12 CHAPTER 1 Although the combination of ageing, multimorbidity and polypharmacy are wellknown important risk factors for drug-related harm, many other factors contribute to an increased vulnerability in this population. Frailty, age-related pharmacokinetic and pharmacodynamic changes, drug-disease interactions, drug-drug interactions, inadequate medication use and health care transitions (e.g. hospital admissions) are examples of such attributable risk factors (Figure 3) [24–26]. Therefore, reducing risk factors associated with drug-related harm requires a multidimensional approach on the levels of healthcare providers, patients, healthcare work environments and primary-secondary care interfaces, as addressed by the World Health Organization (WHO) [2,3,27]. Thus, complex interventions targeting multiple levels in healthcare are needed to enable the best possible outcomes and reduce healthcare expenditures in the growing older population with multimorbidity and polypharmacy. In 2009, the Dutch Ministry of Health, Welfare and Sport initiated a multidisciplinary task force to develop specific recommendations for the reduction of potentially preventable drug-related hospital admissions, which resulted in the HARMWrestling report [28,29]. However, the absolute number of drug-related admissions increased from an estimated 39,000 in 2008 to 49,000 in 2013. Similar to the results in 2008, 10% of hospital admissions in older patients were drug-related, half of which were considered potentially preventable. These findings confirmed that implementing of medication optimisation strategies and the evaluation thereof in clinical practice requires continuous effort .