Digital Health Technologies 
for Remote Data Acquisition 
in Clinical Investigations 
Guidance for Industry, Investigators, 
and Other Stakeholders 
 
 
 
 
 
 
    
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
Center for Devices and Radiological Health (CDRH) 
Oncology Center of Excellence (OCE) 
 
 
 
 
 
 
 
 
 
 
 
 
 
December 2023 
Clinical/Medical 
55626970fnl    
Digital Health Technologies for 
Remote Data Acquisition in Clinical 
Investigations 
Guidance for Industry, Investigators, and 
Other Stakeholders 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs  
and/or 
Office of Communication, Outreach and Development  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002 
Phone: 800-835-4709 or 240-402-8010 
Email: ocod@fda.hhs.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-guidances     
and/or 
Office of Policy 
Center for Devices and Radiological Health 
Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 66, Room 5431 
Silver Spring, MD 20993-0002 
Email: CDRH-Guidance@fda.hhs.gov 
https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/guidance-documents-medical-devices-
and-radiation-emitting-products  
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
Center for Devices and Radiological Health (CDRH) 
Oncology Center of Excellence (OCE) 
 
 
December 2023 
Clinical/Medical 
 
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 4 
III.  REGULATORY CONSIDERATIONS AND ENGAGEMENT WITH THE 
AGENCY ....................................................................................................................................... 5 
IV.  CONSIDERATIONS WHEN USING DIGITAL HEALTH TECHNOLOGIES IN 
CLINICAL INVESTIGATIONS ................................................................................................. 8 
A.  Selection of a Digital Health Technology and Rationale for Use in a Clinical Investigation .. 8 
B.  Digital Health Technology Description in a Submission .......................................................... 10 
C.  Verification, Validation, and Usability Evaluations of Digital Health Technologies ............. 11 
D.  Evaluation of Endpoints Involving Data Collected Using Digital Health Technologies ........ 15 
E.  Statistical Analysis and Trial Design Considerations ............................................................... 17 
F.  Risk Considerations When Using Digital Health Technologies ............................................... 18 
G.  Record Protection and Retention ............................................................................................... 21 
H.  Other Considerations When Using Digital Health Technologies During a Clinical 
Investigation .......................................................................................................................................... 22 
GLOSSARY................................................................................................................................. 27 
APPENDIX A:  EXAMPLES OF POTENTIAL DIGITAL HEALTH TECHNOLOGY 
USE IN CLINICAL INVESTIGATIONS ................................................................................ 28 
APPENDIX B:  EXAMPLE OF SELECTING A DIGITAL HEALTH TECHNOLOGY 
FOR A CLINICAL INVESTIGATION AND JUSTIFYING THE ENDPOINT FOR 
WHICH IT IS USED .................................................................................................................. 30 
  Contains Nonbinding Recommendations 
 
Digital Health Technologies for Remote Data 
Acquisition in Clinical Investigations 
Guidance for Industry, Investigators, and Other Stakeholders1 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic.  It does not establish any rights for any person and is not binding on FDA or the public.  You 
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.  
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the 
title page.   
 
 
I.  INTRODUCTION  
 
A digital health technology2 (DHT) is a system that uses computing platforms, connectivity, 
software, and/or sensors, for health care and related uses.  This guidance provides 
recommendations for sponsors, investigators, and other stakeholders on the use of DHTs for 
remote data acquisition3 from participants in clinical investigations that evaluate medical 
products.4,5
   
 
There is a large spectrum of DHTs available for potential use in a clinical investigation.  DHTs 
for remote data acquisition in clinical investigations can include hardware and/or software6 to 
perform one or more functions.7  Appendix A includes examples of DHTs that can be used for 
 
1 This guidance has been prepared by the Office of Medical Policy in the Center for Drug Evaluation and Research 
(CDER) in cooperation with the Center for Biologics Evaluation and Research (CBER), the Center for Devices and 
Radiological Health (CDRH), and the Oncology Center of Excellence (OCE) at the Food and Drug Administration 
(FDA).  
 
2 Words and phrases in bold are defined, for the purposes of this guidance, in the Glossary. 
 
3 While the focus of this guidance is on DHTs used for remote data acquisition in a clinical investigation, the 
recommendations in this guidance may be applicable when DHTs are used by trial participants at a trial site (e.g., 
continuous glucose monitor reviewed in the clinic).  
 
4 For FDAs regulatory definitions of clinical investigation or investigation, see 21 CFR 50.3(c), 56.102(c), 
312.3(b), and 812.3(h).  For the purposes of this guidance, the terms clinical trial and clinical investigation are used 
interchangeably. 
 
5 For the purposes of this guidance, all references to medical products mean human drugs and biological products, 
medical devices, and combination products (see 21 CFR 3.2(e)) that are regulated by CDER, CBER, or CDRH.   
 
6 This may include software enabled by artificial intelligence (AI). 
 
7 For the purposes of this guidance, for any given DHT, the term function is the distinct purpose of the DHT in a 
clinical investigation, which could be the intended use or a subset of the intended use of the DHT.  DHTs can have 
multiple functions, which may or may not be device functions.  When considering FDA's regulatory approach and 
policy for multiple function device products, see the guidance for industry and FDA staff Multiple Function Device 
 
  1  Contains Nonbinding Recommendations 
 
remote data acquisition in clinical investigations, such as wearables and software applications 
(including mobile apps).  Depending on the intended use8 of a DHT, the DHT may meet the 
definition of a device under the Federal Food, Drug, and Cosmetic Act (FD&C Act).9    
 
This guidance provides recommendations for ensuring that a DHT is fit-for-purpose (i.e., that the 
level of validation10 associated with the DHT is sufficient to support the use, including the 
interpretability of its data in the clinical investigation), which involves considerations of both the 
DHTs form (i.e., design) and function(s) (i.e., distinct purpose(s) within an investigation).  
DHTs may rely on or work with other technologies that support their operation, such as general-
purpose computing platforms (e.g., smartphones) and communication networks.  Therefore, 
when implementing the recommendations in this guidance related to DHTs, sponsors should 
ensure that these other technologies are adequate to support the function(s) of the DHT.  The 
recommendations in this guidance may be relevant to the other technologies used to support 
remote data acquisition in a clinical investigation.  
 
This guidance outlines recommendations intended to facilitate the use of DHTs in clinical 
investigations as appropriate for the evaluation of medical products.  These recommendations 
also address some of the information regarding DHTs that sponsors should include in: 
 
  an investigational new drug application (IND) 
  an investigational device exemption (IDE) application  
  a marketing application  
  a Drug Development Tool (DDT) submission11 
  a Medical Device Development Tool (MDDT) submission12 
 
 
Products:  Policy and Considerations (July 2020).  We update guidances periodically.  For the most recent version 
of a guidance, check the FDA guidance web page at https://www.fda.gov/regulatory-information/search-fda-
guidance-documents#guidancesearch.   
 
8 21 CFR 801.4. 
 
9 See section 201(h) of the FD&C Act for the definition of a device.  How to determine whether a DHT proposed for 
use in a clinical investigation meets the definition of a device under the FD&C Act is outside the scope of this 
guidance.  For further information about FDA digital health regulatory policies, see https://www.fda.gov/medical-
devices/digital-health-center-excellence/ask-question-about-digital-health-regulatory-policies. 
 
10 For the purposes of this guidance, validation is confirmation by examination and provision of objective evidence 
that the selected DHT appropriately assesses the clinical event or characteristic in the proposed participant 
population (e.g., step count or heart rate).  See section IV.C of this guidance for further discussion of validation. 
 
11 See CDERs web page Drug Development Tools (DDT) Qualification Programs, available at 
https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tool-ddt-qualification-programs. 
 
12 See CDRHs web page Medical Device Development Tools (MDDT), available at https://www.fda.gov/medical-
devices/science-and-research-medical-devices/medical-device-development-tools-mddt. 
 
  2  Contains Nonbinding Recommendations 
 
These recommendations address the following topics: 
 
  Selection of DHTs that are suitable for use in clinical investigations 
 
  Description of DHTs in regulatory submissions13 
 
  Verification and validation of DHTs for use in clinical investigations 
 
  Use of DHTs to collect data for trial endpoints  
 
  Identification and management of risks associated with the use of DHTs during clinical 
investigations 
 
  Retention and protection of data collected by DHTs 
 
  Roles of sponsors and investigators related to the use of DHTs in clinical investigations 
 
The following topics are beyond the scope of this guidance: 
 
  Whether a DHT meets the definition of a device under section 201(h) of the FD&C Act14 
  
  Approaches to selecting, modifying, developing, and validating clinical outcome 
assessments (COAs) to measure outcomes of importance to patients in clinical 
investigations.15  
 
While also not addressed in this guidance, some of the considerations in this guidance may be 
helpful for other uses of DHTs, such as the screening and selection of trial participants and the 
enrichment of trial populations.16 
 
13 For the purposes of this guidance, FDA uses the term submission to refer to an IND, an IDE application, a 
marketing application, a DDT submission, or an MDDT submission. 
 
14 See footnote 9. 
 
15 For drugs and biological products, see the web page FDA Patient-Focused Drug Development Guidance Series for 
Enhancing the Incorporation of the Patients Voice in Medical Product Development and Regulatory Decision 
Making, available at https://www.fda.gov/drugs/development-approval-process-drugs/fda-patient-focused-drug-
development-guidance-series-enhancing-incorporation-patients-voice-medical.  In particular, see the draft guidance 
for industry, FDA staff, and other stakeholders Patient-Focused Drug Development:  Selecting, Developing, or 
Modifying Fit-for-Purpose Clinical Outcome Assessments (June 2022).  When final, this guidance will represent 
FDAs current thinking on this topic.  For medical devices, see the web page Clinical Outcome Assessments (COAs) 
in Medical Device Decision Making, available at https://www.fda.gov/about-fda/cdrh-patient-science-and-
engagement-program/clinical-outcome-assessments-coas-medical-device-decision-making.  
 
16 Enrichment is the prospective use of any patient characteristic to select a study population in which detection of a 
drug effect (if one is in fact present) is more likely than it would be in an unselected population.  See the guidance 
for industry Enrichment Strategies for Clinical Trials to Support Determination of Effectiveness of Human Drugs 
and Biological Products (March 2019).   
 
  3  Contains Nonbinding Recommendations 
 
 
This guidance is being issued, in part, to satisfy the mandate under section 3607(a) of the Food 
and Drug Omnibus Reform Act of 2022 (FDORA) to issue guidance regarding the appropriate 
use of digital health technologies in clinical trials.  
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required.  
 
 
II.  BACKGROUND 
 
Advances in technology, including sensors, general-purpose computing platforms, and methods 
for data processing, transmission, and storage have transformed the ability to remotely obtain 
and analyze clinically relevant information from individuals.  DHTs used for remote data 
acquisition are playing a growing role in health care and offer important opportunities in clinical 
research.  For example, DHTs may be used to measure biomarkers and to administer COAs, such 
as patient-reported outcomes and/or performance outcomes.17  Compared to intermittent trial 
visits, the use of DHTs to remotely collect data from trial participants may allow for more-
frequent or continuous data collection.  This may provide a broader picture of how participants 
feel or function in their daily lives.  DHTs provide opportunities to record data from trial 
participants (e.g., biomarkers, performance of activities of daily living, sleep, vital signs) 
wherever the participants may be (e.g., home, school, work, outdoors).  The data collection may 
involve passive monitoring by the DHT or the acquisition of data while participants are actively 
interacting with the DHT.  Data captured by DHTs can often be transmitted directly to 
investigators, sponsors, and/or other authorized parties, with the capability to maintain blinding 
or masking of the data when appropriate.  Note that some clinical investigations may use 
multiple DHTs to measure one or more clinical characteristics or events (see appendix A, 
example 4).  
 
The ability to capture and transmit data remotely increases opportunities for individuals to 
participate in clinical investigations where some or all of the trial-related activities occur at 
locations other than traditional clinical trial sites (decentralized clinical trials).18  Increasing 
access to and use of DHTs in clinical trials can potentially enable the inclusion of diverse and 
underrepresented populations by facilitating decentralized clinical trials.  This could help to 
ensure medical products are safe and effective for the population for which they will be used.  
Reducing the burden on trial participants can also improve trial recruitment, participant 
engagement, and retention throughout the study.  Moreover, use of DHTs in clinical 
 
17 Examples of performance outcomes include tests of visual acuity, memory, and auditory acuity in which 
participant responses to stimuli are analyzed to provide a clinical assessment. 
 
18 See the draft guidance for industry, investigators, and other stakeholders Decentralized Clinical Trials for Drugs, 
Biological Products, and Devices (May 2023).  When final, this guidance will represent FDAs current thinking on 
this topic.   
 
  4  Contains Nonbinding Recommendations 
 
investigations may facilitate inclusion of certain participants with physical or cognitive 
disabilities or pediatric participants.  For example, the use of sensors may be of value to obtain 
data about signs (e.g., scratching, sleep) from cognitively impaired or pediatric participants who 
are unable to report symptoms (e.g., itch, insomnia).  Sponsors should consider what impact the 
use of a DHT in a clinical investigation could have on the cohort participating (e.g., expanding 
participation of geographically dispersed individuals, limiting participation of those unwilling to 
use DHTs). 
 
 
III.  REGULATORY CONSIDERATIONS AND ENGAGEMENT WITH THE 
AGENCY  
 
Some DHTs that may be appropriate for use in a clinical investigation may meet the definition of 
a device under section 201(h) of the FD&C Act.19  Devices intended for use in clinical 
investigations, including DHTs, are exempt from most regulatory requirements applicable to 
devices, including marketing authorization,20 as long as the investigation complies with 
applicable requirements under 21 CFR part 812.    
 
In many cases, FDA regulations do not require submission of an IDE application to FDA for use 
of a device in a clinical investigation.  For example, where a DHT, as proposed for use in a 
clinical investigation of a drug or biological product under an IND, is a nonsignificant risk 
device (i.e., the DHT does not meet the definition of a significant risk device under 21 CFR 
812.3(m)), submission of an IDE application to FDA is not required if the investigation complies 
with the abbreviated requirements in 21 CFR 812.2(b).  In addition, if a clinical investigation 
involving a DHT that is a device falls into one of the categories of exempt investigations under 
21 CFR 812.2(c), submission of an IDE application to FDA is not required.  Further, when an 
approved or cleared device is used in a clinical investigation in accordance with its approved or 
cleared indications for use, submission of an IDE application is not required.21, 22  Although it 
may be uncommon, a DHT that is a device, as proposed for use in a clinical investigation of a 
drug or biological product under an IND, may meet the definition of a significant risk device 
under 21 CFR 812.3(m) and require submission of an IDE application to FDA under 21 CFR 
 
19 See footnote 9. 
 
20 Marketing authorizations for devices include clearance of a premarket notification (510(k)) submission (see 21 
CFR part 807, subpart E); granting of a De Novo classification request (see 21 CFR part 860, subpart D); and 
approval of a premarket approval application (PMA) (see 21 CFR part 814) or a humanitarian device exemption 
application (see 21 CFR part 814, subpart H).  For the purposes of this guidance, an FDA-authorized device is a 
device with marketing authorization. 
 
21 See 21 CFR 812.1 and 812.2(c)(1) and (2). 
 
22 Note that a sponsor must submit an IDE application for a device investigation that involves an exception from 
informed consent under 21 CFR 50.24 or if FDA notifies the sponsor that an IDE application is required for an 
investigation (21 CFR 50.24(d) and 812.20(a)(1)).  
 
  5  Contains Nonbinding Recommendations 
 
812.20 for the same clinical investigation.23  In these cases, when all information required in an 
IDE application under 21 CFR 812.20 is also contained in the IND, FDA generally does not 
intend to request that sponsors submit a separate IDE application.  
 
DHTs that meet the statutory definition of a device under section 201(h) of the FD&C Act are 
also subject to design control requirements, which are basic controls needed to ensure that the 
device being designed will perform as intended.24  For devices that do not have FDA marketing 
authorization and are used only in clinical investigations for remote data collection, the activities 
needed to ensure that devices will perform as intended in the clinical investigation can vary 
depending on the device and its specific function, including its context of use.  For such devices, 
FDAs assessment as to whether the device is fit-for-purpose in the investigation is primarily 
based on the information submitted to the Agency, and this guidance describes the types of 
information that can provide assurance that these devices, when used only for remote data 
collection in clinical investigations, will perform as intended.  Therefore, where sponsors 
conduct the types of verification and validation activities recommended in this guidance to 
ensure that a DHT used only in clinical investigations for remote data collection is fit-for-
purpose, FDA does not intend to otherwise assess sponsors compliance with design control 
requirements, when applicable.25  This policy does not apply when a DHT that is a device is 
intended for use outside of a clinical investigation. 
 
The CDRH Digital Health Center of Excellence, which was established to empower stakeholders 
to advance health care by fostering responsible and high-quality digital health innovation, can 
also serve as a resource on DHTs, including their regulatory status, for sponsors, DHT 
manufacturers, and other stakeholders.26  Sponsors can engage with FDA under the Q-
Submission Program to address whether use of a specific DHT proposed for use in a clinical 
investigation meets the definition of a significant risk device.27 
 
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.28  The responsible 
Center will consult other Centers as needed.  
 
23 For additional information on significant risk and nonsignificant risk devices, see https://www.fda.gov/medical-
devices/investigational-device-exemption-ide/ide-approval-process and the information sheet guidance for IRBs, 
clinical investigators, and sponsors Significant Risk and Nonsignificant Risk Medical Device Studies (January 2006). 
 
24 See 21 CFR 820.30.  
 
25 See 21 CFR 812.1 and 820.30.  Class I devices, other than those listed in 21 CFR 820.30(a)(2), are not subject to 
design controls.  See 21 CFR 820.30(a). 
 
26 For further information about the CDRH Digital Health Center of Excellence, see https://www.fda.gov/medical-
devices/digital-health-center-excellence. 
 
27 See the guidance for industry and FDA staff Requests for Feedback and Meetings for Medical Device 
Submissions: The Q-Submission Program (June 2023). 
 
28 Sponsors should follow each FDA Centers procedures for engaging with the Agency in the context of a 
development program.  For drugs and biological products, see the draft guidance for industry Formal Meetings 
 
  6  Contains Nonbinding Recommendations 
 
 
Developers of DHTs may choose to pursue qualification of DHTs as a DDT or an MDDT for a 
specific context of use.  A qualified DHT may be relied upon in clinical investigations to support 
submissions for drugs or biological products (if qualified as a DDT) or devices (if qualified as an 
MDDT) where the context of use is the same (e.g., measurement of a specific clinical event or 
characteristic in a specific disease population).  Developers of DHTs may choose to submit 
qualification proposals to the appropriate CDER/CBER DDT Qualification Programs29,30 (e.g., 
the COA Program or Biomarker Qualification Program31) and/or CDRHs MDDT Qualification 
Program.32,33  These are voluntary qualification programs that are independent of an individual 
marketing submission for a DHT that is a device or a submission for a clinical investigation that 
uses a DHT to collect data remotely.  Sponsors and other stakeholders also may consider 
submitting DHT-related proposals to the Innovative Science and Technology Approaches for 
New Drugs (ISTAND) Pilot Program, which is designed to expand DDT types by encouraging 
development of DDTs that are out of scope for other DDT qualification programs but may still 
be beneficial for drug development.34   
 
 
 
Between the FDA and Sponsors or Applicants of PDUFA Products (September 2023) and the draft guidance for 
industry Formal Meetings Between the FDA and Sponsors or Applicants of BsUFA Products (August 2023).  When 
final, these guidances will represent FDAs current thinking on these topics.  For medical devices, see the guidance 
for industry and FDA staff Requests for Feedback and Meetings for Medical Device Submissions:  The Q-
Submission Program.  For further information about FDA digital health regulatory policies, see 
https://www.fda.gov/medical-devices/digital-health/ask-question-about-digital-health-regulatory-policies.  For 
combination products, see the guidance for industry and FDA staff Requesting FDA Feedback on Combination 
Products (December 2020).  
 
29 See CDERs web page Drug Development Tools (DDT) Qualification Programs, available at 
https://www.fda.gov/drugs/development-approval-process-drugs/drug-development-tool-ddt-qualification-programs. 
 
30 See the guidance for industry and FDA staff Qualification Process for Drug Development Tools (November 
2020).  
 
31 The draft guidance for industry and FDA staff Biomarker Qualification:  Evidentiary Framework (December 
2018) may also be a helpful resource.  When final, this guidance will represent FDAs current thinking on this topic.   
 
32 See CDRHs web page Medical Device Development Tools (MDDT), available at https://www.fda.gov/medical-
devices/science-and-research-medical-devices/medical-device-development-tools-mddt. 
 
33 See the guidance for industry, tool developers, and FDA staff Qualification of Medical Device 
Development Tools (July 2023). 
 
34 See FDAs web page Innovative Science and Technology Approaches for New Drugs (ISTAND) Pilot Program 
Submission Process, available at https://www.fda.gov/drugs/innovative-science-and-technology-approaches-new-
drugs-istand-pilot-program/innovative-science-and-technology-approaches-new-drugs-istand-pilot-program-
submission-process.  
 
  7  Contains Nonbinding Recommendations 
 
IV.  CONSIDERATIONS WHEN USING DIGITAL HEALTH TECHNOLOGIES IN 
CLINICAL INVESTIGATIONS 
 
This section outlines some considerations for using DHTs in a clinical investigation to help 
ensure they are fit-for-purpose.  Sponsors are encouraged to engage with the DHT manufacturer 
or other parties to leverage any existing information, as appropriate, to support the DHTs 
suitability for use in the specific clinical investigation.  While a sponsor may not control the life 
cycle processes of the DHT, they still should ensure that the DHT remains fit-for-purpose 
throughout its use in a clinical investigation.   
 
A.  Selection of a Digital Health Technology and Rationale for Use in a Clinical 
Investigation 
   
In choosing an appropriate DHT, sponsors should consider the clinical event or characteristic of 
the disease or condition of interest that is to be measured, identify appropriate technical and 
performance specifications of a DHT, and consider the proposed trial population who will be 
using the DHT.  In addition, sponsors should consider the design of the clinical investigation, 
and the characteristics of the DHT that may influence trial participant use (e.g., the design of its 
user interface).   
 
The following are some specific issues that should be considered when selecting a DHT for a 
clinical investigation: 
 
1.  Clinical Trial Population 
 
Among other characteristics, education, language, age, health/physical condition, and technical 
aptitude of trial populations should be considered to ensure that trial participants will be able to 
use the DHT as intended for the purposes of the trial and to facilitate inclusion of diverse 
populations in whom the product is intended to be used.  For example, to use the DHT as 
intended, certain trial participants may need interfaces with large text, buttons, or screens for 
their interactions with the DHT or need the text to be translated into multiple languages.  Section 
IV.C.3 of this guidance discusses usability evaluations to gather feedback on a proposed DHT. 
 
2.  Technical and Performance Specifications 
 
To select the appropriate DHT for a clinical investigation, the sponsor should identify the 
minimum technical and performance specifications35 of the DHT.  If applicable, the sponsor 
should identify a specific product or products (e.g., model and/or version) that meet the 
minimum technical and performance specifications for a DHT to remain fit-for-purpose.  If new 
models and/or versions of the DHT or other technologies become available during the trial, the 
sponsor could consider adding those models and/or versions if they meet the minimum technical 
and performance specifications.   
 
 
35 Technical specifications of DHTs may include, but are not limited to, the operating system, storage capacity, 
and/or sensors to be used in a clinical investigation.  Performance specifications may include, but are not limited to, 
considerations regarding the accuracy, precision, and reliability of the DHT(s). 
  8  Contains Nonbinding Recommendations 
 
3.  Design and Operation of DHTs and Other Technologies  
 
The design and operation of the DHT and other technologies should be considered to determine 
if the DHT is fit-for-purpose. 
 
  DHT design (e.g., material, size, weight, appearance, portability) and ease of use may 
influence whether trial participants will use the DHT for the duration of the clinical 
investigation and in the manner described in the protocol.  These factors may be 
particularly important for DHTs that are wearable, where comfort and convenience may 
influence a trial participants ability and willingness to use the DHT for the duration 
specified in the protocol. 
 
  Some DHTs are designed to provide users with feedback on the measurements made.  If 
participants are able to view data or results from the DHT, it may impact their behavior 
or evaluation of the investigational product.  As noted in the background section of this 
guidance, data captured by DHTs can often be transmitted directly to investigators, 
sponsors, and/or other authorized parties, with the capability to maintain blinding or 
masking of the data when appropriate.  Sponsors should consider all of these factors 
when designing the clinical investigation.    
 
  Power needs, such as battery life and charging recommendations, may influence the 
feasibility of the DHT for data capture and a trial participants ability and willingness to 
use the DHT for the duration specified in the protocol. 
 
  Operational specifications (e.g., data storage capacity, frequency of data transmission) 
should be adequate to minimize missing data.  
 
  DHT alerts (e.g., low battery, poor signal, data not being recorded or transmitted to the 
server) are recommended to help trial participants, trial personnel, and/or sponsors 
prevent loss of data or missing data.  The trial should include processes to ensure that 
trial participants understand how to respond to these alerts. 
 
  Sponsors should consider environmental factors (e.g., temperature, humidity) that may 
affect the performance of DHTs in a clinical investigation. 
 
  Availability and capacity of participant and sponsor network systems should be adequate 
to handle the volume of data obtained, particularly for frequent or continuous recordings. 
 
  9  Contains Nonbinding Recommendations 
 
  Safeguards should be in place to manage cybersecurity risks,36 prevent unauthorized 
access to the DHT and the data it collects, and ensure privacy and security.37 
 
4.  Use of a Participants Own DHT and/or Other Technologies 
 
Sponsors should evaluate the advantages and disadvantages of allowing trial participants to use 
their own DHTs (e.g., continuous glucose monitors) and/or other technologies (e.g., general-
purpose computing platforms such as smartphones and tablets) for remote data acquisition in a 
clinical investigation.  Allowing participants to use their own DHTs or other technologies with 
which they are already familiar may potentially reduce the burden of using additional DHTs or 
other technologies provided by the sponsor.  However, allowing participants to use their own 
DHTs may not be appropriate for DHTs that are customized or highly specialized for specific 
uses (e.g., actigraphy with algorithms customized for participants with a specific movement 
disorder).  
 
Sponsor-provided DHTs or other technologies to support their operation should be available as 
an option to ensure that participants who do not bring their own are not excluded from the 
clinical investigation for that reason.  Sponsor-provided telecommunication services should also 
be made available as needed so that participants who have no or limited access to these services 
are not excluded from the clinical investigation.  
 
B.  Digital Health Technology Description in a Submission38 
 
In submissions that rely on or propose a clinical investigation that includes the use of a DHT,39 
the sponsor should explain how the DHT is fit-for-purpose for use in the clinical investigation.  
The description should include information such as design and related technological 
characteristics of the DHT, data output provided to the sponsor and investigator, and information 
on how the DHT measures the clinical event or characteristic of interest (e.g., use of 
accelerometry to measure steps or use of photoplethysmography to count heartbeats).  For many 
 
36 See the guidance for industry and FDA staff Cybersecurity in Medical Devices:  Quality System Considerations 
and Content of Premarket Submissions (September 2023).  The principles discussed in this guidance may also be 
helpful for addressing cybersecurity risks of DHTs used in clinical investigations of medical products that do not 
meet the definition of a device under section 201(h) of the FD&C Act. 
 
37 See the draft guidance for industry Electronic Systems, Electronic Records, and Electronic Signatures in Clinical 
Investigations:  Questions and Answers (March 2023).  When final, this guidance will represent FDAs current 
thinking on this topic.   
 
38 CDRH takes a least burdensome approach to regulatory questions or issues that arise throughout the total product 
lifecycle for medical devices, including evaluation of premarket submissions.  Least burdensome is defined to be the 
minimum amount of information necessary to adequately address a relevant regulatory question or issue through the 
most efficient manner at the right time.  For medical device submissions, the recommendations in this guidance will 
be implemented consistent with the least burdensome principles outlined in the guidance for industry and FDA staff 
The Least Burdensome Provisions:  Concept and Principles (February 2019). 
 
39 When completing Form FDA 1571 or Form FDA 356h (available at https://www.fda.gov/about-fda/reports-
manuals-forms/forms), applicants should check yes if the submission contains DHT data or a proposal to collect 
DHT data.   
 
  10  Contains Nonbinding Recommendations 
 
commercially available DHTs, the technical specifications and descriptions made publicly 
available and provided by the DHT manufacturer or by right of reference to a master file40 may 
be sufficient.  The sponsor should also describe the flow of data from the DHT to the first 
durable electronic data repository.   
 
To assist the Agency in understanding the sponsors plans for consistent data collection during 
the clinical investigation, sponsors should describe features that impact usability, such as the user 
interface, and how the DHT is worn, operated, and maintained (e.g., charged, calibrated).  
Sponsors should describe how access to the DHT or the data collected from it is controlled to 
ensure privacy and security.  The description should include methods for access control, when 
feasible, to ensure that only appropriate individuals are able to use the DHT or enter information.  
If applicable, the description should also include any options provided to allow the user to report 
information (e.g., symptoms or activities) that can supplement data recordings and help with the 
interpretation of the recording.  
 
To help show how integrity of the data collected with DHTs will be or is maintained, sponsors 
should include information about data management, including collection, storage, transmission, 
and archiving in the submission. 
 
C.  Verification, Validation, and Usability Evaluations of Digital Health 
Technologies 
 
This guidance uses the terms verification and validation to describe steps that help ensure that 
the DHT is fit-for-purpose for remote data collection in a clinical investigation.  Verification and 
validation should be addressed regardless of whether the DHT meets the definition of a device 
under section 201(h) of the FD&C Act.41  For the purposes of this guidance, verification is 
confirmation by examination and provision of objective evidence that the parameter that the 
DHT measures (e.g., acceleration, temperature, pressure) is measured accurately and precisely.  
Validation is confirmation by examination and provision of objective evidence that the selected 
DHT appropriately assesses the clinical event or characteristic in the proposed participant 
population (e.g., step count or heart rate).  Verification is often viewed as part of the validation 
process since validation is highly dependent upon comprehensive testing and other verification 
tasks previously completed at each stage of the development life cycle.  Verification and 
 
40 For information on master files, please see the relevant Centers web page on master files.  CDRH master files: 
https://www.fda.gov/medical-devices/premarket-approval-pma/master-files; CBER master files: 
https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/master-files-cber-regulated-
products; CDER master files: 
https://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/DrugMasterFilesDMFs/
default.htm. 
 
41 The terms verification and validation as used in this guidance are not intended to be synonymous with the terms 
defined in 21 CFR 820.3(aa) and 820.3(z) under the Quality System Regulation for devices (21 CFR part 820) or the 
terms software verification and validation as described in the guidance for industry and FDA staff General 
Principles of Software Validation (January 2002). 
 
  11  Contains Nonbinding Recommendations 
 
validation activities should consider all relevant functions of the DHT in the context of use in the 
clinical investigation.42 
 
Depending on the DHT and its context of use, verification and validation may begin with 
benchtop studies, progress to testing in healthy volunteers, and continue in individuals 
representing the population to be studied in the clinical investigation.43  These studies should 
include demonstration that the clinical event or characteristic to be assessed (e.g., step count or 
heart rate) is consistently and appropriately measured in the population of interest.  For example, 
the algorithm a DHT uses to capture steps in healthy participants may not be applicable for 
participants with Parkinsons disease with a shuffling gait.  Additionally, usability evaluations 
should identify and address any potential use errors or difficulties that trial participants or other 
intended users may experience when using the DHT.  
 
As discussed previously, sponsors can leverage verification and validation data made available 
(1) by DHT manufacturers or other third parties publicly, (2) in device labeling, or (3) by right of 
reference to other FDA submissions, when appropriate.   
 
The following subsections of this guidance present some additional considerations for the 
verification and validation of DHTs (section IV.C.1), interoperability (section IV.C.2), and 
usability evaluations (section IV.C.3).   
 
1.  Further Considerations for Verifying and Validating DHTs 
 
As part of the DHT verification and validation process, sponsors should consider involving DHT 
manufacturers, patients, caregivers, and other technical and clinical experts as appropriate.   
 
Verification confirms that the DHT meets its expected performance specifications.  Verification 
can include conforming to consensus performance standards, when applicable (e.g., International 
Electrotechnical Commission 60601-1) and/or an analysis to identify potential failure modes of a 
DHT and their causes and effects (e.g., failure modes and effects analysis).  For some DHTs and 
clinical investigations, it may be appropriate to identify and specify the conditions (e.g., 
temperature range) under which the DHT meets performance specifications.   
 
Validation studies, including certain usability evaluations, can be conducted in healthy 
volunteers and individuals with varying degrees of disease severity.  Depending on the type of 
 
42 For DHTs that include device software functions, sponsors should address the documentation recommendations in 
the guidance for industry and FDA staff Content of Premarket Submissions for Device Software Functions (June 
2023) when preparing a submission to the FDA. 
 
43 Where a DHT to be used for remote data collection in a clinical investigation meets the definition of a device 
under section 201(h) of the FD&C Act, clinical verification or validation testing of the DHT may meet the definition 
of a clinical investigation subject to applicable requirements under 21 CFR parts 50, 56, and/or 812.  Sponsors 
should engage with FDA through the Q-Submission Program to address whether use of a specific DHT proposed for 
use in a clinical investigation meets the definition of a significant risk device.  See also the guidance for industry and 
FDA staff Requests for Feedback and Meetings for Medical Device Submissions: The Q-Submission Program for 
additional information. 
 
  12  Contains Nonbinding Recommendations 
 
study, it may be conducted in a controlled laboratory setting, in a simulated living environment, 
and/or in a natural living environment.  The appropriate population to consider for these studies 
may depend on who is expected to use the DHT and whether the parameter being measured 
would be similarly obtained from a healthy volunteer and the target patient population for the 
medical product being studied.  
 
Depending on the particular DHT and clinical investigation, the verification and validation 
process may include: 
 
  Comparisons of measurements made by the DHT with reference measurements of the 
clinical event or characteristic (e.g., step count by actigraphy versus step count by 
observation). 
 
  Evaluation of factors that might impact the measurement, such as placement of a 
wearable DHT (e.g., wrist versus hip), or physical interference with the measurement, 
such as participant activities that may be misinterpreted as the clinical event or 
characteristic of interest (e.g., a bumpy car ride misinterpreted as a tremor).   
 
  Evaluation of the calibration process, when applicable.  Certain DHTs may require 
calibration by the user, with or without assistance by trial personnel (e.g., calibrating a 
mobile app or wearable for individual stride length to allow computation of the distance 
covered in a specific time interval).  The calibration process should be validated to ensure 
accurate and precise measurements of the clinical characteristic or event of interest, and 
the appropriate frequency of calibration should be determined. 
 
  Confirmation, either by new studies or by reference to existing data, that measurements 
across protocol-specified DHTs are consistent when the protocol permits use of more 
than one brand or model of DHT to collect the same data in a clinical investigation (see 
sections IV.A.2 and 4).   
 
  Evaluation and justification of potential differences between measurements obtained 
from participants remotely compared to measurements obtained from participants in a 
clinic setting using the same DHT.  A run-in period may be appropriate to ensure reliable 
data collection.   
 
Sometimes, DHT software applications may be used to administer certain COAs remotely (e.g., 
tests of auditory or visual acuity, tests of cognitive function) and may not rely on sensors for 
measurement.  DHT software should be verified and validated to ensure that it is fit-for-purpose.  
 
2.  Interoperability 
 
Sponsors should ensure the ability of connected systems in the clinical investigation to 
effectively and securely exchange information and to use the information that has been 
  13  Contains Nonbinding Recommendations 
 
exchanged.44  FDA encourages the use of public data exchange standards, including those related 
to identification of the data source, as appropriate.  Interoperability of DHTs should be evaluated 
to demonstrate that the interactions on the electronic interface perform as intended and the 
resulting DHT measurements are interpreted appropriately.45,46  
 
3.  Usability Evaluations 
 
Usability evaluations should be conducted to demonstrate that the DHT can be used as intended 
by the trial population, without errors or problems.  Usability evaluations are a critical 
component in confirming the suitability of the DHT in the proposed clinical investigation.  
Usability evaluations should be tailored to the risks and complexities associated with each DHT 
to be used in a clinical investigation.  Usability evaluations should assess if the design of the 
DHT will allow participants in the clinical investigation to use the proposed DHT as directed in 
the trial protocol. 
 
The guidance for industry and FDA staff Applying Human Factors and Usability Engineering to 
Medical Devices (February 2016) discusses important considerations for human factors 
validation testing.47  The principles addressed in that guidance serve an important role in medical 
device development and may be helpful for designing appropriate usability evaluations for DHTs 
proposed for use in clinical investigations of medical products.   
 
When appropriate, sponsors may be able to leverage data from prior human factors evaluations 
to evaluate whether trial participants can appropriately use the DHT (e.g., published studies in 
similar populations) without conducting further usability evaluations in the target study 
population.   
 
When designing usability evaluations, sponsors should consider the following:   
 
  Usability evaluations should assess the ability for participants to efficiently use the DHT 
in a remote setting.  
  
 
44 If DHTs exchange information with other health information technology (IT), the health IT should meet standards 
and implementation specifications according to 45 CFR part 170, subpart B where applicable, or other standards 
developed by consensus-based standards development organizations when standards and implementation 
specifications at 45 CFR part 170, subpart B are not applicable.   
 
45 The guidance for industry and FDA staff Design Considerations and Premarket Submission Recommendations for 
Interoperable Medical Devices (September 2017) discusses important considerations regarding interoperability of 
medical devices.  The principles addressed in that guidance may be helpful for addressing interoperability of DHTs 
used in clinical investigations of medical products. 
 
46 The FDA-recognized series of standards IEEE ISO 11073 Health informaticsPoint-of-care medical device 
communication address interoperability of personal health devices.  The principles addressed in these standards 
may be helpful for addressing interoperability of DHTs used in clinical investigations of medical products.  
 
47 For the purposes of this guidance, human factors evaluations and usability evaluations are considered 
synonymous.      
 
  14  Contains Nonbinding Recommendations 
 
  Usability evaluations are important to ensure proper use of the DHT so that 
measurements obtained from DHTs used in remote settings are accurate and precise.  
 
  Usability evaluations support the accuracy, completeness, and consistency of 
measurements as well as ongoing participant engagement throughout the duration of the 
clinical investigation.   
 
Findings from the usability evaluations can be used to improve the design and functionality of 
the DHT, to improve ease of use, and to inform the instructions for use and training provided to 
trial participants and trial personnel.   
 
D.  Evaluation of Endpoints Involving Data Collected Using Digital Health 
Technologies 
 
The submission should include a description of the endpoint or endpoints that involve data 
collected through a DHT or a combination of DHTs.  Methods of assessing trial participants 
responses to a medical product (e.g., increase in activity as measured by actigraphy, change in 
blood pressure) in a clinical investigation should be well-defined and reliable.48   
 
This section outlines general considerations for justifying endpoints (e.g., primary, secondary, 
exploratory) measured using data collected from DHTs, but does not address any disease-
specific endpoints.49  The principles that guide development of endpoints based on data captured 
by DHTs are the same as the principles for developing endpoints captured by other means.  
Sponsors should obtain input from interested parties (such as patients, caregivers, clinicians, 
engineers, statisticians, and regulators) to ensure that the endpoint is both clinically meaningful 
and the data are adequately captured by the DHT.  Sponsors should discuss their plans for 
endpoint development with the relevant review division.  See appendix B for an example of 
justifying an endpoint using a DHT.50 
 
1.  Defining the Endpoint  
 
A precise definition of an endpoint typically specifies the type of assessment(s) made (e.g., 
activity level, average heart rate, sleep quantity and quality), the timing of those assessments, the 
tool(s) used for the assessment(s), and other details, as applicable, such as if (and if so, how) 
multiple assessments for a trial participant will be combined.  
 
48 See 21 CFR 314.126 and 860.7. 
 
49 FDA has issued many disease-specific guidance documents that may address considerations for using particular 
endpoints in clinical trials of medical products for a given disease.  Sponsors should discuss disease-specific 
endpoints with the relevant review divisions.  For the most recent version of a guidance, check the FDA guidance 
web page at https://www.fda.gov/regulatory-information/search-fda-guidance-documents. 
 
50 The draft guidance for industry, FDA staff, and other stakeholders Patient-Focused Drug Development: 
Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making (April 2023) also 
includes information on endpoint development.  When final, this guidance will represent FDAs current thinking on 
this topic.   
 
  15  Contains Nonbinding Recommendations 
 
 
2.  Established Endpoints  
 
DHTs may serve as new ways to measure clinical characteristics or events that were previously 
measured in a clinical setting (e.g., blood pressure monitoring at home versus in a clinic).  When 
DHT measurements replicate existing measurements (e.g., weight measurements at home versus 
in the clinic) for the same endpoint, a new justification for the choice of the endpoint may not be 
needed.  However, the DHT should still be verified and validated for use in the clinical 
investigation (See section IV.C of this guidance).   
 
3.  Novel Endpoints 
 
Novel endpoints based on data captured by DHTs may provide opportunities for additional 
insight into participant function or performance that was previously not easily measurable (e.g., 
tremors).  While it is possible to measure some aspects of function or performance during 
participant visits to the clinic at a point in time, the use of DHTs potentially provides for their 
measurement over a longer time period and in different settings.   
 
When justifying a novel endpoint using data captured by the DHT, sponsors should address the 
following: 
 
  Whether the endpoint reflects how a participant feels, functions, or survives.  
 
  Whether a biomarker serving as a surrogate endpoint will predict or will be reasonably 
likely to predict clinical benefit. 
 
  Whether the effect of the intervention as captured by the novel endpoint is meaningful to 
the target patient population for the medical product being evaluated. 
 
  How the endpoint relates to other endpoints that are intended to reflect the same concept 
and have been used to support a marketing authorization for a similar indication.  In the 
absence of related endpoints, evidence from other sources of information (e.g., literature 
or input from stakeholders and experts) may support use of the endpoint. 
 
  Whether the novel endpoint is a well-defined and reliable measure of disease severity or 
health status (e.g., mild, moderate, or severe) to allow assessment of disease modification 
or progression. 
 
  When an existing medical product has already received marketing authorization based on 
evidence from a study using an established endpoint for the disease or condition of 
interest and the concept being evaluated by the novel endpoint is similar, it may be useful 
to determine whether the effect of that existing medical product (positive control) can be 
detected using the novel endpoint. 
 
  16  Contains Nonbinding Recommendations 
 
E.  Statistical Analysis and Trial Design Considerations 
 
FDA evaluates data collected via DHTs based on factors including, but not limited to, the 
endpoint under consideration, the medical product under investigation, and the patient population 
in which the product will be used.  Analyses of data collected from DHTs should be discussed in 
a statistical analysis plan. 
 
  The same method for collection of data should be used in all study arms.   
 
  Non-inferiority trial designs may not be appropriate when the effect size of the 
comparator has not been established using similar DHT measurements, making it difficult 
or impossible to define the non-inferiority margin.51,52 
 
  The definition of the endpoints and the source data53 from which the endpoints are 
derived for each trial participant (e.g., average daily number of steps across the treatment 
period) should be prespecified in the statistical analysis plan.54 
 
  Late phase trials should use the estimand framework of the International Council for 
Harmonisation (ICH) guidance for industry E9(R1) to provide a description of the 
treatment effect.  The statistical analysis plan and protocol should consider potential 
events (e.g., post-baseline initiation of an assistive device such as a cane or walker when 
the DHT is an activity tracker) that may affect data collection or the interpretation of 
endpoints.  The statistical analysis plan should describe how these events will be 
accounted for in the analyses (e.g., primary analysis and sensitivity analyses). 
  Use of a DHT to remotely acquire data in a clinical investigation may impact the type and 
amount of missing data.  Sponsors should have a plan in place to reduce the potential for 
missing data (e.g., sponsor and/or investigator automated data monitoring and alerts, 
participant reminders, run-in period for participants, investigator outreach to 
participants) and to address missing data and data quality issues.  These issues might 
overlap with considerations related to risk management plans (See section IV.H.1).  
 
  The study should be designed to ensure the collection of appropriate data needed to 
perform planned analyses.  The protocol and statistical analysis plan should also:  
 
 
51 See the guidance for industry Non-Inferiority Clinical Trials to Establish Effectiveness (November 2016).  
 
52 See the International Council for Harmonisation (ICH) guidance for industry E10 Choice of Control Group and 
Related Issues in Clinical Trials (May 2001). 
 
53 See section IV.G of this guidance  Record Protection and Retention.  
 
54 See the ICH guidance for industry E9(R1) Statistical Principles for Clinical Trials:  Addendum:  Estimands and 
Sensitivity Analysis in Clinical Trials (May 2021).   
 
  17  Contains Nonbinding Recommendations 
 
  Define relevant events and issues that could affect data collection, data quality, and 
analysis, including changes in technology during the study and whether the DHT is 
used as directed 
  Describe strategies for identifying and handling these events and issues 
 
F.  Risk Considerations When Using Digital Health Technologies 
 
Sponsors, investigators, and institutional review boards (IRBs) should consider any risks to trial 
participants associated with use of the DHTs for data collection.55  The risks of using a DHT in a 
clinical investigation can generally be broadly categorized as clinical risks and privacy-related 
risks, although there is some overlap between these two areas.  The following sections describe 
some of the risks pertaining to the use of DHTs that, depending on the specific design of the 
clinical investigation and DHTs used, may need to be assessed by the IRB, communicated in the 
informed consent document, and addressed by the sponsor in the submission.56  
 
1.  Clinical Risks  
 
  The physical features of the DHT should be evaluated for discomfort and risk of injury 
(e.g., wrist band occluding blood supply, skin contacting components causing skin 
irritation).  Evidence from safety testing and usability evaluations conducted by the DHT 
manufacturer, if available, or the sponsor of the clinical investigation may be helpful to 
show that risks associated with use of a DHT by trial participants are minimized. 
 
  If applicable, instructions for re-use, such as processes for cleaning the DHT (e.g., 
electrode sensors) before and after use, should be provided to trial participants to 
prevent infection or other adverse events.57  
 
  When measurements made by DHTs (e.g., glucometers) are used as the basis to modify 
the administration of the investigational product or the treatment of trial participants, it is 
 
55 See 21 CFR parts 50 and 56 for requirements pertaining to the protection of participants in and IRB review of 
clinical investigations.  Research conducted or supported by the Department of Health and Human Services must 
also comply with applicable requirements in 45 CFR part 46.  In addition, we note that sponsors should ensure 
compliance, as applicable, with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) 
Administrative Simplification provisions set forth at 45 CFR parts 160 and 164 and 42 CFR part 2.   
 
56 For example, to approve a clinical investigation, an IRB must determine that, among other things, risks to 
participants are minimized in accordance with 21 CFR 56.111(a)(1), and the informed consent process must describe 
reasonably foreseeable risks or discomforts to the subject under 21 CFR 50.25(a)(2).  In addition, sponsors must 
provide certain information in an IND or IDE application regarding risks to participants and the safety of proposed 
clinical investigations.  See, e.g., 21 CFR 312.23(a)(6)(iii)(g), 312.23(a)(10)(iv), 812.20(b)(2), and 812.25(c). 
 
57 Manufacturers of reusable DHTs that are devices are responsible for having labeling that bears adequate directions 
for use, including instructions on preparing a device for use.  See 21 CFR 801.5(g).  For more information on the 
formulation and scientific validation of reprocessing instructions for reusable devices, see the guidance for industry 
and FDA staff Reprocessing Medical Devices in Health Care Settings:  Validation Methods and Labeling (March 
2015). 
 
  18  Contains Nonbinding Recommendations 
 
critical to evaluate the risk of erroneous measurements resulting in excessive, inadequate, 
or inappropriate treatment. 
 
  Sponsors should consider cybersecurity threats that could potentially impact the 
functionality of the DHT, resulting in a clinical risk to participants (e.g., corrupting the 
output of a continuous glucose monitor).  Accordingly, sponsors should consider FDA 
information on cybersecurity58 to ensure that data can be securely stored and transmitted. 
 
2.  Privacy-Related Risks  
 
Sponsors, investigators, and IRBs should be aware that unique privacy risks may arise when 
DHTs are used in a clinical investigation.  The following should be considered, as applicable: 
 
  The risk of potential disclosure of personally identifiable information or participant 
locations via a breach of the DHT or associated data storage, such as a durable electronic 
data repository. 
 
  DHTs or other technologies may have end-user licensing agreements or terms of service 
that allow sharing of data with other parties, such as the manufacturer of a general-
purpose computing platform used by a DHT.  See section IV.F.3 of this guidance for 
considerations related to informing potential trial participants about who will have access 
to their trial data if they decide to participate. 
 
  To protect data privacy for trial participants, it may be appropriate for sponsors to 
proactively work with manufacturers to modify the end-user license agreement or 
terms of service for the purposes of the study, as applicable.  
 
  Sponsors should ensure that appropriate security safeguards are in place to secure data at 
rest and in transit to prevent access by intervening or malicious parties (e.g., 
cybersecurity threats).   
 
3.  Informed Consent 
 
FDA regulations at 21 CFR part 50 set forth the requirements for obtaining the informed consent 
of participants59 in clinical investigations.  DHTs can be used to obtain electronic informed 
consent in a clinical investigation.60   
 
 
58 Additional information on cybersecurity, including managing cybersecurity risk, is provided by the CDRH Digital 
Health Center of Excellence at https://www.fda.gov/medical-devices/digital-health-center-excellence/cybersecurity 
 
59 FDAs regulations in 21 CFR parts 50, 56, 312, and 812 use the term subject or human subject; however, in this 
guidance, we use the term participant instead. 
 
60 See the guidance for IRBs, investigators, and sponsors Use of Electronic Informed Consent in Clinical 
Investigations:  Questions and Answers (December 2016).  See also the guidance for IRBs, clinical investigators, 
and sponsors Informed Consent (August 2023), section V, question 10 regarding electronic informed consent.  
 
  19  Contains Nonbinding Recommendations 
 
Some considerations for what information to include in the informed consent process regarding 
the DHT being used in a clinical investigation include but are not limited to the following: 
 
  The informed consent process must describe any reasonably foreseeable risks or 
discomforts to participants (see sections IV.F.1 and IV.F.2 of this guidance), including 
reasonably foreseeable risks or discomforts related to the use of the DHT in the clinical 
investigation.61  Information regarding what may be done to mitigate serious risks, and 
risks and discomforts more likely to occur, should also be considered for inclusion.  
 
  When appropriate, a statement must be included indicating that use of the DHT during 
the clinical investigation may involve risks to the participant (or to the embryo or fetus if 
the participant is or may become pregnant) which are currently unforeseeable.62  
 
  The informed consent process should explain the type of information that will be 
collected by the DHT and how that information will be used and monitored.  When 
relevant, participants should be informed of what action to take in case of any concerning 
sign, symptom, or abnormal clinical event (e.g., hypoglycemia or abnormal cardiac 
rhythm) detected by a DHT, such as seeking emergency medical attention, if appropriate.  
 
  The informed consent process should specify who may have access to data collected 
through the DHT during or after the clinical investigation (e.g., sponsors, investigators, 
participants, DHT manufacturers, other specified third parties) and during what time 
frame.63 
 
  An explanation of measures to protect participant privacy and data, and limitations to 
those measures, when DHTs are used should be included. 
 
  If participants may incur additional expense because they are taking part in the clinical 
investigation, the consent process must explain the added costs,64 which could include 
costs for the participants that may result from using the DHT during the clinical 
investigation (e.g., data use charges). 
 
  DHTs or other technologies may be covered by end-user license agreements or terms of 
service as a condition of use, which may, among other things, allow DHT or other 
technology manufacturers and other parties to gain access to personal information and 
data collected by the DHT or other technology.  When applicable, sponsors and 
investigators should ensure that the informed consent process explains to participants that 
 
61 See 21 CFR 50.25(a)(2).  
 
62 See 21 CFR 50.25(b)(1). 
 
63 In addition, the informed consent process must note the possibility that FDA will inspect records identifying the 
participants (21 CFR 50.25(a)(5)). 
 
64 21 CFR 50.25(b)(3). 
 
  20  Contains Nonbinding Recommendations 
 
their data may be shared outside of the clinical investigation, according to the end-user 
license agreement or terms of service.  End-user license agreements and terms of service 
typically are lengthy and use complex terminology.  Sponsors and investigators 
proposing use of DHTs for data collection should understand how such agreements or 
terms of service may affect trial participants and address this information when 
developing informed consent documents.65 
 
G.  Record Protection and Retention 
 
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.66,67 
 
The draft guidance for industry Electronic Systems, Electronic Records, and Electronic 
Signatures in Clinical Investigations: Questions and Answers provides proposed 
recommendations on the use of electronic records in clinical investigations of medical products.  
The draft guidance addresses DHTs that allow for remote data capture directly from trial 
participants during a clinical investigation, as well as related issues pertaining to access controls, 
audit trails, data sources, and inspections. 
 
In planning for record retention in a clinical investigation using DHTs, FDA recommends the 
following: 
 
  Sponsors should discuss with review divisions the type of DHT data recorded from 
participants to be submitted for FDA review.  This may involve complete data, summary 
data, sample data, and/or abnormal data obtained during continuous or frequent 
recording.  FDA may request data in various formats based on the DHT used in a given 
clinical investigation.  For more information on study data formats and a summary of 
requirements for certain submissions, please refer to the FDA Data Standards Catalog.68  
 
  The data output of the DHT to support an endpoint for the clinical investigation, 
including associated metadata (e.g., the times the measurements were made), should 
 
65 For further information, see the Secretarys Advisory Committee on Human Research Protections web page 
Attachment B - Clarifying Requirements in Digital Health Technologies Research, available at 
https://www.hhs.gov/ohrp/sachrp-committee/recommendations/april-7-2020-attachment-b/index.html. 
 
66 See 21 CFR 312.57, 312.58, 312.62, and 312.68. 
 
67 See 21 CFR 812.2(b)(1)(v) and (vi), 812.140, 812.145, and 812.150.  
 
68 See FDA Study Data Standards Resources, available at https://www.fda.gov/industry/fda-data-standards-advisory-
board/study-data-standards-resources, and the Data Standards Catalog, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/data-standards-catalog. 
 
  21  Contains Nonbinding Recommendations 
 
generally be transmitted to a durable electronic data repository.  These data can take the 
form of discrete clinical events measured using built-in analytics or algorithms (e.g., 
heart beats, breaths, steps) or continuous recordings (e.g., electrocardiograms), among 
other things.  DHT data must be maintained according to record retention requirements69 
and should be in human readable form.70  Generally, FDA does not intend to request 
machine or raw data that require electronic processing to be understood (e.g., voltages) 
during an inspection. 
 
  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 sponsors 
prespecified plan. 
 
  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). 
 
H.  Other Considerations When Using Digital Health Technologies During a 
Clinical Investigation 
 
To help ensure the quality and integrity of data, adequate protection of participants, and 
satisfaction of regulatory requirements applicable to clinical investigations, sponsors and 
investigators should consider the following recommendations with respect to clinical 
investigations that involve use of a DHT to remotely acquire data.71  
 
1.  Sponsors Role 
 
The sponsor should: 
 
  Develop and ensure training for trial personnel and trial participants (see section IV.H.3 
of this guidance) on using DHTs according to the protocol (e.g., wearing the DHT for the 
specified time period).  Sponsors should incorporate feedback from usability evaluations 
(see section IV.C.3) into the training.  
 
69 See 21 CFR 312.62(c) and 812.140(d).   
 
70 See 21 CFR 11.10(b). 
 
71 See generally, e.g., 21 CFR part 11, part 50, part 312, and part 812.  See also the ICH guidance for industry 
E6(R2) Good Clinical Practice:  Integrated Addendum to ICH E6(R1) (March 2018).   
 
  22  Contains Nonbinding Recommendations 
 
 
  Develop a plan for technical assistance to trial participants or trial personnel for all DHTs 
used during the trial, which may involve collaboration with DHT or technology vendors 
or other parties. 
 
  Develop a risk management plan to address potential problems trial participants may 
experience when using a DHT or other technology during a clinical investigation.72  
Potential problems may involve, but are not limited to: 
 
  Clinical (see section IV.F.1) and privacy-related (section IV.F.2) risks. 
 
  Participants using the DHT incorrectly. 
 
  Interference between mobile applications or software functions used in a clinical 
investigation and the other potential functions of a DHT or other technology.  This 
may be of particular importance if trial participants are using their own DHTs or other 
technology during the clinical investigation (see section IV.A.4). 
 
  Loss, damage, and replacement of a DHT, including a corrective action plan to 
prevent compromising participant privacy or data integrity. 
 
  DHT malfunction, including failure of associated technology (e.g., general-purpose 
computing platform data transmission failure, loss of battery power). 
 
  Trial participants upgrading or updating a DHT, which may include updates 
associated with general-purpose computing platforms (e.g., hardware or software; 
models or versions) during the clinical investigation (see section IV.H.4). 
 
  Develop a safety monitoring plan as part of the protocol that addresses how abnormal 
measurements related to trial participants safety (e.g., hypoglycemia, arrhythmia, apnea) 
measured by DHTs will be reviewed and managed. 
 
  FDA generally does not expect investigators to monitor DHT data continuously, but 
there may be circumstances where this is clinically necessary.  The safety monitoring 
plan should indicate how frequently investigators will review continuous data, if 
applicable. 
 
  The plan should indicate under what circumstances and how trial participants will be 
informed of abnormal findings detected by the DHT (e.g., critical abnormality alerts).  
The plan should describe how participants and trial personnel should respond to these 
findings.   
 
 
72 Sponsors should consider the risk management plan when developing a monitoring plan for the clinical 
investigation.  See the guidance for industry A Risk-Based Approach to Monitoring of Clinical Investigations 
Questions and Answers (April 2023).   
  23  Contains Nonbinding Recommendations 
 
  As in any trial, the plan should describe what action participants should take in case 
of any concerning sign, symptom, or abnormal clinical event (e.g., palpitations, chest 
pain, syncope), such as seeking emergency medical attention, if appropriate. 
 
  Ensure that data have been transferred from the DHT into a durable electronic data 
repository (see section IV.G of this guidance). 
 
  Develop end-of-study closeout procedures (e.g., when/how data collection and/or 
transmission ends, revocation of system access). 
 
2.  Investigators Role 
 
Investigators should: 
 
  Ensure that trial participants understand what information will be collected by the DHT; 
how that information will be used, monitored, and acted upon; who will have access to 
the data; and how the security and privacy of data collected by the DHT will be 
maintained.  The relevant submission should describe the investigators role in ensuring 
appropriate use of DHTs.  
 
  Provide sponsor-developed training to participants on how to use the DHT according to 
the protocol (e.g., wearing the DHT for the specified time period).  Training can be done 
remotely, as appropriate (e.g., through video conferencing).  
 
  Review data from DHTs as specified in the safety monitoring plan (see section IV.H.1).    
 
3.  Training 
 
Trial participants and trial personnel should be trained on the appropriate use of DHTs.  In some 
situations, it may also be appropriate to provide training to participants caregivers.  Trial 
personnel should be trained on responsibilities for data collection and maintenance of trial 
integrity and quality throughout the investigation.  Any training materials should be included as 
part of the submission.  
 
Training should: 
 
  Occur before trial participants or caregivers begin using the DHT to collect data for the 
purposes of the clinical investigation 
 
  Be scheduled, provided, and documented during the clinical investigation, as appropriate 
(e.g., if changes or updates alter the way sponsors, clinical investigators, other trial 
personnel, trial participants, or caregivers interact with the DHT) 
 
  Be available to trial personnel, trial participants, and/or caregivers having difficulty using 
DHTs during the investigation 
 
  24  Contains Nonbinding Recommendations 
 
Sponsors should consider addressing the following as part of the training for trial participants, 
caregivers, and/or trial personnel, as appropriate: 
 
  Setting up, activating, and operating DHTs  
 
  Confirming that the use of the DHT will be restricted to the trial participants and/or 
caregivers 
 
  Collecting data at appropriate time intervals 
 
  Uploading or syncing data 
 
  Ensuring the security and privacy of data collected by the DHT 
 
  Wearing DHTs appropriately (e.g., location and duration), if applicable 
 
  Properly cleaning the DHTs before or after use, if applicable 
 
  Connecting to wireless or cellular networks 
 
  Handling known adverse events associated with the DHT (e.g., rash from actigraphy 
bands) 
 
  Responding to DHT signals, notifications, errors, hardware upgrades, and software 
updates, including procedures for troubleshooting and instructions for whom to contact 
for unresolved issues   
 
  Verifying that DHTs are being used appropriately and that data are being collected, 
uploaded, or synchronized as planned 
 
4.  DHT Updates and Other Changes 
 
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 
  25  Contains Nonbinding Recommendations 
 
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.     
 
If changes to the measurement have occurred after the update, sponsors should compare data 
from DHTs before and after the update.  Sensitivity analyses may be necessary to evaluate the 
impact of the update.  Sponsors should take steps to mitigate any resulting differences.  Sponsors 
should specify how these differences will be addressed in the analysis of the trial prior to 
unblinding (if applicable) and describe the impact differences may have on trial outcomes.  
Significant changes in the measurement after updates may invalidate the results from a clinical 
investigation.   
 
5.  DHT Error or Loss 
 
Procedures should be in place to identify and address DHT errors (such as those involving 
batteries, sensors, software, etc.) and to provide replacements if the DHT is lost or damaged.  
Contingency plans may provide for alternate data collection and recording mechanisms, if 
possible, during these times.  
 
If malware is detected on a DHT during a clinical investigation, sponsors should pursue 
appropriate corrective action. 
   
  26  Contains Nonbinding Recommendations 
 
GLOSSARY 
 
The following terms are defined for the purposes of this guidance: 
 
context of use:  A statement that fully and clearly describes the way the medical product 
development tool is to be used and the regulated product development and review-related 
purpose of the use. 
 
digital health technology (DHT):  A system that uses computing platforms, connectivity, 
software, and/or sensors for health care and related uses.  These technologies span a wide range 
of uses, from applications in general wellness to applications as a medical device.  They include 
technologies intended for use as a medical product, in a medical product, or as an adjunct to 
other medical products (devices, drugs, and biologics).  They may also be used to develop or 
study medical products. 
 
durable electronic data repository:  An enduring database that is electronically protected from 
alterations and is maintained until the end of the record retention period. 
 
general-purpose computing platform:  A commercial off-the-shelf computing platform, with 
or without wireless connectivity (e.g., smartphone, tablet).   
 
remote data acquisition:  Collection of data from a participants location that is distant from the 
investigator or trial personnel. 
 
sensor:  A transducer that converts a physical, biological, or chemical parameter into an 
electrical signal; for example, temperature, pressure, flow, or vibration sensor.  A sensor is 
typically hardware. 
 
 
  27  Contains Nonbinding Recommendations 
 
APPENDIX A:  EXAMPLES OF POTENTIAL DIGITAL HEALTH TECHNOLOGY 
USE IN CLINICAL INVESTIGATIONS 
 
The following examples are intended to illustrate various types of digital health technologies 
(DHTs) that can be used in clinical investigations.  These examples should not be taken to mean 
that the DHT(s) described do or do not adequately measure an endpoint of interest.   
 
1.  Consumer activity tracker bracelet 
 
  Description of the DHT:  Off-the-shelf consumer activity tracker bracelet with 
sensors and software to measure step count  
  
  Function(s) of the DHT:  Remotely measure a participants steps during a clinical 
investigation as part of the endpoint of interest in the evaluation of a novel orthotic 
device to treat knee osteoarthritis 
 
2.  Memory task mobile application  
 
  Description of the DHT:  A mobile application used by participants on their 
smartphones to complete a clinical outcome assessment (COA) memory task during 
the clinical investigation   
 
  Function(s) of the DHT: (1) Measure participants active performance on a memory 
task during a clinical investigation as part of the endpoint of interest in the evaluation 
of a drug to treat symptoms of Alzheimers disease, (2) send participants a reminder 
to complete the memory task   
 
3.  FDA-authorized continuous glucose monitor device 
 
  Description of the DHT:  FDA-authorized continuous glucose monitor, including a 
sensor and a mobile application, used within its authorized indications for use to 
continuously track hypoglycemic episodes in participants remotely 
  
  Function(s) of the DHT:  During a clinical investigation, remotely (1) measure 
glucose levels continuously, (2) analyze data to identify hypoglycemic episodes as 
part of the endpoint of interest in the evaluation of a drug for the management of 
Type 2 Diabetes, (3) display data to participants, and (4) alert participants of 
hypoglycemic episodes 
 
4.  Multiple DHTs  In this example, the DHTs described in 4a, 4b, and 4c are used 
concurrently as part of a clinical investigation of a medical product to treat a pulmonary 
disease. 
 
  28  Contains Nonbinding Recommendations 
 
a.  FDA-authorized spirometer with smart connectivity 
 
  Description of the DHT:  FDA-cleared spirometer with smart connectivity used 
within its cleared indications for use 
 
  Function(s) of the DHT:  Measure participants pulmonary function daily in the 
participants home environment during the clinical investigation as part of the 
endpoint(s) of interest in the evaluation of a medical product to treat a pulmonary 
disease  
 
b.  Consumer activity tracker bracelet 
 
  Description of the DHT:  Off-the-shelf consumer activity tracker bracelet that 
includes sensors and software intended to measure participants activity 
 
  Function(s) of the DHT:  Remotely measure participants activity (e.g., walking 
and standing bouts) longitudinally during the clinical investigation as part of the 
endpoint(s) of interest in the evaluation of a medical product to treat a pulmonary 
disease  
 
c.  Mobile application where participants rate their functioning each day 
 
  Description of the DHT:  A mobile application participants use with a 
smartphone or tablet (the mobile application is compatible with multiple 
platforms) to rate their function each day  
 
  Function(s) of the DHT:  Remotely collect data on the participants functioning 
each day during the clinical investigation as part of the endpoint(s) of interest in 
the evaluation of a medical product to treat a pulmonary disease 
 
  29  Contains Nonbinding Recommendations 
 
APPENDIX B:  EXAMPLE OF SELECTING A DIGITAL HEALTH TECHNOLOGY 
FOR A CLINICAL INVESTIGATION AND JUSTIFYING THE ENDPOINT FOR 
WHICH IT IS USED1 
 
The following example is intended to describe at a high level a digital health technology (DHT) 
being developed and considered for use in a clinical investigation.  Please note that this 
generalized example should not be taken to mean that the DHT described does or does not 
adequately measure an endpoint of interest.  Sponsors should provide detailed descriptions of the 
DHT and the context of use in their submission. 
 
A portable wearable device to assess sleep parameters in the home setting in trial participants 
with insomnia disorder 
 
A sponsor is developing a new drug for the treatment of insomnia disorder and is considering the 
use of a portable wearable device that has received FDA marketing authorization to remotely 
measure sleep parameters (e.g., latency to persistent sleep, wake after sleep onset, and total sleep 
time (TST)) in the home setting.  The context of use of the DHT in the clinical investigation is 
the same as in the marketing authorization.  Existing methods to assess these sleep parameters in 
clinical investigations are based on diary-recorded participant estimates or on polysomnography 
(PSG) conducted in a sleep laboratory.  The sponsor believes that this DHT will be able to 
measure sleep parameters with greater accuracy and precision than diary-recorded estimates.  
The sponsor also believes that measuring a participants sleep parameters in a home environment 
using a DHT will allow measurements over longer periods of time than PSG and is more 
generalizable than laboratory-based PSG measurements.  The proposed functions of the DHT for 
the clinical investigation are to remotely measure multiple sleep parameters (e.g., sleep latency, 
sleep efficiency, sleep awakening) while participants sleep at home. 
 
Important issues for the sponsor to consider in its development plan may include:2 
 
DHT Selection, Verification, and Validation: 
 
FDA marketing authorization of the DHT may support verification and validation of the DHT if 
the context of use for the clinical investigation falls within the cleared or approved indications 
for use.  Questions that the sponsor should consider when selecting a DHT may include: 
 
1.  How does the DHTs analysis of sleep parameters compare with PSG in terms of 
accurately determining whether patients are awake or asleep at a given point in time? 
 
 
1 This appendix provides a hypothetical, simplified example intended to illustrate considerations related to selecting 
an appropriate DHT to use for remote data collection in a clinical investigation and justifying the endpoint for which 
it is used.  It is not intended to suggest that any particular DHT will be suitable to use for remote data collection in a 
clinical investigation or that data collected from such a DHT will be sufficient to support a regulatory submission to 
FDA. 
 
2 Many of the issues illustrated in this example would be relevant for a sponsor to consider in its development plan 
regardless of whether the DHT at issue meets the definition of a device under section 201(h) of the FD&C Act. 
  30  Contains Nonbinding Recommendations 
 
2.  Are the DHTs measurements reproducible over the range of environmental conditions 
(e.g., temperature, nearby electronics) expected during the clinical investigation? 
 
3.  Are the DHTs measurements consistent across the range of factors (e.g., body 
morphology, skin color, variation in sensor placement, movements during sleep, other 
neurologic or psychiatric conditions, other medications or psychoactive substances) that 
may introduce variability into measurements expected during the clinical investigation? 
 
Usability Evaluation: 
 
The sponsor may consider conducting usability evaluations to assess whether the intended 
population for the clinical investigation will be able to use the DHT as directed in the protocol.  
In designing these evaluations, the sponsor should consider the following: 
 
1.  Is the DHT appropriately designed for use by the intended population for the clinical 
investigation of the drug, including older adult patients and/or their caregivers (if 
applicable)?  For example, will trial participants wear the DHT correctly?   
 
2.  How frequently should the DHT be charged and are there any expected challenges with 
the participants charging practices? 
 
3.  How will participants transmit data from the DHT to the investigator or sponsor? 
 
Endpoint Justification: 
 
This hypothetical DHT would provide data similar to sleep data collected during laboratory-
based PSG.  This DHT would, however, allow for nightly monitoring of sleep activity, whereas 
PSG data are typically collected at only select times relative to the entire duration of the clinical 
investigation (e.g., 2 successive days at baseline and 2 successive days at end of treatment).  The 
increased monitoring frequency presents opportunities to construct endpoints that rely on 
multiple data points (e.g., extended observation period averages and temporal trends). 
 
The sponsor should consider the following when developing an endpoint based on measurements 
using the portable wearable device: 
 
  The sponsor can solicit input from subject-matter experts, clinicians, regulators, patients, 
and/or caregivers to support a proposed endpoint. 
 
  An established endpoint using PSG is the change in TST from baseline to end of treatment.  
Using a DHT for remote data acquisition can permit longitudinal measurement, and the 
primary endpoint could potentially make use of the entire time series of TST values over the 
duration of the clinical investigation.  
 
  Because an endpoint might involve high-volume, high-frequency data (e.g., the entire time 
series of nightly assessments over the duration of the clinical investigation), the sponsor 
should: 
  31  Contains Nonbinding Recommendations 
 
 
  Prespecify the approach for defining an endpoint based on the multiple assessments 

within each participant, the population-level summary measure that compares the 
investigational product to a control, and the statistical analysis methodology. 
 
  Describe the potential scenarios for missing data and the methods for assessing the 

impact of the missing data on trial results.  Types of missing data may include missing a 
group of observations within a day, missing an entire day, or missing an entire week. 
 
  Describe how the DHT measurements compare to traditional PSG measurements and how a 
difference may impact the assessment of a drug effect. 
 
The sponsor may want to consider incorporating clinical outcome assessments (COAs) such as 
patient-reported outcome measures to understand how a trial participant feels and functions 
during the clinical investigation.  Associations between COA and wearable DHT data may 
provide for a broader assessment of sleep parameters and their impact on a participants daily 
activities. 
 
 
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