Medical Policy

 

Subject: Genetic Testing to Confirm the Identity of Laboratory Specimens
Document #: GENE.00041 Publish Date:    09/20/2018
Status: Reviewed Last Review Date:    07/26/2018

Description/Scope

This document addresses the clinical validity and utility of deoxyribonucleic acid (DNA) verification tests intended to validate the identity of laboratory specimens following collection. In particular, the know error® DNA Specimen Provenance Assay (DSPA; Strand Diagnostics, LLC; Indianapolis, IN), is designed to confirm the identity of a biopsy specimen, the ToxProtect™  DNA-verified Urine Drug Test (UDT) (Genotox Laboratories, Austin, TX) is used to verify the identity of urine specimens for drug screening, and other tests that analyze genetic material to identify specimens. (Note: confirmation of specimen identification is a laboratory quality control issue.)

Position Statement

Not Medically Necessary:

Genetic testing to confirm the identity of a laboratory specimen (for example, know error DNA Specimen Provenance Assay [DSPA] or ToxProtect) is considered not medically necessary.

Rationale

The body of evidence regarding the analytical validity, clinical validity, and clinical utility of STR analysis using tests such as the know error DSPA system and the ToxProtect™  DNA-verified UDT is sparse and of low quality. There are a few retrospective and prospective case series that evaluated STR analysis for the purpose of biopsy identity confirmation. There are no studies identified in the peer-reviewed medical literature that specifically evaluate the analytical validity, clinical validity, or the clinical utility of the know error DSPA system or the ToxProtect. Therefore, the medical necessity of these tests during the collection and analysis of laboratory specimens, and their role to confirm an individual’s identity, and reduce or eliminate diagnostic errors has not been established. Confirmation of specimen identification is generally considered a laboratory quality control issue.

Background/Overview

According to the American Cancer Society (ACS), an estimated 1.7 million Americans will be diagnosed with some form of cancer in 2017. In the majority of cases, cancer diagnosis involves the pathological review of a tumor to establish the type and stage of cancer. Procurement and processing of biopsy specimens for pathological review is a complex, multistep process. Errors during surgical pathology review may involve specimen defects, specimen mislabeling, processing errors, and reporting defects. These errors may have serious consequences for disease management given that treatment decisions are often based partially or wholly on pathological findings. It has been estimated that nearly 3 million specimen misidentification events (also known as “specimen provenance errors”) occur annually in the United States, leading to approximately160,000 adverse events. A small study reported such errors in 2.4% of 41 men who had prostate needle biopsies. Another larger study reported that up to 0.4% of prostate specimens were misidentified. Finally, a very large study involving 17,000 prostate biopsies found that the error rate ranged from 0.26% to 0.67% of all specimens (Marberger, 2011; Pfeifer, 2011; Pfeifer, 2013).

A number of methods have been proposed to reduce or eliminate specimen provenance errors, including preoperative timeouts to ensure that the correct individual and correct anatomical site are being sampled; bar coding of specimens; differential coloring of specimens processed at the same time; and radiofrequency identification of specimens. Molecular identity testing using polymorphic DNA markers (often called short tandem repeats or STRs) have been proposed to decipher suspected specimen provenance errors. Another approach involves taking constitutional DNA specimen from all individuals undergoing biopsy at the time of their procedure and then cross-matching all positive pathological results to ensure that no specimen provenance error has occurred (Pfeifer, 2011; Pfeifer, 2013).

The know error DSPA is a polymerase chain reaction (PCR)-based molecular diagnostic test used to confirm that a biopsy specimen belongs to the proper individual for the purposes of making an accurate diagnosis of cancer or other histopathological condition. The know error system involves a DNA verification test that is intended to eliminate diagnostic errors due to specimen provenance complications. The process encompasses four distinct stages: 1) DNA extraction; 2) amplification; 3) separation and analysis; and 4) interpretation and reporting. The DSPA test compares the profile from the biopsy specimen with that determined from DNA isolated from an individual’s reference sample (obtained by a buccal swab at the same time as the biopsy). According to the manufacturer, the know error system has the ability to detect errors that are not generally captured by current laboratory protocols, which may have important implications for human safety in routine surgical pathology practice. The know error DSPA system may help prevent adverse events associated with misdiagnosis, including unnecessary treatment for a healthy individual or delayed treatment for an individual with disease.

STR analysis using the know error DSPA system is not subject to federal regulation by the Food and Drug Administration (FDA). Genetic tests are regulated under the Clinical Laboratory Improvement Amendments (CLIA) Act of 1988. Premarket approval by the FDA is not required provided the assay is performed in a laboratory facility that observes CLIA regulations.

Definitions

Genetic marker: A DNA sequence with a known physical location on a chromosome. 

Histopathology: Microscopic examination of tissue in order to study the signs and characteristics of disease.

Polymerase chain reaction (PCR): A method to analyze a short DNA or RNA sequence to reproduce or amplify selections of this sequence. 

Polymorphic genetic marker: Inherited characteristic that occurs within a given population as two or more traits.

Coding

The following codes for treatments and procedures applicable to this document are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

When services are Not Medically Necessary:
When the code describes a procedure indicated in the Position Statement section as not medically necessary.

CPT

 

81479

Unlisted molecular pathology procedure [when specified as a specimen provenance assay such as know error DSPA]

84999

Unlisted chemistry procedure [when specified as a specimen provenance assay such as know error DSPA]

0007U

Drug test(s), presumptive, with definitive confirmation of positive results, any number of drug classes, urine, includes specimen verification including DNA authentication in comparison to buccal DNA, per date of service
ToxProtect, Genotox Laboratories LTD

0079U

Comparative DNA analysis using multiple selected single-nucleotide polymorphisms (SNPs), urine and buccal DNA, for specimen identity verification
ToxLok™, InSource Diagnostics, InSource Diagnostics

 

 

ICD-10 Diagnosis

 

 

 

All diagnoses

 

References

Peer Reviewed Publications:

  1. Marberger M, McConnell JD, Fowler I, et al. Biopsy misidentification identified by DNA profiling in a large multicenter trial. J Clin Oncol. 2011; 29(13):1744-1749.
  2. Pfeifer JD, Liu J. Rate of occult specimen provenance complications in routine clinical practice. Am J Clin Pathol. 2013; 139(1):93-100.
  3. Pfeifer JD. Clinical next generation sequencing in cancer. Cancer Genet. 2013; 206(12):409-412.
  4. Pfeifer JD, Zehnbauer B, Payton J. The changing spectrum of DNA-based specimen provenance testing in surgical pathology. Am J Clin Pathol. 2011; 135(1):132-138.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. National Library of Medicine (NLM). Genetic Home Reference. June 20, 2017. Available at: http://ghr.nlm.nih.gov/. Accessed on June 05, 2018.
Websites for Additional Information
  1. American Cancer Society (ACS). Cancer facts and statistics. 2017. Available at: http://www.cancer.org/research/cancerfactsstatistics/index. Accessed on June 05, 2018.
  2. know error system®. Be DNA certainTM [Website]. Strand DiagnosticsTM LLC; Indianapolis, IN. Updated 2017. Available at: http://knowerror.com/. Accessed on June 05, 2018.
Index

know error DNA Specimen Provenance Assay (DSPA)
ToxProtect  DNA-verified Urine Drug Test (UDT)

The use of specific product names is illustrative only.  It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

Document History

Status

Date

Action

  09/20/2018 Updated Coding section with 10/01/2018 CPT changes; added 0079U, removed 0020U deleted 09/30/2018.

Reviewed

07/26/2018

Medical Policy & Technology Assessment Committee (MPTAC) review. Updated Scope and Reference sections.

 

03/29/2018

The document header wording updated from “Current Effective Date” to “Publish Date.” Updated Coding section with 04/01/2018 CPT descriptor change for 0020U.

Revised

08/03/2017

MPTAC review. Added the ToxProtect to the INV and NMN statement. Updated Title, Description/Scope, Rationale, Background/Overview and Reference sections.  Updated Coding section to include 08/01/2017 and 10/01/2017 CPT PLA code changes.

Reviewed

08/04/2016

MPTAC review. Updated Reference Section. Removed ICD-9 codes from Coding section.

Reviewed

08/06/2015

MPTAC review. Updated Description/Scope, Rationale, Background/Overview and References sections.

Reviewed

08/14/2014

MPTAC review. Added note to Description/Scope section clarifying that this genetic test is relevant for laboratory quality control issues.

New

05/15/2014

MPTAC review. Initial document development.