Eighty-five of the 103 analyzed RCTs (83%) were registered and 80% (68/85) of the registered trials specified the registration identifier, for example the NCT number, in the study report. In addition, 65% (44/68) of RCTs specifying the registration number also mentioned trial registration explicitly in a full sentence in the abstract and/or main text. Though the ICMJE trial registration policy requires trial registration before the enrollment of the first patient, only 18% of the registered trials had been registered prospectively. The majority were registered retrospectively (53%) or within the same month as the study start date (25%). This implies that with regard to the vast majority of registered trials, it cannot be excluded that initial details of study design, objective, eligibility criteria, or primary and secondary outcomes were changed after study start. For this specific reason, retrospective registration is only suboptimal. On the other hand, retrospective registration is helpful for the identification of trials, especially those still ongoing or not yet published.
The results of only 7 (12%) of the 59 RCTs registered on ClinicalTrials.gov had been submitted to the ClinicalTrials.gov results database. As mentioned before, we did not assess whether these 59 RCTs were ACTs. Thus, it remains unclear whether the legal requirements to submit aggregate summary data to ClinicalTrials.gov really pertain to the included RCTs. Nonetheless, investigators of all trials registered in ClinicalTrials.gov can voluntarily submit summary data to the results database. Though the legal requirement to report results applies only to certain interventional trials, sponsors and investigators should be encouraged to use the results database for timely dissemination of their research findings publicly .
For 28 (47%) of the trials registered on ClinicalTrials.gov there was at least a link provided to publications, which are automatically mapped to these studies by the ClinicalTrials.gov identifier (NCT number). In 29 (48%) cases there was no reporting of results or link to publications available at all.
Nguyen et al. recently published data on the public availability of trial results assessing cancer drugs in the USA. They analyzed 646 trials (including 209 RCTs) regarding results posting at ClinicalTrials.gov and/or publication of results in journals. One year after the completion of the trials, the results of only 9% of all trials (12% of the RCTs) were available at ClinicalTrials.gov . These data are similar to our own results. Moreover, Nguyen et al. reports that, despite the FDAAA, results of almost half of the trials assessing cancer drugs were not publicly available (neither at ClinicalTrials.gov nor in journals) three years after completion of the trials .
Jones et al. recently conducted a cross-sectional analysis of 585 trials with at least 500 participants, which were prospectively registered with ClinicalTrials.gov to estimate the frequency with which results of large RCTs registered with ClinicalTrials.gov are not publicly available. Almost one third (n = 171) of the included 585 RCTs remained unpublished. Of the 171 unpublished RCTs, almost 80% (n = 133) had no results available in the ClinicalTrials.gov results database .
Comparing our findings regarding trial registration to those from disciplines not related to surgery, it seems that the awareness of the need for trial registration has grown in the surgical research community. The proportion of registered RCTs in this study by far exceeds the reported numbers from other recent trials. Milette et al. investigated the transparency of outcome reporting and trial registration of RCTs published in top psychosomatic and behavioral health journals between January 2008 and September 2009 . Of the 63 articles reviewed, only 13 (20.6%) had been registered. A similar proportion of registered trials were reported by McGee et al. who conducted a cohort study of all RCTs in kidney transplantation published between October 2005 and December 2010 and determined trial registration and declaration of registration by authors . Of the 307 included trials, only 74 (24%) had been registered; 44 (59%) of the registered trials declared trial registration details at least within one study report. Moreover, the authors investigated factors associated with trial registration. Trial registration was more likely if the trial was published more than once, in later years, or if it was reported in journals following the ICMJE guidelines. Furthermore, trials conducted in the USA were significantly more likely to be registered than European trials. Trial registration was also less likely for trials not declaring their funding source. Regarding the factors associated with declaration of registration details, McGee et al. found that registered trials were more likely to declare registration details in related reports if they were published in a journal complying with the ICMJE guidelines or in later years (2007 to 2010). Compared to European trials, trials conducted globally were less likely to declare registration details. Interestingly, USA trials were no more or even less likely to declare registration details than trials conducted in Europe.
Califf et al. recently examined the characteristics of clinical trials (in three different medical specialties: cardiovascular, mental health, oncology) registered in ClinicalTrials.gov. Their analysis showed that the proportion of prospectively registered trials increased over time (from 33% in October 2004 to September 2007 to 48% in October 2007 to September 2010) . This is concordant with our results (Table 2).
Reveiz et al. investigated another important aspect of trial registration: its potential influence on reporting quality . The authors conducted a cross-sectional study of 148 RCTs from the highest ranked journals (JCR 2006) and analyzed this sample with regard to adherence to key methodological items of the Consolidated Standards of Reporting Trials (CONSORT) statement and several other secondary outcomes, inter alia trial registration. Of these, 36% of the included RCTs reported trial registration. Reporting quality was significantly better if trial registration was declared in the trial report.
Several studies have examined whether journals publishing original articles in specialties such as urology and pediatrics endorse recommendations aimed at the improvement of publication practice. Meerpohl et al. analyzed the online author instructions of 69 journals indexed in the subject category 'pediatrics’ of JCR 2007 with regard to endorsement of the Uniform Requirements for Manuscripts (URM) of the ICMJE, of five major reporting guidelines, disclosure of conflicts, and trial registration . Only 16 (23%) of the included 69 journals either recommended or required trial registration. This means that more than three quarters of pediatric journals did not require/recommend trial registration in August 2008. One year later, Meerpohl et al. analyzed 41 pediatric open access journals with regard to good publication practice . The authors came to the conclusion that pediatric open access journals mention certain recommendations and guidelines, for example the URM, more frequently than conventional journals, but that the endorsement was still only moderate. Trial registration, for example, was only recommended/required by approximately a third (32%) of the included journals.
Kunath et al. conducted a cross-sectional study of RCTs published in 2009 in urology-related journals indexed in JCR 2009 . Of the 106 included RCTs, 63 (59.4%) were registered. The proportion of reports of registered trials was significantly higher in journals requiring trial registration as a requirement for publication than in journals not mentioning trial registration in their author instructions (71.4% versus 51.6%).
It is, however, not the journal editors’ main responsibility to ensure good publication practice, especially complete trial registration. Primarily, trialists are in charge of registering their trials. Reveiz et al. surveyed the corresponding authors of a random sample of 500 clinical trials published between May 2005 and May 2006 . Of the 275 trialists who completed the questionnaire, 64% supported the registration of all 20 items of the WHO minimum data set that should be recorded for clinical trial registration, while 6% did not support any of them. Only 21% of the respondents had registered all of their trials since 2005. However, 47% declared the intention to provide all 20 items of the WHO data set to a publicly accessible register for future clinical trials. Comparing the respondents who received mixed or only industry funding with those receiving only non-industry funding, the latter were significantly more likely to intend to provide all 20 WHO data set items for future trials.
Looking into the future of trial registration and reporting, their successful implementation as integral parts of clinical research highly depends on the continuous efforts and initiatives taken by trialists, journal editors, ethic boards, and funders.
There are some limitations to this study. We studied a cohort of RCTs published between June 2012 and December 2012. Due to the moderate sample size, the generalizability of the results might be limited. RCTs could have been missed, because the PubMed search was performed only 6 weeks after the evaluated time period. Some citations might not yet have been fully indexed with MeSH terms in MEDLINE. However, the Cochrane RCT filter does not only use MeSH terms to identify RCTs, but also text words within the database’s title/abstract field, which have been validated for identifying RCTs. Thus, the chance to have missed publications reporting an RCT not yet indexed with MeSH terms is relatively low. It is also possible that we erroneously declared a trial as unregistered if it was registered within a register not included in the ICTRP search platform and the registration was not mentioned in the publication. In addition, since the analyzed cohort of RCTs was taken from the ten journals with the highest impact factors (according to JCR 2011) which explicitly required trial registration in their instructions to authors, our results might overestimate the compliancy with trial registration and therefore might not be transferable to the entirety of surgery-related journals. This likely implies a limited external validity of our results.