PMID- 31746730
OWN - NLM
STAT- MEDLINE
DCOM- 20200106
LR  - 20200108
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 58
IP  - 1
DP  - 2020 Jan
TI  - How safe are our studies? Analysis of adverse events in Bayer First-in-Human 
      trials from 2006 to 2016
.
PG  - 10-20
LID - 10.5414/CP203390 [doi]
AB  - PURPOSE: In regard to the current scientific discussion, this analysis aims to 
      broaden the database for a risk evaluation of First-in-Human (FiH) trials with 
      healthy volunteers. MATERIALS AND METHODS: Study documents of each FiH study 
      conducted between 2006 and 2016 for Bayer Clinical Pharmacology Cardiovascular 
      were reviewed for inclusion. Study types, treatments, dose steps, study 
      population, number, incidence, and intensity of treatment-emergent adverse events 
      (AEs) were cumulatively analyzed using descriptive statistics. A comparison to a 
      previous similar analysis (period 2000 - 2005) was made. RESULTS: 22 out of 25 
      studies were included (20 small molecules, 2 biologics) investigating drugs for 
      cardiovascular (9), hematological (7), pulmonary (3), kidney (2), and metabolic 
      (1) diseases. The mean age of subjects was 34.2 years. 1,250 subjects received 
      treatment (950 active, 300 placebo). 952 AEs occurred (0.76 AEs/treatment, 0.85 
      AEs/active treatment, 0.49 AEs/placebo treatment). 88.2% (840/952) of AEs were 
      mild, 11.3% (108/952) moderate, and 0.4% (4/952) were severe. 0.4% (5/1250) of 
      subjects had active drug- or procedure-related serious AEs. The most frequent AE 
      was headache (12.9% (123/952)), the mostly affected system organ class was CNS 
      (14.4% of all subjects). The relative risk for an AE was significantly higher 
      under active drug compared to placebo (1.24, 95% LCL >1). The incidence of AEs 
      increased with higher dose steps. A higher incidence of AEs (active and placebo) 
      in recent compared to previous studies was observed. CONCLUSION: The risk of 
      severe harm for healthy participants was low. The risk to experience any AE was 
      higher under active drug compared to placebo. A trend change towards more 
      frequent reporting of AEs in the recent studies was observed.
FAU - Jung, David
AU  - Jung D
FAU - Boettcher, Michael-Friedrich
AU  - Boettcher MF
FAU - Wensing, Georg
AU  - Wensing G
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
SB  - IM
MH  - *Clinical Trials as Topic
MH  - Drug-Related Side Effects and Adverse Reactions/*epidemiology
MH  - Humans
MH  - Incidence
MH  - *Research Design
EDAT- 2019/11/21 06:00
MHDA- 2020/01/07 06:00
CRDT- 2019/11/21 06:00
PHST- 2019/12/17 00:00 [accepted]
PHST- 2019/11/21 06:00 [pubmed]
PHST- 2020/01/07 06:00 [medline]
PHST- 2019/11/21 06:00 [entrez]
AID - 186035 [pii]
AID - 10.5414/CP203390 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2020 Jan;58(1):10-20. doi: 10.5414/CP203390.