Lessons Learned From a Clinical Trial

Armstrong, Paul W.; Newby, L. Kristin; Granger, Christopher B.; Lee, Kerry L.; Simes, R. J.; Werf, Frans Van de; White, Harvey D.; Califf, Robert M.

doi:10.1161/01.cir.0000148680.83392.50

Cited by 10 publications

(3 citation statements)

References 34 publications

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“…Clinical trials have played a pivotal role in identifying new treatments, refining therapeutic strategies, and forming the evidence base for the development of clinical practice guidelines [1,2]. Clinical trials also help advance our understanding of underlying disease mechanisms and processes and often serve as the final "proof of concept" for hypotheses regarding potentially modifiable risk factors.…”

Section: Introductionmentioning

confidence: 99%

“…One requirement of the CTSAs is the development of community partnerships to increase the number of participants in trials. While historically the majority of trial participants in the United States have come from academic centers, an increasing proportion of participants are now enrolled by community-based practices [1,12,16]. Numerous current community-based healthcare delivery systems have large populations of ethnically diverse enrollees who are followed for long periods of time, and employ many experienced researchers [17].…”

Section: Introductionmentioning

confidence: 99%

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Cardiology clinical trial participation in community-based healthcare systems: Obstacles and opportunities

Somkin

Altschuler

Ackerson

et al. 2008

Contemporary Clinical Trials

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Background-The objective of our study was to examine cardiologists' and organizational leaders' interest in clinical trial participation and perceived barriers and facilitators to participation within ten diverse non-profit healthcare delivery systems. Trials play a pivotal role in advancing knowledge about the safety and efficacy of cardiovascular interventions and tests. Although cardiovascular trials successfully enroll patients, recruitment challenges persist. Community-based health systems could be an important source of participants and investigators, but little is known about community cardiologists' experiences with trials.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cardiology clinical trial participation in community-based healthcare systems: Obstacles and opportunities

Somkin

Altschuler

Ackerson

et al. 2008

Contemporary Clinical Trials

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“…Cardiology has improved outcomes through well-designed, large RCTs and emphasizes a model of cooperation between academia and industry [ 28 ]. Cardiology RCTs adjusted design from lessons learned from earlier missteps.…”

Section: Discussionmentioning

confidence: 99%

Trials in adult critical care that show increased mortality of the new intervention: Inevitable or preventable mishaps?

Russell

Williams

2016

Ann. Intensive Care

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Several promising therapies assessed in the adult critically ill in large, multicenter randomized controlled trials (RCTs) were associated with significantly increased mortality in the intervention arms. Our hypothesis was that there would be wide ranges in sponsorship (industry or not), type(s) of intervention(s), use of DSMBs, presence of interim analyses and early stopping rules, absolute risk increase (ARI), and whether or not adequate prior proof-of-principle Phase II studies were done of RCTs that found increased mortality rates of the intervention compared to control groups. We reviewed RCTs that showed a statistically significant increased mortality rate in the intervention compared to control group(s). We recorded source of sponsorship, sample sizes, types of interventions, mortality rates, ARI (as well as odds ratios, relative risks and number needed to harm), whether there were pre-specified interim analyses and early stopping rules, and whether or not there were prior proof-of-principle (also known as Phase II) RCTs. Ten RCTs (four industry sponsored) of many interventions (high oxygen delivery, diaspirin cross-linked hemoglobin, growth hormone, methylprednisolone, hetastarch, high-frequency oscillation ventilation, intensive insulin, NOS inhibition, and beta-2 adrenergic agonist, TNF-α receptor) included 19,126 patients and were associated with wide ranges of intervention versus control group mortality rates (25.7–59 %, mean 29.9 vs 17–49 %, mean 25 %, respectively) yielding ARIs of 2.6–29 % (mean 5 %). All but two RCTs had pre-specified interim analyses, and seven RCTs were stopped early. All RCTs were preceded by published proof-of-principle RCT(s), two by the same group. Seven interventions (except diaspirin cross-linked hemoglobin and the NOS inhibitor) were available for use clinically at the time of the pivotal RCT. Common, clinically available interventions used in the critically ill were associated with increased mortality in large, pivotal RCTs even though safety was often addressed by interim analyses and early stopping rules.

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