Alison Cave, Chief Safety Officer at MHRA, discusses her role at the MHRA, current key objectives in the organisation and its future ambitions for improving patint healthcare. 

Q: Can you tell us a bit about your background and how you came to be in your current role?

A: My career has been a mixture of scientific research, academic funding roles and medicines regulation. This is the third time I have worked at the Medicines and Healthcare products Regulatory Agency (MHRA). The first time was in 1998, then in 2008 and now most recently in 2021, each time working within the vigilance of medicines. I am very fortunate in that my career has provided me with a really strong grounding in science across a broad range of disciplines, an understanding of the external environment through my scientific funding roles and substantial regulatory experience both at the MHRA and the European Medicines Agency (EMA).

During my time at the EMA, my focus was on how the regulatory system could evolve its evidence-generating capabilities to better meet the challenges of a rapidly changing scientific landscape. This was an experience I built on at UK Research and Innovation (UKRI), in a role focused on healthcare data, which also incorporated the support of novel and integrated diagnostic solutions for the earlier diagnosis of disease. Hence my current role at the MHRA felt like a perfect match for me, where I lead both medicines and devices vigilance with the ambition to underpin surveillance with improved evidence generation.

Q: What does your role involve and what are your favourite aspects of being the Chief Safety Officer at the MHRA?

A: My role at the MHRA includes oversight of the vigilance responsibilities for both medicines and devices, our enforcement duties, as well as our evidence-generating capabilities including the Clinical Practice Research Datalink, device data specialists and epidemiologists. My favourite aspect of my role is the variety of the work, which is constantly challenging, but also being responsible for the vigilance of both medicines and devices. I believe that our new structure, where medicines and devices experts work side by side, will best capture the synergies and expertise across these areas, while avoiding duplication of effort in signal detection, data capture and communications.

alison cave

Q: What initiatives and ways of working, experienced while at the EMA, would you like to bring to the MHRA?

A: At the EMA I was fortunate enough to be able to explore with colleagues across Europe, how best to evolve our evidence generation capabilities, to support decision-making across the product lifecycle. It was clear to us all in 2013 that changes in the scientific, technological and analytical landscape would in turn bring changes to drug development and the delivery of healthcare and that we would need to look beyond traditional sources of evidence to better support our decision-making. I brought that thinking with me to the MHRA where I am incredibly lucky to work with like-minded colleagues who equally wish to harness the power that data and new analytical methodologies can bring. The MHRA has already made great strides, especially during the COVID-19 pandemic where real-time vigilance, utilising AI and proactive data collection were critical parts of the vigilance strategy. We are now aiming to bring the lessons learned from the COVID-19 pandemic to our vigilance of all medical products.

Q: What are your current key objectives and what do you see as the biggest challenges to achieving these?

A: The MHRA is currently at the end of a significant transformation process and our focus in recent months has been in finalising this process. We have now arrived at the point where we can start to capitalise on the opportunities this transformation offers us. The Independent Medicines and Medical Safety Devices Review made a number of recommendations; my key objective is to deliver these. They are: ensuring we have a world-class, comprehensive vigilance system that can promptly detect and monitor signals for all medical products, increasing the safety of medical products used in pregnancy, enhancing the transparency regime for medical devices, evolving our evidence generation capabilities and embracing new technologies to deliver the evidence and insight to support our regulatory actions and critically understand their impact.

There is a lot to do but we have already made a start with the imminent launch of our common vigilance platform called SafetyConnect, which will provide an oversight of safety issues across all medical products and will underpin a common approach to risk assessment and risk management. The programme also delivers a number of technology offerings on the platform which will enable us to exploit machine learning and other analytical approaches to, for example, improve our assessment and categorisation of signals. In fact, we accelerated some of these features to support the COVID-19 vaccine surveillance strategy. It has helped us to assess in a timely manner the large increase in reports received during vaccine deployment due to the sheer size of the vaccination campaign. Importantly, we are also seeking to deliver better patient and public involvement through improved communication and engagement, as well as increased transparency of our reporting, and capturing the outcomes that matter for patients.

Q: Can you tell our readers how you are planning to improve the safety surveillance of medicines and devices in the UK?

A: We plan to improve our vigilance work with better data and better analytics. I am fortunate to have at my fingertips an amazing data resource, the CPRD, which is globally renowned as a health data research service amongst the epidemiology and pharmacoepidemiology research community. This data source is already a representative, longitudinal database encompassing 24% of the UK population with multiple linkages to other health-related datasets, but we have ambitions to increase its scope further in both population coverage and further linked datasets. 

We would like to take onboard new datasets, particularly genomic data. We would also like to expand the utility of synthetic data, for example to support soft ware device and clinical trial development, and also to generate synthetic patient cohorts to simulate intervention effects in those subgroups not typically included in randomised controlled trials or indeed identified, as our knowledge of a benefit-risk profile grows.

Another key priority is to improve our device data capabilities – here the introduction of the unique device identifier (UDI) will be the gamechanger as it will give us for the first time the possibility of unambiguous and accurate identification of a medical device from the manufacturer to use/implantation in patients. The inclusion of UDIs in both internal and external data sources will facilitate effective signal detection but also provide the opportunity to capture long-term outcomes through data linkage in ways that were not possible before; and that is a really exciting prospect.

Q: Could you share your plans to facilitate closer partnership with patients and healthcare professions?

A: We have started taking steps to adopt a new, fresh approach to the way we involve patients, healthcare professionals and the public; one that is more transparent, responsive and systematic. We worked closely with patients to develop our first Patient Involvement Strategy[1], which sets out how we will engage and involve the public and patients at every step of the regulatory journey. Our aim is to ensure that the teams have clear processes for engaging patients and the public in their work and we intend to have these processes embedded across the agency by December 2022.

Some examples of how we will achieve this include developing the use of patient-reported outcomes, so that it is built into all of our licensing decisions and formalising the work of our Patient Group Consultative Forum, including regular attendance from members of the agency’s Executive Committee, so that it becomes truly representative of the whole healthcare landscape. We will improve our understanding of patients’ and the public’s attitude to risk/benefit in relation to the use of medicines and devices and use this understanding to improve our engagement so that they can make informed choices.

We will consider their journey through the health system and the key points at which we can add value and deliver meaningful engagement. This includes the awareness of the Yellow Card scheme, as well as other important safety connection opportunities such as the patient information leaflet. We will also pilot new approaches to design-in patient and public involvement to our processes, including patient and public input in the regular review of patient safety signals and new sections in assessment report templates that act as a prompt to check that patient and public engagement has been considered.

In parallel, we’re developing our new strategy to engage and involve healthcare professionals across the full range of things we do, as we recognise the importance of considering all audiences in delivering the best outcomes for patients. So, as we did with patients and the public strategy, our approach will be informed at every step of the process through consultation with healthcare professionals on what is important to them.

Q: What initiatives are the MHRA currently engaged in to ensure that the patient voice is at the heart of everything the MHRA does?

A: Patient and public involvement is at the heart of the MHRA’s Corporate Plan 2018-23[2] and our Delivery Plan 2021-23.[3] This is a cross-cutting priority: the objectives we have set in our plans have been developed with the needs of patients in mind, and many of the planned changes involve consultation with patients. The Patient Involvement Strategy alone has over twenty individual workstreams and we have already started making these changes to ensure we put patients first across the lifecycle of the products that we regulate.

Our patient group forum includes patients and patient representative organisations who provide us with the patient perspective. We are looking to grow the reach of this group, working with partners across the sector to gain access to a far wider patient population, as well as increasing the size and diversity of our own patient group. It’s this group that has provided the pilot Patient Reference Group for our Innovative Licensing and Access Pathway (ILAP). We’d encourage any organisations that represent patient groups, however small or large, to join our patient group forum so that we can draw upon their expertise and experiences.

Alongside this we are transforming the Yellow Card scheme reporting systems to make it easier and more intuitive for patients to report suspected side effects to the MHRA, including new features such as the ability to update reports. We are also improving the connectivity of reporting systems across the National Health Service (NHS) to ensure that we receive cases even when these are not directly reported through the Yellow Card system. Future upgrades will also include new features to help keep patients up to date with their report as it progresses through the MHRA review process; easier access to real-time safety communications and control over alerts, allowing patients to switch on and off relevant safety communications; and the ability to manage information about healthcare products via a product watch list.

Q: What opportunities do you see for the evolution of benefits and risks evidence generation in the rapidly changing scientific, technological and analytical landscape?

A: Despite advances in drug development and improvement in our scientific understanding of the mechanisms underlying disease, one of the main challenges we have as regulators is to improve our ability to predict and prevent adverse drug reactions (ADRs). Our regulatory initiatives have been helping to improve reporting of ADRs, but we need to advance our understanding of the biological mechanisms underpinning an adverse reaction.

My ambition is therefore to be better at predicting and preventing risk before it occurs, which will enable us to target medicines to those patients most likely to benefit and exclude only those most likely to develop unpleasant or harmful side effects. To tackle this, we have been working on a new project called the Yellow Card Biobank, which could identify where genetics influence those most at risk of an adverse drug reaction and support the downstream development of pharmacogenomic screening tests. It has the potential to ensure patients receive the right treatments, thereby reducing the overall number of ADRs. We hope to be able to capitalise on the unique source of UK-wide detailed ADR data, with over one million yellow cards available within the database, through initiatives such as this, so we can really start to move towards a more personalised prescribing approach based on both benefits and risks.

Q: How can the MHRA be sure that real-world data (RWD) from international partners (including beyond established consortia such as ACCESS and Orbis) is interchangeable and that the contribution from participating patients worldwide is maximised?

A: One of the ways the MHRA has been supporting globally relevant research using RWD is through the support of common data models which allows for the standardisation of data so it can be used for pooled global analyses. The MHRA’s CPRD research database includes anonymised primary care health records for over 60 million patients and has been used for safety surveillance and health research which has been published in over 2900 peer-reviewed publications. This rich longitudinal database has been mapped to the Observational Medical Outcomes Partnership (OMOP) common data model (CDM), in collaboration with the European Health Data Evidence Network (EHDEN) and to the FDA’s Sentinel common data model to facilitate the pooling of global data sources for federated analyses.

Q: How can the MHRA obtain a proportional understanding of the importance of real-world evidence (RWE) versus data derived from controlled interventional clinical studies?

A: The MHRA has developed guidance on the use of real-world data in clinical studies[4] to support regulatory decisions. In this guidance, we emphasise that the use of RWD in clinical studies has the potential to increase the speed and to reduce the cost of development programmes, which would see effective medicines being approved more quickly, or even programmes that were previously thought to be unfeasible becoming feasible without compromising on the strength of the evidence, with the consequent benefit to public health.

The guidance also recognises the value of evidence derived from RWD, which may be more representative of the true effects of a treatment in the community and more generalisable than data from the standardised setting of a traditional clinical trial. I would like to emphasise, however, it is not always a case of which is better or where we could use one approach over another but oft en where the use of diff erent data sources can complement each other to strengthen the evidence generated.

[1] MHRA. Patient Involvement Strategy 2021-25. Available at: Patient_involvement_strategy.pdf ( (accessed 22 April 2022).

[2] MHRA Corporate Plan 2018 to 2023. Available at: MHRA Corporate Plan 2018 to 2023 - GOV.UK ( (accessed 22 April 2022).

[3] The Medicines and Healthcare products Regulatory Agency Delivery Plan 2021-2023. Available at: MHRA_Delivery_Plan_21-23_Final_220203.pdf ( (accessed 22 April 2022).

[4] MHRA guidance on the use of real-world data in clinical studies to support regulatory decisions. Available at: MHRA guidance on the use of real-world data in clinical studies to support regulatory decisions - GOV.UK ( (accessed 22 April 2022).