The utilisation and safety of analgesics: a pharmacoepidemiologic and pharmacogenomic study
Medications such as paracetamol, ibuprofen (also known as non-steroidal anti-inflammatory drugs or NSAIDs) and opioids are a vital tool for patients to relieve pains. But, like all drugs, they can have serious side effects when misused.
For example, most of the opioids in the market were initially developed for the treatment of acute pains or pains from malignant cancers. Still, it has been increasingly used to manage other chronic illness such as osteoarthritis and other musculoskeletal disorders pains. Currently, there is no clinical trial conducted to evaluate opioids safety (side effects) on these chronic conditions, due to the enormous cost and numerous pragmatic issues of following up patients for a long period in trials settings. Although the post-market pharmacoepidemiologic study provides a good evidence complement for clinical trials, it suffers from several limitations in identifying adverse drug effects, which may limit its ability to determine causality. In this project, we propose to use Mendelian randomisation to assess whether adverse effects are causally related to the use of pain relievers.
Furthermore, not all patients respond to the same pain killer in the same way, because the effect of pain killers is influenced by patients' genetic background as well as socio-demographic and environmental factors. Previous small pharmacogenetics studies suggested that gene such as CYP2D6 can significantly affect pain-relieving drugs metabolism. They also indicated individuals who were poor or super metabolisers of these drugs had increased risk of side-effects. Therefore, this project will explore to what extent the genetic factors explain the interpatient variability in response to different pain killers and develop an easy-to-use clinical prediction model to identify patients vulnerable to the severe side effect.
We plan to complete this project in three years and answer the most relevant and pressing questions regarding typical analgesics.
The results from this research could provide better information for decision-makers, doctors, patients and the general population on the safety of common analgesics and valuable evidence to deliver personalised treatment for individual patients.