In 2020, 37,211 people were diagnosed with lung cancer in England. 68% of this population is at an advanced stage and has limited life expectancy. People with advanced lung cancer have complex care needs and often experience high levels of GP appointments, hospital admissions and extended lengths of stay while awaiting diagnosis and treatment.
Timely genomic testing of the tumour can help identify individualised treatments, which can potentially markedly improve the quality and length of life. Delays in identifying specific gene mutations can result in missed opportunities for patients to receive targeted and more effective treatments, ultimately leading to worse outcomes and higher costs for health systems.
Liquid biopsy, a cutting-edge diagnostic method validated through numerous clinical trials, involves testing blood samples for biomarkers like circulating tumour DNA (ctDNA), among others, to detect cancer-related genetic mutations. This less invasive approach offers several benefits, particularly in vulnerable patients with advanced non-small cell lung cancer.
The NHS in England is working towards being a global leader in adopting liquid biopsy testing into a national health service. Recognising the importance of economic assessment and evaluation of the costs and benefits of broader ctDNA testing, Edge Health was commissioned by NHS England to undertake this work to support an ongoing national pilot involving non-small cell lung cancer testing.
Using health economics to understand benefits and costs
Our initial findings in the early phase of the health economics analysis of ctDNA testing combined academic methods with commercial insight and experienced understanding of how the NHS operates to assess the economic implications. This involved collaboration with clinical experts and synthesis of information from various other sources. As a new technology, our analysis considered various clinical scenarios and sensitivities for critical assumptions.
“Implementing ctDNA testing into the routine diagnostic work up of patients with lung cancer is a huge step forward to improving equity of access to state of the art genomic testing for our patients. This will allow patients to receive the best treatment possible for their condition. The input from Edge Health has been invaluable in mapping out a complex pathway, identifying options for ctDNA implementation and their associated cost benefits”.
Professor Sanjay Popat, Consultant Thoracic Medical Oncologist, Royal Marsden Hospital
Outputs from the initial analysis were extrapolated more generally with national data, which helped identify the potential future costs and benefits.
In the context of stage III and IV lung cancer, from early analysis, the application of ctDNA was found to deliver significant benefits relative to its costs. This finding was primarily driven by ctDNA testing enabling earlier blood testing and potentially avoiding tumour genomic testing, which supported patients to access targeted treatments earlier and more consistently – lowering broader system costs. In the next phase of work, pilot data will be analysed to validate these preliminary findings to support the commissioning of the ctDNA test on the genomic national test directory.
Moreover, ctDNA testing is expected to improve equity in genomic testing access substantially, expanding coverage over a broader spectrum of gene mutations and ensuring the inclusion of patients for whom adequate tissue biopsies might not be viable.
Ultimately, incorporating the latest genomics advances into routine healthcare will help deliver the UK government’s vision in “Genome UK: the future of healthcare”.
“The current work of the ctDNA pilot aligns perfectly with the Genomic Medicine Service goals of delivering equitable genomic testing for cancer patients through accessing cutting edge technology and science. This technology will hopefully, if commissioned onto the national test directory, ensure that clinical services can make better-informed decisions faster, have access to precision treatments which will improve patient outcomes, ultimately leading to more efficient use of NHS resources. The work from Edge Health is vital in helping to demonstrate that this advance in care is also economically viable”.
Paul Ryves, Programme Director, North Thames Genomic Medicine Service Alliance.
Contact us to learn more about our approach and how we can help you.
Uptake, logistics and targeting will determine if the vaccine can allow life to return to normal. We built an interactive tool that can help explore the key factors standing between us and vaccine success for all regions in the UK.
by Kieran Dale, Christian Moroy and George Batchelor
The end of the pandemic seems to be in sight. While this is undoubtedly very positive news, many hurdles remain before ending the pandemic is a reality.
There are still many unsolved problems. The necessary regulatory approval that the vaccines are safe to distribute is ongoing. Logistically, producing and transporting vaccines at scale is also a huge challenge. For example Pfizer’s MRNA vaccine typically needs to be stored at -70C, and two doses are required within a strict timeframe).
Here in Great Britain, one survey of almost 1,600 people showed the difference in expected uptake varies considerably between age groups. Only half of surveyed people from 18-24 years of age were more likely than not to take the vaccine, while for people 65+, this figure was 82%.
How many people need to be vaccinated?
While a vaccine would primarily stop vulnerable people from getting ill and dying, there are also effects such as reducing the adverse effects of COVID and lockdown on other population health needs such as cancer. Critically, it also helps create “herd immunity” and slows the spread of the virus.
With an effective vaccine, creating herd immunity in the general population will be the goal. At 90% effectiveness and assuming a reproduction number of 2.5 (how readily the virus spreads), herd immunity can be achieved once 66% of the population is immune from vaccination or having caught the disease – this will reduce R below 1, and the virus will effectively die out.
The size of the population that needs to be vaccinated is larger if the effectiveness is lower or effective R higher. For example, if efficacy is less than the stated 90% (e.g. 80%) and R higher (e.g. 3) then up to 83% of the population would need the vaccine (less as some will have immunity from having caught the disease already) – see chart below.
Other measures to stop the spread would likely remain
However, a vaccine would likely not be the sole intervention to “flatten the curve”. Other measures would still be in place to reduce the reproduction number, such as wearing masks on public transport. One study showed that if a vaccine was the sole intervention, a vaccine with an efficacy of 80% would require at least 75% coverage (R_0 = 3.5) to put a halt to the pandemic. This would likely be lower if people remained socially distant and adhered to government guidance.
Saving lives should be the priority. We have seen evidence from other countries that only those countries that have successfully protected lives also managed to protect the economy. This means that other measures of stopping the spread in the community are still important while the vaccine is being rolled out.
Consequences of low uptake
There are serious consequences for low uptake. These can be broken into three broad categories.
1. Risk-to-life – Low vaccine uptake will increase the reproduction number of COVID, spreading the disease to vulnerable people. Care homes in particular have been at-risk throughout the pandemic, and ensuring high uptake among frail and elderly people will reduce unnecessary loss of life.
The shielded population (people aged 85 and above) and vulnerable population (people aged 66-84) are defined very generally. This provides an overview of the worst affected areas for loss-of-life due to older age profiles. Using a simple case fatality ratio of 2% for the shielded population, 1% for the vulnerable population and 0.1% for the working population, we can define the risk to loss-of-life compared to a baseline (no intervention). Full restrictions put in place will half loss-of-life risk.
2. Risk to the economy – the working age population that is still at-risk can cause a burden on the economy. Not reaching “herd immunity” could result in further measures that would harm businesses, such as curfews and local lockdowns. This will be affected by the size of the working population, uptake, vaccine effectiveness and restrictions.
The equation for this is the proportion of the working population still at-risk of COVID, multiplied by a scaling factor representing restrictions (50% to 150% of risk value)
3. Risk of a third wave – we are currently undergoing a second wave. As the pandemic progresses, fatigue can set in and compliance to government measures can drop. Whether this lockdown will be as effective as the previous one is unknown, although more lockdowns seem unlikely. Studies have shown that decreased perceived effectiveness of lockdown measures was linked to non-adherence. The second wave coincided with worsening weather in the UK. Will this be as much of an issue as we head into warmer months?
Risk of a third wave will also incorporate “high-spreaders” (defined as those aged 6-17). Schools and universities are remaining open, and younger demographics have the potential to spread the virus widely. If herd immunity is reached (the proportion of the population that needs to be vaccinated to beat the virus), there is no risk of a third wave. If this threshold isn’t reached, the risk factor is the proportion of the population that still needs to be vaccinated compared to a baseline of no vaccinations.
Vaccine uptake ideal and worst-case scenarios
Our interactive vaccine impact exploration tool shows which areas of England are affected most :
Three scenarios can be explored in the tool: ideal, expected and worst-case. These outline proportions of population cohorts who are vaccinated, and show risk factors at local authority level for each of the aforementioned risk categories.
As the analysis is based on age profiles at local authority level, it visualises the following outcomes:
· Restrictions reduce risk to loss-of-life but increase risk to the economy.
· The most at-risk areas for loss-of-life will be those with a higher proportion of older people
· Third wave likelihood is highly dependent on the uptake in working population and high-transmission population.
· Herd immunity is reached much more easily with the introduction of an effective vaccine.
Work needs to commence on the logistics of vaccinating the population. This will be the next big challenge, and is key to building public trust that the pandemic can be beaten. Ensuring all the systems are in place to be able to roll-out the vaccination effectively and at-scale is key.
The big obstacles include: sufficient uptake across the population (especially super spreaders!). Super spreader vaccination is key to flatten the curve but only when combined with priority access for at-risk population cohorts efficient distribution that involves the primary care system and strict compliance to vaccine dose schedules.
Enabling success across all of these dimensions is key to save lives, reduce pandemic-induced strain on the economy and remove the threat of a third wave.