SBIR-STTR Award

Direct to Phase II

The overarching goal of this project is to change laboratory practice in the Clinical Immunohistochemistry (IHC) laboratory. IHC is the only clinical laboratory discipline without reference standards and traceable units of measure. This is despite the fact IHC is a major testing format in surgical pathology; a typical hospital IHC lab has a test menu of approximately 200 different tests. As a result, IHC analytic error rates range from 10 – 30% as compared to <1% for other types of clinical laboratory testing. These errors affect both predictive markers (HER2, PD-L1) as well as diagnostic markers (e.g., TTF-1, p53). From the 1950's to the 1970's, the field of Clinical Chemistry broadly adopted these higher standards of practice and error rates plummeted. This project is for the purpose of demonstrating the same benefit in Clinical IHC. This Applicant is uniquely qualified after having surmounted an important technical hurdle. Boston Cell Standards developed the first IHC calibrators with analyte concentrations traceable to a recognized standard - NIST Standard Reference Material 1934. The two Specific Aims of this project are: (1) Identify quantitative calibration ranges for accurate Clinical IHC testing, and (2) measure the benefit that calibrators offer towards reporting accurate test results. These will be the first studies correlating analytic sensitivity with diagnostic sensitivity and specificity. Namely, how many molecules per cell (of the target analyte) must the assay be capable of detecting in order to produce a diagnostically accurate test result? This is important even for qualitative tests that are reported as positive/negative, which are common in IHC. This analysis, while common in other fields of laboratory testing, is new to IHC. The experimental study design uses a Clinical IHC laboratory survey tool comprising a tissue microarray (TMA) and IHC calibrators. The TMA generates diagnostic sensitivity and specificity data while calibrators generate analytic sensitivity data. This project initiates a novel consortium that includes Boston Cell Standards, international IHC proficiency testing agencies, and academia. Although there is precedent in creating high-impact standardization programs for Clinical Chemistry testing, such an organization is unprecedented for IHC. The goal is to create and launch a National Immunohistochemistry Standardization Program, to oversee and execute data-driven studies for integrating reference standards to IHC. The consortium members are active partners in experimental design, execution, and data interpretation. The proposed clinical trial format has already been successfully tested and published with some of the consortium partners. Public Health Relevance Statement This project is aimed at generating the type of patient benefit data that justify a change in medical laboratory practice for immunohistochemistry. This is an international consortium of organizations aiming to standardize cancer biomarker testing of tissue sections, such as biopsies. The Applicant believes that there is a high likelihood that the study data will support a change in laboratory practice because the proposed new practice is already a standard of care in every other field of laboratory testing.

Project Terms:
Adoption ; Affect ; Biological Assay ; Assay ; Bioassay ; Biologic Assays ; Biopsy ; Boston ; Calibration ; Cells ; Cell Body ; Clinical Chemistry ; Clinical Trials ; Data Analyses ; Data Analysis ; data interpretation ; Europe ; Experimental Designs ; Future ; Goals ; Hospitals ; Immunohistochemistry ; Immunohistochemistry Cell/Tissue ; Immunohistochemistry Staining Method ; Laboratories ; Learning ; North America ; Legal patent ; Patents ; Surgical Pathology ; Patients ; Pilot Projects ; pilot study ; Problem Solving ; Publishing ; Reference Standards ; Research Design ; Study Type ; study design ; ROC Curve ; ROC Analyses ; receiver operating characteristic analyses ; receiver operating characteristic curve ; Sensitivity and Specificity ; Stains ; Staining method ; Standardization ; Surveys ; Survey Instrument ; Technology ; Testing ; Tissues ; Body Tissues ; Measures ; TP53 gene ; Antioncogene Protein p53 ; Cellular Tumor Antigen P53 ; Oncoprotein p53 ; P53 ; Phosphoprotein P53 ; Phosphoprotein pp53 ; Protein TP53 ; TP53 ; TRP53 ; Tumor Protein p53 ; Tumor Protein p53 Gene ; p53 Antigen ; p53 Genes ; p53 Tumor Suppressor ; protein p53 ; Journals ; Magazine ; Microscope ; Clinical ; Medical ; Evaluation ; Discipline ; Measurement ; ERBB2 gene ; ERBB2 ; HER -2 ; HER-2 ; HER2 ; HER2 Genes ; HER2/neu ; NEU Oncogene ; NEU protein ; Oncogene ErbB2 ; TKR1 ; c-erbB-2 ; c-erbB-2 Genes ; c-erbB-2 Proto-Oncogenes ; erbB-2 Genes ; herstatin ; neu Genes ; Funding ; editorial ; tool ; programs ; Adopted ; Investigation ; Slide ; Test Result ; Clinical Chemistry Tests ; Performance ; Accuracy of Diagnosis ; diagnostic accuracy ; R44 grant ; Ran 2 ; rat Ran-2 antigen ; rat Ran 2 protein ; novel ; member ; Reporting ; Modeling ; Sampling ; Address ; Academia ; Data ; Diagnostic Sensitivity ; International ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Tissue Microarray ; Tissue Arrays ; Tissue Chip ; Unit of Measure ; follow-up ; Active Follow-up ; active followup ; follow up ; followed up ; followup ; Output ; analytical tool ; high standard ; standard of care ; predictive marker ; predictive biomarkers ; predictive molecular biomarker ; programmed cell death ligand 1 ; B7-H1 ; B7H1 ; CD274 ; PD-L1 ; PDL-1 ; PDL1 ; Programmed Cell Death 1 Ligand 1 ; Programmed Death Ligand 1 ; programmed cell death protein ligand 1 ; diagnostic biomarker ; diagnostic marker ; cancer biomarkers ; cancer markers ; experimental study ; experiment ; experimental research ; detection limit ; accurate diagnostics ;