More is exponentially less: marginal utility in critical care research

Authors

DOI:

https://doi.org/10.17267/2675-021Xevidence.2022.e4722

Keywords:

Clinical trials, Critical care, Intensive care, Marginal utility, Cognitive bias

Abstract

BACKGROUND: Randomized clinical trials (RCT) in critical care mostly return negative results. The research community discusses strategies to improve RCTs design. METHODS: This paper presents a theoretical framework based on marginal utility to treat the problems of hypothesis generation and treatment effects valuation and presents recently published high-quality studies as instances where such a framework predicts irrelevant findings. RESULTS: Blindness to marginal utility, i.e., inobservance of the marginal utility of the proposed intervention, is common in critical care RCTs. CONCLUSION: Critical care RCTs are usually blind to marginal utility and are, therefore, prone to produce irrelevant findings.

Downloads

Download data is not yet available.

References

(1) Ridgeon EE, Bellomo R, Aberegg SK, Sweeney RM, Varughese RS, Landoni G, et al. Effect sizes in ongoing randomized controlled critical care trials. Crit Care. 2017;21(1):132. https://doi.org/10.1186/s13054-017-1726-x

(2) Harhay MO, Wagner J, Ratcliffe SJ, Bronheim RS, Gopal A, Green S, et al. Outcomes and Statistical Power in Adult Critical Care Randomized Trials. Am J Respir Crit Care Med. 2014;189(12):1469-1478. https://doi.org/10.1164/rccm.201401-0056cp

(3) Ospina-Tascón GA, Büchele GL, Vincent, JL. Multicenter, randomized, controlled trials evaluating mortality in intensive care: doomed to fail?. Crit Care Med. 2008;36(4):1311–1322. https://doi.org/10.1097/ccm.0b013e318168ea3e

(4) Aberegg SK, Richards DR, O'Brien JM. Delta inflation: a bias in the design of random-ized controlled trials in critical care medicine. Crit Care. 2010;14(2):R77. https://doi.org/10.1186%2Fcc8990

(5) Streptomycin treatment of pulmonary tuberculosis. Br Med J. 1948;2(4582):769–82. Cit-ed: PMID: 18890300

(6) Encyclopaedia Britannica. Marginal utility [Internet]. 2016. Available from: https://www.britannica.com/topic/marginal-utility

(7) Encyclopaedia Britannica. Reductio ad absurdum [Internet]. 2022. Available from: https://www.britannica.com/topic/reductio-ad-absurdum.

(8) Dankiewicz J, Cronberg T, Lilja G, Jakobsen JC, Levin H, Ullén S, et al. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest. N Engl J Med. 2021;384(24):2283-2294. https://doi.org/10.1056/nejmoa2100591

(9) Schjørring OL, Klitgaard TL, Perner A, Wetterslev J, Lange T, Siegemund M, et al. Low-er or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure. N Engl J Med. 2021;384(14):1301-1311. https://doi.org/10.1056/NEJMoa2032510

(10) Hughes CG, Mailloux PT, Devlin JW, Swan JT, Sanders RD, Anzueto A, et al. Dexme-detomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis. N Engl J Med. 2021;384(15):1424-1436. https://doi.org/10.1056/nejmoa2024922

(11) Olsen HT, Nedergaard HK, Strøm T, Oxlund J, Wian KA, Ytrebø LM, et al. Nonseda-tion or Light Sedation in Critically Ill, Mechanically Ventilated Patients. N Engl J Med. 2020;382(12):1103-1111. https://doi.org/10.1056/nejmoa1906759

(12) Shehabi Y, Howe BD, Bellomo R, Arabi YM, Bailey M et al. Early Sedation with Dex-medetomidine in Critically Ill Patients. N Engl J Med. 2019;380():2506-2517. https://doi.org/10.1056/NEJMoa1904710

(13) National Heart, Lung, and Blood Institute PETAL Clinical Trials Network. Early Neuro-muscular Blockade in the Acute Respiratory Distress Syndrome. N Engl J Med. 2019;380(21):1997-2008. https://doi.org/10.1056/nejmoa1901686

(14) Arabi YM, Al-Hameed F, Burns KEA, Mehta S, Alsolamy SJ, Alshahrani MS, et al. Ad-junctive Intermittent Pneumatic Compression for Venous Thromboprophylaxis. N Engl J Med. 2019;380(14):1305-1315. https://doi.org/10.1056/nejmoa1816150

(15) François B, Cariou A, Clere-Jehl R, Dequin PF, Renon-Carron F, Daix T, et al. Prevention of Early Ventilator-Associated Pneumonia after Cardiac Arrest. N Engl J Med. 2019;381(19):1831-1842. https://doi.org/10.1056/nejmoa1812379

(16) Krag M, Marker S, Perner A, Wetterslev J, Wise MP, Schefold JC, et al. Pantoprazole in Patients at Risk for Gastrointestinal Bleeding in the ICU. N Engl J Med. 2018;379(23):2199-2208. https://doi.org/10.1056/nejmoa1714919

(17) TARGET Investigators. Energy-Dense versus Routine Enteral Nutrition in the Critically Ill. N Engl J Med. 2018;379(19):1823-1834. https://doi.org/10.1056/nejmoa1811687

(18) Sevransky JE, Rothman RE, Hager DN, Bernard GR, Brown SM, Buchman TG, et al. Effect of Vitamin C, Thiamine, and Hydrocortisone on Ventilator- and Vasopressor-Free Days in Patients With Sepsis: The VICTAS Randomized Clinical Trial. JAMA. 2021;325(8):742-750. https://doi.org/10.1001/jama.2020.24505

(19) Johnstone J, Meade M, Lauzier F, Marshall J, Duan E, Dionne J, et al. Effect of Probiot-ics on Incident Ventilator-Associated Pneumonia in Critically Ill Patients: A Randomized Clinical Trial. JAMA. 2021;326(11):1024-1033. https://doi.org/10.1001/jama.2021.13355

(20) Writing Committee and Steering Committee for the RELAx Collaborative Group. Effect of a Lower vs Higher Positive End-Expiratory Pressure Strategy on Ventilator-Free Days in ICU Patients Without ARDS: A Randomized Clinical Trial. JAMA. 2020;324(24):2509-2520. https://doi.org/10.1001/jama.2020.23517

(21) The PEPTIC Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Alberta Health Services Critical Care Strategic Clinical Network, and the Irish Critical Care Trials Group. Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial. JAMA. 2020;323(7):616-626. https://doi.org/10.1001/jama.2019.22190

(22) Lamontagne F, Richards-Belle A, Thomas K, Harrison DA, Sadique MZ, Grieve RD, et al. Effect of Reduced Exposure to Vasopressors on 90-Day Mortality in Older Critically Ill Patients With Vasodilatory Hypotension: A Randomized Clinical Trial. JAMA. 2020;323(10):938-949. https://doi.org/10.1001/jama.2020.0930

(23) Laterre PF, Berry SM, Blemings A, Carlsen JE, François B, Graves T, et al. Effect of Selepressin vs Placebo on Ventilator- and Vasopressor-Free Days in Patients With Septic Shock: The SEPSIS-ACT Randomized Clinical Trial. JAMA. 2019;322(15):1476-1485. https://doi.org/10.1001/jama.2019.14607

(24) Writing Committee for the PROBESE Collaborative Group of the PROtective VEntila-tion Network (PROVEnet) for the Clinical Trial Network of the European Society of An-aesthesiology. Effect of Intraoperative High Positive End-Expiratory Pressure (PEEP) With Recruitment Maneuvers vs Low PEEP on Postoperative Pulmonary Complications in Obese Patients: A Randomized Clinical Trial. JAMA. 2019;321(23):2292-2305. https://doi.org/10.1001/jama.2019.7505

(25) Vincent JL, Francois B, Zabolotskikh I, Daga MK, Lascarrou JB, Kirov MY, et al. Effect of a Recombinant Human Soluble Thrombomodulin on Mortality in Patients With Sepsis-Associated Coagulopathy: The SCARLET Randomized Clinical Trial. JAMA. 2019;321(20):1993-2002. https://doi.org/10.1001%2Fjama.2019.5358

(26) Azoulay E, Lemiale V, Mokart D, Nseir S, Argaud L, et al. Effect of High-Flow Nasal Oxygen vs Standard Oxygen on 28-Day Mortality in Immunocompromised Patients With Acute Respiratory Failure: The HIGH Randomized Clinical Trial. JAMA. 2018;320(20):2099–2107. https://doi.org/10.1001/jama.2018.14282

(27) Writing Group for the PReVENT Investigators. Effect of a Low vs Intermediate Tidal Volume Strategy on Ventilator-Free Days in Intensive Care Unit Patients Without ARDS: A Randomized Clinical Trial. JAMA. 2018;320(18):1872-1880. https://doi.org/10.1001/jama.2018.14280

(28) Harhay MO, Casey JD, Clement M, Collins SP, Gayat E, Gong MN, et al. Contemporary strategies to improve clinical trial design for critical care research: insights from the First Critical Care Clinical Trialists Workshop. Intensive Care Med. 2020;46(5):930-942. https://doi.org/10.1007/s00134-020-05934-6

(29) Abrams D, Montesi SB, Moore SKL, Manson DK, Klipper KM, Case MA, et al. Power-ing Bias and Clinically Important Treatment Effects in Randomized Trials of Critical Ill-ness. Crit Care Med. 2020;48(12):1710–1719. https://doi.org/10.1097/ccm.0000000000004568

(30) ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-33. https://doi.org/10.1001/jama.2012.5669

(31) Shankar-Hari M, Calfee CS. Lack of Clinical Benefit of Interferon ?-1a Among Patients With Severe Acute Respiratory Distress Syndrome: Time to Overhaul Drugs Trials in ARDS?. JAMA. 2020;323(8):713-715. https://doi.org/10.1001/jama.2019.22524

(32) Singer M, Deutschman CS, Seymour CW, Shanker-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. https://doi.org/10.1001%2Fjama.2016.0287

(33) Opal SM, Dellinger RP, Vincent JL, Masur H, Angus DC. The next generation of sepsis clinical trial designs: what is next after the demise of recombinant human activated pro-tein C?*. Crit Care Med. 2014;42(7):1714-1721. https://doi.org/10.1097/ccm.0000000000000325

(34) Van der Poll T, Van de Veerdonk FL, Scicluna BP, Netea MG. The immunopathology of sepsis and potential therapeutic targets. Nat Rev Immunol. 2017;17(7):407-420. https://doi.org/10.1038/nri.2017.36

(35) Nasraway Jr SA. Hyperglycemia during critical illness. JPEN J Parenter Enteral Nutr. 2006;30(3):254-8. https://doi.org/10.1177/0148607106030003254

Downloads

Published

11/04/2022

Issue

Section

Concept Articles

How to Cite

1.
Leite RO. More is exponentially less: marginal utility in critical care research . Evidence [Internet]. 2022 Nov. 4 [cited 2024 Nov. 4];4:e4722. Available from: https://journals.bahiana.edu.br/index.php/evidence/article/view/4722

Most read articles by the same author(s)

1 2 3 4 5 6 7 8 9 10 > >>