Blog >     Decentralized clinical trials, DCTS.

 

By 2011, Pfizer had conducted what would be the first clinical trial that did not require in-person site visits. It used the Internet for recruitment, virtual surveys for screening, electronic diaries, and home delivery of the investigational product to participants' homes, all supported by the US Food and Drug Administration (FDA) and partners such as the Clinical Trials Transformation Initiative. 

In the pre-pandemic period, this term had already evolved. In 2019, an article in Clinical Pharmacology & Therapeutics suggested that the methods and location for data capture are the ideal metrics for defining the decentralization degree in a study. In this sense, they presented three capture use levels:

Through intermediaries:

Studies in which data are transmitted through third parties, e.g., when an intermediary transcribes information from the medical record into an Electronic Case Report form (CRF) or when paper diaries are used and then documented in the CRF.

Mainly virtual:

Studies in which the methodology allows data to be obtained off-site. In these, electronic devices are used by a third party, either patient or study team, to enter the data.

Entirely virtual:

Studies in which there are no intermediaries in the data capture; all data are exported directly to the CRF, e.g., the use of wearable devices such as the gyroscopic accelerometers found in smartwatches.

In 2020, the FDA published the Guidance on Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency. This provided guidance for adopting methods that facilitated decentralization through remote data capture with tools such as remote informed consent, virtual visits, home delivery of the investigational products, and obtaining labs and images locally.

These recommendations were already part of two programs: the Information Exchange and Data Transformation Program (INFORMED), created to promote innovation in scientific data and agile technology, and the FDA's Real World Evidence Program, which defines the terms Real World Evidence RWE and Real World Data RWD, the latter, of particular interest because it refers to real-life data that is also captured in traditional clinical trials, converting them into studies with hybrid design or decentralized clinical trials.

Advantages of decentralized clinical trials

There are several advantages attributed to this trial methodology where, perhaps, its greatest value lies in the fact that the research center and the sponsor are no longer the main actors but rather the participants in these studies.

• They reach more diverse populations, thus ensuring the diversity of clinical trials, which is one of the objectives of these studies

• They provide external validity to clinical trials, one of the main weaknesses of this type of study

• They do not require a specialized center. The evaluations do not have to be carried out in highly complex centers.

• Extend the quality of traditional clinical trials to the participants' homes and workplaces.

• Allow study activities to be conducted from the comfort of the participant's home, increasing adherence, retention, and loyalty for future study participation.

• Connect the real-world context of RWE study data capture with the strictness of traditional clinical trials.

• Enable the use of new technological resources for virtual data capture.

• Improve recruitment by enabling different means of mass outreach and facilitating the informed consent process.

• Decrease patient burden. Most participants are older adults or have chronic or immunological diseases, so in addition to the risk of presenting a complication, attending the research center in person incurs a high cost. In this sense, the FDA Oncology Center of Excellence (OCE) is working to take advantage of the benefits of these studies and evaluate their challenges so that they can be quickly applied in studies with oncology patients who would potentially benefit, considering the characteristics of their disease.

• Allows remote monitoring, one of the main characteristics of research centers during the pandemic to ensure the continuity of ongoing trials or trials that were about to begin recruitment.

• They could decrease the sample size of studies due to the greater availability of continuous or high-frequency data.

• Faster data availability. Cutting down on intermediaries and receiving data directly from the source, making data availability more opportune

Main challenges of decentralized clinical trials

However, just as from the beginning of this concept, some concerns were raised, such as how electronic CRFs could be monitored, there are currently several others about how the quality of traditional clinical trials will not be compromised when adapting to DCTs. If this transition is not made quickly but carefully, the internal validity of the trials themselves could be questioned

• Data privacy. Perhaps one of the main concerns is ensuring data confidentiality; increasingly, government regulators require sponsors and research centers to ensure high standards of cybersecurity.

• For some studies, such as those requiring dose-finding or frequent interventions like biopsies, DCTs present limited options because they need to be offered in a controlled or specialized environment.

• Validations of remote and wearable devices. In order not to affect the validity of the data collected, the devices, surveys, and other methodologies must have assurances for virtual or remote use.

• Data collection in uncontrolled environments. Some of the data will be collected by the participants, so the accuracy of the data cannot be guaranteed, especially when they require exact settings or collection techniques.

• Operating costs. The costs associated with the use of electronic devices and platforms will be an additional budget in DCTs. However, it is expected that these will be offset by the implicit savings that these studies offer.

• Internet access for specific populations. Certain populations are unfamiliar with the use of the Internet and electronic devices, so appropriate training is required for them and their caregivers.

Tools for transitioning to DCTs  

DCTs must go hand in hand with technological advances and take advantage of the great benefits they offer in favor of clinical research. Some of the technological resources that have been progressively included are: 

• Electronic medical records

• Mobile technology

• Telemedicine

• Machine learning algorithms

• Electronic informed consent

• Home visits

• Self-reporting data

• Video conferences.

• Biometric sensors

• Smartwatches and smartphones 

The DCTs gained great strength due to the COVID-19 pandemic; they showed that they are viable and that their methodology is here to stay. Their main feature is that the participant is the main actor in the data's planning, execution, and analysis. They go hand in hand with technological advances to obtain real-life data in studies with controlled design. The FDA supports innovation and digital transformation initiatives for these changes to be successful and that the internal validity of traditional trials is not affected. Hence, a balance point must be sought to guarantee the accuracy of the trials, but at the same time, a flexible way of capturing the data.

Latin America as a region is no stranger to this initiative. During the pandemic, measures were taken to ensure that this methodology was adopted. However, it is the responsibility of the regulatory bodies, sponsors, CROs, and research centers to consolidate these measures by enabling the remote informed consent procedure, home visits, distance follow-up assessments, and virtual recruitment.

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