ReviewTrials2012
A theoretical framework for early human studies: uncertainty, intervention ensembles, and boundaries.
Review in Trials, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed.
- Trial
- Impact of a Collective Intelligence Tailored Messaging System on Smoking Cessation: The Perspect Randomized Experiment.Journal of medical Internet research · 2016Trial
- Supporting evidence in phase 2 cancer trial protocols: a content analysis.Journal of the National Cancer Institute · 2025Article
- A conceptual model and practical guidance for the development, administration, and evaluation of individualized therapies.Frontiers in medicine · 2025Article
- CONSORT-DEFINE explanation and elaboration: recommendations for enhancing reporting quality and impact of early phase dose-finding clinical trials.EClinicalMedicine · 2025Article
- Article
- A normative framework for artificial intelligence as a sociotechnical system in healthcare.Patterns (New York, N.Y.) · 2023Review
- States of Uncertainty, Risk-Benefit Assessment and Early Clinical Research: A Conceptual Investigation.Science and engineering ethics · 2022Article
- Ethics of Early Clinical Trials of Bio-Artificial Organs.Transplant international : official journal of the European Society for Organ Transplantation · 2022Article
- 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
- Considerations for designing and implementing combination HIV cure trials: findings from a qualitative in-depth interview study in the United States.AIDS research and therapy · 2021Article
- Individualized therapy trials: navigating patient care, research goals and ethics.Nature medicine · 2021Review
- Reprioritizing Risk and Benefit: The Future of Study Design in Early-Phase Cancer Research.Ethics & human research · 2019Article
- Preclinical efficacy studies in investigator brochures: Do they enable risk-benefit assessment?PLoS biology · 2018Article
- Print Me an Organ? Ethical and Regulatory Issues Emerging from 3D Bioprinting in Medicine.Science and engineering ethics · 2018Article
- Sex-Divergent Clinical Outcomes and Precision Medicine: An Important New Role for Institutional Review Boards and Research Ethics Committees.Frontiers in pharmacology · 2017Review
- Stakeholder views on participant selection for first-in-human trials in cancer nanomedicine.Current oncology (Toronto, Ont.) · 2016Article
- Rethinking risk assessment for emerging technology first-in-human trials.Medicine, health care, and philosophy · 2016Article
- Article
- The risk-escalation model: a principled design strategy for early-phase trials.Kennedy Institute of Ethics journal · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author.
Funding
Abstract
Clinical development of novel therapeutics begins with a coordinated sequence of early phase clinical trials. Such early human studies confront a series of methodological and ethical challenges. In what follows, I propose a theoretical framework for early human studies aimed at informing the negotiation of these challenges. At the outset of clinical development, researchers confront a virtually undifferentiated landscape of uncertainty with respect to three variables: outcomes, their probability of occurrence, and operation dimensions needed to effectuate favorable outcomes. Early human trials transform this uncertain landscape into one where there are grounds for belief about risk and benefit for various combined operation dimensions. To accomplish this, studies set out with two aims. First, they identify a set of operation dimensions that, when combined as a package (intervention ensemble), elicits a reasonable probability of a target outcome. Second, they define the boundaries of dimension values within an intervention ensemble. This latter aim entails exposing at least some volunteers in early studies to treatments that are inactive or excessive. I provide examples that illustrate the way early human studies discover and delimit intervention ensembles, and close by offering some implications of this framework for ethics, methodology, and efficiency in clinical development of new interventions.
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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.