Title: Use, risk-benefits, and costs of preventive therapies in older people with complex health needs: an analysis of NHS routinely collected data.
Funder: Department of Health and Social Care

Abstract: Background As the UK population ages, the NHS is prescribing more long-term preventive treatments. However, there is poor evidence of the risk-benefit of these treatments in older patients with complex health needs (OPCHN). The open NIHR call on 'complex health and care needs in older people' aims to determine 'when the benefits of continuing with preventive medication become marginal'. Recent NICE multi-morbidity guidelines also recommend research into this, with a focus on osteoporosis (bisphosphonates) and cardio-vascular (statins and anti-hypertensive) therapies.Aims To identify OPCHN in NHS practice (Work package 1); To determine OPCHN's use of and adherence to the preventive therapies listed above (WP2); To assess the risk of adverse drug reactions (ADRs) when using the preventive therapies (WP3); To study the association between stopping such therapies and OPCHN suffering 'preventable' fractures and cardiovascular events (WP4); and To calculate and compare NHS costs associated with OPCHN continuing or stopping the preventive therapies (WP5).Methods Data sources: Routinely collected data from NHS primary care (Clinical Practice Research Datalink, CPRD), linked to inpatient records (Hospital Episode Statistics, HES). Participants: WP1: All patients aged 65+ on 1/1/2012 and registered in the CPRD for 1+ years. WP2-5: Three OPCHN cohorts from the WP1 population: those with high healthcare resource use, frailty, and polypharmacy. Exposures: Bisphosphonate, statin, and anti-hypertensive therapies Outcomes: WP1: OPCHN phenotypes WP2: Population- and patient-level drug utilisation measures WP3: Pre-defined ADRs: upper gastro-intestinal ulcers (bisphosphonates), acute kidney injury (bisphosphonates, anti-hypertensives), liver failure and myopathy (statins), and falls and fractures (anti-hypertensives) WP4: Preventable events: fractures (bisphosphonates) and cardiovascular events (statins and anti-hypertensives) WP5: NHS costs Statistics: WP1: Patients in the top quintile for number of hospital admissions, NICE-recommended electronic frailty index (eFI)[1] score, and number of different drug prescriptions the year before inclusion will form the high healthcare resource use, frailty, and polypharmacy OPCHN cohorts, respectively. WP2: Incidence and prevalence of preventive treatments will be estimated in each OPCHN cohort. Persistence and medication possession ratios will be calculated amongst treatment users. WP3: We will model the risks of each ADR according to treatment use with survival analyses. We will minimise confounding using inverse probability weighting. WP4: We will estimate incidence rates of 'preventable events' and calculate incidence rate ratios for on- vs off-treatment periods using self-controlled case series. WP5: We will develop a cost model mapping the care and events pathways of OPCHN and populate it with WP2-4 findings to estimate NHS hospital and prescription costs associated with continuing or stopping the preventive therapies.Timeline Month M4: Data access M5-10: Data management M11-16: Data analysis WP1 M17-25: Data analysis WP2; dissemination WP1 M26-40: Data analysis WP3-4; dissemination WP2 M41-53: Data analysis WP5; dissemination WP3-4 M54-60: Dissemination WP5; Final study reportImpact and dissemination Our results will inform future NICE multi-morbidity guidelines, will be reported to medicine regulators to promote safer prescribing, and to the scientific community (conferences/manuscripts). We will work with patient representatives and charities (Age UK, Arthritis Research UK) to maximise lay audience dissemination.

Lay abstract: Background As the UK population ages, the NHS is prescribing more long-term preventive treatments. We don't know whether these treatments are helpful and safe in older patients with complex needs, as drug trials usually exclude them. Recent NICE guidelines recommend research on what happens when these patients stop taking preventive therapies. An open NIHR themed call asks: 'When do the benefits of continuing with preventive medication become marginal?'Aims We will identify groups of older people with complex health needs based on their NHS services use, how frail they are, and how many medications they take. We will study how often they are prescribed drugs to prevent bone fractures and cardiovascular disease, whether they finish their prescriptions, and their risks of unwanted side effects. We will also study their risks of fractures or cardiovascular disease if they stop the preventive treatments. We will estimate and compare the costs of these patients continuing or stopping preventive treatments, considering the costs of side effects, fractures, and cardiovascular disease.Methods We will use NHS primary care and linked hospital records, which contain de-identified patient characteristics, GP prescriptions, blood test results, diagnoses, and hospital admission data. We will identify three groups of patients aged 65 and above with complex health needs: patients with many hospital admissions; frail patients, identified using a NICE-recommended score (the electronic frailty index); and patients prescribed many drugs.We will calculate how many patients in each group are given drugs (called bisphosphonates) to prevent fractures, or statins or anti-hypertensive drugs to prevent cardiovascular disease. We will assess how long they were prescribed the drugs and how well they followed treatment directions, by looking at the time between prescriptions.Within each group, we will calculate the risk of a preventive treatment causing unwanted side effects, such as stomach ulcers or liver and kidney problems. We need to compare each group's treatment-users with its treatment-nonusers. People prescribed preventive treatments are probably different from people who aren't - they may have different medical histories, for example -h; so we cannot compare them directly. We will use statistical methods called inverse probability methods to adjust the risks of side effects so that they take the characteristics of the people in each group into account. We can then compare treatment-users with treatment-nonusers.Within each group, we will calculate the risks of fractures and cardiovascular disease while taking and after stopping a treatment to prevent these problems. We will adjust for differences between patients by using each patient as their own control (called a self-controlled case series), so that the only difference is whether they are taking the treatment at the time.We will estimate how much the preventive treatments cost using GP prescriptions. We will use hospital admissions data to estimate hospital costs for fractures, cardiovascular disease, and unwanted side effects.Patient and public involvement A patient with osteoporosis and taking many medications (complex health needs) reviewed this application. This proposal was discussed with representatives of charities including Age UK and Arthritis Research UK. A patient or carer will be invited onto the study advisory board, contributing to managing the proposed research and dissemination. We will organise talks at community centres to discuss our findings with patients and their carers, and (as suggested by Age UK representatives) to explore patient/carer attitudes to the different preventive therapy strategies.Dissemination We will share our findings with scientists (conferences, manuscripts), NHS, and national medicine regulators. We will work with charities, patients and carers to publicise our results: we will design leaflets to share at GP surgeries and hospitals, and will organise talks in community centres.

Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION
Health categories: CARDIOVASCULAR;MUSCULOSKELETAL