Mass Testing: Expensive, Chaotic, and Wasteful
Professor of Public Health Allyson Pollock discusses the pitfalls of mass PCR testing.
The chaos of testing has been well-described by the UK Public Accounts Committee, which stated in October 2021 that the policy ‘had not achieved its main objective’ of preventing transmission and was ‘muddled, overstated and eye-wateringly expensive’. Decades of careful public health evaluation and scrutiny of evidence prior to launch of any tests and screening programmes have been cast aside in the scramble to provide and roll out tests and testing. But while a lot of attention has focused on lateral flow tests, asymptomatic testing, and test and trace, one area that has been relatively ignored is PCR testing. PCR tests are used to confirm either a clinical diagnosis of Covid or, until recently, a positive infection following receipt of a positive lateral flow test used in asymptomatic mass testing.
Although PCR tests are used as the gold standard for infection, they are not tests of infectiousness or infection in that they do not detect the whole live virus. This can only be ascertained through viral culture studies which are expensive and time consuming. Instead, the PCR test uses primers which target gene fragments of the SARS-CoV-2 virus. Some PCR tests may target one or more gene sequences in the viral fragment. During a PCR test, a small amount of this genetic material in a sample is copied multiple times in a process known as amplification. The higher the cycle threshold – in other words, the more times a sample is amplified – the more likely it is to detect trace amounts of viral genome sequence. These trace amounts could either be from live transmissible virus or from RNA fragments from previous infection, which may linger in the body and may give a positive test for as long as 90 days post infection.
The PCR test correlates with symptoms, and people with low cycle threshold (Ct) values (indicating more viral material) are those most likely to be infectious. Thus, when people with symptoms or who have been recently exposed receive a positive PCR result, they will likely be infectious. However, a positive result in someone without symptoms or known recent exposure could be due to the presence of either live or dead virus fragments, and so does not determine whether the individual is infectious and able to transmit the virus to others.
Using a standard low maximum Ct value has been suggested to reduce detection of dead virus; however, this could also cause tests to miss early infection and rising levels of infectiousness in both pre-symptomatic and symptomatic people. The measurement error of Ct values can vary dramatically between labs and manufacturers, which makes it next to impossible to define a universally optimal Ct value for reliable identification of those individuals who are infectious, and herein lies the problem.
It is important to understand what a PCR test does – i.e., which and how many genes the test is targeting and how much amplification is required to detect the RNA fragments. But it is also important to understand how well the test correlates with clinical symptoms. Some people will have mild symptoms or be asymptomatic and less at risk of transmission, and some will have had previous infection. However, the UK government’s testing pillars do not gather data based on clinical symptoms. Ease of use resulted in many people using LFTs intended for mass testing as their first port of call instead of the more complex and lengthy PCR testing route. Thus, the relationship between clinical symptoms, mass testing, and PCR test outcomes is not known.
Writing in the BMJ in summer 2020, Jon Deekes, Anthony Brookes, and I highlighted the wider problems of using PCR tests as part of mass testing to confirm positive lateral flow results:
‘[Confirmatory] PCR tests will deliver positive results in individuals with previous resolved infections, new infections, and potential re-infections, as well as false positives in people genuinely not harbouring the virus (around 0.8% of all tests performed).’
‘Identifying the truly infectious—who must isolate—is not straightforward, even with a clinical history[, as many cases] are asymptomatic, with a risk of transmission roughly half that of symptomatic cases.’
‘Real concern exists that many people who are not infectious (and not likely to become infectious) will receive positive test results, and together with their contacts, will be forced to isolate unnecessarily. In the context of mass surveillance, this could be a majority of those who test positive. Using PCR for population screening—even with a lower maximum Ct value cut off—is not epidemiologically sound. The balance of costs and harms against the potential benefits has not been evaluated.’
Since the introduction of mass testing, PCR has been used as the confirmatory test for many millions of people testing positive with a LFT test. This analysis of over 300 FOI requests on PCR testing make for uncomfortable reading. It exposes the lack of validation and standardisation of the huge number of PCR tests in use in the UK – up to 80 to 85 with the DHSC having approved 32 tests based on regulations. It also shows the huge variation in cycle thresholds, with some tests being as high as 45 and some responses saying there was no ‘specific’ or ‘standard’ cycle threshold. Meanwhile, the EU has recommended repeat PCR testing because of the risk of false positives if a Ct value over 36 is used.
Back in May 2020, as mass testing was being launched, the BMJ published an important and much overlooked letter from scientists in the Public Health Wales Microbiology Department which drew attention to how different PCR tests would generate different results depending on the number of genes they were targeting and different Ct values. Specifically, this letter warned about the risks of generating false positives when prevalence was low, as well as the risk of detecting viral fragments rather than actual positive cases. The authors went on to describe unfortunate impacts of these results:
‘Patients on the transplant waiting list were removed from the list for two weeks. Some of the patients screened pre-operatively had their surgery delayed. Patients screened pre-discharge were kept in hospital, unnecessarily in many cases. All of the low level, likely false positive results from the nursing home residents and staff generated further activity including as a minimum re-swabbing but also triggering track and trace of residents and staff in some cases.’
If policymakers had heeded the warnings and understood the complexity of the tests, as well as the need to ensure that the tests were safe, effective, and acceptable before use, then the summer ‘pingdemic’ and the winter ‘case-demic’ might have been avoided. During these periods, whole swaths of public services were partially closed or suspended, including public transport, schools, and some health services, as well as access for relatives to nursing homes. This was in large part due to the NHS app and test and trace system triggering unnecessary quarantine of individuals with false positive cases, along with their presumed contacts, as a result of mass testing not linked to clinical symptoms.
This is a striking example of what happens when tests are not validated and evaluated prior to implementation, and when complex intervention programmes such as mass testing/screening and contact tracing are not properly evaluated. It seems we have learned nothing from the past failures of screening – described so well by Angela Raffle et al. in their seminal book Screening: Evidence and Practice.
The best thing to do now is to press the reset button and learn the lessons from the billions of pounds wasted and harms done. It is time to stop mass testing and the associated test and trace. It is time to stop using tests outside the manufacturer’s license and authorisation for use. It is time to stop fragmenting and privatising laboratory services. Instead, it is time to reintegrate tests back into clinical care, which is what they were originally developed for. It is time to create a central repository of tests with a sound system for validation against agreed standards. It is time to rebuild capacity within the public health system for laboratories, for evaluating tests, and for local outbreak control. Any proposal for screening or mass testing programmes must be overseen by the UK National Screening Committee and evaluated for cost effectiveness prior to any implementation and roll-out.
For more information on how PCR works:
Prof Allyson Pollock is clinical professor of public health at Newcastle University and honorary professor at UCL. She was director of Newcastle’s Institute of Health & Society, and has set up and directed research and teaching units at Queen Mary University of London and the University of Edinburgh.