Thebroad,long-?termgoalofthisprojectisconsistent,standardizeddiagnostictestingofsurgical specimensbyimmunohistochemistry(IHC).Themethodstoachievethisgoalarewellunderstoodinthe fieldofclinicallaboratorytesting:(1)standardizationofreagentsandprotocols,(2)automationto reducehumanerrors,and(3)theuseofstandardizedcontrolstoprovidetestperformancefeedback. Overthelasttwodecades,thefirsttwoofthesethreemethodswereimplementedforIHCtesting.This grantprojectfocusesonthethird-?-?standardizedIHCcontrols.Currentpracticeteachesnon- standardizedcontrols.Eachhistopathologylabtypicallyprocurestestcontrolsfromleftovertissue samplesinitsownparaffinblockarchives.Thisisastrikinglydifferentpracticefromclinicalblood laboratories,wherestandardizedandvalidatedcontrolsareproducedinlargequantitiesandsold throughcommercialvendors. Wehavedevelopedaninnovativetechnicalsolution,summarizedinaseriesofpublishedjournal articles.Overthelast2yearsandwithNCIfunding,ourbreastcancerIHControlsTMpanelforHER-?2,ER, andPRtestsrecentlyenteredclinicaltestingandwillbesubmittedforregulatoryclearancethisyear (2016). ThisDirect-?to-?PhaseIIproposaladdressesclinicalIHClaboratorypracticebeyondbreastcancer testing.WewillexpandtheIHControlsTMproductportfolio,from3analytes(HER-?2,ER,&PR)to30.The newIHControlsTMpanelscomprisetheGeneralPathology,Melanoma,LungCancer,andHematopathology testportfolios.Thisten-?foldexpansionisfeasiblewithfundingfromasinglePhaseIIgrantbecause:(a) wehavealreadyworkedoutthenuancesofproductdesign,manufactureundercGMP,andtesting,and (b)theadditionalanalyteswillmostlybeclassIproducts.
The SpecificAims ofthisproposalare:(1) creationofthenewIHControlsTMpanels,(2)analyticalvalidation,includingtestingforsensitivity, specificity,productstability,andmanufacturingreproducibility,and(3)clinicalvalidation,including testingforprecision,referenceinterval(expectedlevelofstaining),andlimitofdetection. Theapplicantgroupcomprisesabroad,multi-?disciplinaryteam,includingtheMDPR&Dteam, statisticalsupportfromtheTuftsClinical&TranslationalScienceInstitute(CTSI),surgicalpathologists, andconsultantsforregulatoryaffairs,qualitysystems,andIHCcommercialoperations.Converting clinicallaboratoriesfromhomebrewtostandardizedcontrolswillbeatransformativechange.

Public Health Relevance

This project is to fund the development and clinical regulatory studies for a new, first-in- class, type of clinical test control in the field of (cancer) immunohistochemistry (IHC) testing. These clinical IHC test controls will solve an important problem in the field of cancer testing, relating to variability and inconsistency in IHC testing. Clinical test controls are important for promoting test reproducibility and consistency amongst hospital laboratories. These are the first standardized and quantificable IHC controls.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
1R44CA213476-01
Application #
9253142
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Lou, Xing-Jian
Project Start
2017-05-01
Project End
2019-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Medical Discovery Partners, LLC
Department
Type
DUNS #
126775860
City
Boston
State
MA
Country
United States
Zip Code
02111
Sompuram, Seshi R; Vani, Kodela; Schaedle, Anika K et al. (2018) Quantitative Assessment of Immunohistochemistry Laboratory Performance by Measuring Analytic Response Curves and Limits of Detection. Arch Pathol Lab Med 142:851-862
Vani, Kodela; Sompuram, Seshi R; Schaedle, Anika K et al. (2017) The Importance of Epitope Density in Selecting a Sensitive Positive IHC Control. J Histochem Cytochem 65:463-477
Vani, Kodela; Sompuram, Seshi R; Schaedle, Anika K et al. (2017) Analytic Response Curves of Clinical Breast Cancer IHC Tests. J Histochem Cytochem 65:273-283