Periodic Reporting for period 4 - OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly)
Berichtszeitraum: 2019-05-01 bis 2020-04-30
Many older adults have multiple chronic diseases (multimorbidity) and directly related multiple medications (polypharmacy). However, multimorbid older patients are often excluded from clinical trials, and most guidelines address diseases in isolation. Inappropriate drug prescription and poor drug compliance are common in older people, contribute to up to 30% of hospital admissions, and are related to morbidity and costs. The overall aim of OPERAM was to reduce inappropriate drugs and subsequent drug-related hospital admissions among the older population with multimorbidity through optimization of existing pharmacological therapy. At the end of the fourth reporting period, the data analysis was almost completed. The publication of the results is expected for summer 2020.
OPERAM was divided into 9 work packages, including partners from Belgium, Germany, Greece, Italy, Ireland, Switzerland, and the Netherlands. The core part of the project was the conduct of a large-scale cluster RCT using the STRIP intervention versus usual pharmaceutical care to examine the effect of pharmacotherapy optimization on clinical outcomes (WP1-4 and 7), principally unscheduled drug-related admissions (the primary endpoint). The coordination of the RCT was the responsibility of WP1.
During the RCT 2008 multimorbid older patients with chronic polypharmacy have been successfully recruited and followed-up.
To optimize reliability, a centralized system for monitoring of drug-related hospital admissions was initiated. In order to gain an in-depth understanding of patient experience of hospital-initiated medication changes, a mixed methods study combining both qualitative and quantitative data was conducted. Training and supervision of adjudication activities was being conducted as part of WP4. In total 1732 hospitalisations were adjudicated by a local, independent adjudication committee at each clinical site.
The implemented quality assurance system included monitoring of key performance indicators, on-site monitoring and central data monitoring. Data entry was continuously monitored and the sites were provided with ongoing feedback on potential irregularities. Quality assurance activities were conducted as specified in the monitoring and the data management and validation plan (WP1). In total, the central data monitoring team issued 10989 queries.
After the trial had finished, the applicability of STRIPA 2.0 was assessed. STRIP Assistant Version 3 has been further elaborated and resulted in a unified analytic system with several application- and language-specific database backends. During the fourth period the source code and subsequently integrated risk model for automated medication-to-disease assignments using association rule mining was developed (WP2).
The databases for SR on fall and fall related fractures and on avoidable hospital admissions were created and were checked by a second reviewer. Both databases were completed (WP5).
The specific protocol for falls and fall related fractures has been submitted to PROSPERO (registration number PROSPERO 2019 CRD42019137466) during the fourth period (WP6).
During the fourth period, the cost-effectiveness of the OPERAM trial intervention could be analysed, and the cost-effectiveness analysis based on data related to falls and fractures could be performed. In addition, analysis of the OPERAM trial sub-study data comparing the 3-level and 5-level versions of the European Quality of Life-5 Dimensions instrument has been performed (WP7).
In the fourth reporting period, OPERAM maintained its dissemination activities and its public visibility. Seven Analysis Plans were reviewed and approved by the OPERAM Publication Committee. Three scientific publications have been published, OPERAM results were presented at conferences by the partners, and the website has been continuously been updated. The main publication is expected to be submitted to an appropriate journal in Summer 2020.
All deliverables have been reached according to plan and schedule, and related reports have been submitted to the EC. Several teleconferences with all project partners have taken place for the purpose of close project navigation and progress monitoring. One Contract Amendment has been prepared and submitted to the European Commission. The final meeting of the entire consortium was held in February 2020. (WP9).
During the RCT 2008 multimorbid older patients with chronic polypharmacy have been successfully recruited and followed-up.
To optimize reliability, a centralized system for monitoring of drug-related hospital admissions was initiated. In order to gain an in-depth understanding of patient experience of hospital-initiated medication changes, a mixed methods study combining both qualitative and quantitative data was conducted. Training and supervision of adjudication activities was being conducted as part of WP4. In total 1732 hospitalisations were adjudicated by a local, independent adjudication committee at each clinical site.
The implemented quality assurance system included monitoring of key performance indicators, on-site monitoring and central data monitoring. Data entry was continuously monitored and the sites were provided with ongoing feedback on potential irregularities. Quality assurance activities were conducted as specified in the monitoring and the data management and validation plan (WP1). In total, the central data monitoring team issued 10989 queries.
After the trial had finished, the applicability of STRIPA 2.0 was assessed. STRIP Assistant Version 3 has been further elaborated and resulted in a unified analytic system with several application- and language-specific database backends. During the fourth period the source code and subsequently integrated risk model for automated medication-to-disease assignments using association rule mining was developed (WP2).
The databases for SR on fall and fall related fractures and on avoidable hospital admissions were created and were checked by a second reviewer. Both databases were completed (WP5).
The specific protocol for falls and fall related fractures has been submitted to PROSPERO (registration number PROSPERO 2019 CRD42019137466) during the fourth period (WP6).
During the fourth period, the cost-effectiveness of the OPERAM trial intervention could be analysed, and the cost-effectiveness analysis based on data related to falls and fractures could be performed. In addition, analysis of the OPERAM trial sub-study data comparing the 3-level and 5-level versions of the European Quality of Life-5 Dimensions instrument has been performed (WP7).
In the fourth reporting period, OPERAM maintained its dissemination activities and its public visibility. Seven Analysis Plans were reviewed and approved by the OPERAM Publication Committee. Three scientific publications have been published, OPERAM results were presented at conferences by the partners, and the website has been continuously been updated. The main publication is expected to be submitted to an appropriate journal in Summer 2020.
All deliverables have been reached according to plan and schedule, and related reports have been submitted to the EC. Several teleconferences with all project partners have taken place for the purpose of close project navigation and progress monitoring. One Contract Amendment has been prepared and submitted to the European Commission. The final meeting of the entire consortium was held in February 2020. (WP9).
OPERAM aimed to add important and urgently needed evidence on the optimal pharmacotherapeutic management of multimorbid elderly people with polypharmacy and its impact on relevant clinical outcomes as well as its cost-effectiveness. To date, different screening tools have been developed to assess medication misuse, underuse and overuse; their effect on clinical outcomes must be assessed within the trial before their practicability can be assessed for routine clinical use. Our proposal aimed to assess the effectiveness of an improved version of the existing STRIPA designed to systematically optimize polypharmacy among multimorbid elderly patients and improve their clinical outcomes. Optimization of pharmacotherapy in this rapidly growing patient population could lead to major improvements in the care of older European citizens. The design of the OPERAM RCT aims to overcome the limitations of previous studies assessing the impact of pharmacotherapy optimization on clinical outcomes. The novel aspects of the concept implemented in the OPERAM RCT included: (i) a large sample size, (ii) inclusion of older patients with multimorbidity and polypharmacy, (iii) a structured assessment of medication at hospital admission, (iv) having an adequate follow-up duration of one year, (v) cluster randomisation at the physician level to avoid contamination, and (vi) adjudication of outcomes by an independent and blinded adjudication committee. Furthermore, a recommendation sheet with rationale for prescription medication change recommendations was applied and discussed face-to-face with the prescribing physician in order to increase implementation rates. A qualified team comprising a pharmacist and a physician performed patient counselling in order to increase patients’ compliance to the recommendations. Finally, a recommendation sheet with rationale for recommendations for the general practitioner (GP) was applied to better communicate medication changes during hospitalization and to avoid discontinuation of newly prescribed medication or resumption of previously discontinued medications by patients’ GPs after discharge. An important feature of the OPERAM RCT was the multi-country study design with patient recruitment in Belgium, Ireland, The Netherlands and Switzerland. Final analyses are ongoing and the main publication is expected to be submitted to an appropriate journal in Summer 2020.