Randomised controlled trials – the gold standard for effectiveness research: Study design: randomised controlled trials
Open accessAbstract
RCTs are prospective studies that measure the effectiveness of interventions. Although no study is likely on its own to prove causality, randomisation reduces bias and provides a rigorous tool to examine cause–effect relationships between an intervention and outcome. This is because the act of randomisation in a large study balances participant characteristics (both observed and unobserved) between the groups, allowing attribution of any differences in outcome to the intervention. This is not possible with any other study design, so RCTs are considered the reference standard for driving practice (Tarnow-Mordi et al., BJOG 2017;124:613). In designing an RCT, researchers must carefully select the participants, the interventions to be compared and the outcomes of interest (Lane BJOG 2018;125:1057; Lane BJOG 2018; 125:1504). Once these are defined, the number of participants needed to obtain reliable results is calculated (power calculation). All RCTs should have pre-specified outcomes, and should be prospectively registered with a clinical trials database to avoid selective reporting (Prior et al., BJOG 2017;124:1008–15). With appropriate ethical approvals in place, participants are then recruited and randomly assigned to either the intervention or the comparator group. It is important to ensure that at the time of recruitment there is no prior knowledge of the group to which the participant will be allocated. This is known as concealment and can be implemented using, for example, computer-generated randomisation systems. Following randomisation, RCTs can be blinded if feasible so that the participants, doctors and nurses as well as researchers do not know what treatment each participant is receiving, further minimising bias. In addition to trial registration, a full trial protocol documents full details of all trial processes before commencement (Lane BJOG 2018; 125:1504). Results of RCTs should usually be produced by intention-to-treat analysis (participants analysed in the groups to which they were randomised), as other variations, e.g. per protocol analyses (only participants who completed the treatment originally allocated are analysed) are often regarded as being biased when determining effectiveness. RCTs can have drawbacks, e.g. loss to follow up and missing data can threaten the validity of intention-to-treat analyses. Additionally, problems with generalisability can arise if participants that volunteer to participate are not similar to patients for whom RCT results will be used in the future. Expense is another criticism of RCTs, but this should be balanced against practice without RCTs, which may be even more costly. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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Underpowered RCTs lack the necessary sample size to accurately detect meaningful effects, which can reduce the validity of the results obtained; such trials can have limited scientific impact and informative value.
“Underpowered RCTs lack the necessary sample size to accurately detect meaningful effects, which can reduce the validity of the results obtained; such trials can have limited scientific impact and informative value (Hariton and Locascio 2018).”
From Dental Research in the Digital Age: The Registry-Based Clinical Trial. (2026) · cites this paper as Hariton and Locascio 2018
In the main section (page unavailable), the paper says researchers calculate the number of participants needed to reliably determine whether an intervention–outcome relationship exists. This supports the concern about insufficient sample size, but the paper does not say that underpowered trials have reduced validity, limited scientific impact, or limited informative value. (LLM, conf=0.84)
Experimental — accuracy not yet measuredRCTs are the gold standard for effectiveness research.
“Given the number of studies demonstrating the efficacy of BST for teaching DTT procedures, it is somewhat surprising that more have not conducted RCTs, as this is the gold standard for effectiveness research (Hariton & Locascio, 2018).”
From Training individuals to implement discrete‐trial teaching procedures using behavioral skills training: A scoping review with implications for practice and research (2024) · cites this paper as Hariton & Locascio, 2018
Given the number of studies demonstrating the efficacy of BST for teaching DTT procedures, it is somewhat surprising that more have not conducted RCTs.
“Given the number of studies demonstrating the efficacy of BST for teaching DTT procedures, it is somewhat surprising that more have not conducted RCTs, as this is the gold standard for effectiveness research (Hariton & Locascio, 2018).”
From Training individuals to implement discrete‐trial teaching procedures using behavioral skills training: A scoping review with implications for practice and research (2024) · cites this paper as Hariton & Locascio, 2018
RCTs are generally considered the most reliable method for assessing the efficacy of interventions.
“RCTs are generally considered the most reliable method for assessing the efficacy of interventions [23].”
From Virtual Reality for Addressing Depression and Anxiety: A Bibliometric Analysis (2023) · cites this paper as [23]
RCT designs are less prone to biases inherent with other study designs, which is why they were chosen for this systematic review.
“RCT designs were chosen for this systematic review as they are less prone to biases inherent with other study designs.74”
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Cites
Understanding controlled trials: Why are randomised controlled trials important?
Sibbald, B., & Roland, M. (1998) · BMJ · doi:10.1136/bmj.316.7126.201 · Cited by 807 · see citing works
Bellad, M. B., Tara, D., Ganachari, M. S., Mallapur, M., Goudar, S. S., Kodkany, B., Sloan, N. L., & Derman, R. J. (2012) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.2012.03341.x · Cited by 49 · see citing works
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Milne-Ives, M., Lam, C., De Cock, C., Van Velthoven, M. H., & Meinert, E. (2020) · JMIR mhealth and uhealth · doi:10.2196/17046 · Cited by 393 · see citing works
Beyond Good Intentions: Designing CSR Initiatives for Greater Social Impact
Barnett, M. L., Henriques, I., & Husted, B. W. (2020) · Journal of Management · doi:10.1177/0149206319900539 · Cited by 358 · see citing works
A checklist to assess Trustworthiness in RAndomised Controlled Trials (TRACT checklist)
Mol, B. W., Lai, S., Rahim, A., Bordewijk, E. M., Wang, R., Eekelen, R. V., Gurrin, L. C., Thornton, J. G., Wely, M. V., & Li, W. (2023) · doi:10.21203/rs.3.rs-2119486/v1 · Cited by 149 · see citing works
Mol, B. W., Lai, S., Rahim, A., Bordewijk, E. M., Wang, R., van Eekelen, R., Gurrin, L. C., Thornton, J. G., van Wely, M., & Li, W. (2023) · Research Integrity and Peer Review · doi:10.1186/s41073-023-00130-8 · Cited by 141 · see citing works
Implementation of Cognitive Behavioral Therapy in e–Mental Health Apps: Literature Review
Denecke, K., Schmid, N., & Nüssli, S. (2022) · Journal of Medical Internet Research · doi:10.2196/27791 · Cited by 107 · see citing works
Pedreschi, D., Pappalardo, L., Ferragina, E., Baeza-Yates, R., Barabási, A.-L., Dignum, F., Dignum, V., Eliassi-Rad, T., Giannotti, F., Kertész, J., et al. (2025) · Artificial Intelligence · doi:10.1016/j.artint.2024.104244 · Cited by 102 · see citing works
A systematic review of interventions embedded in curriculum to improve university student wellbeing
Upsher, R., Nobili, A., Hughes, G., & Byrom, N. (2022) · Educational Research Review · doi:10.1016/j.edurev.2022.100464 · Cited by 82 · see citing works
Goldberg, S. B., Sun, S., Carlbring, P., & Torous, J. (2023) · npj Digital Medicine · doi:10.1038/s41746-023-00923-7 · Cited by 75 · see citing works
Yan, L., Martinez-Maldonado, R., Jin, Y., Echeverria, V., Milesi, M., Fan, J., Zhao, L., Alfredo, R., Li, X., & Gašević, D. (2025) · Computers & Education · doi:10.1016/j.compedu.2025.105322 · Cited by 85 · see citing works
Lau, Y., Cheng, J.-Y., Wong, S.-H., Yen, K.-Y., & Cheng, L.-J. (2021) · World Journal of Psychiatry · doi:10.5498/wjp.v11.i4.133 · Cited by 68 · see citing works
Robinson, T., Robertson, N., Curtis, F., Darko, N., & Jones, C. R. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20010745 · Cited by 58 · see citing works
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Menezes, M., Harkins, C., Robinson, M. F., & Mazurek, M. O. (2020) · Research in Autism Spectrum Disorders · doi:10.1016/j.rasd.2020.101639 · Cited by 55 · see citing works
Fotteler, M. L., Mühlbauer, V., Brefka, S., Mayer, S., Kohn, B., Holl, F., Swoboda, W., Gaugisch, P., Risch, B., Denkinger, M., et al. (2022) · JMIR Aging · doi:10.2196/31916 · Cited by 52 · see citing works
Vitale, R., & Kim, Y. (2020) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2020.0048 · Cited by 43 · see citing works
Pettman, D., O'Mahen, H., Skoog Svanberg, A., von Essen, L., Axfors, C., Blomberg, O., & Woodford, J. (2019) · BMJ Open · doi:10.1136/bmjopen-2019-032659 · Cited by 24 · see citing works
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Victorson, D. E., Sauer, C. M., Wolters, L., Maletich, C., Lukoff, K., & Sufrin, N. (2020) · Mindfulness · doi:10.1007/s12671-020-01373-y · Cited by 33 · see citing works
Neo, H. S., Tan, J. H., Ang, W. H. D., & Lau, Y. (2022) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2022.110790 · Cited by 32 · see citing works
Carlisle, S., Ayling, K., Jia, R., Buchanan, H., & Vedhara, K. (2022) · Health Psychology Review · doi:10.1080/17437199.2021.1962386 · Cited by 32 · see citing works
Osborn, R., Dorstyn, D., Roberts, L., & Kneebone, I. (2021) · Journal of Developmental and Physical Disabilities · doi:10.1007/s10882-020-09753-x · Cited by 31 · see citing works
Briggs, A. M., Zohr, S. J., & Harvey, O. B. (2024) · Journal of Applied Behavior Analysis · doi:10.1002/jaba.1024 · Cited by 30 · see citing works
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Carneiro, L., Rosenbaum, S., Ward, P. B., Clemente, F. M., Ramirez-Campillo, R., Monteiro-Júnior, R. S., Martins, A., & Afonso, J. (2022) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2021-2026 · Cited by 23 · see citing works
Hawke, L. J., Nelson, E., O'Brien, P., Crossley, K. M., Choong, P. F., Bunzli, S., & Dowsey, M. M. (2024) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2024.101283 · Cited by 22 · see citing works
“Clinical trials are the gold-standard for evaluating the effectiveness of interventions [1].”
Background(2023) · International Journal of Exercise Science · doi:10.70252/eerp4920 · Cited by 20 · see citing works
Karo, M., Simorangkir, L., Daryanti Saragih, I., Suarilah, I., & Tzeng, H. (2024) · Journal of Nursing Scholarship · doi:10.1111/jnu.12941 · Cited by 20 · see citing works
Dominguez-Rodriguez, A., Martínez-Arriaga, R. J., Herdoiza-Arroyo, P. E., Bautista-Valerio, E., de la Rosa-Gómez, A., Castellanos Vargas, R. O., Lacomba-Trejo, L., Mateu-Mollá, J., Lupercio Ramírez, M. D. J., Figueroa González, J. A., et al. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph191912749 · Cited by 18 · see citing works
FactPICO: Factuality Evaluation for Plain Language Summarization of Medical Evidence
Joseph, S., Chen, L., Trienes, J., Göke, H., Coers, M., Xu, W., Wallace, B., & Li, J. J. (2024) · Proceedings of the 62nd Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers) · doi:10.18653/v1/2024.acl-long.459 · Cited by 17 · see citing works
Relative risk reduction: Misinformative measure in clinical trials and COVID-19 vaccine efficacy
Brown, R. B. (2022) · Dialogues in Health · doi:10.1016/j.dialog.2022.100074 · Cited by 11 · see citing works
“By contrast, absolute measures are used in randomized controlled trials, considered the gold standard of evidence demonstrating cause-effect relationships in clinical treatments and interventions [9].”
Third-wave psychotherapies to promote mental health in epilepsy: An updated systematic review
Makris, T., & Dorstyn, D. S. (2022) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2022.108766 · Cited by 8 · see citing works
CHEK2 knockout is a therapeutic target for TP53-mutated hepatocellular carcinoma
Chen, Y., Zhu, Z., Wu, X., Li, H., Guan, W., & Ren, H. (2024) · Cell Death Discovery · doi:10.1038/s41420-023-01777-4 · Cited by 6 · see citing works
Giovanazzi, A., Gios, L., Mastellaro, M., Gentilini, M. A., Valent, F., Condini, S., Bincoletto, G., Bacchiega, A., Zorzi, A., Malfatti, G., et al. (2023) · Trials · doi:10.1186/s13063-023-07515-6 · Cited by 4 · see citing works
Dental Research in the Digital Age: The Registry-Based Clinical Trial.
Joda, T., Settecase, E., Heitz‐Mayfield, L., Derks, J., Jung, R. E., & Zitzmann, N. U. (2026) · Clinical oral implants research · doi:10.1111/clr.70061 · Cited by 2 · see citing works
Effectiveness of psychotherapy for Hwa-Byung: A systematic review of interventional studies
Kwon, C.-Y., & Lee, B. (2025) · Medicine · doi:10.1097/md.0000000000041315
- Authors
- Hariton, E., & Locascio, J. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Massachusetts General Hospital (US)
- Venue
- BJOG: An International Journal of Obstetrics & Gynaecology
- Publisher
- Wiley
- Published
- 2018-06-19
- Volume
- 125
- Issue
- 13
- Pages
- 1716-1716
- ISSN
- 0306-5456 (ISSN-L)
- 1470-0328
- 1471-0528
- PMC
- PMC6235704
- OpenAlex
- W2809266094
- Cited by
- 1,604
- References
- 2
- Citations by year
- 2026: 215 · 2025: 325 · 2024: 343 · 2023: 270 · 2022: 229 · 2021: 143 · 2020: 68 · 2019: 10
- FWCI
- 45.85
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- BJOG An International Journal of Obstetrics & Gynaecology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (KL2TR001100, UL1TR001102)
- National Center for Advancing Translational Sciences
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Health Sciences › Health Professions › General Health Professions › Health Policy Implementation Science
- Keywords
- randomized controlled trials, intervention effectiveness, causal inference, randomization, bias mitigation, concealment, blinding, clinical trial registration, selective reporting, intention-to-treat analysis, power analysis, loss to follow-up, generalizability, evidence-based medicine, missing data
- MeSH terms
- Humans, Research Design, Randomized Controlled Trials as Topic
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