The Role of the Contextual Cohort to Resolve Some Challenges and Limitations of Comparisons in Pharmacoepidemiology.

In pharmacoepidemiology, comparison studies can provide a useful estimate of the level of increased or decreased risk of specific events with a medication (through a measure of effect). A key focus of pharmacoepidemiological studies is the safety and effectiveness of medicines in their real-world use, and adequate comparisons of effect estimates are critical. However, consideration of guidelines, pharmacoeconomic assessments, and policies for reimbursement have made comparisons in pharmacoepidemiological studies far more difficult to conduct in recent years.

Observational assessment of safety in seroquel (OASIS): a specialist cohort event monitoring (SCEM) study in England.

Background: This study was designed to monitor the short-term (up to 12 weeks) use and safety of quetiapine (Seroquel) extended release (XL) and quetiapine immediate release (IR) prescribed to patients with a clinical diagnosis of schizophrenia, and/or manic episodes associated with bipolar disorder by psychiatrists under normal conditions of use.

Methods: A Specialist Cohort Event Monitoring (SCEM) study was conducted in England February 2010-April 2013. This observational cohort study recruited patients prescribed quetiapine XL within the secondary care setting by psychiatrists.

Systematic benefit-risk assessment for buprenorphine implant: a semiquantitative method to support risk management.

Background: Prior to approval in the European Union, a systematic benefit-risk assessment was required to compare buprenorphine implant to sublingual buprenorphine as part of the license application to the European Medicines Agency.

Objective: The Benefit-Risk Action Team framework was used to describe the overall benefit-risk of buprenorphine implant in comparison to sublingual buprenorphine.

Study Selection/methods: A value tree of key benefits and risks related to the implant formulation of buprenorphine was constructed.

Drugs and life-threatening ventricular arrhythmia risk: results from the DARE study cohort.

Objectives: To establish a unique sample of proarrhythmia cases, determine the characteristics of cases and estimate the contribution of individual drugs to the incidence of proarrhythmia within these cases.

Setting: Suspected proarrhythmia cases were referred by cardiologists across England between 2003 and 2011. Information on demography, symptoms, prior medical and drug histories and data from hospital notes were collected.

Utilisation and Safety of Deferasirox: Results from an Observational Cohort Study in England.

Introduction: Deferasirox (EXJADE, Novartis, UK) is an oral iron-chelating agent primarily used to reduce chronic iron overload in patients receiving blood transfusions for various chronic anaemias and some non-transfusion dependant anaemias.

Objective: The aim of this study was to examine the utilisation and safety of deferasirox used in general practice in England.

Method: A single exposure observational cohort study design was used.

Safety of Atrovent CFC-free inhaler: respiratory events reported from an observational cohort study in England.

Objectives: The aim of the study was to identify any unexpected clinical events associated with starting the new CFC-free formulation of Atrovent MDI in general practice in England.

Methods: An active surveillance cohort study was conducted with a focus on selected clinical events, including respiratory symptoms, in past users of Atrovent CFC MDI ('switchers') and Atrovent naïve users. Incidence density rate ratios (with 99% confidence intervals) for events occurring in the first 3 months of exposure (risk period-ID ) compared to 3 months prior to starting treatment (reference period-ID ) were calculated.

Pattern of Onset and Risk Factors for Peripheral Oedema During Vildagliptin Use: Analysis from the Vildagliptin Prescription-Event Monitoring Study in England.

Introduction: Clinical trials have identified peripheral oedema (PO) as an adverse event of vildagliptin (an oral anti-diabetic drug [OAD]). A post-marketing study (PMS) was conducted to advance the understanding of vildagliptin use and particular safety concerns identified within the risk-management plan. PMS objectives included comparing the hazards between vildagliptin monotherapy and combination therapy for selected a priori identified risks, including PO.

Utilisation and Tolerability of Aliskiren in the Primary Care Setting in England.

Aliskiren (Rasilez), a direct renin inhibitor, is indicated for the treatment of essential hypertension. A postmarketing prescription-event monitoring (PEM) study was conducted in England to monitor the safety and utilization of aliskiren. Summary statistics and event incidence densities were calculated.

Specialist Cohort Event Monitoring studies: a new study method for risk management in pharmacovigilance.

The evolving regulatory landscape has heightened the need for innovative, proactive, efficient and more meaningful solutions for 'real-world' post-authorization safety studies (PASS) that not only align with risk management objectives to gather additional safety monitoring information or assess a pattern of drug utilization, but also satisfy key regulatory requirements for marketing authorization holder risk management planning and execution needs. There is a need for data capture across the primary care and secondary care interface, or for exploring use of new medicines in secondary care to support conducting PASS. To fulfil this need, event monitoring has evolved.

Indicators of drug-seeking aberrant behaviours: the feasibility of use in observational post-marketing cohort studies for risk management.

Background: Problematic prescription drug use is reflected by or associated with drug-seeking aberrant behaviours. Research gaps include lack of post-marketing evidence and instruments. As part of the pharmacovigilance requirements, a risk management plan was developed for fentanyl buccal tablets (FEBT) by the manufacturer, with an additional pharmacovigilance activity requested by the regulatory authority, to investigate the risks of misuse, abuse, criminal use, off-label use and accidental exposure to FEBT after the product became commercially available.

Modified prescription-event monitoring studies: a tool for pharmacovigilance and risk management.

Prescription-Event Monitoring (PEM) is a well established postmarketing surveillance technique designed to monitor the overall safety of newly marketed medicines as used in real-life clinical practice, usually in cohorts of at least 10 000 patients. At the Drug Safety Research Unit in the UK we are now moving towards a more targeted safety surveillance known as Modified PEM (M-PEM). These studies combine the advantages of conventional PEM studies (in monitoring general safety and identification of unexpected risks of a medicine) with that of a more targeted safety study that addresses specific questions (to better understand known or partially known risks with a medicine).

Examining the utilization and tolerability of the non-sedating antihistamine levocetirizine in England using prescription-event monitoring data.

Background: Levocetirizine was launched onto the UK market in September 2001. It is indicated for symptomatic treatment of allergic rhinitis (AR), including persistent AR and chronic idiopathic urticaria.

Objective: The aim of the study was to monitor the safety of levocetirizine prescribed in the primary care setting in England, in the immediate postmarketing period.

Risk of depressive episodes with rimonabant: a before and after modified prescription event monitoring study conducted in England.

Background: Marketing authorization for rimonabant was withdrawn in October 2008, mainly because the psychiatric adverse effects could not be addressed by further risk minimization.

Objective: The aim of the study was to compare the risk of major and minor depressive episodes in the 6 months prior to and the 6 months after starting treatment with rimonabant.

Methods: We conducted a before and after study using the observational cohort technique of Modified Prescription Event Monitoring to compare the risk of major and minor depressive episodes in new users of rimonabant reported in the 6 months before to the 6 months after starting treatment with rimonabant.

Incidence of venous thromboembolism in users of strontium ranelate: an analysis of data from a prescription-event monitoring study in England.

Background: Strontium ranelate is indicated for the treatment of postmenopausal osteoporosis. An association between strontium ranelate and venous thromboembolism (VTE) was identified in an analysis of phase III clinical trials.

Objective: To estimate the incidence of VTE in patients within the strontium ranelate (Protelos(R)) Prescription-Event Monitoring (PEM) study cohort during the first 12 months after starting treatment.

Drug utilization of Intrinsa (testosterone patch) in England: interim analysis of a prescription-event monitoring study to support risk management.

Background: Intrinsa is a transdermal testosterone patch that is indicated for use in hypoactive sexual desire disorder (HSDD) in women who have undergone bilateral oophorectomy and hysterectomy (surgically-induced menopause) receiving concomitant oestrogen therapy.

Objective: To describe the utilization characteristics of the patients prescribed testosterone patch (Intrinsa) based on an interim analysis of an ongoing Prescription-Event Monitoring study in England, and to assess, where possible, if the product is being used within the licensed therapeutic indication.

Methods: In this interim analysis, patients were identified from dispensed prescriptions that had been issued by general practitioners (GPs) for Intrinsa from March 2007.

Safety profile of oxcarbazepine: results from a prescription-event monitoring study.

Purpose: To monitor safety of oxcarbazepine, prescribed in primary care in England, using prescription-event monitoring (PEM).

Methods: Postmarketing surveillance using observational cohort technique of PEM. Exposure data were obtained from dispensed British National Health Service prescriptions issued by general practitioners (GPs) March 2000-July 2003.

Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study.

Background: Varenicline tartrate (Champix), a new smoking cessation medicine, was launched in the UK in December 2006. Varenicline is a highly selective partial agonist of the alpha(4)beta(2) nicotinic acetylcholine receptor (alpha(4)beta(2) receptor). The partial agonistic binding leads to alleviation of symptoms of craving and withdrawal, and simultaneously prevents nicotine from binding to the alpha(4)beta(2) receptor thereby causing reduction in the rewarding and reinforcing effects of smoking.

Hypoglycaemia with oral antidiabetic drugs: results from prescription-event monitoring cohorts of rosiglitazone, pioglitazone, nateglinide and repaglinide.

Background: Hypoglycaemia is an acute complication associated with intensive treatment of patients with diabetes mellitus. This complication poses a major challenge in diabetes management. Furthermore, severe hypoglycaemia may be life threatening.

Risk management and outcomes of adverse events to pioglitazone in primary care in the UK: an observational study.

Background: Pioglitazone is an antidiabetic drug that belongs to the thiazolidinedione (TZD) class of insulin-sensitizing agents. Adverse events to pioglitazone of potential severity are listed in the 'special warnings and special precautions for use' section of the pioglitazone summary of product characteristics (SPC), with recommendations for monitoring and management.

Objective: To describe the risk management and outcomes of recognized TZD class effects in patients prescribed pioglitazone.

Examining the tolerability of the non-sedating antihistamine desloratadine: a prescription-event monitoring study in England.

Background: Desloratadine is a non-sedating, long-acting histamine H(1) receptor antagonist indicated for the symptomatic relief of allergic rhinitis (AR) and chronic idiopathic urticaria in patients aged>12 years.

Objective: To monitor the safety of desloratadine as prescribed in England, using the observational cohort technique of prescription event monitoring (PEM).

Methods: Exposure data were derived from dispensed prescriptions written by primary care physicians (general practitioners [GPs]) for desloratadine (March-May 2001); patient demographics, indication, pattern of use and outcome (event) data were obtained via simple questionnaires returned by GPs.

Use and risk management of carvedilol for the treatment of heart failure in the community in England: results from a modified prescription-event monitoring study.

Background: In the UK, the licence for carvedilol was extended in 1998 to include symptomatic heart failure (New York Heart Association [NYHA] class II and III heart failure) with the recommendation that initiation and up-titration should be under the supervision of a hospital physician. A post-marketing surveillance study was conducted to address the UK regulatory authority's request for monitoring the use and safety of carvedilol prescribed for heart failure in clinical practice.

Aim: To investigate adherence to risk management recommendations for the use of carvedilol for heart failure, monitor how patients' subsequent care was managed and collect event data to evaluate the safety profile of carvedilol used for the treatment of heart failure.