Clinical Evaluation Reports – An Expanding Global Requirement

Regulators globally are increasing their expectations for clinical evaluation of medical devices. Tougher requirements, particularly for higher risk devices and implantables, are the result. In 2016, the European Union released updated guidance for Clinical Evaluation Reports (MEDDEV 2.7.1 Rev. 4, June 2016) entitled, Clinical Evaluation: A Guide for Manufacturers and Notified Bodies Under Directives 93/42/EEC and 90/385/EEC. The Guidance document outlines how to conduct a clinical evaluation report (CER), including demonstrating scientific validity. Requirements for post-market surveillance and clinical follow-up are also outlined. The CER must be updated to reflect post-market surveillance and other findings that could influence the CER’s conclusions. Updates must be submitted at an interval consistent with risk and to acknowledge design changes or important findings in a timely fashion.

What is a Clinical Evaluation Report (CER)?

A CER includes an analysis of clinical data collected from clinical investigation of a manufacturers’ device, or the results of evaluation of equivalent devices. The CER’s purpose is to demonstrate adequate clinical performance and clinical safety of the device.

CERs are a requirement for all medical devices in Europe. Manufacturers must submit a CER to the Notified Body as an attachment to a European CE Technical File. The CE Mark is required to sell or distribute medical devices in Europe. However, not only Europe requires a CER. All medical devices supplied in Australia must have clinical evidence sufficient to demonstrate an appropriate level of safety and performance. Canada requires clinical evaluation as well. Clinical Evaluation Reports are increasingly a global standard.
Clinical Evidence Report = Device Related Clinical Data + Expert Review and Analysis

Information required for a CER must come from sources including:

  • Published clinical literature
  • Manufacturer’s (unpublished) clinical reports and data
  • Post-market safety surveillance
  • Clinical registries
  • Post-market databases such as Food and Drug Administration’s (FDA) Manufacturer and User Facility Device Experience (MAUDE) in the US and National Competent Authority Reports (NCARs) in the EU and the Therapeutic Goods Administration (TGA) in Australia.
  • Analysis of other publicly available sources of alerts, recalls and other relevant information.

Literature-based evaluations require a pre-defined search strategy that is objective and non-biased. Minimum expectations for a clinical literature review should include:

  • Databases defined in advance and justified for applicability and relevance to the device and the region, especially relevant European journals and publications.
  • Search methods and process adhere to a structured framework
  • Terms used for searching the database(s) defined in advance and justified for relevance and completeness
  • Exclusion/inclusion criteria for identification of publications defined in advance and justified

Real World Evidence (RWE)

Many of the data sources required as input into CERs come from the realm of real world data (RWD). Sources of RWD, often defined as patient care related data generated outside of a formal research setting, have grown exponentially over the last decades. RWD sources may include, but are not limited to: electronic health records, pharmacy and payer databases, social media, patient powered research networks, and data derived from wearables, implantables, and home health monitoring devices. Real world evidence (RWE) is generated from analysis of RWD. RWD obtained through registries, post-market safety surveillance, and post-market databases are critical elements defined in a CER.

What About the “Expert Review”?

A very important consideration is the expertise of the CER author(s). Section 6.4 of the Guidance specifically states requirements regarding qualifications for individuals conducting clinical evaluation. Knowledge of regulatory requirements, research methodologies, medical writing, and information management is required. CER authors should have a degree in a relevant field, plus 5 years of relevant professional experience or, absent a degree, 10 years of relevant experience. Manufacturers need to justify personnel choices through CVs and declarations of interest from each individual.

How Exponent Can Help

Exponent’s experience with global regulators, product development, performance and process monitoring, and critical evaluation of clinical and scientific data can help clients in the development of regulatory submission-ready comprehensive CERs. Our broad experience with public and commercial claims and medical records databases, registries, and surveillance data make us particularly qualified to address questions of data quality and appropriateness.

With our team of scientists, engineers, and biostatisticians, Exponent works with clients to develop structured research approaches, and identify and analyze data that have both the quantity and quality of information to address regulatory questions. Not only do we consider validity of a data source, but we can also review other uses of similar data to recommend insights into perceived value by target audience. Exponent works with clients to communicate results to the target audience. Our team has relevant experience in preparing, explaining, and presenting findings to regulators, as well as presenting in public forums and publishing in peer-reviewed journals.