Labs Must Weigh Economics of ALK Mutation Testing Strategies

Antibodies for immunohistochemistry (IHC), fluorescent in situ hybridization (FISH) probes and labor drive the cost of testing for anaplastic lymphoma kinase (ALK) mutations in lung cancer patients. Given the increasing availability of molecularly targeted therapies and the accompanying reliance on genetic mutational analysis, laboratories need to identify the most cost-effective testing approach for their setting, say the authors of a study published Jan. 6 in Diagnostics.

Professional society guidelines support testing for ALK mutations. Many studies have evaluated the inter-test concordance between FISH, the standard method to directly detect ALK rearrangements, and IHC, which detects aberrant proteins resulting from rearrangements. But, little attention has been given to comparing the testing strategies in terms of cost and workflow for laboratories.

The researchers developed a cost-impact model that compared four alternative testing strategies—IHC only, FISH only, IHC pre-screen followed by FISH confirmation, and parallel testing with both IHC and FISH. Key model inputs were derived from a review of the literature and interviews. U.S. IHC and FISH reimbursement rates were based on the Medicare physician fee schedule. Given variance in European markets, the average payment on a per test basis was determined from laboratory interviews.

Ten laboratories were interviewed (three in the United States, three in Germany, two in Spain, one in France, and one in the United Kingdom). Their annual lung cancer-specific ALK testing volume ranged from 150 to 1,500 in the United States and from 200 to 3,600 among European laboratories. Interviews captured information on ALK testing techniques and materials, test volumes, batch size, test configuration (platforms, kits, etc.), average turn-around times, assay workflow, and use of resources/supplies—reagents (anti-ALK antibodies for IHC and probes for FISH), consumables, equipment (light or fluorescent microscopes, automated processors), and personnel (technicians and pathologists).

The researchers found that the IHC alone was the least expensive approach, overall (average cost per sample of $90.07 in the United States and $68.69 in Europe). The IHC FISH parallel strategy (both methods on all patients) is the most expensive (average cost of $441.85 in the United States and $279.46 in Europe). In both

locations, the IHC reflex FISH strategy, in which FISH is performed only on patients who test positive by IHC, is only slightly more expensive than the IHC only strategy. IHC and FISH protocols overlap in some aspects of workflow, such as slide sectioning, processing, incubation (with either anti-ALK antibody or FISH probe), and visualization under light (IHC) or fluorescent (FISH) microscope, however, the researchers found that in practice, turnaround time for ALK analysis varies widely.

"We recognize that there are differences in the choice of antibodies, probes, platforms, level of automation, and involvement of laboratory staff, all of which would have an impact on the cost of different ALK testing strategies," write the authors led by Shivang Doshi, from Boston Healthcare Associates (Massachusetts). "Hence, the total cost of the different ALK strategies will change depending on factors listed above, though it is unlikely to have an impact on the directionality of our findings from the model."

Takeaway: Given the differences in testing costs, turnaround time, and reimbursement, laboratories need to assess the overall costs—of testing and associated treatment decisions—and clinical benefits associated with different ALK testing strategies.