ArticleDrug safety2018
Using Human 'Experiments of Nature' to Predict Drug Safety Issues: An Example with PCSK9 Inhibitors.
Article in Drug safety, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed.
- PCSK9 Loss-of-Function Disrupts Cellular Microfilament Network via LIN28A/HES5/JMY Axis in Neural Tube Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach.European journal of medical research · 2025Review
- Pregnancy 3 months after inclisiran injection: a unique case report including newborn baby monitoring.European heart journal. Case reports · 2025Article
- PCSK9 genetic variants and risk of vascular and non-vascular diseases in Chinese and UK populations.European journal of preventive cardiology · 2024Article
- Genetically proxied low-density lipoprotein cholesterol lowering via PCSK9-inhibitor drug targets and risk of congenital malformations.European journal of preventive cardiology · 2024Article
- Repurposing N-acetylcysteine for management of non-acetaminophen induced acute liver failure: an evidence scan from a global health perspective.Translational gastroenterology and hepatology · 2024Article
- Medication history-wide association studies for pharmacovigilance of pregnant patients.Communications medicine · 2022Article
- Human and Machine Intelligence Together Drive Drug Repurposing in Rare Diseases.Frontiers in genetics · 2021Article
- EHRs could clarify drug safety in pregnant people.Nature medicine · 2020Article
- Leveraging Human Genetics to Identify Safety Signals Prior to Drug Marketing Approval and Clinical Use.Drug safety · 2020Article
- A Phenome-Wide Association Study Uncovers a Pathological Role of Coagulation Factor X duringInfection and immunity · 2019Article
- Genomic and Phenomic Research in the 21st Century.Trends in genetics : TIG · 2019Review
- Comment on "Using Human 'Experiments of Nature' to Predict Drug Safety Issues: An Example with PCSK9 Inhibitors".Drug safety · 2018Article
- Electronic health records: the next wave of complex disease genetics.Human molecular genetics · 2018Review
- When Enough Is Enough: Decision Criteria for Moving a Known Drug into Clinical Testing for a New Indication in the Absence of Preclinical Efficacy Data.Assay and drug development technologies · 2017Article
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Authors and funding
9 authors.
Funding
Abstract
introductionWhen a new drug enters the market, its full array of side effects remains to be defined. Current surveillance approaches targeting these effects remain largely reactive. There is a need for development of methods to predict specific safety events that should be sought for a given new drug during development and postmarketing activities.
objectiveWe present here a safety signal identification approach applied to a new set of drug entities, inhibitors of the serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9).
methodsUsing phenome-wide association study (PheWAS) methods, we analyzed available genotype and clinical data from 29,722 patients, leveraging the known effects of changes in PCSK9 to identify novel phenotypes in which this protein and its inhibitors may have impact.
resultsPheWAS revealed a significantly reduced risk of hypercholesterolemia (odds ratio [OR] 0.68, p = 7.6 × 10
conclusionThis novel methodology provides an opportunity to put in place new mechanisms to assess the safety and long-term tolerability of PCSK9 inhibitors specifically, and other new agents in general, as they move into human testing and expanded clinical use.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.