Objectives
Patient and public involvement (PPI) in clinical research has a well-established infrastructure in the UK, and while there has been good progress within pharmaceutical-industry-sponsored ...research, further improvements are still needed. This review aims to share learnings from quality assessments of historical PPI projects within Pfizer UK to inform future projects and drive PPI progress in the pharmaceutical industry.
Design and setting
Internal assessments of Pfizer UK PPI projects were conducted to identify all relevant projects across the medicines development continuum between 2017 and 2021. Five sample projects were developed into case studies.
Outcome measure
Retrospective quality assessments were performed using the Patient Focused Medicines Development (PFMD) Patient Engagement Quality Guidance (PEQG) tool. Recommendations for improvement were developed.
Results
Retrospective case study analysis and quality framework assessment revealed benefits of PPI to both Pfizer UK and to external partners, as well as challenges and learnings to improve future practice. Recommendations for improvement based on these findings focused on processes and procedures for PPI, group dynamics and diversity for PPI activities, sharing of expertise, the importance of bidirectional and timely feedback, and the use of understandable language in materials.
Conclusions
PPI in medicines development is impactful and beneficial but is still being optimised in the pharmaceutical industry. Using the PFMD PEQG tool to define gaps, share learnings and devise recommendations for improvement helps to ensure that PPI is genuine and empowering, rather than tokenistic. Ultimately, these recommendations should be acted on to further embed PPI as an integral part of medicines development and health research within the pharmaceutical industry. This article includes a plain language summary in the supplement.
The UK Secretary of State for Health and Social Care, Stephen Barclay, has set out plans for an alternative approach to cancer service provision based on a major conditions strategy.1 The six areas ...for inclusion in the strategy are cancer, cardiovascular disease, respiratory disease, dementia, mental health, and musculoskeletal disorders. A holistic approach to patient care can be helpful and there are many scenarios when “integrated, whole-person care”, as promised by this new strategy,1 is appropriate and beneficial; however, understanding comorbidities is vital to treatment outcomes and experiences and a key part of clinical decision making for individual patients, and is very different to merging diseases in a national strategy that will dilute attention to specific areas. A health service that listens to what its patients say and delivers quick and accurate diagnoses, prompt expert treatment, effective follow-up, and innovative treatments for advanced disease will deliver continuous improvements in survival, quality of life, and enhanced quality of care. RW has received honoraria from Boehringer Ingelheim, the Health Research Authority, and Birmingham University for advice as a patient expert; has received support for conference attendance from Sarcoma UK and Sarcoma Patients Advocacy Global Network (SPAGN); is a board member of SPAGN, a member of the National Cancer Research Institute (NCRI) Consumer Forum, and a patient panel member for the Medicines and Healthcare products Regulatory Agency.
People with cancer are at increased risk of hospitalisation and death following infection with SARS-CoV-2. Therefore, we aimed to conduct one of the first evaluations of vaccine effectiveness against ...breakthrough SARS-CoV-2 infections in patients with cancer at a population level.
In this population-based test-negative case-control study of the UK Coronavirus Cancer Evaluation Project (UKCCEP), we extracted data from the UKCCEP registry on all SARS-CoV-2 PCR test results (from the Second Generation Surveillance System), vaccination records (from the National Immunisation Management Service), patient demographics, and cancer records from England, UK, from Dec 8, 2020, to Oct 15, 2021. Adults (aged ≥18 years) with cancer in the UKCCEP registry were identified via Public Health England's Rapid Cancer Registration Dataset between Jan 1, 2018, and April 30, 2021, and comprised the cancer cohort. We constructed a control population cohort from adults with PCR tests in the UKCCEP registry who were not contained within the Rapid Cancer Registration Dataset. The coprimary endpoints were overall vaccine effectiveness against breakthrough infections after the second dose (positive PCR COVID-19 test) and vaccine effectiveness against breakthrough infections at 3–6 months after the second dose in the cancer cohort and control population.
The cancer cohort comprised 377 194 individuals, of whom 42 882 had breakthrough SARS-CoV-2 infections. The control population consisted of 28 010 955 individuals, of whom 5 748 708 had SARS-CoV-2 breakthrough infections. Overall vaccine effectiveness was 69·8% (95% CI 69·8–69·9) in the control population and 65·5% (65·1–65·9) in the cancer cohort. Vaccine effectiveness at 3–6 months was lower in the cancer cohort (47·0%, 46·3–47·6) than in the control population (61·4%, 61·4–61·5).
COVID-19 vaccination is effective for individuals with cancer, conferring varying levels of protection against breakthrough infections. However, vaccine effectiveness is lower in patients with cancer than in the general population. COVID-19 vaccination for patients with cancer should be used in conjunction with non-pharmacological strategies and community-based antiviral treatment programmes to reduce the risk that COVID-19 poses to patients with cancer.
University of Oxford, University of Southampton, University of Birmingham, Department of Health and Social Care, and Blood Cancer UK.
Although supporting and assessing the non-academic “impact” of research are not entirely new developments in higher education, academics and research institutions are under increasing pressure to ...produce work that has a measurable influence outside the academy. With a view to supporting the solution of complex societal issues with evidence and expertise, and against the background of increased emphasis on impact in the United Kingdom's 2021 Research Excellence Framework (REF2021) and a proliferation of impact guides and tools, this article offers a simple, easy to remember framework for designing impactful research. We call this framework “The 7Cs of Impact” – Context, Communities, Constituencies, Challenge, Channels, Communication and Capture.
Drawing on core elements of the Policy Institute at King's College London's
Impact by Design
training course and the authors' practical experience in supporting and delivering impact, this paper outlines how this framework can help address key aspects across the lifecycle of a research project and plan, from identifying the intended impact of research and writing it into grants and proposals, to engaging project stakeholders and assessing whether the project has had the desired impact.
While preparations for current and future REF submissions may benefit from using this framework, this paper sets out the “7Cs” with a more holistic view of impact in mind, seeking to aid researchers in identifying, capturing, and communicating how research projects can and do contribute to the improvement in society.
Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support ...clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). Registry-based cohort study including only people with rare head and neck cancers. to help describe the natural history of rare head and neck cancers; It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed.
Although supporting and assessing the non-academic “impact” of research are not entirely new developments in higher education, academics and research institutions are under increasing pressure to ...produce work that has a measurable influence outside the academy. With a view to supporting the solution of complex societal issues with evidence and expertise, and against the background of increased emphasis on impact in the United Kingdom’s 2021 Research Excellence Framework (REF2021) and a proliferation of impact guides and tools, this article offers a simple, easy to remember framework for designing impactful research. We call this framework: “The 7Cs of Impact” – Context, Communities, Constituencies, Challenge, Channels, Communication and Capture.
Drawing on core elements of the Policy Institute at King’s College London’s
Impact by Design
training course and the authors’ practical experience in supporting and delivering impact, this paper outlines how this framework can help address key aspects across the lifecycle of a research project and plan, from identifying the intended impact of research and writing it into grants and proposals, to engaging project stakeholders and assessing whether the project has had the desired impact.
While preparations for current and future REF submissions may benefit from using this framework, this paper sets out the “7Cs” with a more holistic view of impact in mind, seeking to aid researchers in identifying, capturing, and communicating how research projects can and do contribute to the improvement in society.
Abstract
While robust evidence is one ingredient in the policymaking process, it is by no means the only one. Engaging with policymakers and the policymaking process requires collaborative working ...models, navigating through the experiences, values and perspectives of policymakers and other stakeholders, as well as communicating evidence in an accessible manner. As a response to these requirements, over recent years there has been proliferation of activities that engage producers of evidence (specifically, academics), policymakers, practitioners, and the public in policy formulation, implementation and evaluation. In this article, we describe one engagement approach for facilitating research evidence uptake into policy and practice—an activity called a ‘Policy Lab’—as conducted by the team at The Policy Institute at King’s College London on numerous policy challenges over the past four years. Drawing on our experience in running 15 Policy Labs between January 2015 and September 2019, we (a) provide a guide to how we have run Policy Labs, while sharing our learning on what has worked best in conducting them and (b) demonstrate how these labs can contribute to bringing evidence closer to policymaking, by comparing their characteristics to enablers for doing so identified in the literature. While this approach to Policy Labs is not the only one of its kind, we suggest that these types of Labs manifest characteristics identified in previous studies for influencing the policymaking process; namely: providing a forum for open, honest conversations around a policy topic; creating new networks, collaborations and partnerships between academics and policymakers; synthesising available evidence on a policy topic in a robust and accessible format; and providing timely access to evidence relevant to a policy issue. We recognise the limitations of measuring and evaluating how these Labs change policy in the long-term and recommend viewing the Policy Lab as part of a process for engaging evidence and policymaking and not an isolated activity. This process serves to build a coalition through participation of diverse communities (thereby establishing ‘trust’), work on the language and presentation of evidence (thereby enabling effective ‘translation’ of evidence) and engage policymakers early to respond when policy windows emerge (thereby taking into account ‘timing’ for creating policy action).
There is an urgent need to understand the nature of immune responses against SARS-CoV-2, to inform risk-mitigation strategies for people living with HIV (PLWH). Here we show that the majority of PLWH ...with ART suppressed HIV viral load, mount a detectable adaptive immune response to SARS-CoV-2. Humoral and SARS-CoV-2-specific T cell responses are comparable between HIV-positive and negative subjects and persist 5-7 months following predominately mild COVID-19 disease. T cell responses against Spike, Membrane and Nucleoprotein are the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. We further show that the overall magnitude of SARS-CoV-2-specific T cell responses relates to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH. These findings suggest that inadequate immune reconstitution on ART, could hinder immune responses to SARS-CoV-2 with implications for the individual management and vaccine effectiveness in PLWH.
Natural killer (NK) cell subsets with adaptive properties are emerging as regulators of vaccine-induced T and B cell responses and are specialized towards antibody-dependent functions contributing to ...SARS-CoV-2 control. Although HIV-1 infection is known to affect the NK cell pool, the additional impact of SARS-CoV-2 infection and/or vaccination on NK cell responses in people living with HIV (PLWH) has remained unexplored. Our data show that SARS-CoV-2 infection skews NK cells towards a more differentiated/adaptive CD57
FcεRIγ
phenotype in PLWH. A similar subset was induced following vaccination in SARS-CoV-2 naïve PLWH in addition to a CD56
population with cytotoxic potential. Antibody-dependent NK cell function showed robust and durable responses to Spike up to 148 days post-infection, with responses enriched in adaptive NK cells. NK cell responses were further boosted by the first vaccine dose in SARS-CoV-2 exposed individuals and peaked after the second dose in SARS-CoV-2 naïve PLWH. The presence of adaptive NK cells associated with the magnitude of cellular and humoral responses. These data suggest that features of adaptive NK cells can be effectively engaged to complement and boost vaccine-induced adaptive immunity in potentially more vulnerable groups such as PLWH.
We assessed a cohort of people living with human immunodeficiency virus (PLWH) (n = 110) and HIV negative controls (n = 64) after 1, 2 or 3 SARS-CoV-2 vaccine doses. At all timepoints, PLWH had ...significantly lower neutralizing antibody (nAb) titers than HIV-negative controls. We also observed a delayed development of neutralization in PLWH that was underpinned by a reduced frequency of spike-specific memory B cells (MBCs). Improved neutralization breadth was seen against the Omicron variant (BA.1) after the third vaccine dose in PLWH but lower nAb responses persisted and were associated with global MBC dysfunction. In contrast, SARS-CoV-2 vaccination induced robust T cell responses that cross-recognized variants in PLWH. Strikingly, individuals with low or absent neutralization had detectable functional T cell responses. These PLWH had reduced numbers of circulating T follicular helper cells and an enriched population of CXCR3+CD127+CD8+T cells after two doses of SARS-CoV-2 vaccination.
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•PLWH have lower levels of neutralizing antibodies (nAbs) after SARS-CoV-2 vaccination•Delayed production of nAbs is associated with greater memory B cell (MBCs) disturbance•Additional doses increase nAbs titers and breadth despite persistent MBCs perturbations•SARS-CoV-2 vaccination elicits robust T cell responses in PLWH•PLWH with spike-specific T cells but no nAbs have increased CXCR3+CD127+CD8+T cells
Immunology; Virology
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