Periodic Reporting for period 2 - 4-IN THE LUNG RUN (4-IN THE LUNG RUN: towards INdividually tailored INvitations, screening INtervals, and INtegrated co-morbidity reducing strategies in lung cancer screening)
Periodo di rendicontazione: 2021-07-01 al 2022-12-31
With 338,000 EU-deaths annually, lung cancer is a devastating problem. CT screening has the potential to prevent ten-thousands of lung cancer deaths annually. The positive results of the Dutch-Belgian screening trial (NELSON), with relatively low referral rates, and the NLST in the US, with annual screens only, provided conclusive evidence on the benefits (and possible harms). However, EU-implementation is likely to be limited, slow and of variable quality throughout European countries, and current international guidelines could easily require up to 25 million CT screens annually. The most optimal strategy in risk-based lung-thoracic screening is still unknown regarding the optimal and most cost-effective (e.g. targeted) strategy 1) to recruit high-risk individuals, 2) to integrate smoking cessation and co-morbidity-reducing services, and 3) to determine the preferred personalised (risk-based) screening interval. Personalised regimens based on the baseline CT result can potentially retain 85% of the LC mortality reduction achievable through screening at 45% less screens, thus potentially saving much unnecessary harm associated with screening, and 0.5-1 billion Euros per year.
The heart of 4-IN-THE-LUNG-RUN is a European randomised controlled multi-centred implementation trial amongst 24,000 individuals, at high risk for developing lung cancer, evaluating whether it is safe to have risk-based less intensive screening intervals after a negative baseline CT.
Various methods to improve participation of hard-to-reach individuals will be assessed in five different healthcare settings/countires. Innovative co-morbidity reducing strategies will be tested including other markers on CT imaging, as Calcium Score and COPD. Cost impact and cost-effectiveness analyses using a natural history model will steer implementation. The experienced consortium will strongly interact with key stakeholders, and discuss interim results with key other international initiatives on CT screening, biomarkers, and smoking cessation practices. This proposal will form the evidence base for risk-based lung cancer screening with huge benefits for the EU, on health outcomes, cost savings, and innovation in the long run.
The heart of 4-IN-THE-LUNG-RUN is a European randomised controlled multi-centred implementation trial amongst 24,000 individuals, at high risk for developing lung cancer, evaluating whether it is safe to have risk-based less intensive screening intervals after a negative baseline CT.
Various methods to improve participation of hard-to-reach individuals will be assessed in five different healthcare settings/countires. Innovative co-morbidity reducing strategies will be tested including other markers on CT imaging, as Calcium Score and COPD. Cost impact and cost-effectiveness analyses using a natural history model will steer implementation. The experienced consortium will strongly interact with key stakeholders, and discuss interim results with key other international initiatives on CT screening, biomarkers, and smoking cessation practices. This proposal will form the evidence base for risk-based lung cancer screening with huge benefits for the EU, on health outcomes, cost savings, and innovation in the long run.
The definitive clinical study protocol, nodule management protocol and the acquisition protocol have been agreed by all countries and were finalized. All recruitment materials has been developed for all individual countries: short and long version of the information leaflet, informed-consent form, questionnaires, invitation letter, infographic, script for the standard website, script for the interactive/tailored website, and script for the self-test. Furthermore, all communication materials for participants (recruitment letter, invitation letter, screening test result letter/ Standard Operating Procedure for providing a positive screening test result by phone call) have been developed and finalised. An animation video has been designed to stimulate individuals to consider taking part in the study.
The recruitment documents, which were translated to the relevant languages, were used for the submission of the ethical application forms. Partners have made adjustments to meet the local requirements.
In close collaboration with the Dutch Health Council, the study protocol and recruitment materials/ communication were evaluated carefully during several meetings and formal written responses (between July 2020 and June 2021). Based on their advice, the recruitment materials have been improved. For the Dutch centres, a pilot among the target population is required before the recruitment can start. This pilot and its evaluation are planned for September 2021.Research to optimize the recruitment strategy, especially for the hard-to-reach group, is ongoing and studies started in the UK.
An online data management system was developed to coordinate the trial from begin to end of the trial. Measures to protect the privacy of participants and legal requirements of all centres were carefully implemented in the system. The system consists of several units (central unit = administrative tasks; screening unit = planning of the CT scans and performing of the CT scan; reading unit = reading of the CT scans). These units together thus include the whole screening workflow from recruitment until end of screening. The study protocol and the nodule management protocol were completely implemented in the system. Thereby, the system is configurable to all localities to support the implementation of high-quality lung cancer screening.
Machine learning approaches for lung cancer (and cardiovascular disease and COPD) were developed and implemented in the screening protocol/ data management system to improve biomarker identification and to explore novel algorithms applied to measure those imaging biomarkers.
The recruitment documents, which were translated to the relevant languages, were used for the submission of the ethical application forms. Partners have made adjustments to meet the local requirements.
In close collaboration with the Dutch Health Council, the study protocol and recruitment materials/ communication were evaluated carefully during several meetings and formal written responses (between July 2020 and June 2021). Based on their advice, the recruitment materials have been improved. For the Dutch centres, a pilot among the target population is required before the recruitment can start. This pilot and its evaluation are planned for September 2021.Research to optimize the recruitment strategy, especially for the hard-to-reach group, is ongoing and studies started in the UK.
An online data management system was developed to coordinate the trial from begin to end of the trial. Measures to protect the privacy of participants and legal requirements of all centres were carefully implemented in the system. The system consists of several units (central unit = administrative tasks; screening unit = planning of the CT scans and performing of the CT scan; reading unit = reading of the CT scans). These units together thus include the whole screening workflow from recruitment until end of screening. The study protocol and the nodule management protocol were completely implemented in the system. Thereby, the system is configurable to all localities to support the implementation of high-quality lung cancer screening.
Machine learning approaches for lung cancer (and cardiovascular disease and COPD) were developed and implemented in the screening protocol/ data management system to improve biomarker identification and to explore novel algorithms applied to measure those imaging biomarkers.
The aim of 4-IN-THE-LUNG-RUN concerns the remaining key steps in the development of an optimal risk-based low-dose volume CT lung cancer screening programme for all high-risk European citizens, and to substantially reduce unnecessary harms, while maintaining the huge benefits of lung cancer screening, through a personalised approach.
It is expected that our proposed programme and strategy will decrease health care cost and suffering for patients in the advanced palliative phase by ten-thousands individuals per year. These programmes will reduce the amount of anxiety, false positives, radiation risk and possible complications, all directly benefiting European citizens, proportionally tackling more lower socio-economic groups. Screening cost may be reduced by half compared to the anticipated annual screens in non-risk based screening intervals. Furthermore, the suitability for implementation is an important part of the project design and capacity building programmes and quality assurance schemes will be developed.
Moreover, we ensure special attention to individuals with lower socioeconomic backgrounds, by tailoring different groups differently at recruitment, and encompass all earlier expertise in population-based screening trials across the participating countries into the ethical components (including communication to low risk individuals).
In conclusion, the project will determine if personalised risk-based lung cancer screening (as compared to annual screening): 1) is safe, 2) is less morbid, 3) is more accepted by the hard-to-reach high-risk population, 4) enables prevention (especially smoking cessation) and 5) has greater health care value for decades to come.
It is expected that our proposed programme and strategy will decrease health care cost and suffering for patients in the advanced palliative phase by ten-thousands individuals per year. These programmes will reduce the amount of anxiety, false positives, radiation risk and possible complications, all directly benefiting European citizens, proportionally tackling more lower socio-economic groups. Screening cost may be reduced by half compared to the anticipated annual screens in non-risk based screening intervals. Furthermore, the suitability for implementation is an important part of the project design and capacity building programmes and quality assurance schemes will be developed.
Moreover, we ensure special attention to individuals with lower socioeconomic backgrounds, by tailoring different groups differently at recruitment, and encompass all earlier expertise in population-based screening trials across the participating countries into the ethical components (including communication to low risk individuals).
In conclusion, the project will determine if personalised risk-based lung cancer screening (as compared to annual screening): 1) is safe, 2) is less morbid, 3) is more accepted by the hard-to-reach high-risk population, 4) enables prevention (especially smoking cessation) and 5) has greater health care value for decades to come.