ReviewPediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies2009
Is "rescue" therapy ethical in randomized controlled trials?
Review in Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 2 of them syntheses 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
11 citing papers in PubMed, 2 syntheses or guidelines pooled it, 22 citations in OpenAlex.
- Guidewire-assisted cannulation of the common bile duct for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis.The Cochrane database of systematic reviews · 2022Pooled it
- Guidewire-assisted cannulation of the common bile duct for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis.The Cochrane database of systematic reviews · 2012Pooled it
- Research Ethics Challenges, Controversies and Difficulties in Intensive Care Units-A Systematic Review of Theoretical Concepts.Nursing reports (Pavia, Italy) · 2025Review
- Hoping Against Hope: Ethical Considerations when Trying Unproven Treatments for Seriously Ill Children.Asian bioethics review · 2025Article
- Comparaison of Efficacy and Safety of Fentanyl Transdermal Patch with Oral Ketorolac for Pain Management in Dry Socket: A Randomized Clinical Trial.Journal of maxillofacial and oral surgery · 2024Article
- Integrating Data From Randomized Controlled Trials and Observational Studies to Assess Survival in Rare Diseases.Circulation. Cardiovascular quality and outcomes · 2019Article
- Research as a Standard of Care in the PICU.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2016Review
- It's About Time ….Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2015Article
- Ethics of drug research in the pediatric intensive care unit.Paediatric drugs · 2015Review
- The design of future pediatric mechanical ventilation trials for acute lung injury.American journal of respiratory and critical care medicine · 2010Review
- Collaborative pediatric critical care research network: looking back and moving forward.Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies · 2010Article
Corrections and comments
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Authors and funding
12 authors at 10 institutions in 1 country.
Funding
Abstract
objectiveThere is a commonly held belief that randomized, placebo-controlled trials in pediatric critical care should incorporate "rescue" therapy (open-label administration of active drug) when a child's condition is deteriorating. The ethical, conceptual, and analytic challenges related to rescue therapy in randomized trials can be misrepresented.
designNarrative review.
methodsThe ethical basis of rescue therapy, the equipoise concept, and intention-to-treat analysis are examined in the setting of a hypothetical randomized trial comparing corticosteroids vs. placebo in pediatric septic shock.
findingsThe perceived need for rescue therapy may be partly motivated by the moral imperative to save a child's life. However, allowing rescue therapy in a trial is misconceived and inconsistent with equipoise regarding the efficacy of the study drug. If rescue therapy is permitted, intention-to-treat analysis can only compare immediate vs. delayed use of the study drug. When rescue therapy is beneficial, the observed treatment effect is substantially diminished from true effect of the study drug, leading to increased sample size and thereby placing more children at risk (18 "excess" placebo-arm deaths occur in our hypothetical example). Analysis of a trial incorporating rescue therapy cannot definitively assess overall efficacy of the agent, or distinguish beneficial or harmful treatment effects related to timing of drug use.
conclusionsAlthough a rescue therapy component in a randomized trial may be perceived as ethically desirable, inconsistency of rescue therapy with full equipoise may itself raise significant ethical concerns. Increased sample sizes expose more children to the risks of study participation, including death. Researchers should be aware that clinical trials designed with rescue therapy cannot definitively determine the beneficial or harmful effects of a treatment per se, and can only assess the effects of delayed vs. immediate provision of the treatment.
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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.