Community Research and Development Information Service - CORDIS

H2020

OPERAM Report Summary

Project ID: 634238
Funded under: H2020-EU.3.1.

Periodic Reporting for period 1 - OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly)

Reporting period: 2015-05-01 to 2016-04-30

Summary of the context and overall objectives of the project

Most older adults aged have multiple chronic diseases (multimorbidity) and multiple medications (polypharmacy). However, multimorbid patients are often excluded from clinical trials, and most guidelines address diseases in isolation. Inappropriate drug prescription and poor drug compliance are common in elderly people and contribute to up to 30% of hospital admissions and related morbidity and costs.
The overall aim of OPERAM is to optimise existing pharmacological and non-pharmacological therapy primarily in order to reduce avoidable hospital admissions among the elderly population with multimorbidity. Specifically, OPERAM aims at:
1) Creating new evidence to prevent avoidable hospital admissions through optimising pharmacotherapy in the multimorbid elderly. Therefore, we will perform a multi-centre cluster randomised controlled trial to assess the impact of a structured medication review, performed by a physician and pharmacist, with the Systematic Tool to Reduce Inappropriate Prescribing (STRIP) intervention with aim of the user-friendly STRIP assistant (STRIPA) software to optimise pharmacotherapy and to enhance compliance vs. usual care (WP1-3). We will assess the impact of an intervention with STRIPA on drug-related hospital admissions (DRAs) during a one year follow-up as the primary outcome with currently planned 2000 elderly patients with multimorbidity and polypharmacy. Secondary outcomes will include health care utilisation (comprising unplanned hospitalisations, office visits, urgent care and emergency department visits), mortality, falls, quality of life (QoL), changes in medication and drug compliance (WP4, WP7). In a subgroup, we will also examine patients’ perspectives and preferences (WP4).
2) Obtaining evidence-based data comparing pharmacological and non-pharmacological interventions to prevent common causes of avoidable hospital admissions in the elderly with multimorbidity, including falls, fractures, cognitive function, unscheduled hospital admissions, and major cardiovascular adverse events, and rank these interventions according to their effectiveness and safety using network meta-analyses (NMA; WP5-6). The results of our randomized controlled trial (RCT) on pharmacotherapy optimisation will also be compared with other available interventions. The focus is planned to be on elderly patients with multimorbidity for whom few direct comparison of interventions exist. The results will help the development of of customised patient-centred guidelines addressing the twin problem of multimorbidity-related polypharmacy and inappropriate prescribing that is highly prevalent in this group.
3) Identify the most cost-effective pharmacological and non-pharmacological interventions to prevent avoidable hospital admissions in the multimorbid elderly by analysing the cost-effectiveness and potential costs savings of the structured medication review (studied in the RCT) and of other interventions examined in the network meta-analysis (WP7).
The consortium for OPERAM has been created to address the challenging objectives and find solutions on different levels. On one hand, we will assess the effectiveness of a systematic intervention to reduce inappropriate prescribing using the STRIPA software, compared to usual care, in a clinical trial conducted in four European centres, including Ireland, the Netherlands, Belgium and Switzerland (WP1). The so-called STRIP intervention using the STRIPA software starts with (i) a validated instrument to assess the medication use in a structured way, then (ii) pharmaceutical analysis using the digital STRIPA and (iii) the judgement of the analysis by a physician and pharmacist, followed by (iv) the shared decision making with patients, improvement of compliance and knowledge about the medicines and (v) follow-up and control (WP3). We will use an updated web based tool to help optimise individual drug therapy the STRIPA version 2.0, using the STOPP/START criteria and combining the existing Dutch STRIP software (STRIPA version 1.0) and elements from the Irish Structured Pharmacist Review of Medication (SPRM) software (WP2). 2000 multimorbid elderly men and women, with polypharmacy (i.e. taking ≥ 5 long-term medications) will be randomised into the systematic pharmacotherapy optimisation intervention arm or usual care as control arm (WP1). The primary outcome of the RCT will be the number of drug-related hospital admissions (DRAs) over one year of follow-up. The secondary outcomes will include clinical outcomes such as mortality and falls, health care utilisation, QoL measures, and assessment of medication compliance. A qualitative research in a subsample of patients will be undertaken to assess patients’ perspectives and preferences on pharmacotherapy interventions (WP4). This qualitative survey and the analysis of actual usage data throughout the trial period (WP2) will be used to improve the STRIPA version 2.0 to develop the final STRIPA version 3.0 to be used in clinical practice.
Furthermore, we will perform systematic literature reviews and NMAs in order to identify and compare existing trial data on effective pharmacological and non-pharmacological interventions preventing recognised common causes of hospital admissions in multimorbid elderly, including falls, fractures, cognitive function, unscheduled hospital admissions, and major cardiovascular adverse events (WP5, 6). The final goal is to create a ranking of the most effective evidence-based pharmacological and non-pharmacological interventions for preventing common avoidable causes of hospital admissions. In parallel to these projects, an economic analysis of the results of the RCT and the NMAs will be performed in order to estimate and compare the cost-effectiveness of the different preventive interventions (WP7). The integration of these findings will be used to obtain new evidence for optimal therapeutic management of the rapidly growing population of elderly with multimorbidity and polypharmacy and thus contribute to the development of new customised patient-centred guidelines addressing the issue of multimorbidity in order to improve older people’s QoL and the cost-effectiveness of their healthcare.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

OPERAM is divided into 9 work packages, including partners from Belgium, Germany, Greece, Italy, Ireland, Switzerland, and The Netherlands (see Figure 1). The core part of the project is the conduct of a large-scale cluster RCT using the STRIP intervention versus usual care to examine the effect of pharmacotherapy optimisation on clinical outcomes (WP1-4). In the first year, preparations for the RCT took place and requested a strong collaboration of the involved WP’s, including WP1, WP2, WP3, WP4, and WP7.
The coordination of the RCT is the responsibility of WP1 (Clinical Trial Coordination), who set up a Trial Coordinating Centre (TCC) to ensure a uniform operation of all participating centres according to a high standard by providing the necessary documents and supportive infrastructure during the first year. At the end of the first year, the trial protocol was finalised and the development of standard operational procedures (SOPs), operation manuals, and informed consent procedures to ensure uniform and standardised conduction of the trial among the four recruiting sites in Switzerland, The Netherlands, Ireland, and Belgium, had started. The trial database and the electronic data capturing system started their development in the first year as well. Later on in the project, the conduct of the RCT including proper training of the staff, monitoring of recruitment and follow up, and ascertainment of outcome events will be managed by the TCC that is also responsible for the quality control, including ongoing data review and site monitoring, as well as data management and statistical analyses.
The WP 2 (Method and Software Tool for Optimising Medication) had further improved an existing web based application, the Dutch STRIP, including the STRIPA software, and delivered a functional method to optimise drug therapy with integration of existing national prescribing standards and available medicines from the 4 trial sites. The application is to capture patients’ data and provide clinicians with the necessary information to optimise the individual patient’s drug therapy and highlight adverse drug reaction (ADR) risk. Output datasets will include correctness of drug indications, potential prescribing omissions of beneficial drugs, instances of potentially inappropriate medications, presence of ADRs, potential adverse drug interactions, and dosing advice. Furthermore at the end of the first year, the content of the Dutch STRIPA software was translated and validated into the English language as well as into the languages used at the other trial sites. Further on in the project, end users perspectives will be explored by parallel qualitative research.
WP3’s (Medication Review and Implementation) core task is to operationalise the deployment of the STRIP for the purpose of its use as the intervention in the OPERAM trial. Once generated, the STRIP recommendations will be communicated in printed format and verbally to the patient’s hospital prescribing physician and GP.. In the first year, WP3 started to develop the standard operating procedures describing the practical execution and efficient deployment of the STRIP intervention, and compiled a plan for a pilot testing of the intervention and STRIPA. Apart from the development of the SOP and pilot test and implementation, WP3 will provide training for the primary researchers in the OPERAM trial in the practicalities of STRIP deployment, which will take place before the RCT starts.
WP4 (Clinical Outcomes and Patient Preferences) has developed and validated a reliable structured method to adjudicate DRAs (the primary outcome of the RCT) caused by overuse, misuse and underuse of medications during the first year. The DRA identification method consists of a comprehensive medical record review and review of patient-reported symptoms with the aid of a trigger tool. The developed DRA adjudication guide, to be used in the RCT, includes instructions for data abstraction, screening for potential adverse drug events (ADEs), ADE contribution to index acute admission. WP4 also developed instructions for data abstraction, screening for potential ADEs and adjudication of ADE causality, ADE contribution, a core outcome set (COS) for pharmacotherapy optimisation for multimorbid elderly that will be implemented in the OPERAM RCT. From month 13 onwards, WP4 will concentrate on performing a qualitative analysis to explore the perspective of patients on pharmacotherapy optimisation.
In parallel to the preparations for the RCT in the first year, WP5 finalised a common protocol for systematic reviews using up-to-date methods to identify relevant RCTs evaluating specific pharmacologic and non-pharmacologic interventions to prevent common recognised causes of hospital admissions in elderly patients, including falls, fractures, cognitive function, unscheduled hospital admissions, and major cardiovascular adverse events (WP5). In addition, WP5 had started to compile a database with all relevant data-points required to perform a series of NMAs by WP6. WP6 started developing the statistical analysis plan in order to enable a ranking of the most effective interventions to prevent common causes of hospital admissions in the target population.
WP 7 (Health Economics) will evaluate health economic impact by performing state-of-the-art cost-effectiveness analysis of the STRIP intervention in the RCT and of interventions studied in the NMA. Medical resource use within the RCT, QoL data and unit costs for participating countries will be collected and rigorous deterministic and probabilistic sensitivity analysis performed. During the first year, WP7 implemented a plan for the collection of health economic data alongside the preparation of the RCT in collaboration with WP1, developed a patient booklet to support follow-up data collection, and started developing the health economic analysis plan.
WP8 coordinates, supports, and ensures continuous dissemination and exploitation of the project concept and its results to the scientific community and wider public from the beginning of the project. Several abstracts have been prepared by partners from the consortium to present first works from OPERAM at conferences to share the findings with the scientific community. By the end of the first year, WP8 set up an internal project website, a public website, developed a project flyer and conceived press releases. A publication committee and a publication guideline were developed to coordinate the publications and presentations produced by the investigators during and after (up to 10 years) the project life of OPERAM. Also started in the first year and stretching across the full duration of the project, are WP9 activities regarding the administrative, legal, ethics, and financial management of the overall project.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

OPERAM aims to add important and urgently needed evidence on the optimal therapeutic management of multimorbid elderly people with polypharmacy and its impact on relevant clinical outcomes and its cost-effectiveness. To date, different screening tools have been developed to assess medication misuse and underuse, but their effect on clinical outcomes remains to be proven and their practicality needs to be improved for routine clinical use. Our proposal aims at assessing the effectiveness of an improved version of the existing STRIPA designed to systematically optimise polypharmacy among multimorbid elderly patients and improve their clinical outcomes; if shown to be effective, optimisation of pharmacotherapy using STRIPA could lead to major improvements in the care of elderly European citizens and significantly improved cost-effectiveness of pharmacotherapy.
The design of the OPERAM RCT aims to overcome the limitations of previous studies assessing the impact of pharmacotherapy optimisation on clinical outcomes. The novel aspects of the concept implemented in the OPERAM RCT include a large sample size, inclusion of older patients with multimorbidity and polypharmacy, a structured assessment of medication at hospital admission, having a follow-up duration of one year, cluster randomisation at the physician level to avoid contamination, and adjudication of outcomes by an independent and blinded adjudication committee. Furthermore, a recommendation sheet with rationale for recommendations for prescribing will be applied to increase implementation rates. Patient counselling will be performed by an qualified team formed by a pharmacist and a physician to increase the patients’ compliance to the recommendations. Finally, a recommendation sheet with rationale for recommendations for the general practitioner (GP) will be applied to better communicate medication changes during hospitalisation and avoid discontinuation of newly prescribed medication or resuming previously discontinued medications by GP after discharge. Unique of the OPERAM RCT is additionally that it is a multi-country study with patient recruitment in Belgium, Ireland, The Netherlands and Switzerland.
Parallel to the RCT, NMAs are planned that will allow comparison of pharmacological and non-pharmacological interventions to improve clinical outcomes of high clinical and public health relevance among the elderly population, for whom few direct comparisons exist, i.e. elderly with multimorbidity. NMA is a novel method that allows the synthesis of evidence from a network of interventions where information flows not only directly but also indirectly through connected evidence loops. NMA is increasingly used to integrate direct and indirect evidence in a single analysis.
Health economic evaluation will complement comparative effectiveness research and inform decision makers at a larger scale, e.g. regarding the financing of interventions at the health system level. We will perform a state-of-the-art cost-effectiveness analysis (CEA) alongside the planned RCT to gain an understanding of the cost implications and potential health economic impact of the intervention studied. Health economic comparison with other interventions will be undertaken on the basis of NMAs and aims to improve pharmacotherapy in the elderly population and studied.

OPERAM directly addresses improving innovation capacity and the integration of new knowledge, by controlled comparison of pharmacotherapy optimisation using the software-assisted STRIP in a clinical trial. The STRIP intervention is expected to not only provide more effective and safer pharmaceutical interventions, but also to reduce DRAs caused by suboptimal pharmacotherapy and enhance medication compliance in the elderly population. OPERAM specifically addresses polypharmacy among multimorbid elderly, one of the major challenges for their care. Therefore, the key impact of this project is be to improve healthcare delivery through effective, safe, personalised and cost-effective interventions for the rapidly growing European older population with multimorbidity.
OPERAM will also include patient perspectives, NMAs and health economics studies, in addition to quantifying the effect of software-assisted pharmacotherapy optimisation on DRAs, and thus, will directly address each category of these expected impacts during the course of the project. This approach will increase the likelihood that its results will be of broad relevance. Thus, its expected impacts will be felt at all levels, for patients and for society, economically, and scientifically/medically, as a whole, setting new standards for management of multimorbid elderly patients.
In more details, regarding the impact on patients and society, OPERAM has the potential to contribute to:
• Better quality of life for multimorbid elderly due to decreased side-effects from inappropriate drug prescriptions
• Increased confidence about prescriptions, leading to better compliance by patients Improved operation of the whole medical system, since inappropriate medicines and DRAs would thus be minimised. Such efficiency would be predicted to have economic and scientific/medical impacts
• To help the development of customised patient-centred guidelines that take into account the problems arising with increasing multimorbidity and increasing age among the wider European population.
With regard to the economic impact, OPERAM has the potential to contribute to:
• Reduced costs, because of reduction in overtreatment leading to adverse effects as well as reduction in under-treatment that can both lead to avoidable hospitalisation.
• Exploitation of the validated STRIP software could meet market needs, as it has the potential to be a great innovation. OPERAM is designed to deliver a user-friendly software tool to significantly support health care providers who deal with the growing population of multimorbid elderly with polypharmacy.
Currently being 12 months in the project, OPERAM’s full expected potential impact remains in focus and will be further developed in the following period.

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