1. Translational Research Methodology
Mission
Dr. Miranda Kleijn
Dutch Cancer Society

2. 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

3. 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

4. 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

5. TRWG coding scheme

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

7. 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

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

9. 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

10. Methodology Translational Research Resulting scheme (v2) post-validation

11. 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

12. 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

13. 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.

14. 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.

15. 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

16. Extension of methodology to Health Research Classification System (HRCS)

17. 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.