Childhood obesity is one of the most severe challenges of public health in the twenty-first century, affecting ~41 million children under the age of 5 years (1, 2). The prevalence of overweight and obesity in children started to rise at the end of the 1980's and continues to rise in some countries (3). Childhood obesity increases the risk of having obesity in adulthood and health problems such as diabetes and cardiovascular diseases (4–10). Furthermore, growing prevalence of obesity can place a substantial cost burden to the health-care system. The overall economic cost of obesity worldwide was estimated at $2.0 trillion US dollars in 2012, with an estimated 5.1 billion a year spent on obesity-related diseases by the National Health Service (NHS) (11–13).

Clinical trials rely on the participation of volunteers, involving massive investment of human, material and financial resources (14). Meanwhile, trial researchers have an obligation to participants not only to minimize potential harm, but also to conduct trials scrupulously, and to publicly report their findings in time. Unpublished trial results could violate ethical obligations to participants and compromise existing medical evidence (15). Policies have been enacted to improve the transparency and accountability of trials in recent years. The International Committee of Medical Journal Editors has required registration of interventional trials in a public trials registry [such as ClinicalTrials.gov, a registry of clinical trials implemented in 2000 by the National Library of Medicine-National Institutes of Health (NIH)] as a condition for publication since July 1, 2005 (16). Furthermore, the Food and Drug Administration Amendments Act of 2007 (FDAAA) required that summary results of certain trials should be submitted within 1 year of final collection of data for the primary outcome, including whether the trials concluded according to the predetermined protocol or were discontinued (17). However, despite these increased ethical and legislative requirements, the discontinuation and unreported results of clinical trials remain common.

Although a limited number of studies have cross-sectional descriptions of pediatric trials (18–20), they have not further identified the factors of unreported results and premature termination in pediatric obesity research. In addition, analyses of trial discontinuation and result reporting have primarily focused on adult populations, and the prevalence of these outcomes for pediatric randomized controlled trials (RCTs) remains less well defined (21). We suppose that pediatric clinical trials are easier to stop early because of ethical and recruitment issues. Therefore, we aimed to investigate the factors of results reporting and premature termination of current childhood obesity trials registered in ClinicalTrials.gov and make corresponding recommendations.

Our study showed that among clinicalTrials.gov registered childhood obesity-related intervention trials, trial unreported results were 88.5%, and 4.3% of trials were prematurely terminated. The factors that reduced the risk of unreported outcomes were US-registered clinical studies and drug intervention trials. Factors associated with reduced risk of early termination are NIH or other federal agency funding and large trials. The study also suggests that behavioral interventions play an important role in pediatric obesity clinical trials. Fewer than half of the trials provided information about their trial phase, and fewer than half used blinding.

Like obesity adults, obesity children have the right to receive the highest attainable standard of health care, but there is a lack of evidence regarding the safety and efficacy of treatments for overweight and obesity in children (9). For drug interventions, scientific data from only a limited number of short-term clinical trials are available, therefore, clinical trials with children are of the utmost importance (8–10). Ethical issues and policy requirements make it more difficult to recruit children, leading to the possible early termination of many clinical trials. Previous studies have found that pediatric clinical trials are terminated frequently (19, 20, 26). Thousands of children have participated in these trials, which means considerable inefficiency and a waste of financial resources (18). However, the early termination rate of pediatric obesity trials (4.3%) was lower than that of neonatal clinical trials, pediatric cardiovascular trials, pediatric psychological trials, etc. (21, 27, 28). This was an unexpected result, which may be due to a large number of obese children and the fact that most of the trial interventions are behavioral interventions that are easily accepted by patients, so clinical trials can better recruit patients. Furthermore, our analysis showed that industry-funded trials were more likely to stop early than government-funded or others, which may be because industry-funded clinical trials are more subject to financial and commercial influence than government-funded trials (21). Stefan et al. conducted a retrospective cohort study of pediatric randomized controlled trials in Switzerland, Germany, and Canada and found that the larger sample sizes (Enrollment>100) were less likely to stop early (29), which is consistent with our results. Perhaps because these trials were better organized from the start, the trial design systems built around experienced researchers may be better able to cope with recruitment challenges. In univariate analyses, drug trials were more likely to stop early, which may be due to the high ethical and regulatory requirements of drug trials for children, which may affect enrollment. Prevention trials are also risk factors for early termination, which is consistent with Turner et al. (30). The possible explanation is that prevention trials. One possible explanation is that prevention trials have a comparatively higher time cost to achieve clinical benefits than treatment trials (31). In addition, our analysis found that 11 of 57 (19.3%) intervention trials on childhood obesity did not report the reason for their early termination on ClinicalTrials.gov. The results reporting is especially important if the study is discontinued because of the detection of harm caused by the intervention. Trials involving children should always post reasons for early discontinuation on ClinicalTrials.gov (26). Studies have shown that failure to recruit sufficient numbers of participants and funding problems are the most common reasons for premature termination of clinical trials (32). Our study confirms these findings in childhood obesity trials.

The ethics and regulations of research involving children are widely discussed in the current literature (33–37); however, the reporting of results is ignored. Underreporting remains an important issue in the field of childhood obesity. Therefore, this issue should raise concerns about the overall quality of pediatric clinical trials. Despite the policy of the International Council of Medical Journal Editors (ICMJE), which recommends that all investigators report results (38), we found that the quality of results reported in the childhood obesity registry is still poor. These conclusions are consistent with Yang et al. (18). In clinical studies of mental health and neurology (30, 39). the reporting rates of clinical trial results were 42.3% and 32.2% respectively, both higher than our study results (11.5%). Food and Drugs Administration Amendments Act (FDAAA) and the Final Rule do not mandate that all studies report their results to the registry, which may account for the different reporting rates of study results (15). Similarly, USA-trials and drug trials were more likely to report results on ClinicalTrials.gov, which is related to the policy requiring reporting of the Food and Drugs Administration Amendments Act (FDAAA) and the Final Rule (15). In univariate analyses, industry-sponsored trials are more likely to report results, possibly because industry-sponsored trials more often have favorable results and conclusions (40).

In summary, the problem of unreported results in clinical trials of childhood obesity is serious, and the factors that reduced the risk of unreported outcomes were US-registered clinical studies and drug intervention trials. Furthermore, the factors associated with a reduced risk of early termination are NIH or other federal agency funding and large trials. Our findings may contribute to a better understanding of the etiologies of premature termination and unreported results, thus setting the stage for targeted approaches to improve clinical research.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

LD and JH conceptualized and designed the study and reviewed and revised the manuscript. XW and YL collected and screened the data, carried out the initial analyses, drafted the initial manuscript, and reviewed and revised the manuscript. LY coordinated and supervised data collection and critically reviewed the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

This study was supported by the Key Program of Sichuan Provincial Science and Technology Department, China (No. 2019YFS0194) and the National Natural Science Foundation of China (No. 81873197, No. 72074161, and No.81403276).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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