title: Power Calculations to Select Instruments for Clinical Trial Secondary Endpoints. A Case Study of Instrument Selection for Post-Traumatic Stress Symptoms in Subjects with Acute Respiratory Distress Syndrome.
abstract: BACKGROUND
  After the sample size of a randomized clinical trial (RCT) is set by the power requirement of its primary endpoint, investigators select secondary endpoints while unable to further adjust sample size. How the sensitivity and specificity of an instrument used to measure these outcomes, together with their expected underlying event rates, affect an RCT's power to measure significant differences in these outcomes is poorly understood.
  
  
  OBJECTIVE
  Motivated by the design of an RCT of neuromuscular blockade in acute respiratory distress syndrome, we examined how power to detect a difference in secondary endpoints varies with the sensitivity and specificity of the instrument used to measure such outcomes.
  
  
  METHODS
  We derived a general formula and Stata code for calculating an RCT's power to detect differences in binary outcomes when such outcomes are measured with imperfect sensitivity and specificity. The formula informed the choice of instrument for measuring post-traumatic stress-like symptoms in the Reevaluation of Systemic Early Neuromuscular Blockade RCT ( www.clinicaltrials.gov identifier NCT02509078).
  
  
  RESULTS
  On the basis of published sensitivities and specificities, the Impact of Events Scale-Revised was predicted to measure a 36% symptom rate, whereas the Post-Traumatic Stress Symptoms instrument was predicted to measure a 23% rate, if the true underlying rate of post-traumatic stress symptoms were 25%. Despite its lower sensitivity, the briefer Post-Traumatic Stress Symptoms instrument provided superior power to detect a difference in rates between trial arms, owing to its higher specificity.
  
  
  CONCLUSIONS
  Examining instruments' power to detect differences in outcomes may guide their selection when multiple instruments exist, each with different sensitivities and specificities.
authors: 1 Department of Internal Medicine and.|2 Institute for Healthcare Policy & Innovation, University of Michigan, Ann Arbor, Michigan.
authors: Michael W
authors: MW
authors: Sjoding
authors: 3 Biostatistics Unit, Massachusetts General Hospital and Harvard University, Boston, Massachusetts.
authors: David A
authors: DA
authors: Schoenfeld
authors: 4 Department of Pulmonary and Critical Care Medicine, Intermountain Medical Center and University of Utah School of Medicine, Salt Lake City, Utah.
authors: Samuel M
authors: SM
authors: Brown
authors: 5 Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, Washington.
authors: Catherine L
authors: CL
authors: Hough
authors: 6 Department of Emergency Medicine and.
authors: Donald M
authors: DM
authors: Yealy
authors: 7 Department of Medicine, University of Colorado, Denver, Colorado; and.
authors: Marc
authors: M
authors: Moss
authors: 8 Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Derek C
authors: DC
authors: Angus
authors: 1 Department of Internal Medicine and.|9 Veterans Affairs Center for Clinical Management Research, Ann Arbor, Michigan.
authors: Theodore J
authors: TJ
authors: Iwashyna
mesh_terms: D001279:Atracurium / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003422:Critical Care; D006801:Humans; D019148:Neuromuscular Blockade / Q000523:psychology / Q000706:statistics & numerical data*; D009466:Neuromuscular Blocking Agents / Q000627:therapeutic use*; D017063:Outcome Assessment, Health Care; D016032:Randomized Controlled Trials as Topic; D012121:Respiration, Artificial / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000523:psychology / Q000628:therapy*; D018401:Sample Size; D012680:Sensitivity and Specificity; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis* / Q000453:epidemiology / Q000523:psychology
chemical_list: D009466:Neuromuscular Blocking Agents; D001279:Atracurium; C101584:cisatracurium
keywords: bias; clinical trials; critical care outcomes; sensitivity; specificity