Laboratory Developed Tests – Part 3

| January 13, 2011

This is the third (and last) in a series of posts on Laboratory Developed Tests (LDT).  In this installment, I discuss where to find comparative analysis reviews of LDTs and add a few thoughts on LDT policies for pathology departments, cancer centers, and healthcare systems.  The prior two posts covered the definition of LDTs, the current state of regulatory oversight, and the FDA’s decision to end enforcement discretion and regulate LDTs.

The number and complexity of esoteric molecular oncology tests is rapidly increasing, as are the other demands for patients’ tumor tissue for clinical trials and biorepositories.  If a pathologist or laboratory medical director were fortunate enough to be asked for input on which tests are well validated, where should he/she begin looking for data and evidence-based guidelines?  A PubMed search is always a good place to start, but there are other resources that specifically address some of these questions.

For comprehensive summaries of the available evidence, two of the best sources I have found are the Technology Assessment Reports from the Technology Assessment Program (TAP) at the Agency for Healthcare Research and Quality (AHRQ) and the BlueCross BlueShield Association (BCBSA) Technology Evaluation Center (TEC). 

The Coverage and Analysis Group at the Centers for Medicare & Medicaid Services (CMS) recently asked  TAP at AHRQ to collect the available scientific evidence on the quality and validation of laboratory-developed molecular tests. The report, issued in May of 2010,  summarizes the data and potential areas of concern involving analytical validation, proficiency testing, and lack of adequate control materials for the more sophisticated multi-gene assays.  However, it does not include guidelines or recommendations on the tests themselves. 

The BCBSA TEC is an evidence-based practice center (EPC) for the AHRQ dedicated to comprehensive comparative effectiveness reviews on cancer and infectious diseases. In TEC Assessments, five criteria are used to determine if a technology improves health outcomes: 1) The technology must have final approval from the appropriate governmental regulatory bodies, 2) The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, 3) The technology must improve the net health outcome, 4) The technology must be as beneficial as any established alternatives, and 5) The improvement must be attainable outside the investigational settings.

The TEC Assessments cover a variety of topics and are not limited to laboratory tests.  However, using breast cancer as an example, one can find TEC Assessments on molecular testing and Laboratory Developed Tests (LDTs) that are timely and relevant.  In 2007, the BCBSA TEC published an assessment of breast cancer gene expression profiling tests and concluded that Oncotype Dx (Genomic Health, Redwood City, CA) “provides significant recurrence risk information in addition to conventional criteria for individual patient risk classification” for patients with hormone receptor-positive, lymph node-negative tumors.  In 2010, the BCBS TEC published an assessment of gene expression profiling tests for adjuvant therapy selection for women with lymph node-positive breast cancer, and concluded that Oncotype Dx did not meet TEC criteria for that patient population.

At our institution, the pathology department was recently asked by the cancer center to draft a policy for evaluating the molecular oncology send-out tests with an emphasis LDTs.  By relying heavily on the BCBSA TEC criteria and including a few other issues of concern to us, we drafted the following policy:

1.     The scientific and medical data must permit conclusions about the effect of the test results on clinical management.

2.     The test must have final approval from the appropriate government regulating bodies.

3.     A disease-specific working group in the cancer center (e.g. program directors and regular attendees of breast, lung, sarcoma tumor boards, and others) will review scientific and medical data and regulatory approval status.

4.     The Department of Pathology (i.e. Medical Director of Surgical Pathology, Medical Director of Laboratories, Director of Molecular Diagnostics and appropriate sub-specialty pathologists) will review the scientific and medical data and regulatory approval status after review in #3.

5.     Physicians ordering send-out molecular oncology tests must comply with he conflict of interest policies of the healthcare system and its hospitals.

6.     Physicians ordering send-out molecular oncology tests will inform patients about cost and payment (or lack thereof) by third-party payers.

We presented this draft to the cancer committee for our cancer center, and now the real discussion begins.

What would a set of guidelines for your institution look like?  Are there better sources of information than the ones I mentioned above?  As a pathologist, how much do you want to be involved in advising your clinical colleagues about these tests?  How would a hospital or healthcare system document the compliance of the ordering physicians with conflict of interest policies?  Should patients be informed about cost, and, if so, by whom?


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