The first mention of virtual clinical trials was nearly two decades ago. However, the low amount of information indicated the pharmaceutical industry’s unaroused interest in this form of drug testing at the time. The COVID-19 pandemic has rekindled interest in the topic once more, as VCTs protect both research participants and healthcare experts conducting the trials. With new operational restrictions in place moving into the post-COVID-19 era, VCTs will continue to be integral for the advancements of healthcare.
Completed Virtual Clinical Trials
There have been only two VCTs that have been officially completed in the past five years.
1. Metformin for Rising PSA Remote Trial
This was a pilot study with only fifteen participants. This clinical trial was designed with the intention of “bringing clinical trials to patients” instead of solely “bringing patients to clinical trials” . In this study, men with biochemically recurrent prostate cancer (a rising PSA after definitive local therapy) received the antidiabetic drug, Metformin. The trial integrated telemedicine visits to reduce the burden of in-patient participation. The only in-person requirement was that patients show up on-site for enrolling in the study. The remainder of the 6-month study was conducted via a secure telemonitoring system where monthly visits were carried out on tablets provided to each participant.
The study was not created to see if the drug Metformin worked on men with PSA, as the drug’s efficacy in this scenario was confirmed in other studies. Instead, the researchers tested whether the virtual clinical trial methodology was effective for patients. The results of the study were very positive. All of the participants reported that the study did not disrupt their life tremendously, if at all. These results helped strengthen the argument that virtual trials are better time-management-wise for the patients.
The total time for patient recruitment in most typical clinical studies is around 30% of the total time of the clinical trial, which roughly equals 30 months of development . In comparison, a study comparing virtual studies with traditional studies found that three VCTs took on average 4.0 months (± 1 month) to recruit and enroll the target sample size, compared to 15.9 months (± 7 months) for traditional trials . The trial that evaluated Metformin was finished in six months.
Taken together, VCTs can dramatically reduce trial periods starting at the patient recruitment stage. Since recruitment is considered to be the most significant time consumer in the clinical trial progress, one can see that virtual trials enable more research to be completed faster. In turn, this potentially means less money and resources are spent.
2. Personalized High Tibial Osteotomy (HTO) vs Generic HTO
The second VCT was an observational, case-controlled, prospective study. It was completed in 2019. The researchers created “virtual patients” based on CT scans of real patients who suffer from knee osteoarthritis. The virtual patients were duplicated and had the osteotomy stabilized by a generic HTO plate in one copy of the cohort and a personalized HTO plate in the other copy . The main question to be addressed was: Is the personalized HTO procedure as safe as the most commonly used existing generic HTO procedure? The main evaluation point was to determine the mechanical loads placed upon the tibia, as this is a problem with this procedure. Implantation of the support plate on the tibia was determined by evaluating 3D imaging data. Following that, both the personalized and generic HTO procedures were applied to patients virtually.
The models were loaded with physiological loads experienced during function, and the mechanical states were compared. This virtual clinical trial showcased the ability to evaluate two different types of plates for tibial osteotomies in a virtual space. In addition, the VCT demonstrated the novel concept that clinical trials may no longer require patients’ physical participation to complete a study of medical devices. Instead, they can find the right patient, anonymize them, and then use their information to determine the effects of the subject of the study. This study also showed the power of medical imaging to enhance VCT design and facilitate the process. It was also suggested that these attributes could lower the cost of the entire trial. The ability to create “virtual patients” allows researchers to develop scenarios that would otherwise be considered potentially unethical. For example, giving a patient a generic form of HTO rather than a brand-name form of HTO and depriving them of choice because of a double-blind study could raise moral issues regarding the study and the actions of the researchers. This study is one of the first of its kind. It has shown that studies can be done with real-world data, but not physical patients, and still create reputable results that will impact the world.
Ongoing Virtual Clinical Trials
Though there have been only two officially completed VCTs, there are about eight current clinical trials designated as “decentralized,” “remote,” or “virtual.” All are either recruiting or enrolling patients by invitation at this moment in time. Below, Bioinsider will mention a couple of examples.
Dream Insomnia Study (Currently enrolling)
This is an open-access, open-label, decentralized clinical trial. Through a nine-week remote study, the authors aim to collect data in a real-world environment regarding cognitive behavioral therapy (CBT-I), delivered via a digital therapeutic. Participants with chronic insomnia are eligible for consideration .
Potential participants will answer an online prescreening questionnaire to determine eligibility. Qualifying participants will complete six weekly modules through their personal mobile phone or tablet in nine weeks. A series of the assessment and questionnaires will be administered at set points during the study. Participants will be asked to complete a follow-up module about 26 weeks and at Day 243 and Day 428 after completing treatment. A subset of approximately 34 participants will also be asked to partake in [an] optional user experience sub-study. The participant will be asked to provide study feedback by either completing a five-day diary or an interview. This study aims to quantify the effectiveness of a digital therapeutic on sleep and give voice to the participants by allowing them to write in their own words about how the study went. 
Disturbed Sleep in Progressive Supranuclear Palsy Study (Currently recruiting )
This is an interventional, randomized crossover assignment study. In this study, investigators believe that targeting wake-promoting centers in the brain with a specific medication will improve sleep quality and overall well-being in progressive supranuclear palsy (PSP) . To study this, investigators will be doing a double-blind, within-subject, remote clinical trial with three conditions: suvorexant- which targets a wake-promoting system, zolpidem- a standard hypnotic that engages sleep-promoting systems, and a placebo. Each condition will last one week and be separated by a 1-week washout period on no sleep medications. Investigators will examine sleep patterns and daytime symptoms to determine if suvorexant, zolpidem, or both medications are effective and safe at treating sleep disturbances and improving overall well-being. The outcomes for the study will be measured by a questionnaire given to the participant and by measuring sleep efficiency, which will be measured by actigraphy. This study is expected to finish in June of 2023.
These two studies emphasize that conditions that the participant themselves can monitor are more likely to become potential topics of VCTs. These clinical trials are less likely to disturb participants’ lives as it is up to them to decide what to record and what changes are happening. These VCTs depend on the participants and imply that future trials (virtual or not) will instate more trust in the participants than before. It will also provide a degree of control to the participants, as they will be the ones to record the pertinent information for the trial.
As the number of VCTs increases, so does their value. Within three or four years, five or more virtual clinical trials should be completed, and their successes will be reported. According to the findings from the virtual trials conducted, participants were positively affected by the experience and are more inclined to participate in other clinical trials in the future. Ultimately, this will result in more research being undertaken, which is beneficial to society. Lastly, moving ahead in the post-COVID-19 era, not only the interest but the need for VCTs should make this an exciting healthcare sector in the near future.
About the author:
Nicole Ludwiak is enthusiastic about emerging cancer therapeutics and the potential of technology to advance medical research.
- Metformin for Rising PSA Remote Trial – Full-Text View – ClinicalTrials.gov. (2017). ClinicalTrials.Gov. Metformin for Rising PSA Remote Trial
- Schulthess, D. (2014). Opt-in, Opt-out, & Patient Led Databases Better Patient Outcomes, Faster and Cheaper[Slides]. VitalTransformation.Com. https://vitaltransformation.com/wp-content/uploads/2014/10/DGS_17-10-Opt-in-Opt-out-Patient-Led-Databases-MAPPs-DG3.pdf
- Comparison of study samples recruited with virtual versus traditional recruitment methods. (2020, September 1). PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327265/
- Personalised HTO Versus Generic HTO Virtual Clinical Trial – Full-Text View – ClinicalTrials.gov. (2020). ClinicalTrials.Gov. https://www.clinicaltrials.gov/ct2/show/study/NCT03419598?term=HTO&draw=2&rank=4
- A Remote, 9-week Insomnia Treatment Trial to Collect Real World Data for a Digital Therapeutic – Full-Text View – ClinicalTrials.gov. (2020). ClinicalTrials.Gov. https://www.clinicaltrials.gov/ct2/show/NCT04325464?term=PEAR+003A&draw=2&rank=1
- Treatment of Disturbed Sleep in Progressive Supranuclear Palsy (PSP) – Full-Text View – ClinicalTrials.gov. (2021). ClinicalTrials.Org. https://www.clinicaltrials.gov/ct2/show/NCT04014387?term=Disturbed+Sleep+in+Progressive+Supranuclear+Palsy+Study&draw=2&rank=1