Publication of Clinical Trials in JAMA

Fontanarosa, Phil B.; DeAngelis, Catherine D.

doi:10.1001/jama.2007.28

Cited by 7 publications

(5 citation statements)

References 10 publications

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“…Analysis by an independent academic statistician is an important additional protection. 4 Direct comparisons between the original protocol of the study design and the final description of the study conduct, although perhaps burdensome to reviewers and editors, are also likely to improve the accuracy and the completeness of the reporting of important clinical trials.…”

Section: P<001mentioning

confidence: 99%

“…3 In an effort to improve reporting, JAMA has implemented a policy requiring that an academic statistician conduct the data analysis for all randomized trials. 4 Another approach involves direct comparisons, when available, between study plans in design papers and study conduct in final publications. Even these methods may fail to identify irregularities in the representation of data from clinical trials.…”

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confidence: 99%

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Reporting Mortality Findings in Trials of Rofecoxib for Alzheimer Disease or Cognitive Impairment

Psaty

Kronmal

2008

JAMA

160

101

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Section: P<001mentioning

confidence: 99%

mentioning

confidence: 99%

Reporting Mortality Findings in Trials of Rofecoxib for Alzheimer Disease or Cognitive Impairment

Psaty

Kronmal

2008

JAMA

160

101

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“…Although there was a reduction in mortality with IIT, the difference did not reach the traditionally accepted level of statistical significance in the intention-to-treat analysis. The intention-to-treat analysis is always the most relevant result for any randomized controlled trial as it represents the effect of the treatment in all the patients studied [ 47 ], and the likely outcome if others use the treatment in similar populations of patients. Although the authors reported reduced mortality in patients who stayed in the ICU for three days or more, these patients could not be identified at the time treatment was started and so clinicians can not know to which of their patients this result might apply.…”

Section: Con: Intensive Insulin Therapy Targeting Tight Blood Glucosementioning

confidence: 99%

Pro/con debate: Is intensive insulin therapy targeting tight blood glucose control of benefit in critically ill patients?

Merz

Finfer

2008

Critical Care

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You have decided to develop a protocol for insulin therapy in your intensive care unit (ICU). You wonder about the merit of using intensive insulin therapy (IIT) to maintain tight blood glucose control in your patients. Pro: Intensive insulin therapy targeting tight blood glucose control is of benefit in critically ill patientsHyperglycaemia is a common accompaniment of acute illness. In published trials insulin treatment was required in more than 98% of ICU patients in whom the goal was to maintain normoglycaemia [1][2][3]. The hyperglycaemia is thought to result from a number of processes; elevated levels of cortisol, epinephrine, norepinephrine and glucagon increase gluconeogenesis [4][5][6][7][8] and glycogenolysis [9] whilst insulin resistance leads to a decrease in insulin-stimulated uptake of glucose in heart and adipose tissue. In addition, exercise induced uptake of glucose in skeletal muscle is absent in immobilized critically ill patients [10,11]. Hyperglycaemia may cause harm by direct toxicity and through increased intracellular oxidative stress due to higher mitochondrial peroxide production [12,13]. The clinical consequence of hyperglycaemia appears to be an increase in morbidity and mortality in a variety of clinical settings, including heterogeneous populations of critically ill patients [14]. In trauma patients hyperglycaemia is associated with higher mortality and an increased rate of infectious complications [15] as well as with worse neurological outcome in the subset of patients with traumatic brain injury [16]. In patients with sepsis and haematological malignancy, hyperglycaemia at hospital admission predicts higher mortality [17,18]. Hyperglycaemia has also been associated with higher mortality and poor functional recovery in non-diabetic stroke patients [19], and with increased risk of in-hospital mortality, congestive heart failure and cardiogenic shock after myocardial infarction [20]. In summary, hyperglycaemia is common in critically ill patients and its occurrence is clearly associated with a worse outcome; thus, it is natural to ask whether hyperglycaemia is simply a marker of illness severity, or is hyperglycaemia itself harmful, in which case does normalizing blood glucose improve patients' outcomes?The evidence that short-term treatment of hyperglycaemia is beneficial in acute illness is consistent across a number of populations of patients. Insulin treatment targeting a lower blood glucose concentration significantly reduces long term mortality following myocardial infarction [21], and lowers the risk of cardiovascular disease and cardiovascular events in patients with type I diabetes [22]. A meta-analysis evaluating 35 randomized controlled trials (RCTs) of insulin therapy in critically ill hospitalized patients found a beneficial effect of insulin therapy on mortality; the benefit was limited to trials in which insulin was administered with the goal of achieving a particular blood glucose target [23].Although the majority of studies included in the meta-analysis we...

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“…The use of “evaluable” patients in an analysis rather than the preferred intention-to-treat analysis (5) may lead to bias. In a meta-analysis of antibiotic trials comparing fluoroquinolones with other antibiotics in community-acquired pneumonia (6), Salkind and colleagues reported the results for both evaluable patients (odds ratio [OR] = 1.37; 95% CI = 1.11 to 1.68) and intention-to-treat analysis (OR = 1.22; 95% CI = 1.02 to 1.47).…”

Section: Evaluations Of Efficacymentioning

confidence: 99%

Clinical Trial Design and Selected Drug Safety Issues for Antibiotics Used to Treat Community‐Acquired Pneumonia

Psaty

2008

CLIN INFECT DIS

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High-quality evaluations of both efficacy and safety are essential to characterize the risk-benefit profile of antibiotics. The current US Food and Drug Administration guidelines on trial design for community-acquired pneumonia have several weaknesses, including the failure to insist on the use of double blinding and intention-to-treat analysis. A primary difficulty with noninferiority designs is that poorly conducted studies, which increase noise, are biased toward the conclusion of noninferiority even in the presence of important differences between the test drug and the control drug. Additionally, results of noninferiority trials, in the absence of a well-established anchor, may be difficult to interpret. The US Food and Drug Administration drug-evaluation process includes preclinical studies to assess toxicity and a series of clinical studies involving humans to define efficacy and to identify potential safety problems. When signals are apparent, as they were for telithromycin (liver toxicity in rats, dogs, and monkeys) or for sparfloxacin (prolongation of the QT interval in dogs), it is nonetheless essential that these signals are fully and fairly evaluated in human studies with adequate power. Risks of antibiotic use, such as prolongation of the corrected QT interval and sudden death, may be acceptable in the presence of convincing benefits for patients with severe, life-threatening infections; however, the risk-benefit profile derived from severe infections cannot necessarily be generalized to mild or self-limited infections, for which the same serious drug-associated risks are likely to exceed the benefits. Complete and proper evaluation of both safety and efficacy in specific situations is essential to define the risk-benefit profiles of all drugs, including antibiotics.

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Publication of Clinical Trials in JAMA

Cited by 7 publications

References 10 publications

Reporting Mortality Findings in Trials of Rofecoxib for Alzheimer Disease or Cognitive Impairment

Reporting Mortality Findings in Trials of Rofecoxib for Alzheimer Disease or Cognitive Impairment

Pro/con debate: Is intensive insulin therapy targeting tight blood glucose control of benefit in critically ill patients?

Clinical Trial Design and Selected Drug Safety Issues for Antibiotics Used to Treat Community‐Acquired Pneumonia

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