ArticleKennedy Institute of Ethics journal2014
The risk-escalation model: a principled design strategy for early-phase trials.
Article in Kennedy Institute of Ethics journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Who should be included in first-in-human trials? A systematic review of reasons.Journal of translational medicine · 2025Pooled it
- Self-Management Support Using a Digital Health System Compared With Usual Care for Chronic Obstructive Pulmonary Disease: Randomized Controlled Trial.Journal of medical Internet research · 2017Trial
- Ethical challenges for a new generation of early-phase pediatric gene therapy trials.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Review
- Reprioritizing Risk and Benefit: The Future of Study Design in Early-Phase Cancer Research.Ethics & human research · 2019Article
- Results from Phase I Clinical Trial with Intraspinal Injection of Neural Stem Cells in Amyotrophic Lateral Sclerosis: A Long-Term Outcome.Stem cells translational medicine · 2019Article
- Ethical development of stem-cell-based interventions.Nature medicine · 2019Review
- Afterword: returning to philosophical foundations in research ethics.Journal of medical ethics · 2017Article
- How to keep high-risk studies ethical: classifying candidate solutions.Journal of medical ethics · 2017Article
- One Size Fits All?: Ethical Considerations for Examining Efficacy in First-in-Human Pluripotent Stem Cell Studies.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Adapting Preclinical Benchmarks for First-in-Human Trials of Human Embryonic Stem Cell-Based Therapies.Stem cells translational medicine · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Should first-in-human trials be designed to maximize the prospect of therapeutic benefit for volunteers, prioritize avoidance of unintended harms, or aim for some happy medium between the two? Perennial controversies surrounding initiation and design of early-phase trials hinge on how this question is resolved. In this paper, we build on the premise that the task of early-phase testing is to optimize various components of a potential therapy so that later, confirmatory trials have the maximal probability of informing drug development and clinical care. We then explore three strategies that investigators might use to manage trial risks while optimizing a therapy, using cell therapy for Amyotrophic Lateral Sclerosis (ALS) as an example. We argue that an iterative application of maximin strategies over successive cohorts and trials, which we call the "risk-escalation model," establishes a moral principle that should guide decision-making in early-phase trials.
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.