What are the 4 most important findings from the compass trial?
The 4 most important findings of our analysis of the COMPASS trial are as follows: (1) The lower rate of NCB adverse events with rivaroxaban 2.5 mg twice daily plus ASA versus ASA monotherapy was primarily driven by a reduction in “efficacy” events, whereas the increased risk in severe bleedings was markedly less frequent.
What is the evidence-based approach to critical appraisal?
The evidence-based approach to critical appraisal is described using an example from the urological literature. A three-part assessment of the trial validity, treatment effect, and applicability of results will permit the urologist to critically incorporate medical and surgical advances into practice. Results:
What is critical appraisal in clinical research?
Critical appraisal is the course of action for watchfully and systematically examining research to assess its reliability, value and relevance in order to direct professionals in their vital clinical decision making [1]. Critical appraisal is essential to: Combat information overload; Identify papers that are clinically relevant;
What does the compass trial tell us about secondary prevention strategy?
Despite these limitations, the COMPASS trial marks an important milestone in our search for effective secondary prevention strategy for patients with established cardiovascular disease.
How precise was the treatment effect?
The best estimate of the size of the treatment effect (70 per cent) and the 95 per cent confidence interval about this estimate (7 to 100 per cent) are shown. The best estimate of the treatment effect is that it is clinically worthwhile, but this conclusion is subject to a high degree of uncertainty.
How do you appraise the effectiveness of treatment?
Three broad criteria should be assessed, including the validity of the results, the magnitude and precision of the treatment effect, and the applicability of results to patient care. Evidence-based clinical practice will lead toward higher quality patient care, and should be sought by all practicing urologists.
What was the major outcome of Compass trial?
The COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) demonstrated that in patients with chronic coronary syndromes and/or PAD, the combination of rivaroxaban 2.5 mg twice daily plus acetylsalicylic acid (aspirin) (ASA) 100 mg reduced the risk of cardiovascular events as compared with ...
What is the magnitude of treatment effect?
It is a dimensionless measure of the difference in outcomes under two different treatment interventions. Effect sizes thus inform clinicians about the magnitude of treatment effects. Some methods can also indicate whether the difference observed between two treatments is clinically relevant.
What is an appraisal in research?
Critical Appraisal. Critical appraisal is the process of carefully and systematically assessing the outcome of scientific research (evidence) to judge its trustworthiness, value and relevance in a particular context.
What is Compass trial?
The COMPASS trial, conducted at 602 centers in 33 countries, is a double-blind, double-dummy, randomized trial using a 3-by-2 partial factorial design and involving patients with a history of stable atherosclerotic vascular disease.
What was the inclusion criteria of the compass trial?
Inclusion Criteria Myocardial infarction within the last 20 years. Multivessel coronary disease with symptoms or with history of stable or unstable angina. Multivessel PCI.
Can brilinta be used without aspirin?
Ticagrelor (Brilinta, AstraZeneca) without aspirin, showed benefit in different types of patients with cardiovascular (CV) disease, according to research presented at the American College of Cardiology's Annual Scientific Session Together with World Congress of Cardiology.
How do you describe treatment effect?
General definition The expression "treatment effect" refers to the causal effect of a given treatment or intervention (for example, the administering of a drug) on an outcome variable of interest (for example, the health of the patient).
How do you calculate treatment effect size?
The effect size of the population can be known by dividing the two population mean differences by their standard deviation.
Is effect size the same as treatment effect?
When the meta-analysis looks at the relationship between two variables or the difference between two groups, its index can be called an “Effect size”. When the relationship or the grouping is based on a deliberate intervention, its index can also be called a “Treatment effect”.
What is evidence based critical appraisal?
The evidence-based approach to critical appraisal is described using an example from the urological literature. A three-part assessment of the trial validity, treatment effect, and applicability of results will permit the urologist to critically incorporate medical and surgical advances into practice.
Why are trials stopped early?
However, early termination may introduce bias secondary to chance deviations from the “true effect” of treatment which would decrease if the trial was continued to completion. [15] Small trials and those with few outcome events are particularly prone to this bias if stopped early.[2] For this reason, critical readers of the urology literature should interpret trials terminated early with caution. In the case of the REDUCE trial, it appears that the trial went to completion, so this is not a concern in terms of the validity of the trial.
What is the purpose of randomization?
The purpose of randomization is to balance both known and unknown prognostic factors between control and experimental groups. When successful, randomization assures us that the only prognostic difference between experimental and control groups is the treatment under investigation, and thus, any observed effect of therapy is due to that treatment.
How to minimize bias in RCT?
Therefore, important methodological safeguards , which minimize bias should be reported for any RCT. At the beginning of an RCT, subjects in the experimental and control groups should have a similar prognosis. In order to minimize prognostic differences, patients should be randomized, the randomization process should be concealed, and a balance of known prognostic factorsshould exist between members of each group in the trial.
Why is prognostic balance less certain?
At study's completion, the question of prognostic balance is less certain because of a relatively high rate of loss to follow-up.
Why is blinding important in clinical trials?
Blinding is important to maintaining prognostic balance as the study progresses, as it helps to minimize a variety of biases, such as placebo effects or co-interventions. Empirical evidence of bias exists in trials where blinding was not utilized or was ineffective.[10,11] Five important groups should be blinded, when feasible: patients, clinicians, data collectors, outcome adjudicators, and data analysts [Table 1]. Frequently readers will see the terms “double-blind” or “triple-blind.” These terms may be confusing, and it is preferable to state exactly which groups are blinded in the course of a trial.[12] In surgical trials it is often impossible to blind the surgeon, but it may be feasible to blind patients, and is almost always feasible to blind data collectors and outcome assessors.
What is the validity of clinical trials?
Validity of clinical trials hinges upon balancing patient prognosis at the initiation, execution, and conclusion of the trial. Readers should be aware of not only the magnitude of the estimated treatment effect, but also its precision. Finally, urologists should consider all patient-important outcomes as well as the balance of potential benefits, harms, and costs, and patient values and preferences when making treatment decisions.
What is a compass?
The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial results were highly anticipated; the results were commensurate with expectations set by the news of its premature termination for 'overwhelming efficacy.' So what have we learned from this important study?
How long is the run in phase of rivaroxaban?
The 30-day run-in phase exposed participants to rivaroxaban placebo (twice daily) and once a day aspirin, off all non-study anticoagulants or aspirin therapy. 2 This ensured medication compliance and absence of aspirin associated bleeding. Approximately 8% of the 28,275 non-coronary artery bypass grafting participants included in the study were excluded during this run-in phase (~70% for adherence concerns and ~5% for adverse events that included 23 deaths and 3 major bleeding-related exclusions). Overall, there were 25 participants who had major bleeds during the run-in phase. 2 Skeptics often raise these points as a testament of selection bias and decreased generalizability of the trial findings. In my opinion, they simply encourage us to carefully assess our patients' compliance with existing medications prior to adding a new and probably more expensive twice a day drug.
What is critical appraisal?
Critical appraisal is the course of action for watchfully and systematically examining research to assess its reliability, value and relevance in order to direct professionals in their vital clinical decision making [1].
Why is critical appraisal important?
Critical appraisal is essential to: Combat information overload; Identify papers that are clinically relevant; Continuing Professional Development (CPD). Carrying out Critical Appraisal: Assessing the research methods used in the study is a prime step in its critical appraisal.
What is bias in research?
As bias cannot be measured, researchers need to rely on good research design to minimize bias [8]. To minimize any bias within a study the sample population should be representative of the population.
What is reliability in testing?
Reliability refers to how consistent a test is on repeated measurements. It is important especially if assessments are made on different occasions and or by different examiners. Studies should state the method for assessing the reliability of any measurements taken and what the intra –examiner reliability was [6].
What section should include an absolute comparison of what is already identified in the topic of interest and the clinical relevance of what has?
VI. Discussion section: This section should include an absolute comparison of what is already identified in the topic of interest and the clinical relevance of what has been newly established. A discussion on a possible related limitations and necessitation for further studies should also be indicated.
What is the purpose of reading an abstract?
II. ABSTRACT: Reading the abstract is a quick way of getting to know the article and its purpose, major procedures and methods, main findings, and conclusions.
Why is statistical analysis important?
Correct statistical analysis of results is crucial to the reliability of the conclusions drawn from the research paper. Depending on the study design and sample selection method employed, observational or inferential statistical analysis may be carried out on the results of the study.
What are the results of the compass trial?
The 4 most important findings of our analysis of the COMPASS trial are as follows: 1 (1) The lower rate of NCB adverse events with rivaroxaban 2.5 mg twice daily plus ASA versus ASA monotherapy was primarily driven by a reduction in “efficacy” events, whereas the increased risk in severe bleedings was markedly less frequent. 2 (2) The lower rate of NCB adverse events became more pronounced with increasing follow-up duration as risk of bleeding was front loaded, whereas benefits in terms of reduction of cardiovascular disease events accrued throughout the treatment periods. 3 (3) A higher ARR for NCB adverse outcomes was observed in the investigated high-risk subgroups, resulting in an even lower NNT. 4 (4) Combining risk characteristics increased the ARR and increased the NCB.
How many patients were in the compass trial?
2 In brief, COMPASS was a double-blind, multicenter, randomized clinical trial that enrolled 27 395 high-risk patients with a clinical history of coronary and/or PAD, comparing ASA alone (with rivaroxaban placebo) to the combination of rivaroxaban 2.5 mg twice daily and ASA, or rivaroxaban 5 mg twice daily (with ASA placebo). The study was approved by an institutional review board at each site, and all participants gave informed consent before study procedures. The antithrombotic comparisons in the trial were stopped early after a mean follow-up of 23 months because of clear benefit of rivaroxaban 2.5 mg twice daily plus ASA over ASA alone; we therefore limited our current analysis to this trial population (n = 18 278).
What is the primary outcome of compass?
The primary efficacy outcome of COMPASS was a combination of cardiovascular death, stroke, or MI; the principal safety end point was major bleeding according to modified International Society on Thrombosis and Haemostasis (ISTH) criteria, including fatal bleeding, symptomatic bleeding into a critical organ, bleeding into a surgical site requiring reoperation, and bleeding that led to hospitalization (including presentation to an acute care facility without an overnight stay). The predefined NCB outcome, based on previous anticoagulation trials, 4, 5 was the composite of cardiovascular death, stroke, MI, fatal bleeding, or symptomatic bleeding into a critical organ (including intraarticular, intramuscular with compartment syndrome, intraspinal, intracranial, intraocular, respiratory, pericardial, liver, pancreas, retroperitoneal, adrenal gland or kidney; or bleeding into the surgical site requiring reoperation). 2
Why was the Compass trial discontinued?
The antithrombotic comparisons in the COMPASS trial were discontinued early on the advice of the data and safety monitoring board because of the finding of >4
Who supported the compass study?
The COMPASS study was supported by Bayer.
What are the advantages of NCB?
The predefined NCB offers 2 important advantages over separate assessment of efficacy and safety end points. First, it only encompasses the most severe “efficacy” and “safety” events (ie, MI, stroke, and cardiovascular death as well as fatal bleeding and symptomatic bleeding into a critical organ). As a result, NCB rates are not diluted by events of lesser severity but instead represent a selection of outcomes with serious clinical consequences. Second, the inclusion of these events into 1 composite outcome ensures that each patient is only counted once even if they have multiple events and also allows for an easy and comprehensive assessment of the overall benefit of the new treatment regimen rather than having to separately compare event rates and HRs of several different end points. Although any bleeding event may have an impact on subsequent events, “symptomatic bleeding into a critical organ” was included in the NCB because such life-threatening bleedings have been associated with a >3-fold larger increase in mortality than “major bleedings.” 9 In contrast, the increase in modified ISTH major bleeding events in COMPASS meant that the majority of those bleeding events were neither fatal nor involved bleeding into a critical organ. This conclusion is strengthened by the 18% reduction in all-cause mortality of rivaroxaban 2.5 mg twice daily plus ASA over ASA monotherapy observed in the overall trial. 2