Can frailty predict medication-related harm?

Dr Jennifer Stevenson is a Clinical Pharmacy Lecturer at King’s College London and Guy’s and St. Thomas’ NHS Foundation Trust. Her PhD explored the prediction of medication-related harm in older adults after discharge from an acute episode of care, as part of the PRIME Study. Jennifer, and her colleague Dr Nikesh Parekh (Clinical Research Fellow at Brighton and Sussex Medical School) have looked into the association between frailty and medication-related harm which they presented at the EUGMS Annual Congress in Berlin. Jennifer tweets @JenMStevenson   

The PRIME team almost didn’t make it to Berlin. Fog grounded all planes departing from London Gatwick Airport. The complex systems and supports utilised to ensure that a near-capacity airport can function were damaged, some might say disproportionately to the degree of the insult. Frailty was influencing our travel and was, in part, the cause of our travel; to deliver a platform presentation on “Frailty Predicts Medication-related Harm requiring healthcare: A UK multi-centre prospective cohort study, the PRIME Study”. Overcoming the insult, we made it to Berlin and were awarded best oral communication.

The PRIME Study aimed to develop a risk prediction model that would identify older adults most at risk of experiencing medication-related harm (MRH) after discharge from hospital. This is an attractive line of enquiry. As the study reported, harm is common, and a significant proportion is deemed preventable (37% of participants experienced MRH within 8 weeks of discharge and 52% of cases were potentially preventable). Prediction could facilitate patient prioritisation, case load management and more efficient, and hopefully effective, targeting of interventions – in theory. 

In reality, we are stuck at the identification stage. Systematic review of the literature(ditto) suggests that current prediction models have only modest predictive ability and so are not suitable for clinical practice. Many commonalities exist between these models, including development methods, lack of external validation and a focus on medicines and disease-related predictors. Whilst these variables are important, it is recognised that not all patients with multiple comorbidities and complex medication regimes experience harm from their medicines. 

Moving beyond disease and medicine-related variables and adopting a more holistic approach may be required which incorporates the psychological and social systems that influence medicines. Furthermore, perhaps it is those who have risks, or deficits across multiple systems (disease, medicines and/or psychosocial) that are increasingly vulnerable to MRH.  Parallels may be drawn between this theory and the concept of frailty. Frailty is recognised to increase an individual’s risk of experiencing adverse health outcomes when exposed to an external stressor and when this external stressor is a medicine, the outcome may be MRH.

This hypothesis was supported by the results from the PRIME Study, where a greater number of frail patients experienced MRH than non-frail patients and a significant relationship between frailty and MRH was identified even when potential confounders such as age and polypharmacy were controlled for. Given this, a more holistic approach to MRH may be required and whilst this won’t help foresee flight cancellations, it might help identify those at risk of harm from their medicines.


  1. Parekh N, Ali K, Stevenson JM, Davies JG, Schiff R, Van der Cammen T, et al. Incidence and cost of medication harm in older adults following hospital discharge: a multicentre prospective study in the UK. Br J Clin Pharmacol. 2018 Aug;84(8):1789–97.
  2. Stevenson JM, Williams JL, Burnham TG, Prevost AT, Schiff R, Erskine SD, et al. Predicting adverse drug reactions in older adults; a systematic review of the risk prediction models. Clin Interv Aging. 2014 Sep;1581.


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