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.
PFDD 1: Comprehensive and representative input
Patient-Focused Drug Development: Collecting Comprehensive and Representative Input
Patient experience data encompass a range of inputs, including symptom burdens, treatment impacts, patient preferences, and views on unmet medical needs.
These data inform all stages of medical product development, from discovery to post-market use.
Quantitative methods (e.g., surveys) provide numerical insights, while qualitative methods (e.g., interviews) offer in-depth understanding. Mixed methods combine both for a fuller perspective.Social media and verified patient communities present novel data collection opportunities but require consideration of verification and representativeness challenges.
Probability sampling (e.g., stratified random sampling) is emphasized for generalizability, while non-probability methods (e.g., convenience sampling) are useful for exploratory research. Representativeness ensures that patient input reflects the diversity and heterogeneity of the target population.
Data collection should adhere to good clinical practices and regulatory standards.
Research protocols should address missing data, quality assurance, and confidentiality.
Early collaboration with the FDA is recommended to align on study designs and regulatory requirements.
Recommendations
Define clear research objectives and determine specific research questions before selecting data collection methods.
Use probability sampling methods whenever feasible to ensure representativeness of the target population.
Address data quality through rigorous planning, data management, and adherence to FDA-supported standards.
Incorporate diverse perspectives by including underrepresented patient populations, tailoring methods to specific subgroups as needed.
Leverage existing data sources, such as patient registries and literature, to complement primary data collection efforts.
Regulatory Considerations
Data submitted to FDA should include clear documentation of the study protocol, intended use, and data collection methodologies.
Researchers must comply with human subject protection regulations (e.g., 21 CFR Parts 50 and 56) and good clinical practice guidelines.
For data intended to support regulatory submissions, adherence to FDA-supported data standards (e.g., CDISC) is strongly encouraged.
Missing data should be addressed through pre-planned strategies and summarized in the study report.
Patient experience data must meet methodological rigor to ensure their reliability and relevance for regulatory decision-making.
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.
“External stakeholders should plan how to store their data in advance of starting their study. Researchers should decide how data will best be stored so that the data can be easily retrieved and protected from any type of damage or loss. The approach to data storage should reflect the type of data collected. Regarding duration of data retention, researchers should comply with their IRB and applicable regulations. Principles to consider regarding data storage and handling data include the following (Creswell 2013):
• Create back-up copies of computer files
• Use high-quality equipment for audio-recording information during interviews
• Protect the anonymity of participants by de-identification
• Create a data collection table or database to track and identify data
• Maintain a list of types of data collected.”
– Section III.J (Storing Data), p. 27, Patient-Focused Drug Development: Collecting Comprehensive and Representative Input, Final, 2020 (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.
“When using DHTs to record and transmit data during a clinical investigation, the relevant data captured from the DHT, including all relevant associated metadata, should be securely transferred to and retained in a durable electronic data repository as part of the record of the clinical investigation. FDA regulations include record retention requirements for clinical investigators and sponsors and provide for FDA inspection of certain records relating to a clinical investigation.”
– Section IV.G (Record Protection and Retention), p. 21, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, 2023 (FDA)
“For data collected directly from study participants through DHTs, FDA considers electronic data that are located in the first durable electronic data repository to which the data are transferred to be the source data. These source data should be available for inspection. FDA does not intend to inspect individual DHTs for source data when the data captured by the DHT, including all associated metadata, are securely transferred to and retained in the durable electronic data repository according to the sponsor’s prespecified plan.”
– Section IV.G (Record Protection and Retention), p. 22, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, 2023 (FDA)
“When specified in the protocol, the clinical investigator should review the source data collected from DHTs for participant safety and management. The clinical investigator must maintain and retain these source data as part of the adequate and accurate case histories required under 21 CFR 312.62(b) and (c) and 812.140(a)(3) and (d). The clinical investigator must also permit FDA to access and copy these case history records in accordance with 21 CFR 312.68 and 812.145(b).”
– Section IV.G (Record Protection and Retention), p. 22, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, 2023 (FDA)
“Ensure that data have been transferred from the DHT into a durable electronic data repository (see section IV.G of this guidance).”
– Section IV.H.1 (Other Considerations—Sponsor’s Role), p. 24, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, 2023 (FDA)
“Develop end-of-study closeout procedures (e.g., when/how data collection and/or transmission ends, revocation of system access).”
– Section IV.H.1 (Other Considerations—Sponsor’s Role), p. 24, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, 2023 (FDA)
“Sponsors should plan for unanticipated changes to DHTs or associated technology (e.g., updates needed to resolve a security concern, DHT unavailable due to discontinuation or supply issues) during the clinical investigation whether the DHTs or associated technology are provided by the sponsor or using a “bring your own” approach. DHT updates and other changes during a clinical investigation may lead to inconsistencies in measurements that can impact the evaluation of the trial outcome. Sponsors should keep a record of the timing and nature of any updates for each DHT.
If a DHT or associated technology, such as a general computing platform, is updated during a clinical investigation (e.g., operating system update), sponsors should ensure that the DHT remains fit-for-purpose, such that the updates do not affect the measurements and that verification and validation studies (see section IV.C of this guidance) are still applicable. In situations where the measurements may be affected, it may be necessary to validate the measurements (e.g., using previously collected data or a new prospective study) after introduction of the update to ensure that no changes to the measurements occurred.”
– Section IV.H.4 (Other Considerations—Sponsor’s Role), p. 25, Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, Final, 2023 (FDA)
Risk-based monitoring of clinical investigations
A Risk-Based Approach to Monitoring of Clinical Investigations Questions and Answers
A proactive risk assessment is essential for optimizing study quality by identifying and mitigating risks to human subject protection and data integrity before and during a trial. Monitoring should be comprehensive, addressing not only likely risks identified initially but also less probable, high-impact risks and unanticipated issues that emerge. The effectiveness of a monitoring strategy depends on tailoring its timing, frequency, and methods to study-specific factors like complexity and site experience. Centralized monitoring, as part of a risk-based approach, can detect systemic issues like data omissions or protocol deviations more rapidly than traditional on-site visits alone.
Recommendations
Sponsors should formally document their risk assessment methodologies and ensure these assessments directly inform the creation and revision of monitoring plans. Monitoring plans must be detailed, outlining the study design, specific data sampling strategies, and clear protocols for escalating significant issues. When significant problems are identified, sponsors must conduct a timely root cause analysis and implement corrective and preventive actions. All monitoring activities, findings, and subsequent actions should be thoroughly documented and communicated to sponsor management, clinical site staff, and other relevant parties.
Regulatory Considerations
FDA regulations mandate sponsor oversight and proper monitoring but do not prescribe specific methods, providing the flexibility for sponsors to adopt a risk-based approach. The FDA may request a sponsor’s risk assessment and monitoring plan documentation during an inspection. This guidance represents the Agency’s current thinking and is nonbinding, allowing sponsors to use alternative approaches if they satisfy regulatory requirements. A key focus of monitoring should be to ensure critical trial processes, such as the maintenance of blinding, are protected to maintain overall data and trial integrity.
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.
“How should sponsors follow up on significant issues identified through monitoring, including communication of such issues?
Significant issues should be thoroughly evaluated in a timely manner at the appropriate levels (for example, sponsor, clinical sites) as described in the monitoring plan. A root cause analysis followed by appropriate corrective and preventive actions should be undertaken promptly to reduce the impact of the identified issue on the rights, safety, and welfare of participants in the clinical investigation and/or the integrity of the data. Additionally, the risk assessment and monitoring plan should be reviewed and revised, as needed, to help ensure the risk of recurrence is decreased, or if possible, eliminated. In instances in which corrective actions modify study processes, the protocol and/or associated investigational plans should be amended to reflect changed processes. Related systemic issues should be identified and resolved promptly to help ensure that investigation quality, including the rights, safety, and welfare of investigation participants and data integrity, is maintained.
Examples of preventive and corrective actions that may be warranted include but are not limited to (1) improved training for the clinical investigator and site staff; (2) halting enrollment at a clinical site pending resolution of identified issues; (3) clarifying or revising the protocol and/or other related investigational plans and documents; and/or (4) modifying vendor service agreements to ensure adequate trial support.
Significant issues identified through monitoring and oversight activities and the actions to be taken should be documented and communicated to the appropriate parties, which may include, but are not limited to (1) sponsor management; (2) sponsor teams; (3) clinical sites; (4) institutional review boards; (5) other relevant parties (for example, DMCs and relevant contract research organizations); and (6) applicable regulatory agencies, including FDA, when appropriate. See the 2013 RBM guidance for additional recommendations regarding follow-up and communication of significant issues identified via monitoring.”
– Section III.C (Follow-Up and Communication of Monitoring Results, Q7), p. 9, A Risk-Based Approach to Monitoring of Clinical Investigations—Questions and Answers, Final, 2023 (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:
Industry spotlight
Gathers real-world examples, case studies, best practices, and lessons learned from peers and leaders in the field relevant to this section. Use these insights to accelerate your work and avoid common pitfalls.