Controversies on QALYs

The Limitations of QALY: A Literature Review

After 50 years, valuing health using QALYs is still a daunting task. Basically the debate over ethical considerations, methodological issues and theoretical assumptions, and context or disease specific considerations is still alive. And I would add that it will remain as an open issue. Those that would like a simple metric for a complex issue will fail forever. And this pitfalls are translated to decision making when QALYs are the reference for resource allocation.
I'm unsure about what will be the next step. A recent article explains current limitations, but unfortunately I can't foresee alternative options for the future:

Debate continues to exist on whether QALYs should serve as the central means of health economics analysis. This review examines the potential shortfalls of QALYs, spanning current ethical, methodological, and contextual domains in addition to examining their suitability for regenerative medicine and future technologies. In the UK, NICE currently stipulates a threshold of £20 000 - £30 000 per QALY  when evaluating new therapeutics and/or technologies for NHS adoption, and has used this tool to apply a rational and transparent process to technological adoption for over ten years. Calculating QALY or cost effectiveness thresholds is particularly complex and debate has previously been publicized on whether the value of a QALY should be dictated by first proposing the worth of a QALY and setting the healthcare budget at or below that value, or alternatively, proposing a healthcare budget and then allowing the cost of a QALY to declare itself following purchasing decisions. With the advent of cellular based therapeutics and their comparably high upfront costs, the QALY calculation methodology may need refinement to realise the financial advantages and opportunity costs such interventions may convey – particularly considering the degree of uncertainty associated with them.

Meanwhile we should focus on improving comparative effectiveness of current and new technologies, specially those that are related to precision medicine.

 



 

Dr. Heisenberg's Magic Mirror of Uncertainty, 1998

Duan Michals exhibition in Barcelona

 

Quin hauria de ser el preu adient dels medicaments?

 The Right Price: A Value-Based Prescription for Drug Costs

Ara que la FDA acaba d'aprovar la primera teràpia d'edició genètica mitjançant CRISPR per anèmia de cèl·lules falciformes, ja sabem el preu que ha decidit VERTEX, l'empresa comercialitzadora, 2,2 milions $. A Catalunya poden haver-hi unes 240 persones afectades i per tant l'impacte pressupostari del cost del tractament seria de més de 500 milions (si el preu final fos el que diuen ara). Aquesta és la dimensió del problema que s'acosta. La EMA l'aprovarà el mes de març proper.

Quin hauria de ser el preu adient d'un medicament?. Bona pregunta per un moment com aquest.  Aquesta és precisament la qüestió que tracta un llibre de Peter Neumann et al. que he llegit recentment. Es tracta d'una obra per a tots els públics centrada als USA però que també va més enllà. L'índex ja dona una idea:

PART I. THE ECONOMICS OF PRESCRIPTION DRUGS

1.Introduction

2.The Prescription Drug Market

3.Proposed Solutions for Rising Drug Prices

4.Measuring the Value of Prescription Drugs

PART II. EXPERIENCES MEASURING A DRUG’S VALUE IN THE US AND ABROAD

5.Measuring Drug Value: Whose Job Is It Anyway?

6.Institute for Clinical and Economic Review

7.Other US Value Assessment Frameworks

8.Do Drugs for Special Populations Warrant Higher Prices?

PART III. GETTING TO VALUE-BASED PRICING FOR DRUGS

9.Improving Value Measurement

10.Aligning Prices With Value

11.The Path Forward

La tercera part m'ha interessat especialment perquè planteja qüestions sobre els QALYs que repetidament he explicat en aquest blog, i diu:

If QALYs were a person, they might receive a lot of hate mail. People complain that QALYs are not patient-focused, that they are used as rationing tools by health insurers, and that putting numbers on people’s health is dehumanizing. “The entire superstructure of the QALY methodology is built upon philosophical sand,” wrote one critic in 2019. As we have seen, the use of cost-per-QALY ratios by payers to inform drug coverage and pricing decisions attracts intense opposition in some quarters.

El racionament existeix però hipòcritament ningú en vol parlar, diu.  I els QALYs tenen problemes però,

A philosopher and ethicist, Peter Singer, has observed (with apologies to Winston Churchill), QALYs may be the worst way to measure health, except for all of the others.

I així és. Som davant d'un llibre d'interès, especialment per a reguladors acabats d'arribar al càrrec i no tenen temps de llegir i s'enfronten al pànic escènic. És un llibre relativament curt que ajudarà a posar les idees en el context acurat.

PS. Tinc la impressió que cal superar la lògica del preu i anar cap una concepció diferent de contracte públic de subministrament de teràpies. Ho he explicat en altres ocasions i en canvi aquest llibre no ho reflecteix.

PS. Tinc la impressió que estem davant d'una teràpia amb gran potencial d'efecte crida, molt preocupant. Encara som a temps per regular-ho i evitar que passi com amb els peruans i el CAR-T. O es fa abans o ja serà massa tard i es farà malament.

PS. Aquí teniu un exemple de recerca en un àmbit on ja s'ha trobat la solució, i per tant és inapropiat invertir-hi. Ara bé, algú no se n'ha volgut adonar i uns altres hi estan abocant diners. Trobo a faltar informes sobre recerca fútil.  Si voleu conèixer com s'ha arribat a la solució, ho trobareu aquí.

PS. Antic post sobre guerra injusta, per rellegir ara mateix.

 

Giving the priority to the worse off

Egalitarianism

Finally I've found a book that explains the concept of egalitarianism and its implications with a clear message.

Distributive justice is an area not only of philosophy, but also of several other academic disciplines. For example, the formal analysis of economics is extremely important and valuable for understanding the structure of egalitarian theories of distributive justice. However, it intimidates some people. I believe that the most fruitful way to present theories of distributive justice is to integrate the results of economics and political theory into philosophical analysis.

The concept:

Egalitarianism: a class of distributive principles, which claim that individuals should have equal quantities of well-being or morally relevant factors that affect their life.

What it is not egalitarianism, but maybe you are not aware of:

There are at least four well-known distributive principles that are not egalitarian in the sense I defined above, yet some people think that these are egalitarian in some sense.

The first example is utilitarianism. Utilitarianism can be defined in various ways. Take classical utilitarianism. Classical utilitarianism contends that an act is right if and only if it maximizes the total sum of people’s well-being in a given society. When we calculate the total sum, we assign equal weight to each person’s well-being and simply add up different people’s well-being. Classical utilitarianism endorses assigning equal weight
to every person’s well-being, and it might be claimed that it is egalitarian. However, it is not concerned with how people’s well-being is distributed. Thus, I do not consider it as a form of egalitarianism.

The second example is libertarianism.

The third is the Marxist principle of justice or communism

The fourth is the proportionality principle.

The book reviews several perspectives on egalitarianism with concrete descriptions and comments:

1 Rawlsian egalitarianism
2 Luck egalitarianism
3 Telic egalitarianism
4 Prioritarianism
5 Sufficientarianism

And two specific chapters:

6 Equality and time
7 Equality in health and health care

The chapter on health is specially welcome and is a required reading for health economists, and for supporters of QALYs:

It is obvious that the principle of QALY maximization is utilitarian in spirit. It adds up different people’s good, and claims that we should choose the allocation that maximizes the total good. In the context of health care resource allocation, the good is QALY, which measures health benefit. QALY is added up across individuals to estimate the goodness of different outcomes. Then, the alternative that maximizes the goodness of outcome is chosen. It is not surprising that, according to QALY maximization, it does not matter how QALYs are distributed across individuals. Needless to say, all sorts of objections leveled against utilitarianism are raised against QALY maximization.

Usually, QALY maximization is understood as the unweighted sum of QALYs. However, it does not need to be so.We can make it a weighted sum and give priority to the worse off. If we give priority to the worse off, then it is possible to bring egalitarian concerns to bear on the allocation of health care resources.

One chapter is not enough to disentangle the complexities of QALYs, but it is worth reading.

At the end the author explains his position:

My preferred distributive principle is the aggregate view of telic egalitarianism. I am not
willing to support Rawls’s difference principle, because I agree with Harsanyi(1975) that the difference principle in practice ignores the benefits to the non worst off groups and therefore fails to secure the stability of the basic structure of society. This stands in opposition to Rawls’s claim that the difference principle, together with other principles of justice, guarantees a satisfactory minimum, and therefore secures the stability of the basic structure.

My view is coincidental with the author.


PS The concept of telic (telelological) egalitarianism:

There are two main ways in which we can believe in equality. We may believe that inequality is bad. On such a view, when we should aim for equality, that is because we shall thereby make the outcome better. We can then be called Teleological – or, for short, Telic – Egalitarians. Our view may instead be Deontological or, for short, Deontic. We may believe we should aim for equality, not to make the outcome better, but for some other moral reason. We may believe, for example, that people have rights to equal shares. (Parfit 2000: 84)

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

En Weinstein carrega fort

Legislating against Use of Cost-Effectiveness Information

En Weinstein i en Neumann publiquen a NEJM un article suggerent. Expliquen com la llei norteamericana ha prohibit l'ús dels QALYs com a llindar.
El resum en un paràgraf:

"To be sure, there are legitimate debates about the role of QALYs as the sole benchmark of health gains for purposes of allocating society’s resources. However, acknowledging the measure’s limitations, panels in the United States and Britain and at the World Health Organization have found QALYs preferable to alternative measures of health improvement."

Malgrat que em preocupen els llindars i qui els fixa, em preocupa també que no hi hagi mesures i que seguim conduint mirant el retrovisor.
Per aquí el vent bufa i s'ho emporta tot, fins i tot el que diuen les lleis, que cal avaluar la utilitat terapèutica dels medicaments. Encara no han prohibit els QALYs perquè no interessa establir prioritats, el cafè per a tots és més gratificant però potser és cosa de dies.

Genome sequencing, what's it worth?

Evaluating the Outcomes Associated with Genomic Sequencing: A Roadmap for Future Research

The health economic evidence base for WES -whole exome sequencing- and WGS -whole genome sequencing- is very limited . A recent literature review identified just eight economic evaluations of either WGS or WES, six of which were cost-effectiveness analyses using diagnostic yield as the outcome measure. Only two publications presented cost-utility analyses using quality-adjusted life-years (QALYs) as the measure of health outcomes, as recommended by most health technology assessment (HTA) agencies. However, neither of these cost-utility analyses provides information on health outcomes that HTA agencies can use to inform the translation of NGS technologies into clinical practice for specific disorders.

Last May I wrote a post on this topic. Now James Buchanan and Sarah Wordsworth provide a roadmap for future research with three steps.

First, it is crucial that health economists generate evidence on the clinical utility of genomic sequencing using the methods and metrics that are recommended by HTA agencies. Here, we are primarily referring to the use of preference-based HRQoL instruments such as EQ-5D questionnaires to generate utility weights that can be used to calculate QALYs 

If there is reason to believe that patient wellbeing will change after undergoing genomic sequencing (for example, supportive qualitative evidence), but commonly used HRQoL instruments show no effect, a second step would be to explore the use of alternative health-state valuation techniques to generate utility weights within the QALY framework. The time-trade-off (TTO) technique is one such approach

A third step would be to make full use of existing evidence on the diagnostic yield of WGS and WES. Studies that link this evidence to patient survival and quality of life (for example, trials or observational studies with long-term follow-up), could inform decision making regarding the translation of these technologies into clinical practice.

Unfortunately, it is easier said than done. I'm dubious regarding the potential of QALYs on assessing value of such technology, despite I have no alternative solutions right now.

Exhibition at Saatchi gallery

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?

El llindar de preus dels medicaments

A new value-based approach to the pricing of branded medicines

Els britànics estan revisant en profunditat els fonaments de la fixació de preus de medicaments. El document que acaben de publicar explica les bases sobre el que s'establirien preus segons el valor que aporten els medicaments. I el valor s'obtindria a partir de conèixer el seu cost-efectivitat. En una frase:

Based on the output of the full assessment of value of a product, expressed as a weighted cost per QALY (or alternative measure) the threshold or maximum price would be determined

Encara que el document s'esforça en considerar factors addicionals als QALYs, en realitat el protagonisme que s'espera que juguin esdevé clau per entendre el nou sistema. I sobre els QALYs sabem que hi ha llums i ombres. Cal anar en compte doncs a la seva aplicació. Tema a seguir d'aprop.
Curiosament el document oblida els acords de risc compartit. Una estratègia en la que la indústria i alguns investigadors hi havien dipositat totes les esperances. Llegeixo un article a GS sobre el tema que diu:

Los resultados son interesantes en el sentido de que se muestran las debilidades de este tipo de acuerdos sobre el terreno real: pérdidas de pacientes seguidos a largo plazo, indefinición inicial sobre la eficiencia de la medicación, dudas sobre cómo reconducir el análisis ante la entrada de nuevas opciones terapéuticas, qué decisiones tomar y a través de qué canales si los resultados no son tan buenos como los esperados (¿continuar con el estudio y el acuerdo de riesgo compartido o abandonar? ¿en qué elementos fiar de antemano la decisión de abandonar la financiación de la tecnología? ¿lo decide el NHS o los investigadores independientes?, etc.). En suma, este trabajo alerta sobre la utilización de acuerdos de riesgo compartido en tratamientos cuyos efectos sólo se pueden observar a largo plazo y para los que no se puede disponer de grupo de control.

I a la conclusió final hi trobem:

Los acuerdos de riesgo compartido pueden resultar una herramienta de utilidad para mejorar la eficiencia de las políticas de acceso a los mercados de ciertas innovaciones sanitarias. No obstante, la evidencia empírica disponible aún es escasa. Por ejemplo, en la revisión de Stafinsky et al8 sobre 58 casos revisados, en 47 el estudio de seguimiento no había finalizado o bien no se disponía de información sobre las implicaciones que supuso la evaluación del acuerdo para la toma de decisiones final. Por ello, es ciertamente pronto para opinar sobre los resultados de la aplicación real de este tipo de acuerdos

Vist així, queda clar que poden i no poden resultar una eina per a definir l'accés als medicaments i aquest és el motiu pel que ho han passat per alt al document que comentem.

PS. M'ha interessat el relat nadalenc d'en Pla

El valor d'un any de vida

 VALUING QALY GAINS BY APPLYING A SOCIETAL PERSPECTIVE

D'ençà que es varen formular els QALYs aprofitant la teoria de la decisió i la utilitat esperada, varen aixecar una gran expectativa. Vegeu-ne aquesta revisió a Value in Health. Però alhora la metodologia ha estat objecte de controvèrsia continuada. Llegeixo a Health Economics un article recent que aposta per la valoració social dels anys de vida ajustats per qualitat i ho fa amb una estimació empírica de la disponibilitat a pagar. Aquest és el resum:

Interpreting the outcomes of cost utility analyses requires an appropriately defined threshold for costs per quality-adjusted life year (QALY). A common view is that the threshold should represent the (consumption) value a society attaches to a QALY. So far, individual valuations of personal health gains have mainly been studied rather than potentially relevant social values. In this study, we present the first direct empirical estimates of the willingness to pay for a QALY from a societal perspective. We used the contingent valuation approach, valuing QALYs under uncertainty and correcting for probability weighting. The estimates obtained in a representative sample of the Dutch population (n = 1004) range from €52,000 to €83,000, depending on the specification of the societal perspective.

I tornem a ser on érem. Mitjançant l'estimació d'uns escenaris d'estat de salut (29) en el marc del controvertit qüestionari EQ-5D, s'arriba a unes disponibilitats a pagar que no podem saber-ne amb profunditat si es corresponen amb el valor social. Entre d'altres coses perquè la gent valora els escenaris en funció de si es troba en ells, si si ha trobat o si pot trobar-s'hi en el futur. I això és molt difícil d'ajustar. I sé que ho han fet el millor que han sabut i pogut, però no em convenç. Això vol dir que cal seguir cercant o deixar-ho empíricament al regulador enlloc de preguntar a la gent.

PS. Suggeriment. Feu un cop d'ull a l'article recent d'en Josep Maria Via.  La reflexió és oportuna, convé comprendre millor quina és l'eficiència abans de decidir si cal optar per formes organitzatives de control administratiu, o d'auditoria financera.
Tot i així hi ha una peça que falta. A més d'altres aspectes, l'error governamental inicial va ser no incloure la compensació acurada per amortització i noves inversions dins el sistema de pagament hospitalari. Al mantenir-ho fora del sistema, les subvencions a la inversió en els hospitals concertats van ser una eina clientelar per uns i altres que ha acabat en majoria pública del capital dels hospitals afectats. Convé revertir l'error inicial, situar les coses al seu lloc, i incentivar acuradament per assolir major valor.

Ho vaig dir fa dies. Ara en un pin.
En vull un!

Revisiting efficiency measurement

Health system efficiency: How to make measurement matter for policy and management

A new book by WHO Euro has been published about efficiency measurement. It seems that this is a topic that would need a review and update. Unfortunately you'll not find any new message. Regarding output measurement, you'll find this statement: "QALYs are in principle a widely accepted outcome measure". I'll not comment again about it. QALYs are controversial, and you may find many posts in this blog on this topic. Therefore, this is a book you can skip reading it. You have to revisit efficiency measurement but with a different book.  In order to make measurement matter for policy and management, we do need a robust measurement toolkit. Right now there is too much noise to understand the message.

QALYs and COVID

Revisiting the Economic Cost of Flattening the Curve

The Incidental economist blog provides information regarding QALY in the current pandemic. Forget the cost per QALY (so difficult to estimate in my opinion) and take only the 6,4 QALYs per death avoided.

It updates previous estimates and says:

The table below summarizes the previous calculations and current updates. Our revisited analysis shows that, as the shutdown continues, the cost per QALY gained increases exponentially due to the exponential growth in the total cost of both forgone productivity and business failure.

We previously emphasized that a key challenge in making calculations of this type is the uncertainty around the data inputs. Six weeks later, this still holds true, particularly for the range of QALY losses without a shutdown, i.e. the predicted corona-related deaths in the absence of intervention.

One interesting aspect of this analysis is that as time goes on, the cost per QALY gained will become higher and higher. This is because the net gains will diminish — the lives saved remains constant, but the offsetting life years lost due to other factors increase — while the costs increase exponentially. The key number that remains unknown is the relationship between the length of the lockdown and the number of lives lost.
In our first post, we concluded that the shutdown would meet conventional standards of cost effectiveness only if the deaths avoided was on the high end of the possible range and the costs on the low end — an outcome that seemed unlikely. Revisiting the issue, it is now clear that the cost per QALY gained from the shutdown will be outside the conventional range of acceptability even at the high end of deaths avoided. How far outside the range the shutdown policy will ultimately prove to be is unknown.

Vestits a mida (2)

Individualized Cost-Effectiveness Analysis

Ara es porten els vestits a mida, és la moda del moment. La talla única està en dubte. Ja m'hi vaig referir fa unes setmanes en relació a les guies de pràctica clínica individualitzades. Ara a PLOS hi trobem l'anàlisi cost-efectivitat individualitzat.

El que diuen podrien tenir sentit si no fos perquè es basa tot en els QALYs, tema sobre el que mantinc una incertesa permanent sobre la seva estimació. Si deixem de banda per un moment això, és raonable. La mitjana de cost -efectivitat incremental incomoda a més d'un. Al JAMA va aparèixer fa unes setmanes un comentari ponderat sobre els QALYs. En el fons deia que era tant bo defensar-se dels entusiastes com protegir-se d'aquells que els volen trinxar.

PS. Si algú vol saber què es pot fer per salvar l'euro, l'editorial de WSJ ho explica. Tal com van les coses Grècia fa fallida, i ells mateixos assenyalen que la seva recomanació per l'economia europea és improbable que s'apliqui perquè suposa admetre els errors que s'han comès fins ara. Si finalment és així, hi ha motius fonamentats per a la preocupació.
En un altre article d'opinió als WSJ s'explica molt bé què es pot fer per regular millor els bancs.
Mentrestant, per aquí aprop, el globus sonda del dia: nova retallada de sous a funcionaris. Europa acabarà costant caríssima.

PS. No comment Roche vs. Stanford. 

El valor d'un any de vida

Searchers vs surveyors in estimating the monetary value of a QALY: resolving a nasty dilemma for NICE

Al Regne Unit hi ha estudis que identifiquen el que costa un any de vida ajustat per qualitat:

The most rigorous valuations from the searchers to date are those of Martin et al. (2008) who attempted to estimate what it costs the NHS in England to produce a QALY in the programme areas of cancer and circulatory disease; arriving at values of £11,960 and £19,070, respectively.

La qüestió és: quin és el valor? I no només en aquestes dues àrees sino en les 23 per exemple que són el pressupost per programes del govern britànic. Per a estimar el valor dels QALYs hi ha dues perspectives, des de la demanda (preguntant la disponibilitat a pagar) i des de l'oferta (observant el que el govern està disposat a pagat). Els llindars de valor dels QALYs és objectiu de debat i especialment més des que en JL Pinto et al. va publicar a JHE: Trying to estimate a monetary value for the QALY el 2009. Jo pensava que llegint el títol de l'article al HEPL tindria la solució, però no encara, caldrà esperar. Tot i així paga la pena llegir-lo.
La qüestió que resta oberta és: com podem fer tant d'èmfasi en l'avaluació econòmica si encara no ho tenim resolt?

The drivers of HTA decisions

Decision making by NICE: examining the inuences of evidence, process and context

Two reductionists views can be avoided. There is one that puts all the eggs in one basket of QALYs, the opposite that considers that QALYs are flawed and the solution is far away. Beyond such extremes, there is the need to assess new techonogies, and this is precisely what NICE does. An interesting article revisits the current drivers used by NICE to take decisions. These are the conclusions:

The results suggest that the variability in decisions observed can be explained by a combination of clinical, economic, process and socio-economic factors. The analysis showed that the proportion of restrictions and non-recommendations issued by NICE are increasing over time relative to recommendations. The analysis also confirmed that the demonstration of clinical and economic value is central to NICE decisions.

New factors not previously reported to have an effect on NICE decision making were identified, including the effect of clinical superiority on NICE decision making, the effect of the ICER on the likelihood of both restriction and recommendation and that NICE decision making was sensitive to process variables as well as socioeconomic factors.

Interesting guide to convince those that already have a reductionist mind. The evidence, the process and the context has to be taken into account.

Què cal fer amb les teràpies cost-inefectives que "milloren" l'equitat?

 Distributional Cost-Effectiveness of Equity-Enhancing Gene Therapy in Sickle Cell Disease in the United States

Ara fa un mes parlava de que la mesura del cost-efectivitat d'un medicament amb el cost per any de vida ajustat per qualitat (QALY) se n'havia anat en orris. Dos factors  hi havien contribuït, els preus confidencials i la superació de llindars raonables. Tot plegat posava en qüestió una dinàmica que ha durat dècades i que ha estat el referent de les agències d'avaluació de tecnologies.

Doncs bé, des d'aquí també fa temps que he explicat que calia incorporar la dimensió d'equitat i no només la d'eficiència en l'avaluació econòmica. I justament ara ha començat una nova època, on cal preguntar-nos què hem de fer quan un medicament és cost-inefectiu però en canvi pot ser una estratègia terapèutica equitativa. La metodologia és coneix com Distributional Cost-Effective Analysis (DCEA).

El resultat d'un article recent sobre teràpia genètica en anèmia de cèl·lules falciformes indica això:

Gene therapy versus Standard Of Care for females yielded 25.5 versus 15.7 (males: 24.4 vs. 15.5) discounted lifetime QALYs at costs of $2.8 million and $1.0 million (males: $2.8 million and $1.2 million), respectively, with an ICER of $176 000 per QALY (full SCD population). The inequality aversion parameter would need to be 0.90 for the full Sickle Cell Disease population for gene therapy to be preferred per DCEA standards.

El cost incremental per any de vida ajustat per qualitat està a 176.000$, i això és molt, molt per sobre del llindar. Però llavors entra en joc el paràmetre d'aversió a la diferència (inequality). Diuen que als USA està entre 0,5 i 3,0 i els porta a una conclusió diferent en termes d'equitat. He de revisar com han arribat a aquestes xifres i què signifiquen, cosa que desconec. Ho faré més endavant.

Aquest és el missatge clau en un paràgraf:

Although gene therapy priced across known costs ranging from $2.1 million to $2.8million did not meet conventional standards for cost-effectiveness, our distributional cost-effectiveness findings suggest that gene therapy could meet distributional cost-effectiveness standards based on commonly used equity weights for the U.S. setting in this price range. If one assumes similar therapeutic efficacy in patients  with mild and moderate disease and patients with severe disease, once gene therapy is approved, it could be an equity-enhancing therapeutic strategy for all patients with SCD whose values and  references align with pursuing this course of therapy.

Amb aquest estudi s'inicia doncs el nou paradigma necessari per a justificar preus de teràpies superiors 2 milions de $ per cas: encara que sigui cost-inefectiu, redueix les diferències en salut, malgrat no sabem quin és el nivell de diferència admisible. A aquest paradigma s'hi arriba amb una caixa negra, que és el paràmetre d'aversió a les diferències (inequality) creat per "experts". Desconec quin recorregut li espera a tot això, justificarem els preus desorbitats per motius d'equitat? Caldrà seguir-ho amb atenció.

PS. Si això resol el problema del llindar dels QALYS, alhora en crea un de nou, el del paràmetre d'aversió a la diferència, que alguns en diuen desigualtat. Com es fixa?

PS. Pregunta pertinent davant el nou fàrmac a preu 3,3 milions €, és cost-inefectiu però millora l'equitat, segur? Va dirigit a uns 520 casos de hemofilia A i 60 d'hemofilia B aproximadament. Suposa gastar el 12% del pressupost d'enguany en 580 casos.

PS. Per aquí aprop no preocupa massa ni el cost-efectivitat ni el cost-efectivitat distributiu, massa feina per un regulador que creu molt més en la discrecionalitat ad hoc com a criteri per a la presa de decisions.

 HARDIJANTO BUDIMAN / ALL ABOUT PHOTO AWARDS 2022/

El llindar del cost per QALY se n'ha anat en orris

 Financing and Reimbursement of Approved Advanced Therapies in Several European Countries

El temps passa ràpid i aviat farà 50 anys que en Richard Zeckhauser (1976) va proposar els anys de vida ajustats per qualitat (QALYs) com a mesura per calcular el cost efectivitat incremental d'una intervenció sobre la salut i la vida. A data d'avui s'utilitza de forma sistemàtica a molts països per tal de conèixer el valor relatiu dels nous medicaments. Les mancances que té són moltes, i les he exposades en altres ocasions, però malgrat això és utilitzada per organismes reguladors.

Ara bé, quan la mesura del cost-efectivitat incremental la volem comparar amb el que una societat està disposada a pagar per un QALY, llavors tot s'entrebanca. I la mostra la teniu en aquest quadre que ensenya la situació. Si fa temps es parlava del llindar de 30.000€ per QALY, compareu-ho amb les xifres que surten i veureu que tot està fora de lloc. Poques teràpies avançades estan per sota, i la majoria per sobre i molt per sobre:

Tot plegat confirma, que la idea dels llindars de cost per QALY se n'han anat en orris. Si el cost per QALY no és un referent de la disponibilitat a pagar, aleshores quin és el referent 50 anys després de la seva creació? La mesura pot quedar relegada a un exercici comptable i res més. Per ara, anem donant pals de cec per aquí a prop. Mentrestant, el NICE té els seus criteris que ja està aplicant i que vaig explicar. Roman la incertesa, però hi ha criteris. 

A l'article hi trobareu també els preus notificats i alguns descomptes:

Són preus notificats, no són els preus pagats realment perquè a la negociació apareixen descomptes confidencials. I aquest és un altre problema dels QALYs publicats, si no sabem el cost final pel finançador, com podem dir quin és el cost per QALY?. Aquesta és una qüestió que queda a l'aire, almenys per ara.

A l'article hi trobareu molt més material d'interès per fer-nos una idea de la situació en aquest moment de les teràpies avançades, genètiques, cel·lulars i de teixits.

Overvaluing expensive drugs

A research from University of York has concluded that NICE is overvaluing expensive treatments because its cost threshold - the price at which a treatment is deemed good value for the NHS - is set too high. The threshold value per quality-adjusted life year (QALY) - a measure of the health benefits of a treatment - should be lowered from £30,000 to just £18,317, their analysis found. It suggests the NHS may be wasting money on treatments that are not as good value as first thought. Professor Sculped said:

It is crucial that the cost effectiveness threshold is seen as representing health forgone as the additional costs of new technologies are imposed on the fixed budgets of local commissioners. For decisions made by NICE and many policy options considered by the NHS and DH, this is the key to establishing the value for money of new services.

This is a strong criticism against QALYs, let's see if it has some impact in the near future. Fortunately, the British have the opportunity to debate on it. Nearer here, the press is saying now that 30% of drugs requested for approval were rejected (7 out of 24). No details available, no website, no transparent process. That's alleged democracy, southern style. NTA=Nothing to add.

PS. If you don't want to read the article, have a look at this presentation. I suggest you save it, it may be useful for the future.

PS. As you can see from my blog, in one week, two officials have said different numbers of rejected drugs for public funding (2 vs 7). Does this make any sense? Is there anybody asking for an explanation in Parliament?

PS. Follow the controversy on DSM-5 at BBC News.

PS. Check here how our drug prices have converged to the european average.

PS. Must read: Uwe Reinhardt blog.

PS. Interesting article on 20 years of economic evaluations of cancer.

The Voltaire of health economics

MAYNARD MATTERS
Critical Thinking on Health Policy

For any health economist, Alan Maynard is a reference. We've been reading his contributions for decades and now we can read a book (free to download) that has two parts. The first shows different views of his role on health economics and policy,  while the second is a selected collection of articles and book chapters.
I would like today to highlight what Rudolf Klein says about what he calls "The Voltaire of Health Economics":

I am sceptical about some of the claims to special policy wisdom of economists operating in
the health field. Too many, I find, seem to have a naive faith in QALYs, reflecting methodological innocence and an unreflective utilitarianism. Too many, in my view, appear to think that evidence should guide policy action in situations where only policy action can produce the evidence. Too
often I find myself bemused by statistical wizardry, wondering whether the inevitable simplifications required by modelling don’t exclude crucial dimensions of a complex world

The reasons for my admiration stem from Alan’s specialcombination of energy, moral drive and irreverence.  

Alan is a moralist. For him a failure to act on – or, if need be, generate – the evidence for a policy intervention is an ethical failure. So identifying what interventions give the “biggest bang for the buck” is the moral obligation of all policy makers. He sees a reform of the NHS, or indeed of any health care system, “as an experiment on fellow citizens”, which has to be justified and undertaken responsibly, and not on some ideological whim.

I agree absolutely on Rudolf Klein views.
In chapter 13 you'll find a book chapter "Health Economics: Has it fulfilled its
potential?" that is abstracted by the editor's with this words:

Whilst Maynard argued strongly for the importance of generating and using cost-effectiveness data in decision making, he was concerned that this had encouraged an industry of health economists rolling out economic evaluations. The victory of the health economics perspective in how to ration health care resources led to health economics becoming the slave of the cost-effectiveness industry, feeding regulators such as NICE and also the pharmaceutical and device manufacturers seeking to get their products approved and funded. This distorted the role of health economics and only used a small part of the full repertoire of perspectives and techniques that economics could apply to health and healthcare problems. He argued here that health economists need to keep a strong link with economics as a discipline and apply themselves to a wider range of problems such as supply and demand, the workforce, incentives and behaviour change, pricing and equity.

 As the front page says:

Brilliant, irreverent and almost always right – essays by a sceptical health economist who changed the way we think about policy

A must read.

PS. The best books of 2016 by FT

On NICE and QALYs

It is quite relevant what's going on with value based pricing by NICE. Recent documents are raising greater controversy and a blog post asks if this is the end of the proposal. Today I suggest you have a look at James Raftery contribution to understand the moment (at least in the UK). No politician is interested in such issues.

Els dos dracs

Hic Sunt Dracones: The Future of Health Technology Assessment—One Economist’s Perspective

El mantra del moment és la necessitat d'avaluació econòmica de les prestacions sanitàries. Ho sabem, res de nou. I jo avui em pregunto si recitar aquest mantra ens durà a l'objectiu esperat que és assolir més valor i millor distribuït amb els recursos disponibles. I aquí és on entren dues variables en joc, l'eficiència i l'equitat. Ara com ara, observo al meu voltant un reduccionisme metodològic excessiu, alhora que un enfoc exclusiu en l'eficiència. Com si això de l'avaluació econòmica es pogués resoldre amb la comptabilitat dels QALYS- anys de vida ajustats per qualitat.
Afortunadament, en Tony Culyer ens recorda les dues Ps:

My concerns about HTA relate to the fact that, when applied, it inevitably has a political context. It is political both with a large ‘‘P’’ and a small one. The large ‘‘P’’ relates to the political ideology of health services and springs from the notion of a public interest element of health services. This is an interest that can be cast in many languages, for example, in political language, ‘‘solidarity’’, or in Marxian language, ‘‘from each according to their ability, to each according to their need’’, or in neoclassical economic language,‘‘public goods’’ and ‘‘caring externalities’’. It finds particular expression in the idea, which I think can be first attributed to Archie Cochrane,4 that the only health care warranting public financing or public delivery is health care that is demonstrably effective. The small ‘‘p’’ political context, is the context in which the political creator of the National Institute of Health and Clinical Excellence (NICE), Frank Dobson, when asked as Secretary of State for Health whether he thought it would work, said ‘‘Probably not, but it’s worth a bloody good try.’’ Applied HTA is political both in the sense that it inherently embodies value judgments, including ones about equity or fairness, and in the sense that the identification and acceptance of value judgments of any kind require a process within the body politic; one, moreover, that needs to have particular characteristics if it is to lead to acceptable decisions

L'article cal llegir-lo sencer, i ens explica la història de dos dracs que si desperten poden ser molt entremaliats, necessiten atacar i matar. El primer drac és l'equitat, i com s'incorpora a l'avaluació de tecnologies sanitàries i el segon és la nostra ignorància del procés sobre com integrar precisament l'equitat en aquesta avaluació de tenologies. La dificultat de combinar evidència per articular conceptes poc evidents com és el cas de l'equitat. Si no som capaços de defensar-nos del segon drac o el desterrem, difícilment ens haurem salvat de l'atac del drac número 1. Sobre aquest complex procés comença amb una cita que comparteixo:

‘‘Arguably the biggest threat to our public health care system is not our ability to pay for the increasing cost of care, but rather a loss of public confidence.’’

L'article dona pistes per superar els dos dracs, però tampoc penseu que siguin definitives. I subscric plenament els paràgrafs de conclusió:

"HTA would be wise to broaden its horizons, turning away from what is largely just an algorithm to find ways to take seriously the myriad value and ethical issues, which currently still have the unfortunate appearance of afterthoughts tacked onto, but essentially excluded from, the core decision logic, and to develop an empirical program to rival, mutatis mutandis, that of CEA and CER. After all, nonmonetary values, although less easily measured perhaps than monetary ones, are still subject to empirical estimation, and the values that individuals actually cherish ought, at the least, to inform decision makers’ values. This is not merely a matter of expanding the algorithm but also, as I have tried to show, a matter of developing suitable processes that generate information through the participation of stakeholders while also facilitating the thoughtful assessment of what is known"

PS. Al mateix número del MDM hi ha molt material, que el deixo per un altre dia. I en especial a online first també  de Culyer. Si algú té dificultat d'accedir, només ha de dir-ho.

PS. Bon article d'en Josep Colomer sobre Europa.

PS. Al blog d'en Jason, sobre el frau a la recerca en càncer. Ell creu que és la punta de l'iceberg. Caldrà seguir-ho. A CBS trobareu un 60 minutes.


'Calgary 88', d'Antònia Font. on Vimeo.