To test or not to test (for coronavirus)

A Framework for Comprehensive Assessment of the Value of Diagnostic Test

The Value of Diagnostic Information A comprehensive concept of “Value” for diagnostics

A framework to understand value of lab tests is the following one:

Key principles:

• Apply broad array of patient centric value drivers from various perspectives (Comprehensiveness principle)
• Utilize appropriate range of available evidence, reflecting test type and potential risks-benefits (Evidentiary principle)
• Consider reporting direct and indirect costs incurred and avoided over timeframe appropriate for the test (Cost principle)
• Account for immediate and longer-term test impact and patient benefits in representative patient populations (Specificity principle)
• Include quantified estimates as well as qualitative analyses as appropriate (Flexibility principle)
• Incorporate multiple stakeholders’ perspectives (Engagement principle)
• Disclose why the assessment was initiated, who was involved, its purpose, and the decision-making process (Transparency principle)
• Update assessments regularly to keep up with the rapid technological and clinical changes (Relevancy principles)

 Value drivers can come from four major sources:

• Clinical impact: clinical utility and health outcomes associated with the diagnostic technology. The test needs to measure accurately and reliably the analyte/biomarker of interest (analytical validity); detect, predict the outcomes of interest in a patient population (clinical validity) and inform an appropriate clinical decision (clinical utility). Improved patient safety, tolerability, compliance and physical and psychological wellbeing shall be also taken into account.
• Non clinical patient impact breaks down to patient experience, and patient economics, such as proximity of test delivery, reduced follow-up visits, repeat procedures, improved care plan compliance and reduced burden on care givers.
• Care delivery revenue, and cost impact mostly refer to quality of care metrics and more efficient resource utilization (e.g. readmissions; follow-ups, length of stay, wait times)
• Public and population impact refer to macro implications mainly from population health, burden of disease, patient and caregiver productivity perspectives

AdvaMedDx’s Approach for Effective Value Assessment

Source: A Framework for Comprehensive Assessment of the Value of Diagnostic Tests, AdvaMed, 2017

And clinical impact depends on analytical validity, clinical validity, clinical utility, patient safety and patient response. If you have only one strategy for all the patients, like social distancing in the case of coronavirus, then the information post-test will not change the therapeutic strategy. If the test tries to prevent contagion when social distancing can't be applied (health professionals, politicians, journalists, executives, essential services), than you have to test them if there are symptoms. If the test will add information to existing comorbidities to differentiate from other symptoms, then it makes sense. Therefore, this is the current situation in my country. Test, test, test when it adds value.

Climate change and health

Enviromedics: The Impact of Climate Change on Human Health

These are tough times for the relationship between mankind and the planet. Therefore, this is a good reason to know better the relationship between climate change and health. In this book you'll find the details on each topic.
These are the key issues:

Part I. Climate Change Cascade
2 Climate Change 101: A Primer
3 Heat Waves and Heat Stress
4 Extreme Weather
5 Vector-Borne Diseases
6 Mental Health
Part II. Clear and Present Pathogens
7 Air Degradation
8 Water Security
9 Food Security
10 Allergens
11 Harmful Algal Blooms 

 Many of these modern sources of environmental hazards share a common feature—they derive from human activity as much as or more than from nonhuman sources. Radiation exists in nature, but its concentrated forms on Earth are created by humans. Industries produce the goods that support modern life, while they spin off by-products that can harm the environment and humans. We celebrate the productivity of modern agriculture, but if the runoff of pesticides and antibiotics pollutes the water supply and encourages antimicrobial resistance, we pay a higher price than we realize for food.

Balancing this tradeoff is complicated by the fact that the individuals and interests who typically stand to benefit from a polluting activity are not the same as the ones who will suffer the adverse health and other consequences.

Global externalities and how to fix them. This is one of the greatest challenges nowadays.

A controversial view on confidence with medicine

Medical Nihilism

On Therapeutical  Nihilism and effectiveness (Ch. 11), a philosophical view:

The confidence that a medical intervention is effective ought to be low, even when presented with evidence for that intervention’s effectiveness. How low? I do not think that there can be a precise or general answer. It is enough to say: lower, often much lower, than our confidence on average now appears to be. There is surprisingly little direct study of the confidence that physicians or patients or policy-makers have regarding the effectiveness of medical interventions. However, the confidence typically
placed in medical interventions can be gauged by the resources dedicated to developing, marketing, and consuming such interventions.

What explains the disparity between the confidence placed in medical interventions and the lower confidence that I have argued we ought to have? The ingenious techniques that companies use to market their products—paying celebrities to publicly praise their products, funding consumer advocacy groups, sponsoring medical conferences,  influencing medical education, direct-to-consumer advertising—have been extensively discussed by others. The promise of scientific breakthroughs partly explains this disparity—scientists seeking support for their research programs, and companies building hype for their products, often make bold predictions about the promise of the experimental interventions they are researching, and this can sound convincing when it is put in the language of genomics, proteomics, precision medicine, personalized medicine, and evidence-based medicine. Unwarranted optimism may be based in part on a history of a few successful magic bullets, such as penicillin and insulin—magic bullet thinking gets inappropriately adopted in premature proclamations of game-changing medical interventions, which media outlets promulgate.

Medical nihilism is not the thesis that there are no effective medical interventions. Please do not confuse this. Medical nihilism is, rather, the thesis that there are fewer effective medical interventions than most people assume and that our confidence in medical interventions ought to be low, or at least much lower than is now the case.

As I said, an unconventional and controversial view. We do need measures to assess facts and knowledge, philosophy is not enough. Anyway, I recommend its reading.

Are Pharmaceutical Companies Earning Too Much?

Are Pharmaceutical Companies Earning Too Much?

Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018

The debate about pharmaceutical companies earnings is a never ending story. Now you can find in JAMA an article that reflects the cost of a new drug: $1336 million. This is the summary:

The FDA approved 355 new drugs and biologics over the study period. Research and development expenditures were available for 63 (18%) products, developed by 47 different companies. After accounting for the costs of failed trials, the median capitalized research and development investment to bring a new drug to market was estimated at $985.3 million (95% CI, $683.6 million-$1228.9 million), and the mean investment was estimated at $1335.9 million (95% CI, $1042.5 million-$1637.5 million) in the base case analysis. Median estimates by therapeutic area (for areas with ≥5 drugs) ranged from $765.9 million (95% CI, $323.0 million-$1473.5 million) for nervous system agents to $2771.6 million (95% CI, $2051.8 million-$5366.2 million) for antineoplastic and immunomodulating agents.

Why this new figure is relevant? Because previous estimates said that it was the more than the double!

The mean estimate of $1.3 billion in the present study was lower than the $2.8 billion (in 2018 US dollars) reported by DiMasi et al,

And   my impression is that we have entered in a difficult world to estimate the real cost. Right now many firms are buying research (buying firms that have already a product close to be commercialised) and they are paying a premium for outsourcing research. Therefore, how to estimate the cost in this situations? Uncertain.

David Cutler asks about the earnings of pharma firms and says:

Ledley showed that from 2000 to 2018, the median net income margin in the pharmaceutical industry was 13.8% annually, compared with 7.7% in the S&P 500  sample. This difference was statistically significant, even with controls, although earnings seemed to be declining over time.

Is this positive return differential evidence of too high a return? Not necessarily. The economics of pharmaceuticals are important to consider. Like several other industries (eg, software and motion picture production), the pharmaceutical industry has very high fixed cost and very low marginal cost. It takes substantial investment to discover a drug or develop a complex computer code, but the cost of producing an extra pill or allowing an extra download is minimal. The way that firms recoup these fixed costs is by charging above cost for the product once it is made. If these upfront costs are not accounted for, the return on the marketed good will look very high.

 Paying more than a drug is worth clinically is not a good strategy. Even if a drug is worth a high price socially, pricing patients who need the drug out of the market is a real loss, even if it leads to more innovation in the future. In still another case, price increases for older, generic drugs serve no innovation purpose. But, as a general rule, it is important to be wary of blunt “lower all drug prices” policies.

Cutler doesn't say too much on price according value and about public funding of research. It leaves the initial question open and waiting for adhoc answers. That's it , it's a complicated issue, no general prescriptions, they need to be adjusted to specific conditions without a captured regulator. This last point is the most difficult one to overcome.

Prix Pictet

How to stop ineffective and harmful medical practices

Ending Medical Reversal: Improving Outcomes, Saving Lives

What are medical reversals? We expect that medicine will progress in a generally orderly fashion, with good medical practices being replaced by better ones. We used to use cholestyramine—a horribly tolerated drug that had no effect on patients’ life expectancy—to lower cholesterol after heart attacks. Now we use atorvastatin, a well-tolerated drug backed by robust evidence that it saves lives. This is how medical practice should evolve. Reversal, however, is different. Reversal occurs when a currently accepted therapy is overturned, found to be no better than the therapy it replaced. This often occurs when a practice—a diagnostic tool, a medicine, a procedure, or a surgical technique—is adopted without a robust evidence base.

 Instead of the ideal, which is replacement of good medical practices by better ones, medical reversal occurs when a currently accepted therapy is overturned—found to be no better than the therapy it replaced. Now, you might argue that this is how science is supposed to proceed. In high school, we learned that the scientific method involves proposing a hypothesis and testing to see whether it is right. This is true. But what has happened in medicine is that the hypothesized treatment is often instituted in millions of people, and billions of dollars are spent, before adequate research is done. Not surprisingly, sometimes the research demonstrates that the hypothesis was incorrect and that the treatment, which is already being used, is ineffective or harmful.

So what?

Our medical system is too tolerant of unproven practices. Doctors are too comfortable recommending a practice without real knowledge of whether it is helping or hurting patients. People are too willing to accept practices that seem like they should help. When a medical reversal does occur, most physicians consider it an exception to the rule. 

We need a culture change in medicine. We need to recommit to evidence-based medicine and realize that it is the only rational way to provide care. In this book we have provided a few suggestions for ways we can improve. We do not advocate that these recommendations be immediately implemented but that they be carefully considered, alongside recommendations proposed by other thoughtful analysts, and tested in prospective trials. As we move forward, we must recognize that drastic and dramatic change can often be harmful. We acknowledge that there will be areas of medicine in which, for now, we must tolerate the status quo. As we go through the house of medicine and clean up each room, we have to prioritize.  

Well, let's say that the book focuses on the shadows of medicine, but this is only one part. Generalisations are inacurate. Anyway, good to review it. And medical education is not enough to solve the issue, incentives and culture play a crucial role.

The opportunity costs of excessive medical practice variations

 Atlas de utilización de procedimientos de dudoso valor. Actualización datos 2017

From the new report on practice variations:

La literatura científica abunda en estimaciones de la proporción de asistencia sanitaria cuyo valor para el paciente es cuando menos escaso. Este cuerpo de evidencia no ha hecho sino crecer en la última década, dando origen a varias iniciativas tanto académicas como gubernamentales para identificar y abordar lo que se considera uno de los principales problemas de los sistemas sanitarios modernos. Hay consenso: se trata de un fenómeno altamente prevalente que pone en cuestión el buen uso de los recursos sanitarios.
La actividad sanitaria de dudoso valor incluye tanto la utilización de procedimientos escasamente efectivos o para los que existen alternativas superiores, como el uso de intervenciones efectivas en indicaciones en las que los beneficios para el paciente son prácticamente nulos y en ocasiones incluso generan efectos negativos. Obviamente, para el sistema sanitario y la sociedad que destina los recursos necesarios, el coste oportunidad derivado de este tipo de actividad es sustancial.

So many years talking about it and nothing happens...

Great report, something should be done.
 Angulo-Pueyo E, Seral-Rodríguez M, Ridao-Lopez M, Estupiñán-Romero F, Martínez-Lizaga N, Comendeiro-Maaloe M, Ibañez-Beroiz B, Librero-López J, Millán-Ortuondo E, Peiró-Moreno S, Bernal-Delgado E, por el grupo Atlas VPM. Atlas de variaciones en la práctica médica en utilización de procedimientos de dudoso valor en el Sistema Nacional de Salud, 2017. Marzo 2020; Disponible en: www.atlasvpm.org/atlas/desinversion-2017

PS. Some books I'm waiting for.

Key Indicators for Health

Leading Health Indicators 2030: Advancing Health, Equity, and Well-Being