La gestió de la innovació a les ciències de la vida

Managing Discovery in the Life Sciences

Aquest llibre explora els factors clau que impulsen la invenció en les ciències biomèdiques, centrant-se en com els descobriments es transformen en productes comercialitzables.

El llibre s'estructura al voltant de tres preguntes fonamentals: Quins incentius o recompenses van impulsar el descobriment? D'on provenien els recursos per a la investigació i el descobridor? Com es va traduir el descobriment en un producte comercialitzable? 

El llibre analitza diversos casos d'estudi que mostren els diversos camins i graus d'èxit en el procés de descobriment i comercialització. 

S'hi inclouen exemples com els estatines (inhibidors de la síntesi del colesterol), els inhibidors de l'ECA (utilitzats per tractar la hipertensió), l'angioplàstia (un procediment per obrir artèries bloquejades), el tractament de l'hepatitis C, la recerca de tractaments per a la malaltia d'Alzheimer [2] i la història de la metformina (un medicament per a la diabetis).

El llibre també examina la importància de l'estructura organitzativa per fomentar descobriments comercialitzables. Analitza com els incentius, l'assignació de recursos i la creació de cultures innovadores influeixen en la productivitat i la creativitat en la recerca. 

Finalment, el llibre es pregunta si les polítiques públiques podrien millorar el procés de gestió dels descobriments biomèdics per beneficiar la societat. 

A més a més, el llibre busca desmentir les crítiques infundades dirigides a la indústria biomèdica, especialment a la indústria farmacèutica, posant de manifest els beneficis que ha aportat a la societat a través dels seus descobriments i medicaments. 

El llibre conclou amb una crida a la reflexió sobre com podem augmentar el flux de nous productes sense incrementar els costos de R+D. S'interroga sobre la millor manera d'assignar els fons de recerca bàsica i de traduir els descobriments en productes comercialitzables de forma més ràpida i econòmica.

La teranyina que sosté la financialització dels medicaments, la salut i la vida

 Capitalizing a Cure. How Finance Controls the Price and Value of Medicines

Acabo de llegir un llibre d'accés obert com fa temps que no en trobava cap d'igual. Es tracta d'un treball molt detallat de com el sofosbuvir va sorgir i es va introduir al mercat per capgirar l'Hepatitis C. És un esforç que en Victor Roy, metge i sociòleg, ha estat fent durant molts anys amb un resultat impecable. Va de la financialització dels medicaments, la salut i la vida. Esdevé una peça clau per entendre el que està passant amb el preu dels medicaments i els seus motius. Ho explica amb tot detall i bàsicament el missatge és: si no fem res, això anirà a més. És a dir a preus estratofèrics que uns diuen que es relacionen amb el valor (els mateixos que posen el preu) i uns altres que arribats a un cert punt ja no podem entendre res.

Sobre la qüestió de que els preus són alts per recuperar la inversió en R+D, cal explicar dues coses. En el cas del sofosbuvir la contribució a la recerca finançada públicament va ser determinant. Aquí hi ha un resum:

I la segona. Sobre si l'empresa comercialitzadora va fer Recerca o Cerca, en realitat es va dedicar a cercar mol·lècules com actius financers i va deixar de banda el risc de la recerca en estadis inicials. Per tant es va substituir la R+D per la C+D.

El resum és una empresa, Pharmasset, que el seu funcionament va costar 314 milions entre 1999 i 2011:

I que havia dedicat només 62 milions a la recerca en el sofosbuvir. El 2010 ja es valorava en 5.000 milions sense tenir cap producte al mercat, ni facturació. El 2011 Pharmasset seria comprada per 11.200 milions.

El resum dels dos escenaris al moment de la compra és aquest:

I a la pregunta, què va costar la recerca del sofosbuvir? El quadre següent ho diu tot:

Va costar menys de 1.000 milions en finançament privat, el finançament públic és complex detallar-lo encara que el llibre explica les fonts, que eren nordamericanes i europees.

El sofosbuvir va suposar un canvi en molts aspectes, tant clínics com econòmics. El llibre ho explica amb molta precisió. Parla de creació de valor, però sobretot d'extracció de valor i com es produeix.

Sobre el mecanisme de preus i com es genera l'escalada de preus dels medicaments, aquest gràfic ho mostra clarament:

El preu final del sofosbuvir en el llançament va ser de 94.500$ als USA. L'any 2011 vaig escriure això: La infinita estupidesa. Aquí el vam pagar a 23.500€, i el 2015 més barat, a 7.862€. 

L'argument del llibre és que els preus que observem són fruit d'un disseny financer que estableix expectatives de preu i creixement futur, això és Wall Street i NASDAQ. El segon element que afegeix incentius desmesurats és el sistema de patents i el monopoli que atorga. Per tant la indústria farmacèutica es troba dins aquesta teranyina i la pregunta clau és com sortir-ne de tot plegat.

La resposta de Victor Roy es troba als darrers capítols on reflexiona sobre el paper públic de la investigació, com finançar públicament la recerca i llicenciar privadament la fabricació. Una qüestió sobre la que s'ha debatut molt i s'ha fet molt poc.

La meva recomanació és que ho llegiu i rellegiu amb deteniment, us ajudarà a comprendre el món complex al que ens enfrontem i que si no hi fem res, el desgavell està assegurat. I quan dic desgavell em refereixo més enllà del col·lapse econòmic a la sanitat, a l'accés inequitatiu a serveis de salut essencials i necessaris. Els incentius estan alineats per tal que es compliquin encara més les coses en el futur.

PD. Aquest és un llibre basat en fets i dades. Aquells que espereu un llibre sectari, (contra les farmacèutiques) no cal que el llegiu. No trobareu cap referència a la paraula-concepte neoliberalisme. L'aportació que fa el bengalí Victor Roy és extraordinària precisament per això, perquè evita qualsevol prejudici ideològic, una qüestió que cansa molt als nostres dies, massa.

Pharma, big pharma (17)

 Big Pharma. The Money Behind the Pills

Contents:

Chapter 1

Big Pharma’s New Deal: Acquisition and Little Innovation

Blockbuster Drugs Are So Last Century BY ALEX BERENSON

When Academia Puts Profit Ahead of Wonder BY JANET RAE-DUPREE

Grant System Leads Cancer Researchers to Play It Safe BY GINA KOLATA

Are Doctors Too Wary of Drug Companies? BY PAULINE W. CHEN, M.D.

Valeant’s History of Deal-Making BY WILLIAM ALDEN

Roche to Buy InterMune for $8.3 Billion BY ANDREW POLLACK AND MICHAEL J. DE LA MERCED

Why Are So Few Blockbuster Drugs Invented Today? BY DAN HURLEY

$2.6 Billion to Develop a Drug? New Estimate Makes Questionable Assumptions BY AARON E. CARROLL

Stop Subsidizing Big Pharma BY LLEWELLYN HINKES-JONES

Ways to Fund Research on Rare Diseases THE NEW YORK TIMES

AstraZeneca to Acquire Majority Stake in Acerta Pharma BY CHAD BRAY

Explaining Valeant: The Main Theories BY STEVEN DAVIDOFF SOLOMON

Chapter 2

Monopolies and Exclusivity Drive Price Spikes

Runaway Drug Prices BY THE NEW YORK TIMES

Costly Hepatitis C Drugs for Everyone? BY THE NEW YORK TIMES

New Cholesterol Drugs Are Vastly Overpriced, Analysis Says BY ANDREW POLLACK

Inflated Drug Prices THE NEW YORK TIMES

Drug Goes From $13.50 a Tablet to $750, Overnight BY ANDREW POLLACK

Big Price Increase for Tuberculosis Drug Is Rescinded BY ANDREW POLLACK

Valeant Under Investigation for Its Drug Pricing Practices BY ANDREW POLLACK

Senators Condemn Big Price Increases for Drugs BY ANDREW POLLACK

No Justification for High Drug Prices BY THE NEW YORK TIMES

Another Drug Pricing Ripoff BY THE NEW YORK TIMES

The EpiPen, a Case Study in Health System Dysfunction BY AARON E. CARROLL

The Complex Math Behind Spiraling Prescription Drug Prices BY KATIE THOMAS

The Lesson of EpiPens: Why Drug Prices Spike, Again and Again BY ELISABETH ROSENTHAL

Chapter 3

Disease Branding and the Profusion of Diagnoses

Ritalin Wars BY JUDITH WARNER

Disease Branding BY BEN SCHOTT

Still the ‘Age of Anxiety.’ Or Is It? BY DANIEL SMITH

Ruling Is Victory for Drug Companies in Promoting Medicine for Other Uses BY KATIE THOMAS

A.D.H.D. Seen in 11% of U.S. Children as Diagnoses Rise BY ALAN SCHWARZ AND SARAH COHEN

Is It Really A.D.H.D. or Just Immaturity? BY KJ DELL’ANTONIA

Overselling A.D.H.D.: A New Book Exposes Big Pharma’s Role BY STEVE SILBERMAN

A Profusion of Diagnoses. That’s Good and Bad. BY DHRUV KHULLAR, M.D.

Chapter 4

The Money Behind Epidemics: Preventing, Treating and Healing

For Profit, Industry Seeks Cancer Drugs BY ANDREW POLLACK

F.D.A. Advisory Panel Backs Preventive Use of H.I.V. Drug BY DENISE GRADY

Advocating Pill, U.S. Signals Shift to Prevent AIDS BY DONALD G. MCNEIL JR.

Painkillers Resist Abuse, but Experts Still Worry BY ALAN SCHWARZ

The C.E.O. of H.I.V. BY CHRISTOPHER GLAZEK

The Insanity of Taxpayer-Funded Addiction BY THE NEW YORK TIMES

F.D.A. to Expand Medication-Assisted Therapy for Opioid Addicts BY SHEILA KAPLAN

As Opioid Prescriptions Fall, Prescriptions for Drugs to Treat Addiction Rise BY ABBY GOODNOUGH

Chapter 5

The Trump Administration vs. Big Pharma

The Real Reason Medicare Is a Lousy Drug Negotiator: It Can’t Say No BY MARGOT SANGER-KATZ

The Fight Trump Faces Over Drug Prices BY KATIE THOMAS

Trump Vows to Ease Rules for Drug Makers, but Again Zeros In on Prices BY KATIE THOMAS

Drug Lobbyists’ Battle Cry Over Prices: Blame the Others BY ERIC LIPTON AND KATIE THOMAS

Draft Order on Drug Prices Proposes Easing Regulations BY SHEILA KAPLAN AND KATIE THOMAS

Lower Drug Prices: New Proposals Carry Lots of Promises BY KATIE THOMAS AND REED ABELSON

What Big Pharma Fears Most: A Trump Alliance With Democrats to Cut Drug Prices BY ROBERT PEAR

Trump Proposes to Lower Drug Prices by Basing Them on Other Countries’ Costs BY ROBERT PEAR

Value based health care (2)

 Evaluación de resultados en salud: valor y sostenibilidad para el Sistema Nacional de Salud

Capítulo I. Evaluación de resultados en términos de salud: por qué, ¿cómo, cuándo y para qué?

Capítulo II. Resultados comunicados por los clínicos

Capítulo III. Resultados percibidos por los pacientes

Capítulo IV. Resultados en salud percibidos y comunicados por los observadores: ¿qué son y cómo se miden?

Capítulo V. ¿Cómo incorporar las medidas de resultados en salud a la evaluación económica?

Capítulo VI. Principales técnicas estadísticas y parámetros para medir resultados en salud

Capítulo VII. Metodología disponible para obtener resultados en salud en el mundo real

Capítulo VIII. Resultados en salud a evaluar en diferentes patologías: enfermedades infecciosas

Capítulo IX. Resultados en salud en la infección por VIH

Capítulo X. Resultados en salud en pacientes con hepatitis C crónica

Capítulo XI. Resultados en salud en reumatología

Capítulo XII. Resultados en salud en dermatología

Capítulo XIII. Resultados en salud en aparato digestivo: enfermedad inflamatoria intestinal e intestino irritable

Capítulo XIV. Resultados en salud en esclerosis múltiple

Capítulo XV. Beneficio clínico en oncología: una compleja pregunta

Capítulo XVI. Evaluación de resultados en salud: hematología

Capítulo XVII. Resultados en salud: patología cardiovascular

Capítulo XVIII. Resultados en salud a evaluar en enfermedades raras

Capítulo XIX. Investigación de resultados en salud en niños y adolescentes

A pandemic is not a war

Deadliest Enemy. Our War Against Killer Germs

Key messages from the book:

To review, our greatest threats are:
1. Pathogens of pandemic potential, which essentially means influenza and the downstream effects of antimicrobial resistance.
2. Pathogens of critical regional importance, which include Ebola, coronaviruses like SARS and MERS, other viruses such as Lassa and Nipah, and Aedes-transmitted diseases such as dengue, yellow fever, and Zika.
3. Bioterrorism and dual-use research of concern (DURC), and gain-of-function research of concern (GOFRC).
4. Endemic diseases that continue to have a major impact on the world’s health, particularly among emerging nations, including malaria, tuberculosis, AIDS, viral hepatitis, childhood diarrheal diseases, and bacterial pneumonia.

Priority 1: Create a Manhattan Project–like program to secure a game-changing influenza vaccine and vaccinate the world.
Priority 2: Establish an international organization to urgently address all aspects of antimicrobial resistance.
Priority 3: Support and substantially expand the mission and scope of the Coalition for Epidemic Preparedness and Innovations (CEPI) to fast-track comprehensive public-private vaccine research, development, manufacturing, and distribution for diseases of current or potential critical regional importance.
Priority 4: Launch the Global Alliance for Control of Aedes-Transmitted Diseases (GAAD) and coordinate with the Bill & Melinda Gates Foundation’s malaria strategy, “Accelerate to Zero.
Priority 5: Fully implement the recommendations of the bipartisan report of the Blue Ribbon Study Panel on Biodefense.
Priority 6: Establish an international organization similar to the National Scientific Advisory Board for Biosecurity (NSABB) to minimize the use of DURC and GOFRC to transmit pathogens of pandemic potential
Priority 7: Recognize that TB, HIV/AIDS, malaria, and other life-threatening infectious diseases remain major global health problems
Priority 8: Anticipate climate-change effects
Priority 9: Adopt a One Health approach to human and animal diseases throughout the world.

Opioid epidemic and the need for urgent measures

Addressing Problematic Opioid Use in OECD Countries

Some months ago I explained my concerns about opioid epidemic. I said that the problem is closer than most people think. In the last five years, there has been a 45% growth in publicly funded opioid prescription  in our country. Now OCDE presents the current situation in a report that highlights where we are and what can be done. The key messages are these ones:

• Better Prescribing: Doctors can improve their prescribing practices, for instance, through evidence-based clinical guidelines (e.g. for opioid prescription, for adequate medication-assisted therapy for OUD patients), prescribers training, surveillance of opioid prescriptions, and regulation of marketing and financial relationships with opioid manufacturers. In addition, patients and the general public can also benefit from clear educational materials and awareness interventions to enhance their opioid-related literacy and reduce stigma.
• Better care: Including the expansion of coverage for long-term medication-assisted therapy (e.g. methadone, buprenorphine, naltrexone) coupled with specialised services for infectious diseases management (e.g. HIV, hepatitis) and psychosocial interventions. Some countries have implemented interventions such as the availability of overdose reversal medications for all first responders, needle and syringe programmes, and medically supervised consumption centres.Quality of care must be improved and measured. 
• Better approach: There can be better coordination across the health, social and criminal justice systems. Governments can consider setting up of coordinated networks among the three sectors aiming to facilitate access to integrated services for people with OUD. In addition to health services, social interventions around housing and employment support, and law enforcement uptake of a public health approach are central.
• Better knowledge and research: Including the use of big data and impact evaluations to generate new information from different sources along with the application of advanced analytics. In addition, quality of care measurement should be enhanced in areas such as opioid prescription, OUD health care services, and patient reported indicators (e.g. PROMs, PREMs). Research and development is needed in key areas such as new pain management modalities and OUD treatments.

Ill-prepared for the arrival of new medicines

Pharmaceutical Innovation and Access to Medicines

While in the last years the number of new drugs in the market has been limited, this trend has changed and countries may expect larger bills in the next future. The OECD report explains the main challenges of pharmaceutical innovation and says:

Despite a slowdown in growth in the 2000s, pharmaceutical spending has nevertheless increased sharply in some therapeutic areas, such as oncology and certain rare diseases where many new medicines target small population groups and command high prices. While these may well address unmet needs, they often have prices that may not be justified by the health benefits they confer.

Countries may be ill-prepared for the arrival of novel medicines targeting wide  population groups. In 2013, the first of a new class of very effective but expensive
drugs known as direct-acting anti-virals (DAAs) for hepatitis C created a shock due to the potential budget impact of treating all infected people. Many countries initially restricted access to the most severely affected patients, creating frustration among patients and clinicians alike. Although subsequent entries of alternative products have created competition on prices and allowed payers to expand eligibility to treatment, the initial shock highlighted the lack of readiness of payers for such events.

In some countries, sudden, large price increases for off-patent medicines have made important treatments unaffordable for patients.

Finally, innovation is lacking in certain areas of high-unmet need, such as new antimicrobials, non-vascular dementia, and some rare diseases.

The report summarises different proposals and measures that would be helpful for a government that cares about citizens' welfare. Unfortunately, this is not our case.

Exhibition at Foto Collectanea

A successful implementation of a bad idea

Since 2012 it hasn't been posible to know the price of new drugs funded by NHS. The government considers that they are confidential. This is a clear example of what exactly means transparency and the application of the rule of law. Meanwhile a new strategy has been put into place. Without public prices, the government has decided to set budget ceilings for several innovative drugs: pertuzumab, ivakaftor, telaprevir/simeprevir, abiraterona, pirfenidona y ruxolitinib. And the last one is new drugs for hepatitis C, defined as "therapeutic group" not as a specific molecule. Following this strategy there is a proposal to extend such a model of budget ceilings by ATC, therapeutic classification.
This is really a bad idea that is already being implemented. As you know sometimes there are good ideas badly implemented, and therefore criticized. But in this case, it is a bad idea with a scrupulous implementation. Some officials consider that if they set a budget ceiling, all decisions will be taken  to fit in with it. Clinical decisions follow a different path, not the mechanical and administrative way officials are used to.
The measure represents a tough hit to economic evaluation, because in the next future the government will not be any longer interested in it. Why? Their only concern is about the budget ceiling, the value doesn't matter. A missed opportunity for the development of priority setting under a rational scheme. Health economists should react to such a big mistake.
The saddest  issue is that nobody knows what will happen when the budget ceiling is surpassed. This will be the job for the next government, nobody cares about it right now. Democracy and rule of law are only words subject to interpretation.

PS. All the details about hepatitis C controversy at Boletín AES.

PS. Understanding the foundations of confidential drug pricing, in Forbes.

PS. Explained at Health Affairs:

International Best Practices For Negotiating 'Reimbursement Contracts' With Price Rebates From Pharmaceutical Companies

By: Morgan, Steven; Daw, Jamie; Thomson, Paige

HEALTH AFFAIRS  Volume: 32   Issue: 4   Pages: 771-777   Published: APR 2013

 Abstract

Reimbursement contracts, in which health insurers receive rebates from drug manufacturers instead of paying the transparent list price, are becoming increasingly common worldwide. Through interviews with policy makers in nine high-income countries, we describe the use of these contracts around the globe and identify related policy challenges and best practices. Of the nine countries surveyed, the majority routinely use confidential reimbursement contracts. This alternative to drug coverage at list prices offers benefits but is not without challenges. Payers face increased administrative costs, difficulties enforcing contracts, and reduced information about prices paid by others. Among the best practices identified, policy makers recommend establishing clear and consistent processes for negotiating contracts with relatively simple rebate structures and transparency to the public about the existence, purpose, and type of reimbursement contracts in place. Policy makers should also work to address undesirable price disparities within their countries and internationally, which may occur as a result of this new pricing paradigm.

An illusionary free lunch

Some months ago I started a series of posts under the title "Fasten seat belts". The topic is well known, how new skyrocketing drug prices are distorting budgets and access. Yesterday we got the final resolution. Fasten you seat belt, this is the moment of truth: The government has decided that hepatitis C patients under specific conditions will get treatment. And once he has decided coverage, he concludes that he will not pay the bill. Somebody else will have to do it, autonomous communities governments. Free lunchs exists in Sepharad!
This is a complete mess and it is only the begining, new drugs are knocking at the door. For catalans, this foreign decision represents 470 m €, an additional deficit for the 2015 budget of 5.7%!!! (if all expenditure were charged in one year). Does this make any sense?. Of course Basque country is not included in such arrangements...
There is an objective need to disconnect, the time is getting closer. Things couldn't have been done worse.

The challenge of setting fair priorities

Public views on principles for health care priority setting: Findings of a European cross-country study using Q methodology

The clash between equity and efficiency is featured nowadays with hepatitis C drugs. High prices mean that access requires some kind of prioritisation. An interesting article may help to understand it:

 Resources available to the health care sector are finite and typically insufficient to fulfil all the demands for health care in the population. Decisions must be made about which treatments to provide. Relatively little is known about the views of the general public regarding the principles that should guide such decisions

The tension between equity and efficiency in the health care sector is apparent in a range of routine decisions and practices. For instance, in the prioritisation of patients on a waiting list, the aim to maximise overall health benefits from treatment may be at conflict with that of obtaining an equitable distribution of health and health care.

 Now ask yourself about the following principles to allocate health resources:

(I) “Egalitarianism, entitlement and equality of access”;

II) “Severity and the magnitude of health gains”;

(III) “Fair innings, young people and maximising health benefits”; 

(IV) “The intrinsic value of life and healthy living”; 

(V) “Quality of life is more important than simply staying alive”.

 Are you able to set a ranking? Does a general ranking of priorities always apply to all cases?. Not so easy. This is exactly what they do in the article and the results are:

Given the plurality of views on the principles for health care priority setting, no single equity principle can be used to underpin health care priority setting. Hence, the process of decision making becomes more important, in which, arguably, these multiple perspectives in society should be somehow reflected.

Let's think about the somehow...

PS. Sofosbuvir vs. NICE . And the winner is?

Involved in our own health

People in control of their own health and care

 From King's Fund report:

Different perspectives (p.11)

• A consumerist approach: health and health care is seen as a marketplace in which patients (consumers) are involved by making choices about services, and the health care market responds to their preferences. Patient involvement is then a means to improve quality.
• A democratic approach: people have political, social and economic rights as citizens, and those who use or are affected by a public service should be involved in how it is run, and have certain rights regarding what they receive from that service.
• An ethical and outcomes-based approach: involvement is seen as the ethical thing to do, and the best approach to improve outcomes. This means recognising that good care comprises the application to individual circumstances of evidence-based medicine along with knowledge and experience. Patient involvement is essential to the judgement of relative risk and benefit associated with decision-making.
• A value-based approach: to achieve truly the best value for money from our health and care system, we must know and respond to what people need and want. In this way, we can deliver care that meets their preferences and patients receive ‘the care they need (and no less), and the care they want (and no more)’ (Mulley et al 2012).
• An approach based on sustainability: it is increasingly difficult for health systems to provide the best possible care to everyone as the prevalence of long-term conditions increases and the population ages. By involving people in managing their own health and care, and keeping well and independent, we can minimise our use of services.
• A person-centred care approach: our health and care system should be  focused on its users, promoting independence and co-ordinated around people’s full needs rather than being fragmented and siloed. Patient involvement is an essential component of delivering a more person-centred service that is tailored and responsive to individual needs and values.

The forgotten perspective in the list, though quoted in the text (p.16):  A behavioural economics approach: we try to do our best for our health but the autopilot decides without our full control. Some help (nudging) is needed.

The message:  "Embarking on an honest conversation about rights and responsibilities requires consideration of people’s motivation and the capability to engage."

PS. Nudging and the European Union, by Alberto Alemano.

PS. BIT Publication: EAST.Four simple ways to apply behavioural insights

PS. Regarding Hepatitis C treatment costs, It is good to remember this post by U. Reinhardt:

With this offer curve, a health system confronts the rest of the nation with two morally challenging questions:

1. Is there a maximum price above which society no longer wishes to purchase added QALYs from its health system, even with the most cost-effective treatments (e.g., Point C)?

2. Should that maximum price be the same for everyone, or could there be differentials – for example, a lower maximum price for patients covered by taxpayer-financed health programs (e.g., Medicaid, Tricare, the Veterans Administration health system and perhaps Medicare), a wide range of higher prices for premium-financed commercial insurance, depending on the generosity of the benefit package that the premium covers, and yet higher prices for wealthy people able to pay out of their own resources very high prices to purchases added QALYs for the family?

Fasten seat belts (4)

The times for drug prescription following prioritisation have arrived. Hepatitis C drugs have paved the way for such a move.There were some informal attempts for certain medicines and it was decided by clinical committees (i.e. for rare diseases), but now it has changed. The government has decided who has to get what and when, this is absolutely new. Have a look at this draft of strategic therapy for Hepatitis C treatment.
Any physician asking for hepatitis C drugs will have to explain the compliance with the criteria and ask for approval.
I said some weeks ago that a new paradigm in drug pricing was starting, right now I have to say that drug prescription priorisation by rules is the new trending topic, at least in our neighbourghood. Wether this prioritisation is based by cost-effectiveness criteria remains to be seen.

Fasten seat belts (3)

In former posts I have argued that pharmaceutical pricing is forging a new trend. The summary is in this figure (US prices):

The latest FDA approved drug is Harvoni, for hepatitis C. This new drug will compete with Sovaldi, the best drug launch ever made by the same manufacturer, 9.000 million $ in sales in 9 months.
The soaring costs of drugs is also affecting the generics market in US. Have a look at this blog.
As far as the economy is not growing at the same pace, new resources are needed and this may come from reductions on current drug benefits (price or quantity) or less expenditures in non-pharmaceutical goods. Otherwise the option is to delay access. Is this an option for cost-effective therapies?

Fasten seat belts (2)

Let me ask you a question: Do you agree that your government spends 12% of the pharmaceutical budget in a new drug? I understand that if the answer is yes, you also agree to reduce 12% of current expenditures in patented drugs, reducing quantity, price or the benefit. Otherwise you have to explain clearly where to find 12% of additional resources.
This is what is happening in the UK NHS on new Hepatitis C drug. Have a look at this site for the details. And by now the decision is that it is "prohibitive" and "unaffordable".
Last Sunday CBS 60 minutes broadcasted an interesting report on "eye popping" cost of cancer drugs. I suggest you spend 15 minutes of your time watching it:



Don't miss the details on "financial toxicity" as WSJ highlights. How this can be true?
Nearby, new drug benefits are approved without any known cost-effectiveness-budget impact consideration. This is an example of  alleged "responsive government".

PS. My former post on the same issue.

PS. On bribes, again.

PS. Today this blog has reached the 100.000 visits. That's excellent!!!. I really appreciate your interest in my posts.

Fasten seat belts

We have entered into an unknown new world: drug prices -for innovative drugs- are on track to disappear. The NHS has agreed a cap on expenditure for a hepatitis C (sofobusvir) new drug in €125m without disclosing the unit price. Some people may consider it an opaque strategy in times that politicians claim transparency.
In my opinion, such a situation allows to understand better that the pharmaceutical market for innovative drugs is mostly a monopsony (one buyer) in a monopoly (one seller), it is not a competitive market - and this is what I have always considered. Therefore, resource allocation is the result of a bargaining between both parties, and the unit price is irrelevant. The buyer wants to maximize health,  the seller is maximizing income, this is exactly the struggle.
The key question is: How much is NHS willing to pay for better health?. As far as  the budget is limited, the number of treatments times the price is not the right way to proceed to maximize health under constrained resources.
Any government has to set priorities for expenditure according to expected health value created. This information should be public. In any case, when a new drug is available the government should clearly define which benefits are cancelled and which are acceptable. A responsible minister can't  agree new expenditures without any budget.
Therefore, innovative pharmaceutical market is not really a market -right now is clear- and governments should set priorities according to resources available -right now is also clear that they haven't done it-.
Fasten seat belts, we are entering into trying times without any political compass-gps. Citizens are expecting something different. I still remember when Victor Fuchs told long time ago: usually health economists discuss incremental cost-effectiveness in limited marginal terms, the real issue appears when such an amount is enormous. The case of hepatitis C is the example of such a situation, and only health policy and deliberative democracy are the tools to confront it. Unfortunately, this was not the strategy applied nearby.

PS. Catalonia in contention, at Harvard Political Review. Must read, if you are interested on what's going on. Otherwise, try Bloomberg op-ed or LAtimes.

PS. Reading Francesc-Marc Alvaro op-ed I always learn something.

PS. Rating catalans' well-being by OECD.

Ricard Molina. Muntaner-Velódromo. Galeria Barnadas

Against patents, again

Deadly Monopolies: The Shocking Corporate Takeover Of Life Itself – And The Consequences For Your Health And Our Medical Future

I've just finished reading a book on patents in life sciences. As you know from previous posts , I'm convinced that there is an enormous welfare loss from current patent system. If you have the opportunity to read this book, you'll finally will arrive at the same conclusion. Although it was written before the Supreme Court ruling over the Myriad case, the message is still the same: patents contrain innovation and are extremely costly to the society. The case of Hepatitis C is explained in detail. Until some patents were exhausted there was no possibility to start research. Without such patents, new succesful and (costly) treatments have arisen (and afterwards have been patented again).
An interesting interview in Forbes magazine highlights the key issues of the book. Unfortunately times go by and alternatives to patents are not taking off.

No apte per a pusil·lànimes

L'embolic britànic de la reforma sanitària agafa proporcions insospitades. Llegeixo a FT el comentari oportú d'en Timmins i resto perplex. Sembla que sigui aquí aprop. L'anàlisi aprofundida del desgavell que s'ha produït en el procés de reforma, és molt bona -a mess that will be hard to operate-. Cal llegir-la sencera.
Destaco:

Some lessons are obvious. Do not attempt major reform to a service that touches everyone’s lives without discussing it first. Do not hide plans from the electorate. In a coalition, involve some policy expertise when you are designing your proposals. Do not have the hubris to paint evolution as revolution. Do not legislate more than necessary. And win some support for your plans ahead of launching them.
Medical responsibility for commissioning, however, may mean doctors can sell changes to the public in a way that politicians simply cannot. And doctors may be able to challenge poorly performing medics in ways that managers cannot. But in Mr Lansley’s case, the clinicians were never recruited to the cause, and the managers – needed to help make some of these changes happen – were belittled as mere bureaucrats.
There remains an intriguing, if far from likely, outcome to this drama. Precisely because the reforms build on elements of what was already happening, there may be a greater chance they will work tolerably than the critics will currently accept. In which case, the health secretary, a dogged, obdurate man with some of the world’s worst communication skills, may yet emerge as something of a hero of public service reform.

Com diu l'article, una reforma del NHS que no està a l'abast dels pusil·lànimes. I vist el que explica cal preguntar-se si està feta per als ciutadans.

PS. pusil·lànime. adj. [LC] D’ànim feble i tímid.

PS. La infecció d'hepatitis C al món.

Reflexionem-hi

High-Value Testing Begins With a Few Simple Questions

Sabem que el valor de les proves diagnòstiques sorgeix de la informació marginal que aporten i la capacitat per modificar les probabilitats de patir una malaltia o el canvi en el seu curs. Per tant, el valor en si mateix és informació, un bé intangible crucial per a decidir el tractament. Tota prova diagnòstica té un cost, ara bé per tal que aquest cost acabi convertint-se en valor, de veritat, podem fer algunes preguntes clau que proposa l'Annals:

Did the patient have this test previously?
If so, what is the indication for repeating it?
Is the result of a repeated test likely to be substantively different from the last result?
If it was done recently elsewhere, can I get the result instead ofrepeating the test?
Will the test result change my care of the patient?
What are the probability and potential adverse consequences of a false positive result?
Is the patient in potential danger over the short term if I do not perform this test?
Am I ordering the test primarily because the patient wants it or to reassure the patient?
If so, have I discussed the above issues with the patient?
Are there other strategies to reassure the patient? 

i el darrer paràgraf clau:

Data suggest that unnecessary testing abounds. The Congressional Budget Office has estimated that up to 5% of the nation’s gross national product is spent on tests and procedures that do not improve patient outcomes (6). The sixth edition of the ACP Ethics Manual specifically calls out responsible stewardship of resources as an ethical responsibility of physicians (7) and has been lauded for doing so (8). Such stewardship requires substantial and persistent effort with some hard decisions along the way. Addressing a few simple questions before ordering a test seems to be a reasonably easy way to start the journey toward high-value care.

A tots aquells que vulguin una retallada selectiva i no pas lineal, tal com alguns hem vingut demanant des de l'inici, el mateix Annals ofereix la llista de proves diagnòstiques en situacions clíniques que aportaran poc valor. Només fa falta llegir-ho i dur-ho a la pràctica. Qui s'hi apunta?

PS. La llista de proves diagnòstiques inacurades

1. Repeating screening ultrasonography for abdominal aortic aneurysm following a negative study
2. Performing coronary angiography in patients with chronic stable angina with well-controlled symptoms on medical therapy or who lack specific high-risk criteria on exercise testing
3. Performing echocardiography in asymptomatic patients with innocent-sounding heart murmurs, most typically grade I–II/VI short systolic, midpeaking murmurs that are audible along the left sternal border
4. Performing routine periodic echocardiography in asymptomatic patients with mild aortic stenosis more frequently than every 3–5 y
5. Routinely repeating echocardiography in asymptomatic patients with mild mitral regurgitation and normal left ventricular size and function
6. Obtaining electrocardiograms to screen for cardiac disease in patients at low to average risk for coronary artery disease
7. Obtaining exercise electrocardiogram for screening in low-risk asymptomatic adults
8. Performing an imaging stress test (echocardiographic or nuclear) as the initial diagnostic test in patients with known or suspected coronary artery disease who are able to exercise and have no resting electrocardiographic abnormalities that may interfere with interpretation of test results
9. Measuring brain natriuretic peptide in the initial evaluation of patients with typical findings of heart failure
10. Annual lipid screening for patients not receiving lipid-lowering drug or diet therapy in the absence of reasons for changing lipid profiles
11. Using MRI rather than mammography as the breast cancer screening test of choice for average-risk women
12. In asymptomatic women with previously treated breast cancer, performing follow-up complete blood counts, blood chemistry studies, tumor marker studies, chest radiography, or imaging studies other than appropriate breast imaging
13. Performing dual-energy x-ray absorptiometry screening for osteoporosis in women younger than 65 y in the absence of risk factors
14. Screening low-risk individuals for hepatitis B virus infection
15. Screening for cervical cancer in low-risk women aged 65 y or older and in women who have had a total hysterectomy (uterus and cervix) for benign disease
16. Screening for colorectal cancer in adults older than 75 y or in adults with a life expectancy of less than 10 y
17. Repeating colonoscopy within 5 y of an index colonoscopy in asymptomatic patients found to have low-risk adenomas
18. Screening for prostate cancer in men older than 75 y or with a life expectancy of less than 10 y
19. Using CA-125 antigen levels to screen women for ovarian cancer in the absence of increased risk
20. Performing imaging studies in patients with nonspecific low back pain
21. Performing preoperative chest radiography in the absence of a clinical suspicion for intrathoracic pathology
22. Ordering routine preoperative laboratory tests, including complete blood count, liver chemistry tests, and metabolic profiles, in otherwise healthy patients undergoing elective surgery
23. Performing preoperative coagulation studies in patients without risk factors or predisposing conditions for bleeding and with a negative history of abnormal bleeding
24. Performing serologic testing for suspected early Lyme disease
25. Performing serologic testing for Lyme disease in patients with chronic nonspecific symptoms and no clinical evidence of disseminated Lyme disease
26. Performing sinus imaging studies for patients with acute rhinosinusitis in the absence of predisposing factors for atypical microbial causes
27. Performing imaging studies in patients with recurrent, classic migraine headache and normal findings on neurologic examination
28. Performing brain imaging studies (CT or MRI) to evaluate simple syncope in patients with normal findings on neurologic examination
29. Routinely performing echocardiography in the evaluation of syncope, unless the history, physical examination, and electrocardiogram do not provide a diagnosis or underlying heart disease is suspected
30. Performing predischarge chest radiography for hospitalized patients with community-acquired pneumonia who are making a satisfactory clinical recovery
31. Obtaining CT scans in a patient with pneumonia that is confirmed by chest radiography in the absence of complicating clinical or radiographic features
32. Performing imaging studies, rather than a high-sensitivity D-dimer measurement, as the initial diagnostic test in patients with low pretest probability of venous thromboembolism
33. Measuring D-dimer rather than performing appropriate diagnostic imaging (extremity ultrasonography, CT angiography, or ventilation–perfusion scintigraphy), in patients with intermediate or high probability of venous thromboembolism
34. Performing follow-up imaging studies for incidentally discovered pulmonary nodules 4 mm in low-risk individuals
35. Monitoring patients with asthma or chronic obstructive pulmonary disease by using full pulmonary function testing that includes lung volumes and diffusing capacity, rather than spirometry alone (or peak expiratory flow rate monitoring in asthma)
36. Performing an antinuclear antibody test in patients with nonspecific symptoms, such as fatigue and myalgia, or in patients with fibromyalgia
37. Screening for chronic obstructive pulmonary disease with spirometry in individuals without respiratory symptoms

PS. Salut i crisi a Grècia. Explicat al blog de Liaropoulos. Algú creu que Grècia pot pagar un interès del 34% del bo a 10 anys? Tothom sap que això és qüestió de dies però mira cap un altre costat.

PS. Sobre el tema de falsificació de medicaments, documents de la OMS

Longevitat i despesa

Si com a voltes es diu que volem afegir anys a la vida i vida als anys, aleshores podem preguntar-nos si afegint més diners ho podem aconseguir.
Un cop d'ull a una dècada sencera ens ofereix una resposta: altres països ho han fet millor. En una dècada hem guanyat 2,5 anys de vida tot creixent al 4,5 % anual la despesa sanitària. Algú dirà, per aconseguir salut no tot ha de ser amb serveis sanitaris, cert, ho sé. Un altre dirà, parles d'anys de vida i interessen els anys de vida sense discapacitat. Admetent un cert reduccionisme, el cert és que tenim el gràfic adjunt a Society at a Glance, informe de l'OCDE:



Ja ho veieu, pocs ens superen per la cua (gasten més i assoleixen menys o igual nombre d'anys). Hi trobem UK, Polònia, Txèquia, Eslovàquia, Grècia i Luxemburg. En cap cas crec que el títol del gràfic sigui el més encertat, i la relació causal que s'endevina, més despesa major longevitat, resta lluny de ser explicada acuradament.
Ara que s'acosta l'aprovació de pressupostos i veient això, hi ha motius per a pensar en termes marginals: sabem què n'obtenim a canvi per cada euro addicional gastat en sanitat?

PS. I jo avui em pregunto també, algú sap quants diners hem gastat en bevacizumab per càncer de mama? Ho dic perquè el cost incremental respecte taxans és  de 37.209€ per tractament i ara, just aquest divendres la FDA ha retirat la indicació, són diners llençats. Si multipliquem aquesta xifra pel nombre de tractaments representa un cost d'oportunitat notable per al sistema de salut, ens ho recompensarà EMA i FDA?. Recordeu allò de la impunitat del regulador? Ja en teniu un altre exemple..

PS. Circle és realment la solució màgica als problemes del NHS? Per conèixer-ho consulteu FT

PS. El dia després de les eleccions convé reflexionar encara una mica més que el dia abans. En especial cal que ho facin els que van impulsar una campanya electoral contaminada premeditadament. Els que van ser objecte del meu comentari fa uns dies al blog ja poden reflexionar pausadament sobre el daltabaix, el que va provocar aleshores l'anunci, i els resultats que n'han rebut després. Evidentment carregar-ho tot a un anunci és un despropòsit, però l'anunci cal prendre'l ara en termes de metàfora-boomerang metge-diputat.

PS. L'article de Habermas a FAZ el trobareu resumit a The Guardian.

PS. El que ens trobarem ben aviat, nou medicament per Hepatitis C..

La infinita estupidesa

Si Einstein deia que hi havia dues coses infinites: l'univers i l'estupidesa humana, ara cal afegir-hi una tercera, l'estupidesa de la política sanitària espanyola del moment. Einstein fins i tot dubtava que l'univers fora infinit. Ara, després de l'aprovació de nous medicaments sense pressupost, ja podem confirmar que el cas de la política sanitària no té remei. Un estat de dret que acabava de reformar la constitució sense cap referèndum i que deia que s'havia de posar límits a la despesa pública, just la setmana següent ja se saltava el criteri, tot acceptant noves prestacions sense assenyalar quines es deixaven de pagar. I el que és pitjor, aprovava un medicament que altres països  han posat en dubte la seva efectivitat i per això han deixat en suspens la seva aplicació.
I la cosa va a més. Mentre a Catalunya hi ha retallades de tota mena, el dimarts el ministeri es va tornar a despatxar a gust amb una nota de premsa on aprovava encara més medicaments sense pressupost. I no estem parlant de qüestions menors, em refereixo per exemple a un tema complicat com és l'Hepatitis C. Afecció crònica amb seqüel.les molt greus i costoses que pot afectar al 1,5-2% de la població. Mireu per exemple el cas extrem de prevalença a la població encarcerada a Catalunya, 21% (!).
Aquí ho introduim sense avaluar-ne el cost-efectivitat, cap problema, ens creiem rics!. Al NICE  mentrestant es prenen temps i ho revisen. Totes aquestes actituds em confirmen que aquí encara no ha arribat la crisi i ens trobarem tot d'una amb la catàstrofe.

PS. Si busqueu l'acta de la comissió de preus, no la trobareu (per ara). El ministeri a més encara no ha entès que si s'aprova el preu no significa que sigui finançat i la pífia en la seva nota de premsa.

PS. Tancament de la nota de premsa, (evito comentaris, simplement constatació de l'estupidesa infinita adobada amb cinisme):

La aprobación de estos medicamentos es un ejemplo de la política del Ministerio de Sanidad para reforzar la eficiencia de la prestación farmacéutica, generando ahorros en los presupuestos de las Comunidades Autónomas pero sin dañar la calidad de la prestación al incorporar al sistema público todas aquellas innovaciones terapéuticas que aportan ventajas sustanciales para los pacientes.

PS. No us penseu que el boceprevir és l'únic que es va aprovar, quan llegiu veureu que el fingolimod i el belilumab van passar sense problemes. Altres països abans ho han avaluat i per exemple el NICE ha desaconsellat la seva inclusió al NHS, ho vaig explicar en aquest blog fa unes setmanes (a, b). I encara més, i més fort, dabigatran per indicació de prevenció d'ictus (i jo em pregunto per què la nota de premsa mostra ara una extensió d'indicacions que va fer l'agència AEMPS el passat abril? i com és que el NICE encara ho està revisant i aquí tirem pel dret?)

PS. DCVB. Estupidesa, qualitat d'estúpid  :Propi de gran curtor d'enteniment.