Worldwide Trends in Registering Real-World Studies at ClinicalTrials.gov: A Cross-Sectional Analysis.

Objective: The purpose of this study was to characterize real-world studies (RWSs) registered at ClinicalTrials.gov to help investigators better conduct relevant research in clinical practice. Methods: A retrospective analysis of 944 studies was performed on February 28, 2023. Results: A total of 944 studies were included. The included studies involved a total of 48 countries. China was the leading country in terms of the total number of registered studies (37.9%, 358), followed by the United States (19.7%, 186). Regarding intervention type, 42.4% (400) of the studies involved drugs, and only 9.1% (86) of the studies involved devices. Only 8.5% (80) of the studies mentioned both the detailed study design type and data source in the "Brief Summary". A total of 49.4% (466) of studies had a sample size of 500 participants and above. Overall, 63% (595) of the studies were single-center studies. A total of 213 conditions were covered in the included studies. One-third of the studies (32.7%, 309) involved neoplasms (or tumors). China and the United States were very different regarding the study of different conditions. Conclusion: Although the pandemic has provided new opportunities for RWSs, the rigor of scientific research still needs to be emphasized. Special attention needs to be given to the correct and comprehensive description of the study design in the Brief Summary of registered studies, thereby promoting communication and understanding. In addition, deficiencies in ClinicalTrials.gov registration data remain prominent.

Effect of human probiotics on memory, psychological and biological measures in elderly: A study protocol of bi-center, double-blind, randomized, placebo-controlled clinical trial (CleverAge Biota).

Background: Gut microbiota may influence brain functions. Therefore, we prepared a study protocol for a double-blind, crossover, randomized clinical trial to determine the complex effects of human probiotics on memory, psychological, and biological measures in the elderly. Methods: We selected eligible participants using an effective electronic questionnaire containing the inclusion and exclusion criteria and a brief electronic cognitive test. One-third of the respondents with the worst cognitive scores on the electronic test are randomized to group A, starting with a 3-month probiotic intervention, and to group B, starting with a placebo. In a crossover design, both groups change their intervention/placebo status after 3 months for the next 3 months. Participants refusing longer personal assessments due to the COVID-19 pandemic were randomly allocated to one of two subgroups assessed online. Participants in both groups are matched in age, education, gender, and cognitive scores on electronic testing at baseline. At three time points, participants are assessed using a neuropsychological battery, self-report measures of mood, a physical fitness test, blood, urine, and stool samples, and actigraphy. A subset of participants also provided their biological samples and underwent the neuropsychological battery in an extended testing phase 3 months after study termination to find out the long-term effect of the intervention. Discussion: This is the first trial to address the comprehensive effects of human probiotics on memory and many other measures in the elderly. We assume that the probiotic group will have better outcomes than the placebo group after the first and second trimesters. We expect that the probiotic effect will persist for the next 3 months. These study's findings will contribute to an interesting area of how to improve memory, psychological and biological and other factors naturally and will examine the importance of probiotics for overall health in the elderly. Clinical trial registration: [clinicaltrials.gov], identifier [NCT05051501].

NISO plus 2022 Miles Conrad lecture: The role of a library in a world of unstructured data

Throughout its nearly two hundred year existence, the National Library of Medicine (NLM) (https://www.nlm.nih.gov/) has advanced biomedicine and public health by acquiring, organizing, preserving, and disseminating knowledge essential to health and medicine. NLM has devised many innovations including standard terminologies and messaging formats such as the Journal Article Tag Suite (https://dtd.nlm.nih.gov/) to organize and manage biomedical literature. While scientific communication largely relied on books and journals over the last two hundred years, digital data are quickly forming the substrate of scientific communications. Data come in forms with much less structure than that afforded by publications, and these can vary from observations made during carefully controlled clinical trials to streams of genomic sequences to the counts of footfalls captured by personal devices. Coincidently, an increasingly diverse set of users - from clinicians to laypeople to public health to big pharma to scientists - bring unique perspectives as they draw meaning from new sets of scientific output. How does a modern library meet its mission to acquire, organize, preserve, and disseminate the many outputs of contemporary science? What role do standards play? How does NLM help this diverse set of stakeholders derive meaning from its resources? © 2022 - The authors. Published by IOS Press.

Characteristics of Depression Clinical Trials Registered on ClinicalTrials.gov.

Background: Mental disorders are among the leading causes of the global health-related burden, and depression is one of the most disabling mental disorders. The emergence of the COVID-19 pandemic has created an environment where many determinants of mental health are exacerbated. Many studies have been registered and conducted over the past 16 years, but how to choose the proper design for depression clinical trials remains the main concern. This study aimed to characterize the current status of global depression clinical trials registered on ClinicalTrials.gov. Methods: We examined all the trials registered on ClinicalTrials.gov from 2007 to 2021. Results: Overall, 7623 depression clinical trials were identified for analysis. Of those trials, 6402 (83.98%) were intervention trials and 1212 (15.90%) were observational trials. The majority of intervention types were behavioral (35.2%) and drug (28.55%), with very few procedures, dietary supplements, and diagnostic test studies. In addition, 55.53% of trials enrolled <100 participants. The proportions of trials registered in North America were higher than on other continents. Furthermore, the trials that involved only females (12.6%) were more than only males (0.87%) from 2019 to 2021. Conclusion: Depression clinical trials registered on ClinicalTrials.gov were dominated by small sample size trials, and there is a lack of trials related to COVID-19. The choice of study design is crucial, and properly designed trials can help improve study efficiency and reduce the likelihood of study failure. Given the increased number of RCT trials, the trial quality is gradually improving over the years. In addition, depression trials concentrating on children and older adults need more scientific attention. Further studies related to COVID-19 are needed, given the great damage that causes to people's physical and mental health.

Nanoparticles in Clinical Trials: Analysis of Clinical Trials, FDA Approvals and Use for COVID-19 Vaccines.

Nanoparticles are heterologous small composites that are usually between 1 and 100 nanometers in size. They are applied in many areas of medicine with one of them being drug delivery. Nanoparticles have a number of advantages as drug carriers which include reduced toxic effects, increased bioavailability, and their ability to be modified for specific tissues or cells. Due to the exciting development of nanotechnology concomitant with advances in biotechnology and medicine, the number of clinical trials devoted to nanoparticles for drug delivery is growing rapidly. Some nanoparticles, lipid-based types, in particular, played a crucial role in the developing and manufacturing of the two COVID-19 vaccines-Pfizer and Moderna-that are now being widely used. In this analysis, we provide a quantitative survey of clinical trials using nanoparticles during the period from 2002 to 2021 as well as the recent FDA-approved drugs (since 2016). A total of 486 clinical trials were identified using the clinicaltrials.gov database. The prevailing types of nanoparticles were liposomes (44%) and protein-based formulations (26%) during this period. The most commonly investigated content of the nanoparticles were paclitaxel (23%), metals (11%), doxorubicin (9%), bupivacaine and various vaccines (both were 8%). Among the FDA-approved nanoparticle drugs, polymeric (29%), liposomal (22%) and lipid-based (21%) drugs were the most common. In this analysis, we also discuss the differential development of the diverse groups of nanoparticles and their content, as well as the underlying factors behind the trends.

Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes.

There is a need for safe and effective platform vaccines to protect against coronavirus disease 2019 (COVID-19) and other infectious diseases. In this randomized, double-blinded, placebo-controlled phase 2/3 trial, we evaluate the safety and efficacy of a multi-dose Bacillus Calmette-Guérin (BCG) vaccine for the prevention of COVID-19 and other infectious disease in a COVID-19-unvaccinated, at-risk-community-based cohort. The at-risk population is made of up of adults with type 1 diabetes. We enrolled 144 subjects and randomized 96 to BCG and 48 to placebo. There were no dropouts over the 15-month trial. A cumulative incidence of 12.5% of placebo-treated and 1% of BCG-treated participants meets criteria for confirmed COVID-19, yielding an efficacy of 92%. The BCG group also displayed fewer infectious disease symptoms and lesser severity and fewer infectious disease events per patient, including COVID-19. There were no BCG-related systemic adverse events. BCG's broad-based infection protection suggests that it may provide platform protection against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and other pathogens.

Results Reporting and Early Termination of Childhood Obesity Trials Registered on ClinicalTrials.gov.

Objective: Childhood obesity is one of the most severe challenges of public health in the twenty-first century and may increase the risk of various physical and psychological diseases in adulthood. The prevalence and predictors of unreported results and premature termination in pediatric obesity research are not clear. We aimed to characterize childhood obesity trials registered on ClinicalTrials.gov and identify features associated with early termination and lack of results reporting. Methods: Records were downloaded and screened for all childhood obesity trials from the inception of ClinicalTrials.gov to July 29, 2021. We performed descriptive analyses of characteristics, Cox regression for early termination, and logistic regression for lack of results reporting. Results: We identified 1,312 trials registered at ClinicalTrials.gov. Among clinicalTrials.gov registered childhood obesity-related intervention trials, trial unreported results were 88.5 and 4.3% of trials were prematurely terminated. Additionally, the factors that reduced the risk of unreported outcomes were US-registered clinical studies and drug intervention trials. Factors associated with a reduced risk of early termination are National Institutes of Health (NIH) or other federal agency funding and large trials. Conclusion: The problem of unreported results in clinical trials of childhood obesity is serious. Therefore, timely bulletin of the results and reasons for termination remain urgent aims for childhood obesity trials.

COVID-19 interventional trials: Analysis of data sharing intentions during a time of pandemic.

BACKGROUND: This survey of COVID-19 interventional studies encompasses, and expands upon, a previous publication [1] examining individual participant level data (IPD) sharing intentions for COVID-related trials and publications prior to June 30, 2020. METHODS: Replicating our inclusion criteria from the original survey, we evaluated a larger dataset of 2759 trials and 281 publications in this follow-up survey for willingness to share IPD and studied if sharing sentiment has evolved since the beginning of the pandemic. RESULTS: We found that 18 months into the pandemic, data sharing intentions remained static at 15% for trials registered through ClinicalTrials.gov (ClinicalTrials.gov is a digital registry of information about publicly and privately funded clinical studies in which human volunteers participate in interventional or observational scientific research) prior to September 19, 2021 compared to our initial survey. However, a comparison of declared intentions to share IPD at the time of publication revealed a noticeable shift: affirmative intentions grew from 21.4% (6/28) in our original publications survey to 57% (160/281) in this survey. Within the subset of studies published within journals affiliated with the International Committee of Medical Journal Editors (ICMJE), positive sharing intentions are even higher (65%). CONCLUSIONS: Although intent to share data at the time of registration has not changed from our prior study in June 2020, there is growing commitment to sharing data reflected in the increasing number of affirmative declarations at the time of publication. Actual sharing of data will accelerate new insights into COVID-19 through secondary re-use of data.

Analysis of M-SEIR and LSTM Models for the Prediction of COVID-19 Using RMSLE The impact of Covid-19 on the initiation of clinical trials in Europe and the United States

Summary During an epidemic period, it is important to perform the time forecasting analysis to track the growth of pandemic and plan accordingly to overcome the situation. The paper aims at performing the time forecasting of coronavirus disease 2019 (COVID-19) with respect to confirmed, recovered, and death cases of Karnataka, India. The modified mathematical epidemiological model used here are Susceptible - Exposed - Infectious - Recovered (SEIR) and recurrent neural network such as long short-term memory (LSTM) for analysis and comparison of the simulated output. To train, test, and optimize the model, the official data from Health and Family Welfare Department - Government of Karnataka is used. The evaluation of the model is conducted based on root mean square logarithmic error (RMSLE). The Covid-19 pandemic has a major impact not only on public health and daily living, but also on clinical trials worldwide. To investigate the potential impact of the Covid-19 pandemic on the initiation of clinical trials, we have descriptively analysed the longitudinal change in phase II and III interventional clinical trials initiated in Europe and in the United States. Based on the public clinical trial register EU Clinical Trials Register and clinicaltrials.gov, we conducted (a) a yearly comparison of the number of initiated trials from 2010 to 2020 and (b) a monthly comparison from January 2020 to February 2021 of the number of initiated trials. The analyses indicate that the Covid-19 pandemic affected both the initiation of clinical trials overall and the initiation of non-Covid-19 trials. An increase in the overall numbers of clinical trials could be observed both in Europe and the US in 2020 as compared to 2019. However, the number of non-Covid-19 trials initiated is reduced as compared to the previous decade, with a slightly larger relative decrease in the US as compared to Europe. Additionally, the monthly trend for the initiation of non-Covid-19 trials differs between regions. In the US, after a sharp decrease in April 2020, trial numbers reached the levels of 2019 from June 2020 onwards. In Europe, the decrease was less pronounced, but trial numbers mainly remained below the 2019 average until February 2021.

COVID-19 pandemic response varies by clinical trial sponsor type.

INTRODUCTION: The COVID-19 pandemic has impacted millions of lives globally. To learn more about this disease and find potential diagnostic, therapeutic, and preventative products, the healthcare community has initiated a staggering number of clinical trials. METHODS: ClinicalTrials.gov was reviewed to determine if trial sponsor type had a relationship to time to COVID-19 response, which was defined as the date from disease discovery in Wuhan, China to ClinicalTrials.gov study "First Posted" date. RESULTS: A total of 673 United States (US) sponsored, interventional study listings were retrieved, of which 293 (43.5%) were Industry-sponsored, 349 (51.9%) were Academic sponsored, and 31 (4.6%) were Other sponsor types. Of the Academic studies, 181 (51.9%) were Clinical and Translational Science Award (CTSA) hubs. The average response time for all sponsor types was 189 days, with Academic sponsors having the shortest average response time of 172.6 days (P < 0.001). CTSA hubs had a significantly (P < 0.001) shorter average response time (168.1 days) compared to all other sponsor types (197.4 days). However, while shorter in duration by 9.4 days, response time was not significantly different from non-CTSA sponsors (177.5 days; P = 0.238). Additionally, ANOVA indicated significant relationships (P < 0.001) between funding type, study phase, number of sites, and enrollment size on response time. CONCLUSIONS: Studies posted with the shortest response time were Academic-sponsored trials and included smaller sized investigations of repurposed approved or investigational drugs for the treatment of COVID-19 symptoms. A small second wave of study postings occurred approximately 4 months later, and included small, unique therapies targeting prevention or treatment of COVID-19.

Identifying Core Outcome Sets in COVID-19 Clinical Trials Using ClinicalTrials.gov.

Introduction of core outcome sets (COS) facilitates evidence synthesis, transparency in outcome reporting, and standardization in clinical research. However, development of COS may be a time consuming and expensive process. Publicly available repositories, such as ClinicalTrials.gov (CTG), provide access to a vast collection of clinical trial characteristics including primary and secondary outcomes, which can be analyzed using a comprehensive set of tools. With growing number of COVID-19 clinical trials, COS development may provide crucial means to standardize, aggregate, share, and analyze diverse research results in a harmonized way. This study was aimed at initial assessment of utility of CTG analytics for identifying COVID-19 COS. At the time of this study, January, 2021, we analyzed 120 ongoing NIH-funded COVID-19 clinical trials initiated in 2020 to inform COVID-19 COS development by evaluating and ranking clinical trial outcomes based on their structured representation in CTG. Using this approach, COS comprised of 25 major clinical outcomes has been identified with mortality, mental health status, and COVID-19 antibodies at the top of the list. We concluded that CTG analytics can be instrumental for COVID-19 COS development and that further analysis is warranted including broader number of international trials combined with more granular approach and ontology-driven pipelines for outcome extraction and curation.

The COVID-19 pandemic and new clinical trial activations.

BACKGROUND: The COVID-19 pandemic has caused severe disruptions in care for many patients. A key question is whether the landscape of clinical research has also changed. METHODS: In a retrospective cohort study, we examined the association of the COVID-19 outbreak with new clinical trial activations. Trial data for all interventional and observational oncology, cardiovascular, and mental health studies from January 2015 through September 2020 were obtained from ClinicalTrials.gov . An interrupted time-series analysis with Poisson regression was used. RESULTS: We examined 62,252 trial activations. During the initial COVID-19 outbreak (February 2020 through May 2020), model-estimated monthly trial activations for US-based studies were only 57% of the expected estimate had the pandemic not occurred (relative risk = 0.57, 95% CI 0.52 to 0.61, p < .001). For non-US-based studies, the impact of the pandemic was less dramatic (relative risk = 0.77, 95% CI 0.73 to 0.82, p < .001), resulting in an overall 27% reduction in the relative risk of new trial activations for US-based trials compared to non-US-based trials (relative risk ratio = 0.73, 95% CI 0.67 to 0.81, p < .001). Although a rebound occurred in the initial reopening phase (June 2020 through September 2020), the rebound was weaker for US-based studies compared to non-US-based studies (relative risk ratio = 0.87, 95% CI 0.80 to 0.95, p < .001). CONCLUSIONS: These findings are consistent with the disproportionate burden of COVID-19 diagnoses and deaths during the initial phase of the pandemic in the USA. Reduced activation of cancer clinical trials will likely slow the pace of clinical research and new drug discovery, with long-term negative consequences for cancer patients. An important question is whether the renewed outbreak period of winter 2020/2021 will have a similarly negative impact on the initiation of new clinical research studies for non-COVID-19 diseases.

Coronavirus Disease 2019 Related Clinical Studies: A Cross-Sectional Analysis.

OBJECTIVE: The quality and rationality of many recently registered clinical studies related to coronavirus disease 2019 (COVID-19) needs to be assessed. Hence, this study aims to evaluate the current status of COVID-19 related registered clinical trial. METHODS: We did an electronic search of COVID-19 related clinical studies registered between December 1, 2019 and February 21, 2020 (updated to May 28, 2020) from the ClinicalTrials.gov, and collected registration information, study details, recruitment status, characteristics of the subjects, and relevant information about the trial implementation process. RESULTS: A total of 1,706 studies were included 10.0% of which (n=171) were from France, 943 (55.3%) used an interventional design, and 600 (35.2%) used an observational design. Most of studies (73.6%) aimed to recruit fewer than 500 people. Interferon was the main prevention program, and antiviral drugs were the main treatment program. Hydroxychloroquine and chloroquine (230/943, 24.4%) were widely studied. Some registered clinical trials are incomplete in content, and 37.4% of the 1,706 studies may have had insufficient sample size. CONCLUSION: The quality of COVID-19 related studies needs to be improved by strengthening the registration process and improving the quality of clinical study protocols so that these clinical studies can provide high-quality clinical evidence related to COVID-19.

Ongoing non-industry-sponsored COVID-19 clinical trials in the first trimester of the pandemic: significant differences between the European and the USA approaches.

BACKGROUND: The different features between non-industry-sponsored medicine trials conducted in Europe and the USA to treat COVID-19 patients registered in the first trimester of the pandemic are unknown. METHODS: A search was conducted on four databases looking for ongoing medicine randomized controlled trials (RCTs) and non-RCTs registered current through April 25, 2020. All trials assessing medicines on prophylaxis, special populations, assessing non-medicines and convalescent plasma, were excluded. Of each trial, medicines assessed, design, sample size, registration date, study start and study completion dates, and type of patients were registered. RESULTS: 106 trials were identified, 62 in Europe and 46 in the USA ─with two conducted in both regions. In Europe, 90% were on hospitalized patients, and 70% in the USA (p<0.01). Mean of the estimated time to completion were 7.8 and 13.6 (p<0.001) months for European and USA trials . Multicenter trials were more frequent in Europe (63%) than in the USA (41%) (p=0.031). Masked RCTs were more frequently run in the USA than in Europe (p<0.001). RCTs on hospitalized patients were more commonly conducted in Europe (91%) than in the USA (65%) (p<0.01). CONCLUSIONS: Features of early registered COVID-19 RCTs with medicines in Europe and America had remarkable differences.

Systematic review of registered trials of Hydroxychloroquine prophylaxis for COVID-19 health-care workers at the first third of 2020.

In the absence of a vaccine the medical and scientific community is looking intensely at utilizing a pre or post exposure drug that could decrease viremia. The search for a medication that could reduce risk of serious disease, and ideally of any manifestation of disease from SARS-CoV2, and of asymptomatic shedding of SARS-CoV2 is of urgent interest. Repurposing existing pharmaceuticals is among the approaches to achieve these ends. We performed a systematic review of all interventional studies registered in ClinicalTrials.gov with a focus on one repurposed drug, Hydroxychloroquine (HCQ). The detailed analysis of these studies, some of them already recruiting, provide an overall picture of HCQ use as a COVID-19 prophylaxis around the world. Among the included studies, all but three were randomized and parallel and most of them (74%, 23/31) were double-blinded to quadruple-blinded studies. We found a great diversity in dosing and nearly all the possible scientifically reasonable regimens are under evaluation. This diversity offers benefits as well as challenges. Importantly, the final analysis of these trials should be done through an extensive reading of the results in regard to the clinical design, it will be crucial to carefully read and evaluate the results of each study in regards to the clinical design rather than quickly glancing a 140 characters-based social media message announcing the failure or success of a drug against a disease.