ReviewTrials2014
Comparison of anticipated and actual control group outcomes in randomised trials in paediatric oncology provides evidence that historically controlled studies are biased in favour of the novel treatment.
Review in Trials, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 3 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, 3 syntheses or guidelines pooled it.
- The effectiveness and safety of proton beam radiation therapy in children and young adults with Central Nervous System (CNS) tumours: a systematic review.Journal of neuro-oncology · 2024Pooled it
- Medulloblastoma in children and adolescents: a systematic review of contemporary phase I and II clinical trials and biology update.Cancer medicine · 2017Pooled it
- Economic Evaluations of Pharmaceuticals Granted a Marketing Authorisation Without the Results of Randomised Trials: A Systematic Review and Taxonomy.PharmacoEconomics · 2017Pooled it
- Parental perspectives on access to paediatric oncology clinical trials and treatment options: A cross-sectional survey.Bioinformation · 2024Article
- Casting New Light on Statistical Power: An Illuminating Analogy and Strategies to Avoid Underpowered Trials.American journal of epidemiology · 2022Article
- Summarising salient information on historical controls: A structured assessment of validity and comparability across studies.Clinical trials (London, England) · 2020Article
- Magnetic Steering of Capsule Endoscopy Improves Small Bowel Capsule Endoscopy Completion Rate.Digestive diseases and sciences · 2019Article
- Early phase clinical trials of anticancer agents in children and adolescents - an ITCC perspective.Nature reviews. Clinical oncology · 2017Review
- [Systematic errors in clinical studies : A comprehensive survey].Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft · 2017Review
- [Systematic errors in clinical studies : A comprehensive survey].Zeitschrift fur Rheumatologie · 2017Review
- Regulatory approval of pharmaceuticals without a randomised controlled study: analysis of EMA and FDA approvals 1999-2014.BMJ open · 2016Article
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
backgroundHistorically controlled studies are commonly undertaken in paediatric oncology, despite their potential biases. Our aim was to compare the outcome of the control group in randomised controlled trials (RCTs) in paediatric oncology with those anticipated in the sample size calculations in the protocols. Our rationale was that, had these RCTs been performed as historical control studies instead, the available outcome data used to calculate the sample size in the RCT would have been used as the historical control outcome data.
methodsA systematic search was undertaken for published paediatric oncology RCTs using the Cochrane Central Register of Controlled Trials (CENTRAL) database from its inception up to July 2013. Data on sample size assumptions and observed outcomes (timetoevent and proportions) were extracted to calculate differences between randomised and historical control outcomes, and a one-sample t-test was employed to assess whether the difference between anticipated and observed control groups differed from zero.
resultsForty-eight randomised questions were included. The median year of publication was 2005, and the range was from 1976 to 2010. There were 31 superiority and 11 equivalence/noninferiority randomised questions with time-to-event outcomes. The median absolute difference between observed and anticipated control outcomes was 5.0% (range: -23 to +34), and the mean difference was 3.8% (95% CI: +0.57 to +7.0; P = 0.022).
conclusionsBecause the observed control group (that is, standard treatment arm) in RCTs performed better than anticipated, we found that historically controlled studies that used similar assumptions for the standard treatment were likely to overestimate the benefit of new treatments, potentially leading to children with cancer being given ineffective therapy that may have additional toxicity.
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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.