AUTHORS’ RESPONSE

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:

1. 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.

2. 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.

3. 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.

4. 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.

   1. 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⁾

   2. 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.

   3. 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.

5. 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.

REFERÊNCIAS

• ¹
  Park M, Mendes PV, Zampieri FG, Azevedo LC, Costa EL, Antoniali F, Ribeiro GC, Caneo LF, Cruz Neto LM, 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):253-62.
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  Zigaib R, Noritomi DT. Critical care medicine: extracorporeal oxygenation is feasible in Brazil? Rev Bras Ter Intensiva. 2014;26(3):200-2.
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  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):1351-63. Erratum in Lancet. 2009;374(9698):1330.
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  Zampieri FG, Mendes PV, Ranzani OT, Taniguchi LU, Pontes Azevedo LC, Vieira Costa EL, et al. Extracorporeal membrane oxygenation for severe respiratory failure in adult patients: a systematic review and meta-analysis of current evidence. J Crit Care. 2013;28(6):998-1005.
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  Guérin C, Reignier J, Richard JC, Beuret P, Gacouin A, Boulain T, Mercier E, Badet M, Mercat A, Baudin O, Clavel M, Chatellier D, Jaber S, Rosselli S, Mancebo J, Sirodot M, Hilbert G, Bengler C, Richecoeur J, Gainnier M, Bayle F, Bourdin G, Leray V, Girard R, Baboi L, Ayzac L; PROSEVA Study Group. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med. 2013;368(23):2159-68.

Publication Dates

• Publication in this collection
  Mar 2015