Smoking continues to be the leading preventable contributor to death worldwide. Twin studies have suggested a significant genetic contribution underlying most smoking behaviours (40-70% heritability estimates). Candidate gene studies of […]» Read more
Uncontrolled Extensions of Clinical Trials and the Use of External Controls – scoping opportunities and methods.
Increased interest in real-world evidence (RWE) for clinical and regulatory decision making and the need to evaluate long-term benefits and risks of pharmaceutical products raise the importance of understanding the […]» Read more
A semi-mechanistic pharmacokinetic model for depot medroxyprogesterone acetate and drug-drug interactions with antiretroviral and antituberculosis treatment.
Depot medroxyprogesterone acetate (DMPA) is an injectable hormonal contraceptive, widely used by women of childbearing potential living with HIV and/or tuberculosis. As medroxyprogesterone acetate (MPA) is a CYP3A4 substrate, drug-drug […]» Read more
A drug is granted a license for use after a thorough assessment of risks and benefits based on high quality scientific proof of its efficacy and safety. Many drugs that […]» Read more
Launched in 2002, adalimumab (Humira) is the top revenue-generating drug in the US. Between 2016 and 2019, the US Food and Drug Administration tentatively approved 5 adalimumab biosimilars, yet none […]» Read more
The human leukocyte antigen (HLA) system is the most polymorphic in the human genome that has been associated with protection and predisposition to a broad array of infectious, autoimmune, and […]» Read more
Creatinine clearance is an important tool to describe the renal elimination of drugs in pharmacokinetic evaluations and clinical practice. In critically ill patients, unstable kidney function invalidates the steady state […]» Read more
Pharmacogenetics (PGx) research over the past two decades has produced extensive evidence for the influence of genetic factors on the efficacy and tolerability of antipsychotic treatment. However, the application of […]» Read more
Medication errors during treatment with new oral anticancer agents: consequences for clinical practice based on the AMBORA study.
Patients treated with oral anticancer agents (e.g. kinase inhibitors) are a high-risk population for medication errors due to e.g. polymedication, age, and limited adherence. Systematic evaluations regarding frequencies and causes […]» Read more
The evidence for pharmacogenetics has grown rapidly in recent decades. However, the strength of evidence required for the clinical implementation of pharmacogenetics is highly debated. Therefore, the purpose of this […]» Read more
The Impact of Variability in Patient Exposure During Premarket Clinical Development on Postmarket Safety Outcomes.
We characterized the size of the premarket safety population for 278 small-molecule new molecular entities (NMEs) and 61 new therapeutic biologics (NTBs) approved by FDA between October 1, 2002 and […]» Read more
A Study of Regulatory Challenges of Paediatric Oncology Phase I/II Trial Submissions and Guidance on Protocol Development.
The purpose of this study was to identify key deficiencies in paediatric oncology early phase clinical trial protocols in Germany and to provide guidance for efficient trial protocol development. A […]» Read more
Association between FIASMAs and Reduced Risk of Intubation or Death in Individuals Hospitalized for Severe COVID-19: an observational multicenter study.
Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide […]» Read more
Interaction between SNP Genotype and Efficacy of Anastrozole and Exemestane in Early Stage Breast Cancer.
Aromatase inhibitors (AI) are the treatment of choice for hormone receptor-positive early breast cancer in postmenopausal women. None of the third-generation AIs are superior to the others in terms of […]» Read more
Pharmacogenetic-guided treatment of depression: real-world clinical applications, challenges and perspectives.
Depression is a leading cause of disability worldwide and despite the availability of numerous antidepressants, the lack of standardised criteria to apply personalised prescription is still a major issue. Pharmacogenetic […]» Read more
Assessing the Impact of FDA Breakthrough Therapy Designation Timing on Trial Characteristics and Development Speed.
Congress created the Breakthrough Therapy designation in 2012 to expedite drug development and review through efficient clinical trial design and intensive interaction with United States (US) Food and Drug Administration […]» Read more
Polypharmacy is common among patients taking prescription opioids long-term, and the co-dispensing of interacting medications may further increase opioid overdose risk. To identify non-opioid medications that may increase opioid overdose […]» Read more
This study aimed to analyse associations between genetic variants and the occurrence of clinical outcomes in dabigatran, apixaban, and rivaroxaban users. This was a retrospective real-world study linking genotype data […]» Read more
Quantitative Clinical Pharmacology Supports the Bridging from IV Dosing and Approval of SC Rituximab in B-Cell Hematological Malignancies.
A fixed-dose subcutaneous (SC) formulation of the anti-CD20 antibody, rituximab, has been developed to address safety, infusion time, and patient comfort concerns relating to intravenous (IV) dosing, and has been […]» Read more
Pharmacogenetics (PGx) seeks to enable selection of the right dose of the right drug for each patient to optimize therapeutic outcomes. Most PGx focuses on pharmacokinetics (PK), due to our […]» Read more
Plasmodium vivax is the most widespread human malaria parasite, with 2.5 billion people at risk of infection worlwide. P. vivax forms liver hypnozoites which trigger further symptomatic episodes (relapses) weeks […]» Read more
Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for the use of aminoglycosides based on MT-RNR1 genotype.
Aminoglycosides are widely used antibiotics with notable side effects such as nephrotoxicity, vestibulotoxicity and sensorineural hearing loss (cochleotoxicity). MT-RNR1 is a gene that encodes the 12s rRNA subunit and is […]» Read more
The development of drugs for coronavirus disease 2019 (COVID-19) is a global challenge. In Japan, remdesivir was approved in May 2020 for COVID-19 caused by the severe acute respiratory syndrome […]» Read more
Opioids are commonly prescribed following childbirth, but data are lacking on trends in postpartum opioid prescribing over time. We examined whether a highly-publicized 2006 case report questioning the safety of […]» Read more
Calibrating real-world evidence studies against randomized trials: treatment effectiveness of infliximab in Crohn’s disease.
Real-world evidence (RWE) on the effectiveness of treatments in Crohn’s disease (CD) derived from clinical practice data will help fill many evidence gaps left by randomized controlled trials (RCTs). Emulating […]» Read more
The Orphan Drug Act (ODA) of 1983 was enacted to provide financial incentives to drug sponsors to develop therapies for rare diseases. Although this act increased the number of orphan […]» Read more
Computational tools to assess the functional consequences of rare and noncoding pharmacogenetic variability.
Inter-individual differences in drug response are a common concern in both drug development and across layers of care. While genetics clearly influence drug response and toxicity of many drugs, a […]» Read more
Exposure-Response Relationships in Patients With HER2-Positive Metastatic Breast Cancer and Other Solid Tumors Treated With Trastuzumab Deruxtecan.
Trastuzumab deruxtecan (T-DXd) is a HER2-targeting antibody-drug conjugate composed of a novel enzyme-cleavable linker and membrane-permeable topoisomerase I inhibitor payload. T-DXd has been approved for HER2-positive metastatic breast cancer (BC) […]» Read more
Safety, Tolerability, and Pharmacokinetics of FAAH Inhibitor BIA 10-2474: A Double-Blind, Randomised, Placebo-Controlled Study in Healthy Volunteers.
This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of BIA 10-2474, a FAAH inhibitor, after first administration to healthy male and female subjects. Subjects (n=116) were recruited into this […]» Read more
Cost-sharing increase, medication adherence and hospitalizations in schizophrenia patients: a natural experiment.
Increases in medication cost-sharing rates remain a controversial system-wide cost-containment measure for chronic mental health patients. The objective was to investigate the effects of cost-sharing increases on adherence to prescribed […]» Read more