Hi ha alternatives al llindar dels QALYs?

Determining the efficiency path to universal health coverage: cost-effectiveness thresholds for 174 countriesbased on growth in life expectancy and health expenditures

Alternatives To The QALY For Comparative Effectiveness Research 

Alternatives to QALY-Based Cost-Effectiveness Analysis for Determining the Value of Prescription Drugs and Other Health Interventions

Novel Approaches to Value Assessment Beyond the Cost-Effectiveness Framework

Des d'aquí he mostrat repetidament les dificultats de la fixació de llindars d'anys de vida ajustats per qualitat per decidir cobertura i copsar així el valor de la longevitat i qualitat de vida de les opcions terapèutiques. Avui recupero alguns materials recents que busquen anar més enllà d'aquesta mesura. Es tracta d'una orientació nordamericana perquè les lleis allà no afavoreixen la seva utilització, ans el contrari.

Poso tres referències, una al blog de Health Affairs, un altre oficial, i una tercera de ISPOR. Les alternatives tampoc són del tot satisfactòries però contribueixen al debat.

Ara que Medicare ha de fixar preus màxims per primera vegada, necessita un esquema i aquí va la comparació del que pot fer:

Illustrative comparison of different approaches for CMS to set a maximum fair price

Source: Illustrative evaluation based on author opinion. Notes: evLYG is equal value of life year gained. GRACE is generalized risk-adjusted cost-effectiveness. QALY is quality-adjusted life year. R&D is research and development. Low/Moderate/High refer to the potential of each criterion to achieve the objective.

Cal analitzar en detall la darrera opció, el llindar basat en GRACE+evLYG, ho deixo per un altre dia.

Si voleu tenir els llindars de cost-efectivitat de 174 països fets des d'una perspectiva nova podeu consultar el Lancet:

Cost-effectiveness thresholds per quality-adjusted life-year (QALY) ranged between US$87  (Democratic Republic of the Congo) and $95 958 (USA) and were less than 0·5 gross domestic product (GDP) per capita in 96% of low-income countries, 76% of lower-middle-income countries, 31% of upper-middle-income countries, and 26% of high-income countries. Cost-effectiveness thresholds per QALY were less than 1 GDP per capita in 168 (97%) of the 174 countries. Cost-effectiveness thresholds per life-year ranged between $78 and $80 529 and between 0·12 and 1·24 GDP per capita, and were less than 1 GDP per capita in 171 (98%) countries.

 Si voleu conèixer també les limitacions, s'expliquen a aquest comentari.

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.

 

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 benestar com objectiu preeminent

 Wellbeing. Science and Policy

Fa uns mesos parlava del llibre anterior de Richard Layard, "Podem ser més feliços?", ara el seu darrer llibre és un compendi del que ell en diu ciència del benestar. Jo no sé ben bé si és una ciència, però el que si és cert és que el tema és prou interessant com per fer-hi una ullada. Aquí el trobareu en accés obert. El primer que cal fer és mirar l'índex:

Part I. The Case for Wellbeing:

1. What subjective wellbeing is and why it matters

2. Wellbeing as the goal for society

Part II. Human Nature and Wellbeing:

3. How our behaviour affects our wellbeing

4. How our thoughts affect our wellbeing

5. Our bodies, our genes and our wellbeing

Part III. How Our Experience Affects Our Wellbeing:

6. The inequality of wellbeing: some basic facts

7. Tools to explain wellbeing

8. Explaining wellbeing: a first exploration

9. Family, schooling and social media

10. Health and healthcare

11. Unemployment

12. The quality of work

13. Income

14. Community

15. The physical environment and the planet

Part IV. Government and Wellbeing:

16. How government affects wellbeing

17. How wellbeing affects voting

18. Cost effectiveness and policy choice.

L'estructura del llibre és prou clara i dedica temps a explicar el problema de les mesures de benestar, qüestió sempre controvertida. 

De què depèn el benestar? Doncs d'aquests factors, diu:

De tots, possiblement el capítol menys encertat és el que parla dels gens i el benestar (p.85). La hipòtesi de que els gens no canvien i tenen un paper en el benestar, oblida l'epigenètica i per tant que podem tenir gens que s'activen o no depenent de les condicions amb les que ens trobem. Tema esbiaixat (cap al predeterminisme) i poc elaborat. A tot el llibre hi ha una èmfasi desproporcionada cap a la salut mental, qüestió que ha preocupat de sempre a l'autor.

I al darrer capítol arriba la qüestió crucial: 

The ultimate purpose of wellbeing science is to help us increase wellbeing. Hopefully, readers of this book will by now have learned a little more about themselves, which they can use to improve their own wellbeing and that of others. But what about  policymakers, be they in central or local government, or in NGOs big and small? Are there steps by which wellbeing science could help them improve their contribution to human wellbeing?

Enlloc de mesurar amb QALYs, ell proposa els WELLBYs, anys de vida ajustats per benestar. I llavors proposa els llindars necessaris per a avaluar si cal una política determinada. Molt ideal tot plegat, i pendent d'elaboració a la pràctica. El títol del llibre és suggerent, el seu contingut encara té moltes qüestions pendents per desenvolupar.

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.

Quant estem disposats a pagar pels tractaments genètics?

 Gene Therapies for Sickle Cell Disease. Evidence Report

L'anèmia de cèl·lules falciformes és una malaltia genètica que afecta l'hemoglobina. És causada per l'hemoglobina S, la qual es crea al canviar una glutamina per una valina en les cadenes polipèptiques beta; això provoca que en una situació de baixa tensió d'oxigen, l'hemoglobina es deforma i l'eritròcit adquireix una aparença d'una falç. Aquesta nova forma provoca dificultats pel que fa a la circulació dels glòbuls vermells, s'obstrueixen els vasos sanguinis i causen símptomes com, per exemple, dolor en les extremitats. Els glòbuls vermells també tenen una vida més curta i, a la vegada, això provoca una anèmia, ja que no poden ser reemplaçats a temps (Wikipedia).

L’única cura per malaltia de cèl·lules falciformes és el trasplantament de medul·la òssia o de cèl·lules mare. Com que aquests trasplantaments són arriscats i poden tenir efectes secundaris greus, en general només es fan servir en nens amb malaltia de cèl·lules falciformes greu. Hi ha tractaments que poden ajudar a alleujar els símptomes, disminuir les complicacions i allargar la vida, però res definitiu per ara com un tractament genètic.

Hi ha dos tractaments genètics en desenvolupament i pendents de propera aprovació a la FDA, lovo-cel i exa-cel. Aquest darrer basat en CRISPR. Miro una anàlisi d'efectivitat comparada i costos per QALY i veig que ens situem en 193.000$ de cost per QALY amb el supòsit d'un cost d'adquisició de 2.000.000 $, tant per lovo-cel, com per exo-cel.

El debat sobre els llindars dels QALYs és de final incert. Si ens situem a 30.000€ per QALY, hauriem d'acceptar més de 6 vegades el llindar pel cas d'exa-cel. Si tenim present els costos mitjans sanitaris de la vida, el nostre article de fa 10 anys deia: 111.936€ dones, 81.566€ homes (per cert, convé actualitzar-lo). És a dir que pagaríem per any ajustat per qualitat dues vegades el cost sanitari mitjà de tota la vida. Aquesta és una mètrica que crec interessant de considerar en el debat sobre els llindars. Però malauradament ningú hi pensa per ara.

Crec que convé reflexionar seriosament sobre tot el que ve, ho tenim a prop i no podrem dir que ens ha agafat per sorpresa. Perquè altrament ja sabem el que passarà, aplicarem la regla de rescat i qui dia passa any empeny, que això ho sabem fer molt bé.

Els dos dracs (2)

Algorithms and heuristics of health technology assessments: A retrospective analysis of factors associated with HTA outcomes for new drugs across seven OECD countries

Fa una dècada parlava dels dos dracs que en Tony Culyer va mostrar com a metàfora de l'avaluació de tecnologies. 

En Culyer 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 tecnologies. 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. 

Ara, en Panos Kanavos i col.laboradors revisen què ha passat. S'ha basat l'avaluació de tecnologies en una posició welfarista o extra-welfarista?. Per a contrastar-ho miren a 7 països entre 2009 i 2018. 

I els resultats són:

Our study reinforces arguments in favour of explicitly accounting for social value judgements, adopting risk mitigation strategies for novel therapies with early phase or immature evidence, and sharing of HTA practices across settings in order to avoid duplication of effort when assessing clinical evidence. Overall, our analysis adds to the debate between welfarist and extrawelfarist approaches in health technology  assessment by demonstrating that HTA agencies adopt the latter when making resource allocation  decisions.

Doncs això és el que sembla, una visió utilitarista dels QALYs és del tot insuficient, hem superat el segon drac de Culyer i ha estat vençut, i podem estar satisfets perquè el primer drac ha triomfat. Bé, això és parlar per parlar. Només val per als països de l'estudi i el nostre no hi és, ni hi pot ser...per ara.

PS: Aquí hi ha la referència clau al cost-effectivitat distributiu.

 

La productivitat dels professionals assistencials

La productivitat del treball es pot conèixer mitjançant la mesura de l'output ajustat per les hores treballades. El que pretén és identificar la quantitat del PIB real produïda per una hora de treball. Sabem que la productivitat depèn més enllà de les persones, de la inversió i infraestructures físiques i de l'organització i tecnologia. Quan mirem al sector salut, les coses es compliquen perquè l'output podríem dir que són anys de vida ajustats per qualitat (QALYs), o canvis en esperança de vida saludable però això esdevé molt complex de mesurar i en especial en períodes curts. El que si que podem mesurar és quantes visites i hospitalitzacions s'han realitzat en un període i quants recursos humans en hores s'hi han esmerçat. És una mesura parcial però si fem la mateixa al llarg del temps podrem comparar canvis en la productivitat.

Doncs bé, a Catalunya tenim aquesta mesura aproximada al SISCAT i es diu UME, unitat de mesura estadarditzada, i el detall de com es calcula el trobareu a la p.50 d'aquest informe. Aquesta mesura es troba disponible per a cada hospital i també el número de professionals titulats de grau superior assistencials (en hores a ple temps). La comparació entre hospitals pot donar lloc a alguns equívocs perquè aquesta mesura no ajusta segons risc i per tant hi ha alguns centres que surten "perjudicats" per una mesura imperfecta. No comentaré per tant quins són els millors ni quins els pitjors perquè pot donar lloc a equívocs. Jutgeu vosaltres mateixos mirant la p. 14.

Fixem-nos amb la productivitat agregada dels professionals titulats superiors assistencials que treballen als hospitals, el 2020, un any excepcional de pandèmia, cadascun d'ells va fer 134 UMEs. L'any anterior, el 2019 en van fer 129. L'any 2015 la productivitat en UMEs per professional va ser de 128. Per tant entre 2015 i 2020 la productivitat per professional va augmentar un 4,7%. Però entre el 2015 i el 2019, un 0,8%. A Catalunya per exemple la productivitat del treball al sector serveis va ser de -1,2% entre 2007 i 2013, anys de greu crisi econòmica (p.148). I entre 2001-2013 va ser de -1,1% (p.178). L'output del sector serveis esdevé especialment complex de mesurar i ha donat lloc a molts debats. Qui en vulgui detalls haurà de llegir Baumol.

Així doncs, encara que sabem que la mesura de la productivitat és imperfecta i no considera la qualitat, la comparació en el temps (si el capital, tecnologia i organització es mantenen constants...) ens mostra que els professionals assistencials de grau superior en atenció hospitalitzada va creíxer un 4,7% entre 2015 i 2020 especialment a causa de la pandèmia, perquè altrament fins el 2019 havia crescut el 0,8%. Amb totes les precaucions, aquesta és la dada amb i sense pandèmia. I qui en vulgui conèixer més sobre la controvèrsia de la productivitat al sector salut i serveis en general, aleshores haurà de llegir aquest llibre:

 

PD. Per cert, la darrera dada publicada de la Central de Balanços és de 2020, potser convindria afanyar-se i oferir dades més recents...

PD. Per cert, no trobo els acords que han fet desconvocar la vaga de metges. En un moment que el pressupost de 2023 és un 6,1% inferior, seria encara més rellevant conèixer si hi ha implicacions econòmiques, perquè voldrien dir o reassignació de partides o ampliació de crèdit (més dèficit).

Valuing health

 Measuring and Valuing Health Benefits for Economic Evaluation

This book addresses the theoretical and practical considerations in the measurement and valuation of health benefit with empirical examples and applications to help clarify understanding and make relevant links to the real world. It includes a glossary of key terms and provides guidance on the use of different methods and instruments. This updated edition provides an-up-to date review of the theoretical basis of the QALY; the definition of health; the techniques of valuation (including ordinal); the modelling of health state values (including mapping between measures); a detailed review of generic preference-based measures and other instruments for obtaining health state utility values (with recent developments); cross-cultural issues (including the disability-adjusted life year); the aggregation of QALYs; and the practical issues surrounding the use of utility values in cost-effectiveness models. The book concludes with a discussion on the way forward in light of the substantial methodological differences, the role of normative judgements, and where further research is most likely to take forward this fascinating component of health economics.

Economic evaluation of vaccination

 Evaluating Vaccination Programs That Prevent Diseases With Potentially Catastrophic Health Outcomes: How Can We Capture the Value of Risk Reduction?

Why QALYs doesn't fit for CEA of vaccination?

In the last 5 years, guidelines have been developed for performing cost-effectiveness analyses (CEAs) for the economic evaluation of vaccination programs against infectious diseases. However, these cost-effectiveness guidelines do not provide specific guidance for including the value of reducing the risk of rare but potentially catastrophic health outcomes, such as mortality or long-term sequelae. Alternative economic evaluation methods, including extended CEA, the impact inventory, cost-benefit analyses, willingness to pay or the value of a statistical life, to capture the value of this risk reduction could provide more complete estimates of the value of vaccination programs for diseases with potentially catastrophic health and nonhealth outcomes. In this commentary, using invasive meningococcal disease as an example, we describe these alternative approaches along with examples to illustrate how the benefits of vaccination in reducing risk of catastrophic health outcomes can be valued. These benefits are not usually captured in CEAs that only include population benefits estimated as the quality adjusted life-years gained and reduced costs from avoided cases.

 

What the hell do these people actually mean by "value" in healthcare?

 On the Much Used (and Abused) Word "Value" in Healthcare 

A must read speech by Uwe Reinhardt (RIP). Selected statements:

Now, when I listen to all this prattle on value among people of the real world, I ask myself, what the hell do these people actually mean by that? Well, you typically find it defined as outcomes relative to cost, and then encompassing efficiency. Now, you can have fun with this expression in New England as I had, there were all providers, they were all from the supply side and I said, “It’s a great expression, I never thought of it as an economist but let me play with it. See what you can do with this.” So let’s look at this equation. The first thing you’ll know is that quality is multi-dimensional, it’s a vector. We geeks, have a certain aversion to dividing a vector by a dollar figure. Somehow it is hard to teach this, so we invented this little magic machine that can mush up vectors of quality with vectors of utility, feelings, and out comes this thing called a “qaly” (quality adjusted live year). And you know, Bismarck says you should never inquire how laws are made it’s like making sausages. This is worse, this is actually a little bit like making dog food, but you know earnings per share on an income statement is worse in terms of its reliabilities. So let us look at this ratio where we have value equalling qaly over cost, which, by the way, the inverse of that is just what we call cost effectiveness. 

The more you think about this ratio, you run into a very famous law, Alfred E. Newman’s. Now, who in this audience knows Alfred E. Newman? You’re the most educated. You know kids nowadays don’t know anything, no wonder they’re so weird. They’re not well-read. We all grew up on Mad Magazine which kept us sane. If you hadn’t read Mad Magazine you’d all be nuts by now because Alfred E. Newman understood the world. Here is this famous law, one person’s healthcare cost is another ones healthcare income. Now that’s worth a Nobel laureate. So following Alfred E. Newman’s law, I’m going to write it like this and you can do that to healthcare providers and you see their little eyes ask, could this be true? Who here has ever served on a hospital board? I have on both for profit and not for profit. At any health clinic, what do they talk about: growth, growth, growth. It means revenue, so they don’t want to hear this. They want more qalys and more revenue, that’s what they really want. So, ask yourself this question; has anyone ever thought that the supply side folks want to create value for the patient by cutting their own revenue? I’ve never heard of that. 

Imagine a hospital board with an agenda item: 30 minutes on enhancing value for patients by lowering our revenue. Not thinkable. Has anyone ever seen such a board, or even an agenda item? I have served for over a decade on these boards, and not once. You know growth usually gets an hour; patient safety now gets a half hour. But efficiency, not once have I ever heard of it. It gets worse. We have this equation: revenue equals price times quantity times volume. Can you imagine how obscene that is to a hospital executive? Because they ask, “You mean we can create value by cutting prices? Aren’t prices and quality positively correlated?” And you say, “Why would you say that?” Even if you’re drunk, why would you ever say that? You know, so the hospital raises its price and you get more value.

 Highly recommended!

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.

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

Cost-effectiveness of genome sequencing (3)

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

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

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

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

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

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

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

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


Something is being missed...

Guillem Roma and Marta Roma

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

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

 

Toolkit for comparative effectiveness

Methods in comparative effectiveness research

If comparative effectiveness is the new fram for valuing health technologies, then we need the appropriate toolkit. This is not new, I said the same in 2010 and afterwards in this blog. Right now there is a difference, you may read in this 600 pages book all the details about it (a chapter on machine learnisn is missing).
A clear understanding of comparative effectiveness is precisely what the authors of this report have neglected, unfortunately. It doesn't make any sense to start economic evaluation without an assessment of comparative effectiveness. It doesn't make any sense to back for QALYs as an accounting approach. Forget this guidelines, and suggest to read this book.

This volume covers the main areas of quantitative methodology for the design and analysis of CER studies. The volume has four major sections—causal inference; clinical trials; research synthesis; and specialized topics. The audience includes CER methodologists, quantitative-trained researchers interested in CER, and graduate students in statistics, epidemiology, and health services and outcomes research. The book assumes a masters-level course in regression analysis and familiarity with clinical research.

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.

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

The costs of inaccuracy

The Lifetime Economic Burden of Inaccurate HER2 Testing: Estimating the Costs of False-Positive and False-Negative HER2 Test Results in US Patients with Early-Stage Breast Cancer

Diagnostic tests show different levels of false positive and negatives in the results. The impact of such unwanted results by physicians finally have an impact on health and quality of life of patients. You can check what does this means for HER-2 test in breast cancer in US in this article.

Patients with breast cancer whose tumors test positive for human epidermal growth factor receptor 2 (HER2) are treated with HER2-targeted therapies such as trastuzumab, but limitations with HER2 testing may lead to false-positive (FP) or false-negative (FN) results.

Among 226,870 women diagnosed with EBC in 2012, 3.12% (n = 7,070) and 2.18% (n = 4,955) were estimated to have had FP and FN test results, respectively. Approximately 8400 QALYs (discounted, lifetime) were lost among women not receiving trastuzumab because of FN results. The estimated incremental per-patient lifetime burden of FP or FN results was $58,900 and $116,000, respectively. The implied incremental losses to society were $417 million and $575 million, respectively.

That's a lot. Something should be done to improve accuracy in such tests. It was already known partially. Its cost-effectiveness is sensitive to HER-2 test properties.
However, as Kassirer said:

Absolute certainty in diagnosis is unattainable, no matter how much information we gather, how many observations we make, or how many tests we perform. A diagnosis is a hypothesis about the nature of a patient's illness, one that is derived from observations by the use of inference. Our task is not to attain certainty, but rather to reduce the level of diagnostic uncertainty enough to make optimal therapeutic decisions.

That's it.

Rafel Joan