Patient and Stakeholder Engagement

3 of the Hardest Obstacles We Face in Alzheimer’s Clinical Drug Trials

For the estimated 30 million people worldwide who have Alzheimer’s disease, progress toward understanding and treating this most prevalent form of dementia is frustratingly slow. The few approved drugs address only the condition’s symptoms, though scores of drugs to prevent onset or alter the disease’s course are now under study.

From high screen failure rates to lengthy trials that place heavy demands on patients and caregivers, researchers conducting Alzheimer’s clinical trials face a number of recurring obstacles. Some of the hardest are:

1. Screening challenges. Screen failure rates among patients suspected of having probable Alzheimer’s, as well as prodromal and MCI patients, are as high as 70 percent. Many other neurological conditions present similar symptoms, and both of the techniques used to confirm amyloid plaque deposition in the brain are invasive and otherwise problematic.

One uses a PET scan that requires injecting patients with radioactive tracers, some agents that are not available in all countries. The other requires drawing spinal fluid via lumbar puncture, a procedure that patients generally dislike and that is especially unpopular in Asia. A trial that requires a lumbar puncture is facing substantial recruitment challenges in China and other Asian countries.

2. Regional requirements. Speaking of Asia, it’s difficult to overstate this region’s importance to Alzheimer’s research. The region’s population is huge, and while trial sites in Western countries are highly saturated with studies (nearly 150 trials are currently underway), there is comparatively little Alzheimer’s research in Asia. That not only bodes well for availability of patients, but in particular the availability of the treatment-naïve patients sponsors often prefer.

Among Asian countries, Taiwan presents an added layer of complexity. A significant portion of AE elderly population uses a dialect of official Taiwanese that exists only in the spoken word. Unable to understand the Chinese language used in study scales, these patients need interpreters who represent added time, expense, and the opportunity for translation errors.

3. Patient retention. Alzheimer’s studies tend to take a long time. Expect a Phase III trial to last 18 months, followed by an open-label extension of 18 to 24 months. That requires sponsors to observe cognitive changes over a long period, typically more than 5 neuropsychological scales. That’s a big commitment for generally elderly patients who often have limited mobility and may also have transportation challenges.

Bear in mind, also, that it takes two — patient and caregiver — to take part. Caregivers carry a heavy burden throughout the course of a patient’s treatment, and trial participation can add significantly to that load, especially when the trial site is far from home.

All indications have their nuances, and this is no exception. For example, a possible side effect of some experimental Alzheimer’s drugs is changes to skin pigmentation, and patients in those trials must undergo a full skin exam. It’s not uncommon (again, especially in Asia) for female patients to refuse these exams when the only available dermatologist is male.

What can be done?
Contract research organizations are developing tools and techniques to keep patients engaged and motivated. Sometimes all it takes is a simple courtesy like a prepaid debit card for reimbursement of travel expenses, providing the funds up front in a format that’s easier than requiring the patient to deposit a check mailed after the fact.

Industry also is working harder to work with Alzheimer’s advocacy groups. We’re encouraging those organizations to more freely share patient data, refer patients, and advertise ongoing and upcoming trials. Sponsors and CROs are also a more visible presence at events such as World Alzheimer’s Day, observed each September 21 — meeting patients and their advocates where they live to form stronger bonds and facilitate greater trust.