Contemporary clinical trials
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Contemp Clin Trials · Sep 2011
Continuous safety monitoring for randomized controlled clinical trials with blinded treatment information. Part 1: Ethical considerations.
The protection of patient safety is the principal responsibility of clinical trial investigators, and must be assured even if that were to prevent successful completion of a trial. Yet, the decision to prematurely stop a blinded, randomized controlled clinical trial can be extremely complicated, involving a tangle of ethical, statistical, and practical issues. Questions are quickly answered when conclusive evidence of harm has been established for trial participants, or when the potential for harm exceeds an acceptable limit of comfort for an oversight body. ⋯ Even without early stopping, as a study proceeds, worrisome trends may lead to overzealous (or overly cautious) looks at study data which could jeopardize the integrity of the findings. Trial investigators and safety monitoring groups, aided by objective statistical rules and thoughtful deliberations, share responsibility for patient welfare. Statistical guidelines must not frustrate ethical concerns, but, rather, should be designed to promote the highest ethical and scientific outcomes possible, safeguarding both trial participants and the public - the ultimate beneficiaries of clinical trials.
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Contemp Clin Trials · Sep 2011
Randomized Controlled TrialRationale and design of STOP DVT study: rosuvastatin for the prevention of deep vein thrombosis in patients undergoing total knee replacement arthroplasty--a prospective randomized open-label controlled trial.
Deep vein thrombosis (DVT) frequently occurs in high-risk cardiovascular patients receiving orthopedic surgery, despite prophylactic measures for its prevention. Statins, a class of drugs used to lower cholesterol levels, have been reported to help prevent the development of DVT. ⋯ DVT remains prevalent despite the use of conventional prophylactic measures, in part because certain patients (particularly the elderly) are unable to receive preventive treatment because of a high risk of bleeding complications and co-morbidity. Statins have been shown to have beneficial effects in arterial atherothrombosis and are frequently administered to elderly patients to treat coronary artery. We hypothesize that peri-operative statin treatment may be beneficial in those patients restricted from the conventional prophylaxis for DVT.
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Contemp Clin Trials · Sep 2011
Continuous safety monitoring for randomized controlled clinical trials with blinded treatment information. Part 4: One method.
Standard methods for testing safety data are needed to ensure the safe conduct of clinical trials. In particular, objective rules for reliably identifying unsafe treatments need to be put into place to help protect patients from unnecessary harm. DMCs are uniquely qualified to evaluate accumulating unblinded data and make recommendations about the continuing safe conduct of a trial. ⋯ Close collaboration between the statistician and the clinical investigators will be needed in order to design safety screens with good operating characteristics. Though the math underlying this procedure may be computationally intensive, implementation of the statistical rules will be easy and the continuous screening provided will give suitabley early warning when real problems were to emerge. Trial investigators and trial leadership need these safety screens to help them to effectively monitor the ongoing safe conduct of clinical trials with blinded data.
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Contemp Clin Trials · Sep 2011
Continuous safety monitoring for randomized controlled clinical trials with blinded treatment information. Part 2: Statistical considerations.
If the primary objective of a trial is to learn about the ability of a new treatment to help future patients without sacrificing the safe and effective treatment of the current patients, then a Bayesian design with frequent assessments of the accumulating data should be considered. Unfortunately, Bayesian analyses typically do not have standard approaches, and because of the subjectivity of prior probabilities and the possibility for introducing bias, statisticians have developed other methods for statistical inference that only depend on deductive probabilities. However, these frequentist probabilities are just theories about how certain relative frequencies will develop over time. ⋯ Monitoring clinical trials is a dynamic process which requires flexibility to respond to unforeseen developments. Likelihood ratios allow the data to speak for themselves, without regard for the probability of observing weak or misleading evidence, and decisions to stop, or continue, a trial can be made at any time, with all of the available information. A likelihood based method is needed.