SynthesisClinical trials (London, England)2016
Risks of phase I research with healthy participants: A systematic review.
Synthesis in Clinical trials (London, England), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Integration of healthy volunteers in early phase clinical trials with immuno-oncological compounds.Frontiers in oncology · 2022Pooled it
- Placebo-resistant gut bacteria:Frontiers in cellular and infection microbiology · 2024Trial
- Use of Varied Screening Risk Criteria and HIV Incidence in Phase 1 and 2 HIV Vaccine Trials in South Africa.AIDS and behavior · 2023Trial
- Safety of healthy subjects in first-in-human multiple-dose studies: A pooled analysis.International journal of clinical pharmacology and therapeutics · 2021Trial
- "Stories like ours continue": A phenomenological exploration of the lived experiences of ex-serial clinical trial volunteers in South India.Dialogues in health · 2025Article
- Do people prefer to take part in a clinical trial from home or come to site? A discrete choice experiment in type 2 diabetes mellitus.BMJ open · 2025Article
- The Requirements of Managing Phase I Clinical Trials Risks: The British and Italian Case Studies.Epidemiologia (Basel, Switzerland) · 2024Article
- GutWomen's health reports (New Rochelle, N.Y.) · 2024Article
- Ethical Criteria for Improved Human Subject Protections in Phase I Healthy Volunteer Trials.Ethics & human research · 2022Article
- Risk-benefit analysis of emergency vaccine use.Scientific reports · 2022Article
- Data driven evaluation of healthy volunteer characteristics at screening for phase I clinical trials to inform on study design and optimize screening processes.Clinical and translational science · 2021Article
- Antimicrobial Dosing in Specific Populations and Novel Clinical Methodologies: Obesity.Clinical pharmacology and therapeutics · 2021Review
- The motivations, barriers, and sociodemographic characteristics of healthy Chinese volunteers in phase I research.European journal of clinical pharmacology · 2021Article
- Reexamining Ophthalmic Drugs, Safety and Tolerability in Phase 1 Clinical Trials.Therapeutics and clinical risk management · 2021Article
- Human infection challenge studies in endemic settings and/or low-income and middle-income countries: key points of ethical consensus and controversy.Journal of medical ethics · 2020Review
- Towards Identifying an Upper Limit of Risk: A Persistent Area of Controversy in Research Ethics.Perspectives in biology and medicine · 2020Article
- Picking and Choosing Among Phase I Trials : A Qualitative Examination of How Healthy Volunteers Understand Study Risks.Journal of bioethical inquiry · 2019Article
- Appraising Harm in Phase I Trials: Healthy Volunteers' Accounts of Adverse Events.The Journal of law, medicine & ethics : a journal of the American Society of Law, Medicine & Ethics · 2019Article
- Advancing Ethics and Policy for Healthy-Volunteer Research through a Model-Organism Framework.Ethics & human research · 2019Article
- Reviewing the role of healthy volunteer studies in drug development.Journal of translational medicine · 2018Review
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
BACKGROUND/
aimsTragedies suggest that phase I trials in healthy participants may be highly risky. This possibility raises concern that phase I trials may exploit healthy participants to develop new therapies, making the translation of scientific discoveries ethically worrisome. Yet, few systematic data evaluate this concern. This article systematically reviews the risks of published phase I trials in healthy participants and evaluates trial features associated with increased risks.
methodsData on adverse events and trial characteristics were extracted from all phase I trials published in PubMed, Embase, Cochrane, Scopus, and PsycINFO (1 January 2008-1 October 2012). Inclusion criteria were phase I studies that enrolled healthy participants of any age, provided quantitative adverse event data, and documented the number of participants enrolled. Exclusion criteria included (1) adverse event data not in English, (2) a "challenge" study in which participants were administered a pathogen, and (3) no quantitative information about serious adverse events. Data on the incidence of adverse events, duration of adverse event monitoring, trial agent tested, participant demographics, and trial location were extracted.
resultsIn 475 trials enrolling 27,185 participants, there was a median of zero serious adverse events (interquartile range = 0-0) and a median of zero severe adverse events (interquartile range = 0-0) per 1000 treatment group participants/day of monitoring. The rate of mild and moderate adverse events was a median of 1147.19 per 1000 participants (interquartile range = 651.52-1730.9) and 46.07 per 1000 participants/adverse event monitoring day (interquartile range = 17.80-77.19).
conclusionWe conclude that phase I trials do cause mild and moderate harms but pose low risks of severe harm. To ensure that this conclusion also applies to unpublished trials, it is important to increase trial transparency.
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.