Decentralized Clinical Trials vs Traditional Clinical Trials

Decentralized clinical trials (DCTs) refer to human clinical trials which utilize novel methodologies and technologies such as telemedicine in order to conduct the trial. Unlike the traditional approach of patients coming onsite to the clinic, DCT focuses on incorporating local and mobile caregivers to provide the services needed for the trial.

DCTs have gained considerable support especially in this era of the COVID-19 pandemic. However, DCTs are not an exclusively new interventional study approach. In 2011, Pfizer conducted the first decentralized clinical trial in which no in-person site visits were conducted throughout the study[1].

Recently, the FDA issued a guidance document that outlines general considerations for Sponsors conducting clinical trials during the COVID-19 pandemic. This guidance document includes information regarding utilizing non-traditional methods (e.g. decentralized trials)   as a way of addressing the delays in the release of potential new therapies caused by the pandemic’s disruption of traditional clinical trials.

With the widespread adoption of virtual medicine and remote monitoring technology, there is no doubt that DCT is likely to be the mainstay approach for future human clinical trials. This article outlines the differences between traditional and decentralized trials during each phase of a trial.

The ARG Difference

Our scalable and platform-agnostic decentralized model help our sponsors:

  • Recruit more diverse participant populations
  • Retain more participants by driving engagement
  • Discover more valuable data

Mike Baker,
Senior VP of Business Development

Recruitment and Pre-Screening

Clinical trials employ different methods of recruiting study participants, all of which have both advantages and disadvantages. With studies becoming more complex, it is essential to understand the differences in the recruitment and pre-screening phases of traditional versus decentralized clinical trials.

Conventional study designs

A patient is either referred by their physician, responds to an advertisement (i.e. social media, flyer, radio ad, etc.), or will research treatment opportunities for recruitment onto a clinical trial. A study coordinator then asks the potential participant a series of questions concerning their medical condition to verify their basic inclusion/exclusion criteria. This is traditionally done either at the site or via a phone call. Eligible participants are then scheduled for a clinic visit to begin the informed consent process.

Digital decruitment in decentralized clinical trials

By contrast, DCTs employ a multi-pronged, digital approach in recruiting study participants. Digital advertising includes ads or digital kiosks used to target specific populations. Once an individual sees the ads, they can then choose to self-register for the study via a website, a mobile phone app, or a digital kiosk. The introductory or landing page usually contains a detailed description of the study outlining the benefits and potential risks of participation in the trial. Compensations are also explained on the page[2].

After reading the study description, interested subjects fill an attached pre-screening questionnaire and submit it with a click of a button. Within a few minutes, the potential study subjects receive notifications on whether they meet the criteria for participation or not.

In a traditional clinical trial, the patient usually signs a consent form during the first clinic visit. This is done after the site staff provides the subjects with all the necessary information regarding the study including reading the study description and understanding both benefits and risks of participating in the study. Additionally, the site staff will address any questions before the subject agrees to consent.

After pre-screening, an email containing a link to the electronic Informed Consent Form (eConsent) is sent to the patients who qualify to participate in the study. First, the patients are given time to read the consent. The study investigator then follows up via telemedicine to discuss the consent with the patient and address any questions or concerns.

When everything is clear and the patient is willing to continue with the study, the patient signs the consent form electronically and submits it. The study investigator countersigns the patient’s eConsent to enhance credibility. In some cases, a hard copy of the eConsent may be sent to the patient for signing.

Screening

Subject screening in traditional trials

During the first study site visit, a physician examines the patient, reviews their medical history, and conducts specific tests according to the trial protocol to verify the eligibility for enrolment into the trial.

The decentralized clinical trial screening process

The screening process is multi-layered in the DCT setting. Basic eligibility is established through a pre-screening questionnaire. Subjects who qualify receive a general view of the study before proceeding to sign the electronic consent. Once the patient signs the eConsent, a questionnaire that captures every aspect of the study eligibility is available to the patient.

With the patient’s consent, the e-screener provides the option of integrating the electronic health records, other outpatient data, and medical history into the study’s Electronic Data Capturing (EDC) system. Costs of additional testing may be avoided if the integration is done correctly.

Enrollment

Traditional clinical trial enrollment

Upon satisfying the qualification criteria including a review by medical personnel and the signing of the consent, the patient is considered enrolled in the study.

DCT participant enrollment 

Enrollment in a decentralized clinical study is entirely digitized. From self-registration to screening, every aspect of the trial onboarding is carried out remotely, which eliminates geographical barriers and minimizes disruption of the patient’s daily activities. Participants receive virtual support through email, in-app messaging, or calls to help address any concerns during the enrollment.

To curb fraudulent activities, the enrollment process uses a secure participant identity verification system that captures biometrics, contact source matching, and multifactor identification.

Treatment and Monitoring

Traditional treatment and monitoring

In traditional study designs, on-site treatment is provided during visits and the patient’s relevant data points are recorded in the site database for monitoring. The data collected may include laboratory test results or signs and symptoms.

Patient monitoring in a decentralized design

For treatment, the study equipment or therapy is shipped to the patients following eligibility confirmation and signing of the e-consent. Virtual training on the use of the materials and how to report data is conducted with the patient. For certain types of studies, mobile healthcare givers can be utilized for therapy administration and other services needed.

Patients utilize user-friendly eCOA and ePRO data capturing services which contain diaries and questionnaires to record their symptoms. Wearables, biosensors, and other digital instruments also promote real-time monitoring of patient vitals. Additionally, telehealth visits can be conducted while maintaining compliance with HIPAA and 21 CFR Part 11 requirements.

Retention

Retention of participants in a conventional clinical trial

Traditional trials usually have geographical limitations. The participants need to schedule and complete visits throughout the course of their participation and monitoring during the study. This is likely to cause disruption of participants’’ work, life, and family routines and could lead to poor experience during the trial. Consequently, the retention of patients could be lower compared to decentralized trials.

DCT participant retention

DCTs employ a patient-centric approach and eliminate geographical barriers to study participation by leveraging DCTs employ a patient-centric approach and eliminate geographical barriers to study participation by leveraging telemedicine, cutting-edge information technology, and local or mobile healthcare providers.

Virtual clinic visits, remote data reporting and monitoring used in DCT cause less disruption of participant’s activities, which improves their clinical trial experience. Consequently, there is increased retention of the study participants throughout the study compared to conventional designs.

For example, a non-interventional trial conducted in Switzerland studying lower back pain patients utilized both a decentralized and traditional arm. In the decentralized arm 80% of the participants finished the study versus only 60% on the traditional arm[3].

Follow-up

Follow up in traditional clinical trials

The participant is required to schedule and make site visits in studies that require follow-up. The number of follow-up visits varies from one study to another depending on the duration and other factors.

Follow-up in decentralized studies

For trials that require participant follow-up through professional medical assessments, DCT uses homecare health For trials that require participant follow-up through professional medical assessments, DCT uses mobile healthcare providers such as trained research nurses to perform the procedures.

From blood sampling to polymerase chain reaction swab tests, these processes can be carried out in the participant’s home eliminating the need to visit a site.

Follow-up is also done through telehealth visits while maintaining compliance with HIPAA and 21 CFR Part 11 requirements. 

End of Study

End of study in traditional trials

The study ends with a last visit in which the participants can provide an overview of their results and clinical trial experience. All diaries and documentation is collected from the participant and compensation is issued, if applicable. All data collected is analyzed statistically after cleaning and findings are published. The results of the study are then used to determine the eligibility of market approval.

DCT end of the study

At the end of the study, participants ship the respective study equipment back to the study site. Compensation is then credited to the participant’s account depending on the indicated mode of payment. The data collected is analyzed statistically after cleaning and findings are published. The results are used to determine the progress of the therapy if it enters the market.  

In conclusion, DCTs can serve as a viable alternative to traditional clinical trials. It allows for less disruption in the participants’ lives which can lead to potential better reporting of study outcomes, higher, diverse enrollment and better retention rates.

References

  1. Van Norman G. A. (2021). Decentralized Clinical Trials: The Future of Medical Product Development?∗. JACC. Basic to translational science, 6(4), 384–387. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093545/  
  2. Sommer, C., Zuccolin, D., Arnera, V., Schmitz, N., Adolfsson, P., Colombo, N., Gilg, R., & McDowell, B. (2018). Building clinical trials around patients: Evaluation and comparison of decentralized and conventional site models in patients with low back pain. Contemporary clinical trials communications, 11, 120–126.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072894/
  3. Sommer, C., Zuccolin, D., Arnera, V., Schmitz, N., Adolfsson, P., Colombo, N., Gilg, R., & McDowell, B. (2018). Building clinical trials around patients: Evaluation and comparison of decentralized and conventional site models in patients with low back pain. Contemporary clinical trials communications, 11, 120–126.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072894/