Contributions
Abstract: EP1149
Type: e-Poster
Background
Although HL has good overall disease control, its treatment is associated with an increased risk of late effects (LE), premature mortality, and compromised health-related quality of life (HRQL). Decision making is further complicated by clinical trial results that differ; a growing range of treatment options; and the absence of ideal, objective information on long-term outcomes with modern therapy.
Aims
To develop methods for a large multi-national collaborative to assemble the best available evidence, including detailed information extracted from prominent HL clinical trials, “real world” HL registries & ongoing HL survivorship cohorts in order to establish dynamic HL decision models (DM) to calculate individualized short-term disease outcomes, estimate impact on HRQL, and to project long-term risks (i.e., 30+ years) with modern therapy.
Methods
We formed an international consortium, HoLISTIC (www.hodgkinconsortium.com), consisting of 50+ pediatric & adult HL providers, decision scientists, statisticians, epidemiologists & patient (pt) advocates. We are creating a data repository of individual pt data (IPD) from 16 large contemporary pediatric & adult clinical trials for newly diagnosed HL pts & 6 HL survivorship/registry cohorts (Table), the latter enriched with LE data. We will enhance our prior DM from group level data (Parsons S et al. Brit J Haem 2018) to establish a dynamic DM from IPD. Using statistical & simulation modeling, the enhanced DM will project outcomes of interest including quality-adjusted life years (QALYs) reflecting both morbidity & mortality (early & late). Results will be validated & calibrated against prominent external cohorts (e.g., St. Jude LIFE Cohort & Dutch Hodgkin LE Cohort).
Results
Applying established data science methods, we created a common data model with a data dictionary across all sources resulting in creation of an annotated database. To date, we have fully harmonized IPD from 10 clinical trials (~8,000 HL pts) ranging in size from 165 to 1925 HL pts. At diagnosis, median age was 26 years (IQR 18-38); 52% were male; 43% had B symptoms, 34% had mediastinal bulk and 79% had nodular sclerosis histology. Median follow up was 5.0 years (IQR 3.5-7.4) for clinical trial pts. In addition, we have assembled “real world” data on >600 HL pts from a large community oncology system (Kaiser Permanente Southern California, KPSC) and created a unified data dictionary of the KPSC data and the Mayo/Iowa Molecular Epidemiology Resource HL cohort. Trial IPD harmonization is ongoing in order to create an enhanced DM that includes ‘linkage’ of survivorship/registry pts combined into the same model to help estimate LEs, including pre-mature mortality.
Conclusion
HoLISTIC capitalizes on a new multidisciplinary, International pediatric & adult oncology collaborative that has successfully harmonized extensive IPD, integrated from both clinical trials & HL survivorship/registry cohorts. Furthermore, we developed methods to combine IPD from clinical trials & survivorship cohorts into the same DM to provide objective data delineating the influence that pt (and disease) characteristics and alternative treatment options have on acute outcomes for individual HL pts as well as simulating/estimating future LEs (prior to therapy). The model will also allow for incorporation of updated information as new therapies & knowledge emerge and it will be open source. Additionally, the DM will be converted to a web-based platform to test & evaluate among HL providers & pts at the point of care in order to identify the options best aligned with pts values & preferences.
Session topic: 17. Hodgkin lymphoma - Clinical
Abstract: EP1149
Type: e-Poster
Background
Although HL has good overall disease control, its treatment is associated with an increased risk of late effects (LE), premature mortality, and compromised health-related quality of life (HRQL). Decision making is further complicated by clinical trial results that differ; a growing range of treatment options; and the absence of ideal, objective information on long-term outcomes with modern therapy.
Aims
To develop methods for a large multi-national collaborative to assemble the best available evidence, including detailed information extracted from prominent HL clinical trials, “real world” HL registries & ongoing HL survivorship cohorts in order to establish dynamic HL decision models (DM) to calculate individualized short-term disease outcomes, estimate impact on HRQL, and to project long-term risks (i.e., 30+ years) with modern therapy.
Methods
We formed an international consortium, HoLISTIC (www.hodgkinconsortium.com), consisting of 50+ pediatric & adult HL providers, decision scientists, statisticians, epidemiologists & patient (pt) advocates. We are creating a data repository of individual pt data (IPD) from 16 large contemporary pediatric & adult clinical trials for newly diagnosed HL pts & 6 HL survivorship/registry cohorts (Table), the latter enriched with LE data. We will enhance our prior DM from group level data (Parsons S et al. Brit J Haem 2018) to establish a dynamic DM from IPD. Using statistical & simulation modeling, the enhanced DM will project outcomes of interest including quality-adjusted life years (QALYs) reflecting both morbidity & mortality (early & late). Results will be validated & calibrated against prominent external cohorts (e.g., St. Jude LIFE Cohort & Dutch Hodgkin LE Cohort).
Results
Applying established data science methods, we created a common data model with a data dictionary across all sources resulting in creation of an annotated database. To date, we have fully harmonized IPD from 10 clinical trials (~8,000 HL pts) ranging in size from 165 to 1925 HL pts. At diagnosis, median age was 26 years (IQR 18-38); 52% were male; 43% had B symptoms, 34% had mediastinal bulk and 79% had nodular sclerosis histology. Median follow up was 5.0 years (IQR 3.5-7.4) for clinical trial pts. In addition, we have assembled “real world” data on >600 HL pts from a large community oncology system (Kaiser Permanente Southern California, KPSC) and created a unified data dictionary of the KPSC data and the Mayo/Iowa Molecular Epidemiology Resource HL cohort. Trial IPD harmonization is ongoing in order to create an enhanced DM that includes ‘linkage’ of survivorship/registry pts combined into the same model to help estimate LEs, including pre-mature mortality.
Conclusion
HoLISTIC capitalizes on a new multidisciplinary, International pediatric & adult oncology collaborative that has successfully harmonized extensive IPD, integrated from both clinical trials & HL survivorship/registry cohorts. Furthermore, we developed methods to combine IPD from clinical trials & survivorship cohorts into the same DM to provide objective data delineating the influence that pt (and disease) characteristics and alternative treatment options have on acute outcomes for individual HL pts as well as simulating/estimating future LEs (prior to therapy). The model will also allow for incorporation of updated information as new therapies & knowledge emerge and it will be open source. Additionally, the DM will be converted to a web-based platform to test & evaluate among HL providers & pts at the point of care in order to identify the options best aligned with pts values & preferences.
Session topic: 17. Hodgkin lymphoma - Clinical