PMID- 37532612
OWN - NLM
STAT- MEDLINE
DCOM- 20230828
LR  - 20230906
IS  - 1873-2518 (Electronic)
IS  - 0264-410X (Linking)
VI  - 41
IP  - 38
DP  - 2023 Aug 31
TI  - A review of criteria strictness in "Toxicity Grading Scale for Healthy Adult and 
      Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials".
PG  - 5622-5629
LID - S0264-410X(23)00918-0 [pii]
LID - 10.1016/j.vaccine.2023.07.072 [doi]
AB  - To assess safety in vaccine development, stricter grading scales, such as the 
      "Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
      Preventive Vaccine Clinical Trials" issued by the U.S. Food and Drug 
      Administration (FDA grading scale), are required. However, concern exists that 
      their strictness may lead to an overestimation of some adverse events (AEs). We 
      analyzed the details of AEs in a phase I clinical trial of a preventive vaccine 
      for infectious diseases. In this trial, we observed the high occurrence of Grade 
      1 or greater AEs in hemoglobin changes from baseline value, and hypernatremia, 
      and hypokalemia by FDA grading scale. The range considered as non-AE according to 
      the FDA grading scale shifted or became narrower when compared to reference 
      intervals, especially for a Japanese cohort. For sodium grading, the criterion 
      for hypernatremia was around 2 to mEq/L lower than the upper limit of most 
      standards in several countries. Also, the criterion for hypokalemia was around 
      0.2 mEq/L higher than the lower limit of most standards. Regarding a decrease in 
      hemoglobin from baseline, the criterion of "any decrease" used for a Grade 1 AE 
      was too strict and we suggest this be omitted. Upper and lower limits of AE 
      criteria for sodium and potassium should be equal to, or 10-20% above, the 
      reference interval consistent with other toxicities determined by laboratory 
      tests. Consideration should be given to the issues surrounding the criteria that 
      determine AEs before conducting clinical trials.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Amai, Motoki
AU  - Amai M
AD  - Center for Translational Research, IMSUT Hospital, The Institute of Medical 
      Science, The University of Tokyo, Tokyo, Japan.
FAU - Nojima, Masanori
AU  - Nojima M
AD  - Center for Translational Research, IMSUT Hospital, The Institute of Medical 
      Science, The University of Tokyo, Tokyo, Japan; Division of Advanced Medicine 
      Promotion, The Institute of Medical Science, The University of Tokyo, Tokyo, 
      Japan. Electronic address: nojima@ims.u-tokyo.ac.jp.
FAU - Yuki, Yoshikazu
AU  - Yuki Y
AD  - Department of Human Mucosal Vaccinology, Chiba University Hospital, Chiba, Japan; 
      HanaVax Inc., Chiba, Japan.
FAU - Kiyono, Hiroshi
AU  - Kiyono H
AD  - HanaVax Inc., Chiba, Japan; Chiba University Synergy Institute for Futuristic 
      Mucosal Vaccine Research and Development (cSIMVa), Future Medicine Education and 
      Research Organization, Chiba University, Chiba, Japan; CU-UCSD Center for Mucosal 
      Immunology, Allergy, and Vaccine (cMAV), Departments of Medicine and Pathology, 
      University of California, San Diego, CA, USA.
FAU - Nagamura, Fumitaka
AU  - Nagamura F
AD  - Center for Translational Research, IMSUT Hospital, The Institute of Medical 
      Science, The University of Tokyo, Tokyo, Japan; Division of Advanced Medicine 
      Promotion, The Institute of Medical Science, The University of Tokyo, Tokyo, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230801
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Vaccines)
RN  - 0 (Hemoglobins)
SB  - IM
MH  - Humans
MH  - Adult
MH  - Adolescent
MH  - *Hypernatremia
MH  - *Hypokalemia
MH  - *Vaccines/adverse effects
MH  - Volunteers
MH  - Hemoglobins
OTO - NOTNLM
OT  - Adverse event
OT  - Clinical trial
OT  - Grading scale
OT  - Healthy subjects
OT  - Vaccine safety
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/08/03 01:06
MHDA- 2023/08/28 06:42
CRDT- 2023/08/02 21:53
PHST- 2022/06/28 00:00 [received]
PHST- 2023/07/25 00:00 [revised]
PHST- 2023/07/29 00:00 [accepted]
PHST- 2023/08/28 06:42 [medline]
PHST- 2023/08/03 01:06 [pubmed]
PHST- 2023/08/02 21:53 [entrez]
AID - S0264-410X(23)00918-0 [pii]
AID - 10.1016/j.vaccine.2023.07.072 [doi]
PST - ppublish
SO  - Vaccine. 2023 Aug 31;41(38):5622-5629. doi: 10.1016/j.vaccine.2023.07.072. Epub 
      2023 Aug 1.