
==== Front
Ther Adv Med Oncol
Ther Adv Med Oncol
TAM
sptam
Therapeutic Advances in Medical Oncology
1758-8340
1758-8359
SAGE Publications Sage UK: London, England

10.1177/17588359241276812
10.1177_17588359241276812
Letter to the Editor
On cost-effectiveness analysis, quality-adjusted life years, and cost-effectiveness threshold values of gemcitabine plus nab-paclitaxel versus gemcitabine alone in metastatic pancreatic cancer in the French setting
https://orcid.org/0000-0003-4795-1834
Lazzaro Carlo Studio di Economia Sanitaria, Via Stefanardo da Vimercate, 19, Milan 20128, Italy
Biology and Biotechnologies Department “Lazzaro Spallanzani,” University of Pavia, Pavia 27100, Italy
Conceptualization Data curation Formal analysis Investigation Methodology Supervision Validation Visualization Writing – original draft Writing – review & editing
carlo.lazzaro@tiscalinet.it
2 9 2024
2024
16 1758835924127681216 7 2024
5 8 2024
© The Author(s), 2024
2024
SAGE Publications Ltd unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses
https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
cost-effectiveness analysis
France
gemcitabine
health services research
nab-paclitaxel
pancreatic cancer
cover-dateJanuary-December 2024
typesetterts1
==== Body
pmcDear Editor,

While I gratefully acknowledge Demaziere et al. 1 for quoting a publication I coauthored, 2 I would like to discuss three points their interesting article raised.

In cost-effectiveness analysis (CEA) 3 , cost and effectiveness should be reported as mean, 4 not median (see p. 10, Table 3 1 ). This methodological recommendation is based on three pillars. First, in a basic CEA comparing two healthcare programs (like gemcitabine plus nab-paclitaxel (GEM-NAB) and GEM alone), the incremental cost-effectiveness ratio (ICER) is calculated as the difference between the average cost of GEM-NAB versus GEM alone (incremental cost) divided by the difference between the average effectiveness of GEM-NAB versus GEM alone (incremental effectiveness).2–6 Second, assuming the absence of discounting, 3 when multiplied by the sample size, the mean (but not the median) cost per patient of a given healthcare program gives back its overall cost. 4 Third, healthcare costs follow a positively skewed Gamma distribution, with a long right tail. 7 Therefore, the median of the Gamma distribution is lower than its mean and does not give a true and fair view of the average costs per patient. In addition, the rule of thumb of more than 30 observations for the central limit theorem to kick in does not apply in the case of non-symmetric distribution. 7 As the cost distribution of medical transportation for GEM-NAB patients (see p. 10, Table 3 1 ) does not converge to a standard normal distribution, its median and mean do not (and cannot) overlap. As a result, the median cost per patient (€0) is clearly not a good proxy for the mean cost per patient of that healthcare resource.

I agree with Demaziere et al. 1 that life-years saved (LYS) with GEM-NAB and GEM alone should be weighted by patients’ health-related quality of life (also known as utility). 3 The resulting weight is the sum of health-state-specific patients’ utility subtracted the disutility due to therapy-related grade 3 and 4 adverse events.2,3,5,6 This way the difference in quality-adjusted life years (QALYs) between GEM-NAB and GEM alone (i.e. incremental QALYs) can be calculated and a cost-utility analysis (CUA) 3 performed, as previous research quoted by authors did.2,3,5,6

The last point refers to the local willingness to pay (WTP) for incremental LYS or QALY gained.

The French Health Authority did not explicitly set any WTP but estimated the value of an incremental LYS (€115,000; 2010 values) indirectly from the value of a statistical life (€3 million; 2010 values). 8 In addition, other informal threshold values for the same CEA/CUA outcomes have been proposed for France. They range from €30,000 to €50,000 9 and from €147,093 to €201,398. 10

Both the baseline ICERs (€20,128 and €40,256 per incremental LYS with GEM-NAB) reported by Demaziere et al. (see pp. 10, 11, Health costs analysis 1 ) and most of those shown in one-way sensitivity analysis 3 are lower than almost all the aforementioned threshold values.

Therefore, while GEM-NAB is potentially cost-effective for French national healthcare insurance, the uncertainty surrounding this finding should be further investigated via a cost-effectiveness acceptability curve. 3

None.

Declarations

ORCID iD: Carlo Lazzaro https://orcid.org/0000-0003-4795-1834

Ethics approval and consent to participate: This contribution was exempt from ethical review due to it being a Letter to the Editor.

Consent for publication: Not applicable.

Author contribution: Carlo Lazzaro: Conceptualization; Data curation; Formal analysis; Investigation; Methodology; Resources; Supervision; Validation; Visualization; Writing – original draft; Writing – review & editing.

Funding: The author received no financial support for the research, authorship, and/or publication of this article.

Carlo Lazzaro has no conflicts of interest/competing interests with this Letter to the Editor. Outside this Letter to the Editor, in the past 3 years, Carlo Lazzaro has received teaching fees from the University of Pavia, research grants, speaker or consultancy fees from argenx BV, AstraZeneca S.p.A, Ipsen S.p.A., Janssen-Cilag SPA, Horizon Therapeutics srl, Roche S.p.A., Roche Diagnostics S.p.A., Sanofi s.r.l., Santen GmbH, and Santen Italy S.R.L.

Availability of data and materials: Not applicable.

Declaration of generative artificial intelligence in scientific writing: Carlo Lazzaro declares that no section of this Letter to the Editor was supported by artificial intelligence.

Code availability: Not applicable.
==== Refs
References

1 Demaziere A Mourgues C Lambert C , et al . French multi-institutional cost-effectiveness analysis of gemcitabine plus nab-paclitaxel versus gemcitabine alone as second-line treatment in metastatic pancreatic cancer patients. Ther Adv Med Oncol 2024; 16 : 1–14.
2 Lazzaro C Barone C Caprioni F , et al . An Italian cost-effectiveness analysis of paclitaxel albumin (nab-paclitaxel) + gemcitabine vs. gemcitabine alone for metastatic pancreatic cancer patients: the APICE study. Expert Rev Pharmacoecon Outcomes Res 2018; 18 : 435–446.29641931
3 Drummond MF Sculpher MJ Claxton K , et al . Methods for the economic evaluation of health care programmes. 4th ed. Oxford: Oxford University Press, 2015, pp.5–10, 58, 62, 302.
4 Gray A Clarke PM Wolstenholme JL , et al . Applied methods of cost-effectiveness analysis in healthcare. Oxford: Oxford University Press, 2011, pp.147 , 268–270.
5 Carrato A García P López R , et al . Cost-utility analysis of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in combination with gemcitabine in metastatic pancreatic cancer in Spain: results of the PANCOSTABRAX study. Expert Rev Pharmacoecon Outcomes Res 2015; 15 : 579–589.25991037
6 Gharaibeh M McBride A Bootman JL , et al . Economic evaluation for the US of nab-paclitaxel plus gemcitabine versus FOLFIRINOX versus gemcitabine in the treatment of metastatic pancreas cancer. J Med Econ 2017; 20 : 345–352.27919186
7 Briggs A Nixon R Dixon S , et al . Parametric modelling of cost data: some simulation evidence. Health Econ 2005; 14 : 421–428.15685641
8 Haute Autorité de Santé H . Valeurs de reference pour l’évaluation économique en santé, https://www.has-sante.fr/upload/docs/application/pdf/2014-12/fiche_synthese_vf.pdf (2014, accessed 15 July 2024).
9 Cartier-Bechu C Gherardi A Sivignon M , et al . Is there a threshold in France?: First exhaustive review of published health-economic appraisals by the Haute Autorite De Sante (HAS), (French National Authority for Health). Value Health 2016; 19 : PA490.
10 Téhard B Detournay B Borget I , et al . Value of a QALY for France: a new approach to propose acceptable reference values. Value Health 2020; 23 : 985–993.32828226
