Methodological choices for the clinical development of medical devices

Abstract

Clinical evidence available for the assessment of medical devices (MDs) is frequently insufficient. New MDs should be subjected to high quality clinical studies to demonstrate their benefit to patients. The randomized controlled trial (RCT) is the study design reaching the highest level of evidence in order to demonstrate the efficacy of a new MD. However, the clinical context of some MDs makes it difficult to carry out a conventional RCT. The objectives of this review are to present problems related to conducting conventional RCTs and to identify other experimental designs, their limitations, and their applications. A systematic literature search was conducted for the period January 2000 to July 2012 by searching medical bibliographic databases. Problems related to conducting conventional RCTs of MDs were identified: timing the assessment, eligible population and recruitment, acceptability, blinding, choice of comparator group, and learning curve. Other types of experimental designs have been described. Zelen’s design trials and randomized consent design trials facilitate the recruitment of patients, but can cause ethical problems to arise. Expertise-based RCTs involve randomization to a team that specializes in a given intervention. Sometimes, the feasibility of an expertise-based randomized trial may be greater than that of a conventional trial. Cross-over trials reduce the number of patients, but are not applicable when a learning curve is required. Sequential trials have the advantage of allowing a trial to be stopped early depending on the results of first inclusions, but they require an independent committee. Bayesian methods combine existing information with information from the ongoing trial. These methods are particularly useful in situations where the number of subjects is small. The disadvantage is the risk of including erroneous prior information. Other types of experimental designs exist when conventional trials cannot always be applied to the clinical development of MDs.

Keywords:

• medical device
• randomized controlled trials
• assessment
• clinical development

Acknowledgments

We are grateful to Catherine Denis and Michele Morin-Surocca, head of medical devices assessment department, HAS (French National Authority of Health). We are also grateful to Sophie Stamenkovic for reading this manuscript (HAS [French National Authority of Health]).

Authors’ contributions

MV contributed toward analysis and interpretation of literature; IF contributed toward the acquisitions, analysis, and interpretation of literature; HG contributed toward drafting the work and revising it; PN revised it critically for important intellectual content; JMD revised it critically for important intellectual content; AB had the original idea for this article and gave final approval of the version to be published. All authors read and approved the submitted manuscript. All authors contributed toward data analysis, drafting, and revising the manuscript.

Disclosure

The authors declare that they have no competing interests in this work.