This analysis provides a preliminary overview of clinical registration trials in the pediatric field over the past 12 years, and the results of this analysis provide a basis for understanding of the treatment and prevention of childhood diseases in the United States. From this report, there are a few observations that deserve our attention.
First, the clinical registration trials that we're looking at are trials involving children. Compared to characteristics of clinical registration trials that include the whole population [10], clinical registration trials for children are typically small-scale trials that mainly focus on drug interventions. we describe clinical registry trials involving both children and adults, which are often excluded from pediatric reviews. There is data that shows that RCTS (Randomized Controlled Trials) that recruit children or recruit adults at the same time are more likely to complete trials than those that recruit adults only [15]. According to the data results of this study, compared to trials that include children and adults separately, the completion rate and behavioral intervention rate for trials only for children are higher. On the one hand, the data also suggest a higher completion rate for pediatric clinical registration trials, which may result in less waste of human and financial resources [16].
Second, the data also suggest that in addition to drug intervention trials, clinical trials on behavioral intervention in children are also developing and gradually playing an important role in pediatric clinical intervention research. At the same time, we observed an upward trend in the number of behavioral type registered trials among the interventional trial group in pediatric clinical registered trials. Further analysis of the data showed that although the proportion of drug intervention trials was different for all the other disease types except mental, drug intervention trials still comprised the largest proportion of trials, while behavioral interventional trials have also increased. The proportion of behavioral intervention trials in mental diseases was significantly higher than that proportion in other diseases and presented an increase year by year, but there was no significant change after subgroup classification in children. As of 2001, the World Health Organization reported that one in four people worldwide suffer from a mental health disorder during their lifetime, and 46.6 million people in the United States currently suffer from a mental health disorder [17]. The mental health research community has used ClinicalTrials.gov to help answer such questions about its use of ClinicalTrials.org.
Third, while previous studies have mainly focused on interventional trials, we have also included observational trials in the process of our analysis, and the number of observational clinical trials in children has also increased. Although the registration of randomized trials has been widely accepted, the registration of observational studies remains controversial. For example, studies have shown that registration of observational trials cannot effectively prevent false positive results in observational studies [12]. Some of these studies were registered after their results were published, and post-publication registration is unlikely to have the expected benefits of reducing publication bias or selective analysis and reporting of results, since researchers can selectively register research ideas after the data has been explored [13]. In addition, our study found that the reporting rate for results of registered observational trials was significantly lower than the reporting rate for results of interventional trials. This low reporting rate may partly reflect the longer trial cycle of many observational studies. Previous studies have shown that the full dissemination of research methods and results in a timely and impartial manner is essential for the full realization of research benefits [14]. Therefore, although the registration of observational studies is still controversial, under the background of the registration policy, observational registration trials, especially small and medium-sized prospective cohort trials, still show a significant increase.
Last but not least, we are concerned about the reporting of results for registered trials. Given that policy requires trials to report results, the quality of results reporting of existing pediatric registered trials is still poor and has significant room for improvement. The FDA and the final rule do not mandate that all trials report their results to the registry, which may be the reason that few trials report their results [18] (eTable). In addition, the final rule expanded the proportion of trials that must report results to the registry on January 18, 2017, and therefore, after this date, the reporting of results of registered trials may increase. Clinical trials registered before policy implementation were less likely to report results, and the results of our descriptive analysis were consistent with previous analyses using the ClinicalTrials.gov registry [19]. Funding agencies and types of interventions were associated with results reporting. Dissemination of research results is critical to clinical practice and selective reporting can lead to distortion of knowledge in the field. We conducted a preliminary descriptive analysis of the possible factors influencing the reporting of the results for pediatric registered trials and found that, on the whole, the rate of results reporting of the trials led by industry, the major sponsor, were better. Our analysis also confirms what previous studies have shown: industry sponsors tend to be well-staffed and have a centralized process to support the submission of results, while non-industry sponsors tend to rely on a single investigator with very little centralized support [20]. How to improve the quality of results reporting may be an issue to consider in the future. In this optimization process, we also need to consider the entire life cycle of clinical trials.
Several limitations of our study should be noted. First, there are trials that are not registered with ClinicalTrials.gov or any other publicly accessible registry, and these trials are not included in our evaluation. Although ClinicalTrials.gov is one of the largest international trial registries containing 70% of trials registered under the World Health Organization's international clinical trials registry, it is not an exhaustive list of all clinical trials in the United States [20]. Second, not all trials, for example phase I trials or trials looking at non-drug interventions, meet FDA or final rule requirements [21]. There may be other incentives and norms that bias the registration of trials with certain characteristics, and trends identified by registries reflect at least partial changes in trial reporting rather than changes in how trials are conducted or designed. Thirdly, our study focuses on clinical registration trials involving children, and rigorous analysis of pediatric clinical registration trials may consider dividing child-only registration trials into a separate analysis for comparison. In 2012, a study by Pasquali et al. found that an assessment of the clinical trial site data set could describe the overall mix of clinical trials related to children in the United States, which was previously impossible [22]. Subsequently, descriptive analyses of clinical registration trial characteristics of different pediatric diseases emerged [23] [24] [25]. Fourth, we have only made a preliminary description of observational clinical registered trials. Fifth, our study is only a preliminary description of the current status of clinical trials for children, and further research is needed to analyze the current status and improve the recommendations for registration information so as to provide the public with more transparent and high-quality clinical trial data information for children.