Mechanism used to implement the random allocation sequence (eg, central computer/telephone; sequentially numbered, opaque, sealed containers), describing any steps to conceal the sequence until interventions were assigned.
Examples
“Participants were centrally assigned to randomised study treatment using an interactive web response system (IWRS) . . . Block randomisation schedules were computer generated by a vendor with a block size of 6 in a randomisation ratio of 2:1 and distributed to the IWRS vendor (endpointClinical) for participant randomisation.”1
“For allocation concealment, numbered containers were used. The interventions were sealed in sequentially numbered identical opaque containers according to the allocation sequence.”2
“Furthermore, we employed syringes sequentially numbered and packaged in opaque and sealed containers. Specifically, syringes containing esmolol or placebo were centrally prepared, pre-coded based on the randomization list, and sent sequentially to the operating room immediately before administration.”3
“Allocation was concealed using sequentially numbered, opaque, sealed envelopes (SNOSE) prior to making the incision.”4
“Allocation concealment was done using sequentially numbered, sealed, opaque packages.”5
“The allocation sequence was concealed from the researcher (JR) enrolling and assessing participants in sequentially numbered, opaque, sealed and stapled envelopes. Aluminium foil inside the envelope was used to render the envelope impermeable to intense light. To prevent subversion of the allocation sequence, the name and date of birth of the participant was written on the envelope and a video tape made of the sealed envelope with participant details visible. Carbon paper inside the envelope transferred the information onto the allocation card inside the envelope and a second researcher (CC) later viewed video tapes to ensure envelopes were still sealed when participants' names were written on them. Corresponding envelopes were opened only after the enrolled participants completed all baseline assessments and it was time to allocate the intervention.”6
Explanation
Item 17 discussed generation of an unpredictable sequence of assignments. Of considerable importance is how this sequence is applied when participants are enrolled into the trial. A generated allocation sequence should be implemented by using allocation concealment,7 a critical mechanism that prevents foreknowledge of treatment assignment and thus shields those who enrol participants from being influenced by this knowledge. The decision to accept or reject a participant should be made, and informed consent should be obtained from the participant, in ignorance of the next assignment in the sequence.8 In summary, adequate allocation concealment safeguards knowledge of forthcoming assignments, whereas proper random sequences (item 17) prevent correct anticipation of future assignments based on knowledge of past assignments.
Allocation concealment should not be confused with blinding (item 20). Allocation concealment seeks to prevent selection bias, protects the assignment sequence before and until allocation, and can always be successfully implemented.9 In contrast, blinding seeks to prevent ascertainment bias, protects the sequence after allocation, and cannot always be implemented.7 Without adequate allocation concealment, however, even random, unpredictable assignment sequences can be subverted.9,10
Centralised or third party assignment is especially desirable. Many good allocation concealment mechanisms incorporate external involvement. Use of a pharmacy or central computer or telephone randomisation system are common techniques. Automated assignment systems are likely to become more common.11 When external involvement is not feasible, an excellent method of allocation concealment is the use of numbered containers. The interventions (often medicines) are sealed in sequentially numbered identical containers according to the allocation sequence.12 Enclosing assignments in sequentially numbered, opaque, sealed envelopes can be a good allocation concealment mechanism if it is developed and monitored diligently.13,14 This method can be corrupted, however, particularly if it is poorly executed. Investigators should ensure that the envelopes are opaque when held to the light, and are opened sequentially and only after the participant’s name and other details are written on the appropriate sequentially numbered sealed envelope.13–15
A number of methodological studies provide empirical evidence to support these precautions.9,16–1920–22 Trials in which the allocation sequence had been inadequately or unclearly concealed yielded larger estimates of treatment effects than did trials in which authors reported adequate allocation concealment. These findings provide strong empirical evidence that inadequate allocation concealment contributes to bias in estimating treatment effects.
Despite the importance of the mechanism of allocation concealment, published reports frequently omit such details. Among older studies, the mechanism used to allocate interventions was omitted in reports of 89% of trials on rheumatoid arthritis,23 48% of trials in obstetrics and gynaecology journals,7 and 44% of trials in general medical journals.24 In a more broadly representative sample of all PubMed indexed randomised trials, only 18% reported any allocation concealment mechanism and some of those reported mechanisms were inadequate.25 At the same time, some trials where there is no reporting of allocation concealment may have been properly concealed, as demonstrated by inspection of their protocols.26
Newer studies further illuminate poor reporting of allocation concealment. Unclear reporting (ie, the authors did not provide sufficient information in the paper to allow judgment to be made on the adequacy of method of allocation concealment) was found in 78%27 and 85%19 of trials. Moreover, those two studies determined that only 27%27 and 14%19 used an adequate allocation concealment mechanism, while another found a similar level of 12%.28 A review of trials in journals of traditional Chinese medicine found that only 7% used adequate allocation concealment.29
Fortunately, reporting and conduct may be improving in recent years, for example, after the CONSORT 2010 guidelines were published.30 Another study found that reporting on allocation concealment and sequence generation was much better in journals that endorsed the CONSORT 2010 guidelines than in non-endorsing journals.14 Moreover, that study found that 57% of trials in the sample had used an adequate allocation concealment mechanism.14 However, other empirical studies show only modest improvements, for example, an evaluation of over 176 000 trials31 found that allocation concealment reporting increased from 5.1% in 1966-90 to 19.3% in 2010-18. While any improvement is encouraging, more efforts to improve conduct and reporting remain necessary.
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References
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Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): Two randomised, double-blind, placebo-controlled, phase 3 studies. The Lancet. 2023;401(10383):1159-1171. doi:10.1016/s0140-6736(23)00061-2
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Rai A, Naik D. Evaluation of remineralizing effect of zinc-carbonate hydroxyapatite on the reduction of postrestorative sensitivity: A randomized controlled clinical trial. Journal of Conservative Dentistry. 2023;26(1):56. doi:10.4103/jcd.jcd_300_22
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A M. 2023;73.
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Rattanathanya T, Adulkasem N, Wongcharoenwatana J, Ariyawatkul T, Chotigavanichaya C, Eamsobhana P. Perioperative blood loss reduction using a sterile exsanguination tourniquet for orthopedic femoral-related surgeries in children: A randomized controlled study. Journal of Orthopaedic Surgery and Research. 2023;18(1). doi:10.1186/s13018-023-04046-3
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Padoei F, Mamsharifi P, Hazegh P, et al. The therapeutic effect of n‐acetylcysteine as an add‐on to methadone maintenance therapy medication in outpatients with substance use disorders: A randomized, double‐blind, placebo‐controlled clinical trial. Brain and Behavior. 2022;13(1). doi:10.1002/brb3.2823
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Radford JA, Landorf KB, Buchbinder R, Cook C. Effectiveness of low-dye taping for the short-term treatment of plantar heel pain: A randomised trial. BMC Musculoskeletal Disorders. 2006;7(1). doi:10.1186/1471-2474-7-64
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Schulz KF. Assessing the quality of randomization from reports of controlled trials published in obstetrics and gynecology journals. JAMA: The Journal of the American Medical Association. 1994;272(2):125. doi:10.1001/jama.1994.03520020051014
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Chalmers TC, Levin H, Sacks HS, Reitman D, Berrier J, Nagalingam R. Meta‐analysis of clinical trials as a scientific discipline. I: Control of bias and comparison with large co‐operative trials. Statistics in Medicine. 1987;6(3):315-325. doi:10.1002/sim.4780060320
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Schulz KF. Empirical evidence of bias: Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 1995;273(5):408. doi:10.1001/jama.1995.03520290060030
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Pocock SJ. Statistical aspects of clinical trial design. The Statistician. 1982;31(1):1. doi:10.2307/2988097
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Hopewell S, Dutton S, Yu L-M, Chan A-W, Altman DG. The quality of reports of randomised trials in 2000 and 2006: Comparative study of articles indexed in PubMed. BMJ. 2010;340(mar23 1):c723-c723. doi:10.1136/bmj.c723
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Piaggio G, Elbourne D, Schulz KF, Villar J, Pinol AP, Gülmezoglu AM. The reporting of methods for reducing and detecting bias: An example from the WHO misoprostol third stage of labour equivalence randomised controlled trial. BMC Medical Research Methodology. 2003;3(1). doi:10.1186/1471-2288-3-19
13.
Schulz KF. Subverting randomization in controlled trials. JAMA: The Journal of the American Medical Association. 1995;274(18):1456. doi:10.1001/jama.1995.03530180050029
14.
Clark L, Mitchell N, Hewitt C, Torgerson D. Exploring engagement with authors of randomised controlled trials to develop recommendations to improve allocation concealment implementation and reporting. F1000Research. 2021;10:83. doi:10.12688/f1000research.27918.1
15.
Clark L, Schmidt U, Tharmanathan P, Adamson J, Hewitt C, Torgerson D. Poor reporting quality of key randomization and allocation concealment details is still prevalent among published <scp>RCTs</scp> in 2011: A review. Journal of Evaluation in Clinical Practice. 2013;19(4):703-707. doi:10.1111/jep.12031
16.
Savović J, Jones HE, Altman DG, et al. Influence of reported study design characteristics on intervention effect estimates from randomized, controlled trials. Annals of Internal Medicine. 2012;157(6):429-438. doi:10.7326/0003-4819-157-6-201209180-00537
17.
Thompson M, Van den Bruel A, Verbakel J, et al. Systematic review and validation of prediction rules for identifying children with serious infections in emergency departments and urgent-access primary care. Health Technology Assessment. 2012;16(15). doi:10.3310/hta16150
18.
Savović J, Turner RM, Mawdsley D, et al. Association between risk-of-bias assessments and results of randomized trials in cochrane reviews: The ROBES meta-epidemiologic study. American Journal of Epidemiology. 2017;187(5):1113-1122. doi:10.1093/aje/kwx344
19.
Saltaji H, Armijo-Olivo S, Cummings GG, Amin M, Costa BR da, Flores-Mir C. Impact of selection bias on treatment effect size estimates in randomized trials of oral health interventions: A meta-epidemiological study. Journal of Dental Research. 2017;97(1):5-13. doi:10.1177/0022034517725049
20.
Pildal J, Hrobjartsson A, Jorgensen K, Hilden J, Altman D, Gotzsche P. Impact of allocation concealment on conclusions drawn from meta-analyses of randomized trials. International Journal of Epidemiology. 2007;36(4):847-857. doi:10.1093/ije/dym087
21.
Wood L, Egger M, Gluud LL, et al. Empirical evidence of bias in treatment effect estimates in controlled trials with different interventions and outcomes: Meta-epidemiological study. BMJ. 2008;336(7644):601-605. doi:10.1136/bmj.39465.451748.ad
22.
Wang Y, Parpia S, Couban R, et al. Compelling evidence from meta-epidemiological studies demonstrates overestimation of effects in randomized trials that fail to optimize randomization and blind patients and outcome assessors. Journal of Clinical Epidemiology. 2024;165:111211. doi:10.1016/j.jclinepi.2023.11.001
23.
Gøtzsche PC. Methodology and overt and hidden bias in reports of 196 double-blind trials of nonsteroidal antiinflammatory drugs in rheumatoid arthritis. Controlled Clinical Trials. 1989;10(1):31-56. doi:10.1016/0197-2456(89)90017-2
24.
Altman DG, Doré CJ. Randomisation and baseline comparisons in clinical trials. The Lancet. 1990;335(8682):149-153. doi:10.1016/0140-6736(90)90014-v
25.
Chan AW, Altman DG. Epidemiology and reporting of randomised trials published in PubMed journals. The Lancet. 2005;365(9465):1159-1162. doi:10.1016/s0140-6736(05)71879-1
26.
Mhaskar R, Djulbegovic B, Magazin A, Soares HP, Kumar A. Published methodological quality of randomized controlled trials does not reflect the actual quality assessed in protocols. Journal of Clinical Epidemiology. 2012;65(6):602-609. doi:10.1016/j.jclinepi.2011.10.016
27.
Clark L, Schmidt U, Tharmanathan P, Adamson J, Hewitt C, Torgerson D. Allocation concealment: A methodological review. Journal of Evaluation in Clinical Practice. 2013;19(4):708-712. doi:10.1111/jep.12032
28.
Armijo-Olivo S, Saltaji H, Costa BR da, Fuentes J, Ha C, Cummings GG. What is the influence of randomisation sequence generation and allocation concealment on treatment effects of physical therapy trials? A meta-epidemiological study. BMJ Open. 2015;5(9):e008562. doi:10.1136/bmjopen-2015-008562
29.
He J, Du L, Liu G, et al. Quality assessment of reporting of randomization, allocation concealment, and blinding in traditional chinese medicine RCTs: A review of 3159 RCTs identified from 260 systematic reviews. Trials. 2011;12(1). doi:10.1186/1745-6215-12-122
30.
Zheng SL, Chan FT, Maclean E, Jayakumar S, Nabeebaccus AA. Reporting trends of randomised controlled trials in heart failure with preserved ejection fraction: A systematic review. Open Heart. 2016;3(2):e000449. doi:10.1136/openhrt-2016-000449
31.
Kilicoglu H, Jiang L, Hoang L, Mayo-Wilson E, Vinkers CH, Otte WM. Methodology reporting improved over time in 176,469 randomized controlled trials. Journal of Clinical Epidemiology. 2023;162:19-28. doi:10.1016/j.jclinepi.2023.08.004
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Citation
For attribution, please cite this work as:
Hopewell S, Chan AW, Collins GS, et al. CONSORT
2025 statement: updated guideline for reporting randomised trials.
BMJ. 2025;389:e081123. doi:10.1136/bmj-2024-081123
Reporting Guidelines are recommendations to help describe your work clearly
Your research will be used by people from different disciplines and backgrounds for decades to come. Reporting guidelines list the information you should describe so that everyone can understand, replicate, and synthesise your work.
Reporting guidelines do not prescribe how research should be designed or conducted. Rather, they help authors transparently describe what they did, why they did it, and what they found.
Reporting guidelines make writing research easier, and transparent research leads to better patient outcomes.
Easier writing
Following guidance makes writing easier and quicker.
You work will be read by different people, for different reasons, around the world, and for decades to come. Reporting guidelines help you consider all of your potential audiences. For example, your research may be read by researchers from different fields, by clinicians, patients, evidence synthesisers, peer reviewers, or editors. Your readers will need information to understand, to replicate, apply, appraise, synthesise, and use your work.
Cohort studies
A cohort study is an observational study in which a group of people with a particular exposure (e.g. a putative risk factor or protective factor) and a group of people without this exposure are followed over time. The outcomes of the people in the exposed group are compared to the outcomes of the people in the unexposed group to see if the exposure is associated with particular outcomes (e.g. getting cancer or length of life).
A case-control study is a research method used in healthcare to investigate potential risk factors for a specific disease. It involves comparing individuals who have been diagnosed with the disease (cases) to those who have not (controls). By analysing the differences between the two groups, researchers can identify factors that may contribute to the development of the disease.
An example would be when researchers conducted a case-control study examining whether exposure to diesel exhaust particles increases the risk of respiratory disease in underground miners. Cases included miners diagnosed with respiratory disease, while controls were miners without respiratory disease. Participants' past occupational exposures to diesel exhaust particles were evaluated to compare exposure rates between cases and controls.
A cross-sectional study (also sometimes called a "cross-sectional survey") serves as an observational tool, where researchers capture data from a cohort of participants at a singular point. This approach provides a 'snapshot'— a brief glimpse into the characteristics or outcomes prevalent within a designated population at that precise point in time. The primary aim here is not to track changes or developments over an extended period but to assess and quantify the current situation regarding specific variables or conditions. Such a methodology is instrumental in identifying patterns or correlations among various factors within the population, providing a basis for further, more detailed investigation.
A systematic review is a comprehensive approach designed to identify, evaluate, and synthesise all available evidence relevant to a specific research question. In essence, it collects all possible studies related to a given topic and design, and reviews and analyses their results.
The process involves a highly sensitive search strategy to ensure that as much pertinent information as possible is gathered. Once collected, this evidence is often critically appraised to assess its quality and relevance, ensuring that conclusions drawn are based on robust data. Systematic reviews often involve defining inclusion and exclusion criteria, which help to focus the analysis on the most relevant studies, ultimately synthesising the findings into a coherent narrative or statistical synthesis. Some systematic reviews will include a [meta-analysis]{.defined data-bs-toggle="offcanvas" href="#glossaryItemmeta_analyses" aria-controls="offcanvasExample" role="button"}.
A randomised controlled trial (RCT) is a trial in which participants are randomly assigned to one of two or more groups: the experimental group or groups receive the intervention or interventions being tested; the comparison group (control group) receive usual care or no treatment or a placebo. The groups are then followed up to see if there are any differences between the results. This helps in assessing the effectiveness of the intervention.
Research that aims to gather and analyse non-numerical (descriptive) data in order to gain an understanding of individuals' social reality, including understanding their attitudes, beliefs, and motivation. This type of research typically involves in-depth interviews, focus groups, or field observations in order to collect data that is rich in detail and context. Qualitative research is often used to explore complex phenomena or to gain insight into people's experiences and perspectives on a particular topic. It is particularly useful when researchers want to understand the meaning that people attach to their experiences or when they want to uncover the underlying reasons for people's behaviour. Qualitative methods include ethnography, grounded theory, discourse analysis, and interpretative phenomenological analysis.
Diagnostic accuracy studies focus on estimating the ability of the test(s) to correctly identify people with a predefined target condition, or the condition of interest (sensitivity) as well as to clearly identify those without the condition (specificity).
Prediction Models
Prediction model research is used to test the accurarcy of a model or test in estimating an outcome value or risk. Most models estimate the probability of the presence of a particular health condition (diagnostic) or whether a particular outcome will occur in the future (prognostic). Prediction models are used to support clinical decision making, such as whether to refer patients for further testing, monitor disease deterioration or treatment effects, or initiate treatment or lifestyle changes. Examples of well known prediction models include EuroSCORE II for cardiac surgery, the Gail model for breast cancer, the Framingham risk score for cardiovascular disease, IMPACT for traumatic brain injury, and FRAX for osteoporotic and hip fractures.
Quality improvement research is about finding out how to improve and make changes in the most effective way. It is about systematically and rigourously exploring "what works" to improve quality in healthcare and the best ways to measure and disseminate this to ensure positive change. Most quality improvement effectiveness research is conducted in hospital settings, is focused on multiple quality improvement interventions, and uses process measures as outcomes. There is a great deal of variation in the research designs used to examine quality improvement effectiveness.
A meta-analysis is a statistical technique that amalgamates data from multiple studies to yield a single estimate of the effect size. This approach enhances precision and offers a more comprehensive understanding by integrating quantitative findings. Central to a meta-analysis is the evaluation of heterogeneity, which examines variations in study outcomes to ensure that differences in populations, interventions, or methodologies do not skew results. Techniques such as meta-regression or subgroup analysis are frequently employed to explore how various factors might influence the outcomes. This method is particularly effective when aiming to quantify the effect size, odds ratio, or risk ratio, providing a clearer numerical estimate that can significantly inform clinical or policy decisions.
How Meta-analyses and Systematic Reviews Work Together
Systematic reviews and meta-analyses function together, each complementing the other to provide a more robust understanding of research evidence. A systematic review meticulously gathers and evaluates all pertinent studies, establishing a solid foundation of qualitative and quantitative data. Within this framework, if the collected data exhibit sufficient homogeneity, a meta-analysis can be performed. This statistical synthesis allows for the integration of quantitative results from individual studies, producing a unified estimate of effect size. Techniques such as meta-regression or subgroup analysis may further refine these findings, elucidating how different variables impact the overall outcome. By combining these methodologies, researchers can achieve both a comprehensive narrative synthesis and a precise quantitative measure, enhancing the reliability and applicability of their conclusions. This integrated approach ensures that the findings are not only well-rounded but also statistically robust, providing greater confidence in the evidence base.
Why Don't All Systematic Reviews Use a Meta-Analysis?
Systematic reviews do not always have meta-analyses, due to variations in the data. For a meta-analysis to be viable, the data from different studies must be sufficiently similar, or homogeneous, in terms of design, population, and interventions. When the data shows significant heterogeneity, meaning there are considerable differences among the studies, combining them could lead to skewed or misleading conclusions. Furthermore, the quality of the included studies is critical; if the studies are of low methodological quality, merging their results could obscure true effects rather than explain them.
Protocol
A plan or set of steps that defines how something will be done. Before carrying out a research study, for example, the research protocol sets out what question is to be answered and how information will be collected and analysed.
