Periodic Reporting for period 4 - VALUE-Dx (The value of diagnostics to combat antimicrobial resistance by optimising antibiotic use)
Période du rapport: 2022-04-01 au 2023-03-31
VALUE-Dx is focused on demonstrating the value of diagnostics to combat antimicrobial resistance by optimizing antibiotic use within Europe. If we want to tackle anti-microbial resistance (AMR), we need to ensure that antibiotics are only used when absolutely necessary. However, data shows that in Europe, 30-50% of antibiotics are prescribed unnecessarily. Greater use of diagnostic tests could help to bring this figure down by ensuring that doctors only prescribe antibiotics when absolutely necessary. However, the wider use of diagnostic tests in healthcare is hampered by a lack of insight into their medical, technological and health economical value. In addition, our knowledge about the barriers to their use remains limited. The goal of VALUE-Dx is to generate evidence on the medical, economic, and public health value of diagnostics in treating AMR. To that end, VALUE-Dx will focus its research on community care, which includes medical clinics (including general practice, urgent care centres, accident and emergency and other acute services in hospitals, paediatric care centres, and rehabilitation and long-term care facilities), both in and out of office hours care. lnnovative diagnostics could indeed transform clinical care, especially in community care settings where the majority of antibiotics are prescribed, by reducing uncertainty about potential benefit antibiotics may offer to individuals. Though VALUE-Dx will focus on diagnostic strategies relevant to reducing AMR in Community-Acquired Acute Respiratory Tract lnfections (CA-ARTI), the project’s findings are likely to be relevant for other common infections, including urinary tract infections, blood stream infections, and respiratory tract infections acquired in hospitals. Ultimately, VALUE-Dx should help to transform medical practice by making it easier for doctors to deliver personalized, evidence-based antibiotic prescriptions thanks to the use of innovative diagnostic strategies.
Clinical Algorithm finalized
A clinical algorithm (CA) for diagnosing the aetiology of the community-acquired acute respiratory tract infections (CA-ARTIs) is necessary to limit inappropriate antibiotic prescribing in primary care and consequently curb antibiotic resistance emergence. The VALUE-Dx heuristic algorithm is designed to be able to select an optimal CA for any particular out-patients setting, i.e. list of available point of care diagnostic tests, their performance and cost, and disease prevalence.
Clinical Trials
Point Prevalence Audit Study (PPAS)
The first Point Prevalence Audit Survey (PPAS) in Primary Care and Long Term Care Facilities (LTCF) was completed in April 2020, with 4.995 patients (18 countries) in Primary Care and 418 patients (5 countries) in LTCF. Analyses of the first PPAS was used to inform the selection of the countries to participate in the PRUDENCE Trial.
Due to the success of the first PPAS, the same Primary Care networks were asked to re-open the PPAS and register patient CA-ARTI contacts during the COVID-19 pandemic (PPAS2), to help evaluate the impact of COVID-19 on Primary Care and to compare the pandemic period to the pre-pandemic period.
A third PPAS was opened in February 2021 and a fourth in January 2022, to allow continuity and comparison from/to previous audits, and to link to the perpetual observational study which will be set up as part of ECRAID-Base.
PRUDENCE
The start of the PRUDENCE Trial was postponed until Autumn 2021, due to the ongoing COVID-19 pandemic. The first network was opened and the first patient recruited in December 2021. By 31st March 2023, the trial was open to recruitment in all 10 Primary Care Networks and all 6 Long Term Care Facility Networks, with 1491 participants having been randomised (60% of the recruitment target of 2,500). 1384 Primary Care patients have been recruited (out of a target of 2300) and 107 LTCF patients have been recruited (out of a target of 200).
ADEQUATE
The ADEQUATE trial aims to evaluate the impact of rapid diagnostic testing of pediatric patients with acute respiratory tract infection (ARTI) in emergency departments on hospitalization rates, antibiotic prescriptions, and treatment duration. Highly sensitive molecular tests have increased the detection of respiratory pathogens, but the impact on clinical decision making needs to be further evaluated. The Adequate study aims to evaluate this and to improve the ARTI treatment. In total 9 clinical sites are involved in Adequate study. To date, 4 sites out of 9 are actively enrolling with a total number of patients recruited of 367 out of 520.
Other activities that started during the fourth year of VALUE-Dx:
1. We developed User Requirement Specification (URS)/ Target Product Profile (TPP) documents to facilitate development of diagnostic tests to improve antibiotic use in CA-ARTI.
2. The qualitative analyses on diagnostic-specific HTA policies and views from different stakeholders on the adoption of new diagnostic tests were finalized.
3. As a means of raising awareness on unnecessary prescription and use of antibiotics during the COVID-19 pandemic, a VALUE-Dx communication campaign was held during the World Antibiotic Awareness Week in November 2022.
4. We launched a separate VALUE-Dx webpage to showcase interviews with professionals who work in the AMR field.
A clinical algorithm (CA) for diagnosing the aetiology of the community-acquired acute respiratory tract infections (CA-ARTIs) is necessary to limit inappropriate antibiotic prescribing in primary care and consequently curb antibiotic resistance emergence. The VALUE-Dx heuristic algorithm is designed to be able to select an optimal CA for any particular out-patients setting, i.e. list of available point of care diagnostic tests, their performance and cost, and disease prevalence.
Clinical Trials
Point Prevalence Audit Study (PPAS)
The first Point Prevalence Audit Survey (PPAS) in Primary Care and Long Term Care Facilities (LTCF) was completed in April 2020, with 4.995 patients (18 countries) in Primary Care and 418 patients (5 countries) in LTCF. Analyses of the first PPAS was used to inform the selection of the countries to participate in the PRUDENCE Trial.
Due to the success of the first PPAS, the same Primary Care networks were asked to re-open the PPAS and register patient CA-ARTI contacts during the COVID-19 pandemic (PPAS2), to help evaluate the impact of COVID-19 on Primary Care and to compare the pandemic period to the pre-pandemic period.
A third PPAS was opened in February 2021 and a fourth in January 2022, to allow continuity and comparison from/to previous audits, and to link to the perpetual observational study which will be set up as part of ECRAID-Base.
PRUDENCE
The start of the PRUDENCE Trial was postponed until Autumn 2021, due to the ongoing COVID-19 pandemic. The first network was opened and the first patient recruited in December 2021. By 31st March 2023, the trial was open to recruitment in all 10 Primary Care Networks and all 6 Long Term Care Facility Networks, with 1491 participants having been randomised (60% of the recruitment target of 2,500). 1384 Primary Care patients have been recruited (out of a target of 2300) and 107 LTCF patients have been recruited (out of a target of 200).
ADEQUATE
The ADEQUATE trial aims to evaluate the impact of rapid diagnostic testing of pediatric patients with acute respiratory tract infection (ARTI) in emergency departments on hospitalization rates, antibiotic prescriptions, and treatment duration. Highly sensitive molecular tests have increased the detection of respiratory pathogens, but the impact on clinical decision making needs to be further evaluated. The Adequate study aims to evaluate this and to improve the ARTI treatment. In total 9 clinical sites are involved in Adequate study. To date, 4 sites out of 9 are actively enrolling with a total number of patients recruited of 367 out of 520.
Other activities that started during the fourth year of VALUE-Dx:
1. We developed User Requirement Specification (URS)/ Target Product Profile (TPP) documents to facilitate development of diagnostic tests to improve antibiotic use in CA-ARTI.
2. The qualitative analyses on diagnostic-specific HTA policies and views from different stakeholders on the adoption of new diagnostic tests were finalized.
3. As a means of raising awareness on unnecessary prescription and use of antibiotics during the COVID-19 pandemic, a VALUE-Dx communication campaign was held during the World Antibiotic Awareness Week in November 2022.
4. We launched a separate VALUE-Dx webpage to showcase interviews with professionals who work in the AMR field.
The delivery of a working technology demonstration (POC1) represents an over-achievement, since at the outset of the project it was not considered feasible that a working demonstration of capabilities could be delivered.
The second, third and fourth PPAS were run under H2020 Grant RECOVER and will continue in ECRAID-Base.
The second, third and fourth PPAS were run under H2020 Grant RECOVER and will continue in ECRAID-Base.