Decentralized Clinical Trials: Methods and Benefits of Decentralization

Introduction

Decentralized clinical trials (DCTs) are modernizing clinical trial research, making trials faster and improving patient and research experiences. Interestingly, the concept of decentralization in clinical trials has existed for years, but during the restrictive period of the COVID-19 pandemic in 2020, the potential of decentralized trials was really leveraged and became more evident.

There was an ~80% decrease in new patients entering trials in April 2020 relative to April 2019. This loss of continuity had detrimental consequences for healthcare research, propelling the implementation of decentralization methods, which eventually proved to effectively maintain the integrity of clinical trial research.

Join us as we demystify the decentralization paradigm that is revolutionizing clinical research and discuss its key advantages and challenges. We will also go through some ways to incorporate aspects of decentralization into trials, which can help accelerate them and improve patient and investigator experiences alike.

What is the meaning of decentralization in clinical trials?

Decentralization in clinical trials refers to a shift away from the traditional, centralized model of conducting clinical research. In traditional clinical trials, participants physically visit a single location, such as a clinical research center, to participate in the trial – we could refer to this as a ‘fully centralized’ clinical trial. In contrast, decentralized clinical trials allow for the study to be conducted from multiple locations, including the patient’s home, using remote technologies. Clinical trials could be fully centralized, fully decentralized, or they could be hybrid, combining components of centralized and decentralized approaches.

The potential for a trial or its components to be decentralized depends on the treatment being tested, the potential for adverse events, whether end points are suited to remote measurement, and other factors.

What are the key elements of decentralized clinical trials?

The Clinical Trials Transformation Initiative (CTTI) elaborates upon the decentralization definition for clinical trials with the following key elements:

• There is no primary physical clinical trial site
• Online and remote healthcare technologies, sometimes known as telehealth, are used for patient communication
• Mobile digital technologies and at-home healthcare toolkits are used to capture data
• Local or mobile healthcare professionals (HCPs) are employed

However, these elements are only guidelines, and they can be selectively combined with centralized approaches to form a hybrid approach, depending on the needs of the trial.

Examples of hybrid (partially decentralized) approaches in clinical trials include:

• Reducing the number of on-site visits by having an HCP go to the patient's home for certain visits
• Having the patient wear a device to record parameters that are transmitted digitally, even if they still need to visit the study site for certain treatments or assessments
• Having the patient enter health parameters daily on a mobile phone app, despite also visiting the study site occasionally

Over the last few years, the question has started to shift from whether or not clinical trials can be decentralized to which components can be decentralized. For example, if a study requires 10 visits, can any of those visits be conducted remotely? Visits that may only require collection of information like vital signs or symptom reports could be conducted remotely, while visits requiring specialty exams like MRI scans would still be performed on-site.

How many clinical trials are decentralized?

A 2022 report with contributions from 193 clinical research leaders suggested that 89% of sponsors used at least some component of decentralization in some of their studies. The COVID-19 pandemic certainly played a role in the increasing decentralization of trials; the number of trials with decentralized elements jumped by 50% between 2020 and 2021.

Looking deeper into these statistics, DCT components experiencing the largest increases in use (in 2021 as compared to 2017-2019) included:

• eConsent, increasing by 460%
• Web-based questionnaires, by 448%
• Oximeters (wearable device allowing for at-home measurement of oxygen saturation in the blood), by 317%

Additionally, the most popular digital technologies employed in hybrid and DCTs in 2022 were telehealth, continuous glucose-monitoring devices, eDiaries, smartphones, and mobile apps.

What are the benefits of decentralized clinical trials for participants, investigators, and sponsors?

Given the patient-centric nature of decentralized clinical trials, DCTs have many benefits for participants, but there are also numerous important benefits for investigators and sponsors. We’ll go through some of these benefits in detail below.

Potential benefits to participants:

Decreases burden on participants

Patients can make fewer visits to healthcare facilities and can use remote devices and mobile apps to report and send data, reducing required travel (and associated time, costs, and logistics/planning).

Quick access to clinical operations team

Telehealth allows participants to immediately report any adverse side-effects and investigators can quickly respond with follow-up care and guidance for the patient regarding next steps.

Better communication and overall engagement

Communication between the study staff and the patient plays a key role in patient retention - with virtual communication, patients are more connected to the study staff and can be better supported through consistent interaction. Tools like eCOA also contribute to patients feeling more connected and engaged in the study.

Potential benefits to investigators:

More accurate and robust data

• Real-time data collection increases reporting accuracy, as patients can send information while it is still sharp in their minds. Traditional visits wherein patients may be asked to recall symptoms from days or even weeks before are subject to inaccuracies.
• Opportunity to increase the number and type of data points for a more all-inclusive patient experience. This is especially helpful when determining quality-of-life insights and evidence-based measurements of effectiveness.

More unbiased data

• The "white lab coat" influence is diminished. Participants are more likely to report accurate information when they are at home as opposed to a trial site where the presence of investigators can influence their responses.
• Subjectivity is reduced because participants can send video, image, and audio captures to investigators instead of having to rate or describe concepts they may not be entirely familiar with. This radically reduces the bias and allows investigators to view data objectively.

Easier to ensure patients are on track

Digital platforms increase patient visibility, making it easier to track who is missing reporting or data tasks. These patients can be notified of missing reports sooner, and investigators can quickly provide assistance or support as needed.

Potential benefits to sponsors:

Reduced costs

Decentralized clinical trials can avoid many costs associated with traditional clinical trials related to maintaining one or more physical sites with multiple employees, logistical considerations of on-site monitoring, and organizing and manually validating data.

Accelerated patient recruitment and increased retention rates

• Decentralized recruiting methods can increase the patient pool for recruitment by removing common obstacles to participation like travel distance and associated costs.
• The use of telehealth in decentralized clinical trials maintains open and interactive communication channels between participants and study staff, which improves patient engagement and retention. As participants get their concerns addressed faster and can receive timely personalized responses and care, they are more likely to feel seen and appreciated and thus remain enrolled, resulting in decreased dropout rates.

Improved decision making

Real-time data collection and reporting increase visibility and provide opportunities for earlier insights. Real-time access also means sponsors can quickly identify issues or inconsistencies in trial operations. This allows for effective mitigation protocols that can extend the life of a trial, or if necessary, end it quickly without wasting further resources or potentially causing more harm to patients.

Challenges and potential drawbacks of decentralized clinical trials

As with any innovation, decentralized clinical trials also have their share of potential challenges that can hinder their integration. While it is generally accepted that the potential benefits of hybridized and decentralized trials outweigh the drawbacks, it is still worth noting the potential challenges involved to gain a full understanding. Below are some of the most common limitations that can complicate or prevent the transition of certain trials to decentralized protocols.

Data quality and endpoint validation

The introduction of new data collection methods carries with it a new set of risks. Any technologically enabled tool or device needs to be validated both from a technical and clinical perspective. Wearable devices need to be properly calibrated and maintained, connectivity between devices and servers needs to be ensured, and online surveys must be validated on all potential types of devices patients may use to view them. Patients must be provided with clear instructions on how to use devices at home, and surveys must include explicit instructions to prevent excessive homogeneity in responses which would make data analysis much more complicated. Measures must be put in place to maximize data consistency when it is not collected centrally. Our article on case report forms (CRFs) provides some insight for sponsors on how to design effective forms for collecting homogenous data, which could also be applied to the design of remote patient surveys in DCTs.

Investigator and site capability and workload

Sites and investigators also must be trained to use (and perhaps to do basic troubleshooting of) the technological tools implemented in decentralized trials. Therefore, adequate time and resources need to be invested in ensuring sites and investigators are competent and comfortable with these tools. Decentralized trials require organized logistical processes as well as high-quality technical support. Be understanding; allow time and provide support for the potentially uncomfortable transition to these new methods.

Drug distribution

In DCTs, drugs must be shipped to participants, which poses a significant challenge for several reasons. Firstly, this can significantly increase costs, especially for drugs that need to be shipped under cold storage conditions to maintain their integrity. Secondly, this method risks drug tampering, which could be potentially dangerous for the patient and undermine the clinical trial integrity. Finally, drug distribution regulations vary from country to country, and even state to state, potentially complicating distribution further. For certain drugs, it may simply not be possible to ship them directly to participants. In such cases, consider setting up local distribution sites, even on a temporary basis, to reduce the burden patients would face if asked to travel long distances to pick up their trial medication.

Conclusion

With the leaps and bounds telehealth has taken recently, especially since the COVID-19 pandemic which posed significant logistical barriers to patient travel to central trial sites, a broad range of tools and options are now available for sponsors to decentralize aspects of their trials, or even to decentralize them completely. There continues to be a strong momentum toward more decentralization in trial designs, and the industry is adapting quickly due to the improved patient experiences and enhanced data quality that have been demonstrated in DCTs.