During the recent pandemic, as with many facets of life and business, the design and conduct of clinical trials adapted to limit physical contact between individuals—in this case, those conducting and participating in clinical studies. Many companies opted to use a format that has been around for some time but not frequently used: the Decentralized Clinical Trial, or DCT.

As the name implies, a DCT does not involve a central facility but makes use of technologies such as telemedicine and mobile apps to allow participation from virtually anywhere. While not new, a lack of experience with this approach has proven challenging for companies seeking to conduct remote trials.

[Related: For more GCP insights from the author, view the recording of the webinar, “FDA GCP Inspection Trends Identified Using AI.”]

June webinar - ondemand

At the Society of Quality Assurance 2022 Annual Meeting in Palm Springs, Calif., FDA Office of Regulatory Affairs Bioresearch Monitoring Division I Director Anne Johnson provided FDA’s perspective on DCTs in a presentation titled, “Sponsor Oversight of Decentralized Clinical Trials.”

She noted that the agency has “experienced a rapid surge in pivoting to decentralized designs by necessity during the pandemic.” She reported that the use of DCTs has “sped up the adoption of technology and leveraged services that are closer geographically, available or open to patients and child participants.”

In her presentation, Johnson provided the agency’s perspective on DCTs, including the regulation framework, elements of the decentralized trials, and responsibilities of sponsors for oversight.

This report on her talk will be divided into three parts, as follows:

Part I

  • Background and an overview of the applicable regulations
  •  Elements of DCTs, including the design, benefits, and challenges

Part II

Sponsor oversight responsibilities for DCTs regarding:

  • Electronic informed consent
  • Remote visits
  •  Electronic data considerations

Part III

  • Risk-based monitoring
  • FDA guidance that directly impacts DCTs
  • Points to consider

Part I: Background, Benefits, and Challenges of DCTs

Johnson clarified that FDA regulations do not specify the type of trial a sponsor must conduct, and that sponsor requirements remain the same whether the clinical trial is traditional, decentralized, or a hybrid of the two. Regulations covering trials can be found in 21 CFR 312.50 for drugs and biologics and in 21 CFR 812.40 for medical devices.

What may change with DCTs, she said, is an increase in the use of electronic systems or digital health technologies, making 21 CFR Part 11 on electronic records and signatures applicable.

“The focus of FDA continues to be, and will remain, the protection of the rights of human subjects in trials and the quality and integrity of the data,” Johnson emphasized.

As a preface for her discussion, the regulator made what she termed “an important distinction” in terminology between the terms virtual and decentralized.

Virtual trials are preclinical trials that are conducted by means of computer modeling or computerized simulation (in silico) or by some other type of model.

DCTs, on the other hand, refer to remote interactions with real participants, i.e., clinical trials executed through the use of telemedicine visits or telehealth, mobile and local healthcare providers, and digital health mobile technologies.

Elements of DCTs

DCTs may comprise several terms and elements, Johnson said (Figure 1).

Figure 1 DCTs May Incorporate the Following
FIGURE 1 |  DCTs May Incorporate the Following

Annotating Figure 1, Johnson explained that DCTs can:

  • Incorporate remote study data collection via telemedicine or telehealth
  • Use or incorporate local healthcare providers for investigational product (IP) administration or exams, or lab specimen collections
  • Use and incorporate electronic informed consent and the use of digital health technologies, including electronic systems or components that can be off the shelf or customized
  • Be owned or managed by sponsors or be outsourced and owned and managed by vendors
  • Incorporate various aspects such as patient-reported outcomes or electronic clinical outcome assessments
  •  Incorporate direct-to-subject investigational product shipments

Design of DCTs

The design of DCTs the agency has been seeing comprise a convergence in using many of the factors noted in Figure 1 and integrating them into a clinical investigation. Johnson discussed these factors and gave her perspective on aspects of the design of DCTs.

She suggested sponsors consider that the processes and the procedures must be provided, not just to the staff, but to the site and to the subjects as well, being especially mindful of the electronic interfaces.

It is important to note that in addition to regulatory considerations, there are legal aspects of telehealth and telemedicine to consider as well as trial participants’ expectations of privacy and confidentiality. Validation of the smart tools and computer security along with security threats posed to those electronic systems that are used are also important considerations.

The focus of FDA continues to be, and will remain, the protection of the rights of human subjects in trials

Regarding the data that is captured and stored, consideration must be given to access control points in the electronic system and short and long-term data storage requirements.

Johnson stressed that the education of the trial subject is crucial to the success of any clinical investigation and to accurate data capture. She advised that step-by-step videos and written how-to guides that the average individual will be able to understand and use are “very important to optimizing their experience in the trial and also ensuring that you are obtaining the best quality data possible.”

[Related: From 2007-2022 there were 173 primary 483 observations involving informed consent issued to clinical investigators. Contact us to learn how Redica can help you monitor enforcement actions involving your clinical investigators.]

Clinical Investigator - GCP Informed Consent
Redica Systems Enforcement Analytics | Clinical Investigator Informed Consent 483s

Benefits of DCTs

In her discussion of the benefits and challenges of DCTs, Johnson pointed to work done by a public-private partnership—the Clinical Trials Transformation Initiative (CTTI)—that was published in 2019. The article is titled, “Legal, Regulatory, and Practical Issues to Consider When Adopting Decentralized Clinical Trials: Recommendations From the Clinical Trials Transformation Initiative.”

The benefits of conducting a DCT that CTTI cited include a more efficient clinical trial with lower costs, along with accelerated enrollment of study subjects and increased diversity. DCTs, the group said, have the option to include more participants by removing some of the barriers that are associated with geographic location and limited mobility.

DCTs also allow more convenient participation for people with disabilities, busy schedules, young children, or transportation issues.

The CTTI study concluded that the increase in diversity of the participants makes the trials more representative and that DCTs lessen the burdens of time and travel on the participants.

“It also gave the ability to gather more frequent measurements, more frequent information, and even continuous data in certain ways,” Johnson reported. “In addition, there are the more representative aspects of real-world administration post-approval, because you have a decentralized trial design with a more dispersed population that is participating in it.”

The use of DCTS for rare disease trials of limited, smaller populations that are geographically dispersed allows eligible participants a greater ability to join the trials.

Challenges of DCTs

Challenges encountered in DCTs include aspects of the use of electronic data and federal and local regulatory frameworks.

The robustness of the digital infrastructure is sometimes an issue, which can be compounded by limited experience with a digital, remote, decentralized approach by the study staff, the clinical investigator, and the study subjects.

DCTs also allow more convenient participation for people with disabilities, busy schedules, young children, or transportation issues

There are federal regulatory barriers, “some real and some perceived or anticipated,” Johnson said. She noted that FDA is “very open to considering and encouraging innovative trial designs that are enhanced to get more quality data and get more participants and greater diversity into the trials that are being conducted.”

Also challenging are detailed and highly variable state laws and regulations that include protection of patient information, confidentiality, and prescribing practices for investigational products. “Some of these are very real hurdles that have to be addressed,” Johnson explained.

The more decentralized a clinical investigation, the greater the challenge of ensuring consistency when executing the protocols. DCTs can also be challenging from the standpoint of how data is handled and stored, Johnson said. She recommended a close examination of the data generated—specifically focusing on data reliability and integrity.

Using Redica Systems for Due Diligence

An important part of designing and planning a clinical trial is conducting due diligence on clinical investigators (CIs), Institutional Review Boards (IRBs), and other potential partners to learn about and evaluate any compliance issues they may have had in the past.

In a six-year collection of FDA warning letters issued to CIs of human drug studies, the Redica Systems Expert Model for GCP confirms that “protocol compliance” is the most common category of observation involving “responsibilities of the investigator”—and “dosing issues” is the largest subcategory under “protocol compliance.”

Designed to unearth an actionable level of detail from Redica Systems’ vast collection of inspection documents, the Expert Model for GCP reveals compliance issues found in both FDA warning letters and a 20-year collection of 483s issued to CIs of human studies.

For a better understanding of the Redica System models and how they can help you find and evaluate compliance issues in warning letters and 483s, view a recording of the webinar, “FDA GCP Inspection Trends Identified Using AI.”

Part II examines sponsor oversight responsibilities for DCTs.

Additional Resources

Legal, Regulatory, and Practical Issues to Consider When Adopting Decentralized Clinical Trials: Recommendations From the Clinical Trials Transformation Initiative

Data Integrity and Your Clinical Investigator: What the Data Shows

The Components of “Responsibilities of the Investigator” Observations

Extracting Specific Protocol Violations from Warning Letter Citations

Webinar – FDA GCP Inspection Trends Identified Using AI

June webinar - ondemand

Comparing and Analyzing Russian, UK, and US Top Ten Pharma Inspection Findings FY 2019

Webinar: Comparing and Analyzing Russian, UK, and US Top Ten Pharma Inspection Findings FY 2019

Presented by Jerry Chapman on October 29, 2020

What you will learn:

  • A comparison of 483 observations in FY2019
  • Top 10 Russian Ministry of Health inspection findings
  • Top 10 FDA Warning Letter findings
  • Top MHRA inspection findings
Redica Systems Enforcement Analytics

Get help choosing the right CRO.

Enter your email address and someone will contact you shortly to customize your insights.

Experience the Power of Redica Systems

Complete the form and one of our experts will reach out to you to schedule a demo and answer questions about our subscription options.

INDEX INFORMATION  Redica consolidates regulatory data in real-time on the single largest database for quality, safety, and compliance intelligence.

STRENGTHEN DATASETS Redica machine intelligence algorithms identify and triage risk signals to derive meaning from vast amounts of private and public data.

ANALYZE & INTERPRET PATTERNS Redica instantly models the customer-specific regulatory risks, trends, and opportunities that stand to fundamentally change compliance operations.

Redica Systems Enforcement Analytics

Evaluate Your CDMOs

Enter your email address and someone will contact you shortly to customize your report.

Redica Systems Enforcement Analytics

Compare the inspection history of your CDMO sites.

Enter your email address and someone will contact you shortly to customize your report.

Redica Systems Enforcement Analytics

Compare the enforcement history of your CDMOs.

Enter your email address and someone will contact you shortly to customize your report.

Redica Systems Enforcement Analytics

Monitor compliance at your Clinical Investigator sites.

Enter your email address and someone will contact you shortly to get you started.

Redica Systems Enforcement Analytics

Prepare for inspections of Clinical Investigator sites.

Enter your email address and someone will contact you shortly to provide more Clinical Investigator data about your sites.

Redica Systems Enforcement Analytics

Prepare for your next inspection.

Enter your email address and someone will contact you shortly to explore enforcement trends. 

Redica Systems Enforcement Analytics

Prepare for your next inspection.

Enter your email address and someone will contact you shortly to explore observations and trends. 

Redica Systems Enforcement Analytics

Prepare for your next inspection.

Enter your email address and someone will contact you shortly to run your custom report.

Redica Systems Enforcement Analytics

Compare two companies of your choice.

Enter your email address and someone will contact you shortly to customize your report.

Redica Systems Enforcement Analytics

Upgrade your inspection strategy.

Enter your email address and someone will contact you shortly to get the reports and analysis you need.

Download the Special Report

Download your copy of THE FDA INSPECTION LANDSCAPE IN MID-2020 AND A LOOK AT VIRTUAL INSPECTION

In this summary we identify:

  • Trend analysis of FDA inspections through mid-2020
  • Strategies for preparing and hosting virtual inspections
  • New technologies to support remote inspections

Download the Special Report

CDMO Comparison opt-in

In this summary we identify:

FY2018-FY2020 GMP data for Lonza & Catalent

Top GMP primary citations

Top FDA 483 observations

Panel Discussion – Remote Audits

Panel Discussion opt in image

Featuring Panelists:
—Barbara W. Unger, Unger Consulting, Inc.
—Jerry Chapman, Redica Systems
—Stephanie Gaulding, Pharmatech Associates

Who Will Benefit?
This session will be valuable to GMP quality, regulatory, compliance, and management personnel in FDA-regulated industries who want to have a conversation on remote audits and get to know what is going on in the industry.

Turning Failure into Success

Presented on Tuesday, April 27, 2021 by Steve Greer, Executive Coach, Genesis Assist, and former Quality Leader, Procter and Gamble

What you will learn:

  • How to use the Leadership SOS Model to transform quality culture
  • How to strengthen quality systems to eliminate human error
  • How to generate ideas on how to set your organization up for success for shareholders, FDA, and staff
Redica Systems Enforcement Analytics

Get Full Access to Redica Enforcement Analytics

Enter your email address and someone will contact you shortly to answer all of your questions and get you started.

Quality Management Systems for Small Pharma and Biotech Firms

Webinar: QMS for Small Pharma and Biotech Firms

Presented by Fenton Fong, Founder, Managing Director, & Principal at xCellarate

Get instant access to the webinar video and slides.

What you will learn:

  • Common challenges small pharma firms face when developing a QMS
    Recent enforcement trends involving the Quality Unit
    Impact of the COVID-19 pandemic

Download the Special Report

APAC ad

In this summary we identify:

GMP data from FY2017 to FY2020 for the Asia-Pacific region

Top 3 GMP primary and secondary citations

Top 3 483 observations

Download the Special Report

An Analysis Of MHRA’s Latest Annual GMP Inspection Deficiencies Report

In this summary we identify:

  • Data from 2019 UK MHRA Inspections
  • Trends from 2015, 2016, 2018, and 2019 inspections
  • Conclusions drawn from an analysis of drug inspection data

Experience the Power of Redica Systems

Redica Systems

SEARCH Find the inspection records you want by inspector’s name, company name, site, city, country, etc.

WARNING LETTERS Easily search the largest database of FDA Warning Letters by date, company, FDA office, or subject

SITES Quickly assess inspection records including dates and inspectors across all of your sites

INSPECTIONS Complete list of FDA inspections by date, company, category, and country

Get Complete Access to the Redica Systems Platform

Please submit your email address and one of our team members will contact you shortly to answer all of your questions and get you started with the new Enforcement Analytics platform.

Redica Systems Enforcement Analytics

Upgrade your inspection strategy.

Enter your email address and someone will contact you shortly to get the reports and analysis you need to prepare for your next inspection.

Experience the Power of Redica Systems

Redica Systems Enforcement Analytics

Sign up for your FREE account today and get instant access to Enforcement Analytics.

Champion of Change - 3Cs to Success

Webinar: Champion of Change - 3Cs to Success

Presented by Steve Greer on June 23, 2020

What you will learn:

  • The 3C Model to become a champion of change
  • How to identify game-changing habits and the steps to implement them
  • Ways to develop greater purpose-centered leadership
  • How to generate awareness along with actions to create changes in how you think about challenges and change putting you on a path to lead change successfully in your organization
  •  

Download the Special Report

5 GMP Case Studies Report

What You Will Learn from This Report:

The first countrywide import alert issued by FDA

An inadequate deviation investigation

An inadequate product specifications and a product recall

Process validation issues at a CMO

A different perspective on process validation and the culpability of the quality unit

 

Download the Special Report

Quality Week report sidebar

What You Will Learn from This Report:

How a major pharmaceutical company designed a program to train future leaders in quality

An industry-led initiative to advance the state of quality in the pharma industry

A pharma GMP leader’s tips for supporting quality culture within an organization

An update on FDA’s Quality Maturity Model

Impact of the Global Pandemic on Recent Data Integrity and Regulatory Non-compliance Trends

Webinar: Impact of the Global Pandemic on Recent Data Integrity and Regulatory Non-compliance Trends

Presented by Paul Smith, Agilent Technologies on Aug. 26, 2020

What you will learn:

  • Examples of essential laboratory actions to remain compliant during the pandemic
  • Recent data integrity non-compliance findings and trends
  • Essential strategies to find, understand, and leverage regulatory non-compliance data

Past, Present, and Future of Quality Culture

Presented by Regulatory Compliance Associates Distinguished Fellow Susan Schniepp

What you will learn:

  • How the 2014 FDA quality metrics initiative led to greater focus on quality culture
  • New quality culture tools and standards under development by PDA and other organizations
  • Best practices for quality culture, including case studies with lessons learned

Changing Medical Device Regulations

Presented by Redica Systems 

What you will learn:

  • The latest developments regarding the EU MDR
  • Quality Systems requirements for medical devices
  • Regulatory updates affecting medical devices

Download the Special Report

Combination Product Report

What You Will Learn from This Report:

The latest U.S. and European regulatory developments

The impact of smart combination products

How the EU MDR impacts drug-device combination products

Download the Special Report

5 GMP Case Studies Report

What You Will Learn from This Report:

In-depth analysis of the findings

Lessons learned

How companies can avoid similar shortcomings.

Experience the Power of Redica Systems

Redica Systems Expert Jerry Chapman to Present at SQA Annual Meeting

Index Information Redica consolidates regulatory data in real-time on the single largest database for quality, safety, and compliance intelligence.

Strengthen Datasets Redica machine intelligence algorithms identify and triage risk signals to derive meaning from vast amounts of private and public data.

Analyze & Interpret Patterns Redica instantly models the customer-specific regulatory risks, trends, and opportunities that stand to fundamentally change compliance operations.

Download the 510(k) Sample

What You Will Learn from This Sample:

See how a 510(k) submission is structured

Find out what information to include

Review correspondence between sponsor and FDA

Redica Systems Enforcement Analytics

Unlimited Access to Reports and Data

Enter your email address and someone will contact you shortly.

A.I. for Quality and Compliance Teams

August 3 webinar

Presented by Redica Systems Senior GMP Quality Expert Jerry Chapman

What you will learn:

  • A basic understanding of data sources, machine learning, NLP, and A.I. tools
  • Building and applying Expert Models
  • Two case studies, one on sterile manufacturing/503B and one on data integrity
Redica Systems Enforcement Analytics

Upgrade your CDMO management strategy.

Enter your email address and someone will contact you shortly to get the reports and analysis you need.

Get the scoop on recent data integrity 483 observations!

  • FY 2020 Data Integrity 483 Observations
  • Data Integrity Observations for Human Drugs
  • Observations Falling Under GMP
  •  

Human Factors – Compliance and Applications

June webinar

Presented by Alison Sathe, Founder, Regulatory Mark & Valerie Fenster, Director of Insights and  Human Factors, Kaleidoscope Innovation 

What you will learn:

  • Human factors strategies from simple drug products to complex surgical devices
  • Primary and secondary labeling development and evaluation for usability
  • Human factors activities from product development to post-market
  • International strategies: expectations for human factors in regulatory submissions in international markets

Experience the Power of Redica Systems

Redica Systems Enforcement Analytics

Let us know who you are and we’ll be in touch to answer all of your questions and get you started.

Redica Systems Enforcement Analytics

Keep up with the latest Regulatory Developments on Clinical Trials

Enter your email address and someone will contact you shortly. 

Redica Systems Enforcement Analytics

Save your team valuable time when using External Monitoring.

Enter your email address and someone will contact you shortly. 

Redica Systems Enforcement Analytics

Save time and Resources when using External Monitoring.

Enter your email address and someone will contact you shortly. 

Redica Systems Enforcement Analytics

Get immediate access to the news that matters to your sites.

Enter your email address and someone will contact you shortly. 

Redica Systems Enforcement Analytics

See how we can help you eliminate yet another spreadsheet.

Enter your email address and someone will contact you shortly. 

Redica Systems Enforcement Analytics

Stay ahead of changing regulations.

Enter your email address and someone will contact you shortly to get the data and analysis you need.

Redica Systems Enforcement Analytics

Upgrade your CDMO monitoring strategy.

Enter your email address and someone will contact you shortly to get the data and analysis you need.

Discover the power of the most comprehensive database of 483s in existence.

Our database of over 20,000 483s is retyped and tagged, making it easy to create an Observation Report in seconds.

Eliminate days of work and get your FREE personalized 483 Observation Report.