PMID- 33655485
OWN - NLM
STAT- MEDLINE
DCOM- 20210705
LR  - 20220531
IS  - 2168-4804 (Electronic)
IS  - 2168-4790 (Linking)
VI  - 55
IP  - 4
DP  - 2021 Jul
TI  - Predictability of Severe Adverse Events in Phase 3 Trials from Safety Information 
      on Phase 1 Trials in Oncology Drug Development.
PG  - 667-675
LID - 10.1007/s43441-021-00266-z [doi]
AB  - PURPOSE: Safety information obtained in phase 1 trials is becoming increasingly 
      important with the recent changes in the development strategy of oncology drugs, 
      including the skipping of phase 2 or 3 trials before regulatory approval. This 
      study aimed to investigate the predictive factors for severe adverse events (AEs) 
      in phase 3 trials based on phase 1 trial data. METHODS: The data on phase 1 and 
      phase 3 trials applied for their marketing approval of the newly approved 
      anticancer drugs in Japan were used for analysis. Regression analyses were 
      performed to investigate factors related to the predictability of the occurrence 
      of severe AEs in phase 3 trials based on phase 1 trial data. RESULTS: Thirty-two 
      drugs (80 phase 1 trials and 40 phase 3 trials) were selected for the analyses. 
      As a result of multivariate regression analyses, immune therapy agents 
      (P = 0.009) and a pair of monotherapy in the phase 1 trials and combination 
      therapy in the phase 3 trials (P = 0.017) were associated with low predictability 
      of severe AEs in the phase 3 trials; signal inhibitor agents (P = 0.002) and 
      large number of subjects in phase 1 trials (P = 0.008) were associated with high 
      predictability. A significant relationship between the actual number of subjects 
      in phase 1 trials and the predictability of severe AEs was observed when trials 
      for immune checkpoint inhibitors were excluded (P < 0.001). CONCLUSION: These 
      results should be effectively utilized for the strategic design of early-stage 
      oncology drug development.
FAU - Sawada, Takashi
AU  - Sawada T
AUID- ORCID: 0000-0003-2300-2941
AD  - Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of 
      Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 
      108-8641, Japan. dl18404@st.kitasato-u.ac.jp.
FAU - Kaneko, Masayuki
AU  - Kaneko M
AD  - Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of 
      Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 
      108-8641, Japan.
FAU - Narukawa, Mamoru
AU  - Narukawa M
AD  - Department of Clinical Medicine (Pharmaceutical Medicine), Graduate School of 
      Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 
      108-8641, Japan.
LA  - eng
PT  - Journal Article
DEP - 20210302
PL  - Switzerland
TA  - Ther Innov Regul Sci
JT  - Therapeutic innovation & regulatory science
JID - 101597411
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - *Antineoplastic Agents/adverse effects
MH  - Drug Development
MH  - Japan
OTO - NOTNLM
OT  - Immune checkpoint inhibitors
OT  - Molecular-targeted agents
OT  - Phase 1 trial
OT  - Prediction
OT  - Severe adverse events
EDAT- 2021/03/04 06:00
MHDA- 2021/07/06 06:00
CRDT- 2021/03/03 05:52
PHST- 2021/01/03 00:00 [received]
PHST- 2021/02/11 00:00 [accepted]
PHST- 2021/03/04 06:00 [pubmed]
PHST- 2021/07/06 06:00 [medline]
PHST- 2021/03/03 05:52 [entrez]
AID - 10.1007/s43441-021-00266-z [pii]
AID - 10.1007/s43441-021-00266-z [doi]
PST - ppublish
SO  - Ther Innov Regul Sci. 2021 Jul;55(4):667-675. doi: 10.1007/s43441-021-00266-z. 
      Epub 2021 Mar 2.