NEW YORK (GenomeWeb) – After releasing its first public data on the standards that it has arrived at for sample annotation and submission, the Blood Profiling Atlas in Cancer Consortium (BloodPAC) is pushing forward with its effort to aggregate data from a wide range of liquid biopsy platforms.
Launched in late 2016 as part of former Vice President Joe Biden's Cancer Moonshot initiative, BloodPAC is constructing a data commons that it hopes can help harmonize available liquid biopsy tests, and help standardize protocols for sample collection, preparation, and analysis in future test development.
Some of the consortium's efforts fall on the less exciting side of the spectrum — coming to a consensus, for example, on the minimum amount of pre-analytical information participants should have to submit when sharing data into the system.
Information on standard protocols for sample collection, processing, and analysis are a "prerequisite to the design of clinical studies to demonstrate clinical utility … assay reproducibility, and provide support for [US Food and Drug Administration] approval and payer reimbursement," authors wrote in a paper describing BloodPAC last spring.
The public release in February dealt mainly with this aspect of the process — defining an initial set of "minimal technical data elements" that are necessary if the BloodPAC data commons is to be useful in developing standards for the field.
The 11 data elements are metadata fields that must accompany the submission of all future dataset contributions from consortium members to the BloodPAC Data Commons.
Although BloodPAC's growing database includes both ctDNA and data on other types of analytes like CTCs, the project's executive director Lauren Leiman said this week that the focus in developing these initial minimum elements has been on ctDNA. The same will also be the case for some of the next analyses the group plans to release — from working groups focused on things like developing standards for assay analytical protocols.
BloodPAC's Samples Working Group (led by Novartis' global head of precision medicine Anne-Marie Martin, Memorial Sloan Kettering's Howard Scher, and Genomic Health chief medical officer Phil Febbo) developed the recently-reported MTDEs in a six-month effort in collaboration with the FDA Center for Devices and Radiological Health.
Although most liquid biopsy tests are currently offered as laboratory-developed tests, the diagnostics field has begun to pay close attention to the agency's evolving expectations. For example, during a meeting last year co-sponsored by the FDA and the American Association for Cancer Research, audience members questioned the FDA's Reena Philips regarding the agency's intentions to regulate laboratory tests as it does in vitro diagnostic kits.
As it stands, liquid biopsy tests do not have to be FDA-approved to be offered clinically, as lab tests remain outside of the agency's purview despite moves over the last several years toward changing that.
But there are still benefits to an FDA nod, including an easier path to reimbursement by both Medicare and private insurers. The last year has seen the first FDA approvals of next-generation sequencing tests performed on tumor tissue — most recently of Foundation Medicine's FoundationOne CDx, for which Foundation used the Parallel Review pathway to simultaneously garner FDA approval and a national coverage determination from CMS.
The draft national coverage determination that CMS issued for Foundation doesn't just pertain to that single test. It also lays out a coverage policy for other competing sequencing assays, an important feature of which is an easier path to coverage for tests that have FDA approval over those that are performed in a CLIA-certified lab.
Another important aspect of the draft NCD, which is expected to be updated in a final version by the end of this week, is that it doesn't specify, at least in its current form, that the rules for coverage are limited to tests performed on tissue biopsy samples.
Currently almost all liquid biopsies are LDTs, but major players may be gearing up to submit to the FDA if approval offers an advantage with CMS. For example, Guardant Health said last month that it had received an Expedited Access Pathway designation from the FDA — intended to speed review of breakthrough technologies and medical devices that serve unmet medical needs.
According to Guardant, EAP designation allows more direct access to senior FDA officials, engendering a more collaborative and accelerated review process.
Leiman said that part of the role the FDA plays in BloodPAC is to help the consortium align its efforts with the agency's priorities. Development of pre-analytic standards was an area of intersection that stood out right away.
The task now is to continue to aggregate data that can then be analyzed based on these preanalytical parameters, to help build an alignment on what the standards for sample collection and pre-analytical handling should be for assay validation, and potentially for the FDA as it evaluates data on tests that are submitted for approval.
In its release last month describing the project's 11 agreed-upon MTDE's, BloodPAC also publicized summaries that illustrate how some of the early data submitted by member projects spreads out over these various categories.
This represents categorization of data from 29 studies, 1,147 cases, 3,599 aliquots, and 3,290 samples, of which approximately 75 percent are clinical, BloodPAC reported.
Overall, the database has grown to contain more than five terabytes of raw data, including submissions from companies like Guardant, Foundation Medicine, Genomic Health, PGDx, and Thermo Fisher, as well as academic institutions and pharmaceutical firms.
Matrices on the BloodPAC website provide a snapshot of how the data is beginning to fill out in the different categories, but because the dataset is constantly evolving, the takeaways from these tables is somewhat scattershot.
Leiman said that some other major working group projects this year include another pre-analytical effort which is just getting started, aimed at developing minimal standards for noting patient context variables — not necessarily all clinical variables, but things like patient health and medication use at the time of blood draw, which could affect downstream analysis of their samples.
In addition to that group, the other project that Leiman said is at the forefront with FDA is the analytical protocol working group, which is expected to hold a quarterly meeting this month to present on what it had developed so far.