From The Editor | October 5, 2021

Decentralized Trials Can Overcome The Challenges Of Rare Disease Patients

Ed Miseta

By Ed Miseta, Chief Editor, Clinical Leader
Follow Me On Twitter @EdClinical

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There are 400 million people worldwide who are impacted by more than 7,000 identifiable rare diseases. While individual rare diseases are uncommon, approximately 5% of the world’s population suffers from one. For many of those patients, travelling to a clinic to participate in a trial can be difficult. A new report from technology provider THREAD details how many of the clinical challenges posed by rare disease trials can be alleviated by decentralized trials.

Many patients suffering from rare diseases possess symptoms that impact their mobility. That increases the burden of travelling to clinical sites, which increases the difficulty of sponsors to recruit patients to participate in studies.

The use of decentralized trial technologies, such as telehealth, eCOA, ePRO, eDiaries, wearable devices, and patient apps can move many aspects of trial participation from the clinic to a remote location, such as a patient’s home. This makes trial participation easier for patients and caregivers while maintaining data integrity. Still, the report notes many sponsor companies have been slow to adopt decentralized approaches in rare disease trials.

Rare Disease Challenges

Rare disease trials tend to be more complex than most. Rare diseases are often debilitating and life-threatening. Rare disease trials have a lack of natural history data and well-established clinical endpoints. There are also a limited number of potential patients to participate in the trials. The report notes another issue compounding the problem is regulators. The FDA and EMA often use different criteria for assessing rare disease studies. That will cause sponsor companies to have to create protocols that meet both sets of requirements. Those protocols can increase the study burden on patients and their families.

Since the majority of rare diseases have genetic origins, 50% of rare disease patients are children, and one-third of them are under the age of 5. This further complicates clinical trials, as regulators require a higher level of data and data scrutiny in pediatric trials. Minors participating in a clinical trial also creates a burden for parents and siblings.

For those reasons, designing a trial with decentralized elements needs to begin early. End points need to be established and schedules of events developed that determine which activities and assessments can be performed away from the site. THREAD recommends patients and patient groups be part of those discussions.

For rare disease sponsor companies contemplating the launch of a decentralized or hybrid trial, the report makes the following recommendations.

Clinical Sites

Rare disease patients and sites are relatively low in number. That means patients and caregivers will have to travel long distances to get to the site and possibly require an overnight or extended stay. While decentralized approaches may not entirely eliminate visits to the clinic, they will present additional options to patients and families.

Since rare disease trials are less common than trials for other diseases, sites involved in rare disease research can be less experienced with clinical trials. They may not be familiar with good clinical practice or regulatory requirements that need to be in place. Sponsors should be aware that those sites may need more training and ongoing support. They should be trained on how to introduce decentralized trials to their patients. Sponsors should also be aware of each site’s pain points and what aspects of decentralized trials they may be hesitant to implement. Having that information upfront can reduce problems that might arise during the trial.

Hybrid Versus Decentralized

Rare diseases tend to be severe and life-threatening, which makes a fully decentralized trial unlikely. A hybrid study, with both clinical visits and decentralized aspects, may be the best approach. There is also a close connection between site personnel and their patients. That can make site personnel hesitant to promote a decentralized approach. A hybrid approach that reduces the patient burden while preserving the close personal relationship between sites and patients can convince site personnel to involve their patients in trials.

Drug Delivery Challenges

Challenges with drug delivery are not unique to rare disease trials, but the mode of drug delivery will influence a decentralized approach. Drugs administered by IV or infusion will generally require a site visit and assistance from a medical professional. However, home administration can be accomplished with home health nurses and telehealth allowing a principal investigator to be part of the process. Pills are more easily shipped to patients and technologies can be used to ensure medication adherence. Even if in-clinic administration is required, decentralized elements can be incorporated into a trial to gather data remotely and reduce a patient’s time in the clinic.

Recruitment And Retention

Patient recruitment is an issue in most clinical trials, and approximately 25% of all rare disease trials are terminated due to insufficient recruitment. To overcome that challenge, sponsors must make trial participation as easy as possible. More options for patients to participate in trials would help with recruitment and help with retention. To assist with recruitment, sponsors should engage with patient groups and allow patients to engage in the protocol development process.

The report notes patient advocacy groups for rare diseases can be very influential with patients. Patient groups can help develop protocols that are easier for patients to adhere to. Working with these groups is an opportunity for sponsor companies to pressure test decentralized trial elements such as apps or wearable devices.

To help with recruitment, patient groups can promote the study to patients while bringing credibility to the study. The advocacy group can direct patients to the trial’s landing page where they can learn about the study, self-pre-screen, sign eConsent, and be directed to a participating site. Once enrolled, the decentralized elements can assist with keeping patients enrolled in the trial.

Sponsor companies will still need to decide which decentralized elements are right for a trial. THREAD notes that decision is largely driven by the protocol, patient population, the disease, and more. The phase of the trial is also an important determinant. Early stages and first-in-human studies do not lend themselves to a decentralized approach, which requires PIs to have a close relationship with patients. Which elements will be deployed will depend on the trial protocol and study requirements at each stage of the trial.

Although rare disease studies can be challenging and complex, with qualified patients typically suffering from severe illnesses. Implementing a hybrid approach with decentralized elements can make the studies easier on patients and caregivers while also improving recruitment and retention for the study. Clinic visits can be reduced, and data can be collected more frequently, in some cases continuously. The data gathered can also help researchers develop new endpoints for diseases where there is a lack of historical evidence to draw on.

For more information or to review or receive a copy of the report:  Thread Research,