Sarah T. Gary, PhD

	The 21st Century Cures Act was enacted in 2016 to both accelerate medical product development, and it expresses the need to include both patient experience and patient perspective in the drug development process. In accordance with the Act as well as the Prescription Drug User Fee Act, the FDA is currently developing four new methodological Patient-Focused Drug Development (PFDD) guidance documents for industry that incorporate patient experience data into drug development. The key concepts of each guidance-and their current status-are summarized below.

	Although the updated guidance documents are still in development, researchers should start planning now to incorporate the basic features outlined in the draft guidances and discussion documents, as these concepts will likely be required in future research programs.

		Guidance 1: Whom do you get input from, and why? How do you collect the information?					

		Guidance 2: What do you ask, and why? How do you ask non-leading questions that are well-understood by a wide range of patients and others?					

		Guidance 3: How do you decide what to measure in a clinical trial and select or develop fit-for-purpose clinical outcome assessments (COAs)?					

				Status: Public meeting held October 2018; 

		Guidance 4: Once you have a COA measurement tool and a way to collect data using it, what is an appropriate clinical trial endpoint?					

				Status: Public meeting held December 2019; 

	Guidance 1: collecting comprehensive and representative input 

	Guidance 1 lays the foundation for the Patient-Focused Drug Development series by defining patient experience data and outlining whom to get patient experience data from and how to collect, analyze and report the information obtained. Key points include:

	Includes the “experiences, perspectives, needs, and priorities of patients related to:

		the symptoms of their condition and its natural history

		the impact of their condition on their daily function and quality of life

		input on which outcomes are important to them

		patient preferences for outcomes and treatments

		the relative importance of any of these issues as defined by patients.”

		Define the target population:  Obtain information from the specific population you wish to include in your study. This should compare to the inclusion/exclusion criteria in your protocol.

		Determine who will be providing patient experience data: FDA generally recommends that the patient self-report their experience, unless they cannot reliably do so (e.g. young children, cognitively impaired individuals).  In such cases a clinician or caregiver can report on patient experience data that is observable.

		Determine the study design and research setting: e.g. study type (clinical trial, observational, survey), sampling method, representativeness of the study population, and sample size required.

		Determine the methods for collecting and analyzing patient experience data: qualitative, quantitative, and mixed methods (both qualitative and quantitative).

		Operationalize and standardize data collection and data management:  Considerations include locating patients, sampling strategy, and collecting and managing data.

				Documents (includes medical records, scientific publications)

				Social Media and Identifiable Patient Communities

				Digital Health Technology (includes wearables such as accelerometers, heartrate trackers, etc.)     

	For full methods on collecting and analyzing COAs, the guidance document refers to the FDA Guidance for Industry “Patient Reported Outcome Measures: Use in Medical Product Development to Support Labeling.”

	Guidance 2: methods to identify what is important to patients

	Guidance 2 further expands on the methods to collect representative patient experience data, especially how to identify what matters most to patients in terms of disease burden and treatment and informs COA development and selection. Key points include:

Literature reviews and consultation with subject matter experts should be used to develop research questions and select the appropriate methods, listed below.

				One-on-One Interviews: semi-structured, structured, unstructured interviews

				Focus Groups: 5-10 participants per group 

	Note: “FDA does not have a single recommended interview mode for eliciting patient input”

		Approaches to Asking the Right Questions: Critical for obtaining unbiased patient input					

				Spontaneous responses are ideal, but sometimes participants will need to be prompted

				Avoid leading questions by using a semi-structured interview guide to facilitate discussion, do not suggest an answer, do not assume you know what the subject is feeling or thinking, do not imply that you prefer participant to respond a certain way

Collection of quantifiable data and application of statistics to summarize patient experience data

				Survey administration: self-administered or interviewer-administered

	Note: “Using survey instruments in a clinical trial for screening and/or exit visits may add greater depth to understanding the burden of disease and treatment”

		Considerations for Developing a Survey					

				Survey instructions and items should be well understood by participants, translated and culturally adapted, tested through interviews of target population to make sure the survey is interpreted as intended, and tested for usability if administered electronically

				Avoid poorly defined terms, double-barreled questions, double negatives, or leading questions

This includes research that uses both qualitative and quantitative methods.  

	Note: “FDA encourages researchers to consider the goals and objectives of using a mixed-methods approach and how the results from both qualitative and quantitative research components are intended to be used together.”

	When selecting methods, special populations (children, cognitively impaired, rare diseases) should be taken into consideration.  For example, factors such as limited attention span of children, use of caregivers for patients who are unable to self-report, remote assessment for rare diseases where patients are geographically diverse should be considered when developing surveys and data collection methods.

	Finally, Guidance 2 discusses considerations for using social media. Different social media communities appeal to different segments of the population and therefore a variety of social media communities should be used to obtain the most generalized information.  Other considerations include whether the participant is anonymous, and limitations with ability to verify patient characteristics such as identity and diagnosis.

	Guidance 3 (discussion document): selecting, developing or modifying fit-for purpose clinical outcome assessments

	After identifying what is most important to patients as outlined in Guidance 1 and 2, Guidance 3 outlines how to select, develop or modify a “fit-for purpose” COA that captures patient experience data. Currently, only the discussion document for Guidance 3 is available. This discussion document provides guidance on all four COA types: Patient-Reported Outcome (PRO), Clinician Reported Outcome (ClinRO), Observer-Reported Outcome (ObsRO) and Performance Outcome measures (PerfOs) including mobile health technologies. The discussion document aligns closely with the FDA Guidance “Patient Reported Outcome Measures: Use in Medical Product Development to Support Labeling.”

	Roadmap to COA selection: What to consider when selecting or developing/modifying a COA:

: When requesting review and advice on COAs for use in medical product development programs, the following should be submitted to the FDA:

Articles

The four new methodological Patient-Focused Drug Development guidance documents the FDA is currently developing for the industry that incorporate patient experience data into drug development, summarized.

Sarah T. Gary, PhD

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FDA Patient-Focused Drug Development Guidance Update: Incorporating Patient Experience Data in Clinical Trials