July 21, 2020
I first wrote about the ADAPTABLE clinical trial, being conducted by researchers at the Duke Clinical Research Institute (DCRI), in July 2016. The trial, which DCRI launched with PCORI (Patient-Centered Outcomes Research Institute), hopes to understand the effect of aspirin doses on heart patients.
The trial is a large pragmatic study of patients with established cardiovascular disease. The patients have been randomized to two doses of aspirin, which is an oral anti-platelet medicine used in almost all patients with heart disease. The two doses are 81 milligrams and 325 milligrams, and the trial is open label. Patients were selected from PCORNET, The National Patient-Centered Clinical Research Network created by PCORI.
“We started enrollment in April of 2016 and concluded in June 2019,” says Dr. Holly Robertson, former project lead, global mega trials for DCRI. “We were able to enroll a total of 15,076 patients in the study during that time from 40 clinical centers. Since that time, we have continued following participants to ensure high rates of visit completion, adherence, and retention.”
The study will be completed in 2020 with results expected to be available in early 2021. Although the trial was successful at recruiting and retaining a large number of patients, its major accomplishment may have been in showing how companies can best execute a virtual clinical trial.
A Simple Trial Design
In addition to being randomized by dosage, participants were also randomized to having a virtual visit every three months or every six months. The study hoped to determine the right frequency of visits for a virtual trial.
“Every three- or six-months patients are invited to come back to the portal,” states Robertson. “We asked them to report simple metrics, such as whether they were taking the aspirin and at what dose, if they were not taking it, the reason they stopped, and whether they had been hospitalized.”
The visits were designed to be very easy for patients. They were simple and streamlined, with most patients completing the visit in less than 10 minutes and with very little text entry. Patients were asked about concomitant medications annually to get a better view of their overall health. At the end of the study patients were also asked about the overall study experience. Robertson hopes that information will help researchers determine how to best conduct virtual trials in the future.
Since there were no required clinic visits for the study, patients use a portal to answer questions and input information. The website is smartphone and tablet enabled, and patients were asked to create a username and password when they joined the study. The virtual visit walks them through the information required. It also provides information to users, such as the date of their next visit. The portal is enabled to automatically send email and text notifications to participants to remind them of upcoming virtual visits to the portal.
A Simple Trial Design
In addition to being randomized by dosage, participants were also randomized to having a virtual visit every three months or every six months. The study hoped to determine the right frequency of visits for a virtual trial.
“Every three- or six-months patients are invited to come back to the portal,” states Robertson. “We asked them to report simple metrics, such as whether they were taking the aspirin and at what dose, if they were not taking it, the reason they stopped, and whether they had been hospitalized.”
The visits were designed to be very easy for patients. They were simple and streamlined, with most patients completing the visit in less than 10 minutes and with very little text entry. Patients were asked about concomitant medications annually to get a better view of their overall health. At the end of the study patients were also asked about the overall study experience. Robertson hopes that information will help researchers determine how to best conduct virtual trials in the future.
Since there were no required clinic visits for the study, patients use a portal to answer questions and input information. The website is smartphone and tablet enabled, and patients were asked to create a username and password when they joined the study. The virtual visit walks them through the information required. It also provides information to users, such as the date of their next visit. The portal is enabled to automatically send email and text notifications to participants to remind them of upcoming virtual visits to the portal.
Adapters Provide Insight
As noted earlier, the ADAPTABLE trial was started in 2016, and DCRI quickly embraced the concept of virtual clinical trials. Dr. Schuyler Jones, co-principal investigator of the ADAPTABLE trial, says many companies at that time were looking for ways to make clinical research better and faster, and easier for trial participants.
“We liked the idea of approaching patients to participate in research studies where they live instead of requiring them to visit a clinic or hospital,” says Jones. “We were also asking questions that could easily be answered from home.
Still, there had to be engagements between patients and clinicians. Patients will have questions that need to be answered by a nurse or doctor and we wanted to ensure they had the opportunity to interact with staff the same way they could in a non-virtual trial.”
Early in the trial DCRI engaged with patient partners called ‘Adaptors.’ The Adaptors are a panel of nine patients with a history of heart disease. In fact, all were patients in the health systems DCRI partnered with. The Adaptors participated in every aspect of the study including informed consent, the trial protocol, and the newsletter sent to trial participants. They are also key partners in developing the dissemination of results plan which will include direct notification to all study participants.
“We felt these were critical aspects of the trial,” says Jones. “Since this study would involve fewer in-person visits, we needed that information to ensure we remained on the right track and meeting the needs of patients.”
Information gleaned from the Adaptors was helpful. Robertson cites recruitment letters as one area where their recommendations led to improvements.
“With traditional recruitment letters, IRBs will often want to see a lot of text and information,” she says. “The Adaptors told us to make the materials engaging and explain concepts at a high level but to also allow them to dig deeper into certain areas where they had an interest.
“Those materials were important for the low-touch recruitment we were doing, and the patient partners were critical to designing those materials,” adds Jones.
Consider Technology Access And Knowledge
From the beginning of the study, DCRI also considered the ability of its patients to access required technologies. Robertson notes the study recruited a diverse patient population across the healthcare centers and some do not have consistent access to the Internet. Additionally, she found some are not comfortable with using the Internet to complete at-home visits.
To overcome these challenges DCRI created a central call center to field calls from patients. Patients who do not have Internet access or are not comfortable using the website are called and personnel at the call center assists them with collecting the needed information.
Although the ADAPTABLE study is not testing an investigational drug on sick or dying patients, Jones notes that did not decrease the complexity of the trial.
“None of this is simple,” he states. “Every trial is complex, especially one that recruits 15,000 patients. A trial of that scope requires us to deal with data from multiple sources. We were getting patient reported data from the portal and electronic health records data from the enrolling health centers. Data is also coming from private health plan partners and the Centers for Medicare and Medicaid Services.”
As a virtual study, data collection from study participants to determine what was happening to them had to be collected without burdening patient participants and researchers at the sites. DCRI engaged a company called Mytrus to provide the platform that would manage enrollment, randomization, and collection of patient-reported data. That company is now a part of technology provider Medidata.
“We conducted one of the first large virtual trials,” says Robertson. “We did not have any similar studies that we could look at and emulate. One reason we were successful was our partnership with Medidata. They helped us design a study portal allowing patients to easily enroll and participate, while collecting critical data for the study. They also partnered with us throughout the study and to resolve technical issues and adapt to the evolving needs of the study. They possessed the technical and virtual trial expertise we needed and allowed us to design a portal that has worked well for our patients.”
The feedback from patients and sites was positive. Robertson received good feedback on the initial eConsent process that was performed at home on the patients’ own devices. Patients also liked the ability to complete virtual visits at their own leisure.
Technology Aids Recruitment
The technology used in ADAPTABLE also assisted DCRI with their recruitment efforts. Robertson notes participating sites were able to identify large numbers of eligible patients within their healthcare systems. In fact, over 450,000 patients across the U.S. were approached about participating in the ADAPTABLE study.
“We had to be able to track patients efficiently,” adds Robertson. “When patients logged into the portal, we had to know their enrolling site to provide the right informed consent form and correctly map patient data. We used a coding system developed with Medidata that we called the ‘golden ticket.’ Sites provided eligible patients with a unique golden ticket to use when first logging into the portal. Golden tickets were designed to identify the site as well as the individual patient. This system was critical for DCRI and sites in managing the large volume of patients.”
“Our goal from the very beginning was to conduct a trial with a large number of patients that was better, faster, and easier than other trials of a similar size,” says Jones. “I think this is a model that we have an opportunity to improve on going forward.”
By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical