Chronic pain is estimated to affect approximately 35% of the UK adult population, impacting on daily functioning, sleep patterns and mental health. In addition, chronic pain places a large burden upon health systems with an estimated 20% of primary-care workload related to pain. Relief for pain can be provided by a variety of medications but for severe pain, strong opioids may be recommended. However, opioids have a variety of side effects including those that affect the gastro-intestinal system such as constipation and nausea. These may cause the patient to stop taking the opioid, thereby failing to offer pain relief, or the complications may need additional health interventions resulting in increased health contacts and associated costs. In a previous study we reported that one particular opioid, tapentadol, was associated with fewer gastro-intestinal side effects compared to two other strong opioids (morphine and oxycodone). In this study, we wish to consider the impact of where tapentadol is prescribed in the pain pathway on side effects and health service costs. To do this we wish to select patients in the Clinical Practice Research Datalink (CPRD) treated with tapentadol and define them as either early initiators if they had tapentadol prescribed as their first strong opioid or late initiators if they had tapentadol prescribed following an alternate strong opioid. We then wish to compare rates of gastro-intestinal side-effects and health care utilisation with patients of a similar profile treated with two alternate strong opioids (morphine or oxycodone).
The study aims to determine if there is an association between gastrointestinal outcomes and early treatment with tapentadol compared to treatment with morphine or oxycodone. Patients will be selected from CPRD AURUM with a prescription for tapentadol SR recorded between May 2011 and April 2019. A prior pain pathway will be estimated by combining over-lapping prescriptions of non-opioids, co-analgesics, weak opioids and strong opioids for pain management. First prescription of tapentadol SR will define index date. Patients prescribed tapentadol as the first therapy within the strong opioid category during their pain episode will be defined as early initiators, those prescribed tapentadol subsequent to an alternate strong opioid will be defined as late initiators. Both cohorts of tapentadol patients will be matched to two sets of controls at a ratio of 1:2, the first treated with morphine and the second treated with oxycodone. The primary outcome will be time to adverse gastrointestinal event, secondary outcomes will be time to either constipation or nausea, primary and secondary care resource use and associated costs. Rates of progression to the primary outcome will be presented and compared using Cox proportional hazard models (CPHM) adjusting for smoking status, Charlson Index, total number of contacts with the general practitioner in the year prior to the index date, and quintile of the Index of Multiple Deprivation. Rates of resource use and associated costs will be compared using regression models based on the Poisson and Gamma distributions respectively.
Baseline characteristics; pain aetiology; pain site; adverse events, opioid related disorders, opioid related deaths; primary care contacts, outpatient contacts, accident and emergency contacts, inpatient contacts.
Christopher Morgan - Chief Investigator - Pharmatelligence Limited t/a Human Data Sciences
Christopher Morgan - Corresponding Applicant - Pharmatelligence Limited t/a Human Data Sciences
Garth Baxter - Collaborator - Grünenthal Ltd. UK
Sara Jenkins-Jones - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
Sara Jenkins-Jones - Collaborator - Pharmatelligence Limited t/a Human Data Sciences
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation