Lloyd Fisher | PubMed Health

PubMed2005

Statistical consideration of the strategy for demonstrating clinical evidence of effectiveness--one larger vs two smaller pivotal studies.

As a regulatory strategy, it is nowadays not uncommon to conduct one confirmatory pivotal clinical trial, instead of two, to demonstrate efficacy and safety in drug development. This paper is intended to investigate the statistical foundation of such an approach. The one-study approach is compared with the conventional two-study approach in terms of power, type-I error, and fundamental statistical assumptions. Necessary requirements for a single-study model is provided in order to maintain equivalent evidence as that from a two-study model. In general, one-study model is valid only under a 'one population' assumption. In addition, higher data quality and more convincing and robust results need to be demonstrated in such cases. However, when 'one-population' assumption is valid and appropriate methods are selected, a one-study model can have a better power using the same sample size. The paper also investigates statistical assumptions and methods for making an overall inference when a two-study model has been used. The methods for integrated analysis are evaluated. It is important for statisticians to select correct pooling strategy based on the project objective and statistical hypothesis.

Clinical Trials, Phase III as Topic↗

PubMed2002

Surrogate end points in heart failure.

Because of the increasing number of pharmacologic strategies available for treatment of heart failure (HF), the time has come to reassess the adequacy of end points used to evaluate therapeutic efficacy. Interest in the use of surrogate end points in clinical studies is increasing. A surrogate end point is defined as a measurement that can substitute for a true end point for the purpose of comparing specific interventions or treatments in a clinical trial. A true end point is one that is of clinical importance to the patient (e.g., mortality or quality of life), whereas a surrogate end point is one biologically closer to the disease process (e.g., ejection fraction or left ventricular volume in HF). The prime motivation for the use of a surrogate end point concerns the possible reduction in sample size or trial duration. Such reductions have important cost implications and in some cases may influence trial feasibility. Another, perhaps more important, aspect of measuring surrogate end points is that they increase our understanding of the mechanism of action of drugs and thus may help physicians to take a more enlightened approach in managing their patients. In this article we have analyzed the possible potentials of the surrogate end points in clinical studies of patients with chronic HF. Other uses of possible surrogates are discussed, and the limitations in finding true surrogates are mentioned. At this time we conclude there is no well established surrogate in HF.

Biomarkers↗