SynthesisJournal of translational medicine2025
Who should be included in first-in-human trials? A systematic review of reasons.
Synthesis in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Translational human gut microbiome research: What are the missing pieces of the puzzle?Journal of translational medicine · 2026Review
- Moral Attitudes on Somatic Gene Editing for Inherited Cardiomyopathy: A Qualitative Interview Study with Key Stakeholders in the Netherlands.Journal of bioethical inquiry · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
backgroundFirst-in-human trials mark a significant turning point in translational research, with novel therapies being tested in humans for the first time. Who should be included in FIH trials is a topic of ongoing debate amongst researchers, clinicians, ethicists, and sponsors. Yet, no comprehensive overview of the literature on this topic has been constructed before.
methodsA systematic review of reasons was conducted, following the methodology outlined by Stretch and Sofaer for conducting systematic reviews of argument-based literature. Six online databases were consulted across various disciplines, including medicine (PubMed and Embase), philosophy (The Philosopher's Index and PhilPapers), and multidisciplinary studies (Web of Science and Academic Search Premier). Additionally, relevant books and book chapters were identified through the library of Leiden University. After data extraction and analysis, 80 publications were included.
results181 reasons were identified amongst six potential participant categories: healthy volunteers, patients (general), patients with less advanced-stage diseases, patients with more advanced-stage diseases, vulnerable populations, and diverse participant groups. These reasons relate to six themes: non-maleficence, beneficence, scientific value, efficiency, respect for persons, and justice. This review highlights multiple challenges in the existing literature, including ambiguous or poorly defined reasons and unspecified use of moral theory, framework, or method, the use of beneficence as an important theme for including participants in FIH trials, and the complexity of identifying and defining vulnerable populations.
conclusionsThis review provides the first comprehensive overview of the reasons for and against including potential participant groups in FIH trials. The results highlight considerations that are relevant to reflect upon when determining and justifying participant selection for FIH trials. Additionally, this review offers guidance for further normative inquiry.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.