Every year, one in five people with advanced chronic kidney disease is harmed by their own medications. These patients—98% of whom have multiple long-term conditions—take an average of 8 to 9 drugs daily, but their reduced kidney function makes drug metabolism unpredictable and accumulation dangerous. The World Health Organization calls polypharmacy an urgent patient safety issue, yet there are no evidence-based guidelines for safely reducing or stopping medications—deprescribing—in this group. This project will change that. Using England-wide data from OpenSAFELY-TPP, the researcher will first map current deprescribing patterns and identify which clinical and social factors drive variations. A systematic review will then assess the evidence for ongoing effectiveness, potential harms, and deprescribing of 3 to 5 specific medicines. Finally, a target trial emulation study will test the causal effect of deprescribing one of those drugs on patient outcomes. If successful, the work will provide the first robust evidence base for deprescribing in advanced kidney disease, directly informing future clinical guidelines and reducing medication-related harm for a vulnerable population.
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Research Question For people living with chronic kidney disease stages 4 and 5 (CKD 4/5), what are the patterns of, evidence for, and outcomes following deprescribing? Background Polypharmacy is recognized by the World Health Organization as an urgent and increasing patient safety issue. For some, polypharmacy can lead to unintentional medication-related harm. People living with CKD 4/5, 98% of whom are living with multiple long-term conditions, are at particular risk for harm. They are prescribed on average 8-9 medications each day, and their reduced kidney function can lead to unpredictable metabolism and accumulation of drugs. Each year, 1 in 5 of these individuals experience medication-related harm. A potential way to reduce medication-related harm is by deprescribing. A minority of medicines are contraindicated in CKD 4/5 and are easy to deprescribe, but for most, decisions are less clear. There are currently no evidence-based deprescribing guidelines for people living with CKD 4/5. This project will generate findings to change this, and in turn reduce the risk of medication-related harm for patients. Aim To determine current patterns of deprescribing for people living with CKD 4/5, and generate evidence for the clinical effectiveness and safety of deprescribing that can inform future practice. Objectives Among individuals living with CKD 4/5: Describe the current patterns of deprescribing in England, and identify clinical and sociodemographic factors associated with variances in these patterns. Systematically review and analyse the evidence for: a) ongoing effectiveness, b) potential harms, and c) deprescribing of a set of 3-5 medicines. Design, conduct and evaluate a target trial emulation study to examine the causal effect of deprescribing a medication on relevant outcomes. Methods Work package 1 - Descriptive deprescribing patterns analysis (months 1-15) I will conduct a quantitative analysis of England-wide deprescribing patterns in people living with CKD 4/5 using data from OpenSAFELY-TPP. Cross-sectional and longitudinal analyses will be performed to establish which medicines are being prescribed, how much (and of what) deprescribing is occurring, and what factors are affecting deprescribing patterns. Work package 2 - Systematic review (months 7-20) I will perform a systematic review and meta-analysis to establish the evidence for a) ongoing effectiveness, b) potential harms, and c) deprescribing of medicines, specifically within people living with CKD 4/5. A set of 3-5 medicines will be chosen for study based on the input from patients and supervisors. Work package 3 - Target trial emulation study (months 13-30) I will design a hypothetical randomised controlled trial that studies the causal effect of deprescribing a medicine on outcomes of interest within individuals living with CKD 4/5. The medication (and associated outcomes) will be chosen for study based on evidence from work packages 1 and 2. I will emulate the trial within OpenSAFELY-TPP, and then evaluate its success and limitations. Anticipated impact and dissemination My research will provide a new understanding of the safety and efficacy of deprescribing in people living with CKD 4/5, and lead to post-doctoral work in which I will create evidence-based deprescribing guidelines to benefit patients, clinicians and healthcare services.
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