The Impact of the EU Medical Device Regulation on Clinical Data Requirements
By Beata Wilkinson, Medical Director, Cactus Communications
In May 2017, the EU Medical Device Regulation (MDR) entered into force and, on May 26th, 2020, will apply directly to all the Member States. This regulation is bringing numerous changes, mandating that manufacturers prepare to meet the new requirements in time. In particular, manufacturers must prepare for the transition to MDR’s greater clinical evidence requirements.
"Manufacturers must consider the full range of possible beneficial impacts and effects of their device, based on the understanding of the market, the state of the art and parents’ unmet needs"
Clinical evaluation will need to be performed on all medical devices destined for the EU market. MDR defines clinical evaluation as: “a systematic and planned process to continuously generate, collect, analyse and assess the clinical data pertaining to a device in order to verify the safety and performance, including clinical benefits, of the device when used as intended by the manufacturer”. Clinical evaluation will be conducted with the aim of collecting, appraising and analysing all relevant clinical data. The clinical evaluation, its results, and the clinical evidence derived from it will be documented in a clinical evaluation report (CER).
The main sources of clinical data will be clinical investigation(s), reports published in peer-reviewed scientific literature, other clinical experience, and post-market surveillance, in particular post market clinical follow-up (PMCF). While in the past, reliance on clinical data generated by equivalent devices was widespread, under MDR it will be made much more difficult as it will be necessary to either enter into a contract with the manufacturer of the equivalent device (class III and implantable devices) or ensure sufficient levels of access to the data relating to the equivalent device on an ongoing basis (other classes of devices).
The EU MEDDEV 2.7/1 Rev 4 guide on clinical evaluation introduced a recommendation for a planning stage to ensure preparation of compliant CERs. The MDR will place an even stronger emphasis on the importance of early planning. While there are certain aspects of the Clinical Evaluation Plan (CEP) that are common to both the MEDDEV guide and the MDR, there are many additional requirements in the MDR. These include (selected highlights only): a detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters; a specification of methods to be used for examination of qualitative and quantitative aspects of clinical safety; an indicative list and specification of parameters to be used to determine the acceptability of the benefit-risk ratio for the various uses of the device; and a clinical development plan indicating planned pre-market studies and a PMCF with milestones and potential acceptance criteria. Apart from being the first step in the clinical evaluation of a medical device, the documentation on the CEP is to be included in the application for the assessment of the quality management system. Applications for investigational devices are also to be accompanied by reference to the CEP.
In specifying intended clinical benefits, the manufacturers should be guided by MDR’s definition of clinical benefits: “The positive impact of a device on the health of an individual, expressed in terms of a meaningful, measurable, patient-relevant clinical outcome(s), including outcome(s) related to diagnosis, or a positive impact on patient management or public health.” Manufacturers must therefore consider the full range of possible beneficial impacts and effects of their device, based on the understanding of the market, the state of the art and parents’ unmet needs. This should begin early in the new product design and development process. In the case of devices already on the market, manufacturers will need to gain a deep understanding of the beneficial effects that arise out of the achieved performance of their devices during normal conditions of use in order to ensure the claims being made are realistic and comprehensive. This process will need to continue throughout the lifecycle of the device.
With regard to clinical investigations, the MDR specifies that the endpoints should address the intended purpose, clinical benefits, performance and safety of the device. Although a properly designed clinical investigation should yield useful and comprehensive clinical data, it will not provide insights into all the potential clinical use questions that arise once a new medical device is made widely available for patient use. Real-world observational studies can provide this clinical evidence. In particular, PMCF can confirm safety and performance, identify unknown side-effects and emerging risks, and is decisive in refining and corroborating reasonable predictions of clinical performance over time.
The MDR sets high standards of quality and safety for medical devices. While companies will need to satisfy increased clinical evidence requirements to get their products onto the EU market and keep them there, the enhanced data sets will also enable them to better understand their products, and make more informed decisions about future product development direction and requirements. A significant proportion of device companies not able to meet MDR requirements is expected to go off-market; leaving the field open for superior, probably more expensive, devices that have demonstrated clinical benefits.
With so much clinical data needing to be collected, shared, appraised and analysed, companies will need to explore new data management systems based on artificial intelligence technology and robotic process automation. With multiple systems currently in use, there is typically no single view, and no central portal to display the data. Transitioning to a cloud-based unified platform will enhance access to data, improve data-management efficiencies, and reduce costs of medical device development.
Inevitably, the MDR’s increased requirements for clinical data will strain internal resources and require up-to-date expertise. The adoption of an integrated central data platform capable of managing disparate data should take place early on in a medical device’s development program and is likely to require assistance from external experts. Outsourcing of specialised tasks in the fields of data collection, management and evaluation to experienced partners with dedicated teams of experts such as data scientists and medical writers will allow companies to effectively manage the diverse device-related data, and process clinical insights to support product safety, performance and benefits claims.