Regulatory spotlight
We offer selected excerpts from relevant guidances below, to help you get oriented and understand their significance.
It is your responsibility to fully examine and interrogate these guidances in detail. Click through on individual resource links to be taken to the primary source material.
DHT Steering Committee
Digital Health Technologies (DHTs) for Drug Development
The central principle of the FDA’s program is that Digital Health Technologies (DHTs) offer significant potential to make clinical trials more efficient, patient-centric, and capable of capturing novel data. A key finding is that a collaborative, multifaceted approach is necessary to address the challenges of incorporating DHT-derived data into regulatory decision-making. The program acknowledges that ensuring data quality, validating new endpoints, and establishing clear regulatory expectations are critical for the successful adoption of these technologies in drug development.
Program Activities (Recommendations)
The FDA’s activities in this area function as implicit recommendations for the industry. The agency is actively:
Developing a Framework: Creating and publishing a clear framework to guide the use of DHTs in drug and biological product development.
Engaging Stakeholders: Convening public meetings and workshops to foster collaboration and share learning among patients, biopharmaceutical companies, DHT manufacturers, and academia.
Supporting Demonstration Projects: Funding and overseeing research projects to address critical gaps and demonstrate the reliability and validity of specific digital measures.
Building Internal Expertise: Establishing a DHT Steering Committee and enhancing internal knowledge to ensure consistent and expert review of submissions containing DHT-derived data.
Regulatory Considerations
This webpage emphasizes the FDA’s commitment to creating a clear regulatory framework for the use of DHTs in drug development. It highlights that while DHTs offer great promise, they also present new regulatory challenges related to data integrity, validation, and analysis. The FDA’s approach involves a combination of issuing new regulatory guidance, promoting stakeholder collaboration, and advancing regulatory science. Sponsors are encouraged to engage with the FDA to discuss their use of DHTs in clinical trials to ensure alignment with the agency’s expectations. The establishment of the CDRH Digital Health Center of Excellence provides a dedicated resource for such engagement.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
The Steering Committee will support the implementation of the framework for the use of DHTs in drug and biological product development as well as other commitments identified in the section “Enhancing Use of Digital Health Technologies to Support Drug Development and Review” of the PDUFA VII commitment letter (e.g., public meetings, guidance documents, demonstration projects, technology needs, training).
In addition, the Steering Committee will oversee activities to assist organizational units with consistent approaches to the review of drug submissions that contain DHT-derived data. Further, the Steering Committee will engage with external interested parties on DHT-related issues in human drug development and gather information about the present state of DHTs, including specific challenges in their use…FDA encourages interested parties who are considering the use of DHTs in drug development or conducting a decentralized clinical trials (DCTs) to reach out to the agency early.
– Digital Health Technologies (DHTs) for Drug Development, FDA, 2024
Patient-reported outcome measures
Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims
PRO instruments must demonstrate content validity through patient input and qualitative research, ensuring the instrument measures concepts relevant to the population and condition being studied.
Sponsors must confirm the reliability, construct validity, and ability to detect change for the PRO instrument before use in confirmatory clinical trials.
Statistical analysis plans should address multiplicity, handling of missing data, and cumulative distribution function comparisons to interpret clinical trial results.
Modifications to PRO instruments (e.g., format changes, population adaptations) require evidence that measurement properties are preserved.
Electronic PRO systems must comply with regulatory requirements for data integrity, security, and investigator access.
Recommendations
Develop and validate PRO instruments early in the clinical development process, ensuring alignment with the clinical trial’s endpoint model.
Document all stages of instrument development, including qualitative input from patients, pilot testing, and cognitive interviews.
Use clear and consistent administration procedures, whether paper-based or electronic, to minimize variability and missing data.
Define responder thresholds using anchor-based methods and consider presenting cumulative distribution functions to interpret treatment benefits.
Address cultural and linguistic adaptation of PRO instruments by ensuring equivalent content validity and measurement properties across versions.
Regulatory Considerations
Include detailed descriptions of the PRO instrument, its conceptual framework, and scoring algorithms in regulatory submissions.
Ensure PRO instruments used in clinical trials comply with FDA requirements for record-keeping, data security, and source data accessibility.
Plan for the FDA to review all modifications to PRO instruments, including changes in administration mode or population.
Address missing data in clinical trial protocols and statistical analysis plans, ensuring prespecified handling rules.
Provide evidence that PRO instruments reliably measure the intended concepts across all study populations and data collection methods.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
Sponsors should begin instrument development and evaluation early in medical product development, and engage the FDA in a discussion about a new or unique PRO instrument before confirmatory clinical trial protocols are finalized.
Requests for FDA input should be addressed to the review division responsible for the medical product in question. For the FDA to provide useful early input, sponsors should provide their labeling goals, a hypothesized PRO instrument conceptual framework, and the relationship of the PRO endpoints to other clinical trial endpoints in preliminary endpoint models for the planned confirmatory trials.
– Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims, Section B, pp 5-6. FDA, Final, 2009
Formal meetings related to PDUFA products
Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products Guidance for Industry
The guidance establishes a predictable and efficient framework for formal interactions between the FDA and sponsors. Its core principle is that timely, high-quality communication is critical to a streamlined drug development process. The document clarifies that different stages of development require different types of meetings (e.g., Type A, B, and C), each with specific timelines and objectives. A key principle is that productive meetings depend on the sponsor providing a comprehensive meeting package in advance, allowing the FDA to prepare and provide substantive feedback.
Recommendations for Sponsors
Sponsors are strongly recommended to engage with the FDA early and throughout the drug development process. To ensure a productive meeting, sponsors should clearly articulate the purpose of the meeting, provide specific questions, and submit a well-organized and complete meeting package by the specified deadline. It is recommended that sponsors carefully consider the type of meeting that is most appropriate for their stage of development and the nature of the questions they have. Following the meeting, sponsors should adhere to the timelines and procedures for submitting meeting minutes for the official record.
Regulatory Considerations
This guidance is a key component of the regulatory framework under the Prescription Drug User Fee Act (PDUFA). Adherence to the procedures outlined in this document is a matter of regulatory compliance. The formal meetings described are a critical part of the Investigational New Drug (IND) and Marketing Authorization Application processes. The meeting process is designed to provide regulatory clarity, reduce the risk of clinical holds or refuse-to-file actions, and ultimately support a more efficient and predictable path to drug approval. The written record of these meetings serves as an important part of the administrative file for a product’s development program.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
This guidance provides recommendations to industry on formal meetings between the Food and Drug Administration (FDA) and sponsors or applicants relating to the development and review of drug or biological drug products… This guidance discusses the principles of good meeting management practices and describes standardized procedures for requesting, preparing, scheduling, conducting, and documenting such formal meetings.
Because these meetings often represent critical points in the drug and biological product development, it is important that there are efficient, consistent procedures for the timely and effective conduct of such meetings.
– Section I (Introduction), pp. 1–2, Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Draft Guidance, Procedural, Revision 1, September 2023 (FDA).
There are six types of formal meetings under PDUFA that occur between requesters and FDA staff: Type A, Type B, Type B (end-of-phase (EOP)), Type C, Type D, and Initial Targeted Engagement for Regulatory Advice on CDER and CBER ProducTs (INTERACT).
- Type A meetings are those that are necessary for an otherwise stalled product development program to proceed or to address an important safety issue.
- Type B meetings are as follows:
Pre-investigational new drug application (pre-IND) meetings.
Pre-emergency use authorization meetings.
Pre-new drug application (pre-NDA)/pre-biologics license application (pre-BLA) meetings (21 CFR 312.47).
Post-action meetings requested 3 or more months after receipt of an FDA regulatory action other than an approval (e.g., issuance of a complete response letter, refuse to file).
Meetings regarding risk evaluation and mitigation strategies or postmarketing requirements that occur outside the context of the review of a marketing application.
Meetings held to discuss the overall development program for products granted breakthrough therapy or regenerative medicine advanced therapy (RMAT) designation status. All subsequent meetings for breakthrough therapy or RMAT-designated products will be considered either Type B or possibly Type A meetings if the meeting request meets the criteria for a Type A meeting. - A Type C meeting is any meeting other than a Type A, Type B, Type B (EOP), Type D, or INTERACT meeting regarding the development and review of a product, including meetings to facilitate early consultations on the use of a biomarker as a new surrogate endpoint that has never been previously used as the primary basis for product approval in the proposed context of use.
- A Type D meeting is focused on a narrow set of issues that are used to discuss issues at key decision points to provide timely feedback critical to move the program forward (e.g., often one, but typically not more than two issues and associated questions). Requests could include the following:
A follow-up question that raises a new issue after a formal meeting (i.e., more than just a clarifying question about an FDA response from a prior meeting)
A narrow issue on which the sponsor is seeking Agency input with only a few (e.g., three to five questions total) associated questions
A general question about an innovative development approach that does not require extensive, detailed advice - INTERACT meetings are intended for novel products and development programs that present unique challenges in early development (i.e., before filing of an IND or before having a pre-IND meeting). The issues typically relate to IND requirements, for example, questions about design of IND-enabling toxicity studies (e.g., species, endpoints), complex manufacturing technologies or processes, development of innovative devices used with a drug or biologic, or the use of New Approach Methodologies. INTERACT meetings are intended to facilitate IND-enabling efforts when the sponsor is facing a novel, challenging issue that might otherwise delay progress of the product toward entry into the clinic in the absence of this early FDA input. The sponsor needs to have selected a specific investigational product or a product-derivation strategy to evaluate in a clinical study before requesting an INTERACT meeting.
Section III (Meeting Types), p. 3, Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Draft Guidance, Procedural, Revision 1, September 2023 (FDA).
To promote efficient meeting management, requesters should try to anticipate future needs and, to the extent practical, address relevant and related product development issues in the fewest possible meetings while avoiding meetings with too many questions (or subparts of questions) that would be impractical to discuss in the context of any single meeting.
– Section V (Meeting Requests), p. 7, Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Draft Guidance, Procedural, Revision 1, September 2023 (FDA)
If a written response is requested and deemed appropriate, the FDA will notify the requester of the date it intends to send the written response in the Agency’s response to the meeting request… the Agency may determine that a written response to the sponsor’s questions would be the most appropriate means for providing feedback and advice to the sponsor.
– Section VI (Assessing and Responding to Meeting Requests), p. 10, Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Draft Guidance, Procedural, Revision 1, September 2023 (FDA).
For in person face-to-face, virtual face-to-face, and teleconference meetings, the FDA will schedule the meeting on the available date at which all expected FDA staff are available to attend; however, the meeting should be scheduled consistent with the type of meeting requested (see Table 2 for FDA meeting scheduling time frames).
– Section VI.B (Meeting Granted), p. 11, Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Draft Guidance, Procedural, Revision 1, September 2023 (FDA).
Table 1. FDA Meeting Request/WRO Request Response Timelines…
Table 2. FDA Meeting Scheduling Time Frames…
Table 3. FDA WRO Response Timelines.
– Section VI (Assessing and Responding to Meeting Requests), p. 11, Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Draft Guidance, Procedural, Revision 1, September 2023 (FDA).
Premeeting preparation is critical for achieving a productive discussion or exchange of information… The meeting package should provide information relevant to the discussion topics and enable the FDA to prepare adequately for the meeting.
– Section VII (Meeting Package), p. 12, Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Draft Guidance, Procedural, Revision 1, September 2023 (FDA).
The meeting package should provide summary information relevant to the product and any supplementary information needed to develop responses to issues raised by the requester or review division. It is critical that the entire meeting package content support the intended meeting objectives.
– Section VII.C (Meeting Package Content), p. 13, Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Draft Guidance, Procedural, Revision 1, September 2023 (FDA).
Data to support discussion organized by FDA discipline and question. Protocols, full study reports, or detailed data generally are not appropriate for meeting packages; the summarized material should describe the results of relevant studies and clinical trials with some degree of quantification and any conclusion about clinical trials that resulted. The trial endpoints should be stated, as should whether endpoints were altered or analyses changed during the course of the trial.
– Section VII.C (Meeting Package Content), p. 13–14, Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Draft Guidance, Procedural, Revision 1, September 2023 (FDA).
Because the FDA’s minutes are the official records of meetings, the FDA’s documentation of meeting outcomes, agreements, disagreements, and action items is critical… The FDA will issue the official, finalized minutes to the requester within 30 calendar days after the meeting.
– Section XI (Meeting Minutes), p. 17, Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA Products, Draft Guidance, Procedural, Revision 1, September 2023 (FDA).
FDA recommends that sufficient background information and supporting documents be included… This information might include literature articles, full device description with engineering drawings, proposed labeling, videos, and/or red-lined protocol revisions depending on the specific questions for which feedback is requested.
– Section III.B(4)(a)1) (Pre-Submission – Additional Recommended Submission Contents), p. 21, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, Final, May 29, 2025 (FDA).
If the Pre-Sub is for a nonsignificant risk device study, IDE exempt device study, CW, Dual, or a study you plan to conduct outside the US (OUS) to support a marketing submission, the submitter should consider submitting the entire protocol through the Pre-Sub process prior to initiating the study, particularly if it raises unique scientific or regulatory considerations.
– Section III.B (Q-Submission Processes), p. 23, Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program, Final, May 29, 2025 (FDA).
PFDD 2: What is important to patients
Patient-Focused Drug Development: Methods to Identify What Is Important to Patients
Qualitative Methods: One-on-one interviews provide in-depth individual insights, while focus groups capture diverse perspectives through participant interaction.
Approaches such as Delphi panels and observational methods can complement interviews and focus groups in understanding patient experiences.
Quantitative Methods: Surveys provide structured, quantifiable data and are effective for large populations.
Careful design of questions and response options minimizes bias and improves data quality.
Mixed Methods:Combining qualitative and quantitative techniques enhances understanding and validates findings.
Sequential and concurrent designs can address complex research questions and improve robustness.
Barriers to Self-Report: Special adaptations may be needed for patients with disabilities, pediatric populations, or those with language or cultural differences.
Proxy reporting by caregivers is sometimes necessary but may introduce bias.
Social Media: Useful for real-time or retrospective insights into patient perspectives. Limitations include lack of verified identities and potential bias in user demographics.
Recommendations
Choose data collection methods aligned with research objectives and the target population.
Use open-ended questions for qualitative research to elicit unbiased responses; avoid leading or judgmental prompts.
Pilot test interview guides, surveys, and response options to ensure clarity and relevance.
Integrate cultural and linguistic adaptations for diverse populations in multinational studies.
For mixed-method research, establish clear objectives for combining qualitative and quantitative components and address conflicting findings systematically.
Regulatory Considerations
Data collected through qualitative or quantitative methods must meet regulatory standards for integrity and reliability when submitted to the FDA.
Screening and exit interviews should not interfere with the integrity of ongoing clinical trials; use trained third-party interviewers where appropriate.
Researchers should follow ethical standards and federal regulations when using social media data, ensuring informed consent and data privacy.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
FDA encourages stakeholders to interact early with FDA and obtain feedback from the relevant FDA review division when considering collection of patient experience data related to the burden of disease and treatment.
– Section I (Introduction), p. 2, Patient-Focused Drug Development: Methods to Identify What Is Important to Patients, Final, 2022 (FDA)
PFDD 3: Fit-for-purpose clinical outcome assessments (COAs)
Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments
The guidance applies to four types of Clinical Outcome Assessments (COAs): Patient-Reported Outcomes (PROs), Observer-Reported Outcomes (ObsROs), Clinician-Reported Outcomes (ClinROs), and Performance Outcomes (PerfOs). A COA is considered fit-for-purpose when the validation evidence is sufficient to support its context of use (COU). To determine if a COA is fit-for-purpose, sponsors must clearly describe the Concept of Interest (COI) and the COU, and present sufficient evidence to support a clear rationale for the COA’s proposed interpretation and use. The rationale for using a COA should include up to eight components, such as justification for the COA type, capturing the important parts of the COI, appropriate administration and scoring, minimal influence from irrelevant factors or measurement error, and correspondence with the Meaningful Aspect of Health (MAH). The most direct assessment of how a patient feels or functions (MAH) should be used as the COI whenever possible.
Recommendations
Sponsors should use the Roadmap to Patient-Focused Outcome Measurement to guide the selection, modification, or development of a COA. The process begins with understanding the disease/condition (including patient perspectives) and conceptualizing clinical benefits and risks (defining the MAH, COI, and COU). When feasible, existing COAs are generally preferred, especially for well-established COIs, as this approach is often the least burdensome. If an existing COA is modified or used in a different context, additional evidence (e.g., cognitive interviews, psychometric studies) must be collected to justify its fitness for the new context of use. For new COA development, sponsors should involve patients, document all steps, and generally avoid using the new COA for the first time in a registration (pivotal) trial; a standalone observational study or early phase trial is recommended for evaluation.
Regulatory Considerations
Sponsors are encouraged to interact early and throughout medical product development with the relevant FDA review division to ensure COAs are appropriate for the intended COU. Sponsors should communicate their proposed COA-based endpoint approach, including the MAH, COI, COA type/name/score, and the final COA-based endpoint, ideally using the suggested format. The type and amount of evidence required to support the rationale for a COA’s use is weighed against the degree of uncertainty regarding that part of the rationale. For ClinROs, it is recommended to use an assessor masked to treatment assignment and study visit for primary endpoints, if feasible. FDA strongly discourages proxy-reported measures for concepts known only to the patient (e.g., pain) and recommends using an ObsRO to measure observable behaviors instead when the patient cannot self-report.
Recommendations
Clearly define the concept of interest and its context of use to ensure COAs align with trial objectives.
Use conceptual and measurement frameworks to communicate how COAs measure patient experiences and generate interpretable scores.
Leverage existing COAs where possible, modifying them only when justified, and document all modifications rigorously.
Ensure COAs are accessible and inclusive, incorporating features like large fonts, touch interfaces, or audio assistance for diverse populations.
Conduct early engagement with FDA to discuss COA selection, development, and validation plans.
Regulatory Considerations
Fit-for-purpose validation requires evidence of conceptual alignment, scoring reliability, and sensitivity to clinically meaningful changes.
Digital health technologies used for COAs must comply with FDA’s guidance on data integrity, usability, and technical performance.
COAs intended for regulatory submissions must be developed and validated before pivotal trials to avoid jeopardizing trial outcomes.
Modifications to COAs or scoring methods during trials necessitate justification and revalidation.
Sponsors should submit comprehensive documentation on COA development, including scoring algorithms and item tracking matrices.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
In addition to the general considerations discussed in this guidance, a study may need to meet specific statutory and regulatory standards governing the collection, processing, retention, and submission of data to the FDA to support regulatory decisions regarding a marketed or proposed medical product. This guidance focuses on more general considerations that apply to many types of studies, and you should consult with the review division and applicable guidance regarding any other applicable requirements.
– Section I.A (Overview of FDA Guidances on Patient-Focused Drug Development), p. 2, Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments, October 2025 (FDA)
FDA encourages stakeholders to interact early with FDA and obtain feedback from the relevant FDA review division when considering collection of patient experience data related to the burden of disease and treatment.
– Section I.A (Overview of FDA Guidances on Patient-Focused Drug Development), p. 2, Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments, October 2025 (FDA)
When the sponsor is developing or significantly modifying a COA, FDA does not recommend evaluating measurement properties for the first time in a registration trial, because it may be too late to learn that the COA is not performing as it should, potentially jeopardizing the success of a medical product development program. Earlier trials represent an opportune time to evaluate measurement properties of COAs and sponsors are encouraged to include prospectively planned analyses to inform subsequent trials.
– Section III.C.2.c (No COA Exists for the Concept of Interest: Develop a New COA and Empirically Evaluate), p. 20, Patient-Focused Drug Development: Selecting, Developing, or Modifying Fit-for-Purpose Clinical Outcome Assessments, October 2025 (FDA)
PFDD 4: Incorporating COAs into endpoints
Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making
COA-based endpoints should reflect meaningful patient health aspects and support clear treatment effect inferences.
Selection of endpoints requires a well-supported rationale, including evidence of their importance to patients.
Use of MSD and MSR approaches enhances the interpretation of treatment effects by linking COA scores to meaningful patient experiences. Proper anchors (e.g., global impression of severity) are essential for validating these approaches.
Frequency and timing of COA data collection must align with disease characteristics and study objectives.
Adjustments for potential practice effects and assistive device use are critical for robust outcome measurement.
Proper handling of missing data and sensitivity analyses ensure valid conclusions from COA-based endpoints.
Continuous, ordinal, and dichotomized endpoints require tailored statistical methods for analysis.
Early engagement with the FDA is crucial for aligning study designs and COA approaches with regulatory expectations.
Recommendations
Engage patients and caregivers early to identify meaningful endpoints and assess potential barriers to COA use.
Use anchor-based methods to validate COA scores and define meaningful thresholds for interpretation.
Develop and pilot test study protocols to ensure COA reliability, usability, and alignment with regulatory requirements.
Implement strategies to reduce participant burden, such as concise COA instruments and patient-friendly data collection methods.
Submit comprehensive documentation, including endpoint justification and scoring rationale, to FDA for feedback before trial initiation.
Regulatory Considerations
Endpoints must be supported by evidence of their fit-for-purpose status and alignment with the trial’s objectives.
COAs used in digital or adaptive formats must meet FDA’s standards for usability and data integrity.
Trials with nonrandomized designs require robust measures to mitigate bias in COA-based endpoint analysis.
Thresholds for MSD or MSR must be prespecified and justified with empirical evidence.
Sponsors must follow FDA guidance for submitting COA-based data, ensuring compliance with electronic data standards.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
FDA encourages stakeholders to interact early with FDA and obtain feedback from the relevant FDA review division when considering the collection of patient experience data related to the burden of disease and the benefits, burdens, and harms of treatment. FDA recommends that stakeholders engage with patients and other appropriate subject matter experts (e.g., clinical and disease experts, qualitative researchers, survey methodologists, statisticians, psychometricians, patient preference researchers) when designing and implementing studies to evaluate the burden of disease and treatment, and perspectives on treatment benefits and risks.
– Section I.A (Overview of the PFDD guidance series), p. 2, Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making, Draft, 2023 (FDA).
FDA recognizes that constructing and selecting trial endpoint(s) often involves weighing the strengths and limitations of different approaches. Early in the planning of a clinical trial, sponsors should provide to FDA a well-supported rationale for the selection of the endpoint(s) by explaining why each endpoint is informative for the trial context.
– Section II.A.1 (Selecting and Justifying Endpoints), p. 6, Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making, Draft, 2023 (FDA).
In regulatory decision-making, FDA evaluates how well results of a COA-based endpoint correspond to a treatment benefit that is meaningful to patients… FDA strongly recommends that sponsors seek FDA input as early as possible regarding the evaluation of meaningful treatment benefit.
– Section III (Evaluating the Meaningfulness of Treatment Benefit), p. 18, Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making, Draft, 2023 (FDA).
FDA recommends that sponsors seek FDA input early regarding plans for determining MSDs (III.B.1) or MSRs (III.B.2). Ideally sponsors should evaluate and provide estimates of meaningful differences or scores prior to the start of the registration trial(s).
– Section III.C (Additional Considerations for Justifying Meaningful Differences or Meaningful Score Regions), p. 27, Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making, Draft, 2023 (FDA).
Clinical trials with decentralized elements
Conducting Clinical Trials With Decentralized Elements
Coordination challenges with multiple locations in DCTs.
Variability in data collection across decentralized locations and remote tools.
Challenges in implementing certain statistical approaches in DCTs.
Need for DHTs to be accessible and suitable for all trial participants.
Ensuring compliance with local laws and regulations.
Recommendations
Develop clear protocols for integrating decentralized elements into clinical trials, specifying remote and in-person activities.
Use digital health technologies (DHTs) and electronic systems to streamline data acquisition, informed consent, and investigational product tracking.
Provide training for all stakeholders, including trial personnel, local health care providers, and participants, on decentralized processes.
Implement robust safety monitoring plans to address adverse events in decentralized settings.
Ensure compliance with local and international laws governing telehealth, data privacy, and investigational product use.
Regulatory Considerations
Maintain compliance with FDA requirements under 21 CFR parts 312 and 812 for drug and device trials, respectively.
Document all trial activities and data flows in trial protocols and data management plans, ensuring traceability and integrity.
Ensure informed consent processes meet FDA standards and provide clear communication to participants about decentralized trial activities and data handling.
Address investigational product accountability by documenting IP distribution, storage, and return or disposal.
Design electronic systems for decentralized trials to comply with 21 CFR part 11 requirements for data reliability, security, and confidentiality.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
Specific issues related to the feasibility, design, implementation, or analysis of a DCT should be discussed early with the relevant FDA review divisions.
– Section II (Background), p. 3, Conducting Clinical Trials With Decentralized Elements, Final, 2024 (FDA).
Remote data acquisition
Digital Health Technologies for Remote Data Acquisition in Clinical Investigations
There is a need for comprehensive validation and verification processes for DHTs.
Ensuring data security and privacy is a significant concern.
Usability issues for diverse populations need to be addressed.
There is a lack of clarity on whether certain DHTs meet the definition of a device under the FD&C Act.
The guidance does not establish legally enforceable responsibilities.
Recommendations
Ensure DHTs are fit-for-purpose for clinical investigations.
Implement robust data security measures to protect participant information.
Conduct usability evaluations to ensure DHTs can be used by intended populations.
Engage with FDA early to discuss the use of DHTs in clinical investigations.
Develop a risk management plan to address potential issues with DHT use.
Regulatory Considerations
Verification and validation should be addressed regardless of device classification.
Sponsors should ensure compliance with data protection and privacy regulations.
FDA evaluates DHT data based on endpoints, medical products, and patient populations. Sponsors can engage with FDA’s Q-Submission Program for feedback on DHT usage in clinical trials.
Sponsors should understand the legal implications of using DHTs in clinical investigations.
The guidance provides recommendations but does not establish legally enforceable responsibilities.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
Sponsors should engage early with the appropriate Center responsible for the medical product under investigation to discuss use of DHTs in a specific clinical investigation. – Section III (Regulatory Considerations and Engagement with the Agency), p. 6, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, December 2023 (FDA)
– Section III (Regulatory Considerations and Engagement with the Agency), p. 6, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, December 2023 (FDA)
When the sDHT is a regulated medical device: Cybersecurity in medical devices
Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions
Cybersecurity threats in healthcare are increasingly frequent and severe, posing risks to device safety and clinical care.
Many vulnerabilities arise from third-party software components and interconnected device ecosystems.
Legacy devices often lack adequate cybersecurity controls, leading to increased patient and organizational risks.
Cybersecurity risk management processes must integrate safety and security assessments throughout the device lifecycle.
Transparency in device cybersecurity is crucial for enabling safe integration and use by healthcare providers and end users.
Recommendations
Implement a Secure Product Development Framework (SPDF) for comprehensive cybersecurity throughout the product lifecycle.
Include a Software Bill of Materials (SBOM) for all premarket submissions to track software dependencies and vulnerabilities.
Perform robust cybersecurity testing, including penetration testing and vulnerability assessments.
Enhance device labeling with clear cybersecurity-related instructions and risks for users.
Develop a coordinated vulnerability disclosure plan for postmarket cybersecurity management.
Regulatory Considerations
Adherence to 21 CFR Part 820 Quality System regulation requirements, including design controls and risk management.
Compliance with Section 524B of the FD&C Act for cybersecurity of cyber devices.
Submission of SBOMs and detailed security risk management reports for premarket applications.
Provision of cybersecurity information as part of device labeling to prevent misbranding under Section 502 of the FD&C Act.
Integration of security testing and validation as part of the FDA review process.
Some summaries are generated with the help of a large language model; always view the linked primary source of a resource you are interested in.
FDA understands the need to balance innovation and security in designs especially during clinical trials. In order to ensure security is addressed early in the device design, FDA has identified a subset of the documentation recommended throughout this guidance to submit with IDE applications.
Under 21 CFR 812.25, manufacturers must provide an investigational plan as a part of their IDE application. For investigational devices within the scope of this guidance, FDA recommends that this investigational plan include information on the cybersecurity of the subject device.
Specifically, FDA recommends the following documentation be included as part of IDE applications:
• Inclusion of cybersecurity risks as part of informed consent form (21 CFR 50.25(a)(2) and 21 CFR 812.25(g));
• Global, multi-patient and updateability/patchability views (21 CFR 812.25(c), (d));
• Security use case views for functionality with safety risks (e.g., implant programming) (21 CFR 812.25(c), (d));
• Software Bill of Materials (21 CFR 812.25(c), (d)); and
• General labeling – connectivity and associated general cybersecurity risks, updateability/process (21 CFR 812.25(f)).
FDA intends to review this information in the context of the overall benefit-risk assessment of investigational devices as outlined in FDA’s guidance ‘Factors to Consider When Making Benefit-Risk Determinations for Medical Device Investigational Device Exemptions.’ Therefore, approval of an IDE based on the documentation recommended above does not preclude the possibility of future cybersecurity questions or concerns being raised during review of a subsequent marketing application. This is, in part, due to the understanding that design changes may be needed and the temporal nature of cybersecurity. Cybersecurity improvements will likely be needed between the time of clinical trials and when the device is submitted for marketing authorization (e.g., operating system no longer supported or nearing end of support, third-party software updates).
Appendix 3 (Submission Documentation for IDEs), pp. 50–51, Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions, Final, 2025 (FDA).
Scope of PFDD guidances
The FDA’s Patient-Focused Drug Development (PFDD) Guidance Series “is intended to facilitate the advancement and use of systematic approaches to collect and use robust and meaningful patient and caregiver input that can better inform medical product development and regulatory decision making.”
While the PFDD series provides this key framework, different FDA centers emphasize distinct guidances in their assessments. For instance, the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER) currently utilize PFDD 1 and 2. In contrast, the Center for Devices and Radiological Health (CDRH) uses Principles for Selecting, Developing, Modifying, and Adapting Patient Reported Outcome Instruments for Use in Medical Device Evaluation, for patient-reported outcomes. All centers are also preparing for the implementation of PFDD 3 (finalized Oct 2025) and the forthcoming PFDD 4, which will together replace the older 2009 guidance on Patient-Reported Outcome Measures.
Once you’ve read the guidances, explore these best practices from the field:
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