Do protocols for new randomised trials take previous similar trials into account? Cohort study of contemporary trial protocols
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Objective: To investigate to what extent evidence from previous similar trials or systematic reviews was considered before conducting new trials. Design: Cohort study of contemporary protocols for trials with ethical approval. Methods: All protocols for randomised trials approved by the five ethical committees in Denmark between January 2012 and March 2013 were screened for eligibility. Included protocols were read in full to determine whether a systematic search had been conducted and references were checked to evaluate whether trial rationale and design could be challenged for not adequately considering previous evidence. To investigate whether protocols cited relevant trials, we used simple search strategies that could easily be conducted by researchers without experience with literature searches. Results: Sixty-seven protocols were included. Only two (3%) of the protocols explicitly stated to have conducted a literature search and only one (1%) provided information that allowed the search to be replicated. Eleven (16%) of the protocols described trials where we found the information insufficient to judge if the trial was ethically justified, either due to a comparator that was not supported by the presented evidence (six protocols), because they did not present a rationale for conducting the trial (two protocols), or for both reasons (three protocols). For eight (12%) of the protocols, our search identified trials that could have been relevant to cite as justification. Conclusions: While most protocols seem to adequately consider existing evidence, a substantial minority of trials might lack a sufficient evidence base. Very few trials seemed to have been based on a literature search which makes it impossible to know whether all relevant previous trials had been considered. Rules for ethical approval should include requirements for systematic literature searches to ensure that research participants are not exposed to sub-optimal treatments or unnecessary harms as well as to reduce research waste.
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Previous reviews of trial protocols have found that many do not cite the systematic reviews or trials that exist on the same topic.
“Previous reviews of trial protocols have found that many do not cite the systematic reviews or trials that exist on the same topic.152 153 154”
From SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials (2025) · cites this paper as [154]
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SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials
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- Authors
- Paludan-Müller, A. S., Ogden, M. C., Marquardsen, M., Vive, J., Jørgensen, K. J., & Gøtzsche, P. C.
- Affiliations
- Nordic Cochrane Centre, Rigshospitalet, Copenhagen, Denmark
- Rigshospitalet (DK)
- Corresponding author
- Gøtzsche, Peter Christian
- Venue
- BMJ Open
- Publisher
- BMJ
- Published
- 2019-11
- Volume
- 9
- Issue
- 11
- Pages
- e026661
- ISSN
- 2044-6055 (ISSN-L)
- PMC
- PMC6858261
- OpenAlex
- W2986770308
- Cited by
- 10
- References
- 20
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 3 · 2021: 3 · 2020: 1 · 2018: 1
- FWCI
- 1.17
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- BMJ Open (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Nordic Cochrane Centre
- Laura and John Arnold Foundation
- Topics
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
- Keywords
- randomised trials, literature searching, systematic reviews, research ethics approval, research waste, evidence base, research ethics committees, Denmark
- MeSH terms
- Clinical Protocols, Denmark, Follow-Up Studies, Humans, Registries, Retrospective Studies, Randomized Controlled Trials as Topic
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