Measures to improve reporting
The reason that so many trials are never published is composite. Some initiated trials, not least within surgery, are never completed, often because of recruitment problems (25). Other financial and logistic restrictions may make the road to publication more difficult. These are obstacles that academic and commercial research institutions with more resources behind them are better equipped to manage (5, 23).
A vision of reducing failure to publish to zero is not realistic. However, reporting to trial registries assures access to results irrespective of acceptance from peer-reviewed journals. These accordingly represent a low-threshold channel for making publicly available the results of studies that do not make the grade for publication. Although registry data may be of variable quality, they are often more complete than the data reported when the study is published, with respect both to efficacy and to adverse events (26).
Registry data therefore function as both a supplement and a corrective to selective reporting. Reporting requirements have been made more stringent in recent years, largely as a consequence of pressure from patient organisations and research communities. With effect from 2005, the International Committee of Medical Journal Editors (ICMJE) made a registry-indexed study protocol prior to the start of the study a requirement for publication. Although the majority of journals, including the Journal of the Norwegian Medical Association, have complied with this requirement, compliance is still poor, even in journals with a high impact factor (5).
With the support of health authorities, ClinicalTrials.gov and EUdraCT have cleared the way for sanctions against researchers and institutions that do not fulfil the transparency requirements. In January 2020 the European Court of Justice decided, despite protests from the pharmaceutical industry, to give researchers and health authorities in the EU access to the European Medicines Agency-owned Clinical Study Reports (CSR), which provide detailed information about the design, analysis and findings of clinical trials (27). In Denmark, prompted by the Medicines Agency, it has been made statutory to penalise trial sponsors who fail to report their results to EUdraCT (28). A federal court in the US recently required all trial sponsors to publish the results of completed trials registered in ClinicalTrials.gov up to 2017, with daily fines for lack of reporting (29).
The AllTrials campaign is working to have previously performed, ongoing and future trials made reportable. In this international initiative, universities, ethical committees and medical institutions are urged to work to ensure that their members comply with the requirements of transparency. Central Norwegian research institutions are also supporting the campaign. In 2018, AllTrials launched a tracking instrument to flag sponsors who fail to publish results, both from trials already completed and from future trials (30).
This has proved effective, primarily at academic institutions. For example, twice as many results were recently reported to EUdraCT by German universities in the course of six months as in the preceding six years (31).
It is pointed out in guidelines from the Norwegian National Research Ethics Committees that research results shall as a general rule be made available, and that researchers have an independent responsibility to ensure that their research can benefit research subjects, relevant groups and society in general (32). At present, however, there are no authorities that ensure that results actually are made publicly available, and failure to do so has no practical consequences either.
The research ethics committees should not restrict themselves to approving protocols, but should also assume responsibility for ensuring that the results are made available. For example, all studies that are approved by a regional ethics committee could be sent to a central archive that sets up automatic alerts about deadline overruns to inform the researchers responsible, the study sponsors and the health authorities.