By Shanique Smythe, Halloran Consulting Group
The costs of drug development have increased exponentially over the years, while clinical trial participation and retention have decreased.1 Sponsor companies are seeking new and innovative ways to reduce costs while increasing patient participation by becoming more patient-centric. One such method is through designing a "siteless" trial. Siteless trials offer convenience to patients while being cost-efficient for sponsors. They also allow for a larger geographic reach and more diverse patient population, as patients who normally live in more rural areas now have an opportunity to participate in clinical trials. Having this wider population available for recruitment expands the currently saturated pool of patients who are interested in participating in clinical trials.
How Do Siteless Trials Work?
Siteless trials, also known as virtual or direct-to-patient trials, bring the clinical trial experience to the patient’s home via a central, virtual coordinating site. Patients are able to set their own schedules for procedures, thus reducing the burden of traveling to a clinical site and spending hours there. This particularly works well for rare diseases and other serious illnesses where patients are homebound. All materials needed for a patient visit (i.e., investigational product, wearables, equipment, etc.) are sent to the patient’s home, and study physicians and pharmacists provide support via videoconferencing. Mobile health applications and telehealth technologies are used to capture medical information from patients and, in clinical trials, to transmit remote real-time data directly to the central study site.
Telemedicine technologies such as smartphones and wearable devices allow patients to connect with the trial physician in more ways than ever before, thus improving healthcare and health outcomes. These technologies have been particularly helpful for implementing patient-reported outcomes (PROs). Companies such as CRF Health, Bracket, and uMotif are some of the leaders in electronic clinical outcomes assessments and electronic PROs (ePROs). Even the FDA is excited about these advances. The Center for Devices and Radiological Health established the digital health program to foster collaborations and enhance outreach to digital health customers, as well as develop and implement regulatory strategies and policies for digital health technologies.2 There is also the Mobile Medical Applications Guidance for Industry and Food and Drug Administration Staff, which explains the agency’s oversight of mobile medical apps and devices.3
In addition to flexibility for patients, additional benefits of siteless trials include a reduction in trial costs, an increase in recruitment due to a larger reach of patients, increased data quality, and making medicine more personalized for patients. Without the need for multiple physical sites to conduct study procedures, a full staff complement, or storage facilities, investigator grant payments reduce dramatically, ultimately reducing the overall trial cost. It is also perceived that data quality is improved. The majority of the data is automatically transferred from smartphones or other wearable devices instead of depending on site staff to transfer from source documents to the clinical database.
Companies such as Science 37 are changing the game of clinical research by implementing "clinical research in a box,” whereby clinical trial materials are packaged in a box and shipped to the patient’s home. Science 37 offers a full-service approach with remote investigators and study coordinators who virtually connect with patients to help them through the process. Other companies that offer a semblance of a siteless trial approach include IQVIA, Aces Health, Parallel6, and Medable.
While the premise is to make trial participation more convenient for patients by reducing travel burden and time spent at clinical sites, it can also be seen as putting more responsibility on the patient. Patients now become responsible for receiving the investigational product, completing study assessments, troubleshooting equipment or technology problems, etc. This can be a burden for some patients, particularly older populations and those who are not technologically savvy. Learning how to use the technology can be time-consuming. Training will need to be provided on how to use the technology (i.e., devices for ePRO assessments, wearables), which study assessments are required, timing of assessments, how to administer the IP, etc. The training can be Web-based to allow for flexibility in scheduling, but should be detailed and laid out in a clear manner that can be easily understood by the patient. This will likely require approval by institutional review boards/independent ethics committee (IRBs/IECs) since it is being provided to the patient. Technical support for the wearables and any applications should be made available 24/7 to troubleshoot issues, as well as support by a central site for questions the patient may have regarding the study assessments. A CRO can also be contracted to provide support if a central site is not in place.
The siteless trial model also does not work well for trials that require a lot of office visits or complex procedures. For instance, trials that require radiographic procedures, surgical procedures such as biopsies, or complex investigational product administration may not be ideal because these procedures cannot be done at a patient’s home and/or require a specialist to complete. It is also operationally challenging to have all procedures done virtually. As a compromise, some sponsors opt for a hybrid or “direct-to-patient” approach of keeping some of the more complex procedures at the site while allowing more virtual touch points with the patient. Another option is to contract with a home-trial support vendor that uses licensed, trained clinicians such as registered nurses, phlebotomists, or physicians to perform some of the more complex assessments in the home. This vendor can be used for procedures such as complex IP preparation, obtaining vital signs, laboratory specimen collection and processing, and assessment of adverse events and reporting. They would then be responsible for completing source documents and transmitting the visit information to the central site or clinical database, depending on the contract. Some home-trial support vendors are Medical Research Network, UBC, Symphony Clinical Research, and Marken.
Data security is another potential challenge. Large amounts of patients’ personal data is transmitted via the Internet, particularly when using ePRO devices or wearables. Sponsors need to ensure patients are aware of the risk of data breaches in the informed consent form. The sponsor can also ensure the vendors they contract with use a secure data exchange to minimize the risk of a data breach. If a data breach does occur, the vendor should have a clear communication plan for notifying the sponsor, and ultimately the patients, that their data has been compromised.
There are many benefits to a siteless trial model including cost efficiency, convenience for the patient, data accuracy, and larger geographic reach. There are also challenges that still need to be vetted such as data security, implementation in complex trial designs, and ensuring proper training for patients, particularly those who are agnostic to technology. When designing a siteless or virtual trial, patient population, complexity of procedures, length of trial, and patient burden need to be considered. Sponsors should also consider that a trial does not have to be fully virtual to be beneficial. A hybrid approach, with a combination of in-clinic and home visits, may be a better option depending on the trial requirements and would still offer cost savings and increased patient retention. The use of home-trial support vendors fits in nicely with the hybrid approach and would allow for some of the more complex procedures to be performed in the home, thus reducing the site burden. It would also reduce some of the burden on the patient that a fully virtual trial may cause.
There is still work to be done to overcome the challenges, but the benefits to patients and sponsor companies can already be seen in the current offerings. Siteless trials will likely become more popular as the industry advances development of technology that will allow for a virtual approach.
About The Author:
Shanique Smythe has over 15 years of experience within the pharmaceutical industry, specifically in clinical operations and development. Smythe has experience leading early- and late-phase cross-functional development programs, building clinical operations teams, and developing cross-functional SOPs. She brings a strong global clinical management background in leading Phase 1 to 4 multinational trials across more than 20 countries, touching hundreds of sites and reaching subjects in hard-to-enroll indications. She also served as the operations lead on product development teams, providing operational input into study designs and development plans. She brings a demonstrated track record in developing critical alliances, liaising with customers, and managing third-party vendors.