Summary of findings
Our study provides empirical evidence about the publication tendencies of authorized clinical trials in Hungary, the impact of authorized clinical trials on the scientific reputation of the authorizing country, and the role of multiple registrations in increasing transparency.
A total of 97.3% of authorized and EU CTR -registered clinical trials were initiated by the industry. About 20% of clinical trials were published within one year after trial completion. Trials conducted only within Europe and registered only in the EU CTR register were published significantly later.
Universality is a fundamental principle of science (11); open access publications have therefore the largest impact on the scientific community. In this study, 70.93% of publications were found to be openly accessible to the public. However, we were not able to identify trial characteristics which might influence the access to scientific publications.
Publications with Hungarian co-authors occurred in 21.5% of cases only. Clinical trials with study sites within Europe and trials initiated by the academy resulted more often in scientific publications with Hungarian authors.
Trials registered not only in the EU Clinical Trials Register, but also in the clinicaltrials.gov database were more likely to be identified as full publications. The results of clinical trials available as full scientific papers but absent in registries were in low numbers. However, we found that almost one quarter of results of the investigated clinical trials were available in registries, but not as a full scientific publication.
Strength and limitations of this methodological research study
Our study analyzed a representative sample of trials authorized in Hungary, the results can therefore be generalized to the country. All trials were registered in study registries, thus basic study information was available for all the trials included in our study. All data extractors were trained and the main outcome data were double-checked and double-extracted.
Our study has limitations. The cohort was composed of trials that were authorized and included in the study registry EU Clinical Trials Register by the national authority. Due to the low number of investigator-initiated trials it is difficult to draw firm conclusions on their publication tendencies. Nevertheless, our results may indicate a publication trend also for investigator-initiated trials.
Another limitation is, that the information provided for researchers in the EU Clinical Trials Register on trials defined as completed (when it „has been completed in accordance with the full requirements of the protocol”) might be interpreted in different ways by researchers and may have impacted our results. We searched for scientific publications in 2020 and trials completed within one year before the search date were excluded.
Comparison with other studies
To our knowledge, this is the first study investigating how and to what extent research authorized and conducted in a given country becomes visible and affects the scientific performance of that country.
Authorship issues were already discussed is several papers, dealing mainly with gender distribution of authorship (12, 13); association between sponsorship and authorship (14, 15); under-representation of researchers from specific regions in papers published from research done in these regions (16, 17); and difficulties and possibilities in determining authorship in multicenter clinical trials (18, 19). These studies were mainly based on publication data sets. The approach to prospectively follow trials authorized in a given country until publication and investigate authorship in such a cohort of studies is novel.
There was one large cohort study investigating compliance with requirement to report results on the EU Clinical Trials Register up to December 2016 (8). This study found that trials with a commercial sponsor tend to be substantially more likely to post results on the EU CTR than those with a non-commercial sponsor (68.1% v 11.0%)(8). This is in line with the results of the present study: a significantly higher posting of results in the EU CTR for industry-initiated trials were found (73.1%) than for investigator-initiated trials (11.1%). Besides the need for standardized procedures (20), periodic quality control assessments during trial implementation (21), improved reporting about funding (22), improvement of reporting (23), mandatory trial registration and trial result posting are additional requirements which still are not optimal in case of investigator-initiated trials.
Implications of findings for practice, policy and future research
All interventional clinical trials on medicinal products authorized in the European Union and, without any distinction by type of sponsor, should be registered in the EU Clinical Trials Register. To get a valid picture about research activity on a country level, the EU Clinical Trial Register for trials conducted in Europe should be the first step to register a trial. Trial registration in the clinicaltrials.gov register can further increase the visibility of registered European trials.
The present research shows that a surprisingly low number of clinical trials initiated by the academy are registered in the EU Clinical Trial Register in Hungary. Academic clinical trials have an important place on the map of clinical research. These studies focus on specific questions that arise during clinical care and are extremely important in everyday medical practice; these include but are not limited to facilitating the optimization of a therapy, or the discovery of potential new clinical areas where a therapeutic intervention can be used. Increased transparency and use of results of academic clinical trials is essential for evidence-based medical decision-making and optimal patient management.
Posting trial results in study registries might be the first step to make study results become openly available for the public; however, study results should be published also as a scientific publication as soon as possible after trial completion. Systematic reviewers and guideline developers are advised to search clinical trial registers in addition to electronic databases to identify study results, which have not been published as full text publications at the time of the search.
The present study also showed that the participation of Hungarian researchers in industry-initiated studies on medicinal products has only partial measurable scientific benefits, as Hungarian researchers appear as authors in only a fraction of scientific publication derived from these trials. Several publications not even contain the list of countries of trial participants. In line with the Lancet journals, which strongly support the inclusion of authors from local countries on papers reporting studies from those countries, we also would like to “encourage authors to include researchers who originally collected the data, where possible, and to share expertise in analysis and other skills, so that the research capacity of the country from which the data were obtained is strengthened” (24); i.e. to enable local researchers to fulfil the criteria for authorship developed by the International Committee for Medical Journal Editors.
The scientific performance of universities and countries is evaluated and ranked – despite valuable initiatives for change – based on research productivity (i.e. the number of scientific publications), research impact and research excellence (i.e. the number of scientific papers in high impact journals). Considering that slightly over a fifth of authorized Hungarian trials result in scientific publications with a Hungarian co-authorship, we can conclude that the authorized, mainly industry-initiated clinical trials on medicinal products currently result in limited measurable scientific benefits to the participating researchers and their countries.