New Drug Formulary Management and Utilization: Evidence in Sex, Race, and Ethnicity: 2019-2020

2021 ◽  
pp. 106002802110197
Author(s):  
Christopher A. Keeys ◽  
Benjamin W. Harding ◽  
Gina E. Migneco ◽  
Sina S. Rahini ◽  
Hope B. Coleman
Keyword(s):  
Race And Ethnicity ◽  
Minority Groups ◽  
Demographic Data ◽  
Disease State ◽  
New Drugs ◽  
Utilization Review ◽  
Formulary Management ◽  
The Us ◽  
Approved Drugs ◽  
Fda Approved Drugs

Background It is well established that females and persons of racial and ethnic minorities are frequently underrepresented in clinical trials. These disparities are potentially important aspects of evidence-based formulary management and drug utilization review (DUR) processes. Objective The purpose of this study was to review the demographic composition of pivotal trials and post-approval study requirements for recent FDA-approved drugs, analyzing the representation of minority groups and its generalizability to the US population or corresponding disease state. Methods Drugs approved between July 2019 and June 2020 were identified and demographic data including race, ethnicity, and sex was extracted from their pivotal trials. Demographic data was compared to US demographics and/or the disease state demographics for the respective approved drug. Results There were a total of 85 drugs and 142 pivotal trials included in the study. Compared to the estimated US population, the minority groups with a statistically significant underrepresentation across all pivotal trials included Black or African Americans and American Indian or Alaska Natives. The Hispanic/Latinx population had a statistically significant underrepresentation in 55.4% of trials. Females had a statistically significant underrepresentation in 21.2% of trials when compared to the disease state demographics of the respective approved drug. Conclusion and Relevance Persons of minorities are underrepresented in the generation of evidence of safety and efficacy for many new drugs. Formulary management and DUR offer an integrated strategic opportunity for the clinical community to formally and carefully consider the data on sex, race, and ethnicity to address disparities in health care.

Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies

2019 ◽  
Vol 143 (1) ◽  
pp. 73-77
Author(s):  
Anat Gafter-Gvili ◽  
Ariadna Tibau ◽  
Pia Raanani ◽  
Daniel Shepshelovich
Keyword(s):  
Hematological Malignancies ◽  
New Drugs ◽  
Priority Review ◽  
Regulatory Review ◽  
Regulatory Pathways ◽  
The Us ◽  
Black Box Warnings ◽  
Accelerated Approval ◽  
Drug Approvals ◽  
Approved Drugs

The prevalence of safety-related postmarketing label modifications of medications for hematological malignancies is unknown. We identified 35 new drugs indicated for hematological malignancies approved by the US Food and Drug Administration between January 1999 and December 2014. Characteristics of supporting trials and safety-related label modifications from approval to December 2017 were collected from drug labels. Regulatory review and approval pathways were also collected. New drug approvals were supported by trials with a median of 167 patients (interquartile range 115–316). All drugs were approved based on surrogate endpoints. Twenty-seven drug approvals (77%) were not supported by randomized controlled trials. All drugs received orphan drug designation, and most were granted fast track designation, priority review, and accelerated approval (83, 74, and 60%, respectively). A total of 28 drugs (80%) had postmarketing safety-related label modifications. Additions to black box warnings, contraindications, warnings and precautions, and common adverse reactions were identified in 31, 11, 77, and 46% of drugs, respectively. Five drugs (14%) were permanently or temporarily withdrawn from the US market. Drugs for hematological malignancies are often approved based on limited evidence through expedited regulatory pathways with incomplete safety profiles. Hematologists should be vigilant for unrecognized side effects when prescribing newly approved drugs.

scholarly journals PS4DR: A multimodal workflow for identification and prioritization of drugs based on pathway signatures

2020 ◽  
Author(s):  
Mhammad Asif Emon ◽  
Daniel Domingo-Fernández ◽  
Charles Tapley Hoyt ◽  
Martin Hofmann-Apitius
Keyword(s):  
Gene Expression ◽  
Genome Wide Association Study ◽  
Drug Repositioning ◽  
Heterogeneous Data ◽  
New Drugs ◽  
Gwas Data ◽  
Drug Candidates ◽  
Gene Expression Signatures ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract Background: During the last decade, there has been a surge towards computational drug repositioning owing to constantly increasing -omics data in the biomedical research field. While numerous existing methods focus on the integration of heterogeneous data to propose candidate drugs, it is still challenging to substantiate their results with mechanistic insights of these candidate drugs. Therefore, there is a need for more innovative and efficient methods which can enable better integration of data and knowledge for drug repositioning. Results: Here, we present a customizable workflow ( PS4DR) which not only integrates high-throughput data such as genome-wide association study (GWAS) data and gene expression signatures from disease and drug perturbations but also takes pathway knowledge into consideration to predict drug candidates for repositioning. We have collected and integrated publicly available GWAS data and gene expression signatures for several diseases and hundreds of FDA-approved drugs or those under clinical trial in this study. Additionally, different pathway databases were used for mechanistic knowledge integration in the workflow. Using this systematic consolidation of data and knowledge, the workflow computes pathway signatures that assist in the prediction of new indications for approved and investigational drugs. Conclusion: We showcase PS4DR with applications demonstrating how this tool can be used for repositioning and identifying new drugs as well as proposing drugs that can simulate disease dysregulations. We were able to validate our workflow by demonstrating its capability to predict FDA-approved drugs for their known indications for several diseases. Further, PS4DR returned many potential drug candidates for repositioning that were backed up by epidemiological evidence extracted from scientific literature. Source code is freely available at https://github.com/ps4dr/ps4dr .

scholarly journals Screening of FDA Approved Drugs Against COVID-19 Main Protease: Coronavirus Disease

2020 ◽  
Author(s):  
Vijayakumar Balakrishnan ◽  
Karthik Lakshminarayanan
Keyword(s):  
Vaccine Development ◽  
New Drugs ◽  
World Health ◽  
Wuhan City ◽  
Drug Candidates ◽  
Human Contact ◽  
Main Protease ◽  
Potent Drug ◽  
Approved Drugs ◽  
Fda Approved Drugs

In the end of December 2019, a new strain of coronavirus was identified in the Wuhan city of Hubei province in China. Within a shorter period of time, an unprecedented outbreak of this strain was witnessed over the entire Wuhan city. This novel coronavirus strain was later officially renamed as COVID-19 (Coronavirus disease 2019) by the World Health Organization. The mode of transmission had been found to be human-to-human contact and hence resulted in a rapid surge across the globe where more than 1,100,000 people have been infected with COVID-19. In the current scenario, finding potent drug candidates for the treatment of COVID-19 has emerged as the most challenging task for clinicians and researchers worldwide. Identification of new drugs and vaccine development may take from a few months to years based on the clinical trial processes. To overcome the several limitations involved in identifying and bringing out potent drug candidates for treating COVID-19, in the present study attempts were made to screen the FDA approved drugs using High Throughput Virtual Screening (HTVS). The COVID-19 main protease (COVID-19 Mpro) was chosen as the drug target for which the FDA approved drugs were initially screened with HTVS. The drug candidates that exhibited favorable docking score, energy and emodel calculations were further taken for performing Induced Fit Docking (IFD) using Schrodinger’s GLIDE. From the flexible docking results, the following four FDA approved drugs Sincalide, Pentagastrin, Ritonavir and Phytonadione were identified. In particular, Sincalide and Pentagastrin can be considered potential key players for the treatment of COVID-19 disease.

scholarly journals RepCOOL: computational drug repositioning via integrating heterogeneous biological networks

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Ghazale Fahimian ◽  
Javad Zahiri ◽  
Seyed Shahriar Arab ◽  
Reza H. Sajedi
Keyword(s):  
Breast Cancer ◽  
Biological Networks ◽  
Drug Repositioning ◽  
Machine Learning Algorithms ◽  
New Drugs ◽  
Stage Ii ◽  
Cancer Stage ◽  
New Drug ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract Background It often takes more than 10 years and costs more than 1 billion dollars to develop a new drug for a particular disease and bring it to the market. Drug repositioning can significantly reduce costs and time in drug development. Recently, computational drug repositioning attracted a considerable amount of attention among researchers, and a plethora of computational drug repositioning methods have been proposed. This methodology has widely been used in order to address various medical challenges, including cancer treatment. The most common cancers are lung and breast cancers. Thus, suggesting FDA-approved drugs via drug repositioning for breast cancer would help us to circumvent the approval process and subsequently save money as well as time. Methods In this study, we propose a novel network-based method, named RepCOOL, for drug repositioning. RepCOOL integrates various heterogeneous biological networks to suggest new drug candidates for a given disease. Results The proposed method showed a promising performance on benchmark datasets via rigorous cross-validation. The final drug repositioning model has been built based on a random forest classifier after examining various machine learning algorithms. Finally, in a case study, four FDA approved drugs were suggested for breast cancer stage II. Conclusion Results show the potency of the proposed method in detecting true drug-disease relationships. RepCOOL suggested four new drugs for breast cancer stage II namely Doxorubicin, Paclitaxel, Trastuzumab, and Tamoxifen.

scholarly journals Targeted Therapy for Advanced Thyroid Cancer: Kinase Inhibitors and Beyond

2019 ◽  
Vol 40 (6) ◽  
pp. 1573-1604 ◽  
Author(s):  
Maria E Cabanillas ◽  
Mabel Ryder ◽  
Camilo Jimenez
Keyword(s):  
Thyroid Cancer ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Rapid Evolution ◽  
Anaplastic Thyroid Cancer ◽  
The Us ◽  
Advanced Thyroid Cancer ◽  
Inhibitor Drug ◽  
Approved Drugs ◽  
Fda Approved Drugs

Abstract The treatment of advanced thyroid cancer has undergone rapid evolution in the last decade, with multiple kinase inhibitor drug approvals for each subtype of thyroid cancer and a number of other commercially available drugs that have been studied for this indication. Although most of the US Food and Drug Administration (FDA)–approved drugs are antiangiogenic multikinase inhibitors—vandetanib, cabozantinib, sorafenib, lenvatinib—there are two FDA indications that are mutation specific—dabrafenib/trametinib for BRAF-mutated anaplastic thyroid cancer and larotrectinib for NTRK-fusion thyroid cancer. Furthermore, other mutation-specific drugs, immunotherapies, and novel strategies for advanced thyroid cancer are under investigation. Understanding the molecular basis of thyroid cancer, the drugs of interest for treatment of advanced thyroid cancer, and how these drugs can be administered safely and in the appropriate clinical scenario are the topics of this review.

scholarly journals Repurposing of Linagliptin Similar FDA Approved Drugs as Antidiabetic Agents

2021 ◽  
Vol 10 (4) ◽  
pp. 2766-2776
Keyword(s):  
Metabolic Diseases ◽  
Drug Repurposing ◽  
Binding Energies ◽  
New Drugs ◽  
Epidemic Disease ◽  
Global Epidemic ◽  
Dpp Iv ◽  
Epidemiology Data ◽  
Approved Drugs ◽  
Fda Approved Drugs

Diabetes mellitus is considered a global epidemic disease and is one of the metabolic diseases affecting individuals irrespective of age, sex, and race. According to WHO epidemiology data, the DM prevalence globally has risen from 4.7% to 8.5 % from 1980 to 2014. The discovery of new drugs has become more challenging for the pharmaceutical companies even though major investment has made in the conventional drug discovery approach. To overcome this obstacle, drug repurposing is an emerging field of development where an existing drug is tested for treatment. Successful repurposing of zidovudine, minoxidil, sildenafil, celecoxib, aspirin, and topiramate are reported for respective diseases. The present study focused on the computational approach to fetch the favorable drugs from the pool of FDA approved drugs against diabetes. Initially, structure similarity studies were carried out by using the template structure of standard DPP-IV inhibitor, Linagliptin. About 26 drugs have shown similarity, and the other 14 drugs filtered by Pass Online binding energies are determined by molecular docking at the binding site of DPP-IV (PDB ID 2i78). Among these, pranlukast and mirabegron have shown good binding interactions with dock scores of -13.81 and -13.06.

scholarly journals Potential RNA-dependent RNA polymerase inhibitors as prospective therapeutics against SARS-CoV-2

2020 ◽  
Vol 69 (6) ◽  
pp. 864-873 ◽  
Author(s):  
Rudramani Pokhrel ◽  
Prem Chapagain ◽  
Jessica Siltberg-Liberles
Keyword(s):  
Rna Polymerase ◽  
In Silico ◽  
Species Barrier ◽  
Rna Dependent Rna Polymerase ◽  
Virtual Screen ◽  
The Us ◽  
Approved Drugs ◽  
Dynamics Simulations ◽  
Fda Approved Drugs

Introduction. The emergence of SARS-CoV-2 has taken humanity off guard. Following an outbreak of SARS-CoV in 2002, and MERS-CoV about 10 years later, SARS-CoV-2 is the third coronavirus in less than 20 years to cross the species barrier and start spreading by human-to-human transmission. It is the most infectious of the three, currently causing the COVID-19 pandemic. No treatment has been approved for COVID-19. We previously proposed targets that can serve as binding sites for antiviral drugs for multiple coronaviruses, and here we set out to find current drugs that can be repurposed as COVID-19 therapeutics. Aim. To identify drugs against COVID-19, we performed an in silico virtual screen with the US Food and Drug Administration (FDA)-approved drugs targeting the RNA-dependent RNA polymerase (RdRP), a critical enzyme for coronavirus replication. Methodology. Initially, no RdRP structure of SARS-CoV-2 was available. We performed basic sequence and structural analysis to determine if RdRP from SARS-CoV was a suitable replacement. We performed molecular dynamics simulations to generate multiple starting conformations that were used for the in silico virtual screen. During this work, a structure of RdRP from SARS-CoV-2 became available and was also included in the in silico virtual screen. Results. The virtual screen identified several drugs predicted to bind in the conserved RNA tunnel of RdRP, where many of the proposed targets were located. Among these candidates, quinupristin is particularly interesting because it is expected to bind across the RNA tunnel, blocking access from both sides and suggesting that it has the potential to arrest viral replication by preventing viral RNA synthesis. Quinupristin is an antibiotic that has been in clinical use for two decades and is known to cause relatively minor side effects. Conclusion. Quinupristin represents a potential anti-SARS-CoV-2 therapeutic. At present, we have no evidence that this drug is effective against SARS-CoV-2 but expect that the biomedical community will expeditiously follow up on our in silico findings.

Drug discovery of small molecules for the treatment of COVID-19: A review on clinical studies

2020 ◽  
Vol 21 ◽  
Author(s):  
Bharat Goel ◽  
Nivedita Bhardwaj ◽  
Nancy Tripathi ◽  
Shreyans K. Jain
Keyword(s):  
Small Molecules ◽  
Clinical Studies ◽  
Ebola Virus ◽  
Viral Infections ◽  
New Drugs ◽  
Zoonotic Virus ◽  
Traditional Medicines ◽  
Novel Coronavirus ◽  
Approved Drugs ◽  
Fda Approved Drugs

: Recently, a sudden outbreak of novel coronavirus disease (COVID-19) was caused by a zoonotic virus known as severe acute respiratory syndrome coronavirus (SARS-CoV-2). It has caused pandemic situations around the globe and affecting the lives of millions of people. So far, no drug has been approved for the treatment of SARS-CoV-2 infected patients. As of now, more than 1000 clinical trials are going on for repurposing of FDA approved drugs and for evaluating the safety & efficiency of experimental antiviral molecules to combat COVID-19. Since the development of new drugs may require months to years to reach the market, this review focusses on the potentials of existing small molecule FDA approved drugs and the molecules already in the clinical pipeline against viral infections like HIV, hepatitis B, Ebola virus, and other viruses of coronavirus family (SARS-CoV and MERS-CoV). The review also discusses the natural products and traditional medicines in clinical studies against COVID-19. Currently, 1978 studies are active, 143 completed and 4 posted results (as on June 13, 2020) on clinicaltrials.gov.

Benzodiazepines, Amphetamines, Testosterone and Sildenafil as New Candidates Drugs for Sexual Interest, Desire and/or Arousal Disorder

2021 ◽  
Vol 10 ◽  
Author(s):  
Richard Joseph Wix ◽  
Ezequiel Uribe
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Side Effects ◽  
Sexual Interest ◽  
New Drugs ◽  
Hypoactive Sexual Desire Disorder ◽  
Arousal Disorder ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Desire Disorder

Background: The FDA approved drugs for female sexual interest, desidere and/or arousal disorder (FSIAD), and hypoactive sexual desire disorder (HSDD), however this have low tolerability for patients because its multiple side effects and does not show real therapeutic efficacy. Hypoactive Sexaul Desire affects from 750.000.000 to 1.400.000.000 people worldwide. Methods: In this paper we analyze therapeutic candidate in clinical practice as well as the methodologies clinical trials of possible therapeutic targets of different systems related to the dysfunction. Results: Therefore New Drugs (Benzodiazepines, Amphetamines, Testosterone, Sildenafil or New Compound) Clinical Trials to treat this disorder are necessary.

Classification of Coronavirus (COVID-19) Treatments and Drugs Based on Mechanism of Action, Efficacy, and Safety

2020 ◽  
Vol 9 (2) ◽  
Author(s):  
Mahi Ravi ◽  
William Jackson
Keyword(s):  
Mechanism Of Action ◽  
Death Rate ◽  
Rapid Development ◽  
Mechanisms Of Action ◽  
Efficacy And Safety ◽  
Novel Drugs ◽  
The Us ◽  
Approved Drugs ◽  
Fda Approved Drugs

The recently discovered coronavirus SARS-CoV-2 has forced countries into lockdown, people into quarantines, and economies to a standstill. Currently there are no FDA approved treatments for COVID-19, the disease caused by this new coronavirus strain. With over 2.8 million cases in the US as of July 3 and a death rate of approximately 5.9%, an effective treatment is urgently needed (Center for Disease Control [CDC], 2020). To date there are few comprehensive reviews of therapeutic options for COVID-19. Here we present the general types and mechanisms of action for drugs currently available or in rapid development. This paper highlights FDA approved drugs that can be repurposed and therefore used immediately to test for coronavirus efficacy as well as novel drugs and vaccines specifically targeted to COVID-19 vulnerabilities.

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