Data Monitoring in Clinical Trials or Oracle Wait Interface

Data Monitoring in Clinical Trials

Author: David L Demets

Randomized clinical trials are the gold standard for establishing many clinical practice guidelines and are central to evidence based medicine. Obtaining the best evidence through clinical trials must be done within the boundaries of rigorous science and ethical principles. One fundamental principle is that trials should not continue longer than necessary to reach their objectives. Therefore, trials must be monitored for recruitment progress, quality of data, adherence to patient care or prevention standards, and early evidence of benefit or harm. Frequently, a group of external experts, independent from the investigators and trial sponsor, is charged with this monitoring responsibility, especially for safety and early benefit. This group is referred to by various names, such as a data monitoring committee or a data and safety monitoring board. This book, through a series of case studies presented by many distinguished clinical trial experts, illustrates the complexity of this monitoring process. The editors provide an overview of the process and a summary of a multitude of the lessons learned from the cases presented.

This book should be useful to anyone serving on a data and safety monitoring board, or planning to do so, for colleagues in academia, industry and governmental agencies, and for teaching students in biostatistics, epidemiology, clinical trials and medical ethics. No other text has as extensive a collection of cases which provide insight into the many issues, often conflicting, that must be examined before recommendations to continue or discontinue a trial can be made. While depth in statistical methods is not required, some familiarity with statistical design andanalysis issues in clinical trials is helpful. The cases cover trials which were terminated early for convincing evidence of benefit, or for harmful effects. Cases with complex issues are also included. This series of cases should provide broad background information for potential monitoring committee members and better prepare them for the challenges that may exist in the trials for which they are responsible.

Table of Contents:

1	Monitoring committees : why and how	3
2	Lessons learned	14
3	FDA and clinical trial data monitoring committees	39
	Introduction to case studies showing benefit from the intervention	53
	Assessing possible late treatment effects early : the diabetic retinopathy study experience	55
	Data and safety monitoring in the beta-blocker heart attack trial : early experience in formal monitoring methods	64
	Data monitoring for the aspirin component of the physicians' health study : issues in early termination for a major secondary endpoint	73
	Early termination of the stroke prevention in atrial fibrillation I trial : protecting participant interests in the face of scientific uncertainties and the cruel play of chance	85
	Early termination of the diabetes control and complications trial	93
	Data monitoring in the AIDS clinical trials group study #981 : conflicting interim results	109
	Challenges in monitoring the breast cancer prevention trial	118
	Data monitoring experience in the metoprolol CR/XL randomized intervention trial in chronic heart failure : potentially high-risk treatment in high-risk patients	136
	Stopping the randomized aldactone evaluation study early for efficacy	148
	Data monitoring in the heart outcomes prevention evaluation and the clopidogrel in unstable angina to prevent recurrent ischemic events trials : avoiding important information loss	158
	The data monitoring experience in the candesartan in heart failure assessment of reduction in mortality and morbidity program	166
	Introduction to case studies showing harmful effects of the intervention	179
	Breaking new ground : data monitoring in the coronary drug project	183
	The data monitoring experience in the cardiac arrhythmia suppression trial : the need to be prepared early	198
	Data monitoring in the prospective randomized milrinone survival evaluation : dealing with an agonizing trend	209
	Stopping the carotene and retinol efficacy trial : the viewpoint of the safety and endpoint monitoring committee	220
	Monitoring a clinical trial with waiver of informed consent : diaspirin cross-linked hemoglobin for emergency treatment of post-traumatic shock	228
	Consideration of early stopping and other challenges in monitoring the heart and estrogen/progestin replacement study	236
	Data monitoring in the antihypertensive and lipid-lowering treatment to prevent heart attack trial : early termination of the doxazosin treatment arm	248
	Data monitoring experience in the moxonidine congestive heart failure trial	260
	Data monitoring of a placebo-controlled trial of daclizumab in acute graft-versus-host disease	269
	Introduction to case studies with special issues	281
	Clinical trials of herpes simplex encephalitis : the role of the data monitoring committee	285
	The nocturnal oxygen therapy trial data monitoring experience : problem with reporting lags	292
	Stopping a trial for futility : the cooperative new Scandinavian enalapril survival study II	302
	Lessons from warfarin trials in atrial fibrillation : missing the window of opportunity	312
	Data monitoring experience in the AIDS toxoplasmic encephalitis study	320
	Data monitoring in the randomized evaluation of strategies for left ventricular dysfunction pilot study : when reasonable people disagree	330
	The data monitoring experience in the carvedilol post-infarct survival control in left ventricular dysfunction study : hazards of changing primary outcomes	337
	Controversies in the early reporting of a clinical trial in early breast cancer	346
	Making independence work : monitoring the bevacizumab colorectal cancer clinical trial	360

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Oracle Wait Interface: A Practical Guide to Performance Diagnostics and Tuning

Author: Richmond She

Troubleshoot, tune, and optimize your Oracle database efficiently and successfully every time. This book explains how to take full advantage of the revolutionary Oracle Wait Interface to quickly pinpoint--and solve--core problems and bottlenecks, and increase productivity exponentially.