Decentralized Clinical Trials for 
Drugs, Biological Products, and 
Devices 
 
Guidance for Industry, Investigators, and 
Other Stakeholders 
 
 
 
 
DRAFT GUIDANCE 
 
  This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 90 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance.  Submit electronic comments to https://www.regulations.gov.  Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, Rm. 1061, Rockville, MD 20852.  All comments should be identified with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this draft document, contact (CDER) Ryan Robinson, 240-402-9756; 
(CBER) Office of Communication, Outreach, and Development, 800-835-4709 or 240-402-
8010; (CDRH) Office of Clinical Evidence and Analysis, cdrhclinicalevidence@fda.hhs.gov; or 
(OCE) Paul Kluetz, 301-796-9657.  
 
 
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) 
 
 
May 2023 
Clinical/Medical 
25036308dft    
Decentralized Clinical Trials for 
Drugs, Biological Products, and 
Devices 
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, Rm. 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, Rm. 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) 
 
May 2023 
Clinical/Medical 
     
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
TABLE OF CONTENTS 
 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  RECOMMENDATIONS FOR IMPLEMENTING DCTS ........................................... 3 
A.  DCT Design .................................................................................................................................... 3 
B.  Remote Clinical Trial Visits and Clinical Trial-Related Activities ........................................... 4 
C.  Digital Health Technologies .......................................................................................................... 5 
D.  Roles and Responsibilities ............................................................................................................. 6 
1. The Sponsor ..................................................................................................................................... 6 
2. The Investigator and Delegation of Trial-Related Activities ........................................................... 7 
E.  Informed Consent and Institutional Review Board Oversight ................................................ 10 
F.  Investigational Products in a DCT ............................................................................................. 11 
1. Drugs and Biological Products ..................................................................................................... 11 
2. Medical Devices ............................................................................................................................. 12 
G.  Packaging and Shipping of Investigational Products ............................................................... 12 
H.  Safety Monitoring Plan................................................................................................................ 13 
I.  Software Used in Conducting DCTs .......................................................................................... 14 
GLOSSARY................................................................................................................................. 16 
 
 
 
   
 
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Decentralized Clinical Trials for Drugs, Biological Products, and 
1 
Devices  
2 
Guidance for Industry, Investigators, and Other Stakeholders1 
3 
4   
5   
6  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
7  Administration (FDA or Agency) on this topic.  It does not establish any rights for any person and is not 
8  binding on FDA or the public.  You can use an alternative approach if it satisfies the requirements of the 
9  applicable statutes and regulations.  To discuss an alternative approach, contact the FDA staff responsible 
10  for this guidance as listed on the title page.   
11   
12   
13   
14   
15  I.  INTRODUCTION  
16   
17  This draft guidance provides recommendations for sponsors, investigators, and other 
18  stakeholders regarding the implementation of decentralized clinical trials (DCTs)2 for drugs, 
19  biological products, and devices.3,4,5  In this guidance, a DCT refers to a clinical trial where some 
20  or all of the trial-related activities occur at locations other than traditional clinical trial sites. 
21   
22  In fully decentralized clinical trials, all activities take place at locations other than traditional trial 
23  sites.  These trial-related activities may take place at the homes of trial participants or in local 
24  health care facilities that are convenient for trial participants.  In hybrid DCTs, some trial 
25  activities involve in-person visits by trial participants to traditional clinical trial sites, and other 
26  activities are conducted at locations other than traditional clinical trial sites, such as participants 
27  homes.  
28   
29  FDAs regulatory requirements for investigations of medical products are the same for DCTs and 
30  traditional site-based clinical trials.6  Section 3606(a) of the Food and Drug Omnibus Reform 
 
1 This guidance has been prepared by 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.  
 
2 Words and phrases in bold are defined in the Glossary. 
 
3 See section 201(g) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 321(g)) for the definition 
of a drug.  In this guidance, all references to drugs include both human drugs and biological products, unless 
otherwise specified. 
 
4 See section 351(i) of the Public Health Service Act (PHS Act) (42 U.S.C. 262(i)) for the definition of a biological 
product. 
 
5 See section 201(h) of the FD&C Act (21 U.S.C. 321(h)) for the definition of a device.   
 
6 See 21 CFR parts 312 and 812.  
 
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31  Act (FDORA) directs FDA to issue or revise draft guidance that includes recommendations to 
32  clarify and advance the use of decentralized clinical studies to support the development of drugs 
33  and devices, not later than December 29, 2023.  This guidance provides recommendations 
34  related to FDAs requirements for investigations of medical products when applied to DCTs and 
35  fulfills the requirement set forth in section 3606(a)(1) of FDORA.  The content described in 
36  section 3606(b) of FDORA is further addressed through this guidances reference to the draft 
37  guidance for industry, investigators, and other stakeholders entitled Digital Health Technologies 
38  for Remote Data Acquisition in Clinical Investigations (December 2021).7 
39   
40  In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
41  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
42  as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
43  the word should in Agency guidances means that something is suggested or recommended, but 
44  not required. 
45   
46   
47  II.  BACKGROUND 
48   
49  Many clinical trials already include decentralized elements such that not all trial-related activities 
50  involving participants take place at traditional clinical trial sites.  For example, laboratory tests 
51  are often conducted by clinical laboratory facilities at locations remote from traditional trial 
52  sites.  DCTs have the potential to expand access to more diverse patient populations and improve 
53  trial efficiencies.8  Advances in clinical care using electronic communications and information 
54  technology to interact with trial participants in different locations (i.e., telehealth) allow for 
55  fewer in-person visits to clinical trial sites.  Digital health technologies (DHTs), for example, 
56  have expanded the types of trial-related data that can be obtained remotely from trial 
57  participants.  By enabling remote participation, DCTs may enhance convenience for trial 
58  participants, reduce the burden on caregivers, and facilitate research on rare diseases and 
59  diseases affecting populations with limited mobility or access to traditional trial sites.  This may 
60  help improve trial participant engagement, recruitment, enrollment, and retention of a 
61  meaningfully diverse clinical population. 
62   
63  Fully decentralized trials may be appropriate for investigational products (IPs) that are simple 
64  to administer or use, have well-characterized safety profiles (see section III.F), and do not 
65  require complex medical assessments.  Alternatively, hybrid decentralized trials may be more 
66  appropriate in cases where the administration of an IP or a complex medical assessment needs to 
67  be performed at a clinical trial site and some follow-up assessments could be performed remotely 
68  through online patient-reported outcome measures, via telehealth or in-home visits, or by local 
69  health care providers (HCPs), as appropriate (see section III.B). 
70   
 
7 When final, this guidance will represent FDAs current thinking on this topic.  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. 
 
8 See the guidance for industry Enhancing the Diversity of Clinical Trial Populations  Eligibility Criteria, 
Enrollment Practices, and Trial Designs (November 2020).   
 
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71  Challenges related to DCTs may include coordination of trial activities with individuals and 
72  facilities in multiple locations that are not traditional clinical trial sites.  DCTs generally include 
73  specific plans to facilitate the decentralization of the trial.  These plans should include, as 
74  appropriate, the use of local health care facilities, local HCPs, and local clinical laboratory 
75  facilities; visits to trial participants homes; and direct distribution of the IP to trial participants at 
76  their locations.9  Specific issues related to the feasibility, design, implementation, or analysis of a 
77  DCT should be discussed early with the relevant FDA review divisions.10  Appropriate training, 
78  oversight, and up-front risk assessment and management will be key to implementing a DCT 
79  successfully.   
80   
81   
82  III.  RECOMMENDATIONS FOR IMPLEMENTING DCTS  
83   
84  The sections below provide guidance on specific topics for DCT implementation.  
85   
86  A.  DCT Design 
87   
88  In a DCT, some or all trial-related activities will occur at locations other than traditional clinical 
89  trial sites (e.g., the participants home or local health care facilities).  DCTs may involve a 
90  network of locations where trial personnel and local HCPs work and where trial-related services 
91  (e.g., imaging and laboratory services) are provided, all under the oversight of the investigator. 
92   
93  For inspectional purposes, there should be a physical location where all clinical trial-related 
94  records for participants under the investigators care are accessible and where trial personnel can 
95  be interviewed.  This location should be listed on Form FDA 157211 or for investigational device 
96  exemption (IDE) applications must be included in the IDE application.12   
97   
98  The variability and precision of the data obtained in a DCT may differ from the data in a 
99  traditional site-based clinical trial.  This would not affect the validity of a finding of superiority 
 
9 See 21 CFR 312.57(a), 312.62(a), 812.140(a)(2), and 812.140(b)(2) (describing requirements for disposition of the 
investigational product). 
 
10 See the draft guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants of PDUFA 
Products (December 2017) and the draft guidance for industry Formal Meetings Between the FDA and Sponsors or 
Applicants of BsUFA Products (June 2018).  When final, these guidances will represent FDAs current thinking on 
these topics.  See also the guidance for industry and FDA staff Requests for Feedback and Meetings for Medical 
Device Submissions:  The Q-Submission Program (January 2021).  For applicants preparing abbreviated new drug 
applications (ANDAs), the Office of Generic Drugs in CDER encourages submission of controlled correspondence 
or a pre-ANDA meeting request to discuss the design, analysis, and implementation of a DCT before conducting the 
trial.  See the draft guidance for industry Controlled Correspondence Related to Generic Drug Development 
(December 2022) (when final, this guidance will represent FDAs current thinking on this topic).  For submitting a 
pre-ANDA meeting request, see the revised guidance for industry Formal Meetings Between FDA and ANDA 
Applicants of Complex Products Under GDUFA (October 2022).   
 
11 This information should be entered under Sections 1 and 3 on Form FDA 1572. 
 
12 See 21 CFR 812.20(b).  The investigators address is often the same as the location or institution where the trial is 
being conducted.  However, if the addresses are different, both locations must be included in the IDE application.  
 
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100  in a trial using such data (although it could reduce the effect size), but it could affect the validity 
101  of a finding of non-inferiority.13  Remote assessments may differ from on-site assessments, 
102  particularly when trial participants are responsible for performing their own physiological tests 
103  (e.g., home spirometry).  Assessments performed by local HCPs as part of routine clinical 
104  practice (e.g., evaluation of symptoms) may also be more variable and less precise than 
105  assessments conducted by dedicated trial personnel.  In non-inferiority trials, when the effect size 
106  of an active control drug, for example, has only been determined in a traditional site-based 
107  clinical trial, it may not be reasonable to assume that the same effect size would be seen for the 
108  active control drug in a DCT.  This may present challenges in calculating a non-inferiority 
109  margin.  FDA review divisions should be consulted when planning a non-inferiority trial in a 
110  DCT setting. 
111   
112  B.  Remote Clinical Trial Visits and Clinical Trial-Related Activities  
113   
114  Remote clinical trial visits and clinical trial-related activities are important strategies to make 
115  trials more convenient and more accessible to trial participants.  The following should be 
116  considered when planning remote clinical trial visits or clinical trial-related activities: 
117   
118    In general, investigators can consider telehealth visits instead of in-person visits with trial 
119  participants if no in-person interaction is needed.14  The protocol should specify when a 
120  telehealth visit with a trial participant is appropriate and when a participant should be 
121  seen in person.  
122   
123    In-person visits and trial-related activities can be conducted by trial personnel who are 
124  sent to participants homes or preferred locations.  
125   
126    Depending on the trial protocol, in-person visits and trial-related activities may also be 
127  conducted by HCPs who are located close to trial participants homes but are not part of 
128  the trial personnel.  These local HCPs (such as doctors or nurses) may be used by 
129  sponsors or investigators to perform certain trial-related activities; for example, on a fee-
130  for-service basis.  The trial-related services that they provide should not differ from those 
131  that they are qualified to perform in clinical practice (e.g., performing physical 
132  examinations, reading radiographs, obtaining vital signs).  These services should not 
133  require a detailed knowledge of the protocol or the IP.  
134   
135    Trial-related activities that are unique to research and/or require a detailed knowledge of 
136  the protocol or the IP should be performed by qualified trial personnel who have been 
137  appropriately trained.  When applicable, both trial personnel and trial participants should 
138  be trained on how to conduct or participate in a telehealth visit.   
139   
 
13 See the guidance for industry Non-Inferiority Clinical Trials to Establish Effectiveness (November 2016). 
 
14 See 21 CFR parts 312 and 812.  
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140    During each remote trial visit, investigators should confirm the trial participants identity.  
141  FDA does not endorse any specific identification method.  Sponsors and/or investigators 
142  can consider referring to existing digital identity guidelines.15  
143   
144    Case report forms and other documentation should be completed for telehealth visits, 
145  including the date and time of the visit. 
146   
147    The trial protocol should specify how adverse events identified remotely will be 
148  evaluated and managed.  The protocol should describe how care will be provided for 
149  adverse events that require urgent or in-person attention.  It is the sponsor and 
150  investigators responsibility to ensure that remote clinical trial visits conducted via 
151  telehealth comply with laws governing telehealth in the relevant U.S. States or territories 
152  and other countries, as applicable.   
153   
154  C.  Digital Health Technologies  
155   
156  DHTs may allow transmission of data remotely from trial participants wherever they are located.  
157  The sponsor should consider the following information regarding the use of DHTs in a DCT: 
158   
159    The draft guidance for industry, investigators, and other stakeholders Digital Health 
160  Technologies for Remote Data Acquisition in Clinical Investigations16 provides 
161  recommendations to sponsors, clinical investigators, and other parties for measuring 
162  clinical events and characteristics of interest using DHTs to acquire data remotely from 
163  participants in clinical trials for drugs, biological products, and devices.  The guidance 
164  discusses selection of DHTs for clinical trials; verification, validation, and usability 
165  testing; use of DHTs to collect data for clinical trial endpoints; training on the use of 
166  DHTs; and management of risks related to the use of DHTs in clinical trials.  Other issues 
167  regarding the use of DHTs in clinical investigations are discussed in other FDA 
168  guidances.17 
169   
170    Sponsors should ensure that DHTs used in a DCT are available and suitable for use by all 
171  trial participants.  When a trial permits participants to use their own DHTs, sponsor-
172  provided DHTs should be available as an option to ensure that participants who do not 
 
15 See, for example, National Institute of Standards and Technology (NIST) Digital Identity Guidelines, NIST 
Special Publication 800-63A: Enrollment and Identity Proofing Requirements when developing an identity 
verification plan (https://pages.nist.gov/800-63-3/sp800-63a.html).  
 
16 When final, this guidance will represent FDAs current thinking on this topic. 
 
17 See the revised 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.  For considerations on FDAs oversight of clinical decision support software, see the  
guidance for industry and FDA staff Clinical Decision Support Software (September 2022).  For information on 
patient-reported outcomes and other clinical outcome assessments, see BEST (Biomarkers, EndpointS, and other 
Tools) Resource Glossary, 2016, available at https://www.ncbi.nlm.nih.gov/books/NBK326791.  
 
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173  have a protocol-specified DHT are not excluded from the DCT for that reason (e.g., 
174  lower socioeconomic groups who cannot afford the DHT). 
175   
176  D.  Roles and Responsibilities  
177   
178  The roles and responsibilities of sponsors and investigators are described below.  
179   
180  1.  The Sponsor  
181    
182    Sponsor responsibilities are the same for DCTs and traditional site-based clinical trials.18  
183  Because DCTs may involve many contracted services, sponsors should ensure proper 
184  coordination of the decentralized activities (e.g., use of mobile nurses for at-home visits, 
185  use of local HCPs, direct shipping of IP to participants) (see sections III.B and III.G). 
186   
187    Sponsors should strive for diversity and inclusiveness in trial populations.19  Outreach 
188  through local health care institutions (e.g., pharmacies, clinics) may facilitate recruitment 
189  of diverse participants in areas where there are limited or no traditional clinical trial sites.  
190  Bringing trial-related activities to participants homes, including through the use of 
191  DHTs, may reduce the need for travel and improve engagement, recruitment, and 
192  retention amongst potential participants with challenges accessing traditional clinical trial 
193  sites.  The use of local HCPs close to potential participants homes may improve 
194  engagement, recruitment, and retention of diverse participants (e.g., race, ethnicity, age, 
195  sex, and geographic location).  Further, the use of local HCPs may reduce cultural or 
196  linguistic barriers to participation in clinical trials.  
197   
198    To account for multiple sources of data collection in a DCT, the sponsor should include 
199  at least the following in a data management plan (DMP): 
200   
201  -  Data origin and data flow from all sources to the sponsor (see section III.I) (e.g., a 
202  diagram that depicts the flow of data from creation to final storage) 
203   
204  -  Methods used for remote data acquisition from trial participants, trial personnel, 
205  and contracted service providers (e.g., local clinical laboratory facilities and local 
206  HCPs who perform trial-related activities)20  
207   
208  -  A list identifying vendors for data collection, handling, and management
 
 
18 See 21 CFR parts 312 and 812. 
 
19 See the draft guidance for industry Diversity Plans to Improve Enrollment of Participants from Underrepresented 
Racial and Ethnic Populations in Clinical Trials (April 2022).  When final, this guidance will represent FDAs 
current thinking on this topic.  
 
20 See the revised draft guidance for industry Electronic Systems, Electronic Records, and Electronic Signatures in 
Clinical Investigations:  Questions and Answers and the draft guidance for industry, investigators, and other 
stakeholders Digital Health Technologies for Remote Data Acquisition in Clinical Investigations for 
recommendations related to storage and handling of data.  When final, these guidances will represent FDAs current 
thinking on these topics.  
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209   
210    Sponsors should describe in the trial protocol how operational aspects of the DCT will be 
211  implemented.  This description should cover, but may not be limited to, the following: 
212   
213  -  Scheduled and unscheduled clinical trial visits (remote and in-person, as 
214  applicable) 
215   
216  -  Transmission of reports on activities performed at different locations (e.g., 
217  medical imaging; clinical laboratory tests; and procedures performed at trial 
218  participants home, work, or other local facility) 
219   
220  -  Delivery of IPs to trial participants, if applicable, and accountability for IPs 
221   
222  -  Safety monitoring and management of adverse events 
223   
224    Case report forms should identify when and where data were collected and by whom.  
225   
226    Sponsors must comply with relevant local laws, regulations, and licensing requirements 
227  governing medical practice and IP administration when conducting a DCT.  This may 
228  involve addressing laws in multiple U.S. States, territories, and other countries. 
229   
230    Sponsors must ensure proper monitoring of an investigation.21  As with any trial, 
231  sponsors may use a variety of approaches to monitor DCTs, and the monitoring plan for a 
232  trial should be based on the sponsors risk assessment.22  A trial monitoring plan should 
233  (1) describe how monitoring will be implemented to assess protocol compliance and data 
234  quality and integrity, (2) specify the frequency with which trial records and source 
235  documents will be reviewed, and (3) note any unique aspects related to the DCT 
236  procedures.  FDA encourages risk-based monitoring approaches and use of centralized 
237  monitoring to identify and proactively follow up on missing data, inconsistent data, data 
238  outliers, and potential protocol deviations that may be indicative of systemic or 
239  significant errors.  
240   
241  2.  The Investigator and Delegation of Trial-Related Activities 
242   
243  Investigators are responsible for the conduct of the DCT and the oversight of individuals 
244  delegated to perform trial-related activities, including ensuring that these delegated activities 
245  and/or tasks are conducted according to the investigational plan, applicable regulations, and 
 
21 See 21 CFR 312.50 and 812.40. 
 
22 For detailed information on risk-based approaches to monitor clinical trials, see the guidance for industry A Risk-
Based Approach to Monitoring of Clinical Investigations:  Questions and Answers (April 2023).   
 
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246  relevant laws.23,24  A key difference between DCTs and traditional site-based clinical trials is the 
247  extent to which the investigator uses telehealth, trial personnel working remotely, local HCPs, 
248  and/or DHTs in the conduct of the trial.  Whether the trial can be conducted entirely using 
249  remote visits or a hybrid trial design is appropriate depends on the types of assessments and 
250  procedures needed to collect endpoints and monitor safety.  The decentralized features of the 
251  trial may necessitate additional training,25 coordination, and standard operating procedures to 
252  ensure consistent implementation.  
253   
254    When permitted by the trial protocol, investigators may delegate trial-related activities to 
255  local HCPs to perform trial-related procedures that require in-person interactions with 
256  trial participants (e.g., physical examinations and other medical procedures).26  These 
257  procedures may take place at participants locations or other local health care facilities as 
258  specified by the trial protocol.  
259   
260    Videoconferencing and other technologies may be useful to allow investigators to 
261  oversee trial personnel performing activities described in the trial protocol (e.g., 
262  photographing lesions, fitting wearable sensors) at participants locations. 
263   
264    Investigators should enroll only as many trial participants as they can appropriately 
265  manage to ensure adequate supervision of DCT-related activities.  
266   
267    As for any drug trial subject to 21 CFR 312.53, Form FDA 1572 must be completed by 
268  all investigators.  The decision to include individuals as subinvestigators in a DCT should 
269  be based on their assigned responsibilities.   
270   
271  -  When trial personnel contribute directly and significantly to the trial data, they 
272  should be included on Form FDA 1572 as subinvestigators.27  
273   
274  -  Local HCPs contracted to provide trial-related services that are part of routine 
275  clinical practice (e.g., performing physical examinations, reading radiographs, 
276  obtaining vital signs) and where a detailed knowledge of the protocol, IP, and the 
277  investigators brochure is not necessary should not be listed on Form FDA 1572 
 
23 See 21 CFR 312.60, 312.61, and 812.100.  
 
24 See the guidance for industry Investigator Responsibilities  Protecting the Rights, Safety, and Welfare of Study 
Subjects (October 2009). 
 
25 See 21 CFR 11.10(i). 
 
26 See 21 CFR 312.3 and 812.3. 
 
27 See 21 CFR 312.3 and 312.53.  For more information on subinvestigators, see questions 31 and 32 in the 
information sheet guidance for sponsors, clinical investigators, and IRBs Frequently Asked Questions  Statement of 
Investigator (Form FDA 1572) (May 2010) and the guidance for industry Investigator Responsibilities  Protecting 
the Rights, Safety, and Welfare of Trial Subjects. 
 
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278  as subinvestigators.  However, local HCPs should be included in a task log (as 
279  described below in this section). 
280   
281    For device investigations, investigator responsibilities under 21 CFR part 812 include the 
282  requirement that there be a signed agreement between the investigator and sponsor (see 
283  21 CFR 812.43(c)(4) and 812.100).  A list of all investigators in the study is also required 
284  as part of an IDE application (see 21 CFR 812.20 and 812.150(b)(4)).  Local HCPs 
285  contracted to provide trial-related services that are part of routine clinical practice and 
286  where a detailed knowledge of the protocol or the IP is not required are generally not 
287  considered investigators and should not be included in the IDE list of investigators.  
288  However, these local HCPs should be included in a task log (as described below in this 
289  section). 
290   
291    A critical consideration in a DCT when delegating trial-related activities to local HCPs is 
292  the potential for variability in the approach across different practices (e.g., documenting 
293  vital signs, physical examinations, and evaluation of adverse events).  Quality control 
294  measures should be in place to help reduce variability, including regular review by 
295  investigators of participant data entered by local HCPs, to assess consistency and 
296  completeness of the required procedures.  The type and scope of quality control measures 
297  should be tailored to the criticality of the data and the complexity of procedures done by 
298  the local HCPs.  
299     
300    As part of preparing and maintaining adequate case histories,28 investigators must 
301  maintain a task log of local HCPs who perform trial-related activities. 
302   
303  -  The task log should include (1) the names and affiliations of the local HCPs, (2) a 
304  description of their roles and assigned tasks, (3) the dates these local HCPs are 
305  added to the log, and (4) the locations where these activities are conducted. 
306   
307  -  The task log should be dated and signed by the investigator when initially created 
308  and updated when new local HCPs are added.  The task log should be available to 
309  FDA during inspections. 
310   
311  -  Other health care professionals not involved in the clinical trial who deliver care 
312  to trial participants but not as part of the trial should not be listed on Form FDA 
313  1572, the task log, or a medical device sponsors current list of investigators.  
314  These professionals may include emergency room personnel, hospital personnel, 
315  family physicians, and nurses providing routine care for trial participants with 
316  emergent or existing conditions.  
317   
318    Some trial protocols will include designated clinical laboratory facilities29 to perform 
319  activities required by the protocol (e.g., phlebotomy, x-rays).  Other trial protocols may 
 
28 See 21 CFR 312.62 and 812.140. 
 
29 See the information sheet guidance for sponsors, clinical investigators, and IRBs Frequently Asked Questions  
Statement of Investigator (Form FDA 1572). 
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320  permit the use of a variety of clinical laboratory facilities close to the trial participant to 
321  perform these activities.  Generally, designated clinical laboratory facilities are preferable 
322  to minimize variability, particularly for critical data such as those used to evaluate 
323  outcomes, and to perform investigations and tests that are specialized.  If appropriate, 
324  specimens from trial participants (e.g., blood, sputum) may be collected by remote trial 
325  personnel, local HCPs, or clinical laboratory facilities and sent to designated facilities for 
326  processing.  Local clinical laboratory facilities may be adequate for routine clinical tests 
327  that are well-standardized.   
328   
329    All clinical laboratory facilities should be listed on Form FDA 1572 or in the 
330  investigational plan for device studies under an IDE.  
331   
332    Technicians and other personnel working for clinical laboratory facilities should not be 
333  recorded on the task log or Form FDA 1572.  However, for certain device studies (e.g., in 
334  vitro diagnostic devices), it may be necessary to identify the responsible individual at the 
335  laboratory facility where device testing is done in the task log or IDE application.30 
336   
337    As in any trial, trial participants experiencing any health emergency (e.g., hypoglycemia 
338  or abnormal cardiac rhythm) should seek medical attention at local health care facilities 
339  (such as an emergency room), as appropriate.  With the permission of trial participants, 
340  investigators should attempt to obtain reports from these local health care facilities, and 
341  investigators should also attempt to obtain reports from primary providers of routine 
342  health care when activities take place that are relevant to the trial (e.g., change in 
343  concomitant medications). 
344   
345  E.  Informed Consent and Institutional Review Board Oversight 
346   
347  Obtaining informed consent remotely may be considered as part of a DCT.  Institutional review 
348  board (IRB) oversight is required to ensure the process is adequate and appropriate.31 
349   
350    Investigators may obtain electronic informed consent from trial participants at their 
351  remote locations provided that all applicable regulatory requirements regarding informed 
352  consent are met.32  The process of obtaining electronic informed consent remotely may 
353  include a remote visit if needed. 
354   
 
30 For certain device studies, the laboratory facility is a clinical trial site under 21 CFR part 812, and complete 
information on the site, including the investigator (i.e., responsible individual), is required in the IDE application 
and study records. 
 
31 21 CFR 56.103, 56.104, and 56.105.  
 
32 For FDA regulations about informed consent, see 21 CFR part 50 (including the elements of informed consent 
under 21 CFR 50.25 and the documentation of informed consent under 21 CFR 50.27).  For additional information, 
see the guidance for IRBs, investigators, and sponsors Use of Electronic Informed Consent:  Questions and Answers 
(December 2016). 
 
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355    With a DCT, the informed consent process must include notifying participants of whom 
356  to contact for answers to pertinent questions about the research and research subjects 
357  rights and whom to contact in the event of a research-related injury to the subject.33   
358   
359    The informed consent should describe who will have access to the trial participants 
360  personal health information obtained during the DCT.  
361   
362    FDA recommends the use of a central IRB in DCTs to facilitate efficient review of the 
363  protocol, the informed consent documents, and other relevant trial-related information.34 
364   
365  F.  Investigational Products in a DCT 
366   
367  1.  Drugs and Biological Products 
368   
369  An investigator must administer an IP only to participants under the investigators personal 
370  supervision or under the supervision of a subinvestigator responsible to the investigator.35  The 
371  nature of the IP should be considered when determining whether administration outside of a 
372  clinical trial site in a DCT is appropriate.  IPs that involve complex administration procedures; 
373  have a high-risk safety profile, especially in the immediate post-administration period; or are in 
374  early stages of development such that the safety profile is not well defined may need in-person 
375  supervision by the investigator at a trial site.   
376   
377  For IPs for which the safety profile is well-characterized and that do not involve specialized 
378  monitoring during the immediate period following administration, it may be appropriate for local 
379  HCPs or trial personnel working remotely to administer the IP at local health care facilities or 
380  participants homes.  Hybrid DCTs may be designed for drugs that require supervised but 
381  infrequent (e.g., monthly) administration when administration can be done at trial sites with 
382  follow-up done remotely.  
383   
384  Depending on the safety profile of the IP (e.g., a class of drug with a risk of hypersensitivity, 
385  abuse potential) and the type of trial (e.g., dose escalation trial), sponsors should estimate the 
386  urgency and complexity of care that may be needed based upon risks related to the IP and the 
387  participants underlying condition.  Investigators should take steps to help ensure that 
388  participants have access to an appropriate level of local care. 
389   
390  Drugs best suited for direct shipment to the participants home include those with long shelf lives 
391  and those with good stability profiles.  Drugs that involve specialized handling, shipping, and 
392  storage conditions may not be suited for direct shipment to locations outside the trial site. 
393   
 
33 See 21 CFR 50.25(a)(7).  
 
34 See 21 CFR 56.114 (for a description of arrangements related to use of a central IRB).  For additional information, 
see the guidance for industry Using a Centralized IRB Review Process in Multicenter Clinical Trials (March 2006). 
 
35 21 CFR 312.61.  
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394  2.  Medical Devices 
395   
396  When determining the appropriate use or administration of an investigational device in a DCT, 
397  sponsors should consider the type of medical device, its intended use, its instructions for use, and 
398  whether it is a significant risk or nonsignificant risk device.36   
399    
400  Medical devices suitable for home use (i.e., over-the-counter devices) that do not pose significant 
401  risks to trial participants may be appropriate for use by trial participants without the 
402  investigators direct oversight.  The use of medical devices that are not intended for self-use (i.e., 
403  devices used in hospital or ambulatory care settings) or that pose significant risks to trial 
404  participants should be used or administered by qualified trial personnel with investigator 
405  oversight.  An investigator shall not supply an investigational device to any person not 
406  authorized under 21 CFR part 812 to receive it.37  Certain follow-up procedures needed after 
407  using the medical device or after surgical implantation of the device in trial participants may be 
408  performed by appropriately qualified and trained local HCPs or trial personnel via telehealth 
409  visits, at the homes of trial participants, or in local health care facilities.  A telehealth visit may 
410  be appropriate if an assessment in that setting does not pose significant risk to trial participants 
411  and, in such settings, adverse events can be (and are) properly assessed and documented.   
412     
413  G.  Packaging and Shipping of Investigational Products 
414   
415  Generally, DCTs may allow for the direct distribution of investigational products to trial 
416  participants at their locations.38  The sponsor should consider the following recommendations 
417  regarding packaging, shipping, and storage of IPs in a DCT: 
418   
419    The protocol should describe how the physical integrity and stability of the IP will be 
420  maintained during shipment to trial participants, including appropriate packaging 
421  materials and methods (e.g., temperature control).  Shipping containers should include 
422  clear instructions for handling and storing the IPs and instructions for returning unused 
423  IPs.39, 40   
424   
425    When relevant, DCT personnel should be trained on procedures and appropriate 
426  documentation for handling, packaging, shipping, and tracking IPs. 
427   
 
36 See the information sheet guidance for IRBs, clinical investigators, and sponsors Significant Risk and 
Nonsignificant Risk Medical Device Studies (January 2006).   
 
37 See 21 CFR 812.110.  
 
38 See 21 CFR 312.61. 
 
39 For information about packaging, labeling, and distribution of phase 1 investigational drugs and biological 
products, see section V.G in the guidance for industry CGMP for Phase 1 Investigational Drugs (July 2008). 
 
40 For information about packaging and labeling operations of phases 2 and 3 investigational drug and biological 
products, see section VII in the guidance for industry Preparation of Investigational New Drug Products (Human 
and Animal) (reprinted November 1992). 
 
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428    A central distribution service could be used to ship the IP directly to trial participants.  
429  The investigator or delegated trial personnel must control the release of the IP by the 
430  distributor; monitor receipt and use by trial participants (or participants legally 
431  authorized representatives), according to procedures described in the protocol; and 
432  monitor the return or disposal of any unused product as directed by the sponsor.41   
433   
434    The protocol should describe how investigators will track and document that trial 
435  participants (or participants legally authorized representatives) receive IPs. 
436   
437    The protocol should describe procedures that investigators or participants (or 
438  participants legally authorized representatives) should use to return or dispose of unused 
439  IPs and how this will be documented.42 
440   
441    Sponsors and investigators must comply with applicable Federal, State, and international 
442  laws and regulations that address shipping IPs in their respective jurisdictions.   
443   
444  H.  Safety Monitoring Plan  
445   
446  The sponsor is required to ensure proper monitoring of the investigations and to ensure that the 
447  investigations are conducted in accordance with the general investigational plan and protocols 
448  contained in the IND or IDE applications.43  Sponsors should implement a safety monitoring 
449  plan to ensure the safety and welfare of trial participants in a DCT.  
450   
451    The safety monitoring plan should take the decentralized nature of the clinical trial into 
452  account and ensure that adverse events are appropriately captured and adequately 
453  addressed.44  The monitoring plan should prespecify if and when telehealth visits or in-
454  person visits (e.g., physical examinations) will be scheduled with trial personnel or local 
455  HCPs to collect safety data by (see section III.B). 
456   
457    As in any site-based clinical trial, the safety monitoring plan should describe how 
458  participants are expected to respond to and report adverse events, including where to seek 
459  medical assistance locally when necessary and where to receive follow-up care.45 
460   
 
41 See 21 CFR 312.61, 312.62(a), and 812.110. 
 
42 See 21 CFR 312.62(a) and 812.110(e) (for requirements related to disposition of the IP). 
 
43 21 CFR 312.50 and 812.40.  See also the guidance for industry Oversight of Clinical Investigations  A Risk-
Based Approach to Monitoring (August 2013). 
 
44 Certain late-stage pre-approval or post-approval clinical trials could be able to use selective safety data collection.  
See the ICH guidance for industry E19 A Selective Approach to Safety Data Collection in Specific Late-Stage Pre-
Approval or Post-Approval Clinical Trials (December 2022). 
 
45 For information about the medical care of trial subjects, see section 4.3 in the guidance for industry E6(R2) Good 
Clinical Practice: Integrated Addendum to ICH E6(R1) (March 2018). 
 
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461    Trial participants must be able to contact trial personnel to report adverse events and to 
462  have pertinent questions answered.46  
463   
464    Trial participants should be able to arrange for an unscheduled visit using telehealth or an 
465  in-person visit, as appropriate (see section III.B). 
466   
467    The safety monitoring plan should describe the type of information that will be collected 
468  by a DHT (when used to collect data in a DCT), how that information will be used and 
469  monitored, and what action trial participants or personnel should take in response to 
470  abnormal findings or electronic alerts.   
471   
472    If significant safety risks emerge because of the remote administration or use of an IP, 
473  sponsors must discontinue remote administration or use; notify FDA, the IRB, and all 
474  investigators who have participated in the trial; and determine if the trial should 
475  continue.47 
476    
477    If authorized in the protocol, routine safety monitoring involving laboratory testing and 
478  imaging may be performed using local clinical laboratory facilities close to trial 
479  participants (see section III.D.2).  Investigators should ensure they promptly receive 
480  reports of these services and review them in a timely manner. 
481   
482  I.  Software Used in Conducting DCTs 
483   
484  Sponsors should consider the following regarding software used in a DCT: 
485   
486    Software to support the conduct of DCTs can be run through a variety of platforms (e.g., 
487  tablets, cell phones, personal computers).  Software can be used to perform multiple 
488  functions to manage DCT operations, including:  
489   
490  -  Managing electronic informed consent (e.g., maintaining approved versions of 
491  informed consent, documenting IRB approval, archiving signed forms) 
492   
493  -  Capturing and storing reports from remote trial personnel, local HCPs, and local 
494  clinical laboratory facilities 
495   
496  -  Managing electronic case report forms (eCRFs) 
497   
498  -  Scheduling trial visits and other DCT-related activities 
499   
500  -  Tracking IPs that are shipped directly to trial participants 
501   
 
46 See 21 CFR 50.25(a)(7). 
 
47 See 21 CFR 312.56(d) and 812.46. 
 
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502  -  Syncing information recorded by DHTs 
503   
504  -  Serving as communication tools between DCT personnel and trial participants 
505   
506    Training should be provided to all parties (e.g., trial personnel, local HCPs, and trial 
507  participants) using software to support the conduct of DCTs. 
508   
509    There are several ways local HCPs can submit trial-related data for inclusion in clinical 
510  trial records, including but not limited to the following:  
511   
512  -  If the local HCPs have access to the eCRF, they can enter trial-related data 
513  directly into the eCRFs.48   
514   
515  -  Alternatively, local HCPs can upload forms or documents by using methods of 
516  secure data transfer to investigators.  Investigators or other trial personnel are then 
517  responsible for entering these trial-related data into the eCRF.49  
518   
519    Remote trial personnel or local HCPs submitting trial data directly into the eCRF should 
520  be included in the sponsors list of authorized data originators.50   
521   
522    Software programs that are used to produce and process trial records required by the 
523  FD&C Act and FDA regulations are subject to 21 CFR part 11.  These programs must 
524  ensure data reliability, security, privacy, and confidentiality.51 
525   
526    FDA considers real-time video interactions, including telehealth, as a live exchange of 
527  information between trial personnel and trial participants.  These live interactions are not 
528  considered electronic records and, therefore, are not subject to 21 CFR part 11, but local 
529  laws governing telehealth may apply.  Privacy and security of these real-time visits 
530  should be ensured, and the visits must be documented.52  If this documentation is 
531  captured in electronic form, such documentation is subject to 21 CFR part 11.   
 
48 See the guidance for industry Electronic Source Data in Clinical Investigations (September 2013).   
 
49 See 21 CFR 312.62 and 812.140. 
 
50 See the guidance for industry Electronic Source Data in Clinical Investigations.  As recommended in that 
guidance, [a] list of all authorized data originators (i.e., persons, systems, devices, and instruments) should be 
developed and maintained by the sponsor and made available at each clinical site. 
 
51 See 21 CFR part 11.  See also the guidance for industry Electronic Source Data in Clinical Investigations and the 
revised draft guidance for industry Electronic Systems, Electronic Records, and Electronic Signatures in Clinical 
Investigations:  Questions and Answers (when final, this guidance will represent FDAs current thinking on this 
topic). 
 
52 See 21 CFR 312.62(b) and 812.140(a)(3).  
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532  GLOSSARY 
533   
534  The following terms are defined for the purposes of this guidance: 
535   
536  clinical laboratory facilities:  Clinical laboratories or testing facilities that contribute to or 
537  support the clinical study, such as diagnostic labs performing blood work, imaging centers, or 
538  cardiology labs.  As appropriate, these clinical laboratory facilities may be located close to trial 
539  participants homes.   
540   
541  data management plan (DMP):  A written document that describes the data a sponsor expects 
542  to acquire or generate during the course of a research study; how the sponsor intends to manage, 
543  describe, analyze, and store said data; and what mechanisms will be used at the end of the study 
544  to preserve and share the research data.  
545   
546  decentralized clinical trial (DCT):  A clinical trial where some or all of the trial-related 
547  activities occur at locations other than traditional clinical trial sites.  
548   
549  digital health technology (DHT):  A system that uses computing platforms, connectivity, 
550  software, and/or sensors for health care and related uses.  These technologies span a wide range 
551  of uses, from applications in general wellness to applications as a medical device.  They include 
552  technologies intended for use as a medical product, in a medical product, or as an adjunct to 
553  other medical products (devices, drugs, and biologics).  They may also be used to develop or 
554  study medical products. 
555   
556  investigational product (IP):  Human drugs, biological products, or devices that are being 
557  investigated in a clinical trial.53,54,55 
558   
559  telehealth:  The use of electronic information and telecommunications technologies to support 
560  and promote long-distance clinical health care. 
 
53  See footnote 3. 
 
54  See footnote 4.  
 
55  See footnote 5.  
 
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