Standard requirements for GCP-compliant data management in multinational clinical trials

<p>Abstract</p> <p>Background</p> <p>A recent survey has shown that data management in clinical trials performed by academic trial units still faces many difficulties (e.g. heterogeneity of software products, deficits in quality management, limited human and financial resources and the complexity of running a local computer centre). Unfortunately, no specific, practical and open standard for both GCP-compliant data management and the underlying IT-infrastructure is available to improve the situation. For that reason the "Working Group on Data Centres" of the European Clinical Research Infrastructures Network (ECRIN) has developed a standard specifying the requirements for high quality GCP-compliant data management in multinational clinical trials.</p> <p>Methods</p> <p>International, European and national regulations and guidelines relevant to GCP, data security and IT infrastructures, as well as ECRIN documents produced previously, were evaluated to provide a starting point for the development of standard requirements. The requirements were produced by expert consensus of the ECRIN Working group on Data Centres, using a structured and standardised process. The requirements were divided into two main parts: an IT part covering standards for the underlying IT infrastructure and computer systems in general, and a Data Management (DM) part covering requirements for data management applications in clinical trials.</p> <p>Results</p> <p>The standard developed includes 115 IT requirements, split into 15 separate sections, 107 DM requirements (in 12 sections) and 13 other requirements (2 sections). Sections IT01 to IT05 deal with the basic IT infrastructure while IT06 and IT07 cover validation and local software development. IT08 to IT015 concern the aspects of IT systems that directly support clinical trial management. Sections DM01 to DM03 cover the implementation of a specific clinical data management application, i.e. for a specific trial, whilst DM04 to DM12 address the data management of trials across the unit. Section IN01 is dedicated to international aspects and ST01 to the competence of a trials unit's staff.</p> <p>Conclusions</p> <p>The standard is intended to provide an open and widely used set of requirements for GCP-compliant data management, particularly in academic trial units. It is the intention that ECRIN will use these requirements as the basis for the certification of ECRIN data centres.</p

ETUDE DU DEPISTAGE DES FACTEURS DE RISQUE CARDIOVASCULAIRE EN MEDECINE GENERALE

LYON1-BU Santé (693882101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Combined effect of renal function and serum potassium level in sudden cardiac death in aging hypertensive subjects

In patients with chronic kidney disease, serum potassium level is a factor influencing sudden cardiac death (SCD). The aim of our analysis was to study the combined effect of serum potassium level and renal function on the onset of SCD in elderly hypertensive subjects. Data from the 3620 hypertensive patients aged over 70 years were extracted from three randomized clinical trials included in the INDANA database. During a mean follow up of 4.5 years, 81 patients (2.24%) died from SCD. Mean serum potassium levels and prevalence of chronic kidney disease were not different in patients who died from SCD. In addition to serum potassium and creatinine levels, 14 clinical and biological variables linked to cardiovascular diseases recorded at baseline were analyzed using a Bayesian network. The area under the receiver operating characteristic curve of the Bayesian model reached 0.91. Bayesian inference was used to simulate the combined effects of serum potassium and creatinine levels on SCD. Our analysis, using simulated data from Bayesian model, showed that the estimated probabilities of SCD was significantly increased in case of hyperkalemia (>5.0 mmol/l) and in case of hypokalemia (<3.5 mmol/l) and in case of chronic kidney disease. Combined effects of serum potassium level and renal function revealed that chronic kidney disease increased the probability of SCD whatever the serum potassium level. Our results using a Bayesian model confirm the deleterious effects of hypokalemia, hyperkalemia and chronic kidney disease on SCD in elderly hypertensive patients.status: publishe

Pharmacotherapy for mild hypertension

BACKGROUND: People with no previous cardiovascular events or cardiovascular disease represent a primary prevention population. The benefits and harms of treating mild hypertension in primary prevention patients are not known at present. This review examines the existing randomized controlled trial (RCT) evidence. OBJECTIVE: Primary objective: To quantify the effects of antihypertensive drug therapy on mortality and morbidity in adults with mild hypertension (systolic blood pressure (BP) 140-159 mmHg and/or diastolic BP 90-99 mmHg) and without cardiovascular disease. METHODS: Search: We searched CENTRAL (2011, Issue 1), MEDLINE (1948 to May 2011), EMBASE (1980 to May 2011) and reference lists of articles. The Cochrane Database of Systematic Reviews and the Database of Abstracts of Reviews of Effectiveness (DARE) were searched for previous reviews and meta-analyses of anti-hypertensive drug treatment compared to placebo or no treatment trials up until the end of 2011. Selection criteria: RCTs of at least 1 year duration. Data collection and analysis: The outcomes assessed were mortality, stroke, coronary heart disease (CHD), total cardiovascular events (CVS), and withdrawals due to adverse effects. MAIN RESULTS: Of 11 RCTs identified 4 were included in this review, with 8,912 participants. Treatment for 4 to 5 years with antihypertensive drugs as compared to placebo did not reduce total mortality (RR 0.85, 95% CI 0.63, 1.15). In 7,080 participants treatment with antihypertensive drugs as compared to placebo did not reduce coronary heart disease (RR 1.12, 95% CI 0.80, 1.57), stroke (RR 0.51, 95% CI 0.24, 1.08), or total cardiovascular events (RR 0.97, 95% CI 0.72, 1.32). Withdrawals due to adverse effects were increased by drug therapy (RR 4.80, 95% CI 4.14, 5.57), ARR 9%. AUTHORS' CONCLUSIONS: Antihypertensive drugs used in the treatment of adults (primary prevention) with mild hypertension (systolic BP 140-159 mmHg and/or diastolic BP 90-99 mmHg) have not been shown to reduce mortality or morbidity in RCTs. Treatment caused 9% of patients to discontinue treatment due to adverse effects. More RCTs are needed in this prevalent population to know whether the benefits of treatment exceed the harms