This paper describes an automated, self-administered SalivaDirect™ protocol that decentralizes sample collection and streamlines lab processing to reduce costs of RT-PCR testing for SARS-CoV-2.
It presents the results of a research study to compare the costs and accuracy of a manual, staff-collected protocol (as specified in the SalivaDirect FDA Emergency Use Authorization), with an automated, self-administered protocol, which eliminates the need for medical collection staff and streamlines processing in the lab.
The data indicate that this protocol reduces the internal cost per test by 42% for our end-to-end testing services, with high degrees of sensitivity, specificity, and concordance with the CDC assay.
This significant cost savings suggests that wider implementation of such a decentralized protocol could help achieve health equity goals by lowering economic and logistical barriers to diagnostic testing for SARS-CoV-2.
In March 2020, renegade.bio2 formed as a Public Benefit Corporation to address the urgent need for diagnostic testing for SARS-CoV-2, with the mission of making testing accessible to all. Since then, the company has worked to increase access by reducing PCR assay costs for organizations and individuals.
SalivaDirect3 was developed at the Yale School of Public Health and brought to market by a decentralized network of clinical laboratories as a more affordable solution to the need for rapid, accurate diagnostic testing for COVID-19.
The SalivaDirect EUA4 requires sample collection to be observed by trained medical personnel, which presents challenges for community-based testing. While reagent costs for SalivaDirect are markedly lower than traditional RT-PCR (reverse transcription polymerase chain reaction) methodologies, associated costs (overhead, laboratory staff, and sample collection staff) still present economic and logistical barriers to access.
renegade.bio’s purpose in conducting this research was to validate the ability to lower the cost of collections through self-administration and automation, while retaining high degrees of sensitivity, specificity, and concordance with the CDC test.
Self-Collection Research Study
To determine the effectiveness of individual self-collection of saliva samples, we conducted a 1,000+ person research study in a San Francisco Bay Area school district.
renegade.bio delivered kits to teachers and students, facilitated their registration through Primary.Health, and guided them through self-administration of the test with onscreen instructions, eliminating the need for medical collection staff.
Samples were then couriered to our CLIA-certified, high-complexity laboratory in Oakland, CA and processed within 24 hours.
Verification of SalivaDirect Protocols In-House
To determine the efficacy of SalivaDirect in delivering consistent PCR results, we conducted a bridge study (n=28). We collected 14 positive and 14 negative samples, using three methods for each participant: anterior nares swabs, saliva samples collected via 5 mL polypropylene tube, and saliva samples collected via straw and 2mL Greiner tube.
Samples were accessioned by lab personnel and processed using the CDC assay on the swab samples for reporting to the patient and the state Department of Public Health. SalivaDirect manual and automated processes were also performed on the saliva samples for both positive and negative samples.
Self-Registration and Administration
Over 8,000 teachers and students (n=8,311) were recruited from middle and high schools in the San Francisco Bay Area. Collection kits were delivered to the community at the end of the day on Friday. After receiving their kits, individuals returned home and registered for a test through a custom web application hosted by Primary.Health.
Registrants were guided through step-by-step instructions on how to scan collection device barcodes to associate them with their account. Saliva was collected through a biodegradable straw into the collection vessel. Using a six-inch straw ensured that saliva did not contaminate the outside of the tube.
Self-collected samples were delivered by participants to an on-campus drop-off location. Samples were then couriered to the renegade.bio CLIA-certified laboratory in Oakland, CA. Samples were assessed through validated automated or manual processes, and results were reported to participants and the state within 24 hours samples were received.
SalivaDirect and CDC Concordance
Validation of the SalivaDirect protocol led to a 96% concordance with the CDC test, and sensitivity and specificity were 92.86% and 100% respectively (see Table 1). Though sample size was limited, the data indicate that the assay using self-collected samples is highly effective at detecting the presence of SARS-CoV-2 in nearly 100% of cases.
Registration and Administration Success Rates
Participants were able to self-register their tests in the Primary.Health web application with a 100% success rate (see Table 2). There were no reports of problems with the user registration workflow.
The rate at which participants were able to easily and successfully scan barcodes to associate them with their Primary.Health account was assessed. Participants were asked for subjective feedback, and the number of successful administrations occurring without intervention was counted. The total number of positive administrations was divided by the sample size (n) and multiplied by 100. The administration success rate was determined to be 94% (see Table 2).
Manual vs. Automated Process
To further validate our automation processes with self-administered samples, we evaluated the number of tests with an inconclusive result.
Out of 57 samples processed manually, two were inconclusive (98.2% success rate), while in the automated process, two out of 934 samples were inconclusive (99.7% success rate, see Table 2).
While the number of retests was higher than anticipated for the automated process (67/934), the vast majority of retested samples were reported to the patient within 24 hours.
For manual, staff-administered SalivaDirect tests, renegade.bio targets a COGS (cost of goods sold) per test of around $16, including all non-reagent consumables. Personnel costs (including medical director, lab director, and clinical lab staff) increase the cost per test to about $74. Additional costs include third-party application integration and sample collection fees, insurance, rent, and other overhead. This adds up to a standardized and CMS-accepted cost per test of $100 (see Figure 1A).
By automating laboratory sample processing and decentralizing collection efforts, we were able to drive down renegade.bio costs by 42% (see Figure 1B).
In a change to the FDA-approved collection protocol for SalivaDirect, we found that saliva collection can be self-administered without reducing the accuracy of the test. Done from the comfort of home, self-administered saliva collection is a fast and easy process that could reduce the overall cost per test by $42.
While hurdles remain to the decentralization of collections, user-friendly web applications such as Primary.Health also help increase economic efficiencies of SalivaDirect.
Automated processes for SalivaDirect reduce the cost of laboratory operations and enhance throughput. Though the automated process in our study resulted in approximately 7.2% of retests, compared with 5.3% retests for the manual process, the efficiency of assay performance still allows for results in less than 12 hours and at a reduced cost (26%) per test. Retests were associated with viscosity of saliva samples and the ability to pipette with accuracy.
Transitioning to robotics systems could further enhance the economic efficiencies of SalivaDirect. Implementation of robotics systems is needed to achieve high throughput processing, but this requires an intensive review process by the FDA.
By eliminating the need for medical observation of collections and automating laboratory processing for SalivaDirect testing, renegade.bio has developed a protocol that can significantly reduce testing costs, increasing equity by eliminating logistical and economic barriers to COVID-19 diagnostic testing.
We appreciate the valuable contributions of these colleagues at renegade.bio and Primary.Health:
- renegade.bio. Available at www.renegade.bio. Accessed April 8, 2021.
- Yale Department of Public Health. About SalivaDirect. Available at https://publichealth.yale.edu/salivadirect/. Accessed April 8, 2021.
- U.S. Food and Drug Administration, Emergency Use Authorization for SalivaDirect. Available at https://www.fda.gov/media/141192/download. Accessed April 8, 2021.
Table 1. Diagnostic characteristics of manual and automated SalivaDirect processes when compared with CDC testing methodologies (n=28).
Table 2. Self-administered test success rates, inconclusive rates, and retest rates from a San Francisco Bay Area school district.
Figure 1. Cost breakdown for SalivaDirect assays, comparing the cost of the assay as authorized by the FDA with the cost of streamlined and automated process for a cost reduction of 42%.