Excerpt

The Coverage and Analysis Group at the Centers for Medicare & Medicaid Services (CMS) requested from The Technology Assessment Program (TAP) at the Agency for Healthcare Research and Quality (AHRQ) a horizon scan to summarize the available scientific evidence on the quality of laboratory-developed (“home brew” or “in-house”) molecular tests, which are currently not actively regulated by the U.S. Food and Drug Administration (FDA). CMS has concerns about the quality of laboratory-developed tests and the validation currently being performed on these tests. AHRQ assigned this report to the following Evidence-based Practice Center (EPC): ECRI EPC (Contract Number: 290 2007 10063 I). To help CMS to address its concerns, this horizon scan is intended to: 1) identify types of laboratory-developed molecular tests (LDMTs) currently available for conditions relevant to the Medicare over-65-year-old population, 2) identify the methodologies and the processes that have been developed for the assessment of analytical and clinical performance of molecular tests, 3) summarize the role of Federal agencies in regulating LDMTs, and 4) identify the quality standards that have been developed for molecular tests by regulatory bodies, the industry, and the medical community.

Contents

• Peer Reviewers
• Introduction
  • Scope of this Report
  • Overview of Molecular Testing Technology
  • Key Questions and Organization of this Report
• 1. What Types of Laboratory-Developed Molecular Tests Are Currently Available for Conditions Relevant to the Medicare Over-65-Year-Old Population?
  • Methods
  • Results
• 2. How Is Analytic Validity Established for Laboratory-Developed Molecular Tests?
  • Methods
  • Results
• 3. What Processes Have Been Developed for Examining Clinical Validity and Clinical Utility of Molecular Tests?
  • Methods
  • Results
• 4. How Does CLIA Regulate Molecular Testing?
  • Method
  • Results
• 5. What FDA Guidance Has Been Issued Pertaining to Oversight of Laboratory-Developed Molecular Testing?
  • Methods
  • Results
• 6. What Is the Role of Other Federal Agencies in Regulating Marketing Claims Regarding the Clinical Validity and Utility of Laboratory-Developed Tests Not Currently Being Actively Regulated by FDA?
  • Methods
  • Results
• 7. How Is Proficiency Testing Accomplished for Molecular Tests?
  • Methods
  • Results
• 8. What Guidelines and Standards Exist for Laboratories Conducting Molecular Testing?
  • Methods
  • Results
• Epilogue
• Bibliography
• Appendix A Literature Search Strategies
• Appendix B Catalogue of Molecular Tests Relevant to Medicare Over-65-year Population
• Appendix C Evidence Tables for Chapter 3: Clinical Validity and Utility
• Appendix D Guidelines and Standards for Molecular Testing

Errata Correction date: October 6, 2010: The Quality, Regulation and Clinical Utility of Laboratory-developed Molecular Tests report dated October 6, 2010, includes some minor corrections that were inadvertently overlooked in the previous version of the report linked to the AHRQ Web site in June 2010.

In this corrected version of the report, typographical errors missed in the May 2010 version of the report have been corrected. In addition, all gene names throughout the report were italicized in accordance with naming conventions specified by genenames.org. Lastly, text was added in Chapter 2 citing two references that had previously solely been cited within Table 10 in the May 2010 report.

None of these corrections impact the general findings of the report.

This report is based on research conducted by the ECRI Institute Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract Number 290 2007 10063 I).The findings and conclusions in this document are those of the author(s) who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. No statement in this article should be construed as an official position of the Agency for Healthcare Research and Quality or of the U.S. Department of Health and Human Services.

The information in this report is intended to help health care decision-makers; patients and clinicians, health system leaders, and policymakers, make well-informed decisions and thereby improve the quality of health care services. This report is not intended to be a substitute for the application of clinical judgment. Decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.

This report may be used, in whole or in part, as the basis for development of clinical practice guidelines and other quality enhancement tools, or as a basis for reimbursement and coverage policies. AHRQ or U.S. Department of Health and Human Services endorsement of such derivative products may not be stated or implied.

One of the investigators, Raylene Ballard, serves as an Interdisciplinary Liaison for the American Association for Clinical Chemistry. Dr. Wendy Bruening worked from 1990 – 1992 as a member of the team that discovered the Wilms’ tumor suppressor gene (WT1) while she was an undergraduate student at Massachusetts Institute of Technology (MIT). She receives royalties from MIT related to the patent filed by the university for the gene sequence, but has no control over uses of the gene sequence, and no conflict with the material in this report. None of the other investigators has any affiliations or financial involvement related to the material presented in this report.