Oversight of Laboratory Developed Tests (LDTs) Andrew C.

Oversight of Laboratory Developed Tests (LDTs) Andrew C.

Oversight of Laboratory Developed Tests (LDTs) Andrew C. Fish, Executive Director NCCS Cancer Policy Advocate Training November 13, 2014 Presentation Overview Who is AdvaMedDx? What are diagnostics and how are they currently regulated? What are the concerns with LDTs? How does FDA plan to oversee LDTs?

Questions/Discussion AdvaMedDx.org 2 What are Diagnostics? Diagnostics are tests performed on samples taken from the body, such as blood, tissue, and urine. Clinical Chemistry

Hematology & Cytology Examples: Urinalysis; blood glucose monitor. Measuring essential chemicals to monitor basic bodily functions and uncover abnormal ities. Examples: Pap tests; blood cell counts. Assessment of blood functi ons; identification of cellular pathologies. Immunochemistry and Microbiology

Examples: tumor marker tests, HIV antibody tests, streptococcal throat tests, and urinary tract tests. Detection and identification of disease-causing agents, like bacteria and viruses, as well as the proteins, hormones, and antibodies related to the functions of the bodys immune system. AdvaMedDx.org 4 What are Diagnostics? contd Molecular Diagnostics Molecular diagnostic tests detect target proteins and specific genetic sequences (biomarkers) to help identify disease presence, type, progression, and recurrence risk.

Examples: multivariate-index test to determine risk of breast cancer recurrence; BRAF mutation test to determine late stage melanoma patient candidates for targeted drug therapy. These advanced diagnostic tests help clinicians tailor care to subpopulations and individualsenabling targeted personalized medicine. An important component of personalized medicine is the emerging field of companion diagnostics, in which a molecular diagnostic test is used to identify whether a specific drug (companion with the test) is right for an individual patient. AdvaMedDx.org 5

Cancer Diagnostics Screening Diagnosis (taxonomy of cancer evolving from site-specific to genetic) Prognosis/Recurrence Risk Treatment Selection Monitoring/Follow up AdvaMedDx.org

6 Evaluating Diagnostics Food, Drug, & Cosmetic Act: safe and effective as determined by FDA Means: Analytically valid meets claim of what it measures and how accurately Clinically valid the thing measured is relevant to the disease (and, in many cases, to a care decision)

AdvaMedDx.org 7 What is Risk? Risk = possibility of harm to patient that could result if test results are incorrect Higher risk: When a false result could lead to incorrect and harmful clinical management, an unnecessary invasive procedure, or failure to follow up on a serious condition

The purpose of FDA review is to assure availability of safe and effective tests for the protection of patients. AdvaMedDx.org 8 What are Laboratory Developed Tests? Diagnostic tests are (1) produced by manufacturers for distribution to laboratories or other users, or

(2) produced in and offered by laboratories for use in their own facilities these are laboratory developed tests (LDTs). In addition to LDTs used in professional settings, some labs are marketing their own tests directly to consumers including genetic tests claiming to identify disease risk. AdvaMedDx.org 9 So What is the Issue?

Although both statute and regulation cover LDTs, FDA does not currently enforce its regulations for LDTs. FDA does enforce regulate diagnostics that manufacturers sell to laboratories and other users requiring pre-market assurance of safety and effectiveness. Since 1976, FDA has generally exercised enforcement discretion for LDTs. Why? Because, at that time, LDTs generally were wellunderstood and relatively simple low risk-tests, or used

for rare conditions for which adequate validation would not be feasible. Now, LDTs encompass even the most advanced molecular diagnostics, such as technically complex genetic tests that guide cancer treatment. AdvaMedDx.org 10 Why the Concern with LDTs? FDA: Diagnostic tests are playing an increasingly important role in clinical decision making and disease management, particularly in the context of personalized medicine. LDTs are often used to assess high-risk but relatively common diseases and conditions and to inform critical

treatment decisions. Even when FDA-approved tests are available for a disease or condition, laboratories often continue to use LDTs that have not been reviewed by the agency. LDTs that have not been properly validated for their intended use put patients at risk. Risks include risk of missed diagnosis, wrong diagnosis, and failure to receive appropriate treatment. AdvaMedDx.org 11 So Who Oversees Lab Developed Tests Now? The Centers for Medicare and Medicaid Services (CMS) has oversight authority of clinical

laboratories under the Clinical Laboratory Improvement Amendments of 1988 (CLIA). CLIA establishes laboratory quality standards and ensures that labs are following good lab practices, including testing procedures and the employment of credentialed lab personnel. But CLIA is not a substitute for FDA oversight. Only FDA has the resources and expertise to review LDTs for safety and effectiveness. AdvaMedDx.org 12

What CLIA Does Not Do CMS itself has said CLIA regulations are not a substitute for FDA oversight. Many critical features of FDA oversight are missing from CLIA. F u r t h e r m o r e , C M S d o e s n o t h a v e t h e e x p er t i s e o r r e s o u r c e s t o o v e r s e e L D Ts i n t h e s a m e m a n n e r a s F D A . U n l i k e F D A o v e r s i g h t o f d i a g n o s t i c s , CL I A : D o e s n o t r e g u l a t e t h e s a f e t y a n d e ff e c t i v e n e s s o f d i a g n o s t i c t e s t s ; Does not require pre-market review of tests; Does not require demonstration of clinical validity (whether the test is meaningful for clinical decision making); Does not require systematic adverse event reporting;

Does not have a process for corrections or recalls. A t e s t i s a t e s t a n d pr e s e n t s t h e s a m e r i s k f o r p a t i e n t s r e g a r d l e s s o f w h e t h e r i t i s d e v e l o p e d b y a m a n u f a c t u r e r or a l a b o r a t o r y. P o t e n t i a l h a r m s to patients whose tests return incorrect results include unnecessary t r e a t m e n t s , wi t h t h e i r a c c o m p a n y i n g c o s t s a n d s i d e e ff e c t s , a n d t r e a t m e n t delay or failure to obtain appropriate treatment, all of which lead to worse outcomes for those patients. AdvaMedDx.org 13 Calls for Reform Are Not New

April 2008: HHS Secretarys Advisory Committee on Genetics, Health, and Society (SACGHS) issues report: US System of Oversight of Genetic Testing: A Response to the Charge of the Secretary of Health and Human Services Calls upon FDA to address all laboratory tests, regardless of how they are produced (i.e., as a commercial test kit or laboratory-developed test). AdvaMedDx.org 14

Stakeholders Endorse FDA Oversight Numerous Cancer Advocacy Groups, incl. American Cancer Society American Association for Cancer Research Ovarian Cancer National Alliance Cancer Leadership Council National Coalition for Cancer Survivorship

American Society of Clinical Oncology American Heart Association College of American Pathologists National Health Council College of American Pathologists Society for Womens Health Research AIDS Institute Alliance for Aging Research Mens Health Network AdvaMedDx.org

15 FDA Proposed LDTs Framework October Draft Guidance: Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs). Defines LDT as a test intended for clinical use and designed, manufactured and used within a

single laboratory A risk-based approach start with high risk tests and phase in enforcement over time (9 years). LDTs divided into current three risk categories Class I (low), Class II (moderate), and Class III (high) AdvaMedDx.org 16 Exceptions For Low Risk and Special Needs *Notification/registration and listing and adverse events reporting required AdvaMedDx.org

17 LDTs for Rare Diseases AdvaMedDx.org 18 Traditional LDTs AdvaMedDx.org 19 LDTs for Unmet Needs

AdvaMedDx.org 20 Regulatory Requirements for All LDTs AdvaMedDx.org 21 Regulatory Requirements for High and Moderate Risk LDTs (9 Year Phase In) AdvaMedDx.org

22 Implementation Timeline for All LDTs After Final Guidance AdvaMedDx.org 23 What Happens Now? Stakeholders will comment on draft guidance (comments close February 2 n d ) FDA

will issue final guidance (timing uncertain) Stay tuned regarding Congressional interest AdvaMedDx.org 24 Questions?

Recently Viewed Presentations

  • Health Protection Surveillance Centre Impact of the Pneumococcal

    Health Protection Surveillance Centre Impact of the Pneumococcal

    Mary Corcoran1, Prof Hilary Humphreys2, Suzanne Cotter3, Robert Cunney1, 3, ... 2Education and Research Centre, Royal College of Surgeons in Ireland and Beaumont Hospital. 3Health Protection Surveillance Centre (HPSC), Dublin. Acknowledgements.
  • Iterative Fuzzy Clustering regions of Interest in Skin Lesions

    Iterative Fuzzy Clustering regions of Interest in Skin Lesions

    Iterative Fuzzy Clustering Regions of Interest in Skin Lesions By R. Cucchiara, C. Grana, M. Piccardi Presented by Mohammed Jirari October 23rd, 2002
  • Chapter 7: Technology Acceloraters

    Chapter 7: Technology Acceloraters

    CHAPTER 7: TECHNOLOGY ACCELORATERS. Katy Lovett, CJ Baker, and Matt Snowden. Does technology fit into your hedgehog concept? If yes, carefully select it. If no, do without or settle for less. Technology is an accelerator, not a creator of change.
  • Les verbes réfléchis

    Les verbes réfléchis

    REFLEXIVE VERBS = REFLEXIVE PRONOUN + VERB Reflexive pronouns represent the same person as the SUBJECT. Reflexive pronouns come immediately BEFORE the verb. Note that me, te, and se become m', t', and s' before a vowel sound. Les verbes...
  • An Analysis of Socio-Economic Impact of the New

    An Analysis of Socio-Economic Impact of the New

    It is worthwhile to note that this model of transport cooperatives is rare in Kenya .One SACCO (2NK) has attempted it by operating high capacity buses parallel to the core model of managing the 14-seaters vehicles. According to the Chairman...
  • Michelle Obamas Speech at the 2012 Democratic National

    Michelle Obamas Speech at the 2012 Democratic National

    : The "new" conversation casts Obama in a better light than Romney. If the RNC message was that "times are bad, and Obama hasn't made them any better, so we need a change of leadership," Michelle's goal to is change...
  • Data Collection in the Classroom - Illinois Service Resource ...

    Data Collection in the Classroom - Illinois Service Resource ...

    Step 1- Pick a Data Collection Tool Level Two - Ease of use/ Practicality Given the conditions in your class/school can the data collection tool be used consistently and reliably in different classes and among different staff? ... Use stopwatch...
  • Sikh Identity Lesson 2 - Sikhi Resources

    Sikh Identity Lesson 2 - Sikhi Resources

    Sikh Identity Lesson 2 . WALT: Understand the meaning and significance of the PanjKakkar. Analyse the deeper meanings of Kes and the Dastaar. Greeting Task: Who would like to be a brave Lion or Lioness and share their Khalsa thoughts/poems...