The Food and Drug Administration (FDA) Center for Devices and Radiological Health (CDRH) has issued its first report on patient reported outcomes (PRO) in premarket submissions and post market studies of medical devices . The report outlines the many steps that are being implemented by the FDA to meet the significant increase in PRO data being submitted by medical device manufacturers, with more than 75% of approved investigational device exemptions in 2017 including a PRO measure.
As part of their 2016-2017 strategic priorities, the CDHR made a commitment to partner with patients. One way this has been achieved is by incorporating the patient perspective as evidence in their decisions, including both patient preference information (PPI) and PRO data. PRO measures can be used in medical device regulatory submissions to measure patients’ experience with the device. The CDRH is actively working in this area to increase appropriate use of PRO measures and improve the impact of PRO data as evidence in regulatory decisions and beyond.
PRO data is just as important for use in medical device trials as it is in clinical trials for drugs. As with their use in drug products, PRO measures can capture a patient’s everyday experience with a medical device that often cannot be captured via other measures. Combined with clinical assessments, PRO data can therefore provide a fuller picture of a patient’s symptoms, functioning, and quality of life. Utilising PRO data can also aid in assessing effectiveness outcomes and collecting adverse event data, potentially leading to fewer clinical visits within a trial as patients can report symptoms and events outside of the clinical setting.
High quality information from PRO measures can be used for regulatory purposes, providing valuable evidence for benefit-risk assessments, and information can be used in medical device labelling to communicate the effect of a device on patient symptoms, functioning and quality of life. The CDRH has observed an increase in the use of PROs for regulatory purposes over the last few years (>500% increase in the number of pre-market submissions that include PRO measures over a 6-year period).
Figure 1: Number of submissions including PRO measures for calendar years 2000 – 20151Although developing new PRO measures and utilising existing measures has been encouraged by patient groups, health care community, professional societies and regulatory bodies, the increase in use has been initiated by study sponsors, rather than any advice or initiatives coming from the CDRH, showing the growing interest in PRO data in devices.
Beyond regulatory uses, evidence from PRO measures are useful for decision-makers in the pathway to market, including insurers and health care systems, as part of a value-based framework assessment.
The CDHR recognise that there are still challenges with PRO data and in the report highlight the need to work with sponsors to overcome the following potential barriers:
- The need for training on appropriate, predictable, and least-burdensome use of PRO measures
- The need for increased transparency regarding use of PRO data in regulatory decisions
- The need for additional scientific expertise and capacity for submission review and early consultation and advice during study planning, and qualification of new PRO measures
- Sponsor uncertainty in PRO review policies, such as level of validation required when PRO measures are used for different purposes (e.g. another condition)
The FDA recently launched the Medical Device Development Tool (MDDT) Program which aims to assist sponsors with effective incorporation of PROs as well as other assessment tools into device clinical trials2 . The CDHR state they support and encourage the submission of PRO measures to the MDDT, which aims to evaluate a tool within the selected context of use. Once a tool is qualified by the MDDT, FDA review staff can accept the use of the tool without the need to reconfirm suitability and utility of the tool each time it is used (assuming it is used in the same context); the first PRO measure to be qualified under this program was the Kansas City Cardiomyopathy Questionnaire (KCCQ) on October 19, 2017.The report also states that the CDRH encourages sponsors to engage with them and discuss the use of PRO measures as endpoints pre-submission, which is the recommended point at which to consider including a PRO within a clinical study design. By engaging in early discussions with sponsors, the CDRH aims to facilitate a patient-centric device evaluation approach while reducing the burden of late incorporation in trials. These early interactions between the sponsor and the review division can lead to mutual decision making in determining the most appropriate PRO measure(s) to include for the clinical endpoint of interest, which may make the actual review a smoother and less arduous process.Based on the work that the CDRH has undertaken over the past year, the report states that the Center are keen to continue their work to integrate PRO data in device trials and submissions. Several initiatives have therefore been developed by the Center to help sponsors. These include case studies PRO data capture in different studies (including examples in weight loss devices, orthopaedic devices, and cardiovascular devices). Additionally, the PRO Compendium has been updated to a list of some of the PROs that have been used and reported in medical device pre-market clinical studies submitted to CDRH.
Although including PRO measures in most clinical studies remains voluntary, the release of this report by the CDRH is another step towards highlighting the importance of collecting patient reported data in clinical trials. If you require assistance with selecting, developing, or incorporating PRO measures (or any other clinical outcome assessment measure) into your drug or device trial programme, get in touch with our specialist clinical outcome assessment team at Access@TeamDRG.com.
1Value and Use of Patient-Reported Outcomes (PROs) in Assessing Effects of Medical Devices. CDRH Strategic Priorities 2016-2017. Available from:
2Medical Device Development Tools (MDDT).