AI Article Synopsis
- Noninferiority trials are commonly used in cardiovascular medicine, but they can be difficult to interpret, especially when using absolute risk differences as margins.
- This study reviewed noninferiority trials from major cardiovascular conferences from 2015-2022 to examine the effects of using absolute versus relative noninferiority margins.
- The findings showed that about 22.9% of the trials had different interpretations when recalculated using actual event rates, and many of these trials did not include cautionary notes in their conclusions about the results.
Article Abstract
Background: Noninferiority trials are increasingly common in cardiovascular medicine, but their reporting and interpretation are challenging, particularly when an absolute risk difference is used as noninferiority margin.
Objectives: This study aimed to investigate the effect of using absolute rather than relative noninferiority margins in cardiovascular trials.
Methods: We reviewed noninferiority trials presented at major cardiovascular conferences from 2015 to 2022 and published within the same period. Based on the actual versus anticipated event rates in the control group, we recalculated the absolute noninferiority margin and re-assessed the trial results. The primary outcome of interest was the proportion of trials with a different interpretation after recalculation. Additionally, we analyzed the conclusion statements of these trials to determine if cautionary notes for the interpretation of study results were included.
Results: We analyzed a total of 768 trials, of which 88 had a noninferiority design and 66 used an absolute noninferiority margin. Of 48 comparisons from 45 trials qualifying for the analysis, 11 (22.9%) had divergent results after recalculation of the absolute noninferiority margin based on the observed rather than anticipated event rate. Ten trials originally claiming noninferiority, did not meet it after the margin recalculation. All of them did not include statements suggesting cautionary interpretation of the study results in the conclusion section. Compared with the other trials, these displayed a larger median difference between anticipated and recalculated noninferiority margins (44.7% [IQR: 38.6%-56.7%] vs 15.3% [IQR: -1.5% to 28.9%]; < 0.001).
Conclusions: Recalculating noninferiority margins based on actual event rates, rather than anticipated ones, led to different outcomes in approximately 1 out of 4 cardiovascular trials, with most divergent trials lacking cautionary interpretation. These findings emphasize the importance of using or supplementing the relative noninferiority margin, particularly in studies with significant deviations between observed and expected event rates. This underscores the critical need for enhanced methodological and reporting standards in noninferiority trials, especially those employing absolute margins.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11312784 | PMC |
| http://dx.doi.org/10.1016/j.jacadv.2024.101021 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Aspirin and Hemocompatibility After LVAD Implantation in Patients With Atherosclerotic Vascular Disease: A Secondary Analysis From the ARIES-HM3 Randomized Clinical Trial.
JAMA Cardiol
January 2025
Brigham and Women's Hospital Heart and Vascular Center, Center for Advanced Heart Disease, Harvard Medical School, Boston, Massachusetts.
Importance: The Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study demonstrated that aspirin may be safely eliminated from the antithrombotic regimen after HeartMate 3 (HM3 [Abbott Cardiovascular]) left ventricular assist device (LVAD) implantation. This prespecified analysis explored whether conditions requiring aspirin (prior percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], stroke, or peripheral vascular disease [PVD]) would influence outcomes differentially with aspirin avoidance.
Objective: To analyze aspirin avoidance on hemocompatibility-related adverse events (HRAEs) at 1 year after implant in patients with a history of CABG, PCI, stroke, or PVD.
Oral Glucose-Lowering Agents vs Insulin for Gestational Diabetes: A Randomized Clinical Trial.
JAMA
January 2025
Department of Health Sciences, Faculty of Science, Vrije Universiteit Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.
Importance: Metformin and glyburide monotherapy are used as alternatives to insulin in managing gestational diabetes. Whether a sequential strategy of these oral agents results in noninferior perinatal outcomes compared with insulin alone is unknown.
Objective: To test whether a treatment strategy of oral glucose-lowering agents is noninferior to insulin for prevention of large-for-gestational-age infants.
Comparison of warm sitz bath and electronic bidet with a lower-force water flow for postoperative management after hemorrhoidectomy (BIDLOW).
BMC Surg
January 2025
Department of Surgery, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Aim: Electronic bidets can be a substitute for sitz baths, but no study has examined the use of electronic bidets to manage anal problems.
Methods: A randomized, controlled, single-blind, multicenter, parallel group trial was performed. Patients who underwent hemorrhoidectomy were randomly assigned (1:1) to use the electronic bidet or warm sitz baths for 7 days after hemorrhoidectomy.
Immunogenicity, Safety, and Reactogenicity of Concomitant Administration of the Novavax Vaccine against Omicron XBB.1.5 (NVX-CoV2601) and a 20-valent Pneumococcal Conjugate Vaccine in Adults Aged ≥60 Years: A Randomised, Double-blind, Placebo-controlled, Non-inferiority Trial.
J Infect
January 2025
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria. Electronic address:
Objectives: There is conflicting evidence as to whether the combined administration of two vaccines can lead to poorer immunogenicity and reactogenicity. The co-administration of the Omicron-adapted COVID-19 vaccine from Novavax (NVX-CoV2601) and a 20-valent pneumococcal conjugate vaccine (PCV20) has not been previously investigated.
Methods: In this randomised, double-blind, placebo-controlled, non-inferiority trial, immunocompetent participants aged ≥60 years were randomised in a 1:1:1:1 ratio to four groups: NVX-CoV2601 plus PCV20 (combination group); NVX-CoV2601 plus placebo (NVX-only group); PCV20 plus placebo (PCV20-only group); or placebo plus placebo (placebo group).
Antibiotic prophylaxis to prevent infection in patients with Child-Pugh A cirrhosis with upper gastrointestinal bleed: an open label randomised controlled trial.
Hepatol Int
January 2025
Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
Background And Aims: Although beneficial in reducing the risk of bacterial infections in patients with advanced decompensated cirrhosis after upper gastrointestinal (GI) bleed, the utility of prophylactic antibiotics in those with Child-Pugh A cirrhosis is not known. We studied if prophylactic antibiotics can be withheld in this cohort.
Methods: This was a single-centre, open-label randomised-controlled-trial with non-inferiority design.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!