What question did this study set out to answer?

August 1, 2023VaccineOpen Access

A review of criteria strictness in “Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials”

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Why the study?

Concern exists that the strictness of the FDA Toxicity Grading Scale for preventive vaccine trials may lead to an overestimation of some adverse events.

Does the strictness of the FDA Toxicity Grading Scale lead to an overestimation of adverse events in healthy volunteers in preventive vaccine trials?

Population

Participants in a phase I clinical trial of a preventive vaccine for infectious diseases

Comparison

FDA grading scale criteria vs standard reference intervals

Design

Analysis of adverse event details in a phase I clinical trial

Authors

MAMotoki AmaiUniversity of Tokyo Hospital MNMasanori NojimaTokyo University of Science YYYoshikazu YukiWakayama Medical University

Discussion

Member takes

Implication

Strict FDA scale may overestimate mild AEs in phase I vaccine trials; leaves open whether adjusted thresholds better reflect clinical relevance.

Key Points

To evaluate whether strict criteria in the FDA toxicity grading scale lead to an overestimation of adverse events during preventive vaccine clinical trials.
Analyzed adverse event reports from a phase I clinical trial of a preventive vaccine for infectious diseases in a Japanese cohort.
Compared FDA toxicity grading scale criteria for hemoglobin, sodium, and potassium against international laboratory reference intervals.
Found high rates of Grade 1 or greater adverse events for hypernatremia, hypokalemia, and hemoglobin decreases due to narrower non-adverse event ranges under FDA criteria relative to standard reference intervals.
Identified that hypernatremia criteria were 2 to 3 mEq/L lower than standard upper limits, hypokalemia criteria were 0.2 mEq/L higher than standard lower limits, and the 'any decrease' Grade 1 hemoglobin cutoff was excessively strict.

Structured PICO

Does the strictness of the FDA Toxicity Grading Scale lead to an overestimation of adverse events in healthy volunteers in preventive vaccine trials?

Population

Healthy adult and adolescent volunteers in a phase I clinical trial of a preventive vaccine for infectious diseases (including a Japanese cohort)

Intervention

FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials

Comparator

Standard laboratory reference intervals

Outcome

Overestimation of adverse events (specifically hemoglobin changes, hypernatremia, and hypokalemia)safety

The FDA toxicity grading scale for preventive vaccine trials may be too strict for certain laboratory parameters like sodium, potassium, and hemoglobin, leading to an overestimation of adverse events.

Cite This Study

Amai et al. (2023) studied this question.

synapsesocial.com/papers/6a77d7523da069e66cbdd19e https://doi.org/10.1016/j.vaccine.2023.07.072

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Implication

Strict FDA scale may overestimate mild AEs in phase I vaccine trials; leaves open whether adjusted thresholds better reflect clinical relevance.

A review of criteria strictness in “Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials”

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

A review of criteria strictness in “Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials”

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider