Clinical pharmacology facing the real-world setting: Pharmacovigilance, pharmacoepidemiology and the economic evaluation of drugs.

Traditionally, clinical pharmacology has focused its activities on drug-organism interaction, from an individual or collective perspective. Drug efficacy assessment by performing randomized clinical trials and analysis of drug use in clinical practice by carrying out drug utilization studies have also been other areas of interest. From now on, Clinical pharmacology should move from the analysis of the drug-individual interaction to the analysis of the drug-individual-society interaction. It should also analyze the clinical and economic consequences of the use of drugs in the conditions of normal clinical practice, beyond clinical trials. The current exponential technological development that facilitates the analysis of real-life data offers us a golden opportunity to move to all these other areas of interest. This review describes the role that clinical pharmacology has played at the beginning and during the evolution of pharmacovigilance, pharmacoepidemiology and economic drug evaluations in Spain. In addition, the challenges that clinical pharmacology is going to face in the following years in these three areas are going to be outlined too.

Clinical and Economic Consequences of Inhaled Corticosteroid Doses and Particle Size in Triple Inhalation Therapy for COPD: Real-Life Study.

Objective: To determine the clinical and economic consequences of inhaled corticosteroid doses and particle size in patients on triple-inhalation therapy for COPD. Methods: Patients aged ≥40 years who initiated treatment with multi-inhaler triple-inhaled therapy between 1 January 2015 and 31 March were included and followed for 1 year. Patients were grouped according to inhaled corticosteroid (ICS) dose (low/medium/high) and particle size device (extrafine/non-extrafine particles). Outcome variables were moderate and severe exacerbations, pneumonia and healthcare resource use (HCRU) costs. A multivariate analysis was performed for model correction (p<0.05). Results: A total of 2185 patients (mean age 72.3 years, 82.9% male) were analysed. Of these, 849 (38.9%) patients received low-dose ICS, 612 medium-dose ICS (28.0%) and 724 (33.1%) high-dose ICS. Exacerbations occurred more frequently with increasing IC dose (low: 26.4%, medium: 28.7% and high: 30.4%; p=0.047), as did the proportion of pneumonia (3.4%, 4.2% and 6.9%, respectively (p=0.041)). The annual mean cost/unit was € 2383 for low dose, € 2401 for medium dose and € 2625 for high dose (p=0.024). Four hundred and sixty-two (31.6%) patients used an extrafine particle device and 999 (68.4%) a non-extrafine particle device: the proportion of exacerbations was 24.0% vs 30.4% (p=0.012), and the annual mean cost/unit was € 2090 vs € 2513, respectively (p<0.001). The number of exacerbations was directly correlated with FEV1 (ß= -0.157), age (ß=0.071), Charlson index (ß=0.050) and device type (extrafine: ß=0.049) (p<0.02). Conclusion: In patients with COPD receiving multi-inhaler triple therapy, higher ICS doses were not associated with a further reduction in exacerbations, whereas we found an increased risk of pneumonia. The use of inhaler devices delivering extrafine ICS particle was associated with a lower rate of exacerbations, resulting in lower overall HCRU costs.

Predictors of Over-Anticoagulation in Warfarin Users in the UK General Population: A Nested Case-Control Study in a Primary Health Care Database.

BACKGROUND: Many patients on warfarin therapy often present with supratherapeutic international normalized ratio (INR) levels, resulting from the influence of several patient-specific factors, which have been associated with adverse outcomes. OBJECTIVE: This article aims to identify risk factors for over-anticoagulation (INR levels ≥4) in a cohort of patients taking warfarin. METHODS: A cohort of warfarin users aged 18 to 85 years from January 2005 to April 2013 was identified in The Health Improvement Network U.K. primary care database (N = 12,506). A random date was assigned to all patients within their eligible person-time (index date), and a nested case-control analysis was performed with individuals presenting a first episode of INR level ≥4 after the index date used as cases (N = 699) and patients with non-supratherapeutic INR values (≤3) as controls (N = 9,798). Using unconditional logistic regression models, odds ratios with 95% confidence intervals were calculated adjusted for potential confounders. Two sensitivity analyses were performed with alternative definitions of over-anticoagulation (INR levels ≥5 or > 3). RESULTS: Among the factors examined, the strongest predictors of over-anticoagulation were warfarin indication (in particular, valvular atrial fibrillation and valve replacement), renal failure (with the risk increasing steeply with decreasing estimated glomerular filtration rate), cancer, anaemia, respiratory infections treated with antibiotics, chronic obstructive pulmonary disease treated with ß2-agonists, polypharmacy (≥10 medications), low socio-economic status and residency in rural areas. Similar results were obtained when supratherapeutic levels were defined as INR ≥5 or, alternatively, as INR > 3. CONCLUSION: Predictors of supratherapeutic INR levels found in this study might help physicians identify patients where closer INR monitoring is warranted.

[Use of antihypertensive drugs in Spain (1995-2001)]. / Utilización de antihipertensivos en España (1995-2001).

OBJECTIVES: In the last few years there have been changes in the pattern of consumption of antihypertensive drugs in Spain. This study aimed to describe the pattern of use in Spain from 1995 to 2001, its compliance with guidelines, and its economic impact. An aim of particular interest for our study was the impact of angiotensin II receptor antagonists on the consumption of the drugs from other therapeutic subgroups. PATIENTS AND METHOD: Information on drug utilization was obtained from the ECOM database of the Spanish Ministry of Health, which records the number of packages charged to the National Health System. Data were expressed in defined daily dose (DDD) and DDD per 1000 inhabitants per day (DHD). RESULTS: Antihypertensive consumption in Spain increased from 113.1 DHD in 1995 to 182.8 in 2001 (an increase of 61.65%). In 2001, angiotensin II receptor antagonists accounted for 25% of the costs and 14% of the consumption. Overall, costs increased from 646.42 million euros in 1995 to 1144.77 million euros in 2001. CONCLUSIONS: The consumption of antihypertensive drugs in Spain has increased remarkably in the last 7 years. Likewise, costs have increased proportionately, although the contributions of different therapeutic subgroups have been unequal. The impact of angiotensin II receptor antagonists has been considerable, both on consumption and on costs.