In this series of posts on Laboratory Developed Tests (LDTs), I discuss the history of the regulation of LDTs and impending changes (posts #1 and #2). I also discuss possible criteria that pathologists, treating physicians, and healthcare systems could use to determine which tests are well validated (post #3).
I think there are at least four reasons for pathologists to learn more about LDTs right now: 1) the number of LDTs, particularly in oncology, is rapidly increasing, 2) the demands for fresh and fixed tumor tissue for reserch and biorepositories are also rapidly increasing, 3) some of these assays are associated with significant costs (thousands of dollars per test in many instances), 4) the regulatory oversight of LDTs is undergoing a major change.
Laboratoty Developed Tets (LDTs) are tests that are developed, validated, and performed in only one laboratory. Unlike most tests, LDTs are not sold or distributed to other commercial or hospital-based laboratories. Many of these tests are complex genetic assays, some of which involve analyzing the expression of multiple genes to generate a predictive or prognostic index for a type of cancer or to help determine the site of origin for a metastatic tumor. The tests that analyze multiple genes or evaluate combinations of results were formerly referred to as In Vitro Diagnostic Multivariate Index Assays (IVDMIA) (more on this in the next post). A gene expression profiling test for breast cancer would be one example of an IVDMIA.
Food and Drug Administration (FDA) clearance or approval is not required for LDTs. The laboratory that develops and performs the test is regulated by the Center for Medicare and Medicaid Services (CMS) through the Clinical Laboratory Improvement Amendments (CLIA). The labs obtain a CLIA license and perform all the tests in their own facility. CLIA regulates the development and analytical performance of LDTs, requiring the tests to meet standards for accuracy, precision, total sensitivity, and total specificity. Over the past few years, the disccusion about the regulation of analytical and clinical validation of LDTs and the role of the FDA has intensified. The policy of the FDA, until recently, has been one of “enforcement discretion,” meaning that the FDA believes it has the legal authority to regulate LDTs but has chosen not to. The FDA recently announced an end to its policy of enforcement discretion for LDTs, and a new regulatory framework for LDTs is being drafted (more on that in the next post). This proposed change in the oversight of LDTs has become quite controversial, to say the least.
The explosion in the number of patients tested by LDTs, particularly patients with (or at risk for) breast cancer, has prompted several questions....
Some in the regulatory agencies and healthcare have asked: How are patient safety and the effectiveness of the tests for the intended uses established? Do we want treatment decisions for tens of thousands of patients to be based on tests over which the FDA exercises no oversight? What type of premarket evaluation by the FDA (if any) should be required?
Members of industry and healthcare providers have asked: How will an increased regulatory burden affect assay development? How will analytical and clinical validity be balanced with patient safety and access to cutting-edge technology that may help guide treatment decisions? Will reimbursement for the tests keep up with the anticipated increased costs of development and compliance?
What do you think? Is FDA oversight of LDTs is long overdue or a new and unnecessary barrier to innovation in complex diagnostic testing?
In the next installment, I will briefly discuss recent developments in regulation of LDTs through the end of 2010. Ben Calhoun
Ben Calhoun is a practicing surgical pathologist in Charlotte, North Carolina with expertise in breast pathology. He trained at Yale and Vanderbilt and went to medical school and graduate school at the Medical College of Georgia. He is the Medical Director of Surgical Pathology for Carolinas Laboratory Network and, in his spare time, is an MBA student in the McColl School of Business at Queens University in Charlotte (anticipated graduation in December 2011).
Ben's initial posts have focused on Accountable Care Organizations (ACOs) and Laboratory Developed Tests (LDTs).
- New Facebook Group for Pre-Med and Medical Students Considering Pathology - April 5th, 2010 [April 5th, 2010]
- Virtual Cytology Catalog from i-Path - April 7th, 2010 [April 7th, 2010]
- Mobile technologies will enable patient-centered care, PwC report says - April 8th, 2010 [April 8th, 2010]
- EMRs a 'double-edged sword' for physician communication - April 9th, 2010 [April 9th, 2010]
- FROM THE DARK REPORT and DARK DAILY: Negotiating Pathology Part A Reimbursement with Hospitals: Why the Performance-Based Approach Opens the Door to Increased Value - April 10th, 2010 [April 10th, 2010]
- iPerio - Thoughts about portability of digital pathology practice - April 12th, 2010 [April 12th, 2010]
- ASCP Board of Directors Names New Executive Vice President - April 13th, 2010 [April 13th, 2010]
- Virginia Company Develops Automated TB Detection System - April 13th, 2010 [April 13th, 2010]
- Now on Facebook - April 14th, 2010 [April 14th, 2010]
- Hospitals test iPad for patient education - April 15th, 2010 [April 15th, 2010]
- Consult A Doctor, Inc. Names Retail Clinic Pioneer, Douglas Smith, M.D. as Chief Medical Officer - April 16th, 2010 [April 16th, 2010]
- PathXL: Cloud Computing for Virtual Microscopy - April 19th, 2010 [April 19th, 2010]
- CAP and ASCO Release New ER/PR Testing Guideline - April 20th, 2010 [April 20th, 2010]
- What is the real cost of healthcare? - April 20th, 2010 [April 20th, 2010]
- CALL FOR ABSTRACTS: Medicine 2.0’10: 3rd World Congress on Social Media and Web 2.0 in Health, Medicine, and Biomedical Research on November 29-30, 2010 in Maastricht, The Netherlands. - April 21st, 2010 [April 21st, 2010]
- Blood Test Meant To Analyze Genetic Activity Could Replace Biopsies After Heart Transplantation - April 23rd, 2010 [April 23rd, 2010]
- New Digital Pathology Blog - Digital Pathology Insights from Definiens - April 26th, 2010 [April 26th, 2010]
- World's Smallest, Lightest Telemedicine Microscope - April 27th, 2010 [April 27th, 2010]
- ATA 2010 Meeting Announcement - April 28th, 2010 [April 28th, 2010]
- ASCP 2010 Annual Meeting Digital Pathology Course Offerings - April 29th, 2010 [April 29th, 2010]
- Announcement for Upcoming Aperio Digital Pathology Seminars in Chicago and Cleveland - May 4th, 2010 [May 4th, 2010]
- Will Pathology PACS eliminate injuries or cause different ones? - May 5th, 2010 [May 5th, 2010]
- Axillary Node Dissection, Sentinel Lymph Node Biopsy May Pose More Harm Than Good In Patients With Pure DCIS - May 6th, 2010 [May 6th, 2010]
- Hospital's Emergency Room Use of Telemedicine through Webcam - May 6th, 2010 [May 6th, 2010]
- Dr. Alexander R. Judkins Named Department Head of Pathology Laboratory Medicine at Childrens Hospital Los Angeles - May 10th, 2010 [May 10th, 2010]
- Case of the Week 51 - May 11th, 2010 [May 11th, 2010]
- Telestroke has another success - May 12th, 2010 [May 12th, 2010]
- Amazon's Kindle Showing Promise as Means to Access Medical Literature - May 12th, 2010 [May 12th, 2010]
- "This is what your healthcare is going to look like" - May 13th, 2010 [May 13th, 2010]
- Comments open - May 15th, 2010 [May 15th, 2010]
- Errata and miscellaneous news - May 16th, 2010 [May 16th, 2010]
- Up-to-date News from BioImagene - May 16th, 2010 [May 16th, 2010]
- Case of the Week 52 - May 19th, 2010 [May 19th, 2010]
- “This is what your healthcare is going to look like.” - May 19th, 2010 [May 19th, 2010]
- CBLPath Announces Department of Integrated Diagnostics - June 7th, 2010 [June 7th, 2010]
- A CEO’s Guide to Molecular Diagnostic Reimbursement: Navigating the Many Challenges of Reimbursement and Commercialization - June 7th, 2010 [June 7th, 2010]
- Abstracts Solicited for the Pathology Informatics 2010 Conference in Boston on 19-22 Septembe - June 7th, 2010 [June 7th, 2010]
- Telecytopathology for immediate evaluation of fine-needle aspiration specimens - June 7th, 2010 [June 7th, 2010]
- Definiens Digital Pathology Webinar Announcement: SOX2 Evaluation in NSCLC using Definiens Tissue Studio - June 7th, 2010 [June 7th, 2010]
- Who is on your "A team"? - June 7th, 2010 [June 7th, 2010]
- PATHOLOGY VISIONS ABSTRACT DEADLINE EXTENDED TO JUNE 15 - June 7th, 2010 [June 7th, 2010]
- First edition of Journal of Pathology Informatics has been published! - June 7th, 2010 [June 7th, 2010]
- BioImagene to show its digital pathology solutions at European Congress - June 7th, 2010 [June 7th, 2010]
- Hastings Center Report - Medical Tourism - June 7th, 2010 [June 7th, 2010]
- Hamner Institutes for Health Sciences Selects Definiens Software For Liver Toxicology Study - June 7th, 2010 [June 7th, 2010]
- Definiens Invites Speakers for First International Definiens Symposium this October in Spain - June 7th, 2010 [June 7th, 2010]
- CMS issues NPRM to credential telemedicine - June 7th, 2010 [June 7th, 2010]
- Get ready for global location numbers - June 7th, 2010 [June 7th, 2010]
- Penn State Virtual Microscopy - June 7th, 2010 [June 7th, 2010]
- What if a Ritz-Carlton executive ran your hospital? - June 7th, 2010 [June 7th, 2010]
- Dartmouth-Hitchcock Inks Deal with BioImagene - June 11th, 2010 [June 11th, 2010]
- Flagship Biosciences makes training courses available - June 11th, 2010 [June 11th, 2010]
- Opportunity at ChemImage for Histopathology Algorithm Scientist - June 11th, 2010 [June 11th, 2010]
- Pathology Visions Announces Keynote Speaker; Abstract Deadline Extended - June 11th, 2010 [June 11th, 2010]
- Let's Go Hawks - June 11th, 2010 [June 11th, 2010]
- Case of the Week 53 - June 11th, 2010 [June 11th, 2010]
- Case of the Week 54 - June 14th, 2010 [June 14th, 2010]
- Thoughts on How Digital Pathology Will Usher in New Era of Personalized Medicine - June 15th, 2010 [June 15th, 2010]
- Webinar from CRi on Quantitating Multiple Protein Expression in Intact Tissue - June 15th, 2010 [June 15th, 2010]
- Eye-Candy: Detection of Crypt Volume and Ki67 nuclear biomarkers using Definiens XD - June 16th, 2010 [June 16th, 2010]
- Image Analysis as a Tool for Prognostic and Predictive Biomarkers in Breast Cancer – How Reliable Is It? - June 17th, 2010 [June 17th, 2010]
- CAP Pathologist Service Spotlight Award Announced - June 19th, 2010 [June 19th, 2010]
- Compelling Results from SOX2 Expression Analysis Study in NSCLC using Definiens Tissue Studio - June 19th, 2010 [June 19th, 2010]
- Dako and Omnyx Sign Agreement within Digital Pathology - June 22nd, 2010 [June 22nd, 2010]
- Precision breast panel analysis with the Ventana VIAS Image System - June 22nd, 2010 [June 22nd, 2010]
- Scientists Create 3D Models of Whole Mouse Organs - June 24th, 2010 [June 24th, 2010]
- Is the iPad Radiology's Dream Device For Mobile Healthcare? - June 24th, 2010 [June 24th, 2010]
- Pathology Informatics 2010 - Sept 19-22, Boston, MA - Mark your Calendars - June 27th, 2010 [June 27th, 2010]
- www.GoPathDx.com - June 28th, 2010 [June 28th, 2010]
- Case of the Week 55 - June 28th, 2010 [June 28th, 2010]
- S.C. Medical Board considers anatomic pathology services arrangements - June 29th, 2010 [June 29th, 2010]
- Online Pathology: Moving Forward, Standing Still - July 1st, 2010 [July 1st, 2010]
- Aurora Interactive and PLUS Diagnostics Enters Into a Deal to Power Pathology Labs With Digital Communications Technology - July 1st, 2010 [July 1st, 2010]
- Laboratory Automation White Paper:Achieving Best Practices with Total Laboratory Automation - July 5th, 2010 [July 5th, 2010]
- Update on Rules for Telemedicine Privileges - July 6th, 2010 [July 6th, 2010]
- CAP Virtual Management Conference Now in Webinar Format - July 7th, 2010 [July 7th, 2010]
- http://imasence.com/Dokumente/WSI%20DICOM%20PACS%20Compression%20TIGA.pdf - July 8th, 2010 [July 8th, 2010]
- Beth Israel Pathologists Press for Personalized Medicine Training - July 9th, 2010 [July 9th, 2010]
- Blood smear reveals popular video game character - July 12th, 2010 [July 12th, 2010]
- Webinar Announcement – Introducing: Definiens Tissue Studio 2.0 - July 13th, 2010 [July 13th, 2010]