1. Imaging as a biomarker: standards for change measurements in therapy NIST, Gaithersburg, MD

2. Workshop « Imaging as Biomarker »  General issue: Imaging use for Clinical trials  Organized by NIST  Supported by:  Sponsoring organization: NIH, NCI (Larry Clarke)  FDA  Pharmaceutical industry: PhRMA, big labs  Normalization structures: NIST, NEMA  Professional societies: RSNA, AAPM, SNM, ISMRM, SPIE  Vendors: Siemens, GE, Philips  General issue: Imaging use for Clinical trials  Organized by NIST  Supported by:  Sponsoring organization: NIH, NCI (Larry Clarke)  FDA  Pharmaceutical industry: PhRMA, big labs  Normalization structures: NIST, NEMA  Professional societies: RSNA, AAPM, SNM, ISMRM, SPIE  Vendors: Siemens, GE, Philips

3. The issues (1/2)  Use of imaging to evaluate new treatment efficiency:  Not only a subjective reading of images  But, more and more objective measurements with “quantitative” methods  Examples : Alzheimer desease, lung cancer, arthrosis…  Low efficiency statement of clinical trials  Longs, expensives, and often… no positive result!  …  Use of imaging to evaluate new treatment efficiency:  Not only a subjective reading of images  But, more and more objective measurements with “quantitative” methods  Examples : Alzheimer desease, lung cancer, arthrosis…  Low efficiency statement of clinical trials  Longs, expensives, and often… no positive result!  …

4. The issues (2/2)  Main reasons:  Too often, mediocre quality of image data  No quantitative  Reproducibility issues (intra system and inter systems)  Acquisition protocols non respected → lot of cases are non usable  Data processing differs between different site ( → “site” effect)  Too subjective  Not enough automated  Insufficient quality of clinical data associated  “Local” semantic for clinical information  Resulting bias amplify intrinsic variability of the phenomena  → increase of the necessary number of cases  Data management cost  Because support tools needs to be rebuild case by case  Data cannot be re-used  Despite the politic of sponsoring organizations (dissemination plan)  No sharing infrastructure  Main reasons:  Too often, mediocre quality of image data  No quantitative  Reproducibility issues (intra system and inter systems)  Acquisition protocols non respected → lot of cases are non usable  Data processing differs between different site ( → “site” effect)  Too subjective  Not enough automated  Insufficient quality of clinical data associated  “Local” semantic for clinical information  Resulting bias amplify intrinsic variability of the phenomena  → increase of the necessary number of cases  Data management cost  Because support tools needs to be rebuild case by case  Data cannot be re-used  Despite the politic of sponsoring organizations (dissemination plan)  No sharing infrastructure

5. Solution components, standard based (1/2)  Standard phantoms to calibrate imaging systems  Standard study protocols  To be really identical between machines (patient preparation, image acquisition, pre-processing and applied corrections, reconstruction…)  Standard procedures (guidelines) to manage clinical trials  good comprehension of protocols, physician and technologists education, quality assurance  Meta data and clinical data standardization  Need the use of normalized terminologies, ontologies…  Standard phantoms to calibrate imaging systems  Standard study protocols  To be really identical between machines (patient preparation, image acquisition, pre-processing and applied corrections, reconstruction…)  Standard procedures (guidelines) to manage clinical trials  good comprehension of protocols, physician and technologists education, quality assurance  Meta data and clinical data standardization  Need the use of normalized terminologies, ontologies…

6. Solution components, standard based (2/2)  Management tools adapted to the data and processing management  Scientific calculation  Step sequencing (including quality assurance)  Providing the required traceability  Compatibility issues with current PACS (regarding image management)  Reference implementation (open source shared tools)  Standard processing tools (that can be shared)  Open source  Plug-in or services remotely executable  Standard data  Anatomical atlases  Reference data (e.g. healthy populations )  Management tools adapted to the data and processing management  Scientific calculation  Step sequencing (including quality assurance)  Providing the required traceability  Compatibility issues with current PACS (regarding image management)  Reference implementation (open source shared tools)  Standard processing tools (that can be shared)  Open source  Plug-in or services remotely executable  Standard data  Anatomical atlases  Reference data (e.g. healthy populations )

7. Needs for the future  Medical  No more and less than tomorrow treatments for numerous pathologies  Vendors  Pharmaceutical industry, decrease of validation costs for new medication  Imaging systems industry  New generations of systems. Economical model.  Sharing / interoperability of processing tools  Scientific  Validation of processing and image quantification tools  Diffusion and re-use of tools  Medical  No more and less than tomorrow treatments for numerous pathologies  Vendors  Pharmaceutical industry, decrease of validation costs for new medication  Imaging systems industry  New generations of systems. Economical model.  Sharing / interoperability of processing tools  Scientific  Validation of processing and image quantification tools  Diffusion and re-use of tools

8. What happened since the NIST workshop ?  The Gil Jost (RSNA), Larry Clarke (NCI) and Michael Vannier (University of Chicago) propositions were well received in France and in Europe.  SFR and ESR decided to join RSNA and NCI in an international initiative on biomarkers.  The Gil Jost (RSNA), Larry Clarke (NCI) and Michael Vannier (University of Chicago) propositions were well received in France and in Europe.  SFR and ESR decided to join RSNA and NCI in an international initiative on biomarkers.

9. RSNA meeting  At RSNA meeting, Guy Frija (ESR) and Philippe Grenier (SFR) met Gil Jost (RSNA) and FDA representatives to discuss on this topic.  FDA representatives:  Said that they will greatly appreciate if Europe join the project,  Asked SFR and ESR to investigate to find European partners.  RSNA, SFR and ESR agreed to say that they can be partners of the initiative for all imaging issues, but not leaders. They will transmit users needs on this topic to DICOM and imaging vendors.  At RSNA meeting, Guy Frija (ESR) and Philippe Grenier (SFR) met Gil Jost (RSNA) and FDA representatives to discuss on this topic.  FDA representatives:  Said that they will greatly appreciate if Europe join the project,  Asked SFR and ESR to investigate to find European partners.  RSNA, SFR and ESR agreed to say that they can be partners of the initiative for all imaging issues, but not leaders. They will transmit users needs on this topic to DICOM and imaging vendors.

10. Recent developments  In France:  SFR have contacts with AFSAPS (FDA like French Agency),  Sanofi-Aventis (pharmaceutical lab) is interested.  In Europe:  EMEA (European MEdicine Agency) is interested,  EFPIA (European Federation of Pharmaceutical Industries and Associations) will be contacted soon,  Novartis (pharmaceutical lab) will probably be interested: it is searching for a radiologist to manage a biomarker department.  In France:  SFR have contacts with AFSAPS (FDA like French Agency),  Sanofi-Aventis (pharmaceutical lab) is interested.  In Europe:  EMEA (European MEdicine Agency) is interested,  EFPIA (European Federation of Pharmaceutical Industries and Associations) will be contacted soon,  Novartis (pharmaceutical lab) will probably be interested: it is searching for a radiologist to manage a biomarker department.