Example

“Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial.”25

Explanation

The ability to identify a report of a randomised trial in a bibliographic database depends to a large extent on how it was indexed. Indexers might not classify a report as a randomised trial if the authors do not explicitly report this information.26 To help ensure that a study is appropriately indexed and easily identified, authors should use the word “randomised” in the title to indicate that the participants were randomly assigned to their comparison groups.

Explanation

Transparent and sufficiently detailed abstracts are important because readers often base their assessment of a trial on such information. Some readers use an abstract as a screening tool to decide whether to read the full article. However, not all trials are freely available and some health professionals and other users do not have access to the full trial reports.27

A journal abstract should contain sufficient information about a trial to serve as an accurate record of its conduct and findings, providing optimal information about the trial within the space constraints and format of a journal. A properly constructed and written abstract helps individuals to assess quickly the relevance of the findings and aids the retrieval of relevant reports from electronic databases.28 The abstract should accurately reflect what is included in the full journal article and should not include information that does not appear in the body of the paper. In addition, abstracts should not be a distorted representation of the trial results. Studies comparing information reported in a journal abstract with that reported in the text of the full publication have found claims that are inconsistent with, or missing from, the body of the full article.29303132 Abstracts are also frequently reported with spin defined as a distorted representation of the study results.333435 Authors should avoid selectively reporting only statistically significant secondary outcomes or subgroup analyses. Conversely, omitting important harms from the abstract could seriously mislead interpretation of the trial findings and benefit-to-harms balance that is critical for decision making.3637

An extension to CONSORT 2001 provided a list of essential items that authors should include in a journal (or conference) abstract when reporting the main results of a randomised trial.38 A systematic review of 10 meta-research studies examined the reporting quality of abstracts of randomised trials and found improvements in reporting following publication of this extension.39Table 2 provides a list of essential items to include in an abstract; it is based on the CONSORT for Abstracts extension40 and has been updated to reflect changes made to the main CONSORT checklist. We strongly recommend the use of structured abstracts for reporting randomised trials. They provide readers with information about the trial under a series of headings pertaining to the design, conduct, analysis and interpretation.41 Some studies have found that structured abstracts offer greater value and information coverage than the more traditional descriptive abstracts4243 and allow readers to find information more easily.44 We recognise that journals have their own structure for reporting abstracts. It is not our intention to suggest changes to these formats, but to recommend what information should be reported.

Example

“This study was registered in the Iranian Registry of Clinical Trials under the code IRCT20150531022498N30: https://en.irct.ir/trial/41031. Registered on July 26, 2019.”47

Explanation

The consequences of non-publication of entire trials (ie, publication bias),484950 and of selective reporting of outcomes and analyses within trials, have been well documented.515253 For almost 40 years, there have been growing calls to address these practices. Today, a ubiquitous view recommends trial registration as the best practice to achieve this goal, and inform policymakers and potential participants about ongoing trials. Registering clinical trials, before any assignment of participants, with unique trial identification numbers and other basic information about the trial so that essential details are made publicly available, is a minimum best practice.54555657 Serious problems of withholding data58 led to renewed efforts to ensure registration of randomised trials. The World Health Organization (WHO) states that “the registration of all interventional trials is a scientific, ethical and moral responsibility.”59

In September 2004, the ICMJE established a policy that it would only consider trials for publication if they had been registered before the enrolment of the first participant.60 This policy resulted in a substantial increase in the number of trials being registered.61 However, some trials are still not registered.49 The ICMJE gives guidance on acceptable registries (https://www.icmje.org/about-icmje/faqs/clinical-trials-registration/) and also accepts registration in WHO primary registries (https://www.who.int/clinical-trials-registry-platform/network/primary-registries) and ClinicalTrials.gov. Registers charging a fee to view their content should be avoided to ensure equity of access for everyone, including patients and the public.

The Transparency and Openness Promotion (TOP) guidelines, endorsed and used by thousands of journals, recommends trial registration.62 In a survey of 168 high impact factor medical journals’ “Instructions to authors” in 2014, 78 journals stated that all recent clinical trials must be registered as a requirement of submission to that journal.63 A more recent survey in 2019 of surgical journals publishing randomised trials found that 53 of 82 journals mandated prospective registration.64

Despite recommendations, and mandates in some jurisdictions for clinical trialists to register their trial and evidence that registration deters selective reporting, this is still not happening universally.6566 Authors should provide the name of the registry, the trial’s associated registration number, date of registration and, where possible, the URL for the trial’s registration. We recommend that authors also report whether (or when) the trial results are available on the associated trial register.

Despite the considerable increase in clinical trial registration, there is a strong body of evidence showing the lack of access to trial results.67686970 The latest version of the Declaration of Helsinki states that “Researchers have a duty to make publicly available the results of their research on human participants and are accountable for the timeliness, completeness, and accuracy of their reports . . . Negative and inconclusive as well as positive results must be published or otherwise made publicly available.” In 2015, WHO published a new statement on the public disclosure of trial results, which requests that “the key outcomes are to be made publicly available within 12 months of study completion by posting to the results section of the primary clinical trial registry. Where a registry is used without a results database available, the results should be posted on a free-to-access, publicly available, searchable institutional website of the Regulatory Sponsor, Funder or Principal Investigator.” Some legislations are also in place in the US, UK, and Europe requesting the posting of trial results on clinical trials registry within 12 months after study completion.717273

Authors should indicate whether the trial results are publicly posted to the trial registry, as a preprint (with URL citation) or as published articles (with citations).

Example

“The full trial protocol and the Statistical Analysis Plan can be accessed in the Supplementary Material”.74 This article and supplementary material are open access.

Explanation

A protocol for the complete trial (rather than a protocol of a specific procedure within a trial, such as for the intervention) is important because it prespecifies the methods of the randomised trial, for example, the primary outcome (item 14). Having a protocol provides important context to interpret a trial, implement its findings, and facilitate replication and appraisal of risk of bias. It can also help to restrict the likelihood of undeclared post hoc changes to the trial methods and selective outcome reporting (item 10).757677 Elements that are important to address in the protocol for a randomised trial are described in the SPIRIT 2025 statement.78

A protocol may either include the full statistical analysis plan or may include a section outlining the main principles while referencing and reporting the full statistical analysis plan as a separate, more detailed document. The statistical analysis plan typically includes details about several aspects of the clinical trial, such as the data analysis plan for the primary outcome(s) and all secondary outcomes. Details about what to include in a statistical analysis plan can be found elsewhere.79

The protocol should be signed off by the trial steering committee before the allocation of any participants and data collection. Similarly, the full statistical analysis plan should be signed off by the trial steering committee before the dataset is closed for analysis. This allows transparent documentation of any subsequent changes to either document. In many trials, changes to the protocol and statistical analysis plan may happen after the trial onset for legitimate reasons (eg, in response to challenges that were not anticipated or new evidence). In these cases, each iteration of the protocol and statistical analysis plan should record the changes along with their rationale and timing.

There are several options for authors to consider to ensure their trial protocol, and full statistical analysis plan where applicable, are accessible to interested readers. The protocol and full statistical analysis plan (and their various iterations) can be stored in a repository, such as the Open Science Framework, which is free to use and access for all readers. Openness and accessibility are core elements of open science (see Open science section). Trial protocols and statistical analysis plans can also be published in journals such as Trials and BMJ Open. Open access publication would ensure that any reader, including patients and the public, can access the document. Trial registration (item 2) will also ensure that a minimum set of trial protocol details are available as part of the trial’s registration (https://www.who.int/clinical-trials-registry-platform), but often a registration record leaves large ambiguity about key protocol issues and statistical analyses. The more detailed trial protocol can also be posted on most clinical trial registries.

Ideally, the authors should give access to the protocol signed off by the trial steering committee before the allocation of any participants and data collection with any subsequent changes with their rationale and timing.

When submitting a completed trial report, trial authors can include their protocol as a supplemental document or provide a URL to its location. Such documentation can facilitate peer review and help identify reporting biases.

Examples

“All data requests should be submitted to the corresponding author (AR) for consideration as agreed in our publication plan. Access to anonymised data may be granted following review with the Trial Management Group and agreement of the chief investigator (AR).”80

“Deidentified data collected and presented in this study, including individual participant data and a data dictionary defining each field in the set, will be made available upon reasonable request after publication of this Article, following approval by regulatory authorities. Data can be requested by contacting the corresponding author.”81

Explanation

Data and code sharing can take the transparency of trial reporting to a different, more desirable level. Sharing individual de-identified participant data would be helpful in many ways: verifying results and increasing trust; using data more extensively for secondary analyses; and using data for individual patient data meta-analysis (IPD MA). Data sharing is also associated with increased citations82 (ie, broader dissemination). Some trial groups have worked collaboratively to conduct IPD MA.83 However, for most randomised trials, data sharing does not happen.8485868788 During the covid-19 pandemic, there were many examples of authors’ intentions to share data that then did not transpire (ie, they did not share their data).8789 There is increasing concern that some trials are fraudulent or considered to be so-called zombie trials, which becomes evident only on inspection of the raw data.9091 However, even if zombie trials are not as prevalent as feared, genuine trials can have such an important role and high value that it is important to maximise their utility by making them more open. Detailed documentation of sharing plans may help in this direction.92

All data sharing should abide by the principle of being as open as possible and as closed as necessary throughout a randomised trial’s life cycle (from SPIRIT to CONSORT). It is important to ensure that all the appropriate permissions are included on the patient consent forms. Trials cannot share data that are not fully anonymised without the appropriate patient consent, and full anonymisation can be difficult. Care must be taken to share participant data appropriately to maintain confidentiality. Suitable mechanisms must be in place to appropriately de-identify participant data, and data should only be shared in a safe and secure manner that fits with the consent obtained from participants.

Data sharing typically involves sharing: the underlying data generated from the trial’s conduct; a data dictionary (ie, structure, content, and meaning of each data variable); and other relevant material(s) used as part of the trial’s analysis such as the trial protocol, data management plan, statistical analysis plan, and code used to analyse the data. A trial’s data can be shared in a variety of ways, such as via an institutional repository (eg, belonging to the university associated with the trial’s coordinating centre) and/or a public-facing repository, or by having a bespoke process to provide data. Often, a data use agreement is necessary, which will, at a minimum: prohibit attempts to reidentify or contact trial participants; address any requirements regarding planned outputs of the proposed research (eg, publication and acknowledgment requirements); and prohibit non-approved uses or further distribution of the data.93

In a growing number of jurisdictions, funders such as the National Institute for Health (NIH),94 in the US and the National Institute for Health and Care Research (NIHR) in the UK, alongside other funders such as the Gate’s Foundation, now require researchers to share their data and make the results publicly available for anyone to read. Similarly, some journals are also requiring authors to include a data sharing statement as part of the article submission process (eg, Annals of Internal Medicine, The BMJ, JAMA Network journals, PLoS Medicine).

The process of signalling how data sharing will be achieved is often contained in a data management plan but may also be found in the trial protocol or statistical analysis plan. More complete details regarding developing a data management plan are beyond the scope of this paper. Such details can be found elsewhere.95 Authors should provide some description of where these details can be found (eg, name of repository and URL to data, code, and materials). Sharing may also entail embargo periods, and if so, the choice of an embargo should be justified and its length should be stated.96 If data (or some parts thereof) cannot be shared, the reasons for this should be reported and should be sensible and following ethical principles.

For more complex trials (eg, types of talking therapies, physiotherapy), additional materials to share might include a handbook and/or video to detail the intervention.93 Often these can be shared much more freely than the data, as there are fewer issues with confidentiality.

Examples

“Grant support was received for the intervention from Plan International and for the research from the Wellcome Trust and Joint United Nations Programme on HIV/AIDS (UNAIDS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”97

“Funding: Merck Sharp and Dohme . . . The study funder had a role in the study design, data collection, data analysis, data interpretation, and writing of the report.”98

The article also states that “Merck employees LY, SB, and PB were involved in the conceptualisation of the study, formal analysis, the investigation process, development of the methodology, project administration, drafting the manuscript, and had critically reviewed and edited the manuscript.”98

Explanation

Reporting the funding source(s), and the exact roles of the trial funders, provides important context for readers of a trial report when ascertaining overall methodological rigor (eg, relevance of the type of comparator intervention and eligibility criteria for patients) and risk of bias (eg, selective reporting of favourable results). The trial report should therefore describe details of all funders and the types of funding, as well as the role of the funder in trial design (ie, protocol development), conduct, data analysis, and reporting (ie, interpretation, manuscript writing, and dissemination of results). This should include whether the funder controlled the final decision regarding any of these aspects of the trial, and any mechanisms introduced to minimise funder influence. If the funder had no direct involvement in the trial, that should be stated.

A randomised trial requires considerable funding, typically from pharmaceutical or device companies (industry funding); or from research councils or other scientific or private foundations, or governmental or non-governmental organisations (non-industry funding).99 One study of trials conducted between 2010 and 2015 estimated the median cost per phase 3 drug company trial at $21.4m (£17.21m; €20.7m),100 with substantial variation. The mean cost of clinical trials funded by the NIHR in the UK, reflecting differences in the research and care infrastructure already funded, was lower, but still sizeable—approximately £1.3m—with considerable variation.101 The various types of funders differ in their overall agenda, their reasons for funding a trial, and their propensity to influence the trial.

Funding of a trial typically involves direct monetary support, but financial support may also be provided indirectly in the form of free trial drugs, equipment, or services (eg, statistical analysis or use of medical writers).102 Among the most highly cited clinical trials published in 2019 to 2022, two thirds were funded by industry sponsors, many of whom also provided industry analysts and coauthors.103

Industry funding of trials is associated with conclusions that favour the experimental intervention. A systematic review of 75 methodological studies, comparing industry funded studies with non-industry funded studies (mostly randomised trials), reported that industry funded studies had favourable conclusions more often than non‐industry funded studies (risk ratio 1.34; 95% confidence interval (CI) 1.19 to 1.51).104 Industry funded trials may also report more favourable results (ie, larger estimates of intervention effects) than comparable trials that are funded by non-industry sources. One review of eight published meta-epidemiological studies reported that intervention effects (odds ratios) from industry funded trials were, on average, exaggerated by 5% (95% CI −6% to 15%), although the result was imprecise and consistent with chance findings. However, trials with a high risk of industry funder influence (eg, on trial design, conduct, analysis, and reporting) exaggerated effect estimates by 12% (95% CI 3% to 19%).105 Undue influence on trials from non-industry funders with a strong interest in a specific trial result has been described,106 but has been studied much less.

A review of 200 trials published in 2015107 found that 178 (89%) publications included a funding statement. However, in half of the publications, the role of funder was not reported; in the other half, the reporting was often unclear or incomplete; and undisclosed funding from a for-profit organisation was found in 26 of 54 trials reporting only not-for-profit funding. Another study surveyed authors of 200 trials fully funded by industry and found that funders had been involved in the design of 173 trials (87%), in the data analysis of 146 trials (73%), and in the reporting of 173 trials (87%).102 No clear consensus exists on a monetary threshold for when funding from a source with conflict of interest becomes problematic. It is also unclear whether commercial funding is less important than the degree and type of funder influence on trial design, conduct, analysis, and reporting.

Example

“SYR reports grants from Amgen, Astellas, Daiichi Sankyo, Eisai, Merck, Roche, Zymeworks, Indivumed, MSD, Ono/Bristol Myers Squibb, AstraZeneca, BI, Taiho, Lilly, SN Bioscience. SRF has received honoraria as an invited speaker for Lilly, Eisai, Daiichi Sankyo, MSD, and Ono/Bristol Myers Squibb; has participated on advisory boards for Amgen and Indivumed; and has served as an advisor for Astellas, Daiichi Sankyo, Eisai, LG Biochem, Merck Sharpe Dohme, Ono/Bristol Myers Squibb, and AstraZeneca. D-YO reports grants from AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, Merck Sharpe Dohme, and Handok; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, Bristol Myers Squibb/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, and Merck Sharpe Dohme. M-HR reports research grants from AstraZeneca; consulting fees from Bristol Myers Squibb, Ono, Lilly, Merck Sharpe Dohme, Novartis, Daiichi Sankyo, AstraZeneca, Sanofi, and Astellas; and has received honoraria for lectures, presentations, speakers bureaus, or educational events from Bristol Myers Squibb, Ono, Lilly, Merck Sharpe Dohme, Novartis, Daiichi Sankyo, AstraZeneca, Sanofi, and Astellas . . .

“LY, SB and PB report full-time employment by Merck Sharp and Dohme, a subsidiary of Merck (Rahway, NJ, USA), and stock ownership in Merck. LSW reports consulting fees from Amgen; and has received honoraria for lectures, presentations, speakers bureaus, or educational events from Novartis, Bristol Myers Squibb, Merck Sharpe Dohme, Roche, and Amgen.

“PY, YB, JLee, MGF, JLi, MAL, TC, SQ, SL, and HP declare no competing interests.”98

Explanation

Disclosure of authors’ conflicts of interest provides important context for readers of a trial report when ascertaining the overall methodological rigor of a trial (eg, relevance of the type of comparator intervention and eligibility criteria for patients) and risk of bias (eg, selective reporting of favourable results). Conflicts of interest of all trial manuscript authors should be reported, along with any procedures to reduce the risk of conflicts of interest influencing the trial’s design, conduct, analysis, or reporting.

Conflicts of interest can be defined as “a set of circumstances that creates a risk that professional judgement or actions regarding a primary interest will be unduly influenced by a secondary interest.”108 In the context of authors of a trial report, conflicts of interest imply a risk that investigators’ personal interests and allegiances, or ties with companies or organisations, have undue influence on the design, conduct, analysis, or reporting of a trial. The concept implies a risk of influence and is not indicative of actual wrongdoing.

Conflicts of interest are most often associated with the drug and device industries. Types of financial ties include salary support or grants; ownership of stock or options; honorariums (eg, for advice, authorship, or public speaking); paid consultancy or service on advisory boards and medical education companies; and receipt of patents or patents pending. An analysis of 200 trials from 2015 reported that 57% of trials had at least one author declaring financial conflicts of interests.109

Conflicts of interest may also exist with support from or affiliation with government agencies, charities, and professional and civic organisations. Non-financial conflicts of interest include academic commitments; personal or professional relationships; and political, religious, or other affiliations with special interests or advocacy positions. An analysis of 200 trials found that 4% of trials had at least one author declaring non-financial conflicts of interest.109 There is ongoing discussion on the association between a problematic non-financial conflict of interest and a reasonable point of view.110

A cross sectional study of 190 randomised trials, published in core clinical journals, found that trials with authors’ conflicts of interest had more positive results than trials without. The presence of a financial tie was associated with a positive study outcome (odds ratio 3.23; 95% CI 1.7 to 6.1). This association was also present after adjustment for the stud