scholarly journals Response to commentaries: alcohol intake and total mortality, strengths and limitations of observational studies, waiting for clinical trials

Addiction ◽  
2022 ◽  
Vol 117 (2) ◽  
pp. 329-330
Author(s):  
Augusto Di Castelnuovo ◽  
Simona Costanzo ◽  
Giovanni Gaetano ◽  
Licia Iacoviello ◽  
Keyword(s):  
Clinical Trials ◽  
Observational Studies ◽  
Alcohol Intake ◽  
Total Mortality

scholarly journals Low dose hydroxychloroquine is associated with lower mortality in COVID-19: a meta-analysis of 26 studies and 44,521 patients

2020 ◽  
Author(s):  
Augusto Di Castelnuovo ◽  
Simona Costanzo ◽  
Antonio Cassone ◽  
Roberto Cauda ◽  
Giovanni de Gaetano ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Risk Ratio ◽  
Mortality Risk ◽  
Observational Studies ◽  
Low Dose ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Total Mortality ◽  
Lower Mortality ◽  
Lower Mortality Risk

ABSTRACTBackgroundHydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19, but its association with mortality is not well characterized. We conducted two meta-analyses to evaluate the association between HCQ (with or without azithromycin (AZM)) and total mortality in COVID-19 patients.MethodsArticles were retrieved until October 20th, 2020 by searching in seven databases. Data were combined using the general variance-based method on relative risk estimates.ResultsA total of 26 articles were found (N=44,521 COVID-19 patients, including N=7,324 from 4 randomized clinical trials (RCTs)); 10 studies were valuable for analysing the association of HCQ+AZM. Overall, the use of HCQ was associated with 21% lower mortality risk (pooled risk ratio: 0.79, 95%CI: 0.67 to 0.93; high level of heterogeneity: I2=82%, random effects). This association vanished (1.10, 95%CI: 0.99 to 1.23 and 1.10, 95%CI: 0.99 to 1.23) when daily dose >400 mg or total dose >4,400 mg were used, respectively). HCQ+AZM was also associated with 25% lower mortality risk, but uncertainty was large (95%CI: 0.50 to 1.13; P=0.17). No association was apparent when only pooling the 4 RCTs (13.8% of the overall weight; pooled risk ratio: 1.11, 95%CI: 0.99 to 1.24).ConclusionsHCQ use was not associated with either increased or decreased mortality in COVID-19 patients when 4 RCTs only were evaluated, while a 7% to 33% reduced mortality was observed when observational studies were also included. The association was mainly apparent when pooling studies using lower doses of HCQ. These findings can help disentangling the debate on HCQ use in COVID-19.Key-pointsLow dose hydroxychloroquine was associated with reduced mortality in COVID-19 patients, as seen in observational studies but not in randomised clinical trials, which used high doses of hydroxychloroquine. These findings can help disentangling the debate on hydroxychloroquine use in COVID-19.

scholarly journals EULAR points to consider for conducting clinical trials and observational studies in individuals at risk of rheumatoid arthritis

2021 ◽  
pp. annrheumdis-2021-220884
Author(s):  
Kulveer Mankia ◽  
Heidi J Siddle ◽  
Andreas Kerschbaumer ◽  
Deshire Alpizar Rodriguez ◽  
Anca Irinel Catrina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
At Risk ◽  
Clinical Trials ◽  
Observational Studies ◽  
Task Force ◽  
Musculoskeletal Symptoms ◽  
Subclinical Inflammation ◽  
Consensus Statements ◽  
Clinical Arthritis

BackgroundDespite growing interest, there is no guidance or consensus on how to conduct clinical trials and observational studies in populations at risk of rheumatoid arthritis (RA).MethodsAn European League Against Rheumatism (EULAR) task force formulated four research questions to be addressed by systematic literature review (SLR). The SLR results informed consensus statements. One overarching principle, 10 points to consider (PTC) and a research agenda were proposed. Task force members rated their level of agreement (1–10) for each PTC.ResultsEpidemiological and demographic characteristics should be measured in all clinical trials and studies in at-risk individuals. Different at-risk populations, identified according to clinical presentation, were defined: asymptomatic, musculoskeletal symptoms without arthritis and early clinical arthritis. Study end-points should include the development of subclinical inflammation on imaging, clinical arthritis, RA and subsequent achievement of arthritis remission. Risk factors should be assessed at baseline and re-evaluated where appropriate; they include genetic markers and autoantibody profiling and additionally clinical symptoms and subclinical inflammation on imaging in those with symptoms and/or clinical arthritis. Trials should address the effect of the intervention on risk factors, as well as progression to clinical arthritis or RA. In patients with early clinical arthritis, pharmacological intervention has the potential to prevent RA development. Participants’ knowledge of their RA risk may inform their decision to participate; information should be provided using an individually tailored approach.ConclusionThese consensus statements provide data-driven guidance for rheumatologists, health professionals and investigators conducting clinical trials and observational studies in individuals at risk of RA.

Can We Trust Observational Studies Using Propensity Scores in the Critical Care Literature? A Systematic Comparison With Randomized Clinical Trials*

2015 ◽  
Vol 43 (9) ◽  
pp. 1870-1879 ◽  
Author(s):  
Georgios D. Kitsios ◽  
Issa J. Dahabreh ◽  
Sean Callahan ◽  
Jessica K. Paulus ◽  
Anthony C. Campagna ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Critical Care ◽  
Observational Studies ◽  
Propensity Scores ◽  
Randomized Clinical Trials ◽  
Systematic Comparison

scholarly journals High-cited favorable studies for COVID-19 treatments ineffective in large trials

2022 ◽  
Author(s):  
John P.A. Ioannidis
Keyword(s):  
Clinical Trials ◽  
Randomized Controlled Trials ◽  
Clinical Studies ◽  
Observational Studies ◽  
Randomized Trials ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Wide Dissemination ◽  
Highly Cited Articles ◽  
Highly Cited

Importance. COVID-19 has resulted in massive production, publication and wide dissemination of clinical studies trying to identify effective treatments. However, several widely touted treatments failed to show effectiveness in large well-done randomized controlled trials (RCTs). Objective. To evaluate for COVID-19 treatments that showed no benefits in subsequent large RCTs how many of their most-cited clinical studies had declared favorable results for these interventions. Methods. Scopus (last update December 23, 2021) identified articles on lopinavir-ritonavir, hydroxycholoroquine/azithromycin, remdesivir, convalescent plasma, colchicine or interferon (index interventions) that represented clinical trials and that had received >150 citations. Their conclusions were assessed and correlated with study design features. The ten most recent citations for the most-cited article on each index intervention were examined on whether they were critical to the highly-cited study. Altmetric scores were also obtained. Findings. 40 articles of clinical studies on these index interventions had received >150 citations (7 exceeded 1,000 citations). 20/40 (50%) had favorable conclusions and 4 were equivocal. Highly-cited articles with favorable conclusions were rarely RCTs while those without favorable conclusions were mostly RCTs (3/20 vs 15/20, p=0.0003). Only 1 RCT with favorable conclusions had sample size >160. Citation counts correlated strongly with Altmetric scores, in particular news items. Only 9 (15%) of 60 recent citations to the most highly-cited studies with favorable or equivocal conclusions were critical to the highly-cited study. Conclusion. Many clinical studies with favorable conclusions for largely ineffective COVID-19 treatments are uncritically heavily cited and disseminated. Early observational studies and small randomized trials may cause spurious claims of effectiveness that get perpetuated.

scholarly journals Post-Exposure Effects of Vaccines on Infectious Diseases

2019 ◽  
Author(s):  
Tara Gallagher ◽  
Marc Lipsitch
Keyword(s):  
Clinical Trials ◽  
Observational Studies ◽  
Case Fatality ◽  
Hepatitis E ◽  
Vaccine Preventable Diseases ◽  
Post Exposure ◽  
Vaccine Trials ◽  
Tick Borne Encephalitis ◽  
Pubmed Database ◽  
Definition Of

AbstractMany available vaccines have demonstrated post-exposure effectiveness, but no published systematic reviews have synthesized these findings. We searched the PubMed database for clinical trials and observational human studies concerning the post-exposure vaccination effects, targeting infections with an FDA-licensed vaccine plus dengue, hepatitis E, malaria, and tick borne encephalitis, which have licensed vaccines outside of the U.S. Studies concerning animal models, serologic testing, and pipeline vaccines were excluded. Eligible studies were evaluated by definition of exposure, and their attempt at distinguishing pre- and post-exposure effects was rated on a scale of 1-4. We screened 4518 articles and ultimately identified 14 clinical trials and 31 observational studies for this review, amounting to 45 eligible articles spanning 7 of the 28 vaccine-preventable diseases. For secondary attack rate, this body of evidence found the following medians for post-exposure vaccination effectiveness: hepatitis A: 85% (IQR: 28; 5 sources), hepatitis B: 85% (IQR: 22; 5 sources), measles: 83% (IQR: 21; 8 sources), varicella: 67% (IQR: 48; 9 sources), smallpox: 45% (IQR: 39; 4 sources), and mumps: 38% (IQR: 7; 2 sources). For case fatality proportions resulting from rabies and smallpox, the vaccine efficacies had medians of 100% (IQR: 0; 6 sources) and 63% (IQR: 50; 8 sources) post-exposure. Although mainly used for preventive measures, many available vaccines can modify or preclude disease if administered after exposure. This post-exposure effectiveness could be important to consider during vaccine trials and while developing new vaccines.

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