Incidence and management of inflammatory arthritis in England before and during the COVID-19 pandemic: a population-level cohort study using OpenSAFELY.

Background: The impact of the COVID-19 pandemic on the incidence and management of inflammatory arthritis is not understood. Routinely captured data in secure platforms, such as OpenSAFELY, offer unique opportunities to understand how care for patients with inflammatory arthritis was impacted upon by the pandemic. Our objective was to use OpenSAFELY to assess the effects of the pandemic on diagnostic incidence and care delivery for inflammatory arthritis in England and to replicate key metrics from the National Early Inflammatory Arthritis Audit. Methods: In this population-level cohort study, we used primary care and hospital data for 17·7 million adults registered with general practices using TPP health record software, to explore the following outcomes between April 1, 2019, and March 31, 2022: (1) incidence of inflammatory arthritis diagnoses (rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and undifferentiated inflammatory arthritis) recorded in primary care; (2) time to first rheumatology assessment; (3) time to first prescription of a disease-modifying antirheumatic drug (DMARD) in primary care; and (4) choice of first DMARD. Findings: Among 17 683 500 adults, there were 31 280 incident inflammatory arthritis diagnoses recorded between April 1, 2019, and March 31, 2022. The mean age of diagnosed patients was 55·4 years (SD 16·6), 18 615 (59·5%) were female, 12 665 (40·5%) were male, and 22 925 (88·3%) of 25 960 with available ethnicity data were White. New inflammatory arthritis diagnoses decreased by 20·3% in the year commencing April, 2020, relative to the preceding year (5·1 vs 6·4 diagnoses per 10 000 adults). The median time to first rheumatology assessment was shorter during the pandemic (18 days; IQR 8-35) than before (21 days; 9-41). The proportion of patients prescribed DMARDs in primary care was similar before and during the pandemic; however, during the pandemic, fewer people were prescribed methotrexate or leflunomide, and more were prescribed sulfasalazine or hydroxychloroquine. Interpretation: Inflammatory arthritis diagnoses decreased markedly during the early phase of the pandemic. The impact on rheumatology assessment times and DMARD prescribing in primary care was less marked than might have been anticipated. This study demonstrates the feasibility of using routinely captured, near real-time data in the secure OpenSAFELY platform to benchmark care quality on a national scale, without the need for manual data collection. Funding: None.

Impact of first UK COVID-19 lockdown on hospital admissions: Interrupted time series study of 32 million people.

Background: Uncontrolled infection and lockdown measures introduced in response have resulted in an unprecedented challenge for health systems internationally. Whether such unprecedented impact was due to lockdown itself and recedes when such measures are lifted is unclear. We assessed the short- and medium-term impacts of the first lockdown measures on hospital care for tracer non-COVID-19 conditions in England, Scotland and Wales across diseases, sexes, and socioeconomic and ethnic groups. Methods: We used OpenSAFELY (for England), EAVEII (Scotland), and SAIL Databank (Wales) to extract weekly hospital admission rates for cancer, cardiovascular and respiratory conditions (excluding COVID-19) from the pre-pandemic period until 25/10/2020 and conducted a controlled interrupted time series analysis. We undertook stratified analyses and assessed admission rates over seven months during which lockdown restrictions were gradually lifted. Findings: Our combined dataset included 32 million people who contributed over 74 million person-years. Admission rates for all three conditions fell by 34.2% (Confidence Interval (CI): -43.0, -25.3) in England, 20.9% (CI: -27.8, -14.1) in Scotland, and 24.7% (CI: -36.7, -12.7) in Wales, with falls across every stratum considered. In all three nations, cancer-related admissions fell the most while respiratory-related admissions fell the least (e.g., rates fell by 40.5% (CI: -47.4, -33.6), 21.9% (CI: -35.4, -8.4), and 19.0% (CI: -30.6, -7.4) in England for cancer, cardiovascular-related, and respiratory-related admissions respectively). Unscheduled admissions rates fell more in the most than the least deprived quintile across all three nations. Some ethnic minority groups experienced greater falls in admissions (e.g., in England, unscheduled admissions fell by 9.5% (CI: -20.2, 1.2) for Whites, but 44.3% (CI: -71.0, -17.6), 34.6% (CI: -63.8, -5.3), and 25.6% (CI: -45.0, -6.3) for Mixed, Other and Black ethnic groups respectively). Despite easing of restrictions, the overall admission rates remained lower in England, Scotland, and Wales by 20.8%, 21.6%, and 22.0%, respectively when compared to the same period (August-September) during the pre-pandemic years. This corresponds to a reduction of 26.2, 23.8 and 30.2 admissions per 100,000 people in England, Scotland, and Wales respectively. Interpretation: Hospital care for non-COVID diseases fell substantially across England, Scotland, and Wales during the first lockdown, with reductions persisting for at least six months. The most deprived and minority ethnic groups were impacted more severely. Funding: This work was funded by the Medical Research Council as part of the Lifelong Health and Wellbeing study as part of National Core Studies (MC_PC_20030). SVK acknowledges funding from the Medical Research Council (MC_UU_00022/2), and the Scottish Government Chief Scientist Office (SPHSU17). EAVE II is funded by the Medical Research Council (MR/R008345/1) with the support of BREATHE - The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. BG has received research funding from the NHS National Institute for Health Research (NIHR), the Wellcome Trust, Health Data Research UK, Asthma UK, the British Lung Foundation, and the Longitudinal Health and Wellbeing strand of the National Core Studies programme.

OpenSAFELY: impact of national guidance on switching anticoagulant therapy during COVID-19 pandemic.

BACKGROUND: Early in the COVID-19 pandemic, the National Health Service (NHS) recommended that appropriate patients anticoagulated with warfarin should be switched to direct-acting oral anticoagulants (DOACs), requiring less frequent blood testing. Subsequently, a national safety alert was issued regarding patients being inappropriately coprescribed two anticoagulants following a medication change and associated monitoring. OBJECTIVE: To describe which people were switched from warfarin to DOACs; identify potentially unsafe coprescribing of anticoagulants; and assess whether abnormal clotting results have become more frequent during the pandemic. METHODS: With the approval of NHS England, we conducted a cohort study using routine clinical data from 24 million NHS patients in England. RESULTS: 20 000 of 164 000 warfarin patients (12.2%) switched to DOACs between March and May 2020, most commonly to edoxaban and apixaban. Factors associated with switching included: older age, recent renal function test, higher number of recent INR tests recorded, atrial fibrillation diagnosis and care home residency. There was a sharp rise in coprescribing of warfarin and DOACs from typically 50-100 per month to 246 in April 2020, 0.06% of all people receiving a DOAC or warfarin. International normalised ratio (INR) testing fell by 14% to 506.8 patients tested per 1000 warfarin patients each month. We observed a very small increase in elevated INRs (n=470) during April compared with January (n=420). CONCLUSIONS: Increased switching of anticoagulants from warfarin to DOACs was observed at the outset of the COVID-19 pandemic in England following national guidance. There was a small but substantial number of people coprescribed warfarin and DOACs during this period. Despite a national safety alert on the issue, a widespread rise in elevated INR test results was not found. Primary care has responded rapidly to changes in patient care during the COVID-19 pandemic.

Evaluating the impact of a very low-cost intervention to increase practices' engagement with data and change prescribing behaviour: a randomized trial in English primary care.

BACKGROUND: Unsolicited feedback can solicit changes in prescribing. OBJECTIVES: Determine whether a low-cost intervention increases clinicians' engagement with data, and changes prescribing; with or without behavioural science techniques. METHODS: Randomized trial (ISRCTN86418238). The highest prescribing practices in England for broad-spectrum antibiotics were allocated to: feedback with behavioural impact optimization; plain feedback; or no intervention. Feedback was sent monthly for 3 months by letter, fax and email. Each included a link to a prescribing dashboard. The primary outcomes were dashboard usage and change in prescribing. RESULTS: A total of 1401 practices were randomized: 356 behavioural optimization, 347 plain feedback, and 698 control. For the primary engagement outcome, more intervention practices had their dashboards viewed compared with controls [65.7% versus 55.9%; RD 9.8%, 95% confidence intervals (CIs): 4.76% to 14.9%, P < 0.001]. More plain feedback practices had their dashboard viewed than behavioural feedback practices (69.1% versus 62.4%); but not meeting the P < 0.05 threshold (6.8%, 95% CI: -0.19% to 13.8%, P = 0.069). For the primary prescribing outcome, intervention practices possibly reduced broad-spectrum prescribing to a greater extent than controls (1.42% versus 1.12%); but again not meeting the P < 0.05 threshold (coefficient -0.31%, CI: -0.7% to 0.1%, P = 0.104). The behavioural impact group reduced broad-spectrum prescribing to a greater extent than plain feedback practices (1.63% versus 1.20%; coefficient 0.41%, CI: 0.007% to 0.8%, P = 0.046). No harms were detected. CONCLUSIONS: Unsolicited feedback increased practices' engagement with data, with possible slightly reduced antibiotic prescribing (P = 0.104). Behavioural science techniques gave greater prescribing effects. The modest effects on prescribing may reflect saturation from similar initiatives on antibiotic prescribing. CLINICAL TRIAL REGISTRATION: ISRCTN86418238.

Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts.

OBJECTIVES: To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. METHODS: We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region. RESULTS: In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use. CONCLUSIONS: We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.

A comprehensive high cost drugs dataset from the NHS in England - An OpenSAFELY-TPP Short Data Report.

Background: At the outset of the COVID-19 pandemic, there was no routine comprehensive hospital medicines data from the UK available to researchers. These records can be important for many analyses including the effect of certain medicines on the risk of severe COVID-19 outcomes. With the approval of NHS England, we set out to obtain data on one specific group of medicines, "high-cost drugs" (HCD) which are typically specialist medicines for the management of long-term conditions, prescribed by hospitals to patients. Additionally, we aimed to make these data available to all approved researchers in OpenSAFELY-TPP. This report is intended to support all studies carried out in OpenSAFELY-TPP, and those elsewhere, working with this dataset or similar data. Methods: Working with the North East Commissioning Support Unit and NHS Digital, we arranged for collation of a single national HCD dataset to help inform responses to the COVID-19 pandemic. The dataset was developed from payment submissions from hospitals to commissioners. Results: In the financial year (FY) 2018/19 there were 2.8 million submissions for 1.1 million unique patient IDs recorded in the HCD. The average number of submissions per patient over the year was 2.6. In FY 2019/20 there were 4.0 million submissions for 1.3 million unique patient IDs. The average number of submissions per patient over the year was 3.1. Of the 21 variables in the dataset, three are now available for analysis in OpenSafely-TPP: Financial year and month of drug being dispensed; drug name; and a description of the drug dispensed. Conclusions: We have described the process for sourcing a national HCD dataset, making these data available for COVID-19-related analysis through OpenSAFELY-TPP and provided information on the variables included in the dataset, data coverage and an initial descriptive analysis.

Suboptimal prescribing behaviour associated with clinical software design features: a retrospective cohort study in English NHS primary care.

BACKGROUND: Electronic health record (EHR) systems are used by clinicians to record patients' medical information, and support clinical activities such as prescribing. In England, healthcare professionals are advised to 'prescribe generically' because generic drugs are usually cheaper than branded alternatives, and have fixed reimbursement costs. 'Ghost-branded generics' are a new category of medicines savings, caused by prescribers specifying a manufacturer for a generic product, often resulting in a higher reimbursement price compared with the true generic. AIM: To describe time trends and practice factors associated with excess medication costs from ghost-branded generic prescribing. DESIGN AND SETTING: Retrospective cohort study of English GP prescribing data and EHR deployment data. METHOD: A retrospective cohort study was conducted, based on data from the OpenPrescribing.net database from May 2013 to May 2019. Total spending on ghost-branded generics across England was calculated, and excess spend on ghost-branded generics calculated as a percentage of all spending on generics for every CCG and general practice in England, for every month in the study period. RESULTS: There were 31.8 million ghost-branded generic items and £9.5 million excess cost in 2018, compared with 7.45 million ghost-branded generic items and £1.3 million excess cost in 2014. Most excess costs were associated with one EHR, SystmOne, and it was identified that SystmOne offered ghost-branded generic options as the default. After informing the vendor, the authors monitored for subsequent change in costs, and report a rapid decrease in ghost-branded generic expenditure. CONCLUSION: A design choice in a commonly used EHR has led to £9.5 million in avoidable excess prescribing costs for the NHS in 1 year. Notifying the vendor led to a change in user interface and a rapid, substantial spend reduction. This finding illustrates that EHR user interface design has a substantial impact on the quality, safety, and cost-effectiveness of clinical practice; this should be a priority for quantitative research.

Measuring the Impact of an Open Web-Based Prescribing Data Analysis Service on Clinical Practice: Cohort Study on NHS England Data.

BACKGROUND: OpenPrescribing is a freely accessible service that enables any user to view and analyze the National Health Service (NHS) primary care prescribing data at the level of individual practices. This tool is intended to improve the quality, safety, and cost-effectiveness of prescribing. OBJECTIVE: We aimed to measure the impact of OpenPrescribing being viewed on subsequent prescribing. METHODS: Having preregistered our protocol and code, we measured three different metrics of prescribing quality (mean percentile across 34 existing OpenPrescribing quality measures, available "price-per-unit" savings, and total "low-priority prescribing" spend) to see whether they changed after the viewing of Clinical Commissioning Group (CCG) and practice pages. We also measured whether practices whose data were viewed on OpenPrescribing differed in prescribing, prior to viewing, compared with those who were not. We used fixed-effects and between-effects linear panel regression to isolate change over time and differences between practices, respectively. We adjusted for the month of prescribing in the fixed-effects model to remove underlying trends in outcome measures. RESULTS: We found a reduction in available price-per-unit savings for both practices and CCGs after their pages were viewed. The saving was greater at practice level (-£40.42 per thousand patients per month; 95% CI -54.04 to -26.81) than at CCG level (-£14.70 per thousand patients per month; 95% CI -25.56 to -3.84). We estimate a total saving since launch of £243 thosand at practice level and £1.47 million at CCG level between the feature launch and end of follow-up (August to November 2017) among practices viewed. If the observed savings from practices viewed were extrapolated to all practices, this would generate £26.8 million in annual savings for the NHS, approximately 20% of the total possible savings from this method. The other two measures were not different after CCGs or practices were viewed. Practices that were viewed had worse prescribing quality scores overall prior to viewing. CONCLUSIONS: We found a positive impact from the use of OpenPrescribing, specifically for the class of savings opportunities that can only be identified by using this tool. Furthermore, we show that it is possible to conduct a robust analysis of the impact of such a Web-based service on clinical practice.

Compliance with requirement to report results on the EU Clinical Trials Register: cohort study and web resource.

OBJECTIVES: To ascertain compliance rates with the European Commission's requirement that all trials on the EU Clinical Trials Register (EUCTR) post results to the registry within 12 months of completion (final compliance date 21 December 2016); to identify features associated with non-compliance; to rank sponsors by compliance; and to build a tool for live ongoing audit of compliance. DESIGN: Retrospective cohort study. SETTING: EUCTR. PARTICIPANTS: 7274 of 11 531 trials listed as completed on EUCTR and where results could be established as due. MAIN OUTCOME MEASURE: Publication of results on EUCTR. RESULTS: Of 7274 trials where results were due, 49.5% (95% confidence interval 48.4% to 50.7%) reported results. Trials with a commercial sponsor were substantially more likely to post results than those with a non-commercial sponsor (68.1% v 11.0%, adjusted odds ratio 23.2, 95% confidence interval 19.2 to 28.2); as were trials by a sponsor who conducted a large number of trials (77.9% v 18.4%, adjusted odds ratio 18.4, 15.3 to 22.1). More recent trials were more likely to report results (per year odds ratio 1.05, 95% confidence interval 1.03 to 1.07). Extensive evidence was found of errors, omissions, and contradictory entries in EUCTR data that prevented ascertainment of compliance for some trials. CONCLUSIONS: Compliance with the European Commission requirement for all trials to post results on to the EUCTR within 12 months of completion has been poor, with half of all trials non-compliant. EU registry data commonly contain inconsistencies that might prevent even regulators assessing compliance. Accessible and timely information on the compliance status of each individual trial and sponsor may help to improve reporting rates.

Trends and variation in prescribing of low-priority treatments identified by NHS England: a cross-sectional study and interactive data tool in English primary care.

Objectives NHS England recently announced a consultation seeking to discourage the use of treatments it considers to be low-value. We set out to produce an interactive data resource to show savings in each NHS general practice and to assess the current use of these treatments, their change in use over time, and the extent and reasons for variation in such prescribing. Design Cross-sectional analysis. Setting English primary care. Participants English general practices. Main outcome measures We determined the cost per 1000 patients for prescribing of each of 18 treatments identified by NHS England for each month from July 2012 to June 2017, and also aggregated over the most recent year to assess total cost and variation among practices. We used mixed effects linear regression to determine factors associated with cost of prescribing. Results Spend on low-value treatments was £153.5 m in the last year, across 5.8 m prescriptions (mean, £26 per prescription). Among individual treatments, liothyronine had the highest prescribing cost at £29.6 m, followed by trimipramine (£20.2 m). Over time, the overall total number of low-value prescriptions decreased, but the cost increased, although this varied greatly between treatments. Three treatment areas increased in cost and two increased in volume, all others reduced in cost and volume. Annual practice level spending varied widely (median, £2262 per thousand patients; interquartile range £1439 to £3298). Proportion of patients over 65 was strongly associated with low-value prescribing, as was Clinical Commissioning Group. Our interactive data tool was deployed to OpenPrescribing.net where monthly updated figures and graphs can be viewed. Conclusions Prescribing of low-value treatments is extensive but varies widely by treatment, geographic area and individual practice. Despite a fall in prescription numbers, the overall cost of prescribing for low-value items has risen. Prescribing behaviour is clustered by Clinical Commissioning Group, which may represent variation in the optimisation efficiency of medicines, or in some cases access inequality.

Is use of homeopathy associated with poor prescribing in English primary care? A cross-sectional study.

Objectives Prescribing of homeopathy still occurs in a small minority of English general practices. We hypothesised that practices that prescribe any homeopathic preparations might differ in their prescribing of other drugs. Design Cross-sectional analysis. Setting English primary care. Participants English general practices. Main outcome measures We identified practices that made any homeopathy prescriptions over six months of data. We measured associations with four prescribing and two practice quality indicators using multivariable logistic regression. Results Only 8.5% of practices (644) prescribed homeopathy between December 2016 and May 2017. Practices in the worst-scoring quartile for a composite measure of prescribing quality (>51.4 mean percentile) were 2.1 times more likely to prescribe homeopathy than those in the best category (<40.3) (95% confidence interval: 1.6-2.8). Aggregate savings from the subset of these measures where a cost saving could be calculated were also strongly associated (highest vs. lowest quartile multivariable odds ratio: 2.9, confidence interval: 2.1-4.1). Of practices spending the most on medicines identified as 'low value' by NHS England, 12.8% prescribed homeopathy, compared to 3.9% for lowest spenders (multivariable odds ratio: 2.6, confidence interval: 1.9-3.6). Of practices in the worst category for aggregated price-per-unit cost savings, 12.7% prescribed homeopathy, compared to 3.5% in the best category (multivariable odds ratio: 2.7, confidence interval: 1.9-3.9). Practice quality outcomes framework scores and patient recommendation rates were not associated with prescribing homeopathy (odds ratio range: 0.9-1.2). Conclusions Even infrequent homeopathy prescribing is strongly associated with poor performance on a range of prescribing quality measures, but not with overall patient recommendation or quality outcomes framework score. The association is unlikely to be a direct causal relationship, but may reflect underlying practice features, such as the extent of respect for evidence-based practice, or poorer stewardship of the prescribing budget.

OpenPrescribing: normalised data and software tool to research trends in English NHS primary care prescribing 1998-2016.

OBJECTIVES: We aimed to compile and normalise England's national prescribing data for 1998-2016 to facilitate research on long-term time trends and create an open-data exploration tool for wider use. DESIGN: We compiled data from each individual year's national statistical publications and normalised them by mapping each drug to its current classification within the national formulary where possible. We created a freely accessible, interactive web tool to allow anyone to interact with the processed data. SETTING AND PARTICIPANTS: We downloaded all available annual prescription cost analysis datasets, which include cost and quantity for all prescription items dispensed in the community in England. Medical devices and appliances were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: We measured the extent of normalisation of data and aimed to produce a functioning accessible analysis tool. RESULTS: All data were imported successfully. 87.5% of drugs were matched exactly on name to the current formulary and a further 6.5% to similar drug names. All drugs in core clinical chapters were reconciled to their current location in the data schema, with only 1.26% of drugs not assigned a current chemical code. We created an openly accessible interactive tool to facilitate wider use of these data. CONCLUSIONS: Publicly available data can be made accessible through interactive online tools to help researchers and policy-makers explore time trends in prescribing.

New mechanism to identify cost savings in English NHS prescribing: minimising 'price per unit', a cross-sectional study.

BACKGROUND: Minimising prescription costs while maintaining quality is a core element of delivering high-value healthcare. There are various strategies to achieve savings, but almost no research to date on determining the most effective approach. We describe a new method of identifying potential savings due to large national variations in drug cost, including variation in generic drug cost, and compare these with potential savings from an established method (generic prescribing). METHODS: We used English National Health Service (NHS) Digital prescribing data, from October 2015 to September 2016. Potential cost savings were calculated by determining the price per unit (eg, pill, millilitre) for each drug and dose within each general practice. This was compared against the same cost for the practice at the lowest cost decile to determine achievable savings. We compared these price-per-unit savings to the savings possible from generic switching and determined the chemicals with the highest savings nationally. A senior pharmacist manually assessed whether a random sample of savings were practically achievable. RESULTS: We identified a theoretical maximum of £410 million of savings over 12 months. £273 million of these savings were for individual prescribing changes worth over £50 per practice per month (mean annual saving £33 433 per practice); this compares favourably with generic switching, where only £35 million of achievable savings were identified. The biggest savings nationally were on glucose blood testing reagents (£12 million), fluticasone propionate (£9 million) and venlafaxine (£8 million). Approximately half of all savings were deemed practically achievable. DISCUSSION: We have developed a new method to identify and enable large potential cost savings within NHS community prescribing. Given the current pressures on the NHS, it is vital that these potential savings are realised. Our tool enabling doctors to achieve these savings is now launched in pilot form at OpenPrescribing.net. However, savings could potentially be achieved more simply through national policy change.