Our results indicate that the main reason for discontinuation is patient/participant recruitment, reflected in inflated target sample size estimates and unrealistic recruitment goals. Recruitment issues can delay trials and are directly related to funding. As previously identified, failure to meet recruitment targets due to overoptimistic or inaccurate estimates of recruitment [14] which could be anticipated by conducting a pilot or feasibility study [15]. Delays, due to changes in the protocol, or recruitment issues, also have an impact on researcher retention, often reported to the ISRCTN as another reason to discontinue a trial.
The existing information contained in the ISRCTN database is not detailed or specific enough to allow for the identification of reasons why a trial was discontinued. The information that was available was also difficult to interpret, similar to previous findings, as most data fields did not consist of standardised categories [8]. To allow more in-depth understanding of what factors are associated with completed trials, more information is necessary on actual recruitment, participation of a clinical trial unit or an (independent) trial steering committee. Such information can also help funders to assess if a study is delivering on its objectives.
The International Standards for Clinical Trial Registries (2012[16] and 2018[17]) designed a minimum dataset (Trial Registration Data Set) covering 20 items [18]. Our findings provide evidence of the underlying problem of lack of detail, suboptimal recording, dated information and incomplete reporting of trials which hampers sharing and learning.
Today, funding agencies as well as publishers, request the trial registration number. Information required to register a trial is rarely linked to the primary report once the research is complete resulting in the drop in the relevance of registries after the trial obtains a registration number. However, funding agencies require proof of ethical approval before funding is transferred while journal editors require checklists for the CONSORT [19]., QUOROM [20], STROBE [21] and STARD [22] statements. Consideration should be given to opportunities to bundle all this information as part of an integrated registration process necessary as part of the publication of the trial results.
An addition to these requirements could include the submission of a protocol as part of registration [23]. However, “research is not a car factory” [10] and it is important to acknowledge that adjustments to the design process are expected. Including a protocol should therefore not be a static document upload but allow to make adjustments as part of a well-documented process. Part of this process is already required by journals and included as ‘deviations from the protocol’ in the manuscript.
There are several parties responsible in ensuring access to complete and meaningful information on RCTs conducted throughout the world; the registry, the registrant and other stakeholders such as journal editors, ethical committees and funding agencies [18]. Enforcing measures designed to improve the quality of registration are suggested for journal editors and legislators, but little is known on if or how this is done [16].
Based on our study and to boost learning from others and other trials, we suggest following improvements:
Registries should consider to:
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Provide a downloadable template at the moment of registration which is required when publishing the results of the trial, similar to evidence of ethical approval or statements
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Improve the standardisation of the information provided through the use of standardised categories
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Allow registries to be fully searchable using standardised reporting.
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Extend the information gathered with up to date ethical approval information, CONSORT [19]., QUOROM [20], STROBE [21] and STARD [22] statements, actual recruitment information and other trial procedures
Funding agencies should consider to:
Journal editors should consider to:
Our review of discontinued trials showed that not enough progress has been made to allow learning from other research. Five targeted groups (funders, regulators, journals, academic institutions and researchers) have been identified to play a part in increasing research value. We argue there is a sixth group: the trial registry should provide a common template with up-to-date information to be submitted as part of the publication of the trial results documenting each stage of the research process, from conception, through registration and publication.