ArticlePLoS biology2018
Preclinical efficacy studies in investigator brochures: Do they enable risk-benefit assessment?
Article in PLoS biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed.
- Clinical relevance assessment of animal preclinical research (RAA) tool: development and explanation.PeerJ · 2021Trial
- Supporting evidence in phase 2 cancer trial protocols: a content analysis.Journal of the National Cancer Institute · 2025Article
- Regulation (EU) 536/2014 and the role of ethics committees: a proposal for a review system model.BMJ open · 2024Review
- Synthesizing regulatory guidance for demonstrating preclinical efficacy and translating promising cell therapies to early phase clinical trials: a scoping review.BMC medicine · 2024Article
- Preclinical assessment for translation to humans: The PATH approach for assessing supporting evidence for early-phase trials and innovative care.Med (New York, N.Y.) · 2024Review
- Why Do I Choose an Animal Model or an Alternative Method in Basic and Preclinical Biomedical Research? A Spectrum of Ethically Relevant Reasons and Their Evaluation.Animals : an open access journal from MDPI · 2024Article
- Initial heritable genome editing: mapping a responsible pathway from basic research to the clinic.Medicine, health care, and philosophy · 2023Article
- Translatability of preclinical to early clinical tolerable and pharmacologically active dose ranges for central nervous system active drugs.Translational psychiatry · 2023Review
- Building an infrastructure to support the development, conduct, and reporting of informative clinical studies: The Rockefeller University experience.Journal of clinical and translational science · 2023Article
- [Transparency in clinical research: What contribution does the new EU Regulation 536/2014 make?]Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz · 2023Review
- Predictive validity in drug discovery: what it is, why it matters and how to improve it.Nature reviews. Drug discovery · 2022Review
- The role of systematic reviews in identifying the limitations of preclinical animal research, 2000-2022: part 2.Journal of the Royal Society of Medicine · 2022Article
- Can Any Drug Be Repurposed for Cancer Treatment? A Systematic Assessment of the Scientific Literature.Cancers · 2021Article
- Using the concept of "deserved trust" to strengthen the value and integrity of biomedical research.Accountability in research · 2021Article
- Do we really know how many clinical trials are conducted ethically? Why research ethics committee review practices need to be strengthened and initial steps we could take to strengthen them.Journal of medical ethics · 2021Review
- Commentary on "Investigator brochures for phase I/II trials lack information on the robustness of preclinical safety studies" by Sievers et al.British journal of clinical pharmacology · 2021Article
- Article
- Risk Assessment of Medical Study Procedures in the Documents Submitted to a Research Ethics Committee.Journal of empirical research on human research ethics : JERHRE · 2020Article
- Levelling the Translational Gap for Animal to Human Efficacy Data.Animals : an open access journal from MDPI · 2020Review
- Reporting animal research: Explanation and elaboration for the ARRIVE guidelines 2.0.PLoS biology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human protection policies require favorable risk-benefit judgments prior to launch of clinical trials. For phase I and II trials, evidence for such judgment often stems from preclinical efficacy studies (PCESs). We undertook a systematic investigation of application materials (investigator brochures [IBs]) presented for ethics review for phase I and II trials to assess the content and properties of PCESs contained in them. Using a sample of 109 IBs most recently approved at 3 institutional review boards based at German Medical Faculties between the years 2010-2016, we identified 708 unique PCESs. We then rated all identified PCESs for their reporting on study elements that help to address validity threats, whether they referenced published reports, and the direction of their results. Altogether, the 109 IBs reported on 708 PCESs. Less than 5% of all PCESs described elements essential for reducing validity threats such as randomization, sample size calculation, and blinded outcome assessment. For most PCESs (89%), no reference to a published report was provided. Only 6% of all PCESs reported an outcome demonstrating no effect. For the majority of IBs (82%), all PCESs were described as reporting positive findings. Our results show that most IBs for phase I/II studies did not allow evaluators to systematically appraise the strength of the supporting preclinical findings. The very rare reporting of PCESs that demonstrated no effect raises concerns about potential design or reporting biases. Poor PCES design and reporting thwart risk-benefit evaluation during ethical review of phase I/II studies.
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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.