Decentralized Clinical Trials Guidance

The global decentralized clinical trials (DCTs) market is expected to grow from US$8.8 billion in 2021 to US$14.2 billion by 2026, at a Compound Annual Growth Rate (CAGR) of 10%[1]. The main factors driving the growth of this market include the lockdowns and restrictions during the COVID-19 pandemic, increasing demand for faster and cheaper drug trials, more patients in favor of participating in clinical trials remotely, and the availability of electronic patient-reported outcomes (ePRO), sensors and wearable devices that can capture data from patients in a less burdensome way.

With the increase in the number of DCTs, regulators are starting to take notice. The U.S. Food and Drug Administration (FDA) and regulatory agencies in other countries have issued guidance and regulations on DCTs. This article will explore the regulatory environment for DCTs to help companies comply with evolving regulations. What you will learn from this article:

What are DCTs?
What are the benefits of DCTs?
Regulatory environment for DCTs
The future of DCTs: regulatory opportunities and challenges
Maintaining regulatory compliance in DCTs: How RegASK can help

What are DCTs?

DCTs are defined as trials that are “executed through telemedicine and mobile/local healthcare providers (HCPs), using procedures that vary from the traditional clinical trial model[2].” They are sometimes called remote or virtual clinical trials.

The term “decentralization” infers activities that previously took place at sites can now occur remotely, most often in people’s homes but also at local pharmacies, labs, and other proximate options. Technology sits at the heart of DCTs, providing a level of participant convenience that would otherwise be impossible.

The core components of DCTs usually include eConsent, ePRO, IP supply, telemedicine, wearable digital health devices, home nursing, remote patient monitoring, etc.

What are the benefits of DCTs?

Clinical trials are expensive and time-consuming. Pharmaceutical and biotech companies are strapped with high costs, long development timelines, and high risks of failure. DCTs offer a number of benefits for all stakeholders by making clinical trials more affordable, more efficient, and safer.

The benefits of DCTs include:

– Improved patient recruitment: Patient recruitment is one of the biggest challenges in clinical research. Some patients are reluctant to participate in traditional clinical trials because of the travel time to and from clinic visits. DCTs reduce site visits, offering patients the convenience and flexibility to participate in clinical research from the comfort of their homes.

The reduced site visits (or in some cases no site visits) also geographically expand the boundaries for recruitment, allowing sponsors to reach untapped cohorts, such as rural populations.

– Reduced cost and increased efficiency: Easier recruitment can accelerate timelines and reduce costs. There are also many other efficiencies and money-saving DCT strategies.

The costs of physical site operations can be exorbitant, not to mention their inefficient processes. In a decentralized trial, many of the site fees are reduced or eliminated. Instead, virtual study teams can monitor trial participants remotely for a fraction of the cost, in some cases eliminating the need for physical site teams.

Another area of efficiency occurs through automation. As data is submitted, centralized databases can automatically look for data outliers. Study teams can immediately be notified of anomalies, allowing them to check for errors. This happens as the study is ongoing, instead of waiting for all of the data to be submitted, as in traditional trials. This allows studies to quickly get to database lock, sometimes in as little as a few weeks.

– A more diverse patient population: Due to the global accessibility of trials conducted across different locations, cultures, languages, and ethnic groups, DCTs help achieve diversity in clinical trials.

– Increased patient compliance and retention: By streamlining communications and minimizing site visits, virtual studies reduce the burden of labor-intensive tasks. Subjects are more likely to comply and thus less likely to drop out. DCTs allow for constant contact with the research staff and offer reminders or study-related push notifications to keep participants on track and engaged. Having experienced the benefits of remote research, neither sponsors nor participants will want to go back.

– Streamlined data collection and more accurate data reporting: Site-based studies dictate that health-related data be collected in a lab or clinic. Yet most of the experiences studies seek to capture occur at home, at work, or during some other aspect of daily life.

When participants scramble to fill out study reports on their way to the clinic at the last minute, they are often unable to remember their detailed activities, leading to recall bias. Consequently, data points are lost, and data accuracy can be compromised.

In a decentralized clinical trial, participants can report and record their data in real-time, at the precise moment they experience the symptoms and/or interact with the study products. This data collection can occur through bring-your-own-device ePRO or through wearables and sensors (such as a FitBit) that collect passive data. In the latter, the data is more objective, and in many cases able to deliver stronger efficacy signals.

Centralized data collection means that all data flows from users into one virtual site. Data requires no re-entry, and participants don’t need to recollect the events later on, thus limiting opportunities for error.

Need to know more about DCT regulations? Get in touch with RegASK experts

Regulatory environment for DCTs

The regulatory landscape for DCTs is not as clear-cut as centralized or traditional clinical trials. For example, in a centralized clinical trial, there are specific study procedures and rules set out by the trial sponsor that are followed by compliance staff. With a decentralized trial, the roles and responsibilities of physicians, investigators, sponsors, and other stakeholders may vary in different scenarios – thereby creating ambiguity with respect to the oversight of study procedures and governing rules[3]. In the past, DCTs have been subject to the same regulations and standards that centralized clinical trials follow, such as good clinical practice (GCP). However, the recent changes and a rapid increase in DCTs have led to an urgent need to look at the unique DCT regulatory landscape.

United States

The U.S. FDA is promoting the use of DCTs to advance the collection of real-world data, and the rich data can provide more real-world evidence. In September 2020, FDA launched the Digital Health Center of Excellence to further “the advancement of digital health technologies (DHTs), including mobile health devices, Software as a Medical Device (SaMD), wearables when used as a medical device, and technologies used to study medical products[4].” In December 2021, FDA published the Draft Guidance on Digital Health Technologies for Remote Data Acquisition in Clinical Investigations, providing recommendations to sponsors, investigators, and other stakeholders on the use of DHTs to acquire trial participants’ data remotely[5].

Canada

Health Canada, a department of the Canadian Government responsible for national health policy, has issued several regulatory proposals to help enable and encourage DCTs through regulatory changes that could make DCTs more practical for sponsors[6]. It has also launched a clinical trial regulatory modernization initiative to modernize the clinical trials regulation, where decentralized trials are one of the key aspects[7].

United Kingdom

The Medicines and Healthcare Products Regulatory Agency (MHRA) is the regulatory authority responsible for clinical trials in the United Kingdom. The country published Guidance on Managing clinical trials during Coronavirus (COVID-19)[8] and Guidance on minimizing disruptions to the conduct and integrity of clinical trials of medicines during COVID-19 in 2020[9], and passed the Medicines and Medical Devices Act 2021[10]. These guidance documents and regulations support a decentralized approach and digital health technologies in conducting clinical trials and create a regulatory framework for DCTs.

European Union

On February 4, 2021, the European Commission published an updated version of the Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) Pandemic[11]. The European Union (EU) pharmaceutical legislation, known as the Clinical Trials Regulation, came into effect on 31 January 2022[12]. The guidance and regulation touch base on electronic medical records, remote monitoring, remote data source verification and other DCT-related topics. It should be noted that among the EU states, there is great variability in the regulation of DCT components.

Asia Pacific

The Asia Pacific is believed to be the next frontier for DCTs[13]. The Health Sciences Authority (HSA) of Singapore has issued Guidance on the Conduct of Clinical Trials in Relation to the Covid-19 Situation[14] and the Clinical Trials Guidance – Electronic Consent[15], discussing various topics relating to digital clinical trials. In July 2020, China published Guidelines for the Management of Drug Clinical Trials During the Coronavirus Pandemic, which provides guidance on DCT elements such as electronic informed consent, remote monitoring, and direct-to-patient shipments of investigational therapies. The country, however, is still lacking policies and regulations on DCTs, according to a study by IQVIA[16]. Despite the progress made in recent years, Asia Pacific remains “a clinical development patchwork of regulations and requirements[17].”

Need to know more about DCT regulations? Get in touch with RegASK experts

The future of DCTs: regulatory opportunities and challenges

As DCTs grow in popularity, the regulatory framework and approaches for DCT management will expand. In this section, we will look at the future of regulating DCTs and it might provide opportunities and challenges for DCT solution providers.

1. Increased regulatory acceptance and support for DCTs

More regulatory agencies around the world have recognized the benefits and value of DCTs and planning for new regulatory initiatives to support their implementation[18]. For example, the Danish Medicines Agency has been taking a proactive role in establishing an up-to-date and robust regulatory framework for DCTs[19]. Another example is the Swedish Medical Products Agency, which will “continue to provide regulatory guidance on decentralized elements in clinical trials[20].”

2. Evolving complexity of local regulatory landscape due to country differences

The regulatory environment for DCTs varies significantly from country to country and is constantly changing. This has increased the complexity of navigating the local regulatory landscape and made it difficult to keep up with the changing rules. The lack of consistent standards also means sponsors, CROs, DCT providers and vendors may create a regulatory strategy to focus on priority markets where regulatory barriers are lower.

3. Advancing technology driving new regulatory initiatives

Future regulatory developments in DCTs will be driven by the advent of new digital health and mobile technologies. Since technology in the space is rapidly evolving, regulatory agencies globally will be forced to evolve as well. This could mean lots of changes and a volatile regulatory environment. More regulations on clarifying access to health technologies and technical requirements are expected to be introduced by countries.

4. Higher demand for data privacy and data security

With a greater number of patients’ personal data being collected and shared for clinical trials, protection of participants’ data becomes a top priority and major policy concern among participants, regulators, sponsors and CROs. Sponsors and CROs must not only comply with data privacy laws like GDPR but also demonstrate their compliance to authorities with evidence, documents and audit trails.

Need regulatory support on DCT execution? Get in touch with RegASK experts

Maintaining regulatory compliance in DCTs: How RegASK can help

The demand for compliance has increased as more clinical trials are being conducted remotely in different regions around the world. This means that sponsors and DCT providers are not only responsible for ensuring compliance with their own country’s regulations but also with those of the country where the trial is being conducted.

Some of the critical ways that companies can comply with DCT regulations include:

Identifying and understanding country-specific regulations and guidance, Ask RegASK if you need more information on local and international regulations.
Exploring and assessing how regulations will impact your DCT implementation.
Starting your conversations with regulators early, most regulatory agencies are willing to discuss your study design and provide guidance.

If you are planning or managing DCTs, we know how daunting it can be to navigate the regulatory landscape. That’s why we are here to help. RegASK leverages its market-leading RegAlert regulatory intelligence platform and network of local regulatory experts to guide you through the regulatory process and help you stay ahead of regulatory changes, so you know what it takes to successfully deliver your trials.

RegASK supports CROs and sponsors by providing regulatory solutions in clinical trials. These solutions cover two areas: feasibility and compliance.

Feasibility encompasses providing regulatory landscapes and keeping them updated through automated monitoring. This is particularly challenging for CROs and sponsors alike to keep track and stay compliant as multiple regulations are intertwined (data privacy, clinical regulations, health data, etc.) and there is high inter-country variability. RegASK proposes subscriptions for CROs and sponsors which can access regulatory landscapes, monitor changes, and ask local experts for assistance from early stages (pre-CRO engagement) such as RFP and feasibility, to stages throughout the clinical trial rollout and implementation.
Compliance solutions allow CROs and sponsors to access local experts to provide submission assistance, monitor changes in compliance requirements throughout the trial, avoid delays and optimize refiling. RegASK proposes subscriptions for submission assistance and continued monitoring of local compliance requirements.

Our package of services includes:

An overview of the regulatory landscape on DCT components such as remote consent, ePRO, telemedicine, wearables, etc.
In-depth analysis of local regulatory requirements
Regulatory monitoring of DCT regulations with the RegAlert platform
Local regulatory expert access with Ask RegASK
Clinical Trial Submission packages
Assessment and mitigation of regulatory risks and gaps in DCT execution

With RegASK, you can focus on your R&D while we provide all the necessary support to keep your clinical trials compliant with all regulatory requirements. Contact us today and see how you can benefit from our solutions.

What you'll get with RegASK

Early detection and mitigation of regulatory risks
End-to-end regulatory support throughout your product lifecycle
Strategic consulting to build the optimal business strategy for your commercial success