Adverse drug reactions and targets for deprescribing in high risk older adults

Over the last twenty years, many prescribing tools have been developed and validated to identify inappropriate prescribing (IP) in older adults and assist physicians in medication optimisation. However, these prescribing tools have predominantly focused on identifying IP in the general older adult population, rather than targeting the population cohort that is growing at the fastest rate and that is at the highest risk of IP and adverse drug reactions (ADRs) i.e. older frailer multimorbid patients with a poor survival prognosis. Extensive research on the prevalence of ADRs has been published. However many different definitions of ADRs and many different ADR causality tools have been employed across different studies, making it difficult to compare the results of studies. To confound this area of investigation further, many ADR causality tools are not appropriate to use in older frail multimorbid adults. In addition, a limited amount of research has occurred identifying the morbidity associated with ADRs in older adults. To date, there is no standardized approach to identifying, assessing and reporting ADRs in older adults. This doctoral thesis was designed to (i) standardise the identification, assessment and reporting of ADRs in older adults, (ii) assess ADRs using this new methodology in high risk populations, and (iii) develop and validate a new usable set of criteria called STOPPFrail (Screening Tool of Older Persons Prescriptions in Frail adults with limited life expectancy) to assist deprescribing in older frail multimorbid adults with a poor survival prognosis i.e. patients where the role of preventative therapy is questionable. This thesis comprises eleven chapters. The first chapter is an introduction, divided into four sections i.e. (i) demographic changes and the proportional increase in high risk older adults, (ii) prescribing considerations for older adults, (iii) consequences of IP including ADRs and (iv) potential targets for intervention. The second chapter proposes a methodologically robust way of identifying, assigning causality and reporting ADRs and tests this theory on physicians, pharmacists, biomedical scientists and nurses. The third chapter uses this new ADR methodology to identify the prevalence of ADRs in older adults presenting to hospital. The fourth chapter compares older and younger adults with cancer in terms of multimorbidity, medication use and ADRs using the same methodology proposed in Chapter 2. The fifth chapter develops and validates STOPPFrail criteria, an explicit prescribing tool to assist deprescribing in frail older adults with a poor one year survival prognosis. The sixth chapter describes the inter-rater reliability (IRR) of STOPPFrail criteria between physicians. The seventh chapter, applies STOPPFrail criteria to two representative populations i.e. a proportion of older adults deemed suitable for nursing home care and a proportion of older adults presenting for hospitalisation. Chapter eight considers the relevance of the research data developed in this thesis as well as questions any issues arising from these research studies. Chapter nine contains peer-reviewed articles that were published and awards received during the writing of this thesis. Finally, chapters ten and eleven list the references and appendices, respectively

Methods to reduce prescribing errors in elderly patients with multimorbidity

The global population of multimorbid older people is growing steadily. Multimorbidity is the principal cause of complex polypharmacy, which in turn is the prime risk factor for inappropriate prescribing and adverse drug reactions and events. Those who prescribe for older frailer multimorbid people are particularly prone to committing prescribing errors of various kinds. The causes of prescribing errors in this patient population are multifaceted and complex, including prescribers’ lack of knowledge of aging physiology, geriatric medicine, and geriatric pharmacotherapy, overprescribing that frequently leads to major polypharmacy, inappropriate prescribing, and inappropriate drug omission. This review examines the various ways of minimizing prescribing errors in multimorbid older people. The role of education in physician prescribers and clinical pharmacists, the use of implicit and explicit prescribing criteria designed to improve medication appropriateness in older people, and the application of information and communication-technology systems to minimize errors are discussed in detail. Although evidence to support any single intervention to prevent prescribing errors in multimorbid elderly people is inconclusive or lacking, published data support focused prescriber education in geriatric pharmacotherapy, routine application of STOPP/START (screening tool of older people’s prescriptions/screening tool to alert to right treatment) criteria for potentially inappropriate prescribing, electronic prescribing, and close liaison between clinical pharmacists and physicians in relation to structured medication review and reconciliation. Carrying out a structured medication review aimed at optimizing pharmacotherapy in this vulnerable patient population presents a major challenge. Another challenge is to design, build, validate, and test by clinical trials suitably versatile and efficient software engines that can reliably and swiftly perform complex medication reviews in older multimorbid people. The European Union-funded SENATOR and OPERAM clinical trials commencing in 2016 will examine the impact of customized software engines in reducing medication-related morbidity, avoidable excess cost, and rehospitalization in older multimorbid people

The effect of SENATOR (Software ENgine for the Assessment and optimisation of drug and non-drug Therapy in Older peRsons) on incident adverse drug reactions (ADRs) in an older hospital cohort - Trial Protocol

Background: The aim of this trial is to evaluate the effect of SENATOR software on incident, adverse drug reactions (ADRs) in older, multimorbid, hospitalized patients. The SENATOR software produces a report designed to optimize older patients' current prescriptions by applying the published STOPP and START criteria, highlighting drug-drug and drug-disease interactions and providing non-pharmacological recommendations aimed at reducing the risk of incident delirium. Methods: We will conduct a multinational, pragmatic, parallel arm Prospective Randomized Open-label, Blinded Endpoint (PROBE) controlled trial. Patients with acute illnesses are screened for recruitment within 48 h of arrival to hospital and enrolled if they meet the relevant entry criteria. Participants' medical history, current prescriptions, select laboratory tests, electrocardiogram, cognitive status and functional status are collected and entered into a dedicated trial database. Patients are individually randomized with equal allocation ratio. Randomization is stratified by site and medical versus surgical admission, and uses random block sizes. Patients randomized to either arm receive standard routine pharmaceutical clinical care as it exists in each site. Additionally, in the intervention arm an individualized SENATOR-generated medication advice report based on the participant's clinical and medication data is placed in their medical record and a senior medical staff member is requested to review it and adopt any of its recommendations that they judge appropriate. The trial's primary outcome is the proportion of patients experiencing at least one adjudicated probable or certain, non-trivial ADR, during the index hospitalization, assessed at 14 days post-randomization or at index hospital discharge if it occurs earlier. Potential ADRs are identified retrospectively by the site researchers who complete a Potential Endpoint Form (one per type of event) that is adjudicated by a blinded, expert committee. All occurrences of 12 pre-specified events, which represent the majority of ADRs, are reported to the committee along with other suspected ADRs. Participants are followed up 12 (+/- 4) weeks post-index hospital discharge to assess medication quality and healthcare utilization. This is the first clinical trial to examine the effectiveness of a software intervention on incident ADRs and associated healthcare costs during hospitalization in older people with multi-morbidity and polypharmacy

Incident adverse drug reactions in geriatric inpatients : a multicentred observational study

Background: Adverse drug reactions (ADRs) are common in older adults and frequently have serious clinical and economic consequences. This study was conducted as a feasibility study for a randomized control trial (RCT) that will investigate the efficacy of a software engine to optimize medications and reduce incident (in-hospital) ADRs. This study's objectives were to (i) establish current incident ADR rates across the six sites participating in the forthcoming RCT and (ii) assess whether incident ADRs are predictable. Methods: This was a multicentre, prospective observational study involving six European hospitals. Adults aged 65 years, hospitalized with an acute illness and on pharmacological treatment for three or more conditions were eligible for inclusion. Adverse events (AEs) were captured using a trigger list of 12 common ADRs. An AE was deemed an ADR when its association with an administered drug was adjudicated as being probable/certain, according to the World Health Organization Uppsala Monitoring Centre causality assessment. The proportion of patients experiencing at least one, probable/certain, incident ADR within 14 days of enrolment/discharge was recorded. Results: A total of 644 patients were recruited, evenly split by sex and overwhelmingly of White ethnicity. Over 80% of admissions were medical. The median number of chronic conditions was five (interquartile range 4-6), with eight or more conditions present in approximately 10%. The mean number of prescribed medications was 9.9 (standard deviation 3.8), which correlated strongly with the number of conditions (r = 0.54, p < 0.0001). A total of 732 AEs were recorded in 382 patients, of which 363 were incident. The majority of events were classified as probably or possibly drug related, with heterogeneity across sites (chi(2) = 88.567, df = 20, p value < 0.001). Out of 644 patients, 139 (21.6%; 95% confidence interval 18.5-25.0%) experienced an ADR. Serum electrolyte abnormalities were the most common ADR. The ADRROP (ADR Risk in Older People) and GerontoNet ADR risk scales correctly predicted ADR occurrence in 61% and 60% of patients, respectively. Conclusion: This feasibility study established the rates of incident ADRs across the six study sites. The ADR predictive power of ADRROP and GerontoNet ADR risk scales were limited in this population