Decentralized Clinical Trials: The Way Forward

Updated on March 29, 2023

Introduction

Traditionally, clinical trial activity occurs in person at designated research locations referred to as study sites. Study activities are conducted on-site and in person by a physician called a principal investigator and other clinical research staff such as nurses and clinical research coordinators. The staff often has paper-based questionnaires where they ask the participants questions, write down their answers, and transcribe their responses into a research database. From there the data from the trial is analyzed. It means the participants have to travel to the study site physically, which requires making an appointment ahead of time, making travel arrangements, and possibly taking time out from work.

The Hybrid Approach: Decentralized Clinical Trials 

Decentralized clinical trial promotes a more patient-centric approach by addressing participants’ unmet needs from the traditional clinical trial model. Not all decentralized clinical trials are the same, but all incorporate technology and digital tools, therefore, providing participants the convenience to submit information, interact with the research staff, and complete any activities at home. So by using technology, participants can complete some or even all clinical trial tasks and procedures remotely. For the activities that require in-person interactions at a designated research site, some or all activities can occur at an alternative location. It could be at the participant’s home, place of work, or their own doctor’s office. For example, a mobile phlebotomist could travel to their location for blood samples.

A decentralized clinical trial doesn’t necessarily mean that the person will not interact in person with the research staff. Many decentralized clinical trials are a combination of remote and on-site staff activities. There is still plenty of interaction with the research staff. Similar to telemedicine, different forms of communication are used, like video calls, phone calls, or even text messages. People fill out information pertaining to their participation online rather than traditional paper forms, allowing the research staff to view their responses immediately.

Decentralized clinical trials start from these online forms. Based on their answer, the research staff members might call them for confirmation and to answer any questions they might have. If the participant decides the study is a good fit, they can proceed with electronic informed consent. For example, direct-to-patient study distribution. Other study procedures may require the participant to travel to the study site, for example, for an MRI. The overall plan aims to provide more ease to participants and decrease the burden of travel as much as possible.

Technology in Decentralized Clinical Trials

The use of technology can be intimidating for some, but technology is here to stay and the way forward. Sometimes participants are provided devices like a phone or tablet by the research site. Other times people are asked to use their devices, which generally is more comfortable for them. Another important consideration is to provide the participants with an easy way to contact the research team if they have any questions or face technical difficulties, such as a study email or phone helpline.

Historically, participation in clinical trials required much traveling to the research site. Therefore, technology has provided convenience. Another benefit is that by removing geographical barriers and time constraints, diverse groups of people can participate, which is needed for study data to represent a diverse population. Many areas are underserved due to the distance from research sites, so decentralized trials also open access to remote communities previously unable to participate.

Diversity

According to a 2020 FDA study, 76% of all clinical trial volunteers worldwide are Caucasian, with Asians accounting for 11% and black people of African heritage accounting for 7%. This skewed distribution does not adequately represent the diversity of human populations. According to the FDA, 48 new medicines were approved in 2019 from 46,931 volunteer clinical trial participants. Of those individuals, 9% were Black or African American, whereas, in cancer studies, just 4% were Black or African American. Despite this, this group accounts for 13.4% of the population.

Our world is full of diversity and patient recruitment in clinical trials should represent this accurately. Science has also shown that bodies react differently to medications based on race, gender, or ethnicity. Historically clinical trials have not had accurate representation by many minorities because of multiple reasons, such as lack of access due to geographical location. Through decentralized clinical trials, this lack of diversity can change.

The Benefits of Decentralized Clinical Trial Solutions

Any clinical trial can benefit from some form of decentralizing, which is why decentralized clinical trial technology is here to stay. Below, we outline the benefits of integrating virtual components into a clinical trial.

1. Less burdensome for participants
2. Better compliance and retention rates
3. Improved accuracy
4. Faster trial delivery
5. Reduced cost of data collection
6. More participants and researcher access
7. Participant safety
8. Long-term follow-ups
9. Better decision making

1. Less Burdensome for participants

COVID-19 has shifted dynamics for many industries, and clinical trials are no exception. There has been an increase in the demand for more convenient and less strenuous alternatives is increasing. Participants are not willing to bear the burden of logistics and costs knowing that decentralized clinical trials can offer them suitable alternatives.

• Fewer site visits:

  This means the participant can report via an app remotely without having them visit the research site every time. If the need for a visit arises, participants can visit local labs or pharmacies or choose to have home visits with research staff.

• Reminders and notifications:

  Participants’ smartphones can receive reminders for daily medication or task completion.

• Multi-media training:

  Training videos can help participants or caregivers better understand the study protocol and its responsibilities.

• Sensors and devices:

  Sensors and devices can eliminate the need for participant reporting of vitals and other measurements.

2. Better Compliance and Retention Rates

As decentralized clinical trials make it easier to report, the participants are more likely to see through decentralized clinical trials to the end.

• Easier participant monitoring:

  It becomes easier to track participant tasks and help the patient insight team to participants that need more support.

• More informed and engaged participants:

  Through decentralized clinical trials, we can improve participant engagement through a feedback loop and provide participants access to their data. It can help them to feel more involved in their clinical trial.

3. Improved Accuracy

One of the crucial limitations of on-site reporting is the dependence on participants to fill in their diaries at short intervals. This is called “parking lot syndrome”, where questionnaires are filled haphazardly just before a site visit, resulting in errors and inaccuracies in reporting events.

• More and better data:

  Patients can report symptoms the moment they occur through apps on their mobile devices which are better at capturing experiences and perceptions. Decentralized clinical trials also help sponsors capture real-time data through remote monitoring. By combining the number and nature of data points, we can have a better picture of the participant experience. This approach is especially useful when we are looking into quality-of-life indicators.

• Less missing data:

  Decentralized clinical trials improve patient adherence and reduce human error, therefore, minimizing the risk of missing or incorrect data.

• More simultaneous reporting:

  It is better to report events as soon as they occur because they are fresh in memory. So, through decentralized clinical trials, participants can report events as soon as they occur.

• Real-life data:

  We can obtain data when people are in their natural environment rather than at the clinical research site, which is more accurate.

• Reduced patient subjectivity:

  The usage of gadgets to collect participant data reduces subjectivity. Patient-friendly applications, for example, can simply instruct users to shoot and submit images, videos, or audio recordings straight from their devices. These media outputs can then be rated by experienced raters, reducing the possibility of bias significantly.

4. Faster Trial Delivery

Decentralized clinical trial technology, without a doubt, can help us save time by reducing the clinical trial procedure’s time.

• Faster recruitment and enrollment:

  Through decentralized clinical trials, trial recruitments have become 2 to 4 times faster. We use digital advertising to run ads to targeted audiences. After clicking on the ad, an information page opens up through which they can sign up after answering a few prescreening questions. If they qualify, they can download a mobile app and proceed through to the eConsent and preliminary training for the trial. This process reduces days of work to minutes.

• Faster data collection:

  Automatic notifications help participants report faster and increase compliance which helps speed up data collection.

• Faster data analysis:

  Although decentralized clinical trials do not occur in a single site, their data remains centralized. Cloud-based Electronic Data Capture (EDC systems) ensures that the data from patient reporting, devices, patient history, medical assessments, and other sources are in a single system. Afterward, we can manage and clean the data and speed up the analysis phase.

5. Reduced Cost of Data Collection

Maintaining staff at multiple sites can be expensive. So, directing data from collection from sites to homes drastically reduces costs which can then be directed to the participants. Virtualization allows for one team to handle more data. Direct data entry by the participants also reduces expenses.

6. More Participants and Researchers Access

Clinical trial technology is helping to alter the demographics of clinical trial access. Participants who were previously living far away from the study site are now able to participate from their homes. Digital media ads can target underserved populations increasing diversity. Additionally, opportunities are opening up for academic researchers to become principal investigators (PIs) without additional administrative burdens and costs.

7. Participant Safety

Decentralized clinical trials ensure safety surveillance by the research teams and track behaviors. Traditionally, adverse events (AEs) often were not detected until a scheduled site visit with a healthcare provider—possibly days or weeks after the event occurred. This type of surveillance means adverse events become evident quickly. Participants can respond to a set of questions to determine whether their health status has changed. If yes, the system asks further questions to better understand the issue in more detail. Built-in alerts can help study teams quickly identify participants in need of support or urgent follow-up. A virtual team then contacts via email, phone call, or text message to determine whether an adverse event has occurred and create a digital case report.

8. Long-term Follow-ups

Many clinical trial drugs and devices require long-term follow-ups to track effectiveness over time and to find any safety issues that may not be evident in phase III. Post-study observations requiring follow-ups are sometimes inconvenient for participants and can lead to drop-offs. Virtual tools can minimize long-term study challenges by reducing the burden on participants.

9. Better Decision-making

Unlike in the past, improved speed and accuracy of decentralized clinical trials (along with real-time dashboards) enables sponsors to obtain earlier insight into how their clinical trials are moving forward. This greater visibility into the status of their studies allows them to be ready for any uncertainty.

Adding decentralized clinical trial solutions into any or all stages of the clinical trial journey presents many opportunities for improvement. But, despite the remarkable benefits of decentralization, decentralized clinical trials can nonetheless pose challenges.

Challenges Associated with Decentralized Clinical Trials

Technology is the foundation for future human progress. But, as with any innovation, a few challenges need resolution before the total adaption of this technology. Now we will look at the four most common issues of decentralized clinical trials.

1. Regulatory challenges
2. Systems integrations and adaptation
3. Risk aversions in sponsors and sites 
4. User access

1. Regulator Challenges

In the United States, FDA’s approach toward decentralized clinical trials is encouraging. They have adopted the digitization of multiple steps within a trial. However, adoption outside the United States is not so rapid.

Sponsors must align with proper regulatory guidelines that vary from country to country. Thus,‍ global sponsors need to work towards a tailored approach and account for complexities in trial designs.

2. Systems Integration and Adaptation

As with every digital invention, having appropriate technology is critical. Participants may need to access the system and obtain data from multiple sources like ePRO, devices, EHR records, etc. This increasing complexity can be frustrating and discouraging for trial participants. Project managers must also deal with a lack of integration. Workflows can become unmanageable when systems are not built to manage the exponential expansion in data sources and streams, resulting in mistakes and extended timescales. Other than this, some participants may have more preference for in-person visits, which can also be detrimental to the progress of decentralized clinical trials.

3. Risk Aversion of Sponsors and Sites

Behavioral hurdles by site staff remain one of the biggest challenges to decentralized clinical trial adoption. They are often anxious about changing their working methods. If there is a bad experience or lack of training, even greater resistance to change results. Fortunately, we are seeing a greater willingness on the part of site staff in large organizations to adopt new methods.

4. User Access

It can be misleading to presume that more geographic expansion can translate into universal access. Everyone has different tolerance and ease with technology. While digital literacy has risen, there is still a need to fully adapt to these tools. Older users may need larger fonts for more ease. Other times people from different regions or socioeconomic statuses may not have adequate internet access.

Ethics in Decentralized Clinical Trials

We know there are tremendous opportunities for decentralized clinical trials, but it is necessary to look carefully at some ethical challenges these trials pose. We can classify these ethical issues into the following categories:

1. Patient Safety and Protection of Their Rights

   • Physical safety:

     The safety of drug administrations depends on the expertise and coordination of the participant. Questions arise regarding the handling, storage, and disposal of the study drug. Some people may experience adverse effects which is why certain rules have to be in place.

   • Informational privacy:

     A lot of digital data gets transmitted to the study site. To protect the participants’ privacy, only the most essential data is asked about, even though we have a lot of capacity to capture detailed data. It also depends on the type of device participants use because the digital products have to be validated and meet standards. Network and cybersecurity vulnerabilities also pose a challenge to privacy protection.

   • Well-being:

     Continuous online engagement through notification, unwanted surveillance, and loss of interaction may affect the participants well being.

2. The Scientific Validity of the Trials

   • Data integrity:

     One of the good points about decentralized clinical trials is electronic consent. Participants can read the forms at their ease, but this can make them liable to skim through the paperwork without adequately reading the details. There are also legal questions regarding e-signatures.

   • Study endpoints:

     Study endpoints affect the scientific validity. Questions arise about whether the methods are suitable enough for decentralized clinical trials if they do not have proper study endpoints.

   • Digital divide:

     Lack of education, motivation, skills, access, and appropriate devices may affect how different people perceive decentralized digital trials.

3. Oversight

   • Investigator’s responsibilities:

     An investigator must have the appropriate tools to execute their research. They should have familiarity with digital ethics.

   • Institutional responsibilities:

     Institutions bear responsibility for data safety and monitoring. Duties in decentralized clinical trials are higher than in analog trials, as threats from cybersecurity vulnerabilities arise.

   • Regulatory mandates:

     Decentralized digital requires different types of mandates for ethics review committees.

The Takeaway

Decentralization is by no means a single solution to the ailments of clinical trials, as it has some of its downsides. COVID-19 has been an eye-opener, and the adoption and demand for clinical trials have risen sharply. Therefore decentralized clinical trials should be at the forefront of impacting participant retention, engagement, and satisfaction of the participants. To successfully achieve the inclusion potential of decentralized clinical trials, sponsors should be willing to continue to fund infrastructure and supply technology to prospective participants—at least for the foreseeable future—as needed to ensure equal opportunity.

It is imperative to realize that total decentralization may not always be possible, instead, a hybrid model may often be necessary. As always, incorporating all stakeholders (e.g. participants, investigators, regulators, etc.) early in the planning phase is the best way to reduce complexity and ensure the effective implementation of decentralized clinical trials. Researchers conducting decentralized clinical trials must publicize their findings, emphasizing the effects on participants, personnel, and research data acquired. Such insights will aid in making informed choices concerning the future uses of decentralized clinical trials.

Revival Research Institute conducts clinical trials using the latest cutting-edge technology with a patient-centric approach. We emphasize combining participant ease with modern technology while making sure their privacy and rights remain safeguarded.