# The RATIOS Study: Risk/benefit AssessmenT by IRB review of Phase One Studies

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $451,572

## Abstract

PROJECT SUMMARY/ABSTRACT
The ethical conduct of Phase 1 trials is conditioned on both there being a reasonable ratio between potential
risks and benefits and research candidates being provided with key information about that potential during the
informed consent process. IRBs must carefully assess the scientific information supporting the assessment of
potential risks and benefits in order to meet these conditions. Several hurdles hinder such assessment. While
the FDA carefully vets preclinical safety data that relate to Phase 1 trials, the same is not true for the preclinical
efficacy data needed to support the potential for benefit. Further, IRBs receive no specific guidance regarding
what to look for in preclinical efficacy data or how they should vet scientific claims made about Phase 1
modalities. This lack of guidance is disconcerting given extensive research documenting characteristics of
many preclinical efficacy studies that make it difficult to make reliable inferences about whether a new
treatment modality might eventually be capable of demonstrating clinical efficacy. Such inferences are
especially challenging when it comes to preclinical efficacy studies that employ novel research techniques like
CRISPR-Cas9 and brain organoids. Knowing what inferences about potential efficacy can reliably be made
about new treatment modalities employing novel preclinical tools will be the primary focus of our project. These
are the very inferences that are required if IRBs are to be able to determine that there is a reasonable ratio
between benefits and risks in Phase 1 trials employing new promissory technologies. In this challenging
setting, IRBs could benefit from a structured approach to risk/benefit assessments. This project is designed to
develop and pilot such an approach. To do this, we will conduct quantitative and qualitative research to learn
about current strengths and weaknesses in IRB review of Phase 1 studies. We will complete a national survey
of IRB chairs. Then we will conduct 3 sets of semi-structured interviews with: (a) past Phase 1 trial
investigators, (b) IRB members who review Phase 1 trial applications, and (c) past participants or their legal
representatives of Phase 1 trials. We will use these findings to refine an existing conceptual framework for
assessing the quality and reliability of efficacy data in preclinical studies. From this refined conceptual
framework, we will develop IRB and investigator checklists designed to (a) promote highly-structured weighing
of potential benefits and risks by IRBs in Phase 1 trials and (b) assist Phase 1 investigators to submit more
ethically robust Phase 1 trial applications. We will also develop a novel data analytics and decision-support
interactive software platform to help Phase 1 investigators and IRB members evaluate the evidentiary context
surrounding a given Phase 1 trial. These decision aids will also be used to identify critical disclosures about
potential risks and benefits...

## Key facts

- **NIH application ID:** 10754263
- **Project number:** 5R01NS119622-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Mark Fedyk
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $451,572
- **Award type:** 5
- **Project period:** 2022-01-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10754263

## Citation

> US National Institutes of Health, RePORTER application 10754263, The RATIOS Study: Risk/benefit AssessmenT by IRB review of Phase One Studies (5R01NS119622-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10754263. Licensed CC0.

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