The SOFA score-development, utility and challenges of accurate assessment in clinical trials

Simon Lambden, Pierre Francois Laterre, Mitchell M Levy, Bruno Francois, Simon Lambden, Pierre Francois Laterre, Mitchell M Levy, Bruno Francois

Abstract

The Sequential Organ Failure Assessment or SOFA score was developed to assess the acute morbidity of critical illness at a population level and has been widely validated as a tool for this purpose across a range of healthcare settings and environments.In recent years, the SOFA score has become extensively used in a range of other applications. A change in the SOFA score of 2 or more is now a defining characteristic of the sepsis syndrome, and the European Medicines Agency has accepted that a change in the SOFA score is an acceptable surrogate marker of efficacy in exploratory trials of novel therapeutic agents in sepsis. The requirement to detect modest serial changes in a patients' SOFA score therefore means that increased clarity on how the score should be assessed in different circumstances is required.This review explores the development of the SOFA score, its applications and the challenges associated with measurement. In addition, it proposes guidance designed to facilitate the consistent and valid assessment of the score in multicentre sepsis trials involving novel therapeutic agents or interventions.ConclusionThe SOFA score is an increasingly important tool in defining both the clinical condition of the individual patient and the response to therapies in the context of clinical trials. Standardisation between different assessors in widespread centres is key to detecting response to treatment if the SOFA score is to be used as an outcome in sepsis clinical trials.

Keywords: Clinical Trials; Critical Care trials; Multiple organ failure; SOFA; Sepsis; Sequential Organ Failure Assessment; Surrogate endpoints.

Conflict of interest statement

SL, BF, ML and PFL are all involved in the design and conduct of clinical trials of novel therapeutic agents that utilise the change in SOFA score as a key endpoint. SL reports consultancy fees from Inotrem SA, during the conduct of the study and is the founding director of Critical Pressure Ltd., outside the submitted work. PFL reports personal fees from Inotrem, during the conduct of the study. ML reports non-financial support from Inotrem, during the conduct of the study. BF reports personal fees from Inotrem, during the conduct of the study, and personal fees from Biomérieux, Aridis, Ashai-Kasai, Polyphor, AM-Pharma and Ferring, outside the submitted work.

SL is a founding director of critical pressure ltd, a biotechnology company developing novel vasopressors for the treatment of shock. He also receives consultancy fees from Inotrem SA Ltd. for his work developing novel therapeutics for septic shock.

References

    1. Seymour CW, Liu VX, Iwashyna TJ, Brunkhorst FM, Rea TD, Scherag A, et al. Assessment of clinical criteria for sepsis For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) JAMA. 2016;315(8):762–774. doi: 10.1001/jama.2016.0288.
    1. Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, et al. Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (sepsis-3) JAMA. 2016;315(8):775–787. doi: 10.1001/jama.2016.0289.
    1. Singer M, Deutschman CS, Seymour C, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3) JAMA. 2016;315(8):801–810. doi: 10.1001/jama.2016.0287.
    1. Guideline on clinical investigation of medicinal products for the treatment of sepsis. Edited by European Medicine Agency. CHMP/EWP/4713/03 2006.
    1. Vincent JL, Moreno R, Takala J, Willatts S, Mendonca A, Bruining H. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–710. doi: 10.1007/BF01709751.
    1. Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on “sepsis-related problems” of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793–1800. doi: 10.1097/00003246-199811000-00016.
    1. Marshall JC, Cook DJ, Christou NV, Bernard GR, Sprung CL, Sibbald WJ. Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med. 1995;23(10):1638–1652. doi: 10.1097/00003246-199510000-00007.
    1. Moreno R, Vincent JL, Matos R, Mendonca A, Cantraine F, Thijs L, et al. The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM. Intensive Care Med. 1999;25(7):686–696. doi: 10.1007/s001340050931.
    1. Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001;286(14):1754–1758. doi: 10.1001/jama.286.14.1754.
    1. Pettila V, Pettila M, Sarna S, Voutilainen P, Takkunen O. Comparison of multiple organ dysfunction scores in the prediction of hospital mortality in the critically ill. Crit Care Med. 2002;30(8):1705–1711. doi: 10.1097/00003246-200208000-00005.
    1. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, et al. Sepsis in European intensive care units: results of the SOAP study. Crit Care Med. 2006;34(2):344–353. doi: 10.1097/01.CCM.0000194725.48928.3A.
    1. Lie KC, Lau C-Y, Van Vinh Chau N, West TE, Limmathurotsakul D, for Southeast Asia Infectious Disease Clinical Research N Utility of SOFA score, management and outcomes of sepsis in Southeast Asia: a multinational multicenter prospective observational study. J Intensive Care. 2018;6:9. doi: 10.1186/s40560-018-0279-7.
    1. Vasilevskis EE, Pandharipande PP, Graves AJ, Shintani A, Tsuruta R, Ely EW, et al. Validity of a Modified Sequential Organ Failure Assessment score using the Richmond Agitation-Sedation Scale. Crit Care Med. 2016;44(1):138–146. doi: 10.1097/CCM.0000000000001375.
    1. Fowler AA, III, Truwit JD, Hite RD, Morris PE, DeWilde C, Priday A, et al. Effect of vitamin C infusion on organ failure and biomarkers of inflammation and vascular injury in patients with sepsis and severe acute respiratory failure: the CITRIS-ALI Randomized Clinical Trial. JAMA. 2019;322(13):1261–1270. doi: 10.1001/jama.2019.11825.
    1. Richter S, Stevenson S, Newman T, Wilson L, Menon D, Maas AI, et al. Handling of missing outcome data in traumatic brain injury research: a systematic review. J Neurotrauma. 2019;36(19):2743–2752. doi: 10.1089/neu.2018.6216.
    1. Jakobsen JC, Gluud C, Wetterslev J, Winkel P. When and how should multiple imputation be used for handling missing data in randomised clinical trials – a practical guide with flowcharts. BMC Med Res Methodol. 2017;17(1):162. doi: 10.1186/s12874-017-0442-1.
    1. Tallgren M, Bäcklund M, Hynninen M. Accuracy of sequential organ failure assessment (SOFA) scoring in clinical practice. Acta Anaesthesiol Scand. 2009;53(1):39–45. doi: 10.1111/j.1399-6576.2008.01825.x.
    1. Knaus WA, Wagner DP, Draper EA, Zimmerman JE, Bergner M, Bastos PG, et al. The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Chest. 1991;100(6):1619–1636. doi: 10.1378/chest.100.6.1619.
    1. Academy of Medical Royal Colleges . A code of practice for the diagnosis and confirmation of death. 2010.
    1. Sendagire C, Lipnick MS, Kizito S, Kruisselbrink R, Obua D, Ejoku J, et al. Feasibility of the modified sequential organ function assessment score in a resource-constrained setting: a prospective observational study. BMC Anesthesiol. 2017;17(1):12. doi: 10.1186/s12871-017-0304-8.
    1. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009;302(21):2323–2329. doi: 10.1001/jama.2009.1754.
    1. Luo JC, Lu MS, Zhao ZH, Jiang W, Xu B, Weng L, et al. Positive end-expiratory pressure effect of 3 high-flow nasal cannula devices. Respir Care. 2017;62(7):888–895. doi: 10.4187/respcare.05337.
    1. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Intensive Care Med. 2017;43(3):304–377. doi: 10.1007/s00134-017-4683-6.
    1. Khanna A, English SW, Wang XS, Ham K, Tumlin J, Szerlip H, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377(5):419–430. doi: 10.1056/NEJMoa1704154.
    1. Liu ZM, Chen J, Kou Q, Lin Q, Huang X, Tang Z, et al. Terlipressin versus norepinephrine as infusion in patients with septic shock: a multicentre, randomised, double-blinded trial. Intensive Care Med. 2018;44(11):1816–1825. doi: 10.1007/s00134-018-5267-9.
    1. Arts DG, de Keizer NF, Vroom MB, de Jonge E. Reliability and accuracy of sequential organ failure assessment (SOFA) scoring. Crit Care Med. 2005;33(9):1988–1993. doi: 10.1097/01.CCM.0000178178.02574.AB.
    1. Grissom CK, Brown SM, Kuttler KG, Boltax JP, Jones J, Jephson AR, et al. A modified sequential organ failure assessment score for critical care triage. Dis Med Publ Health Prep. 2010;4(4):277–284. doi: 10.1001/dmp.2010.40.
    1. Gholipour Baradari A, Sharifi H, Firouzian A, Daneshiyan M, Aarabi M, Talebiyan Kiakolaye Y, et al. Comparison of Proposed Modified and Original Sequential Organ Failure Assessment Scores in Predicting ICU Mortality: A Prospective, Observational, Follow-Up Study. Scientifica (Cairo) 2016;2016:7379325.
    1. Greenberg JA, David MZ, Churpek MM, Pitrak DL, Hall JB, Kress JP. Sequential Organ Failure Assessment score modified for recent infection in patients with hematologic malignant tumors and severe sepsis. Am J Crit Care. 2016;25(5):409–417. doi: 10.4037/ajcc2016281.
    1. Demandt AMP, Geerse DA, Janssen BJP, Winkens B, Schouten HC, van Mook WNKA. The prognostic value of a trend in modified SOFA score for patients with hematological malignancies in the intensive care unit. Eur J Haematol. 2017;99(4):315–322. doi: 10.1111/ejh.12919.
    1. Sessler CN, Gosnell MS, Grap MJ, Brophy GM, O'Neal PV, Keane KA, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med. 2002;166(10):1338–1344. doi: 10.1164/rccm.2107138.
    1. Vincent J-L, Takala J, Moreno RP, Sakr Y, Marshall JC. The Richmond Agitation-Sedation Scale should not be used to evaluate neurologic function. Crit Care Med. 2016;44(6):e450. doi: 10.1097/CCM.0000000000001597.
    1. Gordon AC, Perkins GD, Singer M, McAuley DF, Orme RML, Santhakumaran S, et al. Levosimendan for the prevention of acute organ dysfunction in sepsis. N Engl J Med. 2016;375(17):1638–1648. doi: 10.1056/NEJMoa1609409.
    1. Leadership members of American College of Chest Physicians/ Society of Critical Care Medicine. American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med. 1992;20(6):864–74.
    1. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004;30(4):536–555. doi: 10.1007/s00134-004-2210-z.
    1. Dellinger R, Levy M, Rhodes A, Annane D, Gerlach H, Opal S, et al. Surviving Sepsis campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228. doi: 10.1007/s00134-012-2769-8.
    1. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Crit Care Med. 2013;41(2):580–637. doi: 10.1097/CCM.0b013e31827e83af.
    1. Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010;36(2):222–231. doi: 10.1007/s00134-009-1738-3.
    1. STRESS-L protocol. https://wwwisrctncom/ISRCTN12600919?q=&filters=&sort=&offset=4&totalResults=16507&page=1&pageSize=10&searchType=basic-search.
    1. de Grooth H-J, Geenen IL, Girbes AR, Vincent J-L, Parienti J-J, Oudemans-van Straaten HM. SOFA and mortality endpoints in randomized controlled trials: a systematic review and meta-regression analysis. Crit Care. 2017;21(1):38. doi: 10.1186/s13054-017-1609-1.
    1. Garcia-Gigorro R, Saez-de la Fuente I, Marin Mateos H, Andres-Esteban EM, Sanchez-Izquierdo JA, Montejo-Gonzalez JC. Utility of SOFA and Delta-SOFA scores for predicting outcome in critically ill patients from the emergency department. Eur J Emerg Med. 2018;25(6):387–393.
    1. Iba T, Arakawa M, Mochizuki K, Nishida O, Wada H, Levy JH. Usefulness of measuring changes in SOFA score for the prediction of 28-day mortality in patients with sepsis-associated disseminated intravascular coagulation. Clin Appl Thromb Hemost. 2019;25:1076029618824044. doi: 10.1177/1076029618824044.
    1. Mastuda J. The assessment of sofa score predicts mortality and neurological outcome in post-cardiac arrest syndrome patients. J Am Coll Cardiol. 2019;73(9):1217. doi: 10.1016/S0735-1097(19)31824-8.
    1. Ferreira F, Bota D, Bross A, Melot C, Vincent J-L. How changes in SOFA score can predict outcome. Crit Care Med. 1999;27(12):A50. doi: 10.1097/00003246-199912001-00102.
    1. Tee Y-S, Fang H-Y, Kuo IM, Lin Y-S, Huang S-F, Yu M-C. Serial evaluation of the SOFA score is reliable for predicting mortality in acute severe pancreatitis. Medicine (Baltimore) 2018;97(7):e9654. doi: 10.1097/MD.0000000000009654.

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