PMID- 10206079
OWN - NLM
STAT- MEDLINE
DCOM- 19990701
LR  - 20190813
IS  - 0031-6970 (Print)
IS  - 0031-6970 (Linking)
VI  - 55
IP  - 1
DP  - 1999 Mar
TI  - Laboratory data in healthy volunteers: reference values, reference changes, 
      screening and laboratory adverse event limits in Phase I clinical trials.
PG  - 13-9
AB  - OBJECTIVE: Laboratory data are key evaluation procedures for Phase I clinical 
      pharmacology for two reasons. Firstly, laboratory data are used within the 
      screening process to exclude subjects with asymptomatic diseases, which could 
      result in increased danger to themselves or confuse interpretation of the study 
      results. Secondly, during study implementation, safety evaluation and in 
      particular maximum tolerated dose determination have to be done by a case-by-case 
      analysis, sometimes using laboratory adverse events (LAEs). Thus, relevant limits 
      are needed to discriminate between a usual common variation and a significant 
      abnormality, which is considered to be a LAE. This report presents laboratory 
      data distribution, reference values and reference changes and, based on 
      previously published new methods, suggests inclusion limits at screening and 
      laboratory adverse event limits for analysis during study implementation. 
      SUBJECTS AND METHODS: Nine hundred and twenty-seven young healthy male volunteers 
      were recruited in one centre (Association de Recherche Therapeutique). A standard 
      screening process was carried out. Protocols were approved by the local ethics 
      committee. Blood sampling was performed in the same conditions. Reference values 
      (at screening and at baseline) were determined by a non-parametric procedure 
      selecting 2.5% and 97.5% of the distribution of data. Reference changes were also 
      defined as the 2.5-97.5% interval of distribution of the variations between the 
      end of treatment and baseline. Inclusion limit and LAE limit methods of 
      determination used had been specified in previous articles. RESULTS: Detailed 
      results of laboratory data distribution, reference values at screening and at 
      baseline, reference changes, inclusion limits and LAE limits are presented in 
      tables with number of subjects, mean, median, standard deviation, minimal and 
      maximal values and the 2.5-97.5% interval for each laboratory parameter. 
      CONCLUSION: The key aims of this paper are to provide clinical pharmacologists 
      with data, reference values or changes obtained in the real conditions of Phase I 
      study implementation, and to propose relevant limits, either for screening as 
      inclusion limits, or during studies as LAE limits. Thus, these data, reference 
      values and specific limits improve the capacity to screen healthy volunteers and 
      to analyse LAEs during Phase I studies.
FAU - Sibille, M
AU  - Sibille M
AD  - Association de Recherche Therapeutique, Centre Hospitalier Lyon Sud, 
      Pierre-Benite, France. msibille@serveur.dtr.fr
FAU - Deigat, N
AU  - Deigat N
FAU - Durieu, I
AU  - Durieu I
FAU - Guillaumont, M
AU  - Guillaumont M
FAU - Morel, D
AU  - Morel D
FAU - Bienvenu, J
AU  - Bienvenu J
FAU - Massignon, D
AU  - Massignon D
FAU - Durand, D V
AU  - Durand DV
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Eur J Clin Pharmacol
JT  - European journal of clinical pharmacology
JID - 1256165
SB  - IM
MH  - Adult
MH  - Blood Cells
MH  - Blood Chemical Analysis
MH  - Chemistry, Clinical/methods/*standards
MH  - Clinical Trials, Phase I as Topic/adverse effects/*standards
MH  - Humans
MH  - Male
MH  - Reference Values
EDAT- 1999/04/17 00:00
MHDA- 1999/04/17 00:01
CRDT- 1999/04/17 00:00
PHST- 1999/04/17 00:00 [pubmed]
PHST- 1999/04/17 00:01 [medline]
PHST- 1999/04/17 00:00 [entrez]
AID - 10.1007/s002280050586 [doi]
PST - ppublish
SO  - Eur J Clin Pharmacol. 1999 Mar;55(1):13-9. doi: 10.1007/s002280050586.