Equipoise in Research and the Development of Neonatal Interventions for the Management of Respiratory Distress Syndrome: A Historical Perspective

Abstract

The historical review of how evidence was developed for the management of respiratory distress syndrome in premature infants has not been clearly characterized. Knowledge of this process is essential to understand the role of equipoise and its influence on the decision to evaluate interventions as they were implemented in the practice of medicine. We suspect that errant approaches to clinical equipoise secondary to states of false certainty and false uncertainty have been important barriers to the timely acquisition and implementation of evidence-based knowledge necessary to improve outcomes in this fragile population of infants. When confronted with the decision to test an intervention, physicians should question whether they have lost clinical equipoise based on opinion, expertise, or observational data rather than evidence obtained from methodological inquiry; doing so facilitates reaching clinical equipoise and promotes the application of scientific methodology to answer relevant clinical questions. Timely acquisition of evidence-based knowledge can be viewed as an ethical imperative when the status quo may have negative consequences on outcomes for generations.

Keywords

premature infant - respiratory distress syndrome - randomized controlled trials

• References

• 1 Freedman B. Equipoise and the ethics of clinical research. N Engl J Med 1987; 317 (3) 141-145
• 2 Mhaskar R, , B Bercu, B, Djulbegovic B. At what level of collective equipoise does a randomized clinical trial become ethical for the members of institutional review board/ethical committees?. Acta Inform Med 2013; 21 (3) 156-159
• 3 Ubel PA, Silbergleit R. Behavioral equipoise: a way to resolve ethical stalemates in clinical research. Am J Bioeth 2011; 11 (2) 1-8
• 4 Chu J, Clements JA, Cotton EK , et al. Neonatal pulmonary ischemia. I. Clinical and physiological studies. Pediatrics 1967; 40 (4) 709-782
• 5 Harrison VC, Heese HdeV, Klein M. The significance of grunting in hyaline membrane disease. Pediatrics 1968; 41 (3) 549-559
• 6 Gregory GA, Kitterman JA, Phibbs RH, Tooley WH, Hamilton WK. Treatment of the idiopathic respiratory-distress syndrome with continuous positive airway pressure. N Engl J Med 1971; 284 (24) 1333-1340
• 7 Kinsey VE. Etiology of retrolental fibroplasia: preliminary report of a co-operative study of retrolental fibroplasia. Am J Ophthalmol 1955; 40 (2) 166-174
• 8 Silverman WA. Personal reflections on lessons learned from randomized trials involving newborn infants, 1951 to 1967. James Lind Library; 2003. Available at: www.jameslindlibrary.org
• 9 Avery ME, Tooley WH, Keller JB , et al. Is chronic lung disease in low birth weight infants preventable? A survey of eight centers. Pediatrics 1987; 79 (1) 26-30
• 10 Avery ME, Mead J. Surface properties in relation to atelectasis and hyaline membrane disease. AMA J Dis Child 1959; 97 (5, Part 1) 517-523
• 11 Fujiwara T, Maeta H, Chida S, Morita T, Watabe Y, Abe T. Artificial surfactant therapy in hyaline-membrane disease. Lancet 1980; 1 (8159) 55-59
• 12 Hallman M, Merritt TA, Jarvenpaa A-L , et al. Exogenous human surfactant for treatment of severe respiratory distress syndrome: a randomized prospective clinical trial. J Pediatr 1985; 106 (6) 963-969
• 13 Enhorning G, Shennan A, Possmayer F, Dunn M, Chen CP, Milligan J. Prevention of neonatal respiratory distress syndrome by tracheal instillation of surfactant: a randomized clinical trial. Pediatrics 1985; 76 (2) 145-153
• 14 Shapiro DL, Notter RH, Morin III FC , et al. Double-blind, randomized trial of a calf lung surfactant extract administered at birth to very premature infants for prevention of respiratory distress syndrome. Pediatrics 1985; 76 (4) 593-599
• 15 Provost PR, Boucher E, Tremblay Y. Glucocorticoid metabolism in the developing lung: adrenal-like synthesis pathway. J Steroid Biochem Mol Biol 2013; 138: 72-80
• 16 Liggins GC. Premature delivery of foetal lambs infused with glucocorticoids. J Endocrinol 1969; 45 (4) 515-523
• 17 Liggins GC, Howie RN. A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Pediatrics 1972; 50 (4) 515-525
• 18 Avery ME. Historical overview of antenatal steroid use. Pediatrics 1995; 95 (1) 133-135
• 19 Collaborative Group on Antenatal Steroid Therapy. Effect of antenatal dexamethasone administration on the prevention of respiratory distress syndrome. Am J Obstet Gynecol 1981; 141 (3) 276-287
• 20 Dalziel SR, Walker NK, Parag V , et al. Cardiovascular risk factors after antenatal exposure to betamethasone: 30-year follow-up of a randomised controlled trial. Lancet 2005; 365 (9474) 1856-1862
• 21 Horbar JD, Badger GJ, Carpenter JH , et al; Members of the Vermont Oxford Network. Trends in mortality and morbidity for very low birth weight infants, 1991-1999. Pediatrics 2002; 110 (1, Pt 1) 143-151
• 22 Bonanno C, Wapner RJ. Antenatal corticosteroid treatment: what's happened since Drs Liggins and Howie?. Am J Obstet Gynecol 2009; 200 (4) 448-457
• 23 Roberts D, Dalziel S. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2006; (3) CD004454
• 24 Malloy MH. Antenatal steroid use and neonatal outcome: United States 2007. J Perinatol 2012; 32 (9) 722-727
• 25 Tyson JE, Parikh NA, Langer J, Green C, Higgins RD ; National Institute of Child Health and Human Development Neonatal Research Network. Intensive care for extreme prematurity—moving beyond gestational age. N Engl J Med 2008; 358 (16) 1672-1681
• 26 Verder H, Robertson B, Greisen G , et al; Danish-Swedish Multicenter Study Group. Surfactant therapy and nasal continuous positive airway pressure for newborns with respiratory distress syndrome. N Engl J Med 1994; 331 (16) 1051-1055
• 27 Verder H, Albertsen P, Ebbesen F , et al. Nasal continuous positive airway pressure and early surfactant therapy for respiratory distress syndrome in newborns of less than 30 weeks' gestation. Pediatrics 1999; 103 (2) E24
• 28 Rojas MA, Lozano JM, Rojas MX , et al; Colombian Neonatal Research Network. Very early surfactant without mandatory ventilation in premature infants treated with early continuous positive airway pressure: a randomized, controlled trial. Pediatrics 2009; 123 (1) 137-142
• 29 Thomson MA, Yoder BA, Winter VT , et al. Treatment of immature baboons for 28 days with early nasal continuous positive airway pressure. Am J Respir Crit Care Med 2004; 169 (9) 1054-1062
• 30 Allison BJ, Crossley KJ, Flecknoe SJ , et al. Ventilation of the very immature lung in utero induces injury and BPD-like changes in lung structure in fetal sheep. Pediatr Res 2008; 64 (4) 387-392
• 31 Hernandez LA, Peevy KJ, Moise AA, Parker JC. Chest wall restriction limits high airway pressure-induced lung injury in young rabbits. J Appl Physiol (1985) 1989; 66 (5) 2364-2368
• 32 Parker JC, Hernandez LA, Peevy KJ. Mechanisms of ventilator-induced lung injury. Crit Care Med 1993; 21 (1) 131-143
• 33 Björklund LJ, Ingimarsson J, Curstedt T , et al. Manual ventilation with a few large breaths at birth compromises the therapeutic effect of subsequent surfactant replacement in immature lambs. Pediatr Res 1997; 42 (3) 348-355
• 34 Morley CJ, Davis PG, Doyle LW, Brion LP, Hascoet JM, Carlin JB ; COIN Trial Investigators. Nasal CPAP or intubation at birth for very preterm infants. N Engl J Med 2008; 358 (7) 700-708
• 35 Finer NN, Carlo WA, Walsh MC , et al; SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Early CPAP versus surfactant in extremely preterm infants. N Engl J Med 2010; 362 (21) 1970-1979
• 36 Stevens TP, Harrington EW, Blennow M, Soll RF. Early surfactant administration with brief ventilation vs. selective surfactant and continued mechanical ventilation for preterm infants with or at risk for respiratory distress syndrome. Cochrane Database Syst Rev 2007; (4) CD003063
• 37 Bahadue FL, Soll R. Early versus delayed selective surfactant treatment for neonatal respiratory distress syndrome. Cochrane Database Syst Rev 2012; 11 (11) CD001456
• 38 Bhatia R, Davis PG, Doyle LW, Wong C, Morley CJ. Identification of pneumothorax in very preterm infants. J Pediatr 2011; 159 (1) 115-120.e1
• 39 Fischer HS, Bührer C. Avoiding endotracheal ventilation to prevent bronchopulmonary dysplasia: a meta-analysis. Pediatrics 2013; 132 (5) e1351-e1360
• 40 Göpel W, Kribs A, Ziegler A , et al; German Neonatal Network. Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial. Lancet 2011; 378 (9803) 1627-1634
• 41 Kanmaz HG, Erdeve O, Canpolat FE, Mutlu B, Dilmen U. Surfactant administration via thin catheter during spontaneous breathing: randomized controlled trial. Pediatrics 2013; 131 (2) e502-e509
• 42 Tsuji M, Saul JP, du Plessis A , et al. Cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants. Pediatrics 2000; 106 (4) 625-632
• 43 Milan A, Freato F, Vanzo V, Chiandetti L, Zaramella P. Influence of ventilation mode on neonatal cerebral blood flow and volume. Early Hum Dev 2009; 85 (7) 415-419
• 44 Dani C, Bertini G, Cecchi A, Corsini I, Pratesi S, Rubaltelli FF. Brain haemodynamic effects of nasal continuous airway pressure in preterm infants of less than 30 weeks' gestation. Acta Paediatr 2007; 96 (10) 1421-1425
• 45 Rogovik A, Goldman R. Permissive hypercapnia. Emerg Med Clin North Am 2008; 26 (4) 941-952 , viii–ix
• 46 Dilmen U, Özemir R, Tatar Aksoy H , et al. Early regular versus late selective poractant treatment in preterm infants born between 25 and 30 gestational weeks: a prospective randomized multicenter study. J Matern Fetal Neonatal Med 2014; 27: 411-415