Concordance of hospitalizations between Clinical Practice Research Datalink and linked Hospital Episode Statistics among patients treated with oral antidiabetic therapies.

PURPOSE: The ability of the Clinical Practice Research Datalink (CPRD) to ascertain all-cause hospitalizations remains unknown. We determined the proportion of hospitalizations in CPRD that were also recorded in Hospital Episode Statistics (HES), and vice versa, among patients initiating oral antidiabetic (OAD) therapy. METHODS: We conducted a retrospective cohort study from October 2009 to September 2012 among OAD-treated patients registered with general practitioners who contribute to CPRD and consent to HES linkage. In CPRD, we identified initial hospitalizations for each calendar year by an Inpatient Referral, Consultation Type code, or Read code indicating an inpatient episode and determined if an admission date was recorded in HES within ±30 days. We then identified initial HES admission dates and determined if a hospitalization was documented in CPRD within ±30 days. Sensitivity analyses were conducted utilizing HES discharge, rather than admission, dates. RESULTS: Among 8574 OAD-treated HES-linked patients in CPRD, 6574 initial hospitalizations across the study period were identified in CPRD, and 5188 (78.9% [95% CI, 77.9%-79.9%]) were confirmed by a HES admission date within ±30 days (median difference, ±3 days [IQR, 1-7 days]). Among 8609 initial hospital admissions in HES, 4803 (55.7% [95% CI, 54.7%-56.8%]) hospitalizations were recorded in CPRD within ±30 days (median difference, ±4 days [IQR, 1-9 days]). Similar results were observed using HES discharge dates. CONCLUSION: A substantial minority of patient-level hospitalization data are nonconcordant between HES and CPRD. Pharmacoepidemiologic studies within CPRD that seek to identify hospitalizations should consider linkage with HES to ensure adequate ascertainment of inpatient events.

Generalisability of The Health Improvement Network (THIN) database: demographics, chronic disease prevalence and mortality rates.

INTRODUCTION: The degree of generalisability of patient databases to the general population is important for interpreting database research. This report describes the representativeness of The Health Improvement Network (THIN), a UK primary care database, of the UK population. METHODS: Demographics, deprivation (Townsend), Quality and Outcomes Framework (QOF) condition prevalence and deaths from THIN were compared with national statistical and QOF 2006/2007 data. RESULTS: Demographics were similar although THIN contained fewer people aged under 25 years. Condition prevalence was comparable, e.g. 3.5% diabetes prevalence in THIN, 3.7% nationally. More THIN patients lived in the most affluent areas (23.5% in THIN, 20% nationally). Between 1990 and 2009, standardised mortality ratio ranged from 0.81 (95% CI: 0.39-1.49; 1990) to 0.93 (95% CI: 0.48-1.64; 1995). Adjusting for demographics/deprivation, the 2006 THIN death rate was 9.08/1000 population close to the national death rate of 9.4/1000 population. CONCLUSION: THIN is generalisable to the UK for demographics, major condition prevalence and death rates adjusted for demographics and deprivation.

Prescribing trends and drug budget impact of the ARBs in the UK.

OBJECTIVES: Angiotensin II receptor blockers (ARBs) were introduced into the UK antihypertensive drug market at a premium price relative to other antihypertensives during a period of evolving evidence about hypertension treatment. This study aimed to determine the UK antihypertensive drug budget impact as the first ARB market launched in December 1994 and what proportion of the increase was directly attributable to ARBs. METHODS: Prescriptions for oral antihypertensives were identified from The Health Improvement Network database. Drug prices were based on the Chemist & Druggist January 2005 pricelist estimating real expenditure growth. Expenditure increases were disaggregated into the number of patients receiving antihypertensive drug prescriptions, the number of antihypertensive prescriptions per patient treated, and the average drug expenditure per antihypertensive prescription. RESULTS: The annual ARB prescription frequency increased from 0.04% in 1995 to 6.57% in 2004. Expenditure for antihypertensive drugs was estimated at pound465,862,416 in 1995 and pound1,458,268,104 in 2004 (2005 values), reflecting a 213% real rate of increase. Use of ARBs accounted for only 9.3% (range: 5.8%-12.5%) of the average drug expenditure. Treatment prevalence rose from 11.30% in 1995 to 16.90% in 2004, while the average number of antihypertensive drug prescriptions per patient increased from 9.34 to 13.46 per year. The average expenditure per antihypertensive drug prescription increased over time reflecting a product shift toward more expensive therapies. CONCLUSIONS: ARBs accounted for only 9.3% of the 213% increase in antihypertensive drug expenditure after their introduction. A substantial portion of the impact reflected increases in treatment prevalence and in the number of prescriptions per patient.

The importance of defining periods of complete mortality reporting for research using automated data from primary care.

PURPOSE: To define periods of acceptable mortality reporting in primary care and to demonstrate through examples the implication for research using automated medical data. METHODS: Annual death counts were obtained for each primary care practice participating in The Health Improvement Network "THIN" (UK). Expected counts were calculated from national death rates, accounting for the practice's age/sex structure. The standardized mortality ratio (SMR) was calculated with 95% confidence intervals (CI). A visual review process was undertaken to assign the year from which the practice had acceptable mortality reporting (AMR). The process involved reviewer pairs who were blinded to each other's decisions. Patterns of death reporting were checked. The AMR year was applied as a filter to THIN data to assess its impact on the SMR. RESULTS: For most practices the SMR was relatively stable and the AMR year was easily identified with 86% agreement between the blinded reviewer pairs. Applying the AMR to THIN removed under-reporting of death. However, the total computerized follow-up reduced from 37 to 32 million patient-years. Problematic death recording patterns included some practices keeping only live patient records when converting their software systems thereby creating 'immortal periods' prior to this moment, and peaks occurring when practices updated the vital status of their patients' records. CONCLUSIONS: This is the first time that an external standard has been used to assess completeness of mortality in automated primary care data. The resulting AMR year provides a natural filter for research and avoids biases associated with 'immortal periods', record updating and under-reporting.

Glycaemic, weight, and blood pressure changes associated with early versus later treatment intensification with dapagliflozin in United Kingdom primary care patients with type 2 diabetes mellitus.

AIMS: Early treatment intensification for type 2 diabetes mellitus (T2DM) is often required to achieve glycaemic control and avoid longer-term complications. We assessed associations between early versus later dapagliflozin initiation with changes in glucose control, weight, and blood pressure using UK Clinical Practice Research Datalink (CPRD) data. METHODS: People with T2DM aged ≥18 years, initiating dapagliflozin between November 2012 and August 2016 and with prior oral T2DM therapy (N = 3774), were included. The relationship between early (first intensification after metformin or sulfonylurea monotherapy) and later (second or higher-order intensification) dapagliflozin use and baseline changes in glycated haemoglobin A1c (HbA1c; ≥1.0% absolute reduction), weight (≥5.0% relative loss), and systolic blood pressure (SBP; ≥2 mmHg absolute reduction) after 6-12 months were assessed. RESULTS: Overall, 25% of patients (951 of 3774) were early users and 75% (2823 of 3774) were later users. Later users were older, more likely to be men, and had longer disease duration. Early and later users had similar baseline mean HbA1c levels. For early versus later users, respectively, baseline-adjusted mean (95% confidence interval [CI]) reductions were 1.54% (-1.65, -1.44) versus 1.02% (-1.08, -0.97) in HbA1c, 3.31% (-4.37, -2.25) versus 4.06% (-5.05, -3.07) in weight, and 2.50 mm Hg (-3.89, -1.11) versus 2.84 mm Hg (-3.67, -2.01) in SBP. Early versus later use was associated with a greater likelihood of adjusted HbA1c reduction of ≥1% (odds ratio: 1.68, 95% CI: 1.15-2.45). CONCLUSIONS: Glycaemic benefits were greater with early versus later dapagliflozin intensification. These results support broader and earlier dapagliflozin use.

SGLT-2 Inhibitors and Cardiovascular Risk: An Analysis of CVD-REAL.

BACKGROUND: Prior studies found patients treated with sodium-glucose co-transporter-2 inhibitors (SGLT-2i) had lower rates of death and heart failure (HF). Whether the benefits of SGLT-2i vary based upon the presence of cardiovascular disease (CVD) is unknown. OBJECTIVES: This study sought to determine the association between initiation of SGLT-2i therapy and HF or death in patients with and without CVD. METHODS: The CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors) study was a multinational, observational study in which adults with type 2 diabetes were identified. Patients prescribed an SGLT-2i or other glucose-lowering drugs (GLDs) were matched based on a propensity score for initiation of an SGLT-2i. Hazard ratios (HRs) for the risk of death, HF, and HF or death in patients with and without established CVD were estimated for each country and pooled. RESULTS: After propensity score matching, 153,078 patients were included in each group. At baseline, 13% had established CVD. Compared with therapy using other GLDs, initiation of an SGLT-2i was associated with lower risk of death in patients with and without CVD (HR: 0.56; 95% confidence interval [CI]: 0.44 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.63, respectively). There were also associations between SGLT-2i and lower risk of HF (HR: 0.72; 95% CI: 0.63 to 0.82; and HR: 0.61; 95% CI: 0.48 to 0.78, respectively) and the composite of HF or death (HR: 0.63; 95% CI: 0.57 to 0.70; and HR: 0.56; 95% CI: 0.50 to 0.62, respectively) observed in patients with and without established CVD. CONCLUSIONS: In this large, multinational, observational study, initiation of SGLT-2i was associated with lower risk of death and HF regardless of pre-existing CVD. Ongoing clinical trials will provide further evidence regarding the benefit of SGLT-2i in patients without established CVD. (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors [CVD-REAL]; NCT02993614).

Impact of increased influenza vaccination in 2-3-year-old children on disease burden within the general population: A Bayesian model-based approach.

INTRODUCTION: During the 2013-2014 influenza season, Public Health England extended routine influenza vaccination to all 2- and 3-year-old children in England. To estimate the impact of this change in policy on influenza-related morbidity and mortality, we developed a disease transmission and surveillance model informed by real-world data. METHODS: We combined real-world and literature data sources to construct a model of influenza transmission and surveillance in England. Data were obtained for four influenza seasons, starting with the 2010-2011 season. Bayesian inference was used to estimate model parameters on a season-by-season basis to assess the impact of targeting 2- and 3-year-old children for influenza vaccination. This provided the basis for the construction of counterfactual scenarios comparing vaccination rates of ~2% and ~35% in the 2- and 3- year-old population to estimate reductions in general practitioner (GP) influenza-like-illness (ILI) consultations, respiratory hospitalizations and deaths in the overall population. RESULTS: Our model was able to replicate the main patterns of influenza across the four seasons as observed through laboratory surveillance data. Targeting 2- and 3-year-old children for influenza vaccination resulted in reductions in the general population of between 6.2-9.9% in influenza-attributable GP ILI consultations, 6.1-10.7% in influenza-attributable respiratory hospitalizations, and 5.7-9.4% in influenza-attributable deaths. The decrease in influenza-attributable ILI consultations represents a reduction of between 4.5% and 7.3% across all ILI consultations. The reduction in influenza-attributable respiratory hospitalizations represents a reduction of between 1.2% and 2.3% across all respiratory hospitalizations. Reductions in influenza-attributable respiratory deaths represent a reduction of between 0.9% and 2.4% in overall respiratory deaths. CONCLUSION: This study has provided evidence that extending routine influenza vaccination to all healthy children aged 2 and 3 years old leads to benefits in terms of reduced utilization of healthcare resources and fewer respiratory health outcomes and deaths.

Topical prostaglandin fixed combinations in UK primary care: observational study using data from the health improvement network.

PURPOSE: To describe the use of 3 prostaglandin/timolol fixed combinations (FCs) in UK primary care, to summarize characteristics of recipients, and to assess 12-month persistence. METHODS: This retrospective cohort study included first-time recipients of latanoprost/timolol FC, bimatoprost/timolol FC, or travoprost/timolol FC treated between April 1, 2007, and November 30, 2008, identified in The Health Improvement Network database, a large database of anonymized longitudinal electronic medical records of patients treated in UK primary care. Eligible patients were = 18 years old at the index date (date of first prescription). Persistence, defined as a gap =60 days between consecutive prescriptions, was assessed through 12 months post-index for each cohort (Cox proportional hazards models). RESULTS: A total of 2,015 patients were included: latanoprost/timolol FC, n = 898 (44.6%); bimatoprost/timolol FC, n = 733 (36.4%); travoprost/timolol FC, n = 384 (19.1%). The mean age was approximately 72 years across cohorts (p = 0.792). Glaucoma was the diagnosis for >90% of patients in each cohort. Twelve-month persistence was similar across treatments: latanoprost/timolol FC: 38.2%; bimatoprost/timolol FC: 38.6%; travoprost/timolol FC: 38.3% (p = 0.985). Mean time to therapy change for nonpersistent patients was also similar: 143.3 ± 89.8, 151.0 ± 87.9, and 151.8 ± 87.7 days, respectively (p = 0.095). Among persistent patients, additional therapy was prescribed for 36.2%, 41.7%, and 41.5% of patients, respectively. Among nonpersistent patients, 64.0%, 70.4%, and 69.2%, respectively, restarted the index therapy. CONCLUSIONS: The largest proportion of first-time recipients of prostaglandin/beta-blocker FC products treated in UK primary care was prescribed latanoprost/timolol FC. Twelve-month persistence was similar (<40%) across the 3 FCs evaluated.

Evaluation of varenicline as an aid to smoking cessation in UK general practice - a THIN database study.

OBJECTIVES: Varenicline is a licensed smoking cessation medication in the EU, USA and many other countries worldwide. This study was designed to assess its effectiveness in a UK general practice setting. METHODS: The main outcome measure was the rate of smoking cessation, defined as the seven-day point prevalence after six months from starting varenicline. Varenicline users were identified from records in The Health Improvement Network (THIN) database. A questionnaire on smoking cessation was sent to patients who commenced treatment close to the selection date (six months prior to the date of questionnaire dispatch). RESULTS: The response rate was 26.4%: 193 responses were received. Ninety percent had previously attempted to stop smoking and 87.4% had used nicotine replacement therapy during the previous attempt to stop smoking. The overall smoking cessation rate was 49.5%. There was a strong association between the duration of varenicline treatment and smoking cessation. Patients who reported using varenicline for 9-12 weeks were 11 times more likely to stop smoking than those who completed less than two weeks of treatment. There was some evidence that patients with a longer history of smoking were less likely to stop. No association was observed between smoking cessation and: previous number of cigarettes smoked per day; number of previous attempts to stop smoking; or motivations for stopping. CONCLUSIONS: Varenicline appeared to be a useful pharmacological aid to smoking cessation in a general practice setting. The observed effectiveness was similar to the efficacy estimates from previously reported clinical trials. However, the response rate was lower than expected and responders tended to be older, more likely to suffer from chronic obstructive pulmonary disease and to live in more affluent areas than non-responders. Responses were self-reported and not clinically validated therefore recall bias may be an issue.

Comparing cost-effectiveness analyses of anti-hypertensive drug therapy for decision making: mission impossible?

The purpose of this literature review was to compare the methodology used in the most recently published cost-effectiveness studies of antihypertensive treatments, and to identify methodological strengths and weaknesses that indicate the study's potential as a useful, decision-making tool. Based on the results of a search of several databases, spanning the years 1995 to 2000, 10 cost-effectiveness studies were identified. Although the majority of the studies reported their cost-effectiveness ratio in "costs per year of life gained," the studies also considered a varying range of components including additional end points. The methodology used to measure effectiveness, the cost variables included, and the characteristics of the patient population varied significantly across studies. Due to this lack of conformity, it would be difficult, if not impossible, to compare the results and draw conclusions about the relative cost-effectiveness of different types of antihypertensive drug therapies. This lack of uniform comparison across studies is likely to draw criticism from both the clinical and health-care decision-making communities. Future studies within this field should be thorough and useful for decision making. It is suggested that short-term outcomes should include systolic and diastolic blood pressure measurements and long-term outcomes should include end points such as myocardial infarction, stroke, congestive heart failure and renal events. Other positive outcomes such as a more favorable side-effect profile, should be used to enhance the primary outcomes. Additionally, when subpopulations are considered in submodels, studies should address the issue of generalizability. Cost calculations should be transparent and related to the perspective of the study. Modeling the cost-effectiveness of a drug may be an acceptable method provided that data sources and assumptions are valid and transparent.