The first article provides an overview of the regulatory background for the patient-reported outcome instruments when evaluating the safety and effectiveness of medical devices, and also highlights the most important aspects to be considered in this respect.



The Food and Drug Administration (FDA or the Agency), the US regulating authority in the sphere of healthcare products, has published a guidance document dedicated to the principles for selecting, developing, modifying, and adapting patient-reported outcome instruments for use in medical device evaluation. The document is intended to provide additional clarifications and recommendations on the matter to assist medical device manufacturers and other parties involved in achieving and sustaining compliance with the applicable regulatory requirements. It is important to mention that provisions thereof are non-binding, while an alternative approach could be applied, provided such an approach is in line with existing legislation and has been agreed with the Agency in advance. The present document constitutes a final version of the guidance based on the draft pushed by the authority earlier in August 2020. 


Regulatory Background 

The authority acknowledges the importance of information and feedback that could be received from patients. As it is stated by the FDA, patient-reported outcome (PRO) instruments facilitate the systematic collection of how patients feel, function, and survive as valid scientific evidence to support the regulatory and healthcare decision-making process; by integrating patients’ voices through the total product life cycle (TPLC), concepts important to patients can be considered in the evaluation and surveillance of medical devices. 

The present guidance is intended to:

  1. Highlight the main principles used as a basis for PRO instruments;
  2. Assist in implementing PRO instruments by providing additional recommendations; and 
  3. Provide more details about best practices that could be followed to ensure the effectiveness of PRO instruments used. 

The authority additionally emphasizes that the scope of the present guidance is limited to medical devices, so it should not be construed as a replacement for the respective guidance issued by the FDA concerning Patient-Focused Drug Development. 

As further explained by the FDA, PRO instruments could be used to collect additional information that could be useful for assessing the safety and effectiveness of medical devices. Under the general rule, the use of such instruments takes place voluntarily. However, there are specific standards and guidelines to be followed by the parties using these instruments to ensure the accuracy and reliability of results. There are different ways the information can be collected: it can be provided by patients in a form of self-reports, or during an interview. Thus, these instruments are intended to collect information that could be known only to patients since it derives from their experience of interacting with the device. According to the guidance, PRO instruments can include patient diaries, visual analog and numeric rating scales (e.g., measures of pain severity), symptom measures, as well as multi-item, multidomain questionnaires measuring aspects of health-related quality of life (HRQOL). Such instruments could be used to collect additional information in the course of clinical studies. 

It is important to mention that the FDA has already issued several guidance documents dedicated to the patient-reported outcome instruments and measures. These guidance documents provide an overview of the instruments available and describe in detail the way they can be applied. Apart from this, PRO instruments are also covered by the scope of the Medical Device Development Tools framework which confirms that they can be used as one of the ways to obtain scientific evidence. 

The authority also states that the importance of considering patients’ feedback is currently increasing due to the wider use of novel technologies. The information collected by the device of PRO instruments could be useful in evaluating the actual safety and effectiveness of medical devices, benefit-risk assessment, and even in developing labeling and information contained therein (e.g., instructions for use of safety warnings). 

There is a wide range of PRO instruments that could be used at various stages of the total product life cycle, including early development stages and post-market evaluation. However, the authority also mentions that in case PRO instruments are used to collect scientific evidence to support premarket application, their use should be duly justified. 

The present guidance does not provide an exhaustive overview of existing PRO instruments, nor does it provide details on the way these instruments could be improved. Instead, the guidance outlines the key principles to be considered when deciding on the use of PRO instruments, and also describes the best practices for selecting, developing, and modifying them. 


General Considerations 

To assist medical device manufacturers and other parties involved, the Agency highlights the main principles to be considered when using PRO instruments for evaluating the safety and effectiveness of medical devices. According to the guidance, these principles include the following ones: 

  1. Establish and define the concept of interest (COI) they PRO instrument is intended to capture;
  2. Identify the role of the PRO in the clinical study protocol and statistical analysis plan;
  3. Provide evidence showing that the PRO instrument reliably assesses the COI; and
  4. Effectively and appropriately communicate the PRO-related results in the labeling to inform healthcare providers and patient decision-making. 

The authority also emphasizes the importance of ensuring the patient-reported outcome instruments are fit-for-purpose concerning the context of use (COU). To make such a determination, the following aspects should be considered:

  1. Whether the concept evaluated by the device of the PRO instrument is meaningful to patients. 
  2. What is the specific role of such an instrument in the overall evaluation process?
  3. Is there evidence supporting the use of a specific instrument in the appropriate context? 

As further explained by the FDA, the key aspect to be considered when determining the applicability of the patient-reported outcome instrument is the population – the population in which the validation work was performed should be consistent with the intended use population in the clinical study protocol. The same criterion will be later used by the FDA when assessing the applicability of the PRO instrument used. Analysis of population includes but is not limited to taking into consideration the stage of the disease, since the symptoms appearing in different stages could be different as well. At the same time, PRO instruments should not include items that could be misinterpreted or that do not apply to the intended use population. 

In summary, the present guidance highlights the main principles for the use of patient-reported outcome instruments when evaluating the safety and effectiveness of medical devices. The document pays special attention to the way the applicability of specific instruments should be determined. 





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