Optimizing risk predictive strategies in febrile neutropenic episodes in children and young people with malignant disease
Lead Research Organisation:
University of York
Department Name: Centre for Reviews and Dissemination
Abstract
This project will develop a method of identifying children and young adult patients at low risk of harm when they present with febrile neutropenia, a complication of treatment for cancer. This may allow us to reduce the intensity or duration of the aggressive in-patient antibiotic treatment we currently use. The project will use individual patient data (IPD) pooled analysis, where the data from previously conducted studies are brought together and analysed to come to a more precise conclusion than any individual study could.
The project will form an international collaboration to collect the data, which will include researchers, doctors and parents. The analysis will try to find out if there are particular factors that would help us predict which children have the best outcomes. We will start by looking at the simplest information (such as the age of the child, or their diagnosis) and build in more complex data (such as specialized blood test results) to see if these make the prediction more accurate. The results of this analysis will be tested, and the potential economic effects estimated.
The methods used in performing IPD analysis will also be investigated, advancing our understanding of how best to conduct such studies.
The project will form an international collaboration to collect the data, which will include researchers, doctors and parents. The analysis will try to find out if there are particular factors that would help us predict which children have the best outcomes. We will start by looking at the simplest information (such as the age of the child, or their diagnosis) and build in more complex data (such as specialized blood test results) to see if these make the prediction more accurate. The results of this analysis will be tested, and the potential economic effects estimated.
The methods used in performing IPD analysis will also be investigated, advancing our understanding of how best to conduct such studies.
Technical Summary
Aim:
To develop and evaluate an optimal risk stratification regime for paediatric and young adult patients with febrile neutropenia (FNP).
Objectives:
1. To systemically review and critically appraise existing risk stratification models for the prediction of the outcome of febrile neutropenic episodes in child/young adulthood
2. To form a collaborative group to centrally collect individual patient data (IPD) from cohort studies of febrile neutropenia in childhood
3. To undertake an IPD pooled analysis, using regression models to quantify the risk of adverse clinical outcomes according to clinical variables
4. To develop and explore issues around the use of pooled IPD analysis in the development of predictive models
5. To develop and validate a new risk prediction model
6. To undertake an analysis of the potential economic impact of applying the new model in clinical practice
Design:
Evidence synthesis of observational studies of febrile neutropenia in children using an IPD approach.
Methodology:
1. Systematic review of existing paediatric FNP risk stratification guidelines.
2. IPD pooled analysis. An international collaboration will be established to facilitate the central collecting, validation and pooling of data from appropriate studies. The risk variables and outcomes selected for inclusion will be defined by literature review and consideration of the collaborative group. Should consensus fail to emerge, a formal process (Delphi questionnaires) will be used. The primary analysis will be based on the first recorded episode per patient to predict an absence of adverse outcomes (e.g. death, intensive care, or bacteremia). Subsequent episode data will be analysed to assess the independence of these data. The assessment will be by multivariate regression analysis, with variables entered after consideration of their clinical and statistical significance. The model will be tested by cross validation of intrinsic prognostic performance.
3. An analysis will be undertaken the potential economic impact of applying the new model in clinical practice.
4. Methodological refinement of the techniques of IPD pooled analysis will be undertaken (subject to the data obtained). The analyses may address the analysis of missing data, using different imputation models, the relative merits of prospective and retrospectively collected information, the comparison between episodic and patient-centred analyses and the use of categorical outcome variables.
Scientific opportunities:
The development the methodology of IPD pooled analysis for prognostic models.
Medical opportunities:
The appropriate selection of individuals for who FNP therapy could be safely changed from lengthy in-patient spells to short out-patient based treatment, reducing costs and inconvenience.?
To develop and evaluate an optimal risk stratification regime for paediatric and young adult patients with febrile neutropenia (FNP).
Objectives:
1. To systemically review and critically appraise existing risk stratification models for the prediction of the outcome of febrile neutropenic episodes in child/young adulthood
2. To form a collaborative group to centrally collect individual patient data (IPD) from cohort studies of febrile neutropenia in childhood
3. To undertake an IPD pooled analysis, using regression models to quantify the risk of adverse clinical outcomes according to clinical variables
4. To develop and explore issues around the use of pooled IPD analysis in the development of predictive models
5. To develop and validate a new risk prediction model
6. To undertake an analysis of the potential economic impact of applying the new model in clinical practice
Design:
Evidence synthesis of observational studies of febrile neutropenia in children using an IPD approach.
Methodology:
1. Systematic review of existing paediatric FNP risk stratification guidelines.
2. IPD pooled analysis. An international collaboration will be established to facilitate the central collecting, validation and pooling of data from appropriate studies. The risk variables and outcomes selected for inclusion will be defined by literature review and consideration of the collaborative group. Should consensus fail to emerge, a formal process (Delphi questionnaires) will be used. The primary analysis will be based on the first recorded episode per patient to predict an absence of adverse outcomes (e.g. death, intensive care, or bacteremia). Subsequent episode data will be analysed to assess the independence of these data. The assessment will be by multivariate regression analysis, with variables entered after consideration of their clinical and statistical significance. The model will be tested by cross validation of intrinsic prognostic performance.
3. An analysis will be undertaken the potential economic impact of applying the new model in clinical practice.
4. Methodological refinement of the techniques of IPD pooled analysis will be undertaken (subject to the data obtained). The analyses may address the analysis of missing data, using different imputation models, the relative merits of prospective and retrospectively collected information, the comparison between episodic and patient-centred analyses and the use of categorical outcome variables.
Scientific opportunities:
The development the methodology of IPD pooled analysis for prognostic models.
Medical opportunities:
The appropriate selection of individuals for who FNP therapy could be safely changed from lengthy in-patient spells to short out-patient based treatment, reducing costs and inconvenience.?