title: Adverse non-drug-related complaints by healthy volunteers in Phase I studies compared to the healthy general population.
abstract: OBJECTIVE
  Some complaints that are reported as adverse drug reactions by healthy subjects during participation in Phase I studies are common complaints in healthy individuals from the normal population. The objective of this study was to compare the incidence of complaints in a group of 192 healthy volunteers in Phase I studies with a control group of 112 healthy subjects who matched the Phase I group participants in terms of demographic and socioeconomic characteristics, and to investigate the relationship between some psychological factors and the incidence of complaints.
  
  
  METHODS
  Both groups completed a questionnaire on the incidence of complaints during the previous 2 - 4 weeks. Trait anxiety was assessed by the trait scale of the State-Trait Anxiety Inventory (STAI-T), depressive mood by the Beck's Depression Inventory-II (BDI-II) and perceived self-efficacy by the Self-Efficacy Scale (SES).
  
  
  RESULTS
  Compared to the control group, Phase I volunteers presented a significantly lower incidence of stomach pain, back pain, limb or joint pain, headaches, fainting spells, palpitations, shortness of breath, constipation, loose stools or diarrhea, nausea, gas or indigestion, feeling nervous or anxious, feeling restless, getting tired very easily, muscle tension, aches, or soreness, and concentration difficulties. Significant positive correlations were found between the STAI-T and BDI-II scores and the incidence of several complaints; inversely, the SES score correlated negatively with several complaints.
  
  
  CONCLUSIONS
  The incidence of complaints in healthy subjects is not of a random character and depends on psychological characteristics. Volunteers in Phase I studies are a self-selected sample with a lower tendency to report non-drug-related adverse events than their peers from the general population. The impact of this self-selection bias on the assessment of tolerability during Phase I studies deserves further evaluation.
authors.affiliation: Department of Research and Development, BIAL-Portela, SA, S. Mamede do Coronado, Portugal. luis.almeida@bial.com
authors.forename: L
authors.initials: L
authors.lastname: Almeida
authors.forename: R
authors.initials: R
authors.lastname: Coelho
authors.forename: A
authors.initials: A
authors.lastname: Albino-Teixeira
authors.forename: P
authors.initials: P
authors.lastname: Soares-da-Silva
mesh_terms: D016022:Case-Control Studies; D017321:Clinical Trials, Phase I as Topic / Q000009:adverse effects* / Q000523:psychology*; D005260:Female; D006304:Health Status; D006801:Humans; D008297:Male; D010551:Personality; D035842:Research Subjects / Q000523:psychology*; D012923:Social Class; D011795:Surveys and Questionnaires