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.

Linking the Regulatory and Reimbursement Processes for Medical Devices: The Need for Integrated Assessments

“…First of all, whilst it seems appropriate that the type of evidence required prior to approval should match the potential risk of a new device, more stringent requirements to provide clinical data for the efficacy and safety are needed for moderate‐risk to high‐risk devices. Appropriate methodological choices should be implemented in order to choose trial designs that allow to tackle specific challenges raised by the clinical evaluation of MDs (Bernard et al ., ). Linked to this is the need for international harmonisation of regulatory requirements, with efforts to set common risk classification rules.…”

Contemporary Cardiovascular Device Clinical Trials (Trends and Patterns 2001 to 2012)

“…Slow enrollment and failing to meet enrollment targets may lead to early termination of study protocols, which limits statistical power, accrues trial costs, potentially compromises scientific integrity, and jeopardizes patient trust and ethical obligations. 15 Trends toward reduced NA sites are particularly troubling as decreased site-specific clinical trial experience may preclude future device trial participation. Lack of standardized infrastructure for the routine care and management of devices may limit effective ground-level patient recruitment and surveillance.…”

Planning Clinical Trials: The Main Step in Developing New Drugs

“…These two requirements are apparently contradictory since representativeness implies a broad range of differences in the population included [7]. In fact, the selection criteria for patients must be defined to provide the best compromise.…”