Statistical and regulatory issues in nonrandomized medical device clinical studies.

While randomized, well-controlled, clinical trials have been viewed as the gold standard in the evaluation of medical products, it is not uncommon for medical device clinical studies to depart from the paradigm of randomized trials, due to ethical or practical reasons. In nonrandomized studies, the advantages of well-designed and conducted randomized clinical trials are no longer available, and consequently the statistical inference obtained from such studies may carry a lower level of scientific assurance, compared to randomized trials. This paper provides a brief overview of nonrandomized medical device clinical studies in terms of design and statistical analysis as well as regulatory issues, including some challenges that frequently arise in those endeavors.