On December 31, 2020 the four UK Chief Medical Officers (CMOs) published a statement announcing changes to the dosing schedule for the second dose of the Pfizer/BioNTech and University of Oxford/AstraZeneca vaccines. It stated that the interval between the first and second dose should be extended from 3–4 weeks to up to 12 weeks. This rapid response examines the evidence behind this decision.
- Over 1,100 experts have shared with us their concerns about COVID-19 and COVID-impacted areas in the immediate and longer term future.
- This report outlines concerns about research and innovation.
- Experts have concerns about testing and diagnostics. Specifically about the number of tests being carried out, the availability of PCR tests and the accuracy of antigen tests.
- There are also concerns about vaccines. Experts want to know how the Government is speeding up vaccine development and note the possibility of annual vaccinations for some coronaviruses.
- Experts also think there should be more research on therapies for COVID-19 patients, including larger plasma therapy trials.
- Experts also have a range of practical concerns on international collaboration, the validation and approval of innovations, and even manufacturing and distribution of new products.
- Finally there are concerns about the impact of the outbreak on research. Experts worry about the quality of research and data collection and the access to COVID-19 research, noting that some research is not open access.
- You can find all our horizon scanning work on COVID-19 here.
Our survey of over 1,100 experts asked them what their most important concerns were in the short (next 3 months), medium (next 3 to 9 months) and long-term (beyond the next 9 months) relating to the COVID-19 outbreak. Their responses were analysed and synthesised. This synthesis comes from survey responses submitted between 3 and 30 April. Experts raised 355 concerns relating to research and innovation. Below are the areas of concerns that experts have relating to this area.
Testing and diagnostics
Experts raised over 100 concerns about testing and diagnostics. Experts are concerned in the short and medium-term that there are not enough tests being carried out to know who is infected with the virus. They suggest that controlling the future spread of the virus requires testing more of the population to find who is infected. They suggest that those who are infected need to be isolated and anyone who has had contact with them should be identified and tested (known as contact tracing). However, there are concerns about the accuracy and availability of tests for detecting current infection.
Experts note that there are two possible ways of testing for current infection, both using nose and/or throat swabs. One type of test looks for the presence of genetic material of the virus (PCR test). The other type of test looks for the presence of proteins from the surface of the virus (antigen test). Because the virus takes a few days to multiply in the nose and throat, neither of these tests can detect early infection with the virus. Also, experts note that no tests are totally reliable and will lead to false negatives (indicating a person is not infected when they actually are) some of the time. They question how well false negatives are factored into decisions about when people should self-isolate, quarantine or be placed on a COVID-19 ward.
The UK is using PCR tests to check for current infections because antigen tests for this virus are not yet on the market. However, experts note that there are concerns with how quickly PCR tests can be run and whether they can be scaled-up. The majority of PCR tests take a few days to give results and are labour-intensive to carry out. Although rapid PCR tests are becoming available, which take a few hours rather than days, some experts question if these are as reliable. PCR tests also require specific substances to run (reagents). Experts are concerned that if the numbers of PCR tests being run increases, there could be a shortage of the reagents required. Antigen tests are much quicker at detecting viruses, with results available in minutes. They also do not require separate reagents to run because the test kits are self-contained. However, the accuracy of these tests is likely to be lower than PCR tests. If used in hospital, presence of the virus would still need to be confirmed by a PCR test for a clinical diagnosis. Experts suggest that there is a need to develop antigen tests alongside PCR tests to allow testing to scale up.
Experts are concerned in the short and medium-term about how to test people for previous infections from the virus. Serological tests look for antibodies in the blood, which indicate the body has been previously infected and had an immune response to the virus. These tests can give results in minutes. However, some antibody tests available have been found to be unreliable for the current virus. Some experts express concerns that without widespread availability of these tests, it will not be possible to lift some restrictions (such as those on the number of people gathering in an area). They suggest that tests should be available for people to take at home. However, some experts are concerned about making these tests widely available. This is because people may find they have been previously infected and assume they are now immune and cannot be a carrier. They may then behave as if they cannot infect others or be infected. However, immunity from the virus is still not fully understood. They could therefore spread the virus unintentionally.
There are also some concerns in the medium and long-term about the practicalities of developing, manufacturing and distributing tests (see below in ‘Practicalities’).
Example of a typical short-term concern in this area: How is the Government going to ensure that all the required equipment, reagents and scientists are in place for as many virus detection and antibody tests as possible to be carried [out] on infected people, healthcare workers and the general public?
Experts raised over 60 concerns about vaccines. In the short and medium-term they are concerned that without a vaccine, it would not be possible to relax measures to control the virus. Experts want to know how the Government is speeding up the development and trialling of a vaccine for the virus. In the long-term, experts note that there may need to be an ongoing annual vaccination programme for some coronaviruses (as there is currently for some influenza viruses). They note that one dose of vaccine may not provide long-term protection. They also note that vaccination will be ineffective if the virus mutates substantially.
There are also some concerns in the medium and long-term about the practicalities of developing, manufacturing and distributing a vaccine (see below in ‘Practicalities’).
Example of a typical long-term concern in this area: Development of better vaccine strategies and lockdown measures to tackle any pandemic.
Treatments and therapies
Some experts express concern that there is not enough research happening on treatments and therapies for those infected with the virus. They suggest that in the short and medium-term, there should be trials on different drug combinations to find out which are most effective. They also suggest larger trials of plasma therapy (where blood plasma from people who have recovered from the virus is donated to those currently infected with the virus). Experts also note that more research is needed on how drugs used to treat other diseases could be repurposed. For example, experts suggest there should be research on the use of different steroids, antivirals, antimalarials and anti-inflammatories. Some experts express concern that not enough is known about the long-term effect of using ventilators and intubating (inserting a breathing tube) patients who are hospitalised with the virus. In the long-term, some experts suggest that novel technologies could be used to treat the virus. These include genetic medicines, immunotherapy and nanotechnology.
There are also some concerns in the medium and long-term about practicalities of developing, manufacturing and distributing treatments and therapies (see below in ‘Practicalities’).
Example of a typical short-term concern in this area: What are the key strategies to support the research in finding effective drug treatments for COVID-19 for different types of infected patients/population, and what is the role the government will play in enabling and coordinating these efforts nationally?
Experts raised over 70 concerns about the practicalities of developing, manufacturing and distributing new medical products.
In terms of development, experts are concerned that there is not sufficient international collaboration on developing suitable tests, treatments and vaccines. They suggest that international researchers should be incentivised to work together to speed up development. Experts are also concerned that, within the UK, there is not enough collaboration or sharing of data. Some suggest that there should be changes around intellectual property law to ensure that medical developments can be shared. Other concerns include that there are many new products being developed and it is unclear how the Government will choose which products to approve and rollout. For example, experts want to know how effectiveness, cost and scalability will factor into these decisions.
Some experts raise concerns about how innovations will be validated and approved. Experts are concerned that the current validation and approval process takes a long time. Some suggest that the approval process should be shortened. For example, they suggest that clinical testing could be conducted more quickly. However, other experts are concerned that if innovations are expedited then there may be unknown long-term health effects. They are also concerned that not validating products thoroughly may mean they are less accurate or effective than presumed. This could cause long-term issues. For example, if policy relies on an estimated effectiveness of tests or vaccines to work then if this estimate is wrong there could be unchecked spread of the virus.
In terms of manufacturing, experts are concerned that after new products are approved there will be issues making them at-scale in the medium and long-term. Experts note that there may be supply chain issues when making new products. They also note that there is limited manufacturing capacity in the UK and suggest that the manufacturing industry will be less productive than usual (because of workforce issues and workplace social distancing measures). Some suggest that more manufacturers will need to be approved to produce new designs. Other experts are concerned that if new products are produced and approved abroad, the UK will not have sufficient funds set aside to purchase them.
In terms of distribution and use, experts are concerned about various issues in the medium and long-term. Experts are concerned about the logistics of distributing tests, treatments or vaccines across the whole country. They are also concerned that scaling up the number of tests taken will require the use of more labs than are currently being used. They suggest the use of university research, private company and local authority labs may be required to meet demand. Other concerns include how to train enough health workers to administer any new products. In the long-term, some experts are concerned about plans to roll out testing and vaccination. Their concerns include how to decide who to prioritise for receiving tests/vaccines. They also express concern about how the Government would manage such a large public health drive. Key concerns within this are how to ensure enough people would take the tests and vaccines and how to build confidence in the public about the new products.
Example of a typical medium-term concern in this area: The need to perform a cost-benefit analysis of loosening the rules around the development of new treatments and vaccines for covid-19.
Impact on research
Experts raised over 70 concerns about the impact of the COVID-19 outbreak on research. Nearly 50 concerns focus on how it could affect the quality of research in the short, medium and long-term. Experts want to know what measures were in place to ensure that research quality is not sacrificed for the sake of speed. Some experts are concerned that fake or unproven treatments could be promoted during this time. They suggest that the Government needs to use regulatory oversight and track the long-term health impacts of any treatments being promoted. Many experts are also concerned that not enough data are being collected in the short-term that might allow for more thorough research in the future. Experts are also concerned that data and research about the outbreak are not open access (publicly accessible for free). This includes data that the Government has relied on to make decisions. They suggest that all data and research about the COVID-19 outbreak should be open access to allow scrutiny and further research. Nearly 20 concerns focussed on the funding of research not related to the COVID-19 outbreak. Experts are concerned that funding may be directed away from other projects during the short, medium and long-term. They note that if all medical research focuses on COVID-19 then it leaves the UK exposed to threats from other less studied diseases. They also note that non-medical research is key to understanding and rebuilding society in the long-term. Some experts suggest that overall research and development funding should increase in the long-term to ensure the UK is prepared for any future major events.
Example of a medium-term concern in this area: It is extremely important to collect and store the covid-19 data in a systematic way if the UK wants to use the machine learning type research for better management of the patients or allocation of hospitals.
You can find rapid response content from POST on COVID-19 here.
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