Pub Date : 2024-03-04DOI: 10.1101/2024.03.04.24303714
Nina Timmesfeld, Peter Ihle, Robin Denz, Katharina Meiszl, Katrin Scholz, Doris Oberle, Ursula Drechsel-Baeuerle, Brigitte Keller-Stanislawski, Hans H. Diebner, Ingo Meyer
In Germany, there has been no population-level pharmaco-epidemiological study on the safety of the Covid-19 vaccines. One factor preventing such a study so far relates to challenges combining the different relevant data bodies on vaccination with suitable outcome data, specifically statutory health insurance claims data. Individual identifiers used across these data bodies are of unknown quality and reliability for data linkage. As part of a larger pharmaco-vigilance study on the COVID-19 vaccines, called RiCO (German "Risikoevaluation der COVID-19-Impfstoffe", Englisch "Risk assessment of COVID-19 vaccines"), a feasibility study is being conducted to determine the overall confidence level with which existing data can be analysed in relation to the safety of the COVID-19 vaccine. This RiCO feasibility study will establish a dataflow combining claims data and vaccination data for a sub-sample of the total German population, describe data quality for each data set from the various sources, estimate the proportion of the different linkage errors and will develop various approaches for linking the data in addition to the simple form of linkage using a common identifier in order to reduce possible linkage errors. These last three points are the core objective of the feasibility study. A secondary objective is to test the viability of the required dataflow involving multiple stakeholders from different parts of the healthcare system. Results will be published and used to plan the actual pharmaco-vigilance study on the COVID-19 vaccines for Germany, as well as future research on the role of COVID vaccines as risk or protective factors for long-term COVID-19 effects.
{"title":"Determining the feasibility of linked claims and vaccination data for a Covid-vaccine pharmaco-epidemiological study in Germany - RiCO feasibility study protocol","authors":"Nina Timmesfeld, Peter Ihle, Robin Denz, Katharina Meiszl, Katrin Scholz, Doris Oberle, Ursula Drechsel-Baeuerle, Brigitte Keller-Stanislawski, Hans H. Diebner, Ingo Meyer","doi":"10.1101/2024.03.04.24303714","DOIUrl":"https://doi.org/10.1101/2024.03.04.24303714","url":null,"abstract":"In Germany, there has been no population-level pharmaco-epidemiological study on the safety of the Covid-19 vaccines. One factor preventing such a study so far relates to challenges combining the different relevant data bodies on vaccination with suitable outcome data, specifically statutory health insurance claims data. Individual identifiers used across these data bodies are of unknown quality and reliability for data linkage. As part of a larger pharmaco-vigilance study on the COVID-19 vaccines, called RiCO (German \"Risikoevaluation der COVID-19-Impfstoffe\", Englisch \"Risk assessment of COVID-19 vaccines\"), a feasibility study is being conducted to determine the overall confidence level with which existing data can be analysed in relation to the safety of the COVID-19 vaccine. This RiCO feasibility study will establish a dataflow combining claims data and vaccination data for a sub-sample of the total German population, describe data quality for each data set from the various sources, estimate the proportion of the different linkage errors and will develop various approaches for linking the data in addition to the simple form of linkage using a common identifier in order to reduce possible linkage errors. These last three points are the core objective of the feasibility study. A secondary objective is to test the viability of the required dataflow involving multiple stakeholders from different parts of the healthcare system. Results will be published and used to plan the actual pharmaco-vigilance study on the COVID-19 vaccines for Germany, as well as future research on the role of COVID vaccines as risk or protective factors for long-term COVID-19 effects.","PeriodicalId":501447,"journal":{"name":"medRxiv - Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140037780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In clinical drug development, two fundamental questions remain unanswered: what is the success rate of drugs in clinical trial? how does such rate change over time? Herein, a systematic analysis on the dynamic change of drugs' clinical success rates (ClinSRs) using data from 20,398 clinical trial pipelines of 9,682 unique molecular entities during the past two decades was presented. Our analysis discovered that ClinSRs had been declining since the beginning of 21st century, and hit the bottom in recent years even substantially lower than previous estimates. In-depth assessments further reported great variation among the ClinSRs of various diseases, developmental strategies, and drug modalities. A platform ClinSR.org (http://ClinSR.idrblab.org/) was finally constructed online to enable the illustration of how ClinSR dynamically changes over time, automated update of ClinSR for the coming decade, and customized calculation of ClinSRs for any drug group of interest. In sum, this study met the critical demand for accurate, timely and persistent assessment of ClinSR, for now and the future, to aid pharmaceutical and economic decision making.
{"title":"Dynamic Clinical Success Rates for Drugs in the 21st Century","authors":"Ying Zhou, Yintao Zhang, Zhen Chen, Shijie Huang, Yinghong Li, Jianbo Fu, Hongning Zhang, Donghai Zhao, Xichen Lian, Yuan Zhou, Xinyi Shen, Yunqing Qiu, Lianyi Han, Feng Zhu","doi":"10.1101/2024.02.26.24303388","DOIUrl":"https://doi.org/10.1101/2024.02.26.24303388","url":null,"abstract":"In clinical drug development, two fundamental questions remain unanswered: what is the success rate of drugs in clinical trial? how does such rate change over time? Herein, a systematic analysis on the dynamic change of drugs' clinical success rates (ClinSRs) using data from 20,398 clinical trial pipelines of 9,682 unique molecular entities during the past two decades was presented. Our analysis discovered that ClinSRs had been declining since the beginning of 21st century, and hit the bottom in recent years even substantially lower than previous estimates. In-depth assessments further reported great variation among the ClinSRs of various diseases, developmental strategies, and drug modalities. A platform ClinSR.org (http://ClinSR.idrblab.org/) was finally constructed online to enable the illustration of how ClinSR dynamically changes over time, automated update of ClinSR for the coming decade, and customized calculation of ClinSRs for any drug group of interest. In sum, this study met the critical demand for accurate, timely and persistent assessment of ClinSR, for now and the future, to aid pharmaceutical and economic decision making.","PeriodicalId":501447,"journal":{"name":"medRxiv - Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140001723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-29DOI: 10.1101/2024.02.27.24303441
Michael S Ringel, Julie Dethier, Michelle J. Davitt, Maria Denslow, R. Andrew Fowler, Sebastian C. Hasenfuss, Ulrik Schulze
In this paper, we investigate what conditions need to be in place to make progress in combating a disease using a case-control design: we compare cases (diseases with a successful therapy) to controls (diseases without a successful therapy). We find five conditions ('hurdles') must typically be cleared for success: (A) understanding of biological drivers, (B) ability to modulate biology, (C) availability of translational models, (D1) ability to identify patients, and (D2) ability to measure clinical response. This framework is similar to ones deployed to evaluate individual drug candidates but is employed here to make inferences about entire diseases. It can be used to identify diseases most ready for progress, where efforts should be focused to make progress in diseases that are currently intractable, and where the industry could benefit from development of tools to address the hurdle that is most commonly the last to be cleared across diseases-namely, (C) translational models.
{"title":"What does it take to make progress in a disease?","authors":"Michael S Ringel, Julie Dethier, Michelle J. Davitt, Maria Denslow, R. Andrew Fowler, Sebastian C. Hasenfuss, Ulrik Schulze","doi":"10.1101/2024.02.27.24303441","DOIUrl":"https://doi.org/10.1101/2024.02.27.24303441","url":null,"abstract":"In this paper, we investigate what conditions need to be in place to make progress in combating a disease using a case-control design: we compare cases (diseases with a successful therapy) to controls (diseases without a successful therapy). We find five conditions ('hurdles') must typically be cleared for success: (A) understanding of biological drivers, (B) ability to modulate biology, (C) availability of translational models, (D1) ability to identify patients, and (D2) ability to measure clinical response. This framework is similar to ones deployed to evaluate individual drug candidates but is employed here to make inferences about entire diseases. It can be used to identify diseases most ready for progress, where efforts should be focused to make progress in diseases that are currently intractable, and where the industry could benefit from development of tools to address the hurdle that is most commonly the last to be cleared across diseases-namely, (C) translational models.","PeriodicalId":501447,"journal":{"name":"medRxiv - Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140001721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: During hemodialysis (HD), the presence of clots in the dialyzer can diminish the effective surface area of the device. In severe cases, clot formation in the circuit can halt treatment and lead to blood loss in the system. Thus, ensuring proper anticoagulation during HD is crucial to prevent clotting in the circuit while safeguarding the patient from bleeding risks. This study aimed to evaluate anticoagulation outcomes and related factors in HD patients with acute kidney injury (AKI) at selected hospitals in Ethiopia. Method: A prospective, multicenter observational study was carried out between October 1, 2021, and March 31, 2022. The study encompassed all AKI patients undergoing HD at least once during the study period. Descriptive statistics were utilized to summarize the data, and multinomial logistic regression analysis was employed to identify factors associated to clotting and bleeding. Results: Data were gathered from 1010 HD procedures conducted on 175 patients. Extracorporeal circuit clotting was detected in 34 patients during 39 (3.9%) dialysis sessions, while bleeding incidents occurred in 27 patients across 29 (2.9%) sessions. A statistically significant association was found between both the total number of HD treatments and blood flow rate with incidents of clotting. Factors such as length of hospitalization, serum creatinine levels at admission, signs and symptoms associated with uremia, along with utilization of anticoagulants or antiplatelet medications demonstrated an association with bleeding events. Conclusion: Clotting affected 19.4% of participants, while bleeding occurred in 15.4%, underscoring the importance of close monitoring. The frequency of HD sessions and blood flow rate are correlated with clotting, while hospitalization duration, serum creatinine levels, uremic symptoms, and anticoagulant use are associated with bleeding events.
简介：在血液透析（HD）过程中，透析器中出现的血凝块会减小设备的有效表面积。在严重情况下，回路中形成的血凝块会导致治疗中断，并导致系统失血。因此，在血液透析过程中确保适当的抗凝至关重要，这样既能防止回路中出现血凝块，又能保护患者免受出血风险。本研究旨在评估埃塞俄比亚部分医院的急性肾损伤（AKI）血液透析患者的抗凝结果及相关因素：方法：2021 年 10 月 1 日至 2022 年 3 月 31 日期间开展了一项前瞻性多中心观察研究。研究范围包括研究期间至少接受过一次 HD 治疗的所有 AKI 患者。研究采用描述性统计来总结数据，并采用多项式逻辑回归分析来确定与凝血和出血相关的因素：结果：共收集了 175 名患者的 1010 例 HD 手术数据。在 39 次（3.9%）透析过程中，有 34 名患者检测到体外回路凝血，而在 29 次（2.9%）透析过程中，有 27 名患者发生出血。经统计发现，血液透析治疗的总次数和血流速度与凝血事件之间存在明显的关联。住院时间、入院时血清肌酐水平、尿毒症相关体征和症状以及使用抗凝剂或抗血小板药物等因素均与出血事件有关：19.4%的参与者发生了凝血，15.4%的参与者发生了出血，这凸显了密切监测的重要性。血液透析疗程的频率和血流量与凝血有关，而住院时间、血清肌酐水平、尿毒症症状和抗凝药物的使用与出血事件有关。
{"title":"Anticoagulation-related complications and their outcomes in hemodialysis patients with acute kidney injury at selected hospitals in Ethiopia.","authors":"Hanan Muzeyin Kedir, Abdella Birhan Yabeyu, Addisu Melkie Ejigu, Tamrat Assefa Tadesse, Eskinder Ayalew Sisay","doi":"10.1101/2024.02.28.24303493","DOIUrl":"https://doi.org/10.1101/2024.02.28.24303493","url":null,"abstract":"Introduction: During hemodialysis (HD), the presence of clots in the dialyzer can diminish the effective surface area of the device. In severe cases, clot formation in the circuit can halt treatment and lead to blood loss in the system. Thus, ensuring proper anticoagulation during HD is crucial to prevent clotting in the circuit while safeguarding the patient from bleeding risks. This study aimed to evaluate anticoagulation outcomes and related factors in HD patients with acute kidney injury (AKI) at selected hospitals in Ethiopia.\u0000Method: A prospective, multicenter observational study was carried out between October 1, 2021, and March 31, 2022. The study encompassed all AKI patients undergoing HD at least once during the study period. Descriptive statistics were utilized to summarize the data, and multinomial logistic regression analysis was employed to identify factors associated to clotting and bleeding.\u0000Results: Data were gathered from 1010 HD procedures conducted on 175 patients. Extracorporeal circuit clotting was detected in 34 patients during 39 (3.9%) dialysis sessions, while bleeding incidents occurred in 27 patients across 29 (2.9%) sessions. A statistically significant association was found between both the total number of HD treatments and blood flow rate with incidents of clotting. Factors such as length of hospitalization, serum creatinine levels at admission, signs and symptoms associated with uremia, along with utilization of anticoagulants or antiplatelet medications demonstrated an association with bleeding events.\u0000Conclusion: Clotting affected 19.4% of participants, while bleeding occurred in 15.4%, underscoring the importance of close monitoring. The frequency of HD sessions and blood flow rate are correlated with clotting, while hospitalization duration, serum creatinine levels, uremic symptoms, and anticoagulant use are associated with bleeding events.","PeriodicalId":501447,"journal":{"name":"medRxiv - Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140001874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-23DOI: 10.1101/2024.02.22.24303086
Yuchen Guo, Tingjie Guo, Catherijne A.J. Knibbe, Laura B. Zwep, J.G. Coen van Hasselt
Incorporating realistic sets of patient-associated covariates, i.e., virtual populations, in pharmacometric simulation workflows is essential to obtain realistic model predictions. Current covariate simulation strategies often omit or simplify dependency structures between covariates. Copula models are multivariate distribution functions suitable to capture dependency structures between covariates with improved performance compared to standard approaches. We aimed to develop and evaluate a copula model for generation of adult virtual populations for 12 patient-associated covariates commonly used in pharmacometric simulations, using the publicly available NHANES database, including sex, race-ethnicity, body weight, albumin, and several biochemical variables related to organ function. A multivariate (vine) copula was constructed from bivariate relationships in a stepwise fashion. Covariate distributions were well captured for the overall and subgroup populations. Based on the developed copula model, a web application was developed. The developed copula model and associated web application can be used to generate realistic adult virtual populations, ultimately to support model-based clinical trial design or dose optimization strategies.
{"title":"Generation of realistic virtual adult populations using a model-based copula approach","authors":"Yuchen Guo, Tingjie Guo, Catherijne A.J. Knibbe, Laura B. Zwep, J.G. Coen van Hasselt","doi":"10.1101/2024.02.22.24303086","DOIUrl":"https://doi.org/10.1101/2024.02.22.24303086","url":null,"abstract":"Incorporating realistic sets of patient-associated covariates, i.e., virtual populations, in pharmacometric simulation workflows is essential to obtain realistic model predictions. Current covariate simulation strategies often omit or simplify dependency structures between covariates. Copula models are multivariate distribution functions suitable to capture dependency structures between covariates with improved performance compared to standard approaches. We aimed to develop and evaluate a copula model for generation of adult virtual populations for 12 patient-associated covariates commonly used in pharmacometric simulations, using the publicly available NHANES database, including sex, race-ethnicity, body weight, albumin, and several biochemical variables related to organ function. A multivariate (vine) copula was constructed from bivariate relationships in a stepwise fashion. Covariate distributions were well captured for the overall and subgroup populations. Based on the developed copula model, a web application was developed. The developed copula model and associated web application can be used to generate realistic adult virtual populations, ultimately to support model-based clinical trial design or dose optimization strategies.","PeriodicalId":501447,"journal":{"name":"medRxiv - Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139954855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. This is a post-hoc analysis of a double-blinded clinical trial involving 80 generally healthy adults aged 40 to 65 years. The participants received a placebo or daily 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration, blood biological age, homeostatic model assessment for insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline and after supplement. A significant dose-dependent increase in NAD concentration change (NADΔ) was observed following NMN supplementation, with a large coefficient of variation (29.2-113.3%) within group. The increase in NADΔ was associated with an improvement in the walking distance of 6-minute walk test and the SF-36 score. The median effect dose of NADΔ for the 6-minute walk test and SF-36 score was 15.7 nmol/L (95% CI: 10.9-20.5 nmol/L) and 13.5 nmol/L (95% CI; 10.5-16.5 nmol/L), respectively. Because of the high interindividual variability of the NADΔ after NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalized dosage regimens and optimizing NMN utilization. Keywords: nicotinamide mononucleotide, NAD, clinical trial, precision medicine, dietary supplements
{"title":"Towards personalized nicotinamide mononucleotide supplementation: nicotinamide adenine dinucleotide concentration","authors":"Ajla Hodzic Kuerec, Weilan Wang, Lin Yi, Rongsheng Tao, Zhigang Lin, Aditi Vaidya, Sohal Pendse, Sornaraja Thasma, Niranjan Andhalkar, Ganesh Avhad, Vidyadhar Kumbhar, Andrea Britta Maier","doi":"10.1101/2024.02.19.24303025","DOIUrl":"https://doi.org/10.1101/2024.02.19.24303025","url":null,"abstract":"Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. This is a post-hoc analysis of a double-blinded clinical trial involving 80 generally healthy adults aged 40 to 65 years. The participants received a placebo or daily 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration, blood biological age, homeostatic model assessment for insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline and after supplement. A significant dose-dependent increase in NAD concentration change (NADΔ) was observed following NMN supplementation, with a large coefficient of variation (29.2-113.3%) within group. The increase in NADΔ was associated with an improvement in the walking distance of 6-minute walk test and the SF-36 score. The median effect dose of NADΔ for the 6-minute walk test and SF-36 score was 15.7 nmol/L (95% CI: 10.9-20.5 nmol/L) and 13.5 nmol/L (95% CI; 10.5-16.5 nmol/L), respectively. Because of the high interindividual variability of the NADΔ after NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalized dosage regimens and optimizing NMN utilization. Keywords: nicotinamide mononucleotide, NAD, clinical trial, precision medicine, dietary supplements","PeriodicalId":501447,"journal":{"name":"medRxiv - Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139924195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-21DOI: 10.1101/2024.02.19.24303055
Zhixiang Ren, Yiming Ren, Zeting Li, Huan Xu
Mining the potential of traditional Chinese medicine (TCM) in treating modern diseases requires a profound understanding of its action mechanism and a comprehensive knowledge system that seamlessly bridges modern medical insights with traditional theories. However, existing databases for modernizing TCM are plagued by varying degrees of information loss, which impede the multidimensional dissection of pharmacological effects. To address this challenge, we introduce traditional Chinese medicine modernization (TCMM), the currently largest modernized TCM database that integrates pioneering intelligent pipelines. By aligning high-quality TCM and Western medicine data, TCMM boasts the most extensive TCM modernization knowledge, including 20 types of modernized TCM concepts such as prescription, ingredient, target and 46 biological relations among them, totaling 3,447,023 records. We demonstrate the efficacy and reliability of TCMM with two features, prescription generation and knowledge discovery, the outcomes show consistency with biological experimental results. A publicly available web interface is at https://www.tcmm.net.cn/.
{"title":"TCMM: A Unified Database for Traditional Chinese Medicine Modernization and Therapeutic Innovations","authors":"Zhixiang Ren, Yiming Ren, Zeting Li, Huan Xu","doi":"10.1101/2024.02.19.24303055","DOIUrl":"https://doi.org/10.1101/2024.02.19.24303055","url":null,"abstract":"Mining the potential of traditional Chinese medicine (TCM) in treating modern diseases requires a profound understanding of its action mechanism and a comprehensive knowledge system that seamlessly bridges modern medical insights with traditional theories. However, existing databases for modernizing TCM are plagued by varying degrees of information loss, which impede the multidimensional dissection of pharmacological effects. To address this challenge, we introduce traditional Chinese medicine modernization (TCMM), the currently largest modernized TCM database that integrates pioneering intelligent pipelines. By aligning high-quality TCM and Western medicine data, TCMM boasts the most extensive TCM modernization knowledge, including 20 types of modernized TCM concepts such as prescription, ingredient, target and 46 biological relations among them, totaling 3,447,023 records. We demonstrate the efficacy and reliability of TCMM with two features, prescription generation and knowledge discovery, the outcomes show consistency with biological experimental results. A publicly available web interface is at https://www.tcmm.net.cn/.","PeriodicalId":501447,"journal":{"name":"medRxiv - Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139924224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-30DOI: 10.1101/2024.01.27.24301085
Errien M. Williams, Mariam Camara, Jessica L. Goldhirsh, Brian J. Piper
Abstract: Due to the uncertainty of the health effects medical marijuana poses, states differ in their medical marijuana laws (MML). Long-term effects of marijuana are found to be like attention-deficit-hyperactive disorder (ADHD). With amphetamines being prescribed to treat ADHD symptoms we hypothesized that amphetamine prescriptions would increase in states implementing MML. The number of amphetamine prescriptions filled quarterly for each state from 2006 to 2021 were calcu-lated. States with MML and dispensaries opened before 2020 were examined and states with no MML laws were the control. Prism was utilized to visualize the data and conduct four t-tests be-tween the pre and post of MML+ versus MML- states. Three MML+ states were excluded due to limited post-MML data. Among the remaining states, 31 were MML+ and 17 were MML-. No significant differences were found in amphetamine prescribing (p > 0.30). Medical marijuana legalization did not have a statistically significant impact on amphetamine prescribing in Medicaid patients during the analyzed period. Contrary to the hypothesis, the results revealed a non-significant de-crease in prescriptions in MML+ states. Further research with recreational cannabis laws or with electronic health records is warranted. Keywords: Attention Deficit Hyperactivity Disorder; cannabis; stimulant
{"title":"Medical Marijuana Had No Impact on Amphetamine Prescribing in Medicaid","authors":"Errien M. Williams, Mariam Camara, Jessica L. Goldhirsh, Brian J. Piper","doi":"10.1101/2024.01.27.24301085","DOIUrl":"https://doi.org/10.1101/2024.01.27.24301085","url":null,"abstract":"Abstract: Due to the uncertainty of the health effects medical marijuana poses, states differ in their medical marijuana laws (MML). Long-term effects of marijuana are found to be like attention-deficit-hyperactive disorder (ADHD). With amphetamines being prescribed to treat ADHD symptoms we hypothesized that amphetamine prescriptions would increase in states implementing MML. The number of amphetamine prescriptions filled quarterly for each state from 2006 to 2021 were calcu-lated. States with MML and dispensaries opened before 2020 were examined and states with no MML laws were the control. Prism was utilized to visualize the data and conduct four t-tests be-tween the pre and post of MML+ versus MML- states. Three MML+ states were excluded due to limited post-MML data. Among the remaining states, 31 were MML+ and 17 were MML-. No significant differences were found in amphetamine prescribing (p > 0.30). Medical marijuana legalization did not have a statistically significant impact on amphetamine prescribing in Medicaid patients during the analyzed period. Contrary to the hypothesis, the results revealed a non-significant de-crease in prescriptions in MML+ states. Further research with recreational cannabis laws or with electronic health records is warranted. Keywords: Attention Deficit Hyperactivity Disorder; cannabis; stimulant","PeriodicalId":501447,"journal":{"name":"medRxiv - Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139583666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-23DOI: 10.1101/2024.01.22.24301594
Luca Marzano, Adam S. Darwich, Asaf Dan, Salomon Tendler, Rolf Lewensohn, Luigi De Petris, Jayanth Raghothama, Sebastiaan Meijer
The potential of real-world data to inform clinical trial design and supplement control arms has gained much interest in recent years. The most common approach relies on matching real-world patient cohorts to clinical trial baseline covariates using propensity score techniques. However, recent studies pointed out that there is a lack of replicability, generalisability, and consensus. Further, few studies consider differences in operational processes. Systematically accounting for confounders, including hidden effects related to the clinical treatment process and clinical trial study protocol, would potentially allow for improved translation between clinical trial and real-world data and enable learning across translational activities. In this paper, we propose an approach that aims to explore and examine these confounders by investigating the impact of selection criteria and operations on the measurements of outcome. We tested the approach on small cell lung cancer patients receiving platinum-based chemotherapy regimens (n=1,224). The results showed that the discrepancy between real-world and clinical trial data potentially depends on differences in covariate characteristics and operations (e.g., censoring mechanism, the process of pre-trial patient selection related to ECOG-performance status 2 patients). This work builds on current approaches and suggests areas of improvement for systematically accounting for differences in outcomes between study cohorts. Continued development of the method presented here could pave the way for transferring learning across studies and developing mutual translation between the real-world and clinical trials to inform future studies design.
{"title":"Overcoming the discrepancies between RCTs and real-world data by accounting for Selection criteria, Operations, and Measurements of Outcome (SOMO)","authors":"Luca Marzano, Adam S. Darwich, Asaf Dan, Salomon Tendler, Rolf Lewensohn, Luigi De Petris, Jayanth Raghothama, Sebastiaan Meijer","doi":"10.1101/2024.01.22.24301594","DOIUrl":"https://doi.org/10.1101/2024.01.22.24301594","url":null,"abstract":"The potential of real-world data to inform clinical trial design and supplement control arms has gained much interest in recent years. The most common approach relies on matching real-world patient cohorts to clinical trial baseline covariates using propensity score techniques. However, recent studies pointed out that there is a lack of replicability, generalisability, and consensus. Further, few studies consider differences in operational processes. Systematically accounting for confounders, including hidden effects related to the clinical treatment process and clinical trial study protocol, would potentially allow for improved translation between clinical trial and real-world data and enable learning across translational activities. In this paper, we propose an approach that aims to explore and examine these confounders by investigating the impact of selection criteria and operations on the measurements of outcome. We tested the approach on small cell lung cancer patients receiving platinum-based chemotherapy regimens (n=1,224). The results showed that the discrepancy between real-world and clinical trial data potentially depends on differences in covariate characteristics and operations (e.g., censoring mechanism, the process of pre-trial patient selection related to ECOG-performance status 2 patients). This work builds on current approaches and suggests areas of improvement for systematically accounting for differences in outcomes between study cohorts. Continued development of the method presented here could pave the way for transferring learning across studies and developing mutual translation between the real-world and clinical trials to inform future studies design.","PeriodicalId":501447,"journal":{"name":"medRxiv - Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-17DOI: 10.1101/2024.01.16.24301341
Muktar B. Ahmed, Anwar Mulugeta, Niran Okewole, Klaus Oliver Schubert, Scott R. Clark, Conrad O. Iyegbe, Azmeraw T. Amare
Background Pharmacogenomic studies on psychiatric drugs have slowly identified genetic variations that influence drug metabolism and treatment effectiveness in patients with mental illness. Because most of these studies predominantly centered on people of European descent, there remains a substantial knowledge gap on the clinical implications of current pharmacogenomic evidence in multi-ancestry populations such as Africans. Thus, whether pharmacogenomic (PGx) genetic testing implemented in European populations would be valid for a population of African origin is unknown. The objective of this review was to appraise previous psychiatric pharmacogenomic studies in Africa and highlight challenges and opportunities to initiate PGx testing in the region.
{"title":"Pharmacogenomic diversity in psychiatry: Challenges and Opportunities in Africa","authors":"Muktar B. Ahmed, Anwar Mulugeta, Niran Okewole, Klaus Oliver Schubert, Scott R. Clark, Conrad O. Iyegbe, Azmeraw T. Amare","doi":"10.1101/2024.01.16.24301341","DOIUrl":"https://doi.org/10.1101/2024.01.16.24301341","url":null,"abstract":"<strong>Background</strong> Pharmacogenomic studies on psychiatric drugs have slowly identified genetic variations that influence drug metabolism and treatment effectiveness in patients with mental illness. Because most of these studies predominantly centered on people of European descent, there remains a substantial knowledge gap on the clinical implications of current pharmacogenomic evidence in multi-ancestry populations such as Africans. Thus, whether pharmacogenomic (PGx) genetic testing implemented in European populations would be valid for a population of African origin is unknown. The objective of this review was to appraise previous psychiatric pharmacogenomic studies in Africa and highlight challenges and opportunities to initiate PGx testing in the region.","PeriodicalId":501447,"journal":{"name":"medRxiv - Pharmacology and Therapeutics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139499119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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