Challenges and lessons learned from a long-term postauthorisation safety study programme of rivaroxaban in Europe.

Objectives: To describe opportunities and challenges experienced from the four pharmacoepidemiological database studies included in the rivaroxaban post authorisation safety study (PASS) programme and propose ways to maximise the value of population-based observational research when addressing regulatory requirements.

Design: PASS programme of rivaroxaban carried out as part of the regulatory postapproval commitment to the European Medicines Agency.

Setting: Clinical practice in Germany, the Netherlands, Sweden and the UK (electronic health records)-undertaken by pharmacoepidemiology research teams using country-specific databases with different coding structures.

Current Practices and Challenges When Submitting Patient Experience Data for Regulatory Decisions by the US Food and Drug Administration: An Industry Survey.

Objectives: To understand industry practices and challenges when submitting patient experience data (PED) for regulatory decisions by the US Food and Drug Administration (FDA).

Methods: A two-part online survey related to collection, submission, and use of PED by FDA in regulatory decision-making (part 1) and a best-worst exercise for prioritizing potential PED initiatives (part 2) was completed by industry and contract research organization (CRO) members with ≥ 2 years of recent experience with patient-reported outcome (PRO), natural history study (NHS), or patient preference (PP) data; and direct experience with FDA filings including PED.

Results: A total of 50 eligible respondents (84% industry) completed part 1 of the survey, among which 46 completed part 2.

Long-COVID-19 clinical and health outcomes: an umbrella review.

Background: A growing interest in long-term sequelae of COVID-19 has prompted several systematic literature reviews (SLRs) to evaluate long-COVID-19 effects. However, many of these reviews lack in-depth information on the timing, duration, and severity of these conditions.

Objectives: Our aim was to synthesize both qualitative and quantitative evidence on prevalence and outcomes of long-term effect of COVID-19 through an umbrella review.

Long-Term Adherence and Persistence to Low-Dose Aspirin for the Prevention of Cardiovascular Disease: A Population-Based Cohort Study.

Methods: Using information from electronic health records in Germany and the United Kingdom (UK) in a common data model, we followed adults with ≥2 low-dose aspirin prescriptions (75-100 mg) during 2007-2018 for up to 10 years. Included individuals had no low-dose aspirin prescriptions in the year before the follow-up started (date of first low-dose aspirin prescription) and ≥12 months' observation. Adherence was determined using the medication possession ratio (MPR), and persistence was defined as continuous treatment disregarding gaps between prescriptions of <60 days; analyses were undertaken according to indication (primary/secondary CVD prevention).

The epidemiology of severe malaria at Manhiça District Hospital, Mozambique: a retrospective analysis of 20 years of malaria admissions surveillance data.

Background: Most malaria burden estimates rely on modelling infection prevalence to case incidence data, with insufficient attention having been paid to the changing clinical presentation of severe disease and its relationship with changing transmission intensity. We present 20 years of longitudinal surveillance data to contribute to the understanding of the relationship between malaria transmission and the burden and clinical presentation of severe malaria and to inform policy.

Methods: This retrospective analysis of clinical surveillance hospital data included all children younger than 15 years admitted with malaria to Manhiça District Hospital (MDH), Mozambique, from July 1, 1997, to June 30, 2017.

ISPE-Endorsed Guidance in Using Electronic Health Records for Comparative Effectiveness Research in COVID-19: Opportunities and Trade-Offs.

As the scientific research community along with healthcare professionals and decision makers around the world fight tirelessly against the coronavirus disease 2019 (COVID-19) pandemic, the need for comparative effectiveness research (CER) on preventive and therapeutic interventions for COVID-19 is immense. Randomized controlled trials markedly under-represent the frail and complex patients seen in routine care, and they do not typically have data on long-term treatment effects. The increasing availability of electronic health records (EHRs) for clinical research offers the opportunity to generate timely real-world evidence reflective of routine care for optimal management of COVID-19.

Safety and effectiveness of low-dose aspirin for the prevention of gastrointestinal cancer in adults without atherosclerotic cardiovascular disease: a population-based cohort study.

Objective: To assess the association between low-dose aspirin and the incidence of colorectal cancer (CRC), gastric cancer (GC), oesophageal cancer (EC) and gastrointestinal bleeding (GIB) in adults without established atherosclerotic cardiovascular disease.

Design: Cohort study with propensity score matching of new-users of aspirin to non-users.

Setting: Clinical Data Analysis and Reporting System database, Hong Kong.

Trends in the use of oral anticoagulants, antiplatelets and statins in four European countries: a population-based study.

Purpose: To evaluate time trends in the prevalence of antithrombotic and statin use in four European countries.

Methods: Using population-based data from the United Kingdom, Denmark, Spain and Italy between 2010 and 2018, we calculated standardized annual prevalence proportions of antithrombotics and statin use, and changes in prevalence proportions (2018 vs. 2010).

Public health impact of low-dose aspirin on colorectal cancer, cardiovascular disease and safety in the UK - Results from micro-simulation model.

Background: Low-dose aspirin therapy reduces the risk of cardiovascular disease and may have a positive effect on the prevention of colorectal cancer. We evaluated the population-level expected effect of regular low-dose aspirin use on cardiovascular disease (CVD), colorectal cancer (CRC), gastrointestinal bleeding, symptomatic peptic ulcers, and intracranial hemorrhage, using a microsimulation study design.

Methods: We used individual-level state transition modeling to assess the impact of aspirin in populations aged 50-59 or 60-69 years old indicated for low-dose aspirin usage for primary or secondary CVD prevention.

Patient Preferences of Low-Dose Aspirin for Cardiovascular Disease and Colorectal Cancer Prevention in Italy: A Latent Class Analysis.

Background: Patients taking low-dose aspirin to prevent cardiovascular disease (CVD) may also benefit from a reduced risk of colorectal cancer (CRC).

Objective: The aim was to examine the preferences of people eligible for preventive treatment with low-dose aspirin and the trade-offs they are willing to make between CVD prevention, CRC prevention, and treatment risks.

Methods: A cross-sectional study using a discrete choice experiment (DCE) survey was conducted in Italy in 2019 to elicit preferences for three benefit attributes (prevention of ischemic stroke, myocardial infarction, and CRC) and four risk attributes (intracranial and gastrointestinal bleeding, peptic ulcer, and severe allergic reaction) associated with use of low-dose aspirin.

Association Between Low-Dose Aspirin Use and Colorectal Cancer Incidence in Taiwan.

Importance: Population-based East Asian data have corroborated reports from non-Asian settings on the association between low-dose aspirin and a lower risk of colorectal cancer (CRC).

Objective: To evaluate the association between duration and recency of low-dose aspirin use and CRC risk.

Design, Setting, And Participants: This nested case-control study included individuals who initiated aspirin use and matched individuals who did not use aspirin.

Incorporating patient generated health data into pharmacoepidemiological research.

Epidemiology and pharmacoepidemiology frequently employ Real-World Data (RWD) from healthcare teams to inform research. These data sources usually include signs, symptoms, tests, and treatments, but may lack important information such as the patient's diet or adherence or quality of life. By harnessing digital tools a new fount of evidence, Patient (or Citizen/Person) Generated Health Data (PGHD), is becoming more readily available.

Rationale and design of a European epidemiological post-authorization safety study (PASS) program: rivaroxaban use in routine clinical practice.

Background: Rivaroxaban is a highly selective factor Xa inhibitor approved for use in Europe for multiple indications.

Study Design And Methods: The European rivaroxaban epidemiological post-authorization safety study (PASS) program consists of seven complementary observational studies. For four of the studies, data are obtained from health-care databases in the UK, the Netherlands, Germany, and Sweden.

Bleeding associated with low-dose aspirin: Comparison of data from the COMPASS randomized controlled trial and routine clinical practice.

Randomized controlled trials (RCTs) have strong internal validity but often have limited external validity. Observational studies have good generalizability and an increasing role in key healthcare decision making. We compared incidence rates of intracranial and major gastrointestinal bleeds in the low-dose aspirin arm (N = 9126) of the COMPASS double-blind RCT (conducted at 602 centres in 33 countries) with those from an observational cohort of preventative low-dose aspirin users (N = 54,140) in a primary care database representative of the UK general population - The IQVIA Medical Research Data UK (IMRD-UK).

Incidence of second primary malignancies in metastatic castration-resistant prostate cancer: results from observational studies in three countries.

This reports some of the first incidence rate (IR) estimates of second primary malignancies (SPMs) in men with metastatic castration-resistant prostate cancer (mCRPC) in three countries. Claims data from the German Pharmacoepidemiological Research Database; registry data from the Prostate Cancer Data Base Sweden; and combined registry-claims data from the US Surveillance, Epidemiology and End Results-Medicare database were analyzed to obtain overall survival and incidence of SPMs in men with mCRPC. SPMs occurred in 308 German (n = 2360), 273 Swedish (n = 2849) and 172 US (n = 2234) men with mCRPC.

Low-dose aspirin and risk of gastric and oesophageal cancer: A population-based study in the United Kingdom using The Health Improvement Network.

There is increasing interest regarding potential protective effects of low-dose aspirin against various gastrointestinal cancers. We aimed to quantify the association between use of low-dose aspirin and risk of gastric/oesophageal cancer using a population-based primary care database in the UK. Between January 2005 and December 2015, we identified a cohort of 223 640 new users of low-dose aspirin (75-300 mg/day) and a matched cohort of nonusers at the start of follow-up from The Health Improvement Network.

Effect of Proton Pump Inhibitors on Risks of Upper and Lower Gastrointestinal Bleeding among Users of Low-Dose Aspirin: A Population-Based Observational Study.

Estimates of the effect of proton pump inhibitors (PPIs) on risks of upper and lower gastrointestinal bleeding (UGIB and LGIB) among low-dose aspirin users in routine clinical practice are variable (UGIB) or lacking (LGIB). We aimed to establish these risks in the same observational study population. Using UK primary care data, we followed 199,049 new users of low-dose aspirin (75-300 mg/day) and matched non-users at start of follow-up to identify incident UGIB/LGIB cases.

Overall survival and second primary malignancies in men with metastatic prostate cancer.

Background: Among prostate cancer (PC) patients, over 90% of distant metastases occur in the bone. PC treatments may be associated with side effects, including second primary malignancies (SPM). There is limited information on the incidence of SPM among men with bone metastatic PC (mPC) and among men with bone metastatic castration-resistant PC (mCRPC).

The effect of low-dose aspirin on colorectal cancer prevention and gastrointestinal bleeding according to bodyweight and body mass index: Analysis of UK primary care data.

Background: Meta-analysis of trial data suggests that in primary cardiovascular disease (CVD) prevention bodyweight modifies low-dose aspirin's effects on colorectal cancer (CRC) and major bleeding risk. We sought to investigate whether these effects are seen in patients with or without CVD in routine clinical practice by undertaking sub-analyses of data from two cohort studies with nested-case-control analyses.

Methods: We followed ~200,000 new users of low-dose aspirin (75-300 mg/day) and a matched cohort of non-users to identify incident cases of CRC/upper gastrointestinal bleeding (UGIB).

Incidence of Skeletal-Related Events in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the US.

Background And Objective: Skeletal-related events (SREs) are common in men with bone metastases and have negative consequences for patients with castration-resistant prostate cancer (CRPC), including pain, reduced quality of life, and increased mortality. We estimated incidence rates of first SREs in a cohort of men with CRPC in the Surveillance, Epidemiology, and End Results-Medicare database.

Methods: We included men aged ≥ 65 years with a prostate cancer diagnosis in 2000-2011 if they had no prior malignancy (other than nonmelanoma skin cancer) and had surgical or medical castration with subsequent second-line systemic therapy, which was used to infer castration resistance.

Corrigendum to "Incidence of Second Primary Malignancies in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the United States".

[This corrects the article DOI: 10.1155/2019/4387415.].

Prostate cancer with bone metastasis in Beijing: an observational study of prevalence, hospital visits and treatment costs using data from an administrative claims database.

Objectives: To estimate the prevalence of prostate cancer with bone metastasis in Beijing, and to estimate hospital visits and direct treatment costs among male urban employees with the disease in Beijing.

Design: Cross-sectional observational study.

Setting And Participants: Patients with prostate cancer and bone metastasis from the Urban Employee Basic Medical Insurance database covering the employed population of Beijing, China, from 2011 to 2014.

Are risk minimization measures for approved drugs in Europe effective? A systematic review.

: The effectiveness of risk minimization measures (RMMs) requires evaluation. This study aims to evaluate the results of cross-sectional surveys assessing the effectiveness of RMMs in Europe (EU RM Surveys) and review the regulatory consequences. : The authors searched for study reports and manuscripts of completed EU RM surveys in the EU PAS Register, MEDLINE, and Google between 01/2011 and 01/2018.

Low-dose aspirin and risk of upper/lower gastrointestinal bleeding by bleed severity: a cohort study with nested case-control analysis using primary care electronic health records from the United Kingdom.

Risks of low-dose aspirin-associated upper and lower gastrointestinal bleeds (UGIB/LGIB) may vary by severity and presence of cardiovascular disease (CVD). No study has quantified these risks for UGIB and LGIB in the same real-world study population. Using UK primary care data, 199,049 new users of low-dose aspirin (75-300 mg/day) and 1:1 matched non-users were followed to identify incident UGIB ( = 1843)/LGIB ( = 2763) cases.

Incidence of Second Primary Malignancies in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the United States.

Background: New therapies for castration-resistant prostate cancer (CRPC) may be associated with increased risk of second primary malignancies (SPM). We therefore estimated the population-based incidence of SPM among patients with CRPC in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We also estimated the proportion of men with CRPC with bone metastases and overall survival.