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Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making

DraftCenter for Drug Evaluation and Research Center for Biologics Evaluation and Research Center for Devices and Radiological Health04/05/2023

Description

This guidance (Guidance 4) is the fourth in a series of four methodological patient-focused drug development (PFDD) guidance documents that describe how stakeholders (patients, caregivers, researchers, medical product developers, and others) can collect and submit patient experience data and other relevant information from patients and caregivers to be used for medical product development and regulatory decision-making.

Scope & Applicability

Product Classes

3
Biological product

Defined in section 351 of the Public Health Service Act

Combination Product

Products combining drug, device, or biological constituents; Generally recommended for Enhanced Documentation; Requires 14971-based framework incorporating ICH Q9; A drug-device combination where the device constituent part detects ingestion.

Medical product

To determine whether a medical product has a positive, meaningful effect; The document discusses determining whether a medical product produces a meaningful effect.; comparing a new product A to a current product B

Stakeholders

6
Caregivers

Individuals providing information for medical product development; Participants in facilitated discussions and observational studies

Patient communities

Early engagement with patient communities can improve the patient-centeredness of trial procedures.

Patient Community

sponsors might consider seeking input from members of the patient community

Caregiver

It may be a hardship for patients and/or caregivers to attend in-person; Individuals who may assist patients or provide observations when patients cannot self-report.; conducted with caregivers to obtain similar feedback

Medical product developers

Stakeholders who collect and submit patient experience data

Sponsor

Entity responsible for submitting applications under section 524B

Regulatory Context

Attributes

10
Clinically meaningful change

Determining the significance of changes in COA-based endpoints

Practice effects

Improvement in PerfO tasks due to repetition rather than health improvement

Ordinal scale

When a COA-based endpoint is on an ordinal scale

95% confidence interval

Used to evaluate if the overall survival HR excludes a threshold

Meaningful score regions

MSRs are used to interpret the meaningfulness of treatment effects by specifying the meaning of individual COA scores.

Meaningful score difference

MSDs are used to inform the choice of meaningful score differences in COA scores.

Meaningful treatment benefit

FDA evaluates how well results of a COA-based endpoint correspond to a treatment benefit that is meaningful to patients; interpreting the meaningfulness of continuous COA-based endpoints

Change-from-baseline

Endpoint construction method measuring difference from initial state

Score threshold

Prespecified value used for dichotomization of data

Clinically meaningful treatment effect

statistical significance does not indicate whether the detected effect corresponds to a clinically meaningful effect

Related CFR Sections (2)

Related Warning Letters (10)

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    Maria A. Carballosa, M.D.

    2025-12-23
  • Unapproved New Drug/Unlicensed Biological Product/Biologics License Application (BLA)

    Celularity, Inc

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  • Sponsor/Investigator

    Verdure Sciences, Inc.

    2025-11-18
  • Clinical Investigator (Sponsor)

    Pamela K. Den Besten, DDS, MS

    2025-09-30
  • Clinical Investigator/Sponsor

    Ralph A. DeFronzo, M.D.

    2025-09-23
  • Clinical Investigator

    Shirish M. Gadgeel, M.D.

    2025-09-09
  • Clinical Investigator

    Mark J. Savant, M.D

    2025-07-15
  • Clinical Investigator

    Peter Michael, M.D.

    2025-07-01
  • Clinical Investigator (Sponsor)

    American Behavioral Research Institute, LLC

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  • Bioresearch Monitoring Program

    Amy Lightner, MD

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See Also (8)