First a probe purchase, then an academic consortium

Drs. Segal and Aisner knew the collaborative group of labs could do even more together: scientific projects, provide validation support, approach regulators and payers. They decided to turn the group into a formal organization and worked with the Association of Pathology Chairs to do so. “It’s an organization with the same reason for being,” Dr. Segal explained. For the APC, it’s to support academic pathology. For GOAL, it’s to support academic molecular pathology. “We’re an important part of that for them, so they took us under their wing” and provided guidance.

GOAL was incorporated in Washington, DC, in 2020, and its application for 501(c)(3) status was approved in 2022. The group assembled and ratified bylaws and established an initial board of managers.

GOAL’s lab-focused mission is to help drive the advancement of genomic testing at academic and nonprofit labs by facilitating inter-institutional cooperation and leveraging group resources and expertise to lower development and implementation barriers. The patient-focused mission is to expand access to personalized biomarker testing, accelerate implementation of tests for new biomarkers nationally, and, through data mining and scientific projects, help drive future biomarker discovery. “This is how we’ll decide whether we’ve been successful,” Dr. Segal said.

Nine volunteer labs that already have live GOAL-based panels are participating now in a concordance study to demonstrate the fidelity of this approach. Twenty-five selected FFPE DNA specimens with 100 pathogenic variants were distributed to the nine labs for each lab to run through its normal processes and generate data. They also put in place a cloud-based consensus bioinformatics pipeline (DRAGEN Somatic Pipeline via Illumina Connected Analytics) to process the labs’ raw data and generate a second set of results. If the two sets of results were discordant and the consensus pipeline fixes it, that could indicate a bioinformatics difference at a particular lab, he said. If it is, “we can dig in and see what contributes to it, and that’s the type of thing I don’t believe any other concordance study has done to date.”

“Overall our study supports the hypothesis that we can attain excellent concordance using our shared probe chemistry,” Dr. Segal said. Of 898 expected variant calls, only one was found to be discordant due to a wet lab issue.

To determine whether the nine labs were not only concordant but also correct, they built in external variant allele frequency confirmation using digital droplet PCR (ddPCR). “We’ve done 11 of them so far, and we are not only agreeing with each other but are correct.”

Future analyses of the data will investigate tumor mutation burden, copy number calling, and other metrics. The group is also making extra DNA, he said, and will give it to GOAL labs to aid in validation of their tests. “A lab could join, get the probes, set up the library prep, use these samples, and, even if they wanted to run the Illumina DRAGEN pipeline off the shelf, very quickly be at 99.7 percent concordance.” This is far quicker than the experience of most laboratories working independently on NGS test development, he said, while preserving the ability to customize an assay, which pre-kitted solutions cannot do.

They plan to use the study’s results to push back on the premise that all laboratory-developed tests are equally risky, to approach payers about improving reimbursement, and to engage pharmaceutical companies in discussion about multisite clinical trial testing.

The next project is a shared curation platform to help labs interpret new and unknown variants. “The one question we always have that we’re never able to answer is, who’s seen this variant and what did they say about it? Did they grade it pathogenic or not and what did they write?” The public databases don’t have that information, Dr. Segal said. “So we’re siloed again in terms of our interpretation of variants.”

The GOAL model could work for labs beyond molecular pathology. Specialty reference testing is one example. “What if the academic centers got together and shared an expert network nationally so that they could say, ‘If your case is difficult, not only will it be reviewed by the top people at UChicago but also by 28 experts across the country who will share it digitally and come up with a consensus diagnosis.’” Approaching outreach testing in this way, Dr. Segal said, “is a more powerful marketing play that would raise all ships across all of the networks for those who wanted to try it.”

Another example would be coming together for the infrastructure of digital pathology, including negotiating with data storage providers. Data storage costs associated with digital pathology are one of the things that prevent many from bringing digital pathology in, he noted.

Resident and fellow education is yet another example. “Maybe we can share the load—come up with content together, even teach our residents as a group over Zoom,” which would lighten the curriculum development load and give residents and fellows a chance to meet and talk.

Another possibility: the integration of existing or novel technology. “Anything in the lab that’s bothering you and is difficult” and that working with others at other academic centers can help, he said. “The elephant in the room from a technology standpoint is artificial intelligence. I don’t know how we’re going to manage that one, but the only way we’re going to manage it is together.”

“We need to make sure we’re out ahead of it so we know what’s under the hood, how it’s working, and its benefits and limitations, and to secure a good place in this future for pathologists.”

Sherrie Rice is editor of CAP TODAY.