
crisis of R&D productivity, and is cutting its own investment. And it favours a particular approach to the commercialisation of science, based on protectable intellectual property and venture capital based spinouts – despite the evidence that this model rarely works. Our health and social care system is under growing strain, and as the NHS marks its 70th birthday this month, there is renewed debate about its long-term affordability. Too often, the biomedical bubble distracts attention and draws resources away from alternative ways of improving health outcomes. Only 5 per cent of health research funding is spent on researching ways of preventing poor health. And more than half is spent in three cities - London, Oxford and Cambridge - despite variations in life expectancies of up to eight years across the country. This paper argues for a more balanced distribution, aligned to what the evidence clearly shows are crucial social, economic, environmental and behavioural determinants of better health outcomes.

 Food for thought.

Shomei Tomatsu in Barcelona

Fake lab tests

Bad blood

We all know that we live in a post-truth society. But this may have strong effect in your health. The case of Theranos, a US lab is explained in an excellent book by John Carreryrou is a precise example. You create an expectation that with a blood drop all tests can be done, you develop the narrative, the social and entrepreneurial support, and...while the regulator is on vacation (as usual) you perform fake test that can endanger your health. Imagine that your coefficient of variation is 34-48%, while it should be less than 10%!. The results may hurt you directly.
The book provides a lot of details:

As for the lab itself, it was a mess: the company had allowed unqualified personnel to handle patient samples, it had stored blood at the wrong temperatures, it had let reagents expire, and it had failed to inform patients of flawed test results, among many other lapses

And strong messages for start-up investors:

By positioning Theranos as a tech company in the heart of the Valley, Holmes channeled this fake-it-until-you-make-it culture, and she went to extreme lengths to hide the fakery. Many companies in Silicon Valley make their employees sign nondisclosure agreements, but at Theranos the obsession with secrecy reached a whole different level.

FT recommends this book for this summer, and I agree that it will help you to understand and avoid similar fake business that we can detect around us. It should never happen again.

Cost-effectiveness of new (genomic) benefits, it's just the begining

HERC database of health economics and genomics studies 
Cost-effectiveness of cell-free DNA in maternal blood testing for prenatal detection of trisomy 21, 18 and 13: a systematic review

Just yesterday our government suddenly decided to introduce a new benefit in public insurance coverage: contingent DNA based non-invasive prenatal screening. And the question is: does someone know if this new benefit is cost-effective?
You can get the answer after reading this review article, and the summary is:

 In total, 12 studies were included, four of them performed in Europe. Three studies evaluated NIPT as a contingent test, three studies evaluated a universal NIPT, and six studies evaluated both. The results are heterogeneous, especially for the contingent NIPT where the results range from NIPT being dominant to a dominated strategy. Universal NIPT was found to be more effective but also costlier than the usual screening, with very high incremental cost-effectiveness ratios. One advantage of screening with NIPT is lower invasive procedure-related foetal losses than with usual screening. In conclusion, the cost-effectiveness of contingent NIPT is uncertain according to several studies, while the universal NIPT is not cost-effective currently.

If this is so, since uncertainty is the word that better reflects its current cost-effectiveness, why do the have introduced? Because they don't care about it. These are not the best days for a health economist (and for the society as a whole). Maybe it's just the begining of a new world without scarcity, and I can't figure out.

Manuel Anoro

Health care access in EU

BENCHMARKING ACCESS TO HEALTHCARE IN THE EU.Report of the Expert Panel on effective ways of investing in Health

If access is one of the main features of any health system, we do need better measures to understand the current situation. This is my conclusion after reading the report. Differences across EU countries (and within countries!) are huge in unmet needs , in copayments, in catastrophic expenditures... The surprising figure for me was that Spain is at the top of out of pocket expenditures as a share of household expenditures (3.5%) with Latvia. I have to check it. If so, bad news. Universal healthcare is being questioned. Does someone care about it?

Saul Leiter, Barcelona exhibition

Cost-effectiveness of genome sequencing (3)

Application of next-generation sequencing to improve cancer management: A review of the clinical effectiveness and cost-effectiveness

Once again, there is no need for cost-effectiveness if there is not a clear message on the analytical validity, clinical validity and utility of a diagnostic test.
A new article want to shed light on cancer and NGS, and says:

Our search for cost‐effectiveness studies on NGS in cancer care yielded 2037 articles. Only 6 articles included cost‐effectiveness studies of the application of NGS (targeted gene panel) in cancer

The 6 selected reports could be separated into 2 types. Three of the articles assessed the cost‐effectiveness of recommending patients receiving targeted therapy matching their genetic mutation identified via NGS; and the remaining 3 articles assessed the cost‐effectiveness of using NGS as part of the screening program to direct patients or high risk family members into prophylactic treatment

Two out of 3 articles in the “targeted therapy” group reported that NGS and targeted therapy was not cost-effective (Table 3A), using an ICER threshold of US$100 000 per Quality Adjusted Life
Year (QALY) gained. An ICER of less than US$100 000/QALYs gained is generally considered favourable for funding in the United States

Two out of the 3 articles in the “screening” group reported that the use of NGS was cost‐effective (Table 3B), that is, under US$100 000 per QALY gained.loser surveillance.

 In our evaluation of the effectiveness of NGS, we found that NGS is effective at identifying mutations in cancer patients, and we reported that 37% of the diagnosed patients proceeded to receive therapy matching their genetic profile. However, with only 6 articles available that assess the cost-effectiveness of NGS in various settings, it remains an area for future research to determine whether the technology is cost-effective in routine cancer management

Summary: the message is that there is no message with such a few observations!


Something is being missed...

Guillem Roma and Marta Roma

Value creators and extractors

The Value of Everything: Making and Taking in the Global Economy

The rethorics of value is usually plagued with deliberate misunderstandings. Specially, those that quote themselves as value creators may appear on a close look as a value extractors. This is precisely what the book of Marianna Mazucatto does. It identifies the patterns to assess value creation and extraction and the private of public and private roles.Chapter 7 on Extracting Value through the Innovation Economy is specially helpful. You'll find there the patents as a value extraction process or the pharmaceutical pricing discussed in detail. Therefore, a must read.

In modern capitalism, value-extraction is rewarded more highly than value-creation: the productive process that drives a healthy economy and society. From companies driven solely to maximize shareholder value to astronomically high prices of medicines justified through big pharma's 'value pricing', we misidentify taking with making, and have lost sight of what value really means. Once a central plank of economic thought, this concept of value - what it is, why it matters to us - is simply no longer discussed.

 The logical outcome of a combination of monopoly and rigid demand is sky-high prices, and this is precisely what is happening with specialty drugs. It explains why pharmaceutical companies enjoy absurdly high profit margins: in addition to the normal profit rate, they earn huge monopoly rents.59 A value-based assessment of the kind NICE carries out can be helpful because it reduces demand for the monopolists’ drugs and prevents them from charging whatever price they choose. The downside, however, is that increased elasticity of demand for drugs comes at the cost of leaving some patients without the medicines they need, because pharmaceutical companies may not cut their prices enough to treat everyone who needs the drug if doing so would reduce profit margins by more than the companies want.

The improvement of the healthcare access and quality

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study 2016

While the global consensus on universal health care is a fact, healthcare access is really diverse. Among countries you can check the differences in the new article that has appeared in Lancet.

From 1990 to 2016, 186 of 195 countries and territories significantly increased their HAQ Index score, with several middle-SDI countries, including China, the Maldives, Equatorial Guinea, Peru, and Thailand achieving among the most pronounced gains. 

 In 2016, HAQ Index performance spanned from a high of 97·1 (95% UI 95·8–98·1) in Iceland, followed by 96·6 (94·9–97·9) in Norway and 96·1 (94·5–97·3) in the Netherlands, to values as low as 18·6 (13·1–24·4) in the Central African Republic, 19·0 (14·3–23·7) in Somalia, and 23·4 (20·2–26·8) in Guinea-Bissau. The pace of progress achieved between 1990 and 2016 varied, with markedly faster improvements occurring between 2000 and 2016 for many countries in sub-Saharan Africa and southeast Asia, whereas several countries in Latin America and elsewhere saw progress stagnate after experiencing considerable advances in the HAQ Index between 1990 and 2000. Striking subnational disparities emerged in personal health-care access and quality, with China and India having particularly large gaps between locations with the highest and lowest scores in 2016. In China, performance ranged from 91·5 (89·1–93·6) in Beijing to 48·0 (43·4–53·2) in Tibet (a 43·5-point difference), while India saw a 30·8-point disparity, from 64·8 (59·6–68·8) in Goa to 34·0 (30·3–38·1) in Assam.

 The measurement has been done with 32 causes from which death should not occur in the presence of effective care to approximate personal health-care access and quality by location and over time. This means that death registries should be available and reliable, and we know that there is no standard practice across countries. Anyway, the message is clear, most of the world is improving access to better healthcare and this is good news.

Aminata’ (2013) by Omar Victor Diop

Evorafrica exhibition

The p53 nightmare

p53 and Me

This week you'll find a short piece in NEJM, a story written by a physician on how detecting a genetic p53 mutation changed her views. Key message:

Genetic knowledge is power only if both clinician and patient are equipped to move beyond a result and toward action, even if that merely means living well with what we know. I believe we need an expanded definition of genetic counseling; we require more data, yes, but also more sophisticated and sensitive ways of assimilating such data. And not just into databases we can mine to see what happens to people like me, but into programs for learning to live with uncertainty.

A must read

The spanish flu, a century later

Pale Rider: The Spanish Flu of 1918 and How it Changed the World

Laura Spinney has made a great job with her latest book "The Pale Rider". For those that are interested on the largest recent epidemy and public health crisis -the spanish flu of 1918,- this is the book to read. I enjoyed specially the details of what should be avoided, and nobody cared about it. The conflict between religion and medicine. You'll not get the precise number of deaths, but it was an enormous tragedy in social terms.
The book also explains how physicians were exposed to the disease without any tools and how it was arriving to the remote and less inhabited places of the world.
It is specially helpful to recognise how vulnerable are all of us, still now. Highly recommended.

PS. You'll find it also in spanish, "El jinete pálido"

Theranos: a massive fraud and epic failure

The Theranos deception on CBS News 60 Minutes

The weirdest health financing system of the world (2)

Tracking Universal Health Coverage: 2017 Global Monitoring Report

If I had to summarise the best outcome of health policy in the last century in western countries, I would say mandatory health insurance. No doubt. And the joint report by WHO and WB reminds us that there is still a long way to achieve such goal for the whole population in the world.  Mandatory insurance is the most efficient way to solve the failures of the health insurance market. We al know the details and difficulties that arise as a result of information asymmetries and opportunistic behaviour.
Therefore the recommendation is clear, for those that already have a mandatory system, keep on it. This is precisely what hasn't happened here. In 2012 the system changed from universal towards a social security based membership funded by taxes. The weirdest health financing system of the world.

Maya Fadeeva with Club des Belugas

Measuring morbidity in large populations

MODELIZACIÓN ECONÓMICA DEL AJUSTE POR RIESGO DEL GASTO SANITARIO PER CÁPITA SEGÚN MORBILIDAD EN LA COMUNIDAD VALENCIANA

There is a unique study on measuring morbidity in a large population. In Valencia (4.7 million inhabitants) the Clinical Risk Group classification system has been applied. And you may find the results comparing the whole population, and one Department (Denia). The study shows details about the utilization and costs related with morbidity. Interesting application that replicates former ones. Epidemiologists, clinicians, policy makers and managers should be interested in using these approaches for taking decisions.

Pablo Picasso, by Arnold Newman

Changing the production function of diagnostic tests

Next-generation diagnostics with CRISPR

Last week while reading Science I noticed a short and crucial article. Up to now CRISPR technology was focused on gene editing, now we can say that its usefulness is widening into diagnostics. It may change completely molecular diagnostics of "infectious diseases through detection of Zika virus (ZIKV), Dengue virus (DENV), and human papillomavirus (HPV) in human  samples, and noninfectious diseases, such as detection of gene mutations in circulating cell-free DNA from lung cancer patients." The production founction of lab testing would change completely.
Several articles explain details about it. The fight for patents is going to start again on CRISPR diagnostics. And this are unfortunately bad news.
Anyway, Science article reminds us:

These emerging diagnostic tools will by necessity be compared to standard diagnostics to ensure sensitivity and specificity and will need to be field-tested to guarantee performance in patient care settings, as environmental conditions and end-user application might affect performance. Proven assays, if affordable, promise to improve care in resource-limited settings where undifferentiated febrile illness is the norm and where gaps or delays in diagnosis, targeted care, and infection control contribute to infectious disease mortality and spread.

More details in The Verge.

Cost-effectiveness of genome sequencing (2)

Application of next-generation sequencing to improve cancer management: A review of the clinical effectiveness and cost-effectiveness

If you want to go deeper on the issue, have a look at this article. It is focused on one disease, cancer and tries to combine clinical effectiveness and cost effectiveness. Sounds good. At the end you'll see that the number of available studies is limited (6), but that's the situation and these are the conclusions:

We report the rate of successfully detecting mutations from the clinical studies. The incremental cost-effectiveness ratio and sensitivity analysis outcomes are reported for the cost-effectiveness articles. Fifty-six articles reported that sequencing patient samples using targeted gene panels, and 83% of the successfully sequenced patients harboured at least 1 mutation.

 In our evaluation of the effectiveness of NGS, we found that NGS is effective at identifying mutations in cancer patients, and we reported that 37% of the diagnosed patients proceeded to receive therapy matching their genetic profile. However, with only 6 articles available that assess the cost-effectiveness of NGS in various settings, it remains an area for future research to determine whether the technology is cost-effective in routine cancer management.

PS. Today this blog has surpassed its 200.000 visits. That's great! Thank you for your loyalty.

Sally Mann, On the Maury, 1992, gelatin silver print, Private collection.

Washington National Gallery, current exhibition

Cost-effectiveness of genome sequencing

Are whole-exome and whole-genome sequencing approaches cost-effective? A systematic review of the literature

It is quite difficult to talk about value in genetic tests without any reference to analytical validity, clinical validity and clinical utility. Once these three issues are appropriately solved, then we need to assess costs. Cost effectivenes makes sense once this three steps are covered successfully.
An analysis of cost-effectiveness of whole genome/exome sequencing it sounds too generic if there is no reference to specific baseline that allows to estimate incremental cost-effectiveness ratios.
That's the reason why a recent article trying to review existing studies fails to achieve any conclusion.

The current health economic evidence base to support the more widespread use of WES and WGS in clinical practice is very limited. Studies that carefully evaluate the costs,
effectiveness, and cost-effectiveness of these tests are urgently needed to support their translation into clinical practice.

 Let's start focusing on the assessment of three key perspectives before entering into a black hole.

Diagnosing diseases and editing genes

CRISPR: The gene-editing tool revolutionizing biomedical research
The WIRED Guide to Crispr
A New Startup Wants to Use Crispr to Diagnose Disease

Take your time and read Wired and watch CBSNews. It will provide an exciting perspective of CRISPR. And just to end, imagine that diagnostic tests could be based on CRISPR while you read the last piece of WIRED.
We are closer than you may think.

Mental health: the problem and what can be done

THRIVE: How Better Mental Health Care Transforms Lives and Saves Money

I have to recognise it. Mental health is a difficult issue, and all the efforts to decrease its impact on individual and social welfare are not enough by now. The book by Layard and Clark is a useful reference. I had to read it since long time. It says:

Mental illness is the great hidden problem in our societies, so most people are amazed when they hear the scale of it. In the Western world today one in six of all adults suffers from depression or a crippling anxiety disorder. Roughly a third of households currently include someone who is mentally ill.

I don't know the exact figure, but I agree with the statement.

Mental illness is not just a problem for those it affects directly. It also imposes huge costs on the rest of society. So the case for tackling the problem is not just humanitarian—it is also a matter of plain economics. Mental health problems diminish work, increase crime, and make additional demands on physical health care.

So, what is the cost? The answer is huge. Layard and Clark provide some figures. And in the second part of the book, they review the alternative approaches to the issue. A highly recommended book by one of the greatest economists of our time.

PS Great Tribute to Uwe Reinhardt in NYT by Paul Krugman.

Medicine as a data science (2)

The Evolution of Patient Diagnosis: From Art to Digital Data-Driven Science

Currently medical diagnosis is driven by a standard way to proceed. We could say that the pattern of the decision flow has not changed for years.

A physician takes a history, performs an examination, and matches each patient to the traditional taxonomy of medical conditions. Symptoms, signs, family history, and laboratory reports are interpreted in light of clinical experience and scholarly interpretation of the medical literature.

Data availability, and specifically genetic data could change completely diagnostic process.

Initiatives to develop genetic reference data at the population level could be grouped into 3 categories.First are well-known databases of genotype-phenotype relationships
as observed and submitted by researchers (eg, Online Mendelian Inheritance in Man, ClinVar, and the National Human Genome Research Institute’s Genome-Wide Association Study [GWAS] Catalog). Second are databases, such as the Genome Aggregation Database (gnomAD), the next iteration of the ExomeAggregation Consortium (ExAC) database, and the 1000 Genomes Project, that aggregate sequences
collected from other studies for secondary use. Third, patients and other study participants are invited to donate data to registries like GenomeConnect or enroll
in cohorts like the National Institutes of Health All of Us initiative, which is recruiting 1 million patients to contribute biological samples and EHR data for research.

The reference to these databases is crucial to understand what's going on in US medicine, and how european medicine stands behind.
JAMA article develops the concept of Clinical Information Commons:

There should be a new compact between patients and the health system, such that captured data and biospecimen by- products of the care deliverysystem should be aggregated and linked to build a clinical information commons (CIC) to aid diagnosis

I agree. Saluscoop started as an alternative focused in this approach. As usual, the big question is: who is going to invest in a digital commons?. Unless governments take this initiative as a whole, the future of a data driven medicine is uncertain.

Adrian Piper: A Synthesis of Intuitions, 1965–2016

MoMA, New York, New York

Sat 31 Mar 2018 to Sun 22 Jul 2018

Equity and QALYs, terra ignota

Incorporating equity in economic evaluations: a multi-attribute equity state approach

Ptolemy used the term terra ignota for regions that have not been mapped or documented. QALYs were born for maximizing health, without any distributive considerations. All the efforts to introduce equity in QALYs have failed up to now. The cartography of QALYs has a pending dimension.
Maybe this dimension is not possible to be defined under a technical perspective, its a societal and policy issue. And at this level decisions are difficult to take.
Anyway, after reading this article you may reach a similar conclusion than mine, or otherwise you can be optimistic about it. It's up to you.

PS. Today I'll give the kenote speech at Col.legi d'Economistes de Catalunya: "La producció eficient i equitativa de salut".

Ai Weiwei

DROPPING A HAN DYNASTY URN

Man and machine, sharing the decision making effort

Big Data and Machine Learning in Health Care

From JAMA article

It is perhaps more useful to imagine an algorithm as existing along a continuum between fully human-guided vs fully machine-guided data analysis. To understand the degree to which a predictive or diagnostic algorithm can said to be an instance of machine learning requires understanding how much of its structure or parameters were predetermined by humans. The trade-off between human specification of a predictive algorithm’s properties vs learning those properties from data is what is known as the machine learning spectrum

 Higher placement on the machine learning spectrum does not imply superiority, because different tasks require different levels of human involvement. While algorithms high on the spectrum are often very flexible and can learn many tasks, they are often uninterpretable and function mostly as “black boxes.” In contrast, algorithms lower on the spectrum often produce outputs that are easier for humans to understand and interpret.

The meta-informational challenge of molecular data

The future of DNA sequencing

Where does DNA sequencing goes from here?. Nowadays, this is an appropriate question to pose.  The answer appears in an article in an interesting article in Nature.

Now, geneticists would like to have DNA sequences for everyone on Earth, and from every cell in every tissue at every developmental stage (including epigenetic modifications), in health and in disease. They would also like to get comprehensive gene-expression patterns by sequencing the complementary DNA copies of messenger RNA molecules.

In a mere 40 years, the central goal of putting molecular data about cells to practical use has changed from an informational challenge to a meta-informational one. Take clinical applications of genome-sequence data. It may soon be possible to use DNA sequencing routinely to analyse body fluids obtained for any clinical purpose. But only a vast amount of well-organized data about the multi-year medical histories of millions of people will provide the meta-information needed to establish when to ignore such data and when to act on them.

The uncertain cost of clinical trials

How much do clinical trials cost?

A research on seven top pharmaceutical companies has provided fresh data about costs of clinical trials:

For the trials in the data set, the median cost of conducting a study from protocol approval to final clinical trial report was US$3.4 million for phase I trials involving patients, $8.6 million for phase II trials and $21.4 million for phase III trials.

If you compare these data with the total drug costs (2.6 billion), you may ask yourself how all these costs are estimated. Maybe all this information is wrong and useless.

PS. Waiting for the new book on Theranos scandal

Pharma sales 2017

Kupka au Grand Palais

Why is it so difficult to implement policies?

Governance and the Law

If you want to know an updated approach to policy reforms, then you have to read the World Development Report 2017
The main messages:

• Successful reforms are not just about “best practice.” To be effective, policies must guarantee credible commitment, support coordination, and promote cooperation.
• Power asymmetries can undermine policy effectiveness. The unequal distribution of power in the policy arena can lead to exclusion, capture, and clientelism.
• Change is possible. Elites, citizens, and international actors can promote change by shifting incentives, reshaping preferences and beliefs, and enhancing the contestability of the decision making process.
• Three guiding principles for rethinking governance for development are:
• Think not only about the form of institutions, but also about their functions.
• Think not only about capacity building, but also about power asymmetries.
• Think not only about the rule of law, but also about the role of law

You'll understand that the key element of any reform goes beyond evidence on what works and consensus. It should be clearly designed following specific steps. I suggest you have a look at it.

El gran Guillem Roma amb Alessio Arena

Integrating genome and epigenome studies

The Key Role of Epigenetics in Human Disease Prevention and Mitigation

I've said it many times: beware of snake-oil sellers. Nowadays you may find it everywhere, specially on internet. You may get a genetic test for a disease that creates a false illusion of safety, or another that provides an unnecessary and avoidable concern. Only evidence based prescribed tests can be considered appropriate.
Therefore, if you want to confirm that genome is not enough, you have to check the review at NEJM on epigenetics. At the end of the article you'll find the explanation on why we do need integrated genome and epigenome association studies. You'll understand that cancer is fundamentally an epigenetic disease.
The current knowledge is changing quickly some conventional truths and "known unknowns" that we've had for years. This is good news for citizens, and bad news for snake-oil sellers if detected. Governments should help citizens on this screening effort, and protect citizens from fake medical information.

Practice makes perfect (2)

The Volume–Outcome Relationship Revisited: Practice Indeed Makes Perfect

Why is it so difficult to accept it? There is wide "evidence for the practice-makes-perfect hypothesis by showing that volume is a driving factor for quality". Unfortunately, the opportunities for the health system are still larger than it should be. There is a resistance in organizations, there is inertia, and all these drivers play a role. In planned health systems, there is no reason to be strict on it.
Just for those that are dubious, I would suggest a look at this article and to my former post.

Parov Stelar

The smart money in tech would not have made this mistake

It's about Theranos. You may find my previous posts in this link. Now SEC has confirmed that was a "massive fraud". That's it. If you want a good analysis check FT.
Microfluidics is not an easy prêt-à-porter technology. Many people knew it but Mrs Holmes has been selling it as snake-oil. And as usual in these cases, the end of the film is already written. She can't go to the lab for the next 10 years, a fine, and the company may be closed. All started with and article by Mathew Herper in WSJ. An innocent article with an innocent question that she couldn't answer. That's all. Silicon valley smart money would not have made this mistake.

Modigliani exhibition in Tate Gallery now

The miracle of bread and fish

According to the Gospels, a large crowd had gathered and was following Jesus. Jesus called his disciples to him and said:

"I have compassion for these people; they have already been with me three days and have nothing to eat. I do not want to send them away hungry, or they may collapse on the way."

His disciples answered:

"Where could we get enough bread in this remote place to feed such a crowd?"
"How many loaves do you have?" Jesus asked.
"Seven," they replied, "and a few small fish."
"Jesus told the crowd to sit down on the ground. Then he took the seven loaves and the fish, and when he had given thanks, he broke them and gave them to the disciples, and they in turn to the people. They all ate and were satisfied. Afterward the disciples picked up seven basketfuls of broken pieces that were left over. The number of those who ate was four thousand men, besides women and children. After Jesus had sent the crowd away, he got into the boat and went to the vicinity of Magadan (or Magdala)."

Now let's imagine one country and his health expenditure in 2007 and 2017, let's think about a figure, let's say 1,186€. This was the per capita expenditure in 2017. What was the per capita expenditure one decade earlier? 1€ less!!! It was 1,185€. This is a miracle, if you take inflation into account the reduction of expenditure is huge. Technology and ageing were not the drivers of expenditure growth because there was no growth!
Between 2017 and 2016 the growth was 5.9% in public expenditure. In private health insurance  expenditure it was 5,4%. That's it.
If you have to think about health expenditure miracles, have a look at Catalonia, it's incredible.
And it is so incredible that today our government is in exile, or in prison, or bail pending trial. Today the spanish police has entered in our government palace and has arrested one high official.
This is the rogue state where the majority wants to leave, and unfortunately we are alone, prosecuted and it's not possible to decide the new president. Europe forgets the attack on civil liberties. Shame.

Now

Allocating expenditures to diseases

Guidelines for Measuring Disease Episodes: An Analysis of the Effects on the Components of Expenditure Growth

One of the most interesting reports by OECD was produced 15 years ago. The title was "A Disease-based Comparison of Health Systems What is Best and at what Cost?". The approach was clear, in order to compare health systems we do need to focus on specific diseases and its costs and outcomes.
Now you can read in Health Services Research an interesting article that shows what and how you should do to measure episodes. The comparison between person based and episode based approach is useful and it depends on the goals of research. For insurers and health population managers: episode-based. For officials and statistical offices: person-based
All the stuff on decomposition of health expenditures should be readjusted after reading this article. A hard work forward.

PS. OECD made an update on 2013. Good news.

The rethorical work of modern medicine

Bodies in Flux; Scientific Methods for Negotiating Medical Uncertainty

Evidence and persuasion play a crucial role in everyday task of any physician. That is, knowing the evidence of what works, and persuading that the treatment will succeed in a specific disease.

But how are evidential worlds assembled from bodies in perpetual flux? From where does medicine’s evidential weight hail? What protocols and procedures elevate everyday
biological activities to positions of argumentative authority?

 Defining and diagnosing disease is a kind of quixotic empiricism. It requires taking what’s known now and making best guesses about what’s to come. Yet, as physicist and philosopher David Bohm (1981) argues, “all is flux”

 After nearly a decade of studying evidential construction in the biomedical backstage, I have identified four specific methods with which medical professionals attune to corporeal flux in cancer care: evidential visualization, assessment, synthesis, and computation.

These are the approaches that a new book highlights in detail. In chapter 6 I suggest you read the section "Medical care as phronesis",

Phronesis is one of “the five expressions of care discussed in Book VI of the Ethics” and is a “mode that deals with the contingent and the possible”. Typically, phronesis (defined by Aristotle in the Nicomachean Ethics as “prudence”) is set counter to another rhetorical construct, metis.

A book highly recommended for those that want a fresh perspective on evidence based medicine and rethorics.

Medicine trends

The future of medicine

A new supplement in Nature explains the main trends in Medicine. It is really helpful to have a quick look focused on those approaches that are the more promising for the next future. From the issue, I would pick one article: A CRISPR edit for heart disease, A one-off injection to reduce the risk of cardiovascular disease is now a prospect thanks to advances in gene editing.This is amazing, it changes current perspectives on the first cause of death worldwide (18 million people per year).

 In 2014, Musunuru and his team showed that more than half of Pcsk9 genes in the mouse liver could be silenced with a single injection of an adenovirus containing a CRISPR–Cas9 system directed against Pcsk9. This led to a roughly 90% decrease in the level of Pcsk9 in the blood and a 35–40% fall in blood LDL cholesterol⁴. Next, they used a mouse engineered to contain human liver cells, and tuned the CRISPR–Cas9 payload to target human PCSK9⁵. The team succeeded in showing that the human gene can also be switched off.

This is changing the focus of drug research, and a recent article explains the new approach.  Let's see if finally delivers what they say.

Setting priorities explicitly (or not)

PRIORITISING HEALTH SERVICES OR MUDDLING THROUGH

A chapter of this book explains who does what in prioritisation (resource allocation and rationing).
I've found of interest this classification of rationing:

• Rationing by denial. Exclusion of specific services or treatments from the National Health System portfolio (often explicitly) or from one healthcare provider (near always implicitly) that believes that such treatment or service is inappropriate.
• Rationing by selection. Exclusion of some patients of some treatments because they do not meet certain eligibility criteria fixed by the regulator (often explicitly) or the provider (near always implicitly). 
• Rationing by delay. The demand that cannot be met by a rigid offer remains on hold (waiting list) and the wait acts as a barrier to access and, in many cases, as a de facto denial of care. 
• Rationing by deterrence. Barriers placed, either consciously or unconsciously, by the healthcare providers that make it difficult for patients to find out about, and book appointments with, some healthcare services. 
• Rationing by deflection. Patients being shunted off to another institution, agency or programme. 
• Rationing by dilution. Services continue being offered to patients, but with fewer resources, and the quality of care gets worse

 And the summary:

In conclusion, adequate priority setting is not about choosing either to muddle through implicit rationing or to be corseted by an exhaustive, rigid and explicit interventionist structure at the macro, meso and micro decision-making levels. This dichotomy fails to capture the complexity of priority setting in practice. We need more and better explicit priority setting, not to substitute but to improve implicit priority setting.

 

 Weegee by Weegee

In vitro, veritas

El Diagnóstico In Vitro Hoy. Un cambio de paradigma en la calidad de vida y en el proceso de atención a los pacientes

A new report highlights the role of clinical laboratory in medical decision making. Though its increasing complexity, it requires larger recognition in terms of the value that creates. Some selected statements:

Desde el punto de vista de los costes, el IVD es económicamente muy accesible, tanto por su competitividad en costes de producción como por no necesitar de grandes inversiones iniciales en equipamiento: – El IVD consume una proporción de recursos de los hospitales muy baja, inferior en todos los estudios al 4% del coste hospitalario y supone en promedio un 0,8% del total del gasto sanitario4. – La mayoría de equipamientos se ceden mediante la contratación de los reactivos, lo que elimina la barrera de inversión inicial para su adquisición 

El Diagnóstico In Vitro es sin duda el proceso diagnóstico más utilizado con carácter habitual. A diferencia de otros grandes equipamientos diagnósticos que se utilizan muy selectivamente, el IVD se utiliza masivamente para la gran mayoría de pacientes y en la mayoría de los actos asistenciales.

Paradójicamente, y a diferencia de otros equipamientos, el IVD es cada vez más complejo tecnológicamente, pero también más simple en su utilización. La innovadora y alta tecnología incorporada internamente contrasta con la apariencia de simplicidad. – Si se compara con otros equipamientos médicos de alta tecnología, como los de diagnóstico por la imagen o de cirugía robótica, los equipamientos de IVD, cada vez más pequeños, automatizados y fáciles de utilizar, tienen una visibilidad más bien escasa.

I suggest a close look.

 Yesterday Impressionist Art Auction at Christie's

Resource allocation principles and process

Public Preferences About Fairness and the Ethics of Allocating Scarce Medical Interventions

Fair allocation of health care resources is a challenge that we can't solve strictly with some criteria or principles. Of course, we do need some benchmark but we require a fair and transparent process. This is precisely the focus of a chapter by Govind Persad in a recent book. The key issue is how in fact resources should be allocated.

Society is ultimately interested not only in empirical surveys of how its members believe medical interventions should be allocated, but also in answers to the normative question of how medical resources should be allocated.

Survey methods, experts opinion,...

Even though public attitudes do not directly determine the solution to moral problems, empirical research into public attitudes can be useful in a variety of  ways. By showing which beliefs are popular among the public, or which beliefs are points of division, empirical research can help to focus moral inquiry on those claims or beliefs, thereby ensuring that philosophical reasoning is relevant to real-world problems. Furthermore, even though popularity does not constitute correctness, the unpopularity of a normative position can justify placing it under scrutiny.

Pharma R&D failure and success

Clinical Development Success Rates 2006-2015

In the russian rulette as a lethal game of chance you may have 1/6 chance of being shot. If the chamber of the revolver holds 6, a 16,6%.
In drug industry the probability of R&D failure is 90.4%. We all know that in the drug cost we are paying also for failures, but we forget the figure.

These are the key takeaways of the report:

• The overall likelihood of approval (LOA) from Phase I for all developmental candidates was 9.6%, and 11.9% for all indications outside of Oncology.
• Rare disease programs and programs that utilized selection biomarkers had higher success rates at each phase of development vs. the overall dataset.
• Chronic diseases with high populations had lower LOA from Phase I vs. the overall dataset.
• Of the 14 major disease areas, Hematology had the highest LOA from Phase I (26.1%) and Oncology had the lowest (5.1%).Sub-indication analysis within Oncology revealed hematological cancers had 2x higher LOA from Phase I than solid tumors.
• Oncology drugs had a 2x higher rate of first cycle approval than Psychiatric drugs, which had the lowest percent of first-cycle review approvals. Oncology drugs were also approved the fastest of all 14 disease areas.
• Phase II clinical programs continue to experience the lowest success rate of the four development phases, with only 30.7% of developmental candidates advancing to Phase III.

PS. The growth in R&D expenses was 14% in 2016, while revenues grew 4% (p.36).

Public funding of succesful Pharma R&D

Contribution of NIH funding to new drug approvals 2010–2016

If we consider the 210 new molecular entities (NMEs) approved by the Food and Drug Administration from 2010–2016, then you'll find that NIH funding contributed to published research associated with every one. A PNAS article explains that:

Collectively, this research involved 200,000 years of grant funding totaling more than $100 billion. The analysis shows that 90% of this funding represents basic research related to the biological targets for drug action rather than the drugs themselves. The role of NIH funding thus complements industry research and development, which focuses predominantly on applied research. This work underscores the breath and significance
of public investment in the development of new therapeutics and the risk that reduced research funding would slow the pipeline for treating morbid disease.

This public funding is forgotten in the costs of a new molecule. Although in the price, the manufacturer surplus doesn't remunerate such contribution. Some adjustment should be applied, to be fair.

 Brassai at Mapfre Foundation in Barcelona

Digital medicine, or just medicine

Digital medicine, on its way to being just plain medicine

You may remember at the begining of this century. Everybody was talking about e-business and right now nobody talks about it, because it is just business.The same will happen with digital medicine, it ill be just medicine in the next future. A future that is closer than you may think. And this is what E. topol explains in the editorial of the new open journal, and says_

And finally, quite paradoxically, we hope that npj Digital Medicine is so successful that in the coming years there will no longer be a need for this journal, or any journal specifically focused on digital medicine.

I agree. But meanwhile, somebody should review current syllabus and studies of medicine, to introduce a change in the profession and the scope of practice.

Spending a lot for many years: understanding persistence

Long-Term Health Spending Persistence among the Privately Insured in the US

If you don't want to read this article, check this presentation. It is one of the best efforts to understand persistence of health expenditures. Summarised findings:

First, persistence by demographic characteristics is generally lower than persistence by co-morbidities. Because co-morbidities are harder to assess, particularly for new enrollees, than demographics, this highlights the need for robust risk prediction models. 

Second, people with a co-morbid condition relative to those without the condition are considerably more likely to be in the top 10 per cent of spenders in year t regardless of whether they were in the top 10 per cent in year t–1. However, people with a co-morbid condition are even more likely to be in the top 10 per cent in year t if they were also in the top 10 per cent in year t–1.

Third, those most likely to be in and remain in the top 10 per cent are those with myocardial infarction, congestive heart failure and peptic ulcer disease and in several psychiatric diagnostic groupings, which indicates that these conditions might be appropriate targets for longer-term disease management programmes.

Fourth, although most conditions are less common at younger ages, when they do occur they are more predictive ofpersistently high spending at younger ages, as almost all conditions have the highest predicted probabilities on being in the top 10 per cent of spenders in the following year when they occur at ages under 25 and the lowest predicted probabilities when they occur in the 65-and-over population. Essentially, the presence of a condition at a younger age more clearly differentiates a person’s health care trajectory from that of their peers.

These are conclusions for US population, closer studies are needed.
PS. An article written 23 years ago, on concentration and an abstract 11 years ago.

How morbidity explains health expenditures in ageing

Ageing and healthcare expenditures: Exploring the role of individual health status

Everybody admits that ageing increases health expenditures. However the dynamics of this growth, and the factors that contribute it, are less known. In our recent article, we explain why morbidity is the main factor that explains growth of health expenditures in ageing. In our analysis, closeness to death is not the main cause.

Regardless of the specific group of healthcare services, HCE at the end of life depends mainly on the individual health status. Proximity to death, sex, and marginally age approximate individual morbidity when it is excluded from the model. The inclusion of morbidity generally improves the goodness of fit. These results provide implications for the analysis of ageing population and its impact on HCE that should be taken into account.

We do need further research on the cost and intensity of care in the last months of life, and this is our next challenge.

Diversity and differences in nature and society

Inequality in nature and society

If the title of an article is about "inequality", our brain starts thinking inmediately about equality, with some moral background. It's unavoidable. If the title is "diversity and differences", than we admit it as statement. I would suggest to have a look at this interesting article in PNAS that compares what happens in society and in nature, please forget any previous influence of values.

As a first illustration of the similarities of patterns in nature and society, consider the wealth distribution of the world’s richest individuals compared with the abundance distribution of the Amazon’s most common trees (Fig. 1 A and B). The patterns are almost indistinguishable from one another. For a more systematic comparison, we also analyzed the Gini indices of a wide range of natural communities and societies (Fig. 1 C and D). The Gini index is an indicator of inequality that ranges from 0 for entirely equal distributions to 1 for the most unequal situation. It is a more integrative indicator of inequality than the fraction that represents 50%, but the two are closely related in practice (SI Appendix, section 3). Surprisingly, Gini indices for our natural communities
are quite similar to the Gini indices for wealth distributions of 181 countries (data sources listed in SI Appendix, section 1).

This is only a statement that you can confirm.

 Our analysis suggests that even if all actors are equivalent, in the absence of counteracting forces, there is an intrinsic tendency for significant inequality to arise from multiplicative chance effects. Although the surprising similarity between inequality of species abundances and wealth may have the same roots on an abstract level, this does not imply that wealth inequality is “natural.” Indeed, in nature, the amount of resources held by individuals (e.g., territory size) is typically quite equal within a species.

Now the metaphor has been clarified. Differences in wealth does not imply that are "natural". Fortunately our country is less different now than before. We have moved from a Gini of 33 in 2013 to 31.4 in 2016, quite good. You'll not find this reflected in any newspaper -it seems that this statement does not sells issues-, though these are the official figures.

Estimating health expenditures

Modeling Health Care Expenditures and Use

The skewed distribuition of health expenditures with a large number of 0 observations poses difficulties. A recent article in Annual Review of Public Health explains the details and the right approach, in my opinion.

We compare estimation and interpretation of the effect of a change in insurance policy on health care expenditures using OLS and a two-part model. The two-part model is based on a statistical decomposition of the density of the outcome into a process that generates zeros and a process that generates positive values. A logit or probit model typically estimates the parameters that determine the threshold between zero and nonzero values of the outcome. In general, alternative specifications of the binary choice model (the first part) yield nearly identical results. However, the choice of model for the distribution of the outcome conditional on it being positive (the second part) is critically important. Different models can yield quite different results.We use a generalized
linear model to estimate the parameters that determine positive values. Generalized linear models accommodate skewness in natural ways, give the researcher considerable modeling flexibility, and fit health care expenditures extremely well.

The use of two parts models, and GLM is the standard approach to take into account. The book Health econometrics using Stata is the key reference.

On experts and priorities

Priorización de intervenciones sanitarias. Revisión de criterios, enfoques y rol de las agencias de evaluación

Often I hear that prioritisation of benefits could be solved by evaluation agencies and the appropriate application of cost-effectiveness analysis. As times goes by, I'm convinced that this is a way to avoid if we consider how priorities should be set. In other words, leaving this issue to a technical perspective is not enough. There is a need for a deliberative way to tackle the complexities of prioritisation.
Anyway, if you want to know a review that takes as given the experts view, check this article. If you want to understand the whole issue from a broader perspective, then read the book I quoted in this post some months ago.

 Carlos Diaz at Sala Parés