Statistical Appraisal of 6 Recent Clinical Trials in Cardiology: JACC State-of-the-Art Review.

In the past 12 months, many important new clinical trials in cardiology have had their first conference presentation and publication. This paper presents a constructive critical appraisal of 6 key studies. In time order of first presentation, they are CABANA, ATTR-ACT, COAPT, DECLARE, REDUCE-IT, and AUGUSTUS. For each study, the aim herein is to document and interpret the main findings, paying attention to new findings, their research context, and study limitations. These topical examples also provide methodological insights pertinent to future clinical trials research

Challenging Issues in Clinical Trial Design: Part 4 of a 4-Part Series on Statistics for Clinical Trials.

As a sequel to last week's paper on the fundamentals of clinical trial design, this paper tackles related controversial issues: noninferiority trials, the value of factorial designs, the importance and challenges of strategy trials, Data Monitoring Committees (including when to stop a trial early), and the role of adaptive designs. All topics are illustrated by relevant examples from cardiology trials

Design of Major Randomized Trials: Part 3 of a 4-Part Series on Statistics for Clinical Trials.

This paper provides practical guidance on the fundamentals of design for major randomized controlled trials. Topics covered include the choice of patients, choice of treatment and control groups, choice of primary and secondary endpoints, methods of randomization, appropriate use of blinding, and determination of trial size. Insights are made with reference to contemporary major trials in cardiology

Categorisation of continuous risk factors in epidemiological publications: a survey of current practice

BACKGROUND: Reports of observational epidemiological studies often categorise (group) continuous risk factor (exposure) variables. However, there has been little systematic assessment of how categorisation is practiced or reported in the literature and no extended guidelines for the practice have been identified. Thus, we assessed the nature of such practice in the epidemiological literature. Two months (December 2007 and January 2008) of five epidemiological and five general medical journals were reviewed. All articles that examined the relationship between continuous risk factors and health outcomes were surveyed using a standard proforma, with the focus on the primary risk factor. Using the survey results we provide illustrative examples and, combined with ideas from the broader literature and from experience, we offer guidelines for good practice. RESULTS: Of the 254 articles reviewed, 58 were included in our survey. Categorisation occurred in 50 (86%) of them. Of those, 42% also analysed the variable continuously and 24% considered alternative groupings. Most (78%) used 3 to 5 groups. No articles relied solely on dichotomisation, although it did feature prominently in 3 articles. The choice of group boundaries varied: 34% used quantiles, 18% equally spaced categories, 12% external criteria, 34% other approaches and 2% did not describe the approach used. Categorical risk estimates were most commonly (66%) presented as pairwise comparisons to a reference group, usually the highest or lowest (79%). Reporting of categorical analysis was mostly in tables; only 20% in figures. CONCLUSIONS: Categorical analyses of continuous risk factors are common. Accordingly, we provide recommendations for good practice. Key issues include pre-defining appropriate choice of groupings and analysis strategies, clear presentation of grouped findings in tables and figures, and drawing valid conclusions from categorical analyses, avoiding injudicious use of multiple alternative analyses

Long-Term Use of Cardiovascular Drugs Challenges for Research and for Patient Care

AbstractLittle is known about the benefits and risks of the long-term use of cardiovascular drugs. Evidence from randomized clinical trials (RCTs) rarely goes beyond a few years of follow-up, but patients are often given continuous treatment with multiple drugs well into old age. We focus on 4 commonly used cardiovascular drug classes: aspirin, statins, beta-blockers, and angiotensin-converting enzyme inhibitors given to patients after myocardial infarction. However, the issues raised apply more broadly to all long-term medications across cardiovascular diseases and the whole of medicine. The evidence and limitations of RCTs are addressed, as well as current practice in pre-licensing trials, the increasing problems of polypharmacy (especially in the elderly), the lack of trial evidence for withdrawal of drugs, the role of regulatory authorities and other stakeholders in this challenging situation, and the potential educational solutions for the medical profession. We conclude with a set of recommendations on how to improve the situation of long-term drug use

Critical Appraisal of the 2018 ACC Scientific Sessions Late-Breaking Trials From a Statistician's Perspective.

The late-breaking clinical trials presentations at the American College of Cardiology Scientific Sessions in March 2018 are an important contribution to the field of cardiology. This paper presents a constructive critical appraisal of 7 key studies: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), VEST (Vest Prevention of Early Sudden Death Trial), SECURE-PCI (Statins Evaluation in Coronary Procedures and Revascularization), TREAT (Ticagrelor in Patients with ST-Elevation Myocardial Infarction treated with Pharmacological Thrombolysis), POISE (PeriOperative ISchemic Evaluation), SMART-DATE (Safety of 6-Month Duration of Dual Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome), and CVD-REAL 2 (Comparative Effectiveness of Cardiovascular Outcomes in New Users of SGLT-2 Inhibitors). For each study, our aim is to document and interpret the main findings, noting particularly when "positive spin" appears to occur, and to provide a balanced account of each study, paying attention to both constructive new findings and study limitations. These topical examples also provide useful general insights on what to look for when critiquing clinical trial presentations and publications