Translational Research Methodology Mission www.icrpartnership.org Dr. Miranda Kleijn Dutch Cancer Society

Translational Research What is Translational Research (TR)? The transition from basic research to clinical testing. Bench-to-bedside Why is analysis of TR important for cancer research organizations? Trends in TR are important for funding decisions Acceleration of the transition from basic research to clinical testing More new treatments to the patients

Methodology Translational Research Dilemma CSO code not developed to recognize translational research (TR). TRWG coding scheme for translational research Double coding of 76,581 grants in ICRP database too time-consuming Goal Indicating which CSO codes coincide with TR by analysis of projects coded with both CSO and TRWG coding methods Intended result Use CSO coding system as tool to identify TR CSO TRWG Broad outline to detect TR

CSO coding scheme 1. Biology 2. Etiology 3. Prevention 1.1 Normal functioning 1.2 Alteration chromosomes 1.3 Oncogenes and tumor suppressor genes 1.4 Progression and metastasis 1.5 Resources and infrastructure 2. Etiology 2.2 Endogenous factors 2.3 Interactions 2.4 Resources and infrastructure 3. Prevention 3.1 Interventions to prevent cancer 3.2 Nutritional science 3.3 Chemoprevention 3.4 Vaccines 3.5 Complementary and alternative approach 3.6 Resources and infrastructure 4. Early detection, diagnosis and prognosis 4.1 Development and discovery 4.2 Evaluation 4.3Testing in clinical setting 4.4 Resources and infrastructure 5. Treatment 5.1 Localized - Development 5.2 Localized - Clinical 5.3 Systemic - Development 5.4 Systemic - Clinical 5.5 Localized + Systemic 5.6 Complementary and alternative approach 5.7 Resources and infrastructure 6. Control, survivorship, outcome 6.1 Care and survivorship 6.2 Surveillance 6.3 Behavior 6.4 Cost analysis 6.5 Education 6.6 Ethics 6.7 Complementary and alternative approach 6.8 Resources and infrastructure 7. Scientific model systems 7.1 Development 7.2 Application 7.3 Resources and infrastructure

TRWG coding scheme

Methodology Translational Research Dutch Cancer Society (DCS) expanded TWRG coding scheme to fit all types of research in DCS portfolio

Methodology Translational Research: Approach Assumptions before investigation Description of CSO codes was used to map translational research roughly into specific CSO categories Awards either wholly or partly coded to specific CSO codes are considered translational Approach Awards from CCRA or NCI* coded ONLY to one CSO code Manual mapping of awards to basic or translational (early/late/clinical) research Check with TWRG coding performed by CCRA or NCI Creation of a map of CSO vs TR *CCRA = Canadian Cancer Research Alliance *NCI = National Cancer Institute

Methodology Translational Research Resulting scheme (v1) We then tested this using 2 pilot datasets

Methodology Translational Research: Validation Validation of the method Comparison of two datasets manually coded to TRWG and CSO with the CSO-based TR coding scheme KWF awards coded to an adapted TRWG system ICRP bladder cancer awards coded manually to TRWG Translational projects (KWF) ICRP bladder cancer projects 137/139 (99%) of awards classed as TR by manual coders were also classed as TR by the CSO method. 81/83 (98%) of awards classed as TR by manual coders were also classed as TR by the CSO method. Result: Using the CSO as a proxy for TR worked well and was within expected margins of error

Methodology Translational Research Resulting scheme (v2) post-validation

TR TR (early) TR/clinical TR (patient) 1. Biology 1.1 Normal functioning 1.2 Alteration chromosomes 1.3 Oncogenes and tumor suppressor genes 1.4 Progression and metastasis 1.5 Resources and infrastructure 2. Etiology 2.2 Endogenous factors 2.3 Interactions 2.4 Resources and infrastructure 3. Prevention 3.1 Interventions to prevent cancer 3.2 Nutritional science 3.3 Chemoprevention 3.4 Vaccines 3.5 Complementary and alternative approach 3.6 Resources and infrastructure 4. Early detection, diagnosis and prognosis 4.1 Development and discovery 4.2 Evaluation 4.3Testing in clinical setting 4.4 Resources and infrastructure 5. Treatment 5.1 Localized - Development 5.2 Localized - Clinical 5.3 Systemic - Development 5.4 Systemic - Clinical 5.5 Localized + Systemic 5.6 Complementary and alternative approach 5.7 Resources and infrastructure 6. Control, survivorship, outcome 6.1 Care and survivorship 6.2 Surveillance 6.3 Behavior 6.4 Cost analysis 6.5 Education 6.6 Ethics 6.7 Complementary and alternative approach 6.8 Resources and infrastructure 7. Scientific model systems 7.1 Development 7.2 Application 7.3 Resources and infrastructure

Methodology Translational Research Sufficiently robust to use CSO sub-codes as a proxy for TR Significantly reduces manual coding time Introduces consistency between different coders/organizations Caveats Additional category of ‘patient-focused TR’ was added for clarity Cancer survival, health services and behavioral/education research is difficult to classify into a standard ‘basic – translational – clinical’ scheme Often contains late translational/clinical research Prevention research (CSO3) is called ‘Translational’ research Research is not split out into clear translational/clinical boundaries. Research is spread from early – late translation / clinical in the TRWG scheme

Methodology Translational Research Issues with prevention codes - Examples: Research program encompasses both biology of chemoprevention (early TR) and a phase II trial (late TR/clinical) but is (appropriately) coded to CSO3.3. This is then coded to “Translational” in this scheme.

Trends in Translational Research in ICRP database Using the ICRP TR method: Initial results from our forthcoming data report suggest that TR (especially early/translational) has risen from 63% of the portfolio in 2005 to 67% in 2012, indicating that organizations’ efforts to increase TR are successful.

Extension of methodology to Health Research Classification System (HRCS) HRCS = a system for classifying and analysing biomedical and health research funding. Research Activity Codes Used to classify the type of research activity (from basic to applied). 48 codes divided into eight groups: Underpinning Aetiology Prevention Detection and Diagnosis Treatment Development Treatment Evaluation Disease Management Health Services

Extension of methodology to Health Research Classification System (HRCS)

Methodology Translational Research Conclusions CSO (or HRCS) can be used as a tool to identify TR Automated methodology Trends in translational research funding can now be identified easily ICRP will use this methodology to monitor trends in TR funding.