Much focus in the news has been placed on treatments and vaccines for COVID-19 — and rightly so. This pandemic has created the greatest worldwide disruption of modern life in recent history. But in order for trials to continue safely now — and new trials to begin in the future — the availability, accessibility, and accuracy of COVID-19 tests need to be carefully considered.
COVID-19 testing is critical to the reopening of our economy and a successful return to safe clinical research. Many precautions have been put in place, such as personal protective equipment, social distancing, symptom checking, increased disinfection procedures, and commitment to ensuring at-risk populations are not participating in Phase I trials at this time. But COVID-19 testing is the piece that will allow us to resume trials with confidence and low risk.
Testing has suffered two main limitations: accuracy and supply chain.
Here at Spaulding, we’re committed to researching the tests and implementing them in the most logical way possible. The available COVID-19 tests, when combined the right way, provide a lot of information and the ability to rule out infection when a patient is admitted to a study. But an understanding of the benefits and limitations of each test needs to be weighed carefully.
Molecular PCR test— This test demonstrates the presence of proteins unique to COVID-19 that are detectable early on in infection when the virus is actively replicating. It is the gold standard for confirmation of COVID-19 cases. Detection of the viral RNA is only possible when someone is actively infected.
- The FDA has given Emergency Use Authorization to 37 of these tests for Moderate to High Complexity laboratories. Limitations to these tests in the Phase I trial environment are supply, cost, and timing of results. Nasopharyngeal swabs are required for specimen collection and, as everyone reading the news has heard, they are in short supply. However, searching outside typical supply chain routes, the swabs can be found, and their availability increases weekly. Test cost can range from $150–$250. This is feasible for confirmation of suspected cases, but is not the best choice for testing at screening and again at check-in to a trial. Finally, timing is anywhere from one hour to two days if a send-out. Rapid results are more ideal for screening procedures.
- Three tests have received Emergency Use Authorization for CLIA-waived point of care testing. These tests are ideal for Phase I screening due to rapid turnaround time of 15–30 minutes and low cost. However, these tests are currently in high demand and short supply. These may be a great option in the next 1–2 months, but are currently not available.
Serology test — Antibody tests show the presence of antibodies in the blood responding to a COVID-19 infection. IgM antibodies demonstrate infection earlier than IgG. Antibody titers begin to rise three days after infection, with an acute response in seven to 14 days. IgG antibodies can be detected 14 days after initial infection, in some tests with 100% sensitivity. This antibody test is very important, not only for clinical research, but for community monitoring. It can tell us if a participant has already had the infection and has developed an immune response.
- Antibody tests are quite accessible for Phase I trial sites with an on-site clinical laboratory. Many of the analyzers used for HIV and hepatitis serology testing in clinical trials can be updated to acquire one of the newly developed COVID-19 antibody tests and cost is not prohibitive.
- This is a great test for employees as they are returning from remote work and to monitor the ongoing health of employees. It also should be considered for the monitoring of participants throughout the duration of a trial.
- The limitation of this test is that it does not detect COVID-19 in early onset.
- There are currently many point of care antibody tests available at a low price that have not received emergency use authorization. It is important to research the accuracy of these tests before implementing, especially given the lack of traditional methods of FDA approval. Given the lack of point of care tests available, finding a manufacturer of these tests with a quality reputation and good quality control documentation may be an alternative option that needs to be considered.
Proceeding With Caution
The ideal testing for Phase I clinical trials is a combination of the above tests. Most Phase I sites have set up an isolated triage environment before admission to screening or a waiting area. This currently includes a temperature check and symptom review, and would be the ideal setting for a point of care rapid antibody test. Any positive result would be confirmed by molecular testing and the participant sent home for at least two weeks before being retested. Any symptomatic participants or suspected cases would not proceed to check-in.
At check-in for confinement, the screening procedures would be repeated. A PCR test at check-in is the most ideal. IgM antibody tests could be repeated at Day Four of confinement to ensure infection is not developing. If a participant develops symptoms during confinement, they would be isolated and monitored, and a PCR test performed.
We all know this pandemic is rapidly evolving, and what may look like the best testing method today could be largely different in the future. With the goal of conducting our trials in the safest way possible as well as serving our customers and the very important drugs they are developing, it is imperative to establish a testing method that will give all of us the confidence to safely move forward.
Spaulding Clinical Research