Surrogate Sample Framework

What is the issue?

Currently, the speed at which innovative and improved diagnostics are developed can be hampered by the difficulty in obtaining clinical specimens. This may be due to a variety of reasons, such as rare markers, lack of specimens with markers at the high or low end of the range, specimen stability, the difficulty in obtaining certain specimens due to clinical practice, or patient care taking precedence over the ability to collect specimens under defined conditions. The use of surrogate samples can foster innovation when clinical specimens are difficult to obtain.

The efficiency, predictability, and cost of in vitro diagnostic (IVD) development directly impacts timely patient access to IVDs. The collection of human specimens for testing is a central aspect of IVD validation. When unable to obtain a sufficient number or volume of appropriately characterized patient samples to validate IVD performance, surrogate samples provide a path to efficient validation. In vitro diagnostic device (IVD) validation studies are most efficient when both developers and government approvers are aligned on study design and data expectations. In the absence of alignment, there is the risk of costly repeat of expensive and time-consuming studies, longer development timelines, and inefficient use of biological test materials.

The use of surrogate samples as an element of IVD validation studies is not new. A review of historical data, knowledge, and experience of IVD developers demonstrates surrogate samples play an important role in the validation of IVDs[1]. However, the lack of commonly agreed to terminology and defined experimental framework regarding the use of surrogate samples in IVD performance studies reduces the predictability, timeliness, and efficiency of IVD development, thus increasing cost and reducing patient access to new and innovative medical devices.

What is the goal of this project?

MDIC and its partners collaborated to create the Surrogate Sample Framework. The Framework proposes uniform terminology and recommendations where surrogate samples might be justifiably used in IVD validation studies. Ultimately, the goal of the Surrogate Sample Framework is to improve IVD innovation, reduce inefficient use of costly biological test materials, and ultimately improve timely patient access to safe and effective IVDs.

The framework aligns stakeholders as to the preferred surrogate sample selection by IVD performance study as well as definitions and terminology of surrogate samples and related terms.

What has the project produced so far?

A Surrogate Sample Framework addresses these discrepancies to promote more efficient study design and reduce inefficient use of biological test materials by:

  • Creating a uniform definition of surrogate sample supplemented with a diverse array of examples
  • Outlining general principles and considerations when designing and selecting surrogate samples
  • Presenting a hierarchy to aid in the selection and design of surrogate samples
  • Establishing study specific principles accompanied by a hierarchy for each study type

Download the framework here

A survey was conducted providing an analysis of real world examples of the use of surrogate samples to document established uses of surrogate samples to verify or validate the safety and effectiveness of an IVD medical device.

[1] See Survey Report at www.mdic.org/clinicaldx/survey/ and Submission Analysis Report at www.mdic.org/mdicx/#archive