The Clinical Practice Research Datalink (CPRD) is an ongoing primary care database of anonymised medical records from general practitioners, with coverage of over 11.3 million patients from 674 practices in the UK. With 4.4 million active (alive, currently registered) patients meeting quality criteria, approximately 6.9% of the UK population are included and patients are broadly representative of the UK general population in terms of age, sex and ethnicity. General practitioners are the gatekeepers of primary care and specialist referrals in the UK. The CPRD primary care database is therefore a rich source of health data for research, including data on demographics, symptoms, tests, diagnoses, therapies, health-related behaviours and referrals to secondary care. For over half of patients, linkage with datasets from secondary care, disease-specific cohorts and mortality records enhance the range of data available for research. The CPRD is very widely used internationally for epidemiological research and has been used to produce over 1000 research studies, published in peer-reviewed journals across a broad range of health outcomes. However, researchers must be aware of the complexity of routinely collected electronic health records, including ways to manage variable completeness, misclassification and development of disease definitions for research.

Data Resource Profile: Clinical Practice Research Datalink (CPRD)

https://thelancet.com/pdfs/journals/lancet/PIIS0140-6736(16)00620-6.pdf

Clinical workload in UK primary care: a retrospective analysis of 100 million consultations in England, 2007–14

Purpose The South London and Maudsley National Health Service (NHS) Foundation Trust Biomedical Research Centre (SLaM BRC) Case Register and its Clinical Record Interactive Search (CRIS) application were developed in 2008, generating a research repository of real-time, anonymised, structured and open-text data derived from the electronic health record system used by SLaM, a large mental healthcare provider in southeast London. In this paper, we update this register's descriptive data, and describe the substantial expansion and extension of the data resource since its original development.

Participants Descriptive data were generated from the SLaM BRC Case Register on 31 December 2014. Currently, there are over 250 000 patient records accessed through CRIS.

Findings to date Since 2008, the most significant developments in the SLaM BRC Case Register have been the introduction of natural language processing to extract structured data from open-text fields, linkages to external sources of data, and the addition of a parallel relational database (Structured Query Language) output. Natural language processing applications to date have brought in new and hitherto inaccessible data on cognitive function, education, social care receipt, smoking, diagnostic statements and pharmacotherapy. In addition, through external data linkages, large volumes of supplementary information have been accessed on mortality, hospital attendances and cancer registrations.

Future plans Coupled with robust data security and governance structures, electronic health records provide potentially transformative information on mental disorders and outcomes in routine clinical care. The SLaM BRC Case Register continues to grow as a database, with approximately 20 000 new cases added each year, in addition to extension of follow-up for existing cases. Data linkages and natural language processing present important opportunities to enhance this type of research resource further, achieving both volume and depth of data. However, research projects still need to be carefully tailored, so that they take into account the nature and quality of the source information.

https://bmjopen.bmj.com/content/bmjopen/6/3/e008721.full.pdf

Cohort profile of the South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) Case Register: current status and recent enhancement of an Electronic Mental Health Record-derived data resource

There is a paucity of data on incidence, prevalence and mortality associated with non-cystic fibrosis bronchiectasis.Using the Clinical Practice Research Datalink for participants registered between January 1, 2004 and December 31, 2013, we determined incidence, prevalence and mortality associated with bronchiectasis in the UK and investigated changes over time.The incidence and point prevalence of bronchiectasis increased yearly during the study period. Across all age groups, the incidence in women increased from 21.2 per 100 000 person-years in 2004 to 35.2 per 100 000 person-years in 2013 and in men from 18.2 per 100 000 person-years in 2004 to 26.9 per 100 000 person-years in 2013. The point prevalence in women increased from 350.5 per 100 000 in 2004 to 566.1 per 100 000 in 2013 and in men from 301.2 per 100 000 in 2004 to 485.5 per 100 000 in 2013. Comparing morality rates in women and men with bronchiectasis in England and Wales (n=11 862) with mortality rates in the general population from Office of National Statistics data showed that in women the age-adjusted mortality rate for the bronchiectasis population was 1437.7 per 100 000 and for the general population 635.9 per 100 000 (comparative mortality figure of 2.26). In men, the age-adjusted mortality rate for the bronchiectasis population was 1914.6 per 100 000 and for the general population 895.2 per 100 000 (comparative mortality figure of 2.14).Bronchiectasis is surprisingly common and is increasing in incidence and prevalence in the UK, particularly in older age groups. Bronchiectasis is associated with a markedly increased mortality.

https://erj.ersjournals.com/content/erj/47/1/186.full.pdf

Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study.

Cardiovascular disease (CVD) presents a significant burden to the UK. This review presents data from nationally representative datasets to provide up-to-date statistics on mortality, prevalence, treatment and costs. Data focus on CVD as a whole, coronary heart disease (International Classification of Diseases (ICD):I20–25) and cerebrovascular disease (ICD:I60–69); however, where available, other cardiovascular conditions are also presented. In 2012, CVD was the most common cause of death in the UK for women (28% of all female deaths), but not for men, where cancer is now the most common cause of death (32% of all male deaths). Mortality from CVD varies widely throughout the UK, with the highest age-standardised CVD death rates in Scotland (347/100 000) and the North of England (320/100 000 in the North West). Prevalence of coronary heart disease is also highest in the North of England (4.5% in the North East) and Scotland (4.3%). Overall, around three times as many men have had a myocardial infarction compared with women. Treatment for CVD is increasing over time, with prescriptions and operations for CVD having substantially increased over the last two decades. The National Health Service in England spent around £6.8 billion on CVD in 2012/2013, the majority of which came from spending on secondary care. Despite significant declines in mortality in the UK, CVD remains a considerable burden, both in terms of health and costs. Both primary and secondary prevention measures are necessary to reduce both the burden of CVD and inequalities in CVD mortality and prevalence.

https://heart.bmj.com/content/heartjnl/101/15/1182.full.pdf

The epidemiology of cardiovascular disease in the UK 2014

Since its inception in the mid-1980s, the General Practice Research Database (GPRD) has undergone many changes but remains the largest validated and most utilised primary care database in the UK. Its use in pharmacoepidemiology stretches back many years with now over 800 original research papers. Administered by the Medicines and Healthcare products Regulatory Agency since 2001, the last 5 years have seen a rebuild of the database processing system enhancing access to the data, and a concomitant push towards broadening the applications of the database. New methodologies including real-world harm-benefit assessment, pharmacogenetic studies and pragmatic randomised controlled trials within the database are being implemented. A substantive and unique linkage program (using a trusted third party) has enabled access to secondary care data and disease-specific registry data as well as socio-economic data and death registration data. The utility of anonymised free text accessed in a safe and appropriate manner is being explored using simple and more complex techniques such as natural language processing.

https://journals.sagepub.com/doi/pdf/10.1177/2042098611435911

Recent advances in the utility and use of the General Practice Research Database as an example of a UK Primary Care Data resource

Background and Objectives Reduced mobility in patients with amyotrophic lateral sclerosis (ALS) is hypothesized to increase the risk of venous thromboembolism (VTE). A few small, single-center studies have investigated the risk of VTE in patients with ALS. Given the high morbidity and mortality associated with VTE, further understanding of the risk in patients with ALS may inform clinical care. The objective of this study was to investigate the incidence of VTE in patients with ALS compared with controls without ALS. Methods Patients were identified from a US health insurance claims database, Optum's deidentified Clinformatics Data Mart Database, between 2004 and 2019. ALS cases were defined as patients aged 18 years or older with (1) 2 or more ALS claims at least 27 days apart including at least 1 claim from a neurologist visit or (2) 1 or more ALS claims and a prescription for riluzole or edaravone. Each ALS case was matched on age and sex to 5 controls without ALS. VTE was defined as at least 1 claim for VTE and at least 1 anticoagulant prescription or VTE-related procedure within 7 days before and 30 days after a VTE claim date. Incidence rates were reported per 1,000 person-years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model. Results Among 4,205 ALS cases and 21,025 controls, incident VTE occurred in 132 ALS cases (3.1%) and 244 controls (1.2%). Incidence rates of VTE were 19.9 per 1,000 person-years (95% CI 16.7–23.6) in ALS cases compared with 6.0 per 1,000 person-years (95% CI 5.0–7.1) in controls. ALS cases were about 3 times more likely to develop VTE (HR 3.3, 95% CI 2.6–4.0), with similar results among men and women. The median time to first VTE was 10 months from the initial ALS claim in ALS cases. Discussion Consistent with previous smaller studies, a higher incidence rate of VTE was observed in a large sample of patients with ALS from across the United States, as compared to matched controls. The markedly increased risk underscores the importance of preventive efforts and careful monitoring for VTE in patients with ALS and may have implications for the management of ALS.

https://cp.neurology.org/content/neurclinpract/13/1/e200110.full.pdf

Increased Risk of Venous Thromboembolism in Patients With Amyotrophic Lateral Sclerosis

/pdf/correction-to-comparative-all-cause-mortality-among-a-large-1zjsh915.pdf

Correction to: Comparative All-Cause Mortality Among a Large Population of Patients with Spinal Muscular Atrophy Versus Matched Controls

Spinal muscular atrophy (SMA) is a rare neuromuscular disease characterized by progressive muscular atrophy and weakness. Nusinersen was the first treatment approved for SMA. Per the US label, the nusinersen administration schedule consists of three loading doses at 14-day intervals, a fourth loading dose 30 days later, and maintenance doses every 4 months thereafter. Using two large US databases, we evaluated real-world adherence to nusinersen with its unique dosing schedule among generalizable populations of patients with SMA.Patients with SMA treated with nusinersen, likely to have complete information on date of treatment initiation, were identified in the Optum® de-identified electronic health records (EHR) database (7/2017-9/2019), and in the Merative™ MarketScan® Research Databases from commercial (1/2017-6/2020) and Medicaid claims (1/2017-12/2019). Baseline demographics, number of nusinersen administrations on time, and distribution of inter-dose intervals were summarized.Totals of 67 and 291 patients were identified in the EHR and claims databases, respectively. Most nusinersen doses were received on time (93.9% EHR, 80.5% claims). Adherence was higher during the maintenance phase (90.6%) than the loading phase (71.1%) in the claims analysis, in contrast with the EHR analysis (95.5% and 92.6%, respectively), suggesting that not all loading doses of nusinersen may be accurately captured in claims. Inter-dose intervals captured in both databases aligned with the expected dosing schedule.Most nusinersen doses were received on time, consistent with the recommended schedule. Our findings also highlight the importance of careful methodological approaches when using real-world administrative databases for evaluation of nusinersen treatment patterns.Adherence to medicines in the real world is important for patients with chronic disease to see long-term benefits of treatment. This study shows the importance and challenges of measuring adherence using real-world administrative data sources. This is especially important for drugs given through lumbar puncture with unique dosing schedules, such as nusinersen for the treatment of spinal muscular atrophy. In this study, most patients with spinal muscular atrophy received their nusinersen doses on time. 

/pdf/examining-real-world-adherence-to-nusinersen-for-the-3cp6y32o.pdf

Susan Eaton

Papers

Recent advances in the utility and use of the General Practice Research Database as an example of a UK Primary Care Data resource

Increased Risk of Venous Thromboembolism in Patients With Amyotrophic Lateral Sclerosis

Correction to: Comparative All-Cause Mortality Among a Large Population of Patients with Spinal Muscular Atrophy Versus Matched Controls

Examining Real-World Adherence to Nusinersen for the Treatment of Spinal Muscular Atrophy Using Two Large US Data Sources