Pay-for-Performance incentives for specialised services in England: a mixed methods evaluation.

BACKGROUND: A Pay-for-Performance (P4P) programme, known as Prescribed Specialised Services Commissioning for Quality and Innovation (PSS CQUIN), was introduced for specialised services in the English NHS in 2013/2014. These services treat patients with rare and complex conditions. We evaluate the implementation of PSS CQUIN contracts between 2016/2017 and 2018/2019. METHODS: We used a mixed methods evaluative approach. In the quantitative analysis, we used a difference-in-differences design to evaluate the effectiveness of ten PSS CQUIN schemes across a range of targeted outcomes. Potential selection bias was addressed using propensity score matching. We also estimated impacts on costs by scheme and financial year. In the qualitative analysis, we conducted semi-structured interviews and focus group discussions to gain insights into the complexities of contract design and programme implementation. Qualitative data analysis was based on the constant comparative method, inductively generating themes. RESULTS: The ten PSS CQUIN schemes had limited impact on the targeted outcomes. A statistically significant improvement was found for only one scheme: in the clinical area of trauma, the incentive scheme increased the probability of being discharged from Adult Critical Care within four hours of being clinically ready by 7%. The limited impact may be due to the size of the incentive payments, the complexity of the schemes' design, and issues around ownership, contracting and flexibility. CONCLUSION: The PSS CQUIN schemes had little or no impact on quality improvements in specialised services. Future P4P programmes in healthcare could benefit from lessons learnt from this study on incentive design and programme implementation.

Comparing biparametric to multiparametric MRI in the diagnosis of clinically significant prostate cancer in biopsy-naive men (PRIME): a prospective, international, multicentre, non-inferiority within-patient, diagnostic yield trial protocol.

INTRODUCTION: Prostate MRI is a well-established tool for the diagnostic work-up for men with suspected prostate cancer (PCa). Current recommendations advocate the use of multiparametric MRI (mpMRI), which is composed of three sequences: T2-weighted sequence (T2W), diffusion-weighted sequence (DWI) and dynamic contrast-enhanced sequence (DCE). Prior studies suggest that a biparametric MRI (bpMRI) approach, omitting the DCE sequences, may not compromise clinically significant cancer detection, though there are limitations to these studies, and it is not known how this may affect treatment eligibility. A bpMRI approach will reduce scanning time, may be more cost-effective and, at a population level, will allow more men to gain access to an MRI than an mpMRI approach. METHODS: Prostate Imaging Using MRI±Contrast Enhancement (PRIME) is a prospective, international, multicentre, within-patient diagnostic yield trial assessing whether bpMRI is non-inferior to mpMRI in the diagnosis of clinically significant PCa. Patients will undergo the full mpMRI scan. Radiologists will be blinded to the DCE and will initially report the MRI using only the bpMRI (T2W and DWI) sequences. They will then be unblinded to the DCE sequence and will then re-report the MRI using the mpMRI sequences (T2W, DWI and DCE). Men with suspicious lesions on either bpMRI or mpMRI will undergo prostate biopsy. The main inclusion criteria are men with suspected PCa, with a serum PSA of ≤20 ng/mL and without prior prostate biopsy. The primary outcome is the proportion of men with clinically significant PCa detected (Gleason score ≥3+4 or Gleason grade group ≥2). A sample size of at least 500 patients is required. Key secondary outcomes include the proportion of clinically insignificant PCa detected and treatment decision. ETHICS AND DISSEMINATION: Ethical approval was obtained from the National Research Ethics Committee West Midlands, Nottingham (21/WM/0091). Results of this trial will be disseminated through peer-reviewed publications. Participants and relevant patient support groups will be informed about the results of the trial. TRIAL REGISTRATION NUMBER: NCT04571840.

Challenges of Shared Decision-making by Clinicians and Patients With Low-risk Differentiated Thyroid Cancer: A Systematic Review and Meta-Ethnography.

Importance: Several international guidelines have endorsed more conservative treatment of low-risk differentiated thyroid cancer (LRDTC), yet patients are facing more treatment options with similar oncologic outcomes and are expressing feelings of confusion, dissatisfaction, and anxiety. Shared decision-making, which considers the patient's values and preferences along with the most reliable medical evidence, has been proposed to optimize patient satisfaction in the context of the current clinical equipoise. Objectives: To understand key individual and behavioral factors affecting the patient and clinician decision-making process in treatment decision for LRDTC. Evidence Review: This systematic review and meta-ethnography involved a comprehensive literature search of MEDLINE, Embase, PubMed, and CINAHL databases for qualitative and mixed-method studies on patient and clinician experiences with the decision-making process for LRDTC treatment. The quality of the studies was assessed using the Mixed Methods Appraisal Tool; meta-ethnography was used for data analysis. Primary and secondary themes of the included studies were extracted, compared, and translated across articles to produce a lines-of-argument synthesis. Findings: Of 1081 publications identified, 12 articles met the inclusion criteria. The qualitative synthesis produced 4 themes: (1) a bimodal distribution of patient preferences for treatment decisions; (2) clinician anxiety affected equipoise and biased their recommendations; (3) clinicians struggled to identify patient concerns and preferences; and (4) the clinician-patient relationship and psychosocial support were key to shared decision-making but were frequently overlooked. Conclusions and Relevance: The findings of this systematic review and meta-ethnography emphasize the need for better patient-clinician communication, particularly with respect to eliciting patient concerns and preferences. With an ever-increasing pool of thyroid cancer survivors, future efforts should be directed at establishing and evaluating tools that will aid in shared decision-making for treatment of patients with LRDTC. Trial Registration: PROSPERO Identifier: CRD42022286395.

STIMULATE-ICP: A pragmatic, multi-centre, cluster randomised trial of an integrated care pathway with a nested, Phase III, open label, adaptive platform randomised drug trial in individuals with Long COVID: A structured protocol.

INTRODUCTION: Long COVID (LC), the persistent symptoms ≥12 weeks following acute COVID-19, presents major threats to individual and public health across countries, affecting over 1.5 million people in the UK alone. Evidence-based interventions are urgently required and an integrated care pathway approach in pragmatic trials, which include investigations, treatments and rehabilitation for LC, could provide scalable and generalisable solutions at pace. METHODS AND ANALYSIS: This is a pragmatic, multi-centre, cluster-randomised clinical trial of two components of an integrated care pathway (Coverscan™, a multi-organ MRI, and Living with COVID Recovery™, a digitally enabled rehabilitation platform) with a nested, Phase III, open label, platform randomised drug trial in individuals with LC. Cluster randomisation is at level of primary care networks so that integrated care pathway interventions are delivered as "standard of care" in that area. The drug trial randomisation is at individual level and initial arms are rivaroxaban, colchicine, famotidine/loratadine, compared with no drugs, with potential to add in further drug arms. The trial is being carried out in 6-10 LC clinics in the UK and is evaluating the effectiveness of a pathway of care for adults with LC in reducing fatigue and other physical, psychological and functional outcomes at 3 months. The trial also includes an economic evaluation which will be described separately. ETHICS AND DISSEMINATION: The protocol was reviewed by South Central-Berkshire Research Ethics Committee (reference: 21/SC/0416). All participating sites obtained local approvals prior to recruitment. Coverscan™ has UK certification (UKCA 752965). All participants will provide written consent to take part in the trial. The first participant was recruited in July 2022 and interim/final results will be disseminated in 2023, in a plan co-developed with public and patient representatives. The results will be presented at national and international conferences, published in peer reviewed medical journals, and shared via media (mainstream and social) and patient support organisations. TRIAL REGISTRATION NUMBER: ISRCTN10665760.

The impact of the COVID-19 pandemic on cardiovascular disease prevention and management.

How the Coronavirus Disease 2019 (COVID-19) pandemic has affected prevention and management of cardiovascular disease (CVD) is not fully understood. In this study, we used medication data as a proxy for CVD management using routinely collected, de-identified, individual-level data comprising 1.32 billion records of community-dispensed CVD medications from England, Scotland and Wales between April 2018 and July 2021. Here we describe monthly counts of prevalent and incident medications dispensed, as well as percentage changes compared to the previous year, for several CVD-related indications, focusing on hypertension, hypercholesterolemia and diabetes. We observed a decline in the dispensing of antihypertensive medications between March 2020 and July 2021, with 491,306 fewer individuals initiating treatment than expected. This decline was predicted to result in 13,662 additional CVD events, including 2,281 cases of myocardial infarction and 3,474 cases of stroke, should individuals remain untreated over their lifecourse. Incident use of lipid-lowering medications decreased by 16,744 patients per month during the first half of 2021 as compared to 2019. By contrast, incident use of medications to treat type 2 diabetes mellitus, other than insulin, increased by approximately 623 patients per month for the same time period. In light of these results, methods to identify and treat individuals who have missed treatment for CVD risk factors and remain undiagnosed are urgently required to avoid large numbers of excess future CVD events, an indirect impact of the COVID-19 pandemic.

The Use of a Discrete Choice Experiment Including Both Duration and Dead for the Development of an EQ-5D-5L Value Set for Australia.

BACKGROUND/AIMS: Discrete choice experiments (DCEs) with either duration included an attribute or with dead included as an option can be used as a stand-alone approach to value health states. This paper reports on a DCE with both of these features to develop an EQ-5D-5L value set for Australia. METHODS: A DCE was undertaken using a large Australian panel of internet respondents, from which a sample of more than 4000 Australian adults was chosen, stratified to be population representative on age and gender. The DCE contained 500 choice triplets, with two EQ-5D-5L health states with duration, and dead as the third option. Each respondent answered 12 choice sets from the 500, stating both the best and worst options from the three available. The design was constructed to estimate a utility algorithm with main effects plus some key interaction terms. A variety of approaches to parameterising interactions, and to anchoring the value set on the required 0-1 scale, were tested. A preferred Australian adult utility algorithm for use in cost-utility analysis was then generated. RESULTS: In total, 4477 people completed at least one choice set and were included in the analysis. The results reflected the monotonic structure of the EQ-5D-5L, in that moving from no problems to extreme problems led to worsening utility in each dimension. Inclusion of interaction terms demonstrates that the disutility of the first dimension moving to a poor level (defined as either level 5, or level 4 or 5) had a large impact, but subsequent dimensions moving to a poor level had a relatively smaller disutility. DISCUSSION: This work develops a value set for the EQ-5D-5L in Australia, and also provides a range of methodological insights which can inform future work using a stand-alone DCE to value health in other countries.

Protocol for a MULTI-centre feasibility study to assess the use of 99mTc-sestaMIBI SPECT/CT in the diagnosis of kidney tumours (MULTI-MIBI study).

INTRODUCTION: The incidence of renal tumours is increasing and anatomic imaging cannot reliably distinguish benign tumours from renal cell carcinoma. Up to 30% of renal tumours are benign, with oncocytomas the most common type. Biopsy has not been routinely adopted in many centres due to concerns surrounding non-diagnostic rate, bleeding and tumour seeding. As a result, benign masses are often unnecessarily surgically resected. 99mTc-sestamibi SPECT/CT has shown high diagnostic accuracy for benign renal oncocytomas and other oncocytic renal neoplasms of low malignant potential in single-centre studies. The primary aim of MULTI-MIBI is to assess feasibility of a multicentre study of 99mTc-sestamibi SPECT/CT against a reference standard of histopathology from surgical resection or biopsy. Secondary aims of the study include obtaining estimates of 99mTc-sestamibi SPECT/CT sensitivity and specificity and to inform the design and conduct of a future definitive trial. METHODS AND ANALYSIS: A feasibility prospective multicentre study of participants with indeterminate, clinical T1 renal tumours to undergo 99mTc-sestamibi SPECT/CT (index test) compared with histopathology from biopsy or surgical resection (reference test). Interpretation of the index and reference tests will be blinded to the results of the other. Recruitment rate as well as estimates of sensitivity, specificity, positive and negative predictive value will be reported. Semistructured interviews with patients and clinicians will provide qualitative data to inform onward trial design and delivery. Training materials for 99mTc-sestamibi SPECT/CT interpretation will be developed, assessed and optimised. Early health economic modelling using a decision analytic approach for different diagnostic strategies will be performed to understand the potential cost-effectiveness of 99mTc-sestamibi SPECT/CT. ETHICS AND DISSEMINATION: Ethical approval has been granted (UK HRA REC 20/YH/0279) protocol V.5.0 dated 21/6/2022. Study outputs will be presented and published nationally and internationally. TRIAL REGISTRATION NUMBER: ISRCTN12572202.

Does a working day keep the doctor away? A critical review of the impact of unemployment and job insecurity on health and social care utilisation.

While the negative impact of unemployment on health is relatively well established, the extent to which that impact reflects on changes in health and social care utilisation is not well understood. This paper critically reviews the direction, magnitude and drivers of the impact of unemployment and job insecurity on health and social care utilisation across different care settings. We identified 28 relevant studies, which included 79 estimates of association between unemployment/job insecurity and healthcare utilisation. Positive associations dominated mental health services (N = 8 out of 11), but not necessarily primary care (N = 25 out of 43) or hospital care (N = 5 out of 22). We conducted a meta-analysis to summarise the magnitude of the impact and found that unemployed individuals were about 30% more likely to use health services compared to those employed, although this was largely driven by mental health service use. Key driving factors included financial pressure, health insurance, social network, disposable time and depression/anxiety. This review suggests that unemployment is likely to be associated with increased mental health service use, but there is considerable uncertainty around primary and hospital care utilisation. Future work to examine the impact across other settings, including community and social care, and further explore non-health determinants of utilisation is needed. The protocol was registered in PROSPERO (CRD42020177668).

A new sexual wellbeing paradigm grounded in capability approach concepts of human flourishing and social justice.

Over the last twenty years, there has been a growing interest in measuring sexual wellbeing, including by a WHO/UNFPA working group in 2007, which sought clarity on key dimensions and asked for indicators of these to be devised. However, there remains a lack of conceptual clarity surrounding the concept of sexual wellbeing, which may create variation in what is being assessed and to what we are referring. This paper proposes one way in which to achieve conceptual clarity might be through the utilisation of a Capability Approach, thereby posing a new set of normative questions about what sexual wellbeing is. The central argument in this paper is for researchers, theorists and practitioners to focus more fully on a person's freedom to achieve sexual wellbeing within a particular social and cultural context. We suggest the kinds of data that might need to be captured to operationalise and measure such an understanding. By offering new critical insights, we hope to drive forward empirical and methodological development in the evaluation of sexual wellbeing.

How is the Societal Perspective Defined in Health Technology Assessment? Guidelines from Around the Globe.

Some researchers have argued that the aim of an economic evaluation should be to offer guidance on resource allocation based on public interest from a societal perspective. The application of a societal perspective in health technology assessment (HTA), while common in many published studies, is not mandated in most countries, and there is limited discussion on what the societal perspective should encompass. This study aimed to systematically compare and contrast the HTA guidelines in different countries. HTA methods guidelines were identified through international HTA networks, such as the Professional Society for Health Economics and Outcomes Research (ISPOR) and Guide to Economic Analysis Research (GEAR). The respective HTA agencies were grouped into two categories: well-established and newly developed, based on the establishment date. Data extracted from the guidelines summarised the methodological details in the reference cases, including specifics on the societal perspective. The database search yielded 46 guidelines, and 65% explicitly considered the societal perspective. The maturity of these agencies is reflected in their attitudes towards the societal perspective; the societal perspective is defined in 73% of the guidelines of well-established agencies and only 56% of those of newly developed agencies. The guidelines from multipayer healthcare systems are more likely to consider the societal perspective. Although most guidelines from the well-established agencies recommend the inclusion of a societal perspective, the types of costs and consequences that should be included and the recommended approaches to valuing them are variable. The direct costs to family and carers were included in 73% of the societal perspective definitions, while non-health outcomes were considered in only 40%. Most HTA guidelines lack clear guidance on what to include under specific perspectives. Considering the recent advancements in economic evaluation methods, it is timely to rethink the role of the societal perspective in HTA guidelines and adopt a more comprehensive perspective to include all costs and consequences of healthcare services.

STIMULATE-ICP-Delphi (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways Delphi): Study protocol.

INTRODUCTION: As mortality rates from COVID-19 disease fall, the high prevalence of long-term sequelae (Long COVID) is becoming increasingly widespread, challenging healthcare systems globally. Traditional pathways of care for Long Term Conditions (LTCs) have tended to be managed by disease-specific specialties, an approach that has been ineffective in delivering care for patients with multi-morbidity. The multi-system nature of Long COVID and its impact on physical and psychological health demands a more effective model of holistic, integrated care. The evolution of integrated care systems (ICSs) in the UK presents an important opportunity to explore areas of mutual benefit to LTC, multi-morbidity and Long COVID care. There may be benefits in comparing and contrasting ICPs for Long COVID with ICPs for other LTCs. METHODS AND ANALYSIS: This study aims to evaluate health services requirements for ICPs for Long COVID and their applicability to other LTCs including multi-morbidity and the overlap with medically not yet explained symptoms (MNYES). The study will follow a Delphi design and involve an expert panel of stakeholders including people with lived experience, as well as clinicians with expertise in Long COVID and other LTCs. Study processes will include expert panel and moderator panel meetings, surveys, and interviews. The Delphi process is part of the overall STIMULATE-ICP programme, aimed at improving integrated care for people with Long COVID. ETHICS AND DISSEMINATION: Ethical approval for this Delphi study has been obtained (Research Governance Board of the University of York) as have approvals for the other STIMULATE-ICP studies. Study outcomes are likely to inform policy for ICPs across LTCs. Results will be disseminated through scientific publication, conference presentation and communications with patients and stakeholders involved in care of other LTCs and Long COVID. REGISTRATION: Researchregistry: https://www.researchregistry.com/browse-the-registry#home/registrationdetails/6246bfeeeaaed6001f08dadc/.

Which countries need COVID-19 vaccines the most? Development of a prioritisation tool.

BACKGROUND: The COVID-19 pandemic and associated non-pharmaceutical interventions (NPIs) have affected all countries. With a scarcity of COVID-19 vaccines there has been a need to prioritize populations, but assessing relative needs has been challenging. The COVAX Facility allocates vaccines to cover 20% of each national population, followed by a needs assessment that considers five quantitative metrics alongside a qualitative assessment. The objective of this study was to identify the most important factors for assessing countries' needs for vaccines, and to weight each, generating a scoring tool for prioritising countries. METHODS: The study was conducted between March and November 2021. The first stage involved an online Delphi survey with a purposive and snowball sample of public health experts, to reach consensus on country-level factors for assessing relative needs for COVID-19 vaccines. The second stage involved a discrete choice experiment (DCE) to determine weights for the most important factors. RESULTS: Responses were received from 28 experts working across 13 different countries and globally. The most common job titles reported were director and professor, with most based in national public health institutes (n = 9) and universities (n = 8). The Delphi survey found 37 distinct factors related to needs. Nine of the most important factors were included in the DCE. Among these, the most important factor was the 'proportion of overall population not fully vaccinated' (with a mean weight of 19.5), followed by 'proportion of high-risk population not fully vaccinated' (16.1), 'health system capacity' (14.2), 'capacity to purchase vaccines' (11.9) and the 'proportion of the population clinically vulnerable' (11.3). CONCLUSIONS: Several factors exist, extending beyond those currently used, which may lead to some countries having a greater need for vaccines compared to others. By assessing relative needs, this scoring tool can build on existing methods to further the role of equity in global COVID-19 vaccine allocation.

STIMULATE-ICP-CAREINEQUAL (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways) study protocol: Defining usual care and examining inequalities in Long Covid support.

INTRODUCTION: Individuals with Long Covid represent a new and growing patient population. In England, fewer than 90 Long Covid clinics deliver assessment and treatment informed by NICE guidelines. However, a paucity of clinical trials or longitudinal cohort studies means that the epidemiology, clinical trajectory, healthcare utilisation and effectiveness of current Long Covid care are poorly documented, and that neither evidence-based treatments nor rehabilitation strategies exist. In addition, and in part due to pre-pandemic health inequalities, access to referral and care varies, and patient experience of the Long Covid care pathways can be poor. In a mixed methods study, we therefore aim to: (1) describe the usual healthcare, outcomes and resource utilisation of individuals with Long Covid; (2) assess the extent of inequalities in access to Long Covid care, and specifically to understand Long Covid patients' experiences of stigma and discrimination. METHODS AND ANALYSIS: A mixed methods study will address our aims. Qualitative data collection from patients and health professionals will be achieved through surveys, interviews and focus group discussions, to understand their experience and document the function of clinics. A patient cohort study will provide an understanding of outcomes and costs of care. Accessible data will be further analysed to understand the nature of Long Covid, and the care received. ETHICS AND DISSEMINATION: Ethical approval was obtained from South Central-Berkshire Research Ethics Committee (reference 303958). The dissemination plan will be decided by the patient and public involvement and engagement (PPIE) group members and study Co-Is, but will target 1) policy makers, and those responsible for commissioning and delivering Long Covid services, 2) patients and the public, and 3) academics.

The Real-World Impact of Vaccination on COVID-19 Cases During Europe's Fourth Wave.

Objectives: Disease control is important to limit the social, economic and health effects of COVID-19 and reduce the risk of novel variants emerging. Evidence suggests vaccines are less effective against the Omicron variant, but their impact on disease control is unclear. Methods: We used a longitudinal fixed effects Poisson regression model to assess the impact of vaccination on COVID-19 case rates across 32 countries in Europe from 13th October to 01st January 2022. We controlled for country and time fixed effects and the severity of public health restrictions. Results: Full vaccination coverage increased by 4.2%, leading to a 54% reduction in case rates across Europe (p < 0.001). This protection decreased over time but remained significant at 5 weeks after the detection of Omicron. Mean booster vaccination rates increased from 2.71% to 24.5% but provided no significant additional benefit. For every one-unit increase in the severity of public health restrictions, case rates fell by a further 2% (p = 0.019). Conclusion: Full vaccination significantly limited the spread of COVID-19 and blunted the impact of the Omicron variant, despite becoming less useful over time.

Information Asymmetry in Hospitals: Evidence of the Lack of Cost Awareness in Clinicians.

BACKGROUND: Information asymmetries and the agency relationship are two defining features of the healthcare system. These market failures are often used as a rationale for government intervention. Many countries have government financing and provision of healthcare in order to correct for this, while health technology agencies also exist to improve efficiency. However, informational asymmetries and the resulting principal-agent problem still persist, and one example is the lack of cost awareness amongst clinicians. This study explores the cost awareness of clinicians across different settings. METHODS: We targeted four clinical cohorts: medical students, Senior House Officers/Interns, Mid-grade Senior Registrar/Residents, and Consultant/Attending Physicians, in six hospitals in the United Kingdom, the United States, Australia, New Zealand and Spain. The survey asked respondents to report the cost (as they recalled) of different types of scans, visits, medications and tests. Our analysis focused on the differential between the perceived/recalled cost and the actual cost. We explored variation across speciality, country and other potential confounders. Cost-awareness levels were estimated based on the cost estimates within 25% of the actual cost. RESULTS: We received 705 complete responses from six sites across five countries. Our analysis found that respondents often overestimated the cost of common tests while underestimating high-cost tests. The mean cost-awareness levels varied between 4 and 23% for different items. Respondents acknowledged that they did not feel they had received adequate training in cost awareness. DISCUSSION: The current financial climate means that cost awareness and the appropriate use of scarce healthcare resources is more paramount than perhaps ever before. Much of the focus of health economics research is on high-cost innovative technologies, yet there is considerable waste in the system with respect to overtreatment and overdiagnosis. Common reasons put forward for this include defensive medicine, poor education, clinical uncertainty and the institution of protocols. CONCLUSION: Given the role of clinicians in the healthcare system, as agents both for patients and for providers, more needs to be done to remove informational asymmetries and improve clinician cost awareness.

The impact of pausing the Oxford-AstraZeneca COVID-19 vaccine on uptake in Europe: a difference-in-differences analysis.

BACKGROUND: Several countries paused their rollouts of the Oxford-AstraZeneca coronavirus disease-19 (COVID-19) vaccine in mid-March 2021 due to concerns about vaccine-induced thrombosis and thrombocytopenia. Many warned that this risked damaging public confidence during a critical period of pandemic response. This study investigated whether the pause in the use of the Oxford-AstraZeneca vaccine had an impact on subsequent vaccine uptake in European countries. METHODS: We used a difference-in-differences approach capitalizing on the fact that some countries halted their rollouts whilst others did not. A longitudinal panel was constructed for European Economic Area countries spanning 15 weeks in early 2021. Media reports were used to identify countries that paused the Oxford-AstraZeneca vaccine and the timing of this. Data on vaccine uptake were available through the European Centre for Disease Control and Prevention COVID-19 Vaccine Tracker. Difference-in-differences linear regression models controlled for key confounders that could influence vaccine uptake, and country and week fixed effects. Further models and robustness checks were performed. RESULTS: The panel included 28 countries, with 19 in the intervention group and 9 in the control group. Pausing the Oxford-AstraZeneca vaccine was associated with a 0.52% decrease in uptake for the first dose of a COVID-19 vaccine and a 1.49% decrease in the uptake for both doses, comparing countries that paused to those that did not. These estimates are not statistically significant (P = 0.86 and 0.39, respectively). For the Oxford-AstraZeneca vaccine only, the pause was associated with a 0.56% increase in uptake for the first dose and a 0.07% decrease in uptake for both doses. These estimates are also not statistically significant (P = 0.56 and 0.51, respectively). All our findings are robust to sensitivity analyses. CONCLUSIONS: As new COVID-19 vaccines emerge, regulators should be cautious to deviate from usual protocols if further investigation on clinical or epidemiological grounds is warranted.

The role of microvesicles as biomarkers in the screening of colorectal neoplasm.

BACKGROUND: Colorectal cancer (CRC) is the second cause of cancer death worldwide. The role of circulating microvesicles as a screening tool is a novel, yet effective approach that warrants prioritised research. METHODS: In a two-gate diagnostic accuracy study, 35 patients with benign colorectal polyps (BCRP) (n = 16) and colorectal cancer (CRC) (n = 19) were compared to 17 age-matched healthy controls. Total annexin-V positive microvesicles and sub-populations positive for selected biomarkers relevant to bowel neoplasm were evaluated in patients' plasma using flow cytometry. Statistical methods including factor analysis utilising two component factors were performed to obtain optimal diagnostic accuracy of microvesicles in identifying patients with colorectal neoplasms. RESULTS: Total plasma microvesicles, and sub-populations positive for CD31, CD42a, CD31+/CD42a-, EPHB2, ICAM and LGR5 (component factor-1) were able to identify patients with BCRP and CRC with a receiver operator curve (AUC) accuracy of a 100% (95% CI: 100%-100%) and 95% (95% CI: 88%-100%), respectively. To identify patients with BCRP, a cut-off point value of component factor-1761 microvesicles/µl demonstrated a 100% sensitivity, specificity and negative predictive value (NPV) and a 93% positive predictive value (PPV). To identify patients with CRC, a cut-off value of component factor-1 3 439 microvesicles/µl demonstrated a 100% sensitivity, specificity and NPV and a 65% PPV. CEA+ microvesicles sub-population were significantly (p < 0.02) higher in CRC in comparison to BCRP. CONCLUSIONS: Microvesicles as biomarkers for the early and accurate detection of CRC is a simple and effective tool that yields a potential breakthrough in clinical management.

Defining a Core Data Set for the Economic Evaluation of Precision Oncology.

OBJECTIVES: Precision oncology is generating vast amounts of multiomic data to improve human health and accelerate research. Existing clinical study designs and attendant data are unable to provide comparative evidence for economic evaluations. This lack of evidence can cause inconsistent and inappropriate reimbursement. Our study defines a core data set to facilitate economic evaluations of precision oncology. METHODS: We conducted a literature review of economic evaluations of next-generation sequencing technologies, a common application of precision oncology, published between 2005 and 2018 and indexed in PubMed (MEDLINE). Based on this review, we developed a preliminary core data set for informal expert feedback. We then used a modified-Delphi approach with individuals involved in implementation and evaluation of precision medicine, including 2 survey rounds followed by a final voting conference to refine the data set. RESULTS: Two authors determined that variation in published data elements was reached after abstraction of 20 economic evaluations. Expert consultation refined the data set to 83 unique data elements, and a multidisciplinary sample of 46 experts participated in the modified-Delphi process. A total of 68 elements (81%) were selected as required, spanning demographics and clinical characteristics, genomic data, cancer treatment, health and quality of life outcomes, and resource use. CONCLUSIONS: Cost-effectiveness analyses will fail to reflect the real-world impacts of precision oncology without data to accurately characterize patient care trajectories and outcomes. Data collection in accordance with the proposed core data set will promote standardization and enable the generation of decision-grade evidence to inform reimbursement.