British journal of clinical pharmacology
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Br J Clin Pharmacol · Jul 2021
ReviewSubgroup analysis in haematologic malignancies phase III clinical trials: A systematic review.
To assess the appropriateness of the use and interpretation of subgroup analysis in haematology randomized clinical trials (RCTs). ⋯ The subgroup claims reported in haematology RCTs lack credibility, even when the claims are strong. Information about subgroup difference should be interpreted cautiously.
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Br J Clin Pharmacol · Jun 2021
Review Meta AnalysisComparison of infection risks and clinical outcomes in patients with and without SARS-CoV-2 lung infection under renin-angiotensin-aldosterone system blockade: Systematic review and meta-analysis.
Angiotensin-converting enzyme-2 (ACE2) is the receptor for SARS-CoV-2. Animal studies suggest that renin-angiotensin-aldosterone system (RAAS) blockers might increase the expression of ACE2 and potentially increase the risk of SARS-CoV-2 infection. ⋯ ACEIs reduce the risk of getting infected with the SARS-CoV-2 virus. Blocking the RAAS may decrease all-cause mortality in COVID-19 patients. ACEIs also reduce the risk of non-COVID pneumonia. All-cause mortality due to non-COVID pneumonia is reduced by ACEI and potentially by ARBs.
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Br J Clin Pharmacol · Apr 2021
ReviewEfficacy and safety outcomes of proposed randomized controlled trials investigating hydroxychloroquine and chloroquine during the early stages of the COVID-19 pandemic.
To assess whether randomized clinical trials (RCTs) proposed to evaluate the treatment of patients with COVID-19 with hydroxychloroquine (HQ) or chloroquine early in the pandemic included plans to measure outcomes that would translate into meaningful efficacy/effectiveness and safety outcomes. ⋯ The RCTs investigating HQ or chloroquine during the early stages of the COVID-19 pandemic included heterogeneous and insufficient approaches to measure efficacy/effectiveness and safety relevant to patients and clinical practice. These findings provide insights to inform clinical and regulatory decisions that can be drawn about the efficacy/effectiveness and safety of these agents in patients with COVID-19. Trialists need to adapt quickly to the research progress on COVID-19, ensuring that core outcome measures are assessed in ongoing RCTs.
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Br J Clin Pharmacol · Apr 2021
Using genetics to understand the role of antihypertensive drugs modulating angiotensin-converting enzyme in immune function and inflammation.
Angiotensin-converting enzyme 2 (ACE 2) is the binding domain for severe acute respiratory syndrome coronavirus (SARS-CoV) and SARSCoV-2. Some antihypertensive drugs affect ACE2 expression or activity (ACE inhibitors and angiotensin II receptor blockers [ARBs]), suggesting use of other hypertensives might be preferable, such as calcium channel blockers (CCBs). Given the limited evidence, the International Society of Hypertension does not support such a policy. ⋯ Varying effects of different classes of antihypertensives on immune and inflammatory markers do not suggest antihypertensive use based on their role in ACE2 expression, but instead suggest investigation of the role of antihypertensives in immune function and inflammation might reveal important information that could optimize their use in SARSCoV-2.
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Br J Clin Pharmacol · Mar 2021
ReviewThe impact of the global COVID-19 pandemic on the conduct of clinical trials: Return to normalcy by considering the practical impact of a structured ethical analysis.
During the outbreak of the COVID-19 pandemic many clinical trials were abruptly halted. Measures to contain the pandemic are currently taking effect and societies in general and healthcare systems in particular are considering how to return to normalcy. This opens up the discussion when and how clinical trials should be restarted while the COVID-19 pandemic has not yet resolved, and what should happen in case of a resurgence of the virus in the coming months. ⋯ The framework applied provides a structured approach for all clinical trials stakeholders and thereby prevents unclear reasoning in a complex situation. While it is essential to prevent the virus from resurging and focus on developing a COVID-19 treatment as soon as possible, it is just as important to our society that we continue developing new drugs for other conditions. In this article we argue that the situation for clinical trials is not essentially different from the pre-COVID-19 era and that an overcautious approach will have negative consequences.