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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.

TitlePower 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.
Publication TypeJournal Article
Year of Publication2017
AuthorsSjoding MW, Schoenfeld DA, Brown SM, Hough CL, Yealy DM, Moss M, Angus DC, Iwashyna TJ
Corporate AuthorsNHLBI Prevention and Early Treatment of Acute Lung Injury(PETAL) Network
JournalAnn Am Thorac Soc
Volume14
Issue1
Pagination110-117
Date Published2017 Jan
ISSN2325-6621
KeywordsAtracurium, critical care, Humans, Neuromuscular Blockade, Neuromuscular Blocking Agents, Outcome Assessment, Health Care, Randomized Controlled Trials as Topic, Respiration, Artificial, Respiratory Distress Syndrome, Sample Size, Sensitivity and Specificity, Stress Disorders, Post-Traumatic
Abstract

RATIONALE: 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.OBJECTIVES: 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).MEASUREMENTS AND MAIN 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.

DOI10.1513/AnnalsATS.201608-585OC
Alternate JournalAnn Am Thorac Soc
PubMed ID27788018
PubMed Central IDPMC5291478
Grant ListU01 HL123031 / HL / NHLBI NIH HHS / United States
U01 HL123020 / HL / NHLBI NIH HHS / United States
U01 HL122989 / HL / NHLBI NIH HHS / United States
U01 HL123009 / HL / NHLBI NIH HHS / United States
K24 HL089223 / HL / NHLBI NIH HHS / United States
U01 HL123004 / HL / NHLBI NIH HHS / United States
U01 HL123008 / HL / NHLBI NIH HHS / United States
U01 HL123022 / HL / NHLBI NIH HHS / United States
U01 HL123023 / HL / NHLBI NIH HHS / United States
U01 HL123027 / HL / NHLBI NIH HHS / United States
U01 HL122998 / HL / NHLBI NIH HHS / United States
T32 HL007749 / HL / NHLBI NIH HHS / United States
U01 HL123018 / HL / NHLBI NIH HHS / United States
U01 HL123033 / HL / NHLBI NIH HHS / United States
U01 HL123010 / HL / NHLBI NIH HHS / United States