title: Nonserious adverse events in randomized trials with opioid-dependent pregnant women: direct versus indirect measurement.
abstract: OBJECTIVE
  How best to measure the occurrence of adverse events during a randomized clinical trial is an issue that has not been adequately examined in the research literature. Focus of this study was on the examination of the relative frequency of occurrence of adverse events directly recorded during the conduct of the trial compared to an indirect determination of adverse events derived from data collected as part of the trial.
  
  
  METHODS
  A secondary analysis of nonserious adverse events that occurred in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) Study was undertaken. MOTHER was a randomized clinical trial of methadone versus buprenorphine in 175 opioid-dependent pregnant women.
  
  
  RESULTS
  The two methods of recording adverse events failed to agree on where differences in the frequency of occurrence of adverse events between the medication conditions might exist. Moreover, indirect assessment indicated all participants had experienced at least one adverse event, yet indirect coverage of adverse events was incomplete.
  
  
  CONCLUSIONS
  Findings suggest indirect examination of occurrence of adverse events should be cautiously undertaken, because indirect assessment of adverse events makes no distinction between what might be simply typical variation in behavior rather than systematic changes in behavior attributable to study condition, and lacks coverage of the full spectrum of adverse events.
  
  
  CONCLUSIONS
  Contemporaneous direct measurement of adverse events likely yield reasonably valid estimates of the rate of occurrence of the adverse events, while indirect measu-rement of adverse events may not be sufficiently reliable.
authors.affiliation: RTI International, Research Triangle Park, Triangle Park, NC 27709, USA. hjones@rti.org
authors.forename: Hendrée E
authors.initials: HE
authors.lastname: Jones
authors.forename: Karol
authors.initials: K
authors.lastname: Kaltenbach
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Heil
authors.forename: Susan M
authors.initials: SM
authors.lastname: Stine
authors.forename: Mara G
authors.initials: MG
authors.lastname: Coyle
authors.forename: Amelia M
authors.initials: AM
authors.lastname: Arria
authors.forename: Kevin E
authors.initials: KE
authors.lastname: O'Grady
authors.forename: Peter
authors.initials: P
authors.lastname: Selby
authors.forename: Peter R
authors.initials: PR
authors.lastname: Martin
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D002047:Buprenorphine / Q000009:adverse effects*; D003625:Data Collection / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008691:Methadone / Q000009:adverse effects*; D058850:Opiate Substitution Treatment / Q000009:adverse effects*; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*
chemical_list: D000701:Analgesics, Opioid; D002047:Buprenorphine; D008691:Methadone