Drug Trials Research Articles

Accurate non-invasive detection of MASH with fibrosis F2-F3 using a lightweight machine learning model with minimal clinical and metabolomic variables

BackgroundThere are no known non-invasive tests (NITs) designed for accurately detecting metabolic dysfunction-associated steatohepatitis (MASH) with liver fibrosis stages F2-F3, excluding cirrhosis—the FDA-defined range for prescribing Resmetirom and other drugs in clinical trials. We aimed to validate and re-optimize known NITs, and most importantly to develop new machine learning (ML)-based NITs to accurately detect MASH F2-F3. MethodsClinical and metabolomic data were collected from 443 patients across three countries and two clinic types (metabolic surgery, gastroenterology/hepatology) covering the entire spectrum of biopsy-proven MASLD, including cirrhosis and healthy controls. Three novel types of ML models were developed using a categorical gradient boosting machine pipeline. These were compared with 24 biomarker, imaging, and algorithm-based NITs with both known cutoffs for MASH F2-F4 and re-optimized cutoffs for MASH F2-F3. ResultsNFS at a − 1.455 cutoff attained an AUC of 0.59, the highest sensitivity (90.9 %, 95 % CI 84.3–95.4), and NPV of 87.2 %. FIB4 risk stratification followed by elastography (8 kPa) had the best specificity (86.9 %) and PPV (63.3 %), with an AUC of 0.57. NFS followed by elastography improved the PPV to 65.3 % and AUC to 0.62. Re-optimized FibroScan-AST (FAST) at a 0.22 cutoff had the highest PPV (69.1 %). ML models using aminotransferases, metabolic syndrome components, BMI, and 3-ureidopropionate achieved an AUC of 0.89, which further increased to 0.91 following hyperparameter optimization and the addition of alpha-ketoglutarate. These new ML models outperformed all other NITs and displayed accuracy, sensitivity, specificity, PPV, and NPV up to 91.2 %, 85.3 %, 97.0 %, 92.4 %, and 90.7 % respectively. The models were reproduced and validated in a secondary sensitivity analysis, that used one of the cohorts as feature selection/training, and the rest as independent validation, likewise outperforming all other NITs. ConclusionsWe report for the first time the diagnostic characteristics of non-invasive, metabolomics-based biomarker models to detect MASH with fibrosis F2-F3 required for Resmetirom treatment and inclusion in ongoing phase-III trials. These models may be used alone or in combination with other NITs to accurately determine treatment eligibility.

Study on Drug Repurposing for ALS Treatment Using Pre-trained Knowledge Graph Embeddings: Methods and Findings

In this study, research has been conducted using pre-trained knowledge graph embedding for drug repurposing in treating ALS (Amyotrophic Lateral Sclerosis), and its results have been presented. Drug repurposing studies for ALS have been carried out through two main methods: disease-drug relationship and genes-drugs relationship. Drug repurposing recommendations for ALS have been provided by predicting connections between disease and drug entities on the DRKG (Drug Repurposing Knowledge Graph). The findings obtained from the study have been evaluated by comparing them with the list of clinical trial drugs obtained from Drugbank. DRKG has been utilized as a comprehensive biological knowledge graph containing genes, compounds, diseases, biological processes, side effects, and symptoms. This graph has proven to be an effective resource for extracting information related to ALS disease. In drug repurposing studies, drugs obtained through disease-drug relationships have been compared with the list of clinical trial drugs associated with ALS, yielding significant results. Additionally, interactions between genes associated with ALS and drugs related to these genes have been examined in studies conducted through gene-drug relationships. The results obtained from the study demonstrate that DRKG is an effective resource for identifying drugs with potential therapeutic effects in the treatment of ALS. The findings suggest that drug repurposing studies could offer new and effective solutions for the treatment of ALS, marking a significant step forward in this regard.

84. Improving Traditional Registrational Trial Endpoints: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Acute Bacterial Skin and Skin-Structure Infections

Abstract Background The ideal primary endpoint for acute bacterial skin and skin-structure infection (ABSSSI) trials is unknown and regulatory guidance differs between U.S. and Europe. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis and interpretation of clinical trials that incorporates a benefit-risk evaluation and provides a global assessment of patient experience. Methods Drawing on prior work from the Antibacterial Resistance Leadership Group (ARLG), a multidisciplinary committee of experts in infectious diseases, clinical trial design, drug regulation, and patient experience adapted a generalized infectious diseases DOOR for ABSSSI trials (Figure 1). We then retrospectively applied this to two previously published, noninferiority, double-blind, randomized, registrational, ABSSSI trials comparing omadacycline to linezolid OASIS-1 and OASIS-2, Figure 2) to demonstrate how DOOR could be applied. We compared the DOOR distribution and probability of having a more desirable outcome between treatment groups and performed DOOR component analyses. Results For both trials, the ABSSSI DOOR demonstrated similar overall clinical outcomes between treatment groups. In OASIS-1, the probability that a participant treated with omadacycline would have a more desirable outcome than a participant treated with linezolid was 50.7% (95% confidence interval [CI], 47.7%−53.8%) (Figure 3). In OASIS-2, the probability that a participant treated with omadacycline would have a more desirable outcome than a participant treated with linezolid was 51.0% (95% CI, 48.1%–53.8%) (Figure 4). Overall, the DOOR components (clinical failure, infectious complications, serious adverse events, and death) were rare, although the DOOR component analysis provided a more in-depth understanding of the potential trade-offs between efficacy and safety when comparing omadacycline to linezolid. Conclusion DOOR can be informative in registrational ABSSSI trials. Using DOOR can provide clinicians with a better understanding of the clinical outcomes of patients with skin infections. Future trials using DOOR prospectively can continue to inform how to best use DOOR in ABSSSI trials. Disclosures Deborah Collyar, B.Sci, Apellis Pharmaceuticals, Inc.: Advisor/Consultant|Kinnate Biopharma: Advisor/Consultant Sumathi Nambiar, MD MPH, Johnson and Johnson: Stocks/Bonds (Public Company) Carol Hill, PhD, Glaxo SmithKline: Retirement Health, Cash Balance Plan|Glaxo SmithKline: Stocks/Bonds (Public Company) Thomas L. Holland, MD, Karius, Inc: Advisor/Consultant Sarah B. Doernberg, MD, MAS, Basilea Pharmaceutica: Grant/Research Support|F2G Limited: Grant/Research Support|Genentech: Advisor/Consultant|Gilead Biosciences: Grant/Research Support|Janssen/J+J: Advisor/Consultant|Pfizer, Inc: Grant/Research Support|Regeneron, Inc: Grant/Research Support|Shinogi: Grant/Research Support Henry Chambers, MD, Merck: Stocks/Bonds (Private Company)|Moderna: Stocks/Bonds (Private Company) Vance G. Fowler, MD, MHS, Affinergy: Advisor/Consultant|ArcBio: Stocks/Bonds (Private Company)|Armata: Advisor/Consultant|Astra Zeneca: Advisor/Consultant|Astra Zeneca: Grant/Research Support|Basilea: Advisor/Consultant|Basilea: Grant/Research Support|ContraFect: Advisor/Consultant|ContraFect: Grant/Research Support|Debiopharm: Advisor/Consultant|Destiny: Advisor/Consultant|EDE: Grant/Research Support|Genentech: Advisor/Consultant|Genentech: Grant/Research Support|GSK: Advisor/Consultant|Janssen: Advisor/Consultant|Karius: Grant/Research Support|MedImmune: Grant/Research Support|Merck: Grant/Research Support|sepsis diagnostics: Patent pending|UptoDate: Royalties|Valanbuio: Stocks/Bonds (Private Company)|Valanbuio: Stocks/Bonds (Private Company) Scott R. Evans, PhD, M.S., Abbvie: Advisor/Consultant|Advantagene: Advisor/Consultant|Akouos: Advisor/Consultant|Apellis: Advisor/Consultant|AstraZenenca: Advisor/Consultant|BARDA: Advisor/Consultant|Breast International Group: Advisor/Consultant|CDC: Grant/Research Support|Clover: Advisor/Consultant|DayOneBio: Advisor/Consultant|Degruyter: Editorial service|Duke University: Advisor/Consultant|Eli Lilly: Advisor/Consultant|FDA: Advisor/Consultant|Frontier Science Foundation: Board Member|Genentech: Advisor/Consultant|GSK: Advisor/Consultant|Henry Jackson Foundation: Grant/Research Support|International Drug Development Institute: Advisor/Consultant|Johson & Johnson: Advisor/Consultant|Medtronic: Advisor/Consultant|NIH: Grant/Research Support|Novartis: Advisor/Consultant|Pfizer: Advisor/Consultant|Rakuten: Advisor/Consultant|Roche: Advisor/Consultant|Takeda: Advisor/Consultant|Taylor & Francis: Book royalties|Teva: Advisor/Consultant|University of Penn: Advisor/Consultant|Vir: Advisor/Consultant|Wake Forest University: Advisor/Consultant|Washington University: Advisor/Consultant Helen Boucher, MD, ASM: Honoraria|Elsevier: Honoraria|Sanford Guide: Honoraria

Characteristics of Trials Preceding FDA Approval of Novel Psychiatric Drugs

This cross-sectional study reports on the study design characteristics of clinical trials for novel psychiatric drugs approved by the US Food and Drug Administration.

SERCA2a dysfunction in the pathophysiology of heart failure with preserved ejection fraction: a direct role is yet to be established.

With rising incidence, mortality and limited therapeutic options, heart failure with preserved ejection fraction (HFpEF) remains one of the most important topics in cardiovascular medicine today. Characterised by left ventricular diastolic dysfunction partially due to impaired Ca2+ homeostasis, one ion channel in particular, SarcoEndoplasmic Reticulum Ca2+-ATPase (SERCA2a), may play a significant role in its pathophysiology. A better understanding of the complex mechanisms interplaying to contribute to SERCA2a dysfunction will help develop treatments targeting it and thus address the growing clinical challenge HFpEF poses. This review examines the conflicting evidence present for changes in SERCA2a expression and activity in HFpEF, explores potential underlying mechanisms, and finally evaluates the drug and gene therapy trials targeting SERCA2a in heart failure. Recent positive results from trials involving widely used anti-diabetic agents such as sodium-glucose co-transporter protein 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) agonists offer advancement in HFpEF management. The potential interplay between these agents and SERCA2a regulation presents a novel angle that could open new avenues for modulating diastolic function; however, the mechanistic research in this emerging field is limited. Overall, the direct role of SERCA2a dysfunction in HFpEF remains undetermined, highlighting the need for well-designed pre-clinical studies and robust clinical trials.

Polydopamine nanoparticles loaded with sodium ferulate for targeted therapy of myocardial infarction in endothelial cells.

Myocardial infarction (MI) is a leading cause of heart failure and death in cardiovascular diseases. Most drug trials currently fail due to inadequate local drug activity and side effects. In this study, we developed a novel polydopamine (PDA) nano delivery system that carries sodium ferulate (SF) and is modified with RGD peptides (SF/RGD-PDA NPs) for precise targeted delivery. SF is a clinical adjuvant for cardiovascular and cerebrovascular diseases but lacks targeting and has a short half-life. PDA, known for its excellent biocompatibility and surface modifiability, serves as an effective carrier. SF was loaded onto PDA through π-π stacking, while RGD was attached via a Michael addition reaction, resulting in stable SF/RGD-PDA NPs with an average particle size of 206.13 nm. In vitro and in vivo studies indicate that this targeted formulation has good safety. Targeting studies showed a 2.19-fold increase in nanoparticle accumulation in the heart and a 5.94-fold increase in cellular uptake efficiency. Pharmacodynamic studies revealed a 1.45-fold increase in endothelial cell proliferation, a 1.46-fold increase in angiogenesis rate, and a significant reduction in MI area. These findings suggest that SF/RGD-PDA NPs can improve endothelial cell function and reduce MI area through targeted delivery.

The association between clinical trial participation, drug costs, and performance in the Oncology Care Model (OCM).

It has long been assumed that academic oncology practices are disadvantaged in value-based payment programs, due to patient complexity and research costs. This assumption not been tested. The Oncology Care Model (OCM) was a Medicare alternative payment model, which sought to curb costs while improving care. We assessed the impact of clinical trial (CT) participation on two outcomes: 1. cost and 2. practice performance among three participating NCI designated cancer centers using a random effects meta-analysis. The mean total Medicare cost per episode was $42,225 for CT episodes and $34,937 for non-CT episodes. Despite higher total costs, CT episodes were more likely to be under spending targets than non-CT episodes (odds ratio 0.37 (CI 0.25, 0.48). Drug costs in CT episodes were lower than in non-CT episodes, although this was only statistically significant at the largest volume practice. In conclusion, CTs may offer an advantage in value-based programs.

P0348 Ultrasound enterography with a novel ultrasound contrast agent for Crohn’s Disease

Abstract Background Gastrointestinal ultrasound (GIUS) is a method with both high sensitivity and specificity for evaluating disease activity in patients with Crohn’s disease. However, detecting and classifying stenosis and ulcerations can be challenging with GIUS. Developing an ultrasound method for detecting and categorising these findings would be of significant benefit to these patients. GIUS using an oral ultrasound contrast agent containing microbubbles is a new method with the potential to improve the intestinal ultrasound examination in patients with Crohn’s disease. The goal of this study is to investigate if intestinal ultrasound with oral contrast containing Sonazoid microbubbles in a PEG solution is a feasible and safe method in patients with Crohn’s disease. Methods 24 patients with Crohn’s disease in the terminal ileum (TI) was examined with ileocolonoscopy and intestinal ultrasound with oral contrast in a phase 2, single centre prospective cross-sectional drug trial. The ultrasound examination was done using Logiq E10 in contrast hybrid mode after ingestion of 1ml Sonazoid mixed with 500ml of PEG. The quality of the examination was graded 0-3 based on the amount of contrast in the lumen. In grade 3 the terminal ileum filled completely with contrast, and this was considered a successful examination. The contrast grade and transit time to TI after ingestion was documented along with symptoms, side effects and disease activity using "Mobile Health Index for Crohn’s Disease" before and after the study visit (1). Results All the included patients completed the ultrasound examination. The examination had a feasibility of 96 % as 23/24 patients achieved contrast effect grade 3 in TI with a clear separation of the intestinal wall and lumen. Average time from ingestion to grade 3 contrast effect in the TI was 20.8 min. Average duration of contrast effect grade 3 in the TI was 50.4 min. 50% of the patients had self-limiting diarrhea after the examination, however using paired samples T test there was no significant difference in average disease activity measured by MHICD before and after the examination (p=0.685). 96% of the patients agreed or completely agreed to undergo the examination again. Conclusion All except one patient achieved successful grade 3 contrast effect in the terminal ileum with a clear separation of the lumen and intestinal wall. Half of the patients had self-limiting diarrhea, but there was no increase in Crohn’s disease activity after the contrast examination. According to our study, ultrasound with oral contrast consisting of 1ml Sonazoid and 500ml PEG is a feasible and safe method to examine patients with Crohn’s disease.

Treating Hematological Malignancies With OR-2100, an Orally Bioavailable Prodrug of Decitabine.

DNA methylation is an enzyme-driven epigenetic modification that must be precisely regulated to maintain cellular homeostasis. Aberrant methylation status, especially hypermethylation of the promoter sites of tumor-suppressor genes, is observed in human malignancies and is a proven target for cancer therapy. The first-generation DNA demethylating agents, azacitidine and decitabine, are widely used for treating several hematological malignancies. In addition, orally bioavailable prodrugs of azacitidine and decitabine have recently been approved by the FDA. We have developed a silylated derivative of decitabine, OR-2100, which is resistant to degradation by cytidine deaminase and orally bioavailable. It has efficacy against several human hematological malignancies in xenograft mouse models with less hematotoxicity than decitabine. Since DNA demethylating agents are combined with molecularly targeted drugs in clinical use and trials, we think that the less hematotoxic profile of OR-2100 makes it suitable for use as a combination therapy. In this article, we review the therapeutic approach in hematological malignancies with the DNA demethylating agent OR-2100.

Military influences on the evolution of clinical trials throughout history.

Clinical trials of drugs, procedures, and other therapies play a crucial role in advancing medical science by evaluating the safety, efficacy, and optimal use of medical interventions. The design and implementation of these trials have evolved significantly over time, reflecting advancements in medicine, ethics, and methodology. Early historical examples, such as King Nebuchadnezzar II's and his captives' dietary experiment and Ambroise Paré's treatment of gunshot wounds, laid some foundational principles of trial design. The momentum of clinical trial development increased notably with James Lind's 1747 trial for scurvy and continued to progress during World War I with innovations in blood transfusion techniques. World War II (WWII) marked a pivotal moment with breakthroughs in oncology, including the development of the first modern chemotherapeutic agents derived from mustard gas and the introduction of the randomized controlled trial, credited to British epidemiologist Austin Bradford Hill, which revolutionized trial design. More recent conflicts, such as those in Vietnam, Iraq, and Afghanistan, have driven advancements in trauma care, heroin addiction treatment, and hemorrhage management. In response to historical abuses committed by the Nazis during WWII, the evolution of clinical trials has increasingly emphasized ethical standards, particularly informed consent, starting with the Doctors' Trial and the Nuremberg Code. This article discusses how military needs and wartime innovations have shaped modern clinical research, highlighting the interplay between military imperatives and medical progress. Ultimately, clinical trials play an essential role in advancing medical science and improving patient outcomes.

Impact of Preventive Intravenous Amiodarone on Reperfusion Ventricular Fibrillation in Patients With Left Ventricular Hypertrophy Undergoing Open-Heart Surgery: Randomized Controlled Clinical Trial.

Ventricular fibrillation (VF) is a vicious arrhythmia usually generated after removal of the aortic cross-clamp (ACC) in patients undergoing open-heart surgery, which could damage cardiomyocytes, especially in patients with left ventricular hypertrophy (LVH). Amiodarone has the prominent properties of converting VF and restoring sinus rhythm. However, few studies concentrated on the effect of amiodarone before ACC release on reducing VF in patients with LVH. The study was designed to explore the effectiveness of prophylactic intravenous amiodarone in reducing VF after the release of the ACC in patients with LVH. A total of 54 patients with LVH scheduled for open-heart surgery were enrolled and randomly divided (1:1) into 2 groups-group A (amiodarone group) and group P (placebo-controlled group). Thirty minutes before removal of the ACC, the trial drugs were administered intravenously. In group A, 150 mg of amiodarone was pumped in 15 minutes. In group P, the same volume of normal saline was pumped in 15 minutes. The primary outcome was the incidence of VF 10 minutes after removal of the ACC. The incidence of VF was lower in group A than in group P (30% vs 70%, P=.003). The duration of VF, the number of defibrillations, and the defibrillation energy were also lower in group A than in group P (P<.001, P=.002, and P=.002, respectively). After the end of cardiopulmonary bypass, the heart rate and mean arterial pressure were lower in group A, and the mean pulmonary arterial pressure and the dose of vasoactive drugs were higher than those in group P (P<.001, P<.001, P=.04, and P=.02, respectively). However, there were no significant differences in the use of vasoactive-inotropic agents and hemodynamic status between the 2 groups before the end of surgery. In patients with LVH who undergo open-heart surgery, amiodarone can be safely used to reduce the incidence of VF, the duration of VF, the frequency of defibrillation, and the energy of defibrillation after ACC removal.

Q&A with Lin Shen.

Professor Lin Shen, MD, graduated from Xuzhou Medical College in 1984 and Beijing Medical University in 1995. She trained at the US National Institutes of Health in 2000, focusing on therapies for gastrointestinal tumors. Currently, she is director of the Department of Gastrointestinal Oncology and Department of Early Drug Development Center, Peking University Cancer Hospital. Specializing in gastrointestinal oncology, she focuses on gastric, esophageal, colorectal, pancreatic, and gastrointestinal neuroendocrine cancers. She has led and participated in various national and international drug trials and steering committees.

Canine mammary tumors as a promising adjunct preclinical model for human breast cancer research: similarities, opportunities, and challenges.

Despite significant progress in the field of human breast cancer research and treatment, there is a consistent increase in the incidence rate of 0.5 percent annually, posing challenges in the development of effective novel therapeutic strategies. The failure rate of drugs in clinical trials stands at approximately 95%, primarily attributed to the limitations and lack of reliability of existing preclinical models, such as mice, which do not mimic human tumor biology. This article examines the potential utility of canine mammary tumors as an adjunct preclinical model for investigating human breast cancer. Given the numerous similarities between canine and human breast cancer, canines present a promising alternative model. The discussion delves into the intricate molecular and clinical aspects of human breast cancer and canine mammary tumors, shedding light on the tumors' molecular profiles, identifying specific molecular markers, and the application of radiological imaging modalities. Furthermore, the manuscript addresses the current constraints of preclinical cancer studies, the benefits of using canines as models, and the obstacles linked to the canine mammary tumors model. By concentrating on these elements, this review aims to highlight the viability of canine models in enhancing our understanding and management of human breast cancer.

Nelonemdaz and Patients With Acute Ischemic Stroke and Mechanical Reperfusion

Nelonemdaz selectively antagonizes the 2B subunit of the N-methyl-d-aspartate glutamate receptor and scavenges free radical species. To evaluate whether nelonemdaz enhances the clinical outcomes of patients with acute ischemic stroke undergoing emergent reperfusion therapy. This multicenter double-blind placebo-controlled randomized phase 3 trial (December 25, 2021, to June 30, 2023, in South Korea) recruited patients with acute ischemic stroke who met the following criteria: National Institutes of Health Stroke Scale score greater than or equal to 8, Alberta Stroke Program Early Computed Tomography score greater than or equal to 4, and endovascular thrombectomy within 12 hours after stroke onset. Patients were assigned in a 1:1 ratio to receive intravenous infusions of nelonemdaz twice a day for 5 days or a matching placebo. The primary end point was a favorable shift in the modified Rankin scale (mRS) 12 weeks after stroke onset. The secondary end points included various composites of the mRS at 5 and 12 weeks, symptomatic intracranial hemorrhage, and infarct volume. Both intention-to-treat and per-protocol analyses were conducted. A total of 496 patients were enrolled across 24 Korean stroke centers, of whom 39 dropped out (254 men [55.6%]; mean [SD] age, 72.9 [12.1] years). Baseline characteristics of study participants did not significantly differ. For the primary end point, the distribution of the mRS scores at 12 weeks did not significantly differ between the nelonemdaz and placebo groups (common odds ratio, 0.95; 95% CI, 0.69-1.31). For the secondary end points, a median of mRS at 5 weeks (3 vs 3) and mRS 0 at 12 weeks (18.1% vs 18.2%) did not differ substantially between groups. The occurrence of symptomatic intracranial hemorrhage (2.7% vs 0.9%) and infarct volume within 24 hours of the last trial drug infusion (42 vs 38 mL) did not differ significantly between groups. No serious adverse events were reported regarding the trial drug and placebo. In this randomized clinical trial, nelonemdaz did not meet the primary efficacy end point compared with placebo. ClinicalTrials.gov Identifier: NCT05041010.

Estimating direct tissue effects versus weight loss effects of incretin-based drugs for obesity on various chronic conditions.

The extent to which newer, incretin-based drugs for obesity improve disease outcomes via weight loss versus the direct effects of these drugs is the subject of intense interest. Although reductions in major adverse cardiovascular events appear to be predominantly driven by the direct tissue effects of such drugs, the associated weight loss effects must be relevant to the benefits observed in other major outcomes, albeit to differing extents. In this Personal View, we draw on evidence to support that weight loss is at least partly responsible (albeit to differing extents) for the reported benefits of incretin-based drugs for obesity in people living with heart failure with preserved ejection fraction, hypertension, chronic kidney disease, and type 2 diabetes. Concurrently, we propose that drug-induced weight loss is largely responsible for the reported improvements in osteoarthritis, obstructive sleep apnoea, and metabolic dysfunction-associated steatohepatitis outcomes. However, more evidence is needed to solidify these observations, including, when possible, trials comparing the effects of incretin-based drugs for obesity with calorie-reduced diets on both outcomes and mechanistic pathways. Such evidence has implications for public health and the design of future trials of novel drugs for obesity.

Open Innovation or Traditional Patenting Strategies to Efficiently Address Health Emergencies? How Patent Information Was Used Towards Effective Treatments for COVID-19.

During the 1150 days of COVID-19 pandemic there were great efforts to develop efficient treatments for the disease. After this long time, some drugs emerged as treatment for COVID-19. Some of them are new drugs, most of them, known drugs. These developments were triggered by information already available in patent documents. Pharmaceutical companies, therefore, rushed to conduct drugs evaluations and trials in order to deliver to the world a reasonable treatment that could reach the majority of its population. However, it is not immediately clear how companies operated to reach their goals. The ability of open innovation to achieve results assertively and faster than closed innovation strategies is questioned and therefore, it is questioned whether pharmaceutical companies use open innovation to face COVID-19. In this work, data available on patent databases were mined to inform about the scientific and technological panorama of selected drugs tested for COVID-19 treatment and to understand the perspectives of such developments during the pandemic. This study evidenced that most treatments were based on known drugs, that some of the initially promising drugs were abandoned during the pandemic, and that it was able to inform if open innovation and collaborations were explored strategies. This study evidenced that the developments during COVID-19 were not based on open innovation by revealing a patent race towards the treatment development, but with practically no collaborations or information exchange between companies, universities, and research facilities.

Defining ai applications in clinical routine

Despite the enormous interest in AI solutions for medical care the implementation has proven to be difficult. Issues include science of deep learning related to dataset shift, accidental fitting of confounders, unintended discriminatory bias, and generalization to new populations, logistical difficulties in implementation, sociocultural changes and patient perception, costs and burdens associated with false positives and false negatives, and number of non‐gradable images. The present talk will focus on the opportunities of AI. These may be related to improved diagnosis of disease but more likely to screening for common eye conditions such as diabetic retinopathy or glaucoma. In genomic medicine AI can recognize complex patterns of genetic variations linked with disease susceptibility and predict a spectrum of phenotypes. This topic is related to precision medicine and clinical decision support in order to tailor medical care to individual patients based on their unique characteristics. Population health management, establishment of working groups and guidelines, enhancing patient education, and clinical trial design and drug development are also discussed as potential areas of AI application in ophthalmology.

ODDB: An interactive database for clinical and translational research in ocular diseases

Aims/Purpose: To develop and validate a comprehensive web‐based interactive database of ocular diseases, including information of, for instance, associated genes, biomarkers, and medications.Methods: Initially, a thorough literature review was conducted to identify key ocular diseases and their associated genes and biomarkers. Data was then curated from multiple reputable sources, including peer‐reviewed journals, clinical trial repositories and drug regulatory agency databases. Advanced data integration techniques were employed to link various data types. The database interface was designed to allow intuitive navigation and robust querying capabilities, ensuring ease of access and data utilization. The database underwent internal testing to ensure user friendliness as well as data accuracy and reliability.Results: The resulting web‐based database encompasses detailed information on a wide array of ocular diseases. The diseases are categorized based on location of primary pathology in various parts of the eye, such as the cornea, retina, and optic nerve, among others. For each disease, the database provides a comprehensive list of biomarkers and associated genes, derived from scientific literature. Additionally, the database includes information of drug regulatory agency‐approved drugs and drugs currently undergoing clinical trials, with detailed descriptions of their therapeutic targets, mechanisms of action and clinical efficacy. The database also features tools for epidemiological analysis.Conclusions: This user‐friendly database of ocular diseases is a valuable resource for the scientific community, providing a wealth of information that can aid in the advancement of ophthalmology research. By consolidating data of biomarkers, genes, drugs and epidemiology, the database supports basic and clinical research, and facilitates the development of new therapeutic strategies. This initiative sets a precedent for future databases in other medical disciplines.

ODDB: An interactive database for clinical and translational research in ocular diseases

Aims/Purpose: To develop and validate a comprehensive web‐based interactive database of ocular diseases, including information of, for instance, associated genes, biomarkers, and medications.Methods: Initially, a thorough literature review was conducted to identify key ocular diseases and their associated genes and biomarkers. Data was then curated from multiple reputable sources, including peer‐reviewed journals, clinical trial repositories and drug regulatory agency databases. Advanced data integration techniques were employed to link various data types. The database interface was designed to allow intuitive navigation and robust querying capabilities, ensuring ease of access and data utilization. The database underwent internal testing to ensure user friendliness as well as data accuracy and reliability.Results: The resulting web‐based database encompasses detailed information on a wide array of ocular diseases. The diseases are categorized based on location of primary pathology in various parts of the eye, such as the cornea, retina, and optic nerve, among others. For each disease, the database provides a comprehensive list of biomarkers and associated genes, derived from scientific literature. Additionally, the database includes information of drug regulatory agency‐approved drugs and drugs currently undergoing clinical trials, with detailed descriptions of their therapeutic targets, mechanisms of action and clinical efficacy. The database also features tools for epidemiological analysis.Conclusions: This user‐friendly database of ocular diseases is a valuable resource for the scientific community, providing a wealth of information that can aid in the advancement of ophthalmology research. By consolidating data of biomarkers, genes, drugs and epidemiology, the database supports basic and clinical research, and facilitates the development of new therapeutic strategies. This initiative sets a precedent for future databases in other medical disciplines.

A RANDOMISED CONTROLLED CLINICAL STUDY TO EVALUATE THE EFFECT OF SHATAPUTI ABHRAKA BHASMA IN KSHEENA RETAS VIS-A-VIS OLIGOSPERMIA

Background: Ksheena retas is a condition where Shukra is moderately decreased, especially in the middle age due to etiology undefined in this type, the body growth, pubertal development and level of Shukra may be normal initially until the etiological factors bring about a fall.Here the cause could be Aharajanya (Katu, Kashaya Rasa), Viharajanya (Abhighata), Vyadhikarshaaa etc. it leads to qualitative or quantitative decrease in the retas.In the present context ksheenaretas can be taken as quantitative decrease in the sperm count. Oligospermia is defined as a reduction in the sperm count below 20 million. it is a major cause of male infertility which is characterized by reduced level of sperm. In the literature, it is mentioned as alpamatrasnehapana (24ml) act as deepana and vrishya.Shataputi Abhraka Bhasma is mentiond as param vrushya and shukrala in the literature in the present study this ShataputiabhrakaBhasma is administerd as trial drug. so an attempt was made in the present study to evaluate the efficacy of shataputi Abhraka Bhasma in trial group B and shatavaryadigritha(indigenous formulation) in control group A. Objective:To evaluate the effect of ShataputiAbhraka Bhasma in ksheenaretas vis-a-vis Oligospermia. Method: It is a Randomised controlled clinical study with pre and post-test design. Shatavaryadighrita (indigenous formulation) prepared was administerdin group A for 30 days. AndShataputiabhraka Bhasmain group B for 30 days. Results: Mean sperm count of 13.125mill/ml was increased in control group A and mean sperm count of 2.7143mill/ml was decreased in trial group B after the intervention. Conclusion: it can be concluded from the result that control drug shatavaryadigritha is effective in the management of Ksheena retas and Shataputi Abhraka Bhasma proved insignificant.