Post-market evaluation of serology-based point of care tests

In response to the COVID-19 pandemic, the Therapeutic Goods Administration (TGA) has expedited the approval (with conditions) of COVID-19 tests including tests intended for laboratory use and those intended for use by specified health professionals at the point of care (POC). Approval was based on the studies manufacturers were able to provide at the time of application.

Accurate identification of a COVID-19 infection based on serology results, particularly those obtained from tests used at the POC, requires an understanding of the antibody response profile which is currently not well defined. It is known that these tests can fail to detect COVID-19 if testing is performed in the acute phase of the infection prior to the development of detectable antibodies. If this 'negative' result is incorrectly interpreted the person may be told they haven't been infected when they may have been infected and may be infectious. Results need to be interpreted, in conjunction with clinical presentation, by a suitably qualified health care professional who can provide a patient with appropriate advice and treatment if required.

As part of a Post Market Review the TGA is now reviewing all approved serology-based COVID-19 POC tests to verify their ability to detect antibodies to SARS-COV-2 (the virus that causes COVID-19), taking into consideration the timeframes for an individual to develop detectable levels of antibody. The Peter Doherty Institute for Infection and Immunity (the Doherty Institute), has been engaged by the Department of Health to assist with the post-market verification process of these tests, to inform their best use. However reports by other Australian laboratories or comparable international regulators may also be taken into consideration.

To date, the Doherty Institute has completed its validation of twenty-three different serology-based POC tests approved by the TGA. Samples of the twenty-three POC tests were provided from the following manufacturers (note some devices have multiple sponsors):

Doherty Institute's validation

The validation performed by the Doherty Institute for these twenty-three devices suggests that manufacturers have claimed a better sensitivity compared to that observed in the Doherty Institute studies (when compared to a molecular-based method). The Doherty Institute studies did demonstrate that the sensitivity of most tests improved with increasing duration (i.e. longer time) between sample collection and symptom onset up to approximately 20-30 days post-symptom onset.

It should be noted that none of the manufacturers claim that these tests should be used as a sole basis for diagnosis of COVID-19 and advise that results need to be interpreted along with other clinical findings and consideration should be given to further testing.

Some of the variation observed between the different manufacturers' claims and the Doherty Institute's findings can be attributed to sample size and sampling bias and it is apparent that different patient populations and samples taken at different times post onset of symptoms can significantly influence the performance of the tests. The Doherty Institute also noted that a direct comparison with the manufacturers' claims was difficult as the performance information provided in the IFUs was limited. However four of the devices, the GenBody COVID-19 IgM/IgG, the Innovita 2019-nCoV Ab Test, PCL COVID19 IgG/IgM Rapid Gold and the Diagnostic Kit for IgM/IgG Antibody to Coronavirus (SARS-CoV-2), produced results that differed significantly from the manufacturer's claims and performed poorly in comparison to similar devices evaluated by the Doherty Institute.

The Doherty Institute's studies, along with other evaluations performed by Australian and international laboratories confirm that the sensitivity of these tests in the early stages of infection is poor and that they shouldn't be used for the diagnosis of acute COVID-19 infection. This conclusion is consistent with current advice from the Public Health Laboratory Network, the Royal College of Pathologists of Australasia and the TGA that these tests must be used with caution due to the potential for these tests to fail to detect COVID-19 during the acute phase of the illness, prior to the development of antibodies.

Based on the Doherty Institute's findings it is recommended that serology-based COVID-19 POC tests should not be used until at least two weeks post onset of symptoms. As yet not enough is known about the adequacy of the COVID-19 immune response or duration of immunity. Whether there is a role for these tests in determining immunity for return to work purposes or for population-level surveillance remains to be seen.

Post-market regulatory action

The TGA has requested the sponsors of these devices to provide further information on the clinical studies undertaken by the manufacturer to support the performance of these devices. This includes a re-evaluation of the clinical performance studies including stratification of results according to different periods post onset of symptoms and will provide a better basis for comparing the manufacturer's claims against the Doherty Institute's findings. This will inform the need for any subsequent regulatory action which may include changes to the IFUs to include more detail about the test sensitivity for samples collected at different time points post onset of symptoms; and additional warnings to inform the user of the limitations of test. Other regulatory action includes suspension or cancellation of non-compliant or poor performing tests from the ARTG. Further information can be found via the post market review of COVID-19 point-of-care tests page.