Considerations when planning and conducting large global observational studies: Experience from the DISCOVER study of patients with type 2 diabetes.

DISCOVER is a global programme of observational research that includes patients with type 2 diabetes initiating second-line glucose-lowering therapy from 38 countries worldwide, including many with little or no previous epidemiological data available. More than 15,000 patients were followed-up for 3 years, and comprehensive data were collected using a standardized electronic case report form at enrolment, and 6, 12, 24 and 36 months. The study has formed the basis for a long-term registry that is intended to expand the geographic and clinical scope of the study and allow data collection beyond 3 years. In this review, critical aspects of study planning and implementation are summarized, along with challenges that were faced, to provide a resource for researchers planning similar studies. In particular, it is essential to set realistic expectations regarding the degree of study representativeness that can be achieved, allow for sufficient time to obtain ethics committee approval, develop tools to help recruit patients effectively, ensure that data collection systems are robust, user-friendly and adaptable, plan adequate remote and on-site monitoring, maximize patient retention through continuous engagement with study sites and ensure that everyone involved in the study forms a friendly and effective team. Observational studies such as DISCOVER are crucial for understanding disease epidemiology and management in real-world settings. They are also increasingly used by governmental, regulatory and payor agencies for post-marketing surveillance and when considering new drug submissions. The development of future studies of similar scope and ambition to DISCOVER is encouraged.

Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study.

BACKGROUND: There are increasing concerns about risks associated with aspirin discontinuation in the absence of major surgery or bleeding. We investigated whether long-term low-dose aspirin discontinuation and treatment gaps increase the risk of cardiovascular events. METHODS: We performed a cohort study of 601 527 users of low-dose aspirin for primary or secondary prevention in the Swedish prescription register between 2005 and 2009 who were >40 years of age, were free from previous cancer, and had ≥80% adherence during the first observed year of treatment. Cardiovascular events were identified with the Swedish inpatient and cause-of-death registers. The first 3 months after a major bleeding or surgical procedure were excluded from the time at risk. RESULTS: During a median of 3.0 years of follow-up, 62 690 cardiovascular events occurred. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37; 95% confidence interval, 1.34-1.41), corresponding to an additional cardiovascular event observed per year in 1 of every 74 patients who discontinue aspirin. The risk increased shortly after discontinuation and did not appear to diminish over time. CONCLUSIONS: In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding was associated with a >30% increased risk of cardiovascular events. Adherence to low-dose aspirin treatment in the absence of major surgery or bleeding is likely an important treatment goal.

Statin prescription patterns, adherence, and attainment of cholesterol treatment goals in routine clinical care: a Danish population-based study.

PURPOSE: To examine the annual rate and cumulative prevalence of statin use in Denmark 2004-10, including adherence of use and attainment of cholesterol targets. METHODS: We included all individuals aged 18-86 years with a first statin prescription in Northern Denmark in 2004-10. We calculated the annual rate and cumulative prevalence of statin use. We examined cholesterol values before and after start of statins and the proportion reaching targets according to European guidelines and cardiovascular risk group. RESULTS: The study population consisted of 161,646 new statin users (51% men; median age 62 years). The peak rate of new statin initiators occurred in 2008, and a cumulative prevalence of 94 users per 1,000 population was reached in 2010. In total, 98% of new users started with simvastatin. Eighty-eight percent (142,897) did not switch statin type during follow-up. Overall persistence was 84%. The reduction in median total cholesterol in new statin users was 28% (from 6.3 mmol/L to 4.5 mmol/L), while it was 43% (from 4.0 mmol/L to 2.3 mmol/L) for low-density lipoprotein cholesterol. Among patients with very high cardiovascular risk, 66% attained the recommended total cholesterol target; corresponding figures were 74% among high-risk patients and 80% among low- to moderate-risk patients. Corresponding figures for low-density lipoprotein cholesterol were 54%, 82%, and 88%, respectively. CONCLUSIONS: Statin use has become very prevalent in Danish adults, with high adherence. Cholesterol reduction after statin initiation is similar to that found in clinical trials, yet a substantial proportion of patients does not reach target cholesterol levels.