ACMG Studies Provide Lessons in Genetic Test Ordering Management

As use of clinical molecular testing skyrockets, many believe a closer examination of ordering patterns is warranted. Molecular tests have the potential to offer key diagnostic information. However, if not properly ordered these tests can be expensive and still not provide the needed answers to key clinical questions.

A few early studies have shown that misorders are common and can result from clerical errors, misunderstanding of genetics, or inappropriate testing sequences. These misorders can both be costly to the health care system and delay appropriate diagnosis and treatment. As a result of increasing health care costs associated with molecular testing, many institutions are undertaking a review of test orders in formal genetic test utilization management (GTUM) programs.

Three studies presented recently at the American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting (Tampa, Florida; March 8-12) demonstrate the savings associated with improving molecular test ordering practices. The early results of existing GTUM programs can provide guidance to laboratories and medical systems on the benefits of reviewing genetic test orders.

Substantial Savings Realized Through Test Review
GTUM led to improved financial management of the testing process, including limiting of patient financial liability and increasing institutional reimbursement, according to an oral presentation at ACMG by Julie Kaylor, a certified genetic counselor at Arkansas Children’s Hospital. Additionally, the review of testing orders led to further refinement of the GTUM program by addressing additional sources of ordering errors.

Arkansas Children’s Hospital’s GTUM program was implemented to assess the potential fiscal and clinical benefits of improved appropriateness of genetic test orders. The program relies upon a laboratory genetic counselor to review genetic tests sent to reference laboratories. In the study presented at ACMG, test order appropriateness was determined through a review of the medical records, literature searches, and cost analysis. The GTUM program required follow up of inappropriate test orders with the ordering physician to discuss potential test modifications.

The initial phase of the GTUM program (from July 2012 through December 2014) reviewed 4,079 tests with 5 percent (n=217) requiring modification. This yielded $353,676 in cost avoidance through genetic test modification with an average cost avoidance of $1,679 per each modification.

With the addition of a revised protocol that included confirmation of insurance prior authorization, the utilization management program yielded $102,335 in savings from January to September 2015. The revised protocol led to a review of 506 tests, with 12 percent requiring modification (n=61) with an average cost avoidance of $1,677 per modification.

Common Genetic Test Misorders
Continuous improvement to the GTUM review process is possible through evaluation of the types of common misorders, according to an oral presentation by David Stevenson, M.D., from Stanford University. While many common ordering mistakes can be easily rectified, orders made for tests without adequate evidence of clinical utility remain a large problem for laboratories.

The GTUM service at Stanford University Medical Center consists of a genetic counselor, a molecular pathologist and a medical geneticist. Beginning in December 2014, all high-complexity, sendout molecular tests were systematically reviewed. Discussions with the ordering clinicians occur, as needed. Five types of genetic test misorders were identified: those with questionable clinical utility (controversial orders), clerical errors, redundant testing, tests with better alternatives available, and uncategorized or miscellaneous misorders. The percent of modifications or cancellations per category were calculated to estimate the impact of the intervention.

Over a 10-month period, 544 genetic test orders were reviewed. These orders primarily included clinical exomes and large gene sequencing panels. Overall, the GTUM intervention reduced misorders by half (from 14 percent or 75 misorders to 6.4 percent or 35 misorders). Analysis by misorder type showed the GTUM intervention:

• Completely eliminated clerical errors and redundant testing (2.4 percent and 1.1 percent of the total test orders, respectively, to zero for both misorders).
• Cut tests with better alternatives available from 4.2 percent to 0.9 percent.
• Only slightly impacted controversial misorders (5.7 percent to 5.3 percent).

“Due to the lack of widely accepted and precisely defined guidelines for the utilization of many high-complexity molecular tests (clinical exomes and some large gene panels), a significant portion of our misorders (41 percent) fell under the controversial category, a group that was negligibly affected by the UM intervention,” Stevenson explained. “Identification of the types of misorders and classification of tests reviewed accordingly allows for a better evaluation of the impact of a UM intervention. Strategies other than UM may be necessary to reduce misorders of the controversial type.”

Cyto Test Review Yields Smaller Savings Than Molecular Send Outs
Over a one-month period, a team consisting of a pediatric genetic counselor and a pediatric pathologist at Vanderbilt University Medical Center, reviewed molecular tests that were sent to outside vendor labs and cyto tests (karyotypes and microarrays) conducted through our institutional lab. The review assessed whether the test ordered answered the intended clinical question and whether the most appropriate vendor lab was chosen based on methodology, genes included in panels, and price. If multiple tests were ordered together, the possibility of reflex testing was evaluated.

Over the study period, the team reviewed molecular tests for 90 patients (two-thirds were pediatric). The majority (93 percent) was deemed appropriate based on the clinical indication. Changes were recommended to 35.5 percent of tests and cancelling 3.3 percent of tests was recommended. The potential institutional cost savings associated with the recommendations ranged from $31,179 to $45,219. The molecular test review took 23 hours. Over the same study period, cyto tests were reviewed for 68 patients, of which 12 were inpatients at the time of the test order. Again, the majority (95 percent) of tests ordered answered the intended clinical question. The review team recommended changing nine test orders and cancelling four tests with a potential cost savings of $2,248. A total of four hours were spent reviewing the cyto tests.

The recommended test order changes focused on ordering reflex testing versus concurrent testing and identifying comparable tests available at a lower cost through use of an online database.

“Many of these recommended changes not only benefited the institution by decreasing costs but also benefited the patient as they were tested with an expanded panel increasing the chance of identifying the genetic etiology of the patient’s condition,” writes Laura Fairbrother, from Vanderbilt, in an ACMG poster presentation. “We conclude that review of all genetic tests could be worthwhile based on a cost savings and quality optimization.”

Takeaway: Existing GTUM programs show the cost savings and improvements to patient care associated with reviewing the appropriateness of genetic test orders. Evaluation of GTUM programs can also inform further improvements to the test order review process.