In WP1, the main tasks carried out in the first two years of the project included preparing pilot studies by developing protocols for the retrospective and prospective pilot studies that were initiated in the project’s third year. The studies aim to investigate the (potential) vaccine-preventable disease burden in ageing adults in two regions, Denmark and Valencia in Spain. The retrospective pilot study protocol and prospective pilot study protocol synopsis were submitted during the second year of the project.
Retrospective Pilot Study
Based on the different outputs, it was decided by the Consortium to focus on the retrospective pilot study on Pneumococcal pneumonia (PP) and Invasive extra-intestinal pathogenic Escherichia coli Disease (IED). In the second year, a protocol was developed to implement the retrospective eHR database pilot studies in the aging population in both regions.
The first requirement before developing the protocol was to build disease progression models (outcome trees) for the two diseases. These outcome trees describe the disease progression pathways over time by chronologically ordering all the health states associated with the diseases. The outcome tree for PP and EID was constructed in WP1 using standard definitions and descriptions of disease progressions through consultation with experts and by literature review. The protocols were submitted and approved by the ethical committees. Subsequently, requests were made to data providers in the regions so that the retrospective pilot studies could be initiated in VITAL’s third year.
Running parallel during VITAL’s second year, WP1 prepared the pilot prospective study that aimed to assess the impact of Acute Respiratory Infection (ARI) and bacteremia hospitalization on quality of life, frailty, and disability in ageing populations. The first step developed a synopsis, that is, a longitudinal observational study in multiple hospital centers in France, Italy and Spain. The study includes patients aged 65 plus years who present to an emergency department or infectious disease, internal medicine, or geriatric hospital wards with bacteremia and/or acute respiratory infection. There are two controls for every case: the typical control patient will be of the same age and same sex and be without suspicion of infection, and has been hospitalized during the past or upcoming month in the same center. All cases and controls will be followed-up for six months and quality of life and frailty will be longitudinally assessed using standardized instruments. Subsequently, the full protocol of the prospective study was prepared, and the study was initiated at the end of the second reporting period, initially in three countries.
Delays and Next Steps
The recruitment of patients and patient follow-up in the prospective study continued in the project’s third year. Adjustments were made to limit the number of COVID cases enrolled to avoid over-representation of COVID cases and under-representation of other infections. Discussions continue about enrolling a fourth country in the prospective study.
For the retrospective study, the statistical analysis plan has been prepared. It describes in detail how the data for the retrospective study will be managed and analyzed, and what output is expected from the analysis. The protocol and statistical analysis plan will be evaluated and adjusted during the pilot phase of the study in the ageing populations in Denmark and the Valencia region. The data extracting process by the data providers has faced a delay due to competing COVID related activities. Currently being analyzed, data from the Valencia region became available in September. Data extraction for Denmark is still in process. The deadline for the intermediate report of the pilot study has been extended for six months.