Analysis Of Clinical Trial Data Research Articles

Defining Successful Intubation on the First Attempt Using Both Laryngoscope and Endotracheal Tube Insertions: A Secondary Analysis of Clinical Trial Data

Successful intubation on the first attempt has historically been defined as successful placement of an endotracheal tube (ETT) using a single laryngoscope insertion. More recent studies have defined successful placement of an ETT using a single laryngoscope insertion followed by a single ETT insertion. We sought to estimate the prevalence of first-attempt success using these 2 definitions and estimate their associations with the duration of intubation and serious complications. We performed a secondary analysis of data from 2 multicenter randomized trials of critically ill adults being intubated in the emergency department or ICU. We calculated the percent difference in successful intubations on the first attempt, median difference in the duration of intubation, and percent difference in the development of serious complications by definition. The study population included 1,863 patients. Successful intubation on the first attempt decreased by 4.9% (95% confidence interval 2.5% to 7.3%) when defined as 1 laryngoscope insertion followed by 1 ETT insertion (81.2%) compared with when defined as only 1 laryngoscope insertion (86.0%). When successful intubation with 1 laryngoscope and 1 ETT insertion was compared with 1 laryngoscope and multiple ETT insertions, the median duration of intubation decreased by 35.0 seconds (95% confidence interval 8.9 to 61.1 seconds). Defining successful intubation on the first attempt as placement of an ETT in the trachea using 1 laryngoscope and 1 ETT insertion identifies attempts with the shortest apneic time.

Abstract LB143: Improving treatment outcomes: a digital solution for remote patient monitoring of stomatitis for patients receiving Dato-DXd

Abstract Instances of stomatitis are very painful and compromise nutrition and oral hygiene as well as induce an increased risk for local and systemic infection. Stomatitis is a well-known toxicity of radiotherapy, chemotherapy and other targeted therapies and is associated with dose interruptions, reductions, and treatment discontinuation. For upcoming Dato DXd phase III trials, the mitigation strategies included patient education delivered at the site and supported by printed material to foster continued adherence to an oral care protocol (OCP). The study team thought to leverage digital technology, namely patient-provisioned smartphones to bring the OCP right “to the patients’ fingertips”, while enabling health care providers at the site to monitor onset or worsening of stomatitis for each patient. The digital solution consists of a patient interface for data acquisition and personalized education/behavioral reinforcement, and a clinician interactive data dashboard to access, in real time, patients’ records of stomatitis-related symptoms and their impact on nutrition and hydration, respectively. For a few days post infusion, the solution surfaces personalized illustrated vignettes to provide the participant with simple recommendations for self-care and probe to contact the clinical site team when symptom(s) reach a given morbidity threshold. The clinical team can visualize data on demand or upon being prompted, to quickly assess trends towards stomatitis worsening and decide on the next course of action. This solution for remote patient monitoring of stomatitis risk is deployed in four studies and is planned for an additional three, reaching approximately a total of 7,000 patients across 49 sites in 16 countries. Early feedback from patients confirmed the engaging design, the low burden daily usage, and the perceived utility of the solution. Patients who had experienced stomatitis previously indicated that such a solution would have given them confidence to engage with their site sooner to receive care. Further structured feedback from clinical study teams and analyses of clinical trial data are planned to inform patients’ sustained compliance using the solution and its effectiveness in mitigating high grade of stomatitis and helping patients to better manage their treatment and outcomes. Citation Format: Rebecca H. Wray, Elisabeth Piault, Lucie Miller-Potucka, Jill A. Bell, Rick Fairhurst, Sabrina S. Khan, Micah J. Maxwell, Neelima Denduluri, Leora Horn. Improving treatment outcomes: a digital solution for remote patient monitoring of stomatitis for patients receiving Dato-DXd [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB143.

Abstract 5464: Predictive biomarkers for PD-1 and PD-L1 checkpoint inhibitor response in NSCLC: An analysis of clinical trial and real-world data

Abstract Importance: Largest analysis combining clinical trial and real-world data (RWD) to assess the clinical utility of biomarkers for anti-PD-1/PD-L1 checkpoint inhibitors (CPI) in NSCLC patients. Objective: To assess the association between tumor PD-L1, TMB and blood analytes with clinical outcomes in patients with advanced NSCLC following CPI therapy. Design: Retrospective cohort study with patients stratified into high and low biomarker groups. Correlation with treatment outcome in the different biomarker groups was investigated and compared between patients treated with CPI versus chemotherapy. Setting: Data derived from electronic health records mostly from community oncology settings were combined with clinical trial data. Participants: Starting with 71850 patients with advanced NSCLC who received CPI or chemotherapy, we selected 24152 patients from an electronic health record-derived de-identified NSCLC clinicogenomic database (CGDB) from a real-world cohort and nine Roche atezolizumab trials. Patients were diagnosed between January 2011 and February 2020 (data collection cut-off date). Main Outcomes and Measures: Drug response was assessed by RECIST criteria for clinical trials and real-world response for RWD. Durable response was defined as having CR/PR without progression during the study period of 270 days. Associations of biomarker levels with treatment outcomes were analyzed using Fisher’s exact test. Results: High expression of PD-L1 on tumors (≥50%) were associated with lower risk of resistance to CPI (odds ratio [OR] 0.21; 95% CI = 0.14, 0.32; P< .001). The association was stronger in patients who had prior chemotherapy than first line CPI, with non-squamous than squamous histology, and smokers than non-smokers. Higher TMB (≥9.57 mut/Mb) was also associated with durable response (OR = 0.41; CI = 0.30, 0.55; P< .001). The combination of high TMB and PD-L1 expression was the strongest predictor of durable response (OR = 0.04; CI = 0.00, 0.20; P< .001). There was no evidence of an association between PD-L1/TMB and response to chemotherapy, suggesting a CPI-specific predictive effect. In contrast, blood analytes were prognostic, having correlation with clinical outcome irrespective of treatment type. Conclusion: This study supports the predictive utility of PD-L1 expression and TMB for NSCLC patients receiving CPI therapy and further elucidates their utility in patient sub-populations. Citation Format: WeiQing Venus So, David Dejardin, Eva Rossmann, Jehad Charo. Predictive biomarkers for PD-1 and PD-L1 checkpoint inhibitor response in NSCLC: An analysis of clinical trial and real-world data. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5464.

Abstract 5062: Small molecule superoxide dismutase mimetic avasopasem manganese for the mitigation of cisplatin induced ototoxicity

Abstract Introduction: Avasopasem manganese (GC4419) is a selective superoxide dismutase mimetic which has recently completed a Phase 3 clinical trial (NCT03689712) demonstrating a significant reduction in the severity of oral mucositis in patients receiving standard cisplatin and radiotherapy for head and neck squamous cell carcinoma (HNSCC). Up to 66% of HNSCC patients experience ototoxicity from platinum-based chemotherapy, resulting in tinnitus and hearing loss. The analysis of clinical trial data also revealed that patients treated with GC4419 in addition to cisplatin (cis) and radiotherapy reported less tinnitus than those treated with standard therapy alone. The generation of reactive oxygen species has long been recognized as an important contributor to cis-induced hearing loss; therefore, we hypothesize that administration of GC4419 with cisplatin can prevent ototoxicity by scavenging superoxide. Results: Organotypic cultures using postnatal day 2 or 3 mouse cochlea were treated with cis 4 µM and 0.5, 2, or 4 µM GC4419 for 24 hours. The explants were then stained for anti-myosin-VIIa. Hair cells were counted, and it was determined that 4 µM cis was sufficient to cause a decrease in hair cell numbers and GC4419 dose as low as 2 µM protected against this biological endpoint. To assess the effects of GC4419 on hearing loss in vivo, CBA/CaJ mice were treated as follows: 5 mice (1 female, 4 males) received 3 mg/kg cis IP, 4 mice (2 males and 2 females) received vehicle, 3 mice (2 females, 1 males) received 10 mg/kg IP GC4419, and 5 mice (2 females, 3 males) were treated with GC4419 10 minutes prior to cisplatin injection. Cis and GC4419 were administered for four consecutive days followed by two days of GC4419. The animals were allowed 8 recovery days, with Normosol SQ and high calorie food administered, prior to a second repetition of the treatment cycle. This protocol for cis dosing was found to be lethal in three mice in the cisplatin only group. Auditory brainstem response testing was performed before and after treatment, revealing elevated hearing thresholds in cis treated mice but not in mice treated with GC4419 and cis. Additionally, the cis treatment group experienced greater weight loss than the mice treated with GC4419 and cis Separately, in an H1299 tumor xenograft model in nu/nu mice, GC4419 5 mg/kg IP BID over 14 days was shown not to interfere with, and in fact somewhat increased, the tumor growth delay with cis 5 mg/kg IP QW x 3. Conclusion: These results support the hypothesis that treatment with the SOD mimetic GC4419 can reduce cis induced ototoxicity by scavenging superoxide and justify further studies to determine if this mechanism based approach can be implemented in cancer therapy. (Supported by a sponsored research agreement between the University of Iowa and Galera Therapeutics, Inc.) Citation Format: Keegan A. Christensen, Osama Tarabichi, Sei Sho, Hidaly Hernández, Bryce Hunger, Melissa A. Fath, Jeffery Keene, Robert Beardsley, Marlan Hansen, Douglas R. Spitz. Small molecule superoxide dismutase mimetic avasopasem manganese for the mitigation of cisplatin induced ototoxicity. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5062.

Abstract 5879: Defining the cancer Immunogram using multimodal analysis to guide immunotherapy in diffuse large B cell lymphoma

Abstract (a) Expansion of therapeutic strategies against diffuse large B-cell lymphoma (DLBCL) offers new opportunities to fight aggressive non-Hodgkin's lymphoma. Therapy approaches, such as R-CHOP and stem cell transplant, and CAR-T cell therapies are now available for the treatment of DLBCL. While the role of the tumor microenvironment (TME) during the therapeutic response is now recognized, the spatial organization and the communication between the diverse factors that compose the TME remains to be fully understood. In this study, we describe a new immunogram tool to help clinical researchers measure the tumor microenvironment contribution to drug efficacy or toxicity in DLBCL context. (b) In a previous work, using a high-quality testing and innovative multimodal and integrative approach, we constructed the first Veracyte Biopharma Atlas for DLBCL lesions. Based on this knowledge and the understanding of the immune contexture of tumors, we constructed an immunogram using the scoring of clinically relevant biomarkers. Our immunogram scoring approach is composed of key features driving computational derivation of DLBCL Atlas clusters, which include immune gene signatures, immune cell phenotyping combined with spatial information, and genomic and clinical parameters. (c) Patterns that strongly associated with CAR-T treatment response were determined. In addition, promising results have been obtained in the prediction to CAR-T toxicity related to T-regulatory cells or R-CHOP response with transcriptomic signature. (d) Retrospective analysis of CAR-T clinical trial data and tumor biopsies highlighted the Veracyte Immunogram as a powerful tool to score the patient probability of response to CAR-T. This work provides the framework for identification of predictors of response to therapy, potential targets of interest or biomarkers that could be applied in future clinical trials. Citation Format: Michael D. Mattie, Regis Perbost, Sarah Turcan, Corinne Danan, Frederick L. Locke, Sattva S. Neelapu, David B. Miklos, Caron A. Jacobson, Lazaros J. Lekakis, Yi Lin, Armin Ghobadi, Jenny J. Kim, Zixing Wang, Allen Xue, Simone Filosto, Nathalie Scholler, Jerome Galon. Defining the cancer Immunogram using multimodal analysis to guide immunotherapy in diffuse large B cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5879.

FDA Oncology Center of Excellence Crowdsourcing Initiative: Outreach to the Scientific Community to Identify Research Questions for Pooled Analyses of Oncology Clinical Trial Data.

The FDA Oncology Center of Excellence recently launched a crowdsourcing pilot to request ideas from the scientific community for research questions that FDA could address with pooled analyses of clinical trial data submitted to the agency for regulatory purposes. This effort builds on FDA's track record of publishing pooled analyses to explore scientific questions that cannot be addressed in a single trial due to limited sample size. The research crowdsourcing pilot tested a new approach for obtaining external input on regulatory science activities, because FDA is generally unable to share patient-level data outside of the agency due to federal disclosure laws and regulations protecting different types of data submitted in regulatory applications. We received 29 submissions over the 28-day crowdsourcing campaign, including one research idea that we are exploring for possible follow-up. Based on our experience with this pilot, we learned that crowdsourcing is a promising new approach to gather external input and feedback. We identified opportunities to build understanding in the external oncology community about the types of data typically included in regulatory applications and expand the dissemination of published FDA pooled analyses to help inform future drug development and clinical practice.

Surviving Sepsis Campaign.

Surviving Sepsis Campaign.

Health utilities and quality-adjusted life years for patients with amyotrophic lateral sclerosis receiving reldesemtiv or placebo in FORTITUDE-ALS

AimsTo estimate the health utilities and quality-adjusted life years (QALYs) in patients with amyotrophic lateral sclerosis (ALS) receiving reldesemtiv versus placebo in FORTITUDE-ALS.Materials and methodsWe performed a post hoc analysis of clinical trial data from FORTITUDE-ALS (NCT03160898). This Phase IIb, double-blind, randomized, dose-ranging, placebo-controlled, parallel-group, 12-week trial evaluated reldesemtiv in patients with ALS. Health utilities from the five-level version of the EuroQol five-dimensional questionnaire (EQ-5D-5L) were estimated using ALS Functional Rating Scale-Revised (ALSFRS-R) scores collected during the trial. QALYs were estimated using the area under the curve method.ResultsThe full analysis set consisted of 456 patients (reldesemtiv n = 342, placebo n = 114), who received at least one dose of the double-blind study drug, and had ALSFRS-R assessed at baseline and at least one post-baseline assessment. The difference in EQ-5D-5L utility least-squares (LS) mean change from baseline to week 12 for reldesemtiv versus placebo, adjusted for baseline values, was statistically significant (0.03, 95% confidence interval [CI]: 0.01, 0.05; p = .0008). The incremental QALY of reldesemtiv versus placebo adjusted for baseline utility values showed a modest, but statistically significant, difference (0.004, 95% CI: 0.001, 0.007; p = .0058).ConclusionsThis post hoc analysis of FORTITUDE-ALS suggests that reldesemtiv showed a modest but significant benefit in health utilities and QALYs compared with placebo. Future long-term studies that include direct collection of EQ-5D-5L data will be needed to confirm our findings. ClinicalTrials.gov identifierNCT03160898

Tocilizumab in giant cell arteritis: an update for the clinician.

The recent approval of tocilizumab (TCZ) for the treatment of giant cell arteritis (GCA) has changed the landscape for management of this disease. Herein, we review recent literature addressing practical questions for the clinician regarding the use of TCZ in GCA. We evaluate efficacy of TCZ across different disease phenotypes, optimal dosing and formulation, treatment-related toxicity, recommendations for monitoring disease, and duration of therapy. Post-hoc analyses of a large clinical trial and real-world data suggest efficacy of TCZ across various disease phenotypes in GCA, and support use of weekly subcutaneous dosing over every-other-week dosing. More data are needed to guide duration of TCZ therapy, optimal disease activity monitoring in patients treated with TCZ, and to speak to efficacy in GCA with large vessel involvement. TCZ has added valuably to the treatment arsenal in GCA, though more data are needed to guide optimal use of the drug.

Long-Term Durability of Certolizumab Pegol in Patients with Rheumatoid Arthritis Over 5 Years: An Analysis of Pooled Clinical Trial Data.

There is a paucity of data on how patient characteristics may affect the long-term durability of certolizumab pegol (CZP) in patients with rheumatoid arthritis (RA). This study therefore aimed to investigate CZP durability and reasons for discontinuation over 5years between different subgroups of patients with RA. Data were pooled from 27 clinical trials in RA patients. Durability was defined as the percentage of patients randomized to CZP at baseline who were still on CZP treatment at a given timepoint. Post hoc analyses of clinical trial data on CZP durability and reasons for discontinuation among different patient subgroups were conducted using Kaplan-Meier curves and Cox proportional hazards modeling. Patient subgroups included: age (18- < 45/45- < 65/ ≥ 65years), gender (male/female), prior tumor necrosis factor inhibitor (TNFi) use (yes/no), and disease duration (< 1/1- < 5/5- < 10/ ≥ 10years). Among 6927 patients, the durability of CZP was 39.7% at 5years. Patients aged ≥ 65years had a 33% greater risk of CZP discontinuation than patients 18- < 45years (hazard ratio [95% confidence interval]: 1.33 [1.19-1.49]) and patients with prior TNFi use had a 24% greater risk of discontinuing CZP than patients without (1.24 [1.12-1.37]). Conversely, greater durability was observed among patients who had a baseline disease duration of ≥ 1year. Durability did not differ in the gender subgroup. Of the 6927 patients, the most common reason for discontinuation was inadequate levels of efficacy (13.5%); followed by adverse events (11.9%); consent withdrawn (6.7%); lost to follow-up (1.8%); protocol violation (1.7%); other reasons (9.3%). CZP durability was comparable with durability data on other bDMARDs in RA patients. Patient characteristics that were associated with greater durability included younger age, TNFi-naïvety, and disease duration ≥ 1year. Findings may be helpful in informing clinicians on a patient's likelihood of discontinuing CZP, based on their baseline characteristics.

Estimands for atopic dermatitis clinical trials: Expert opinion on the importance of intercurrent events.

Despite the emergence of novel targeted treatments for atopic dermatitis (AD), there is a lack of guidelines on standardizing analysis of clinical trial data. To define and estimate meaningful treatment comparisons, several factors, including intercurrent events, must be taken into account. Intercurrent events are defined as events occurring after treatment initiation that affect either the interpretation or existence of the measurements associated with clinical questions of interest. Due to the relapsing, unpredictable nature of AD, intercurrent events frequently occur in AD trials, such as use of rescue therapy for intense itch and sleep deprivation. Despite the impact of intercurrent events in AD, they are often handled in an inconsistent manner across trials, which limits results interpretation. The estimand framework is increasingly used to estimate treatment effects while accounting for intercurrent events. This review explores how guidance from the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) on the use of estimands can be applied to support AD clinical trial design and analysis. We propose that estimands are used in AD trials and defined early during trial design. The use of estimands can provide clinicians with interventional trial results that are more reflective of clinical practice, help facilitate comparisons across clinical trials, and are more informative to enable improved treatment selection for patients.

Post hoc analysis of SUSTAIN 6 and PIONEER 6 trials suggests that people with type 2 diabetes at high cardiovascular risk treated with semaglutide experience more stable kidney function compared with placebo

Glucagon-like peptide-1 receptor agonists reduce albuminuria and may stabilize the estimated glomerular filtration rate (eGFR) in people with type 2 diabetes (T2D). In this post hoc analysis of the SUSTAIN 6/PIONEER 6 trials encompassing 6480 participants at high cardiovascular risk (semaglutide, 3239 participants; placebo, 3241 participants), we investigated the effects of semaglutide versus placebo on eGFR decline. Pooled data by treatment were evaluated for annual eGFR change (total annual eGFR slope in ml/min per 1.73 m2) from baseline to end of treatment and time to persistent eGFR reductions of 30%, 40%, 50% and 57% or more, including subgroup analyses by baseline eGFR (30 to under 60 or 60 and over ml/min per 1.73 m2). In the overall population, the estimated treatment difference (ETD; semaglutide versus placebo) in annual eGFR slope was significant at 0.59 ml/min per 1.73 m2 (95% confidence interval 0.29; 0.89). The ETD was numerically largest in the 30 to under 60 ml/min per 1.73 m2 eGFR subgroup, 1.06 ml/min per 1.73 m2(0.45; 1.67), but no significant interaction was observed for treatment effect by subgroup. Hazard ratios (semaglutide versus placebo) for time to persistent eGFR decline were under 1.0 for all eGFR thresholds in the overall population; and were numerically lower in the baseline eGFR 30 to under 60 ml/min per 1.73 m2 subgroup versus the overall population, although no significant interaction was observed for treatment effect by subgroup. Thus, pooled analyses of clinical trial data in patients with T2D suggest that semaglutide may reduce the rate of eGFR decline.

Predictive biomarkers for PD-1/PD-L1 checkpoint inhibitor response in NSCLC: an analysis of clinical trial and real-world data

BackgroundMany biomarkers have been proposed to be predictive of response to anti-programmed cell death protein-1 (PD-1)/anti-programmed death ligand-1 (PD-L1) checkpoint inhibitors (CPI). However, conflicting observations and lack of consensus call...

PP01.78 Brain Metastasis in Patients With KRAS Mutant Advanced NSCLC Receiving Docetaxel: Pooled Clinical Trial Data Analysis

PP01.78 Brain Metastasis in Patients With KRAS Mutant Advanced NSCLC Receiving Docetaxel: Pooled Clinical Trial Data Analysis

Bayesian Design Study of the TGN1412 Trial

Objective: This study considers the Bayesian design of clinical trials from the perspective of a comparative study of the Bayesian approach for the TGN1412 clinical trial. The Bayesian setting analyses the statistical issues of the TGN1412 trials’ first in man studies, which include the details of the Northwick Park trial, and the clinical study design recommendations are implemented. Methods: The clinical trial data analysis was carried out to screen the structural evidence of the trial outcomes. Hierarchical modeling is implemented with structural priors to get the most efficient Bayesian outcomes. Findings: We concentrated on determining the best model for the clinical pathway of randomization and Bayesian design of experiments. Novelty: The Bayesian design of experiments is widely used for outcome prediction under various treatments in order to validate the trial’s dosing periods. The purpose of this paper is to compare the growth models for Phase I trial results. Current research on Bayesian designs incorporates simulation studies on the effects of design variables. Keywords: Clinical Trial; Bayesian; Efficacy; Dose Limiting Event; Desirable Outcome; Treatment Effects; Cohort Effects; Dose Response

Opportunities and challenges in application of artificial intelligence in pharmacology.

Artificial intelligence (AI) is a machine science that can mimic human behaviour like intelligent analysis of data. AI functions with specialized algorithms and integrates with deep and machine learning. Living in the digital world can generate a huge amount of medical data every day. Therefore, we need an automated and reliable evaluation tool that can make decisions more accurately and faster. Machine learning has the potential to learn, understand and analyse the data used in healthcare systems. In the last few years, AI is known to be employed in various fields in pharmaceutical science especially in pharmacological research. It helps in the analysis of preclinical (laboratory animals) and clinical (in human) trial data. AI also plays important role in various processes such as drug discovery/manufacturing, diagnosis of big data for disease identification, personalized treatment, clinical trial research, radiotherapy, surgical robotics, smart electronic health records, and epidemic outbreak prediction. Moreover, AI has been used in the evaluation of biomarkers and diseases. In this review, we explain various models and general processes of machine learning and their role in pharmacological science. Therefore, AI with deep learning and machine learning could be relevant in pharmacological research.

Comparing translational success rates across medical research fields - A combined analysis of literature and clinical trial data.

Many interventions that show promising results in preclinical development do not pass clinical tests. Part of this may be explained by poor animal-to-human translation. Using animal models with low predictability for humans is neither ethical nor efficient. If translational success shows variation between medical research fields, analyses of common practices in these fields could identify factors contributing to successful translation. We assessed translational success rates in medical research fields using two approaches: through literature and clinical trial registers. Literature: We comprehensively searched PubMed for pharmacology, neuroscience, cancer research, animal models, clinical trials, and translation. After screening, 117 review papers were included in this scoping review. Translational success rates were not different within pharmacology (72%), neuroscience (62%), and cancer research (69%). Clinical trials: The fraction of phase-2 clinical trials with a positive outcome was used as a proxy (i.e., an indirect resemblance measure) for translational success. Trials were retrieved from the WHO trial register and categorized into medical research fields following the international classification of disease (ICD-10). Of the phase-2 trials analyzed, 65.2% were successful. Fields with the highest success rates were disorders of lipoprotein metabolism (86.0%) and epilepsy (85.0%). Fields with the lowest success rates were schizophrenia (45.4%) and pancreatic cancer (46.0%). Our combined analyses suggest relevant differences in success rates between medical research fields. Based on the clinical trials, comparisons of practice, e.g., between epilepsy and schizophrenia, might identify factors that influence translational success.

Comparing translational success rates across medical research fields - A combined analysis of literature and clinical trial data_suppl1

Comparing translational success rates across medical research fields - A combined analysis of literature and clinical trial data_suppl1

Predicting risk factors for pediatric mortality in clinical trial research: A retrospective, cross-sectional study using a Healthcare Cost and Utilization Project database.

Incorporating real-world data using "big data" analysis in healthcare are useful to extract specific information for healthcare delivery system improvement. All-cause mortality is an essential measure to enhance patient safety in clinical trial research, especially for underrepresented pediatric participants. This study aimed to determine the associations between pediatric mortality and patient-specific factors using the Healthcare Cost and Utilization Project (HCUP) database. Data from the 2019 the HCUP Kids' Inpatient Database (KID) were used to conduct a logistic regression analysis to determine associations between pediatric patients' the chance of survival and their demographic and socioeconomic background, discharge records, and hospital information. Total number of diagnoses (OR = 0.84), total number of procedures (OR = 0.86), length of stay (OR = 1.04), age intervals greater than 1 year (OR > 1.0), transfer into the hospital from a different acute care (OR = 0.34), major diagnoses of multiple significant trauma (OR = 0.03) or hepatobiliary system and pancreas (OR = 0.10), region of hospital - west and midwest (OR > 1.0), and medium or larger hospital bed size (OR > 1.0) were all significantly associated with the chance of survival for patients participating in pediatric clinical trials (p < 0.05). Real-world clinical trial data analysis showed the potential improvement area including reallocating trial resources to promote trial quality and safe participation for pediatric patients. Pediatric trials need tools that are developed using user-centered design approaches to satisfy the unique needs and requirements of pediatric patients and their caregivers. Safe intrahospital transfer procedures and active dissemination of successful trial best practices are crucial to trial management, adherence, quality, and safety.

Introducing the fragility index-A case study using the Term Breech Trial.

The fragility index (FI) is a sensitivity analysis of the statistically significant result of a clinical study. It is the number of hypothetical changes in the primary event of one of the two cohorts in a 1-to-1 comparative trial to render the statistically significant result non-significant (ie, to alter the P-value from ≤0.05 to >0.05). The FI can be compared with the patient drop-out rates and protocol violations, which, if much higher than the FI, may arguably suggest less robustness/stability of the trial's results. To illustrate the concept, we have chosen the Term Breech Trial (TBT) as a case study. The TBT results favor planned cesarean birth, as opposed to planned vaginal delivery, in the term singleton fetus with breech presentation. Our analysis shows that the FI of the TBT is 21, which is small in comparison to the number (hundreds) of protocol violations present. Some experts have suggested the inclusion of the FI in data analysis and subsequent discussion of clinical trial data. Routine use of such a metric may be valuable in encouraging readers to maintain a healthy degree of skepticism, especially when interpreting trial results which may directly influence clinical practice.