VaxSEEN

This week, the WHO announced that the COVID-19 pandemic was no longer considered a global health emergency. Although this is a milestone to be celebrated, it does not reflect the day-to-day experience of the immunosuppressed (IS) or otherwise clinically vulnerable. Although vaccine uptake within IS groups (typically 3-7% of the general population) has been relatively strong and global distribution efforts have ring-fenced supply to meet their needs, evidence of vaccine failure in these patients - including breakthrough infections and poor seroconversion (antigenic response) - makes it clear that, even when made available, inoculation does not guarantee immunity for our vulnerable.

Moreover, the exclusion of the IS from vaccine development trials and differentiated vaccine benefit-risk analysis makes the scheduling, dosing and pacing of vaccination for these patients more trial and error than a precise science. Just like the problematic overfitting associated with the term BAME, continuing to collapse this diverse spectrum of immunodeficiency (spanning under-active to overactive immune systems) into one aggregated clinical risk group erases potentially vital sub-trends in vaccine effectiveness (VE) and suitability. If unaddressed, these knowledge gaps have the following immediate implications: 

1. Worse infection outcomes for IS patients: Even when vaccinated, the immunosuppressed are disproportionately represented in cohorts hospitalised for COVID or influenza. Without dedicated VE research, we cannot be sure if this is a medical inevitability or a result of our failure to properly monitor their needs. 

2. Exacerbated vaccine hesitancy: Uncertainties around immunosuppressed patients' personal benefit-risk profile is the most typically cited cause of vaccine refusal in this group.

3. Inefficiencies in global vaccine distribution efforts: Limited supplies of vaccines or vaccine alternatives need to be prioritised for those set to benefit most from them - stocks are wasted otherwise. This cannot be accomplished without establishing which IS subtypes either do not respond to vaccination or are at elevated risk for debilitating adverse events once inoculated. At present, researchers, clinicians and global health agencies alike find it difficult to advise on key vaccine decisions for these complex patients - including when to temporarily suspend immunosuppressive regimens to maximise vaccine response or schedule boosters to combat antigenic waning. 

4. Calls for a more prescriptive approach to vaccination cannot be met: Unlike any other therapeutic in medicine, vaccination remains comparatively 'one size fits all'. The prescription vaccination agenda will only be made possible when supported by differentiated vaccine benefit-risk research.

5. Elevated risks of pathogenic mutation or antimicrobial resistance: Due to their difficulty clearing infections, the IS are common vectors for pathogenic mutation or AMR. This risk is increased when we do not know how to optimally vaccinate or treat the immunosuppressed (prophylactically or reactively).

More optimistically, by identifying immunocompromised sub-groups that perform comparatively immunocompetently in response to vaccination, we can add to the evidence base required to tailor shielding recommendations in future - ensuring only those at critical risk post-infection face the social and economic consequences of doing so - and help to reduce the psychological burden that many patients face during times of high transmission. 

Sat within Oxford University's RCGP-RSC (RSC), we are producing a real-time and open-access platform to differentiate COVID and seasonal influenza vaccine effectiveness, uptake, and adverse effects amongst immunosuppressed patient groups - the first of its kind. With the support of EMIS Health, the UK Health Security Agency, Health Data Research UK and the Alan Turing Institute, VaxSEEN will link national disease surveillance datasets to identify the immunosuppressed sub-categories that are most vulnerable to vaccine-preventable illness and at risk of vaccine failure, accelerated waning or side effects. If supported by MIT Solve, we have ambitions, and the capability, to extend VaxSEEN oversight to include additional vaccines, clinical risk group categories and provide more detailed demographic breakdowns (e.g. how subgroup vaccine benefit-risk profiles differ between ethnicity, gender, age-group, BMI, comorbidities, household income etc.) to make data more generalisable to international markets. Conversations have already begun to access US data to check the external validity of UK-based insights. The data arms of VaxSEEN are as follows:

To obtain precision data on vaccine benefit, we utilise a combination of routinely collected, pseudonymised medical record (n = 19 million; linked to health registries, hospital outcomes and vaccine records) and biological specimen data (UK-wide virology and serology sampling). Unlike comparable national disease surveillance networks, this confluence of real-time vaccine uptake, national disease exposure, breakthrough infection and antibody waning data - provided with their wraparound patient demographics and onward health outcomes - is unique to the RSC. This vaccine benefit dataflow provides approved researchers with a holistic and differentiable view of the vaccinated and unvaccinated experience for all patients; our findings here already support UKHSA and the Joint Committee on Vaccine and Immunisation to make vaccine scheduling and dosing decisions for vulnerable groups and on broadening access to expensive alternatives such as monoclonal antibodies, convalescent plasma and antivirals. Such insights are as relevant for fragile contexts as they are for established medical systems. Should it provide indications of widespread vaccine failure amongst certain patient types or accelerating demand for therapeutics, this dataflow has the potential to inform real-time vaccine recomposition and production changes by pharmaceutical companies and vaccine distribution strategies for global health agencies - a vast improvement to the retrospective work that is conducted currently.

To obtain precision data on vaccine risk, these same linked medical records are used to differentiate incidences of adverse events experienced post-vaccination. However, unique to the RSC, we augment this passive surveillance dataflow with a direct-to-patient means of reporting side effects immediately post-vaccination. VaxSEEN's adverse events reporting tool is a collaboration between the RSC, EMIS Health and PeopleWith, their chosen mobile survey provider. This technology responds to changes detected in patients' vaccine records and invites them to share their 10-day post-vaccine experience via time-sensitive text links. Once integrated into the medical record, this novel pharmacovigilance pathway controls for issues of false recall and data capture failures while building out researchers' understanding of the time-course and severity of side effects - neither of which have yet been researched in immunosuppressed groups. 

This work is dedicated to the health and wellbeing of the immunosuppressed, a group that is typically excluded from pharmacological development trials and – thereby – underserved therapeutically despite being at elevated risk of critical clinical outcomes or long-term debilitation once infected with vaccine-preventable illness. 

The VaxSEEN platform will help to ensure that health decision-makers and pharmaceutical companies are provided with the evidence base they need to best serve the interests of this vulnerable group, providing data on how the benefits and risks associated with various vaccines differ between subgroups. Identifying those subgroups at greater risk for vaccine non-response, accelerated waning, breakthrough infection and/or serious adverse events post-inoculation in this way safeguards these high-risk patients and represents a significant step towards the more prescriptive approach to vaccination that has been called for by patients and health care professionals alike. Likewise, alerting pharmaceutical companies that their products might be underserving these groups is a call to action for real-time vaccine recomposition or product redevelopment - something that, up until now, has only been possible after new waves or 'seasons' of infectiousness have already passed.

Taking a more personalised medicine approach to monitoring, vaccinating and treating the immunosuppressed has already been seen to maximise their health outcomes. VaxSEEN's value in this will be especially acute during periods of high transmission, helping to inform the prioritisation of tests, shielding notices, booster doses and time-sensitive vaccine alternatives. Although VaxSEEN's constituent data flows are currently only representative of the UK population, this type of intelligence is still of significant value for lower-income settings or emergency contexts. Its insights would be highly informative to the strategic priorities of global vaccine distribution initiatives such as COVAX, the Gates Foundation and the Clinton Health Access Initiative, for example. 

Finally, presenting data on subgroup specific benefit-risk profiles in a patient-accessible manner will also contribute to wider efforts to allay vaccine hesitancy; by logging into VaxSEEN, patients will be able to obtain line of sight into the vaccine experiences of those they can really identify with. Great effort will be taken to ensure that the VaxSEEN platform is as intuitive as possible for layman users and that it contextualises all risk and effectiveness data to prevent misinterpretation. 

Once VaxSEEN has established its value for COVID and seasonal influenza vaccine benefit-risk transparency and precision surveillance for the immunosuppressed, it has the capacity to scale up and extend its oversight to the performance of other vaccine types within additional clinical risk groups. 

The RSC is an internationally renowned source of information, analysis and interpretation of primary care data. It represents a 55-year disease surveillance legacy with UKHSA and its predecessor bodies and comprises of teams dedicated to data management, research and practice-patient-participant support. This partnership has won the trust and active engagement of the clinicians and patient base that makes up its over 1900 general practice membership – over 250 of which contribute to the surveillance virology and serology sampling efforts that has propped up UK disease response and public health decision-making for over half a century, most notably during the last pandemic. Its national representativeness and real-time nature (data flows are updated daily) makes it a rigorous source of intelligence for international health agencies including the WHO. 

Operating within this Trusted Research Environment, VaxSEEN has privileged access to the scale and diversity of data sources needed to tackle these questions of precision vaccination amongst the immunosuppressed. The RSC uses a combination of hashed NHS numbers of date of birth to link primary care medical records (updated daily) to secondary sources including birth/death registries, real-time virology and serology and hospital outcomes. Furthermore, ML's links with the Turing Institute and American institutions such as Columbia and NYU give her unprecedented opportunities for advanced clinical informatics and comparative insight generation. Her working partnership with EMIS Health also provides ML with access to a product suite capable of automating immunosuppressed patient identification and, with their consent, onboarding into remote study. This mesh of data sources and partnerships allows VaxSEEN to 1. access high-risk populations at the sample sizes needed to meet research power requirements (ensuring all resultant insights are statistically rigorous) 2. understand wraparound variables including breakthrough infections (virology), vaccine waning (serology) and clinical outcomes (registry/ hospital data) and 3. appraise if trends and sub-trends observed are robust between international health markets to assist vaccine policymaking and global distribution. 

VaxSEEN leverages these established working relationships with practice managers, clinicians, and patients and the RSC’s overall track record for conducting both decentralised and in-practice clinical trials. For example, our direct-to-patients adverse events reporting work leverages existing RSC mechanisms for PPIE including focus groups and in-practice communication channels and data visualisation platforms. Feasibility studies to understand the acceptability and accessibility of this new VaxSEEN adverse events reporting tool from the perspective of patients and clinicians are currently underway with opportunities for co-design in the coming months. This work also complements EMIS Health’s own established clinical networks to ensure the innovation associated with VaxSEEN is non-disruptive to clinical workflows. Finally, ML's position within HDRUK and previous work as a Tony Blair Institute for Global Change Progress Fellow has given her significant awareness current barriers and opportunities represented by digital health innovation. Her work originating a new Health Data Linkage work stream within HDRUK is based on ongoing collaborations with clinical interest groups from the grass-roots to most senior ranks of national and international public health decision-making. These are contacts and experiences she will leverage to ensure VaxSEEN's success.

RSC surveillance supports public health decision-making at the regional, national and international level. Thanks to close links with EU stakeholders, RSC data flows have informed public health decision-making at the European level, most notably regarding influenza preparedness and response via the I-MOVE initiative. Moreover, the RSC's track record for conducting high-quality decentralised clinical trials - most notably, and recently, the PRINCIPLE study, has established it as a globally relevant source of intelligence when it comes to optimising patient treatment pathways. These examples demonstrate how influential RSC research initiatives are capable of becoming when matched with appropriate partners.

The RSC's 19 million patient membership base (constituting 1900 general practices) is nationally representative, meaning that trends identified through its real-time analytics are likely reflective across the whole of the UK. As such, at this moment in time, VaxSEEN stands to benefit the entirity of the UK's immunosuppressed population in the first instance. This equates to a conservative estimate of 500,000 patients, though this figure inflates significantly when immunosuppressed definitions that include all cancer patients (over 3 million in the UK) or diabetes type 1 (400,000 in the UK) are applied.

VaxSEEN's links with American institutes and early conversations around comparative research are set to extend its reach and relevance even further. By widening our data pools in this way, we can ensure that VaxSEEN's subdivided benefit-risk profiles are as accurate as possible. However, MIT Solve support will be needed to build out links with other international markets - especially those with less established public health services - to ensure that its benefit-risk profiling is capable of reflecting the vaccine experiences of the immunosuppressed in low-income countries as well as higher-income counterparts. 

We are applying to MIT Solve for the following reasons:

1. Commercial advice: Support is needed on how to potentially license a second, more private-sector oriented version of VaxSEEN without causing repetitional damage or undermining our social impact goals. This is especially sensitive if current or prospective grants with government or corporate philanthropic organisations have to operate within strict codes of conduct or tax codes e.g. 501(c)(3).

2. M&E support - As a data visualisation platform, it is difficult for us to be able to directly attribute changes in vaccine trends or other health observations to our work. As such, we need to move beyond loose positive externalities to establish clear metrics of quantified impact. Examples here could include those that are web traffic-based, engagement-based or are more indicative of the scale of the initiative e.g new international partnerships and affiliations, new diseases covered, new vaccines appraised etc. 

3. Legal support - Although the RSC has healthy working relationships with  several global pharmaceutical and biotech companies, we want to make sure we are prepared for potential legal disputes over VaxSEEN reporting that certain products are suboptimal for the immunosuppressed. We are well aware of how vulnerable confidence is in vaccination, and want to make sure the way that we present our data does not in any way jeopardise uptake, but reassures patients as to their efficacy and safety. That said, we have a duty to the public health to also indicate if certain vaccine types are more effective than others for subgroups and this may cause conflict. Likewise, we need legal counsel on how to protect ourselves from accusations of harm should our platform be wrongly perceived as a clinical decision-making tool. The intention of VaxSEEN is to improve patient decision-making, not instruct it and early input from a legal expert on how to create copy that makes our data's limitations clear will be essential for preventing liability suits.

4. Standalone funding - Current RSC funding is primarily reserved for general population disease surveillance. Although this guarantees the financial stability of the data streams that will underpin VaxSEEN, it means that additional funds are required to either enhance these data flows or release immunosuppressed-specific products. Furthermore, despite the pandemic making the most compelling case possible for maintaining disease surveillance infrastructure, trends in government expenditure indicate that this cannot be depended upon. Injecting the VaxSEEN initiative with capital now will ensure the platform is in the best possible place - ideally at scale - should cuts come in subsequently.

5. Access to international markets - Once we have established VaxSEEN as an authoritative platform for vaccine benefit-risk transparency in the UK, we are looking for opportunities to expand to the lower-income contexts that might benefit more from the intelligence it provides on optimal resource allocation. Mentorship from the Bill and Melinda Gates Foundation on how to identify effective collaborators and implementation partnerships will be invaluable to this end.

6. Technological upskilling - The VaxSEEN team can always benefit from additional capabilities in advanced clinical informatics, particularly around data harmonisation if international collaborations (with incompatible health record data) are eventually onboarded to the platform. 

Disease surveillance infrastructure does not currently lend itself to differentiating either vaccine performance or safety between immunosuppressed subgroups – in part due to major inconsistencies around defining and subdividing this risk group across the global research landscape. Despite encompassing a spectrum of conditions and associated treatments, these patients are often addressed as a homogenous entity instead, affecting the visibility of sub-trends and, as a result, the confidence in which clinicians can recommend vaccination scheduling to specific patient types. Until there is clarity on which immunosuppressed subgroups are at highest risk for vaccine failure, waning or adverse events, it remains difficult to ascertain individual benefit-risk. This, alongside their frequent exclusion from development trials, is an often-cited justification for vaccine hesitancy amongst the immunosuppressed themselves.

The VaxSEEN platform will therefore be the first to differentiate and display vaccine benefit-risk metrics by immunosuppressed subgroups. Presenting more bespoke vaccine benefit-risk profiles to patients represents a major step forward for both personalised medicine and emergency disease response; such work will inform resource allocation in cost-constrained environments and the prioritisation of certain groups for boosting, adjuvants or alternatives including antiviral or monoclonal treatments. As a result, VaxSEEN will catalyse the prescriptive approach to vaccination that is so long overdue. It will provide actionable intelligence on optimal vaccine brand, schedule, pacing, dose and wraparound treatments for different patient groups. VaxSEEN's early warning functionalities will ensure that any indications of underperformance by certain vaccines will be communicated to their manufacturers in real-time to facilitate vaccine recomposition or boosting. 

The technologies that underpin VaxSEEN show high levels of innovation - setting trends for the entire research community to adopt. For example, our VaxSEEN adverse events reporting tool identifies, onboards and transfers patient data without ever providing researchers with identifiable information. This precludes the need for formal eConsent forms - something that has affected the practicality of decentralised research as taking a patient's name and signature to do so (let alone finding a way of both distributing this signed eConsent form back to the patient for their records and retaining copies for upwards of ten years) would reidentify them for the first time. Instead, the only person within this reporting cadence who has access to patient information are their general practitioners as part of their usual care. Patients are made aware that by submitting their answers they are giving their consent to participate in research in de-identified way (meaning their answers cannot be traced back to them). By having this innovative research process approved by figures in medical ethics at the University of Oxford, the research community can use the VaxSEEN adverse events reporting tool as best practice for frictionless, real-time data collection and analysis. 

Finally, the RSC's vaccine effectiveness dataflow utilises a unique confluence of medical record and biological sampling data - this distinguishes it from comparable disease surveillance networks and ensures our vaccine effectiveness calculations are backed up with biological evidence. We are able to check whether performance data is reflected in antigenic production or virological swabs. 

Impact goals:

1. To improve vaccine benefit-risk transparency, maximising health outcomes  in clinical risk groups while reducing vaccine hesitancy.

2. To advance prescriptive and personalised vaccination.

3. To optimise the impact of vaccine equity initiatives by creating an evidence-base for effective resource allocation amongst the immunosuppressed. 

4. To make the decision to vaccinate feel as personal as possible.

Means of achieving impact goals:

1. Launching the first iteration of VaxSEEN next year - first functionalities will include bringing together RSC vaccine effectiveness and pharmacovigilance (passive and enhanced) data streams and presenting initial benefit-risk profiles for immunosuppressed subgroups. 

2. Expand vaccine oversight and benefit-risk profiling to include performance data on additional vaccines; build out demographic differentiability of data. Scale use of mobile adverse reaction reporting tool and partner with MHRA Yellow Card to augment overall UK pharmacovigilance. 

3. Expand risk group coverage to include chronic kidney disease, neurological disorders and other clinically extremely vulnerable groups (as defined by Green Book).

4. Expand VaxSEEN to US market - ensuring that insights align between two healthcare systems (nationalised vs public-private)

5. Create partnerships with additional markets and global health agencies or initiatives - explore how the VaxSEEN evidence base can benefit emergency or low-income contexts and resource allocation. 

6. Build upon existing healthy working partnerships with pharmaceutical companies, ensuring that any indications of vaccine underperformance are perceived as constructive feedback to inform real-time recomposition. 

Metrics of impact:

1. VaxSEEN online traffic e.g. daily / weekly/ monthly site users. 

2. Expansion to other risk groups and vaccine types

3. Adoption and engagement with VaxSEEN adverse event reporting tool 

4. Number of countries submitting data to VaxSEEN

5. Partnerships with local implementation partners to promote and action VaxSEEN insights in sensitive settings.

6. Academic publications that cite VaxSEEN insights

7. Layman publications that cite VaxSEEN insights

8. Partnerships with high-level institutions including governments, public health agencies or initiatives (national and international), UN agencies etc. 

9. Reduced turnaround time between indications of vaccine underperformance and recomposition, boosting or targeted triage onto prophylactics.

10. Partnerships with pharmaceutical and biotechnology industries

Positive externalities:

1. Improvements to immunosuppressed vaccine uptake in countries either inputting data into VaxSEEN or where VaxSEEN data is readily available - ideally hitting WHO recommendations of over 75%. 

2. Reduced incidence of immunosuppressed patients in hospitalised/ ICU cohorts.

3. Reduced mortality rate of immunosuppressed patients from vaccine-preventable illness.

3. Reduced incidence of poor or zero seroconversion in immunosuppressed blood data. 

4. Reduced incidence of breakthrough infections/ overall case rate of vaccine preventable illness in vulnerable patients. 

VaxSEEN's theory of change is to supply the precision evidence-base on vaccine benefit-risk within and between vulnerable groups to optimise patient health outcomes, resource allocation and uptake, and support the prescription vaccination agenda. 

The problem: there is currently no understanding how vaccine effectiveness (benefit) or adverse events (risk) differs between different types of immunosuppressed patients. Vaccination within this group is more trial and error than precision evidence-based at this moment in time, undermining patient outcomes, potentially wasting limiting vaccine supplies and exacerbating vaccine hesitancy and rejection. 

The solution: combining and enhancing national disease surveillance data flows to provide more personalised vaccine benefit-risk profiles for immunosuppressed subgroups (in the first instance) and inform a more prescriptive approach to vaccination in such high-risk patient groups. 

Fundamentally, our theory of change pins around the following core assumptions:

1. That vaccines and their alternatives, additions or adjuvants should be prioritised for those seen to benefit most from them. 

2. That evidence-based clinical decision making improves health outcomes

3. That personalised data improves health outcomes

4. That real-time data improves health outcomes

5. That active surveillance (e.g. direct-to-patient research) enhances passive surveillance pathways (e.g. record-based monitoring of vaccine effectiveness and pharmacovigilance)

6. That improving pharmaceutical transparency builds trust and reduces hesitancy amongst patients. 

These assumptions have been built on the basis of previous randomised control trials, observational research, patient involvement and engagement efforts, systematic review of relevant literature and partnerships with market leaders/ thought leaders in public health. 

VaxSEEN utilises world-leading, pseudonymised disease surveillance flows. These are made up of sophisticated data linkages (spanning primary, secondary and tertiary care, health registries, vaccine records and real-time virology and serology sampling) and are nationally representative with a 19 million patient membership, and rising. As discussed, this positions VaxSEEN to reflect trends within the immunosuppressed and broader risk groups at a level that is generalisable to their underpinning disease populations. The granularity of data available to us enables us to differentiate benefit-risk outcomes on a disease, vaccine brand, and even vaccine batch basis. 

All information from computerised medical records are extracted via Apollo Medical Software Solutions (https://www.wellbeingsoftware.com/solutions/product/apollo/) and the Morbidity Information Query Export Syntax (MIQUEST) tool in accordance with standard operating procedures in data extraction, psuedonymisation and transfer. Pseudonymisation and onward data linkage is facilitated via a non-reversible 'hash' algorithm as close to source as possible. This process occurs daily to provide a real-time picture of population health. 

All VaxSEEN data are held on dedicated secure servers at the RCGP data and analytics hub in the Clinical Informatics and Health Outcomes Research Group, University of Oxford. This trusted research environment is situated behind a firewall within the University’s network. Provided that our strict deidentification and security requirements are met, VaxSEEN will facilitate opportunities for other medical record providers to submit their own data. It is our ambition to eventually host an international data pool within our own secure confines to ensure that insights obtained at the UK level can be compared to those experienced within international markets and emergency contexts where possible. 

VaxSEEN's data flows are differentiated by our fully populated immunosuppressed code list (SNOMED-CT clinical codes and prescription codes). It is also ICD-10 compatible to maximise harmonisation should international expansion occur. This code list has been divided into clinically-relevant and medical record compatible immunosuppressed subgroups to automate the differentiation of vaccine benefit and vaccine risk data flows. This code list is unique to the efforts of the RSC and has been through multiple iterations of validation. This process can be replicated for all clinical risk groups to expand VaxSEEN oversight once it has established itself as authoritative intelligence for immunosuppressed vaccine performance.

Our vaccine risk data flow (adverse events) is enhanced by our direct-to-patient adverse event reporting tool. As specified above, this research cadence is innovative by way of the sophisticated technology it is underpinned by. Here, the EMIS Recruit product automates the distribution of text invitations to eligible patients from participating research general practices to onboard onto our side effect reporting tool. These text messages are time sensitive, meaning they are sent in response to a change detected in the patient's vaccine record and are only viable for 10 days after this date. This ensures all data reported are contemporaneous and minimise false recall or misattribution of symptoms. 

This patient survey is hosted on the PeopleWith platform, a leading and patient-centred health-monitoring app. Unique patient identification numbers will be supplied in the invitation text message these patients receive to link them to a uniquely configured version of this platform to submit their side effects anonymously. This patient survey data augments the RSC's ongoing medical record based pharmacovigilance data stream, ensuring that more detail can be captured the on side effect types, severity and time course that these patients experience. At this moment in time, it has not yet been established whether the immunosuppressed experience more or less side effect post-vaccination, for example, let alone whether these risks are consistent between subgroups.

Microsoft Power BI and Tableau are used to bring together these data flows and present differentiated vaccine benefit-risk profiles in a layman-oriented manner. This leaner version of VaxSEEN will always be publicly available, empowering patients to have informed discussions with their healthcare providers on their best course of vaccination. There is then capacity to create licensable versions of VaxSEEN, providing more detailed or bespoke data breakdowns of vaccine performance data, for private and governmental stakeholders. 

Diversity, equity and inclusivity is one of the founding principles of VaxSEEN; it is wholly dedicated to understanding and safeguarding our most underserved patient groups. RSC datasets are completely nationally representative. This means our work can accurately appraise how trends differ between those with different conditions, comorbidities, socioeconomic backgrounds and other underrepresented population demographics. This constitutes a major step forward in terms of both identifying and mitigating stubborn health inequalities. 

As an organisation, the RSC's make-up maps onto these founding principles and data characteristics. Our data team is almost entirely female-identified - a major accomplishment given the male-dominance of computer science and STEM more generally. Furthermore, all primary investigators within the RSC are female. The RSC is also dedicated to advancing opportunities for early career professionals, offering a number of internship and high-impact research opportunities for undergraduate and post-graduate summer students. We also prioritise our office culture, ensuring that academic publications and opportunities are sincerely allocated based on contribution and merit - this is in stark comparison to many academic-based institutions where either primary investigators or laboratory leads dominate first authorship, op-ed or conference opportunities. By taking what could be seen as low-level cultural issues so seriously, we make it clear that diversity, inclusion and promotion on the basis of hard work and scientific aptitude will always come first. Finally, the Department of Primary Care Health Sciences at Oxford University in which the RSC is now based recently obtained its Athena Swan Gold for female advancement - this reputation is one that each and every laboratory group and associated organisation aims to protect. 

As a finalist for the ‘Future Stars of Tech: Diversity Advocate’ Award, ML is well-versed in the ways in which emergent technologies and advanced clinical informatics can perpetuate, rather than mitigate, existing inequalities. She has a strong track record for promoting the needs of stigmatised and underserved communities with past work alongside the Wellcome Trust to understand how to combat health data hesitancy in Black, Asian and Mixed groups and work with Medway Council to design trans-inclusive sexual health services. She takes matters of diversity and inclusion incredibly seriously and incorporates them by-design in all her analytics, data interpretations and subsequent policy recommendations. 

The RSC is a nonprofit - this means its operations are dependent on winning either government or philanthropic support. However, as will be elaborated upon below, we have an exceptional track record in securing this with over half a century of high-valuation governmental support to our name. Our working relationship with UKHSA and its predecessor bodies has unlocked the funding, testing capabilities, laboratory space and epidemiological talent that has propelled our disease surveillance to best practice nationally. We are now placed within high-level decision making bodies including national vaccine surveillance groups with inroads to both the Joint Committee on Vaccination and Immunisation and the Department of Health and Social Care. 

Commercial partnerships with major clinical record companies have also proven valuable for scaling the work and impact of the RSC. Both the UK's largest clinical record companies - EMIS and TPP - are supporting our surveillance efforts. As discussed, their affiliation also provides access to their full technology suite as well as additional data capabilities.

Finally, our international network of research partners positions the RSC and all spin-out initiatives as world leading intelligence. 

That said, as discussed, we are looking for advice on prospective means of monetising the VaxSEEN platform - especially if our international markets express an interest in replicating our efforts and enhancing our data flows. 

As discussed, our theory of change and ambitions for social impact require that we keep VaxSEEN open source. Doing so, and in a layman accessible format, will ensure that the immunosuppressed have the information they need to have productive discussions with their healthcare providers on how to optimise their vaccination outcomes. We intend to host this platform on the RSC website for this purpose, but may seek out an online presence with health initiatives and agencies including COVAX and the WHO. If this open-source model was the only go-forward version of VaxSEEN, then grants and government service contracts would remain the primary means of securing our financial sustainability. 

That said, there is scope to create a more private sector- and government-oriented version of VaxSEEN that would require a license fee be paid for access. This would provide tailored analytics for each pharmaceutical company on their products' performance and limitations for certain risk groups to facilitate their in-season reproduction or recomposition. Likewise, value for money metrics could be produced for government stakeholders whereby each vaccine could be analysed on the basis of reduced hospitalisations and other positive financial externalities. However, all metrics will remain patient-centred, where improved patient care and health outcomes - and public savings associated - are the only dimensions up for comparison. 

Should VaxSEEN obtain brand recognition value and there is appetite from other markets to replicate our work, we could explore options to ensure use of our IP is remunerated. However, VaxSEEN is committed to principles of Open Science; we would support any new efforts to become a success in serving their own clinically vulnerable populations.

At this moment in time, the financial sustainability of the RSC is primarily assured by ongoing government contracts. However, the 55 year track record of securing this support is demonstrative of the value of the RSC to UK disease surveillance efforts and of the stability of our future. Although the exact financial value of these contracts is not appropriate for disclosure, publicly-available transparency documents provide illustrative monthly sums (over £50k in February 2022). 

We have also seen great success securing high-value, multi-year grants from global public health interest groups including the Wellcome Trust, EU Horizon 2020, the NIHR, the ECDC, WHO-Europe etc. We also have established working relationships with global pharmaceutical and biotechnology companies including AstraZeneca, Eli Lily, GSK, Sanofi, Seqirus, Takeda, Novo Nordisk and Roche. These relationships will be crucial for the design of any pharmaceutical oriented versions of VaxSEEN that can be licensed to ensure its ongoing financial security. 

As an Oxford-MRC iCASE Scholar, ML has received funding from EMIS Health, the Medical Research Council, the Tony Blair Institute for Global Change and the Alan Turing Institute.