Hospital Universitario de GetafeAzienda Sanitaria FirenzeCardiff Metropolitan UniversityGO EverycycleiDeTraDiabetes FrailInserm Institue NationalJenaLife LengthMosaiques DiagnosticsNiche Science and TechnologyServizio Sanitario RegionaleSistemas GenomicosUniversitat InnesbruckUniversidad AutonomaUniversitat De ValenciaWorld Health OrganizationYouHealth ABCentre Hospitalier Universitaire de Toulouse (CHUT)San Raffaele S.p.A. (San Raffaele)Italian National Research Council

Study Details

What is fraility?

Frailty is a clinical condition characterised by a significant decline in an older person’s ability to carry out activities of daily living and comprises changes associated with ageing, chronic disease and lifestyle. Frailty is highly prevalent in people older than 65 years (prevalence rates range from 7 to 16.3%) and this prevalence tends to increase with age.

In scientific terms, frailty is defined as a clinical syndrome in which three or more of the following are present: unintentional weight loss (≥4.5 kg in past year), self-reported exhaustion, weakness (grip strength), slow walking speed, and reduced physical activity.

One key feature of frailty is its association with disability. Frailty often precedes the development of disability sometimes by several years. Even though an individual’s natural progression is from non-frail to frail and disabled, a significant percentage of frail individuals are able to improve in terms of their functional status. Frailty can also be associated with other adverse clinical outcomes such as hospitalisation or ultimately even death.

What makes frailty so relevant?

Predictions of population demographics for the 21st century indicate that a modest increase in life expectancy will see a sharp increase in the personal and public health burden associated with disability. The early detection of frailty provides an opportunity to intervene on the pathway leading to disability. This is even so more relevant as recovery from disability is unlikely.

Despite this, the factors that predict the occurrence of frailty are yet to be clearly identified. Results from a study in women – the Women’s Health Aging Study II - revealed that some currently poorly defined characteristics associated with muscle function help predict the risk of frailty. It is well known that the progression from frailty to disability is dependent upon many factors but to date no study has specifically investigated the use of these factors as predictors of the risk of an individual becoming frail, developing a disability or responding to treatment. The FRAILOMIC initiative aims to address this issue.

What is frailomic?

FRAILOMIC is an international initiative that aims to identify the markers, or biomarkers, of the processes that turn frailty into disability. The main objective of the study is to develop clinical instruments that can predict the risk of frailty, improve the diagnostic accuracy of frailty in day-to-day practice and assess prognosis in terms of disability and adverse outcomes (in particular hospitalisation and loss of autonomy).

The FRAILOMIC consortium comprises seven small- and medium-sized enterprises, six universities, two leading research centres, four hospital-based research groups and the World Health Organization. The initiative brings together 20 institutions from nine countries (Austria, France, Germany, Italy, Spain, Switzerland, Sweden, the United Kingdom and the United States) and will be led by Professor Leocadio Rodríguez Mañas of the Hospital Universitario de Getafe, Madrid, Spain.

 

How will the aim of frailomic be achieved?

The study comprises two main phases, Phase 1 (or the Exploratory phase) and Phase 2 (or the Validation phase).

Phase 1 – Exploratory phase

Exploratory studies will be performed using blood and urine samples collected from approximately 75,000 older people. These samples are currently stored in bio-banks and were collected from well-established, well-characterised cohorts. Laboratory biomarkers will be identified. These findings will be combined with information on clinical biomarkers obtained from the same cohort in order to identify the biomarkers that predict the risk of frailty (risk biomarkers), detect frailty (diagnostic biomarkers) and assess the progression of frailty (prognostic biomarkers).

During this phase, some sub-studies will be performed in discrete populations, particularly older individuals with risk factors that make them more susceptible to develop frailty such as cardiovascular disease.

Phase 2 – Validation phase

The predictive capacity, diagnostic accuracy and prognostic value of each biomarker identified in Phase 1 will be tested in Phase 2. This testing will be performed prospectively and in cohorts different to those used in Phase 1. The main aim is to generate statistical models that will incorporate both laboratory and clinical biomarkers. The best fit models will be selected after testing the validity of the risk, diagnostic and prognostic biomarkers in the cohorts participating in Phase 2. These models will aid in the development of ready-to-use kits to be used in the clinic. These kits will help clinicians to identify those individuals at the highest risk of developing frailty, to make a diagnosis and to assess how frailty will progress.

 

Work Packages

WP1

The aim of this WP is to implement the system for detection of the biomarkers. The biomarkers showing a relationship with ageing (including vascular senescence/ageing), strength, frailty, muscle biology and the energy balance will be selected. Some of the partners have originally identified these biomarkers and have developed/optimised the methods that allow their quantification. The samples will either be provided by bio-banks (Phase 1) or will be newly drawn from the participants in the studies (Phase 2).

WP2

The aim of this WP is to identify the biomarkers (clinical and laboratory biomarkers) that can predict the risk of frailty (risk biomarkers), detect frailty (diagnostic biomarkers) or assess the progression of frailty (prognostic biomarkers). As there is a high risk of confounder effects and of false positive associations, in order to minimise bias the design of the analysis that will identify the biomarkers in each category will be different.

WP3

The aim of this WP is to prospectively test and validate the predictive capacity, diagnostic accuracy and prognostic value of each biomarker identified in Phase 1. Best fitted models will be established.

WP4

The aim of this WP is to identify biomarkers of that can predict the risk of frailty, detect frailty or assess the progression of frailty diagnosis in older individuals with risk factors that make them more susceptible to develop frailty namely diabetes, obesity and cardiovascular disease.

WP5

The aim of this WP is to provide the biomarkers that will be tested in Phase 2 as well as in special populations, to validate those biomarkers and to build and validate the models (set of biomarkers) needed to generate the Best Fitted Models. In addition, sensitivity analysis will be performed using alternative criteria of frailty.

WP6

The aim of this WP is to achieve maximum exploitation and dissemination of the results obtained in this project. The ways and means by which the project results are to be exploited will be identified. The wide diffusion of the project results from both a scientific and an industrial point of view will be achieved via dissemination processes.

WP7

The aim of this WP is to provide the overall management of the financial, administrative and consortium activities. It will also ensure that the contractual obligations towards the Commission are properly fulfilled.