Decentralized Clinical Trials and the FDA: What the FDA Regulatory Framework Means for DCTs

Because trial methodology has changed, there’s a common myth that the rules need to be or will be re-written. In the United States, however, the Food and Drug Administration’s longstanding regulations guiding clinical trials (21 CFR 312.50 for drugs and biologics and 21 CFR 812.40 for medical devices) remain relevant, no matter the trial design. In fact, it’s not the FDA’s position to tell sponsors how to design a trial. Instead, the agency believes a trial should be built to maintain the well-being and safety of patients and the integrity of the data; whether it’s a DCT or a traditional trial that does this doesn’t matter.

While sponsors should use Good Clinical Practice (GCP) as the guiding principle when designing a decentralized clinical trial, the FDA has released some guidance particular to digital health technologies (DHTs) that is important to understand. This article intends to help sponsors interpret this guidance, as well as the current regulatory framework and what it means for decentralized clinical trials.

Read on for insights about:

The FDA’s trajectory toward DCT acceptance.
FDA guidance on digital health technologies (DHTs) and what it means for DCTs.
Projected future changes to guidance.
Key considerations for sponsors when implementing DCTs.

‍

The Path to FDA Acceptance of Decentralized Clinical Trials (DCTs)

Pre-COVID, technology and process initiatives to expand patient access, streamline clinical trials, and harmonize regulations were already under way. But, at that time, adoption was limited. Risk aversion among sponsors—along with a general preference for “sticking to what works”—left little room for exploration. The FDA, however, was supportive of decentralized methods before COVID-19, emphasizing the importance of efforts to “bring new innovations and advances to patients who need them faster and more efficiently.”

Below is a look at FDA actions that illustrate an openness to innovative trial methods:

2016: With the 21^st-Century Cures Act, regulatory authorities institute new processes to modernize clinical trial designs and speed the review of certain innovative medical devices.
2017: The FDA and Duke University enter a public-private partnership, forming the Clinical Trials Transformation Initiative (CTTI) to identify practices to enhance the quality and efficacy of studies and to encourage a mainstream dialogue surrounding the use of mobile technologies in clinical research.
2018: The FDA, via CTTI, highlights the potential advantages of DCTs, when compared to trials conducted at more centralized clinical trial sites. Cited advantages include faster recruitment, improved retention, greater control and convenience for participants, and increased participant diversity
2020 to 2021: The FDA publishes several iterations of COVID-19 clinical trials guidance document ation to minimize clinical research delays and disruptions. Included was guidance on the use of alternative methods for safety assessments (e.g.: phone contact, virtual visits), alternative locations for assessments (e.g.: local labs or imaging centers), alternative secure study supply delivery methods (e.g.: shipment directly to subjects’ homes), alternative administration methods (e.g.: home nurses or self-administration), as well as virtual assessments and central and remote monitoring programs.
December 2021: The FDA issues draft guidance on the use of Digital Health Technologies for Remote Data Acquisition in Clinical Investigations. This document acknowledges that the inevitable shift from analog to decentralized trials will continue due to the ability of DHTs to exploit varied and continuous data collection. It also highlights the clinical, privacy, and consent risks associated with this evolution and recommends policies and procedures to mitigate these risks. (Below we take a more in-depth look at what this guidance means for DCTs.)
June 2022: The FDA released draft guidance on selecting and developing COAs. In this guidance, the FDA states that DHTs (such as mobile apps) can be used to collect COAs as long as the concept of interest and the context of use are clearly identified. ‍
December 2022: The FDA published a Digital Health Policy Navigator, a tool to help determine whether a product's software functions are the potential focus of FDA oversight. Device functionalities deemed to pose a risk to patient safety if not functioning as intended may be subject to premarket authorization, De Novo premarket approval, and/or adverse event reporting.
‍

The FDA’s Current Position on DCTs

FDA guidelines don’t indicate any preference or recommendation for a specific clinical trial model. Rather, the agency insists the chosen model—whether traditional, decentralized, or hybrid—adhere to good clinical practice (GCP) and minimize the risk to trial integrity and participant safety. This flexible view of clinical trial options places emphasis on the need for a holistic approach to designing and conducting trials. As Jane Miles recently commented in a MedCity News article: “The FDA isn’t treating these guidances as checklists. Rather, the agency’s goal is to spur a macro shift in clinical trials.”
‍

Discover ways to de-risk your DCT while complying with FDA requirements.

‍

Examining The FDA Regulatory Provisions for DCTs

Despite this macro view, the FDA does recognize some challenges to preserving data integrity and privacy when it comes to remote data capture in decentralized clinical trials. To address this, the FDA released draft guidance in December of 2021 on the use of digital health technologies (DHTs) or software-based applications within clinical trials to record electronic data on clinical outcome assessments (eCOAs), performance outcomes (ePerfOs), and patient-reported outcomes (ePROs).

In this guidance, the FDA highlights several important points that can help to de-risk DCTs:

1. Freely given informed consent should be obtained from every subject prior to clinical trial participation.

The FDA has supported the use of eConsenting—especially during the pandemic—as it has enabled patients to maintain social distance and encouraged remote visits. 
Patients’ identities should be authenticated using secured logins or government-approved ID confirmations to ensure the person consenting is the same person who's participating in the study.

2. Sponsors and study teams must weigh anticipated benefits against risks and inconveniences.

The clinical team must verify and validate DHTs as fit for the purpose.
Services of local healthcare providers for investigational product (IP) administration, exams, or lab specimen collections must in no way compromise the safety and privacy of trial participants.

3. Clinical trials should be scientifically sound and described in a clear, detailed protocol approved by an IRB (Institutional Review Board) or IEC (Independent Ethics Committee)

Decentralized Clinical Trials and FDA approval with Obvio Health

DHTs used in clinical investigations are exempt from requirements to obtain marketing approval or clearance, as long as they are not otherwise deficient.
Sponsors seeking to validate the context of a DHT's usage within a clinical trial can participate in a voluntary program called Medical Device Development Tool (MDDT) Qualification Program to de-risk trial development.
If the DHTs are collecting data on novel endpoints, there must be proper justification for their use in the clinical investigation to ensure FDA approval.

4. Trial personnel and participants must be appropriately trained and qualified.

Sponsors must ensure trial participants have the educational and appropriate training to correctly use the tools in remote trials. There must also be proper and systematic training of all personnel associated with the trial.

5. The quality, integrity, and privacy of data must be maintained.

All clinical trial information, regardless of the media used, should be recorded, handled, and stored in a way that facilitates its accurate reporting, interpretation, and verification.
In cases where remote devices are used, special care must be taken to ensure the integrity of trial data.
DHTs must be evaluated for their ability to keep data private and secure from unauthorized access.

6. Interoperability of data should be safeguarded against inconsistencies.

Remote data collection can lead to inconsistencies in reporting versus site-based assessments, compromising the ability of principal investigators (PIs) to evaluate patients holistically. For example, consumer health technologies, such as wearables, are often not designed to interface with clinical data collection tools. Leonard Sacks from the Office of Medical Policy, CDER at the FDA cites another example, observing that travel nurses report medications differently than hospital or pharmacy records, which can lead to disparities in interpreting patient discharge or adverse event reports. Sacks recommends a supervisory structure that plans for and stewards the integration and aggregation of data from multiple data sources to ensure consistency during inspections.

7. Proper documentation and audit trails are required.

Sponsors and CROs must document and include all variables in their clinical trial datasets, irrespective of the location of patient assessment.
All data information captured using DHTs must be recorded and retained for auditing purposes. This usually requires agreements with DHT vendors.

8. Technical support should be available and equal to technology in use.

Patient-owned technology such as smartphones, tablets, and wearables like smartwatches can be used within trials.
Incorporation of remote study data collection leveraging telemedicine or telehealth technologies must be backed by appropriate technology and solid procedures to support patients with any technical need.
Trial-specific tools must be accessible to and understood by the recruited population, taking into consideration age, education, language, health, and technical capabilities. (e.g.: User interfaces should be legible for older patients and translated into the appropriate language for non-native speakers.)
‍

Clues to Future Changes in FDA Guidance

If you’re good at reading tea leaves, the FDA has indicated areas ripe for updated guidance. Most of the guidance, though, takes aim at all clinical trials and doesn’t single out a particular study design. Of course, because DCTs are indeed clinical trials, they will likely be impacted.

1. Digital health technologies: In September 2022, the FDA issued three new final guidance documents in the digital health space—clinical decision support (CDS) software, mobile medical applications, and medical device data systems—as well as a report summarizing its findings on the Software Precertification (Pre-Cert) Pilot Program. The agency’s recent efforts signal that it’s moving toward more oversight of digital health companies. It’s worth noting that mobile medical apps used solely for research (such as DCT platforms), while falling outside of this guidance, may be subject to investigational device exemption regulations if that research involves human subjects.

2. Emergency use authorizations: In a January 31, 2023 update, the FDA highlighted that the end of the public health emergency surrounding the COVID-19 pandemic will not impact the FDA’s ability to authorize devices—including tests, treatments, and vaccines—for emergency use. However, as referenced below, it is likely that the path to accelerated approvals will be impacted going forward.

In addition, any emergency use authorizations for medical devices that were issued during the pandemic now have to seek alternate pathways and re-apply, either by the clearance or pre-market approval route.

3. Accelerated approvals: At the close of 2022, Congress gave the FDA more power over the accelerated approval program. This program allows drugs with data on predicted clinical outcomes to launch while awaiting confirmatory results from post-market trials. Congress recognized that, in many cases, drugs will stay on the market for years without this confirmatory data. The new law requires sponsors to report twice a year on post-market trials and gives the FDA power to withdraw drugs when sponsors don’t meet these requirements. In light of the new law’s passage, and an expected increase in FDA oversight, a growing number of sponsors will likely explore DCT methods for post-market trials due to their convenience and cost benefits.

4. Diversity in clinical trials:  In April 2022, the FDA issued diversity plans to improve clinical trial enrollment of participants from underrepresented racial and ethnic subgroups. Decentralized clinical trials, which often use targeted social media to recruit from a broader sample of the population, have the potential to expand awareness and access to trials. Moving forward, the FDA may assess submissions based in part on the data that illustrates safety and efficacy on a diverse cohort.
‍

‍

Key Considerations for Sponsors When Implementing DCTs

The debate about the relevance of decentralization in clinical trials appears to be waning. But, the challenges of finding the right balance of site-based versus remote trial components remains. A meta-analysis of 640 Phase III trials for novel therapeutics reveals 54% of them failed. Additional analyses point to flawed study design as one of the key factors most likely to drive poor results. As sponsors seek to navigate the risk-and-reward tradeoffs in designing their studies, they can benefit from experience and advice of peers who were early adopters in the space:

1. Find a competent CRO partner with deep clinical, data science, technology, and regulatory expertise—one that’s able to interpret FDA guidance and help you to design your study for optimal efficiency and accuracy with minimal risk. Carefully weigh the tradeoffs between patient centricity (providing ease and choice) and the level of granularity needed to meet endpoints.

2. Begin discussions with regulatory bodies as early as possible. Because DCTs are still relatively new, the approval process requires transparency and embracing a learning curve on the part of all parties. Informing and educating FDA partners on intentions is key to success.

3. Do your homework. Conduct research and gather as much data as is available on similar methodologies and on any early results from internal testing. Leverage any and all available data to project outcomes. As Craig Lipset, Founder of DTRA, explains: “The industry needs to be better at predictive analytics to better understand and forecast what patients might need in the future … in order to make better and more rational use of expensive resources.”
‍

Decentralized clinical trials FDA conclusion

When designing a study, sponsors should think first about “the protection of human subjects in trials and the quality and integrity of the data.” In many instances, this focus will lead sponsors to decentralized methods. If that’s the case, instead of shying away, sponsors should engage with the agency to gain its support. When you look at what the FDA has said about DCTs in the past decade, it’s clear the agency accepts clinical trial innovation when executed for the right reasons.

DCTs have the ability to reduce participant burden, increase trial diversity, produce more real-world data, and may get therapeutics to market faster. And, that’s a win for everyone involved: the patients, the sponsors, and the FDA.

Blog

Decentralized Clinical Trials and the FDA: What the FDA Regulatory Framework Means for DCTs

No items found.

Read on for insights about:

The FDA’s trajectory toward DCT acceptance.
FDA guidance on digital health technologies (DHTs) and what it means for DCTs.
Projected future changes to guidance.
Key considerations for sponsors when implementing DCTs.

‍

The Path to FDA Acceptance of Decentralized Clinical Trials (DCTs)

Below is a look at FDA actions that illustrate an openness to innovative trial methods:

2016: With the 21^st-Century Cures Act, regulatory authorities institute new processes to modernize clinical trial designs and speed the review of certain innovative medical devices.
2017: The FDA and Duke University enter a public-private partnership, forming the Clinical Trials Transformation Initiative (CTTI) to identify practices to enhance the quality and efficacy of studies and to encourage a mainstream dialogue surrounding the use of mobile technologies in clinical research.
2018: The FDA, via CTTI, highlights the potential advantages of DCTs, when compared to trials conducted at more centralized clinical trial sites. Cited advantages include faster recruitment, improved retention, greater control and convenience for participants, and increased participant diversity
2020 to 2021: The FDA publishes several iterations of COVID-19 clinical trials guidance document ation to minimize clinical research delays and disruptions. Included was guidance on the use of alternative methods for safety assessments (e.g.: phone contact, virtual visits), alternative locations for assessments (e.g.: local labs or imaging centers), alternative secure study supply delivery methods (e.g.: shipment directly to subjects’ homes), alternative administration methods (e.g.: home nurses or self-administration), as well as virtual assessments and central and remote monitoring programs.
December 2021: The FDA issues draft guidance on the use of Digital Health Technologies for Remote Data Acquisition in Clinical Investigations. This document acknowledges that the inevitable shift from analog to decentralized trials will continue due to the ability of DHTs to exploit varied and continuous data collection. It also highlights the clinical, privacy, and consent risks associated with this evolution and recommends policies and procedures to mitigate these risks. (Below we take a more in-depth look at what this guidance means for DCTs.)
June 2022: The FDA released draft guidance on selecting and developing COAs. In this guidance, the FDA states that DHTs (such as mobile apps) can be used to collect COAs as long as the concept of interest and the context of use are clearly identified. ‍
December 2022: The FDA published a Digital Health Policy Navigator, a tool to help determine whether a product's software functions are the potential focus of FDA oversight. Device functionalities deemed to pose a risk to patient safety if not functioning as intended may be subject to premarket authorization, De Novo premarket approval, and/or adverse event reporting.
‍

The FDA’s Current Position on DCTs

Discover ways to de-risk your DCT while complying with FDA requirements.

‍

Examining The FDA Regulatory Provisions for DCTs

In this guidance, the FDA highlights several important points that can help to de-risk DCTs:

1. Freely given informed consent should be obtained from every subject prior to clinical trial participation.

The FDA has supported the use of eConsenting—especially during the pandemic—as it has enabled patients to maintain social distance and encouraged remote visits. 
Patients’ identities should be authenticated using secured logins or government-approved ID confirmations to ensure the person consenting is the same person who's participating in the study.

2. Sponsors and study teams must weigh anticipated benefits against risks and inconveniences.

The clinical team must verify and validate DHTs as fit for the purpose.
Services of local healthcare providers for investigational product (IP) administration, exams, or lab specimen collections must in no way compromise the safety and privacy of trial participants.

3. Clinical trials should be scientifically sound and described in a clear, detailed protocol approved by an IRB (Institutional Review Board) or IEC (Independent Ethics Committee)

DHTs used in clinical investigations are exempt from requirements to obtain marketing approval or clearance, as long as they are not otherwise deficient.
Sponsors seeking to validate the context of a DHT's usage within a clinical trial can participate in a voluntary program called Medical Device Development Tool (MDDT) Qualification Program to de-risk trial development.
If the DHTs are collecting data on novel endpoints, there must be proper justification for their use in the clinical investigation to ensure FDA approval.

4. Trial personnel and participants must be appropriately trained and qualified.

Sponsors must ensure trial participants have the educational and appropriate training to correctly use the tools in remote trials. There must also be proper and systematic training of all personnel associated with the trial.

5. The quality, integrity, and privacy of data must be maintained.

All clinical trial information, regardless of the media used, should be recorded, handled, and stored in a way that facilitates its accurate reporting, interpretation, and verification.
In cases where remote devices are used, special care must be taken to ensure the integrity of trial data.
DHTs must be evaluated for their ability to keep data private and secure from unauthorized access.

6. Interoperability of data should be safeguarded against inconsistencies.

Remote data collection can lead to inconsistencies in reporting versus site-based assessments, compromising the ability of principal investigators (PIs) to evaluate patients holistically. For example, consumer health technologies, such as wearables, are often not designed to interface with clinical data collection tools. Leonard Sacks from the Office of Medical Policy, CDER at the FDA cites another example, observing that travel nurses report medications differently than hospital or pharmacy records, which can lead to disparities in interpreting patient discharge or adverse event reports. Sacks recommends a supervisory structure that plans for and stewards the integration and aggregation of data from multiple data sources to ensure consistency during inspections.

7. Proper documentation and audit trails are required.

Sponsors and CROs must document and include all variables in their clinical trial datasets, irrespective of the location of patient assessment.
All data information captured using DHTs must be recorded and retained for auditing purposes. This usually requires agreements with DHT vendors.

8. Technical support should be available and equal to technology in use.

Patient-owned technology such as smartphones, tablets, and wearables like smartwatches can be used within trials.
Incorporation of remote study data collection leveraging telemedicine or telehealth technologies must be backed by appropriate technology and solid procedures to support patients with any technical need.
Trial-specific tools must be accessible to and understood by the recruited population, taking into consideration age, education, language, health, and technical capabilities. (e.g.: User interfaces should be legible for older patients and translated into the appropriate language for non-native speakers.)
‍

Clues to Future Changes in FDA Guidance

‍

Key Considerations for Sponsors When Implementing DCTs

Decentralized clinical trials FDA conclusion

Blog

Decentralized Clinical Trials and the FDA: What the FDA Regulatory Framework Means for DCTs

No items found.

Read on for insights about:

The FDA’s trajectory toward DCT acceptance.
FDA guidance on digital health technologies (DHTs) and what it means for DCTs.
Projected future changes to guidance.
Key considerations for sponsors when implementing DCTs.

‍

The Path to FDA Acceptance of Decentralized Clinical Trials (DCTs)

Below is a look at FDA actions that illustrate an openness to innovative trial methods:

2016: With the 21^st-Century Cures Act, regulatory authorities institute new processes to modernize clinical trial designs and speed the review of certain innovative medical devices.
2017: The FDA and Duke University enter a public-private partnership, forming the Clinical Trials Transformation Initiative (CTTI) to identify practices to enhance the quality and efficacy of studies and to encourage a mainstream dialogue surrounding the use of mobile technologies in clinical research.
2018: The FDA, via CTTI, highlights the potential advantages of DCTs, when compared to trials conducted at more centralized clinical trial sites. Cited advantages include faster recruitment, improved retention, greater control and convenience for participants, and increased participant diversity
2020 to 2021: The FDA publishes several iterations of COVID-19 clinical trials guidance document ation to minimize clinical research delays and disruptions. Included was guidance on the use of alternative methods for safety assessments (e.g.: phone contact, virtual visits), alternative locations for assessments (e.g.: local labs or imaging centers), alternative secure study supply delivery methods (e.g.: shipment directly to subjects’ homes), alternative administration methods (e.g.: home nurses or self-administration), as well as virtual assessments and central and remote monitoring programs.
December 2021: The FDA issues draft guidance on the use of Digital Health Technologies for Remote Data Acquisition in Clinical Investigations. This document acknowledges that the inevitable shift from analog to decentralized trials will continue due to the ability of DHTs to exploit varied and continuous data collection. It also highlights the clinical, privacy, and consent risks associated with this evolution and recommends policies and procedures to mitigate these risks. (Below we take a more in-depth look at what this guidance means for DCTs.)
June 2022: The FDA released draft guidance on selecting and developing COAs. In this guidance, the FDA states that DHTs (such as mobile apps) can be used to collect COAs as long as the concept of interest and the context of use are clearly identified. ‍
December 2022: The FDA published a Digital Health Policy Navigator, a tool to help determine whether a product's software functions are the potential focus of FDA oversight. Device functionalities deemed to pose a risk to patient safety if not functioning as intended may be subject to premarket authorization, De Novo premarket approval, and/or adverse event reporting.
‍

The FDA’s Current Position on DCTs

Discover ways to de-risk your DCT while complying with FDA requirements.

‍

Examining The FDA Regulatory Provisions for DCTs

In this guidance, the FDA highlights several important points that can help to de-risk DCTs:

1. Freely given informed consent should be obtained from every subject prior to clinical trial participation.

The FDA has supported the use of eConsenting—especially during the pandemic—as it has enabled patients to maintain social distance and encouraged remote visits. 
Patients’ identities should be authenticated using secured logins or government-approved ID confirmations to ensure the person consenting is the same person who's participating in the study.

2. Sponsors and study teams must weigh anticipated benefits against risks and inconveniences.

The clinical team must verify and validate DHTs as fit for the purpose.
Services of local healthcare providers for investigational product (IP) administration, exams, or lab specimen collections must in no way compromise the safety and privacy of trial participants.

3. Clinical trials should be scientifically sound and described in a clear, detailed protocol approved by an IRB (Institutional Review Board) or IEC (Independent Ethics Committee)

DHTs used in clinical investigations are exempt from requirements to obtain marketing approval or clearance, as long as they are not otherwise deficient.
Sponsors seeking to validate the context of a DHT's usage within a clinical trial can participate in a voluntary program called Medical Device Development Tool (MDDT) Qualification Program to de-risk trial development.
If the DHTs are collecting data on novel endpoints, there must be proper justification for their use in the clinical investigation to ensure FDA approval.

4. Trial personnel and participants must be appropriately trained and qualified.

Sponsors must ensure trial participants have the educational and appropriate training to correctly use the tools in remote trials. There must also be proper and systematic training of all personnel associated with the trial.

5. The quality, integrity, and privacy of data must be maintained.

All clinical trial information, regardless of the media used, should be recorded, handled, and stored in a way that facilitates its accurate reporting, interpretation, and verification.
In cases where remote devices are used, special care must be taken to ensure the integrity of trial data.
DHTs must be evaluated for their ability to keep data private and secure from unauthorized access.

6. Interoperability of data should be safeguarded against inconsistencies.

Remote data collection can lead to inconsistencies in reporting versus site-based assessments, compromising the ability of principal investigators (PIs) to evaluate patients holistically. For example, consumer health technologies, such as wearables, are often not designed to interface with clinical data collection tools. Leonard Sacks from the Office of Medical Policy, CDER at the FDA cites another example, observing that travel nurses report medications differently than hospital or pharmacy records, which can lead to disparities in interpreting patient discharge or adverse event reports. Sacks recommends a supervisory structure that plans for and stewards the integration and aggregation of data from multiple data sources to ensure consistency during inspections.

7. Proper documentation and audit trails are required.

Sponsors and CROs must document and include all variables in their clinical trial datasets, irrespective of the location of patient assessment.
All data information captured using DHTs must be recorded and retained for auditing purposes. This usually requires agreements with DHT vendors.

8. Technical support should be available and equal to technology in use.

Patient-owned technology such as smartphones, tablets, and wearables like smartwatches can be used within trials.
Incorporation of remote study data collection leveraging telemedicine or telehealth technologies must be backed by appropriate technology and solid procedures to support patients with any technical need.
Trial-specific tools must be accessible to and understood by the recruited population, taking into consideration age, education, language, health, and technical capabilities. (e.g.: User interfaces should be legible for older patients and translated into the appropriate language for non-native speakers.)
‍

Clues to Future Changes in FDA Guidance

‍

Key Considerations for Sponsors When Implementing DCTs

Decentralized clinical trials FDA conclusion

Blog

Decentralized Clinical Trials and the FDA: What the FDA Regulatory Framework Means for DCTs

No items found.

Read on for insights about:

The FDA’s trajectory toward DCT acceptance.
FDA guidance on digital health technologies (DHTs) and what it means for DCTs.
Projected future changes to guidance.
Key considerations for sponsors when implementing DCTs.

‍

The Path to FDA Acceptance of Decentralized Clinical Trials (DCTs)

Below is a look at FDA actions that illustrate an openness to innovative trial methods:

2016: With the 21^st-Century Cures Act, regulatory authorities institute new processes to modernize clinical trial designs and speed the review of certain innovative medical devices.
2017: The FDA and Duke University enter a public-private partnership, forming the Clinical Trials Transformation Initiative (CTTI) to identify practices to enhance the quality and efficacy of studies and to encourage a mainstream dialogue surrounding the use of mobile technologies in clinical research.
2018: The FDA, via CTTI, highlights the potential advantages of DCTs, when compared to trials conducted at more centralized clinical trial sites. Cited advantages include faster recruitment, improved retention, greater control and convenience for participants, and increased participant diversity
2020 to 2021: The FDA publishes several iterations of COVID-19 clinical trials guidance document ation to minimize clinical research delays and disruptions. Included was guidance on the use of alternative methods for safety assessments (e.g.: phone contact, virtual visits), alternative locations for assessments (e.g.: local labs or imaging centers), alternative secure study supply delivery methods (e.g.: shipment directly to subjects’ homes), alternative administration methods (e.g.: home nurses or self-administration), as well as virtual assessments and central and remote monitoring programs.
December 2021: The FDA issues draft guidance on the use of Digital Health Technologies for Remote Data Acquisition in Clinical Investigations. This document acknowledges that the inevitable shift from analog to decentralized trials will continue due to the ability of DHTs to exploit varied and continuous data collection. It also highlights the clinical, privacy, and consent risks associated with this evolution and recommends policies and procedures to mitigate these risks. (Below we take a more in-depth look at what this guidance means for DCTs.)
June 2022: The FDA released draft guidance on selecting and developing COAs. In this guidance, the FDA states that DHTs (such as mobile apps) can be used to collect COAs as long as the concept of interest and the context of use are clearly identified. ‍
December 2022: The FDA published a Digital Health Policy Navigator, a tool to help determine whether a product's software functions are the potential focus of FDA oversight. Device functionalities deemed to pose a risk to patient safety if not functioning as intended may be subject to premarket authorization, De Novo premarket approval, and/or adverse event reporting.
‍

The FDA’s Current Position on DCTs

Discover ways to de-risk your DCT while complying with FDA requirements.

‍

Examining The FDA Regulatory Provisions for DCTs

In this guidance, the FDA highlights several important points that can help to de-risk DCTs:

1. Freely given informed consent should be obtained from every subject prior to clinical trial participation.

The FDA has supported the use of eConsenting—especially during the pandemic—as it has enabled patients to maintain social distance and encouraged remote visits. 
Patients’ identities should be authenticated using secured logins or government-approved ID confirmations to ensure the person consenting is the same person who's participating in the study.

2. Sponsors and study teams must weigh anticipated benefits against risks and inconveniences.

The clinical team must verify and validate DHTs as fit for the purpose.
Services of local healthcare providers for investigational product (IP) administration, exams, or lab specimen collections must in no way compromise the safety and privacy of trial participants.

3. Clinical trials should be scientifically sound and described in a clear, detailed protocol approved by an IRB (Institutional Review Board) or IEC (Independent Ethics Committee)

DHTs used in clinical investigations are exempt from requirements to obtain marketing approval or clearance, as long as they are not otherwise deficient.
Sponsors seeking to validate the context of a DHT's usage within a clinical trial can participate in a voluntary program called Medical Device Development Tool (MDDT) Qualification Program to de-risk trial development.
If the DHTs are collecting data on novel endpoints, there must be proper justification for their use in the clinical investigation to ensure FDA approval.

4. Trial personnel and participants must be appropriately trained and qualified.

Sponsors must ensure trial participants have the educational and appropriate training to correctly use the tools in remote trials. There must also be proper and systematic training of all personnel associated with the trial.

5. The quality, integrity, and privacy of data must be maintained.

All clinical trial information, regardless of the media used, should be recorded, handled, and stored in a way that facilitates its accurate reporting, interpretation, and verification.
In cases where remote devices are used, special care must be taken to ensure the integrity of trial data.
DHTs must be evaluated for their ability to keep data private and secure from unauthorized access.

6. Interoperability of data should be safeguarded against inconsistencies.

Remote data collection can lead to inconsistencies in reporting versus site-based assessments, compromising the ability of principal investigators (PIs) to evaluate patients holistically. For example, consumer health technologies, such as wearables, are often not designed to interface with clinical data collection tools. Leonard Sacks from the Office of Medical Policy, CDER at the FDA cites another example, observing that travel nurses report medications differently than hospital or pharmacy records, which can lead to disparities in interpreting patient discharge or adverse event reports. Sacks recommends a supervisory structure that plans for and stewards the integration and aggregation of data from multiple data sources to ensure consistency during inspections.

7. Proper documentation and audit trails are required.

Sponsors and CROs must document and include all variables in their clinical trial datasets, irrespective of the location of patient assessment.
All data information captured using DHTs must be recorded and retained for auditing purposes. This usually requires agreements with DHT vendors.

8. Technical support should be available and equal to technology in use.

Patient-owned technology such as smartphones, tablets, and wearables like smartwatches can be used within trials.
Incorporation of remote study data collection leveraging telemedicine or telehealth technologies must be backed by appropriate technology and solid procedures to support patients with any technical need.
Trial-specific tools must be accessible to and understood by the recruited population, taking into consideration age, education, language, health, and technical capabilities. (e.g.: User interfaces should be legible for older patients and translated into the appropriate language for non-native speakers.)
‍

Clues to Future Changes in FDA Guidance

‍

Key Considerations for Sponsors When Implementing DCTs

Decentralized clinical trials FDA conclusion

Blog

Decentralized Clinical Trials and the FDA: What the FDA Regulatory Framework Means for DCTs

No items found.

Read on for insights about:

The FDA’s trajectory toward DCT acceptance.
FDA guidance on digital health technologies (DHTs) and what it means for DCTs.
Projected future changes to guidance.
Key considerations for sponsors when implementing DCTs.

‍

The Path to FDA Acceptance of Decentralized Clinical Trials (DCTs)

Below is a look at FDA actions that illustrate an openness to innovative trial methods:

2016: With the 21^st-Century Cures Act, regulatory authorities institute new processes to modernize clinical trial designs and speed the review of certain innovative medical devices.
2017: The FDA and Duke University enter a public-private partnership, forming the Clinical Trials Transformation Initiative (CTTI) to identify practices to enhance the quality and efficacy of studies and to encourage a mainstream dialogue surrounding the use of mobile technologies in clinical research.
2018: The FDA, via CTTI, highlights the potential advantages of DCTs, when compared to trials conducted at more centralized clinical trial sites. Cited advantages include faster recruitment, improved retention, greater control and convenience for participants, and increased participant diversity
2020 to 2021: The FDA publishes several iterations of COVID-19 clinical trials guidance document ation to minimize clinical research delays and disruptions. Included was guidance on the use of alternative methods for safety assessments (e.g.: phone contact, virtual visits), alternative locations for assessments (e.g.: local labs or imaging centers), alternative secure study supply delivery methods (e.g.: shipment directly to subjects’ homes), alternative administration methods (e.g.: home nurses or self-administration), as well as virtual assessments and central and remote monitoring programs.
December 2021: The FDA issues draft guidance on the use of Digital Health Technologies for Remote Data Acquisition in Clinical Investigations. This document acknowledges that the inevitable shift from analog to decentralized trials will continue due to the ability of DHTs to exploit varied and continuous data collection. It also highlights the clinical, privacy, and consent risks associated with this evolution and recommends policies and procedures to mitigate these risks. (Below we take a more in-depth look at what this guidance means for DCTs.)
June 2022: The FDA released draft guidance on selecting and developing COAs. In this guidance, the FDA states that DHTs (such as mobile apps) can be used to collect COAs as long as the concept of interest and the context of use are clearly identified. ‍
December 2022: The FDA published a Digital Health Policy Navigator, a tool to help determine whether a product's software functions are the potential focus of FDA oversight. Device functionalities deemed to pose a risk to patient safety if not functioning as intended may be subject to premarket authorization, De Novo premarket approval, and/or adverse event reporting.
‍

The FDA’s Current Position on DCTs

Discover ways to de-risk your DCT while complying with FDA requirements.

‍

Examining The FDA Regulatory Provisions for DCTs

In this guidance, the FDA highlights several important points that can help to de-risk DCTs:

1. Freely given informed consent should be obtained from every subject prior to clinical trial participation.

The FDA has supported the use of eConsenting—especially during the pandemic—as it has enabled patients to maintain social distance and encouraged remote visits. 
Patients’ identities should be authenticated using secured logins or government-approved ID confirmations to ensure the person consenting is the same person who's participating in the study.

2. Sponsors and study teams must weigh anticipated benefits against risks and inconveniences.

The clinical team must verify and validate DHTs as fit for the purpose.
Services of local healthcare providers for investigational product (IP) administration, exams, or lab specimen collections must in no way compromise the safety and privacy of trial participants.

3. Clinical trials should be scientifically sound and described in a clear, detailed protocol approved by an IRB (Institutional Review Board) or IEC (Independent Ethics Committee)

DHTs used in clinical investigations are exempt from requirements to obtain marketing approval or clearance, as long as they are not otherwise deficient.
Sponsors seeking to validate the context of a DHT's usage within a clinical trial can participate in a voluntary program called Medical Device Development Tool (MDDT) Qualification Program to de-risk trial development.
If the DHTs are collecting data on novel endpoints, there must be proper justification for their use in the clinical investigation to ensure FDA approval.

4. Trial personnel and participants must be appropriately trained and qualified.

Sponsors must ensure trial participants have the educational and appropriate training to correctly use the tools in remote trials. There must also be proper and systematic training of all personnel associated with the trial.

5. The quality, integrity, and privacy of data must be maintained.

All clinical trial information, regardless of the media used, should be recorded, handled, and stored in a way that facilitates its accurate reporting, interpretation, and verification.
In cases where remote devices are used, special care must be taken to ensure the integrity of trial data.
DHTs must be evaluated for their ability to keep data private and secure from unauthorized access.

6. Interoperability of data should be safeguarded against inconsistencies.

Remote data collection can lead to inconsistencies in reporting versus site-based assessments, compromising the ability of principal investigators (PIs) to evaluate patients holistically. For example, consumer health technologies, such as wearables, are often not designed to interface with clinical data collection tools. Leonard Sacks from the Office of Medical Policy, CDER at the FDA cites another example, observing that travel nurses report medications differently than hospital or pharmacy records, which can lead to disparities in interpreting patient discharge or adverse event reports. Sacks recommends a supervisory structure that plans for and stewards the integration and aggregation of data from multiple data sources to ensure consistency during inspections.

7. Proper documentation and audit trails are required.

Sponsors and CROs must document and include all variables in their clinical trial datasets, irrespective of the location of patient assessment.
All data information captured using DHTs must be recorded and retained for auditing purposes. This usually requires agreements with DHT vendors.

8. Technical support should be available and equal to technology in use.

Patient-owned technology such as smartphones, tablets, and wearables like smartwatches can be used within trials.
Incorporation of remote study data collection leveraging telemedicine or telehealth technologies must be backed by appropriate technology and solid procedures to support patients with any technical need.
Trial-specific tools must be accessible to and understood by the recruited population, taking into consideration age, education, language, health, and technical capabilities. (e.g.: User interfaces should be legible for older patients and translated into the appropriate language for non-native speakers.)
‍

Clues to Future Changes in FDA Guidance

‍

Key Considerations for Sponsors When Implementing DCTs

Decentralized clinical trials FDA conclusion

Blog

Decentralized Clinical Trials and the FDA: What the FDA Regulatory Framework Means for DCTs

No items found.

Read on for insights about:

The FDA’s trajectory toward DCT acceptance.
FDA guidance on digital health technologies (DHTs) and what it means for DCTs.
Projected future changes to guidance.
Key considerations for sponsors when implementing DCTs.

‍

The Path to FDA Acceptance of Decentralized Clinical Trials (DCTs)

Below is a look at FDA actions that illustrate an openness to innovative trial methods:

2016: With the 21^st-Century Cures Act, regulatory authorities institute new processes to modernize clinical trial designs and speed the review of certain innovative medical devices.
2017: The FDA and Duke University enter a public-private partnership, forming the Clinical Trials Transformation Initiative (CTTI) to identify practices to enhance the quality and efficacy of studies and to encourage a mainstream dialogue surrounding the use of mobile technologies in clinical research.
2018: The FDA, via CTTI, highlights the potential advantages of DCTs, when compared to trials conducted at more centralized clinical trial sites. Cited advantages include faster recruitment, improved retention, greater control and convenience for participants, and increased participant diversity
2020 to 2021: The FDA publishes several iterations of COVID-19 clinical trials guidance document ation to minimize clinical research delays and disruptions. Included was guidance on the use of alternative methods for safety assessments (e.g.: phone contact, virtual visits), alternative locations for assessments (e.g.: local labs or imaging centers), alternative secure study supply delivery methods (e.g.: shipment directly to subjects’ homes), alternative administration methods (e.g.: home nurses or self-administration), as well as virtual assessments and central and remote monitoring programs.
December 2021: The FDA issues draft guidance on the use of Digital Health Technologies for Remote Data Acquisition in Clinical Investigations. This document acknowledges that the inevitable shift from analog to decentralized trials will continue due to the ability of DHTs to exploit varied and continuous data collection. It also highlights the clinical, privacy, and consent risks associated with this evolution and recommends policies and procedures to mitigate these risks. (Below we take a more in-depth look at what this guidance means for DCTs.)
June 2022: The FDA released draft guidance on selecting and developing COAs. In this guidance, the FDA states that DHTs (such as mobile apps) can be used to collect COAs as long as the concept of interest and the context of use are clearly identified. ‍
December 2022: The FDA published a Digital Health Policy Navigator, a tool to help determine whether a product's software functions are the potential focus of FDA oversight. Device functionalities deemed to pose a risk to patient safety if not functioning as intended may be subject to premarket authorization, De Novo premarket approval, and/or adverse event reporting.
‍

The FDA’s Current Position on DCTs

Discover ways to de-risk your DCT while complying with FDA requirements.

‍

Examining The FDA Regulatory Provisions for DCTs

In this guidance, the FDA highlights several important points that can help to de-risk DCTs:

1. Freely given informed consent should be obtained from every subject prior to clinical trial participation.

The FDA has supported the use of eConsenting—especially during the pandemic—as it has enabled patients to maintain social distance and encouraged remote visits. 
Patients’ identities should be authenticated using secured logins or government-approved ID confirmations to ensure the person consenting is the same person who's participating in the study.

2. Sponsors and study teams must weigh anticipated benefits against risks and inconveniences.

The clinical team must verify and validate DHTs as fit for the purpose.
Services of local healthcare providers for investigational product (IP) administration, exams, or lab specimen collections must in no way compromise the safety and privacy of trial participants.

3. Clinical trials should be scientifically sound and described in a clear, detailed protocol approved by an IRB (Institutional Review Board) or IEC (Independent Ethics Committee)

DHTs used in clinical investigations are exempt from requirements to obtain marketing approval or clearance, as long as they are not otherwise deficient.
Sponsors seeking to validate the context of a DHT's usage within a clinical trial can participate in a voluntary program called Medical Device Development Tool (MDDT) Qualification Program to de-risk trial development.
If the DHTs are collecting data on novel endpoints, there must be proper justification for their use in the clinical investigation to ensure FDA approval.

4. Trial personnel and participants must be appropriately trained and qualified.

Sponsors must ensure trial participants have the educational and appropriate training to correctly use the tools in remote trials. There must also be proper and systematic training of all personnel associated with the trial.

5. The quality, integrity, and privacy of data must be maintained.

All clinical trial information, regardless of the media used, should be recorded, handled, and stored in a way that facilitates its accurate reporting, interpretation, and verification.
In cases where remote devices are used, special care must be taken to ensure the integrity of trial data.
DHTs must be evaluated for their ability to keep data private and secure from unauthorized access.

6. Interoperability of data should be safeguarded against inconsistencies.

Remote data collection can lead to inconsistencies in reporting versus site-based assessments, compromising the ability of principal investigators (PIs) to evaluate patients holistically. For example, consumer health technologies, such as wearables, are often not designed to interface with clinical data collection tools. Leonard Sacks from the Office of Medical Policy, CDER at the FDA cites another example, observing that travel nurses report medications differently than hospital or pharmacy records, which can lead to disparities in interpreting patient discharge or adverse event reports. Sacks recommends a supervisory structure that plans for and stewards the integration and aggregation of data from multiple data sources to ensure consistency during inspections.

7. Proper documentation and audit trails are required.

Sponsors and CROs must document and include all variables in their clinical trial datasets, irrespective of the location of patient assessment.
All data information captured using DHTs must be recorded and retained for auditing purposes. This usually requires agreements with DHT vendors.

8. Technical support should be available and equal to technology in use.

Patient-owned technology such as smartphones, tablets, and wearables like smartwatches can be used within trials.
Incorporation of remote study data collection leveraging telemedicine or telehealth technologies must be backed by appropriate technology and solid procedures to support patients with any technical need.
Trial-specific tools must be accessible to and understood by the recruited population, taking into consideration age, education, language, health, and technical capabilities. (e.g.: User interfaces should be legible for older patients and translated into the appropriate language for non-native speakers.)
‍

Clues to Future Changes in FDA Guidance

‍

Key Considerations for Sponsors When Implementing DCTs

Decentralized clinical trials FDA conclusion

Blog

Decentralized Clinical Trials and the FDA: What the FDA Regulatory Framework Means for DCTs

No items found.

Read on for insights about:

The FDA’s trajectory toward DCT acceptance.
FDA guidance on digital health technologies (DHTs) and what it means for DCTs.
Projected future changes to guidance.
Key considerations for sponsors when implementing DCTs.

‍

The Path to FDA Acceptance of Decentralized Clinical Trials (DCTs)

Below is a look at FDA actions that illustrate an openness to innovative trial methods:

2016: With the 21^st-Century Cures Act, regulatory authorities institute new processes to modernize clinical trial designs and speed the review of certain innovative medical devices.
2017: The FDA and Duke University enter a public-private partnership, forming the Clinical Trials Transformation Initiative (CTTI) to identify practices to enhance the quality and efficacy of studies and to encourage a mainstream dialogue surrounding the use of mobile technologies in clinical research.
2018: The FDA, via CTTI, highlights the potential advantages of DCTs, when compared to trials conducted at more centralized clinical trial sites. Cited advantages include faster recruitment, improved retention, greater control and convenience for participants, and increased participant diversity
2020 to 2021: The FDA publishes several iterations of COVID-19 clinical trials guidance document ation to minimize clinical research delays and disruptions. Included was guidance on the use of alternative methods for safety assessments (e.g.: phone contact, virtual visits), alternative locations for assessments (e.g.: local labs or imaging centers), alternative secure study supply delivery methods (e.g.: shipment directly to subjects’ homes), alternative administration methods (e.g.: home nurses or self-administration), as well as virtual assessments and central and remote monitoring programs.
December 2021: The FDA issues draft guidance on the use of Digital Health Technologies for Remote Data Acquisition in Clinical Investigations. This document acknowledges that the inevitable shift from analog to decentralized trials will continue due to the ability of DHTs to exploit varied and continuous data collection. It also highlights the clinical, privacy, and consent risks associated with this evolution and recommends policies and procedures to mitigate these risks. (Below we take a more in-depth look at what this guidance means for DCTs.)
June 2022: The FDA released draft guidance on selecting and developing COAs. In this guidance, the FDA states that DHTs (such as mobile apps) can be used to collect COAs as long as the concept of interest and the context of use are clearly identified. ‍
December 2022: The FDA published a Digital Health Policy Navigator, a tool to help determine whether a product's software functions are the potential focus of FDA oversight. Device functionalities deemed to pose a risk to patient safety if not functioning as intended may be subject to premarket authorization, De Novo premarket approval, and/or adverse event reporting.
‍

The FDA’s Current Position on DCTs

Discover ways to de-risk your DCT while complying with FDA requirements.

‍

Examining The FDA Regulatory Provisions for DCTs

In this guidance, the FDA highlights several important points that can help to de-risk DCTs:

1. Freely given informed consent should be obtained from every subject prior to clinical trial participation.

The FDA has supported the use of eConsenting—especially during the pandemic—as it has enabled patients to maintain social distance and encouraged remote visits. 
Patients’ identities should be authenticated using secured logins or government-approved ID confirmations to ensure the person consenting is the same person who's participating in the study.

2. Sponsors and study teams must weigh anticipated benefits against risks and inconveniences.

The clinical team must verify and validate DHTs as fit for the purpose.
Services of local healthcare providers for investigational product (IP) administration, exams, or lab specimen collections must in no way compromise the safety and privacy of trial participants.

3. Clinical trials should be scientifically sound and described in a clear, detailed protocol approved by an IRB (Institutional Review Board) or IEC (Independent Ethics Committee)

DHTs used in clinical investigations are exempt from requirements to obtain marketing approval or clearance, as long as they are not otherwise deficient.
Sponsors seeking to validate the context of a DHT's usage within a clinical trial can participate in a voluntary program called Medical Device Development Tool (MDDT) Qualification Program to de-risk trial development.
If the DHTs are collecting data on novel endpoints, there must be proper justification for their use in the clinical investigation to ensure FDA approval.

4. Trial personnel and participants must be appropriately trained and qualified.

Sponsors must ensure trial participants have the educational and appropriate training to correctly use the tools in remote trials. There must also be proper and systematic training of all personnel associated with the trial.

5. The quality, integrity, and privacy of data must be maintained.

All clinical trial information, regardless of the media used, should be recorded, handled, and stored in a way that facilitates its accurate reporting, interpretation, and verification.
In cases where remote devices are used, special care must be taken to ensure the integrity of trial data.
DHTs must be evaluated for their ability to keep data private and secure from unauthorized access.

6. Interoperability of data should be safeguarded against inconsistencies.

Remote data collection can lead to inconsistencies in reporting versus site-based assessments, compromising the ability of principal investigators (PIs) to evaluate patients holistically. For example, consumer health technologies, such as wearables, are often not designed to interface with clinical data collection tools. Leonard Sacks from the Office of Medical Policy, CDER at the FDA cites another example, observing that travel nurses report medications differently than hospital or pharmacy records, which can lead to disparities in interpreting patient discharge or adverse event reports. Sacks recommends a supervisory structure that plans for and stewards the integration and aggregation of data from multiple data sources to ensure consistency during inspections.

7. Proper documentation and audit trails are required.

Sponsors and CROs must document and include all variables in their clinical trial datasets, irrespective of the location of patient assessment.
All data information captured using DHTs must be recorded and retained for auditing purposes. This usually requires agreements with DHT vendors.

8. Technical support should be available and equal to technology in use.

Patient-owned technology such as smartphones, tablets, and wearables like smartwatches can be used within trials.
Incorporation of remote study data collection leveraging telemedicine or telehealth technologies must be backed by appropriate technology and solid procedures to support patients with any technical need.
Trial-specific tools must be accessible to and understood by the recruited population, taking into consideration age, education, language, health, and technical capabilities. (e.g.: User interfaces should be legible for older patients and translated into the appropriate language for non-native speakers.)
‍

Clues to Future Changes in FDA Guidance

‍

Key Considerations for Sponsors When Implementing DCTs

Decentralized clinical trials FDA conclusion