Medications for chronic obstructive pulmonary disease: a historical non-interventional cohort study with validation against RCT results.

Background: Chronic obstructive pulmonary disease treatment is informed by randomised controlled trial results, but it is unclear if these findings apply to people excluded from these trials. We used data from the TORCH (TOwards a Revolution in COPD Health) randomised controlled trial to validate non-interventional methods for assessing the clinical effectiveness of chronic obstructive pulmonary disease treatment in the UK Clinical Practice Research Datalink, before applying these methods to the analysis of people who would have been excluded from TORCH.

Objectives: To validate the use of non-interventional Clinical Practice Research Datalink data and methods for estimating chronic obstructive pulmonary disease treatment effects against trial results, and, using validated methods, to determine treatment effects in people who would have been excluded from the TORCH trial.

Real world effects of COPD medications: a cohort study with validation against results from randomised controlled trials.

Real-world data provide the potential for generating evidence on drug treatment effects in groups excluded from trials, but rigorous, validated methodology for doing so is lacking. We investigated whether non-interventional methods applied to real-world data could reproduce results from the landmark TORCH COPD trial.We performed a historical cohort study (2000-2017) of COPD drug treatment effects in the UK Clinical Practice Research Datalink (CPRD).

A threshold trajectory was revealed by isolating the effects of hemoglobin rate of rise in anemia of chronic kidney disease.

Background: To assess cardiovascular risk among various hemoglobin (Hb) rates of rise (RoR) in chronic kidney disease (CKD) patients with anemia who have initiated therapy with erythropoiesis stimulating agents (ESAs).

Methods: Observational cohort of CKD patients initiating ESA therapy from the Centricity database, 1990-2011. Proportional hazards models tested the hypothesis that a slower Hb RoR (0 < g/dl/month ⩽ 0.

Real-world effects of medications for chronic obstructive pulmonary disease: protocol for a UK population-based non-interventional cohort study with validation against randomised trial results.

Introduction: Chronic obstructive pulmonary disease (COPD) is a progressive disease affecting 3 million people in the UK, in which patients exhibit airflow obstruction that is not fully reversible. COPD treatment guidelines are largely informed by randomised controlled trial results, but it is unclear if these findings apply to large patient populations not studied in trials. Non-interventional studies could be used to study patient groups excluded from trials, but the use of these studies to estimate treatment effectiveness is in its infancy.

Benefit-risk assessment in a post-market setting: a case study integrating real-life experience into benefit-risk methodology.

Purpose: Difficulties may be encountered when undertaking a benefit-risk assessment for an older product with well-established use but with a benefit-risk balance that may have changed over time. This case study investigates this specific situation by applying a formal benefit-risk framework to assess the benefit-risk balance of warfarin for primary prevention of patients with atrial fibrillation.

Methods: We used the qualitative framework BRAT as the starting point of the benefit-risk analysis, bringing together the relevant available evidence.

Development of a novel regulatory pharmacovigilance prioritisation system: an evaluation of its performance at the UK Medicines and Healthcare products Regulatory Agency.

Background: The prioritisation of drug safety issues for further evaluation or regulatory action is critical to ensure that acceptable timelines and appropriate resource allocation are defined to meet public health and regulatory obligations.

Objective: Our objective was to develop, pilot and implement a novel tool for prioritising pharmacovigilance issues within the Medicines and Healthcare products Regulatory Agency (MHRA).

Methods: An initial system was developed empirically and then piloted over a 10-month period in the pharmacovigilance signal management meeting at the MHRA that discusses potential pharmacovigilance issues, and determines, through consensus, their priority and a timescale for action.

Menopausal hormone therapy and risk of gastrointestinal cancer: nested case-control study within a prospective cohort, and meta-analysis.

Use of menopausal hormone therapy (HT) has been associated with reduced risk of colorectal cancer; evidence for its effect on other gastrointestinal cancers is limited. We conducted a nested case-control study within a UK cohort, and meta-analyses combining our results with those from published studies. Our study included women aged 50+ in the UK General Practice Research Database (GPRD): 1,054 with oesophageal, 750 with gastric and 4,708 with colorectal cancer, and 5 age- and practice-matched controls per case.

Risks and benefits of (pharmaco)epidemiology.

Pharmacoepidemiology is a relatively young scientific discipline that has seen tremendous growth in interest over the past two decades. This is partly due to changes in the approval of new drugs, which often now require proactive studies to monitor and extend the knowledge of safety in the postauthorization period. Pharmacoepidemiology studies are observational in nature, in contrast to the randomized controlled trial which is the mainstay of drug development.

Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort.

Objective: To examine the hypothesis that risk of oesophageal, but not of gastric or colorectal, cancer is increased in users of oral bisphosphonates.

Design: Nested case-control analysis within a primary care cohort of about 6 million people in the UK, with prospectively recorded information on prescribing of bisphosphonates.

Setting: UK General Practice Research Database cohort.

Post-licensure comparison of the safety profile of diphtheria/tetanus/whole cell pertussis/haemophilus influenza type b vaccine and a 5-in-1 diphtheria/tetanus/acellular pertussis/haemophilus influenza type b/polio vaccine in the United Kingdom.

General practitioner consultation data were used to compare the reactogenicity in infants of a 5-in-1 acellular pertussis vaccine (DTaP(5)/Hib/IPV) introduced in the United Kingdom in 2004 to the 4-in-1 whole cell-pertussis vaccine (DTwP/Hib) that it replaced. For each vaccine the incidence in the week following vaccination was compared to other periods to obtain a relative incidence. A lower relative incidence of crying, fever and local reactions was seen with DTaP(5)/Hib/IPV than DTwP/Hib.

New approaches to drug safety: a pharmacovigilance tool kit.

The importance of pharmacovigilance - the ongoing assessment of the safety of a marketed medicine - has been increasingly appreciated in recent years, owing in part to high-profile safety issues with widely used drugs. In response, strategies to improve the collection, integration and analysis of data related to post-marketing drug safety are being initiated or enhanced. In this article, we summarize the key tools that are available for pharmacovigilance, discuss which might be the most appropriate to use in different situations and consider the future directions of the field.

Investigation of the temporal association of Guillain-Barre syndrome with influenza vaccine and influenzalike illness using the United Kingdom General Practice Research Database.

In 1976, the national swine influenza vaccination program in the United States was suspended because of an increased risk of Guillain-Barré syndrome. Subsequent studies of seasonal influenza vaccine have given conflicting results. The authors used the self-controlled case series method to investigate the relation of Guillain-Barré syndrome with influenza vaccine and influenzalike illness using cases recorded in the General Practice Research Database from 1990 to 2005 in the United Kingdom.

Prescribing of hormone therapy for menopause, tibolone, and bisphosphonates in women in the UK between 1991 and 2005.

Objective: The purpose of this study was to examine recent trends in the prescribing of hormone therapy for menopause, tibolone, and bisphosphonate preparations for the prevention or treatment of osteoporosis, in the UK in relation to publication of research evidence on the health effects of hormone therapy and subsequent changes in prescribing advice.

Methods: Individual patient-level data were obtained on the prescribing of hormone therapy, tibolone, and bisphosphonates by general practitioners in the UK between 1991 and 2005 to women aged 40 years and older in the UK General Practice Research Database. Overall and age-specific prescribing prevalence were calculated for each therapy type.

Bell's palsy and parenteral inactivated influenza vaccine.

Concern about a possible increased risk of Bell's palsy after parenteral inactivated influenza vaccine was raised following the publication in 2004 of a Swiss study in which there was an increased risk following the nasal inactivated formulation of the vaccine. When data from passive reporting systems in the United States and the United Kingdom were examined there was some evidence of increased reporting following the parenteral vaccine. A large population based study using the General Practice Research Database (GPRD) was therefore performed to test the hypothesis that there was an increased risk of Bell's palsy in the three months following parenteral inactivated influenza vaccine.

Comparison of hospital episodes with 'drug-induced' disorders and spontaneously reported adverse drug reactions.

Aims: To compare Hospital Episode Statistics for 'drug-related' admissions with spontaneously reported adverse drug reactions (ADRs) using UK Yellow Card data for the period 1996-2000.

Methods: This was a descriptive study for which we matched the relevant datasets in respect of time, place, evidence of hospitalization and disease terminology. The principal outcome was the ratio of ADRs leading to hospitalization which had been reported spontaneously during the whole study period.

Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia.

Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans.