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To: The economic effect of extracorporeal membrane oxygenation to support
adults with severe respiratory failure in Brazil: a hypothetical
analysis
Para: Efeito econômico do uso da oxigenação
extracorpórea para suporte de pacientes adultos com insuficiência
respiratória grave no Brasil: uma análise
hipotética
1Secretaria Municipal de Saúde de Porto Alegre - Porto Alegre (RS), Brazil.
✉
Corresponding author: Ângelo Zambam de Mattos, Rua Professor
Annes Dias, 154/1.103, Zip code: 90020-090 - Porto Alegre (RS), Brazil. E-mail:
angmattos@hotmail.com
Issue date 2015 Jan-Mar.
This is an Open Access article distributed under the terms of the Creative
Commons Attribution Non-Commercial License which permits unrestricted
non-commercial use, distribution, and reproduction in any medium, provided the
original work is properly cited.
This letter regards the study published by Park et al.,(1) which deserved an interesting editorial.(2) The initiative of health technology
economic evaluation is of great importance. Nevertheless, some issues of this study need
further discussion.
The authors of the study performed a cost-effectiveness analysis, comparing the treatment
of adults with severe respiratory failure with and without extracorporeal membrane
oxygenation (ECMO), and reached the following surprising result: ECMO would probably not
only be cost-effective, but, in one scenario, it could even be cost-saving in
Brazil.(1) However, from a
conceptual point of view, an economic evaluation should be conducted after a new
intervention is proven effective.
The only randomized clinical trial regarding this matter published after the lung
protective ventilation era(3) has several
methodological problems. One of them is that patients randomized to ECMO were treated in a
single specialized center, while controls were treated in up to 92 different centers, using
different treatment protocols. Consequently, the survival of patients allocated to the
control group (50%) was much lower than that of patients randomized to ECMO, who were
treated in the ECMO center without receiving ECMO (82%). Another problem is that while ECMO
was better than the control strategy regarding survival or severe disability (compound
outcome), there was no significant difference between treatments in terms of the survival,
and severe disability was detected in a single patient of the control group.(3)
Moreover, in a meta-analysis published by some of the authors responsible for this economic
evaluation, the main analysis did not find a significant difference between ECMO and
conventional therapy regarding survival (odds ratio = 0.71, 95% confidence interval = 0.34
- 1.47, p = 0.358). The authors concluded that there was insufficient evidence to recommend
ECMO.(4)
Considering the abovementioned, we understand that it is rather soon to perform an economic
evaluation regarding ECMO, and we think efforts should be concentrated on defining whether
this is an effective treatment option for adult respiratory distress syndrome.
Regarding the results of the Brazilian cost-effectiveness analysis,(1) the ECMO costs were substantially lower
than those presented in the piggy-back economic evaluation by Peek et al.(3) Although some differences could be
explained by the specific characteristics of each country, it is not reasonable to think
that while ECMO would be associated to an incremental cost-effectiveness ratio (ICER) of
31,112 US dollars per QALY in the United Kingdom (UK),(3) it would be associated with an ICER between -280 and 7 Brazilian
reais per QALY in Brazil.(1) This
difference could be explained by the Brazilian study not accounting for medical
professional costs or costs related to the transportation of the patients to the ECMO
center. In this context, it would also be interesting to understand why Brazilian patients
undergoing ECMO spent less time in the intensive care unit and in the hospital than
patients who did not use ECMO,(1) which
is the exact opposite of what happened in the UK.(3) Moreover, it would have been interesting to evaluate, in the
decision tree, the role of the prone positioning strategy, which has positive outcomes with
low incremental costs.(5)
Therefore, the results of this cost-effectiveness analysis should be interpreted with
caution.
Ângelo Zambam de Mattos, Diego Silva Leite Nunes - Secretaria Municipal de
Saúde de Porto Alegre - Porto Alegre (RS), Brazil.
Footnotes
Conflicts of interest: None.
REFERENCES
1.Park M, Mendes PV, Zampieri FG, Azevedo LC, Costa EL, Antoniali F, Ribeiro GC, Caneo LF, Cruz LM, Neto, Carvalho CR, Trindade EM, Grupo de investigadores ERICC. grupo de ECMO do Hospital Sírio Libanês e do Hospital das
Clínicas de São Paulo The economic effect of extracorporeal membrane oxygenation to support
adults with severe respiratory failure in Brazil: a hypothetical
analysis. Rev Bras Ter Intensiva. 2014;26(3):253–262. doi: 10.5935/0103-507X.20140036. [DOI] [PMC free article] [PubMed] [Google Scholar]
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3.Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, Firmin RK, Elbourne D, CESAR trial collaboration Efficacy and economic assessment of conventional ventilatory support
versus extracorporeal membrane oxygenation for severe adult respiratory failure
(CESAR): a multicentre randomised controlled trial. Lancet. 2009;374(9698):1351–1363. doi: 10.1016/S0140-6736(09)61069-2. Erratum in Lancet. 2009;374(9698):1330. [DOI] [PubMed] [Google Scholar]
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adult patients: a systematic review and meta-analysis of current
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We thank Mattos and Nunes for their careful reading, comments and concerns about our
study.(1) Since April 2011, the
Brazilian Health Ministry has created a system devoted to the care for health technology
assessment, which is called “Comissão Nacional de
Incorporação de Tecnologias para o SUS (CONITEC)”. Moreover,
the method for technology incorporation is positively complex and accomplishes an
extensive and detailed literature review (efficacy analysis) of the potential long-term
impact in quality of life (utility analysis), cost analysis, cost-utility analysis,
public consultation and a re-analysis of all cited steps. Undoubtedly, it consists of a
step towards developing health, economy and culture in Brazil. Brazil is a middle-income
country where health costs and cost utility are considered before any technology is
incorporated in the public healthcare system because health technology can potentially
add unnecessary or disproportional costs in spite of the utility, resulting in further
inequalities to our nation. This is a very important open debate.
In answer to the letter authors’ concerns:
The study in question(1) was
based on real Brazilian epidemiological data(2) and local experience with respiratory extracorporeal
membrane oxygenation (ECMO).(3)
In spite of the representative data, the assumptions of a modeled decision tree
analysis produce estimated conclusions; therefore, the study was considered a
hypothetical one.
The finding of a negative cost-utility ratio classifies a procedure as an
acceptable cost or as a cost-saving one; however, it ascertains the degree of
uncertainty around the estimate. Moreover, the manuscript discusses its economic
significance.
About the ECMO efficacy: the European, USA and Agência
Sanitária de Vigilância Sanitária (ANVISA)
regulators accepted those published trials as having sufficient efficacy evidence
to allow for market approval. Effectiveness, however, depends on the team
skills.
The authors expressed methodological concerns about the CESAR trial.(4) We would like to highlight that
CESAR was a pragmatic trial about efficacy and economical evaluation in the United
Kingdom.
Severe acute respiratory distress syndrome patients were transferred to a
referral center, where, after an initial observational period, the patient
was only placed on ECMO if improvement on conventional support was not
observed. (Therefore, it is intuitive that of transferred hypoxemic patients
who improved without ECMO, 18%, were indeed less severe patients, explaining
the low mortality of this subgroup. Furthermore, the natural history of this
disease observed in the control arm of the three randomized studies
demonstrates all-cause mortality of 50%-92%.) This strategy of transference,
observation, and, if necessary, ECMO support was cost-effective for this UK
health technology assessment.(4)
The combined analysis of death and severe disability in the CESAR trial is
straightforward once the severe acute respiratory distress syndrome (ARDS)
patients commonly have severe long-term disabilities.(5) Furthermore, the conceptual
frame of cost-utility analysis focuses on the lifetime gained with quality,
QALY.
Although the control groups were from 92 different centers, each center was
strongly advised to apply low tidal volumes of 6 - 8mL/kg with a plateau
pressure lower than 30cmH2O according to the ARDS network
guidelines and group trial.(6) The resulting low number of events of severe disability
shows that the best support was offered for patients enrolled in both
groups.
The letter authors also quote lack of evidence of ECMO efficacy, which was cited
in a recent Brazilian systematic review and metanalysis(7) about adult patients with three studies. Two of
these studies evaluated patients with severe influenza A (H1N1) pneumonitis in
France(8) and the United
Kingdom.(9) These studies
had retrospective data analysis with propensity score matching. Both studies were
positive when all ECMO supported patients were analyzed. However, due to the
extreme severity of the ECMO group and absence of pairs with such severity in the
control group, some patients in the control group were replicated. When
replications were excluded, the final results of this metanalysis did not favor
the use of ECMO. Additionally, the pregnant and more severe patients of the ECMO
supported group were excluded from such negative analysis.(8) It is notable that ECMO selection
criteria include those more severe patients and pregnant women. Therefore, such
results are sensitive to the analysis.
In summary, the first Brazilian ECMO technology costs required hypothetical analysis;
however, the data analysis is ongoing in the Brazilian environment. The best currently
available evidence shows that ECMO is a salvage therapy for selected patients. There
were current examples in the influenza A H1N1 epidemics and in Porto Alegre after the
Santa Maria Boate Kiss disaster when a Canadian assistance team offered ECMO support for
three surviving patients. The model of the ECMO reference centers was and is being
adopted internationally. ECMO is a complex technology requiring in-depth training. It is
worth evaluating severely ill patients,(4,9) which can help to answer
this question for the Brazilian citizens.
Marcelo Park, Pedro Vitale Mendes, and Evelinda Marramon Trindade, on behalf of
authors - Hospital das Clínicas, Faculdade de Medicina, Universidade de
São Paulo - São Paulo (SP), Brazil.
REFERENCES
1.Park M, Mendes PV, Zampieri FG, Azevedo LC, Costa EL, Antoniali F, et al. The economic effect of extracorporeal membrane oxygenation to
support adults with severe respiratory failure in Brazil: a hypothetical
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investigators Clinical outcomes of patients requiring ventilatory support in
Brazilian intensive care units: a multicenter, prospective, cohort
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supporting severely ill patients using extracorporeal membrane
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in adult patients: a systematic review and meta-analysis of current
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A(H1N1)-induced acute respiratory distress syndrome: a cohort study and
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