Legal and ethical framework for global health information and biospecimen exchange - an international perspective.

BACKGROUND: The progress of electronic health technologies and biobanks holds enormous promise for efficient research. Evidence shows that studies based on sharing and secondary use of data/samples have the potential to significantly advance medical knowledge. However, sharing of such resources for international collaboration is hampered by the lack of clarity about ethical and legal requirements for transfer of data and samples across international borders. MAIN TEXT: Here, the International Clinical Trial Center Network (ICN) reports the legal and ethical requirements governing data and sample exchange (DSE) across four continents. The most recurring requirement is ethical approval, whereas only in specific conditions approval of national health authorities is required. Informed consent is not required in all sharing situations. However, waiver of informed consent is only allowed in certain countries/regions and under certain circumstances. The current legal and ethical landscape appears to be very complex and under constant evolution. Regulations differ between countries/regions and are often incomplete, leading to uncertainty. CONCLUSION: With this work, ICN illuminates the unmet need for a single international collaborative framework to facilitate DSE. Harmonising requirements for global DSE will reduce inefficiency and waste in research. There are many challenges to realising this ambitious vision, including inconsistent terminology and definitions, and heterogeneous and dynamic legal constraints. Here, we identify areas of agreement and significant difference as a necessary first step towards facilitating international collaboration. We propose the establishment of a working group to continue the comparison across jurisdictions, create a standardised glossary and define a set of basic principles and fundamental requirements for DSE

Safety of statins

Statins are considered to be the first-line therapy for reducing low-density lipoprotein (LDL) cholesterol levels in patients at high risk for atherosclerotic cardiovascular disease. Although favorable results from a large number of controlled clinical trials underline the benefits of statin therapy, the safety of statins receives much attention. Controlled trials and clinical practice have demonstrated that, except for cerivastatin, statins are generally safe; indeed, the frequency of clinically relevant adverse effects is rather low. Rosuvastatin is the newest member in the group, having both attractive potency and superior maximal therapeutic efficacy. In this review, the safety of statins is discussed with special reference to rosuvastatin and in the light of relevant data from comprehensive clinical trial series of rosuvastatin as well as pharmacoepidemiological studies and reports of health authorities

Direct Inhibition of Renin

From the beginning of the history of renin angiotensin system (RAS) with the renal extracts in 1898 it still continues to be exciting. After angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs), direct renin inhibitors (DRI) recently entered the RAS arena. With the increasing evidence, RAS inhibition is an important treatment strategy in hypertension. Results of ongoing and future clinical trials with specific populations and focusing on protection of end-organ damage will enrich our knowledge and understanding on direct renin inhibition

Effects of valsartan on stress-induced changes of serum vascular endothelial growth factor and nitric oxide in mice

This study investigated the effects of renin- angiotensin system ( RAS) blockade on stress- induced changes of serum vascular endothelial growth factor ( VEGF) and nitric oxide ( NO) in mice. Chronic stress increased the serum NO levels significantly compared to control group ( p =.0172). Valsartan, an angiotensin II receptor antagonist, alone, did not make significant difference versus control group. In chronic stress + valsartan group, serum NO levels decreased nonsignificantly compared to chronic stress group. There was a nonsignificant increase in serum VEGF levels after chronic stress. Valsartan alone or with chronic stress did not significantly affect the serum VEGF levels. In conclusion, there was no correlation between NO and VEGF changes during the stress response. In this respect, there may be other mechanisms to explain the stress- induced NO increase

RENIN INHIBITORS IN DIABETES AND HYPERTENSION: AN UPDATE

The coexistence of hypertension and diabetes increases the incidence of cardiovascular events and long-term morbidity and mortality. Blood pressure should be controlled with the most appropriate drugs as well as tight blood glucose control in patients with diabetes and hypertension. RAAS (Renin Angiotensin Aldosterone System) blockers have an important role in the treatment of these patients, in this sense, ACEi and ARB remained the major treatment option in hypertension guidelines. The most recent RAAS blocker to be approved by the FDA was aliskiren in 2007, a renin inhibitor. Studies showed that aliskiren is as effective as other antihypertensive drugs and has a safety profile similar to placebo. The potent renin inhibitor aliskiren directly inhibits the RAAS system at its rate limiting step and differently from other RAAS blockers; it decreases plasma renin activity (PRA). Although the relationship of increased PRA levels and cardiovascular risk has been shown, it is unclear if the PRA decrease provided by aliskiren has an impact on clinical outcomes and cardiovascular endpoints. On the other hand, large trials like ASPIRE, AVANT-GARDE, ALTITUDE, ASTRONAUT, which investigated the combination of aliskiren with other RAAS blockers, failed to show the expected outcomes or resulted with an increased incidence of adverse effects, which raised more questions. As a result of the ALTITUDE trial, combination of aliskiren with an ACEi or ARB is not recommended in patients with hypertension and diabetes, or at least moderate renal dysfunction. Trials designed to prove aliskiren's efficacy in new indications like diabetes, may face similar problems related to dual RAAS blockade because in the majority of cases, the optimal treatment is achieved with an ACEi or ARB. In this conjuncture, the increase in adverse events seen with aliskiren might be related to dual RAAS blockade rather than aliskiren directly. For instance, it is unclear whether the adverse event incidence would be the same, less, or higher if ALTITUDE was designed to investigate ACEi and ARB combination without aliskiren. In fact, every new molecular entity and mechanism of action faces the same barriers. For the time being, differentiating points like PRA lowering effects as an add-on therapy to calcium channel blockers or hydrochlorothiazide, and the populations that might have additional benefit, should be carefully investigated

The Efficacy and Safety of Triple vs Dual Combination of Angiotensin II Receptor Blocker and Calcium Channel Blocker and Diuretic: A Systematic Review and Meta-Analysis

Many hypertensive patients require 2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple combination of angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics. Medical literature between January 1990 and April 2012 was reviewed systematically and data from eligible studies were abstracted. Data were analyzed using random-effects models. Of the 224 studies screened, 7563 eligible patients from 11 studies were included. Triple combinations of ARBs (olmesartan or valsartan), CCBs (amlodipine), and diuretics (hydrochlorothiazide) at any dose provided more blood pressure reduction in office and 24-hour ambulatory measurements than any dual combination of these molecules (P<.0001 for both). Significantly more patients achieved blood pressure targets with triple combinations (odds ratio, 2.16; P<.0001). Triple combinations did not increase adverse event risk (odds ratio, 0.96; P=.426). Triple combinations at any dose seem to decrease blood pressure more effectively than dual combination of the same molecules without any remarkable risk elevation for adverse events. Further prospective studies evaluating the efficacy and safety of triple combinations, especially in the form of single pills, are required. J Clin Hypertens (Greenwich). 2012;00:0000. (c) 2012 Wiley Periodicals, Inc