Top Five Rules for Success in Decentralized Trials
The global coronavirus pandemic catapulted the emerging field of decentralized clinical trials (DCTs) to the forefront of clinical research in a matter of months. With new approaches like home nursing, telehealth, direct-to-patient (DTP) drug shipments, and mobile sensors, DCTs are making it easier for patients to participate in trials, especially for those who live far away, are too sick to travel, or are too busy.
Parexel’s DCT experience spans more than 100 fully decentralized or hybrid trials, and more than 250 trials with DTP drug shipments. Patients’ needs and insights are central to how we design and conduct trials, so we talked with Parexel DCT experts to find out what they have learned. Here are their top five rules for a successful DCT:
- Anticipate and mitigate DCT-specific risks.
Traditional trials carry plenty of risks: Missing or erroneous data, improper drug handling, and accidental unblinding, to name a few. With DCTs, these risks may be more obvious—and that enables study designers to mitigate them through careful planning.
For example, a patient in a clinical trial always has the right to withdraw from the study for any reason. But some therapies can’t be stopped immediately: patients need to take increasingly lower (titrated) doses and taper off the treatment gradually for safety reasons. In a traditional site-based trial, the titration process is explained and handled by site staff. In a DCT, we prepare a study-specific titration kit that is distributed to patients at the start of the study. If they withdraw at any time, the instructions and medication doses are pre-packaged and ready to go.“Smarter” processes can also help deliver investigative medicinal products (IMPs). In a DCT, if we know that we must control the temperature of an IMP from site to storage in a patient’s home, we build layered systems, including specially trained couriers to transport it in a temperature-controlled environment with a monitor that provides continuous readouts. If an IMP drops below or goes above the specified range, the courier does not deliver it.
- Think through every aspect of DTP logistics.
Sponsors tend to focus on IMP delivery when they think about DTP logistics, but there is a lot more to it. Effective DTP operations also involve study support materials (such as patient instructions), devices, consumables, sample collection, the return and reconciliation of unused IMP, and packaging materials, among other things. Successful DTP logistics require attention to detail and an overall view of the IMP supply and storage chain.
Parexel recently conducted a trial where we supplied patients with study-specific ‘smart’ refrigerators that registered activity. Since some patients could not easily accommodate an extra refrigerator in their home or apartment, we checked each participant’s size and space requirements. This is the level of detail that is necessary, yet easy to overlook, when devising a DTP delivery system.
- Embrace the expertise and motivation of patients and their caregivers.
Conventional wisdom in the pharmaceutical industry was: “We need to restrict information about the inner workings of clinical trials, or it will confuse and discourage patients.” At Parexel, we’ve found just the opposite. Patients and caregivers—especially those with chronic and rare diseases—are often experts in their condition. And they eagerly assume responsibilities in DCTs.For example, diabetes patients know how to inject themselves, and kids who have grown up with diabetes are adept with electronics and devices. Patients with rare and orphan diseases, particularly those who live far from academic research centers, are deeply knowledgeable and motivated.
Since COVID-19 hit in late 2019, patients in clinical trials have adapted to new devices and telehealth visits in what The Lancet recently called a “fast, effective readjustment.” The results demonstrate that giving patients and caregivers more responsibility provides enormous benefits.
DCT trial designers can learn a lot by asking patients, caregivers, and advocacy groups the right questions. Does the treatment being tested address a relevant patient need? Can it be administered in a non-site setting? For this patient population, is a DCT the right approach?
- Adjust protocols for better compliance at home.
If your goal is 100% patient compliance for a DCT, and you have restricted time windows for the activities in your protocol, you are not likely to succeed.
For example, we recently worked with a sponsor to tweak the protocol design of a DCT because it was unrealistic. The study specified that patients record their blood pressure twice per day within two 90-minute windows over six months. However, patients with young children to care for, mobility problems, or chronic pain would have difficulty doing that. So instead of keeping a rigid timeframe and seeing, say, 50% compliance, we broadened the time windows and achieved 80%.
- Ask your patients to define patient-friendly.
Often trial planners theorize in meetings about what would work best for patients, but only patients know. To bring that knowledge to planning, talk with patients, caregivers, and sites, and solicit practical feedback about what they need.
For example, some patients do not find home nursing visits convenient or desirable. In certain cultures, chronic or serious illness or disability is taboo, a sign of weakness, or even a trigger for harsh judgment and shunning by the community, so having nurses visit the patient at home risks their privacy. Others may feel embarrassed by constrained economic circumstances such as several generations or many individuals living in one home. Or by a psychological disorder such as hoarding. If research shows that your target patient population doesn’t want home nursing, consider local community centers or even hotels for nursing visits.
Parexel DCT experts who contributed to this article:
Innovation Ambassador and Head of Clinical Trial Supplies & Logistics Product Management
Associate Director, Integrated Solutions, Clinical Trial Supplies & Logistics
Solutions Architect and Program Director
Associate Director, Patient Innovation Center
Director, Patient Innovation Center