Alzheimer’s Disease Clinical Trials Planning

Karen Rosenzweig, Senior Director, US Operations

Scientific efforts to prevent, manage or better understand Alzheimer’s disease progression make news headlines every day. In today’s biopharmaceutical product pipeline, there are more than 300 open Alzheimer’s disease clinical trials, according to a cursory search on Clinicaltrials.gov.

Even with disappointing results from the recent Phase III study involving tau protein, other positive news is emerging related to more precise diagnostic tools, promising early phase results of immunotherapy vaccines and a unique investment approach.

Increased public awareness can bring more attention to research funding needs, and encourage clinical trial participation on a global scale.

Expanded patient access, however is only half of the equation for clinical trial success. Alzheimer ’s disease is among the most challenging type of clinical trial to conduct. If Alzheimer’s disease is relatively new to your product portfolio, consider these recommendations:

Prevalence. Alzheimer ’s disease is a global epidemic, affecting nearly 50 million people worldwide. While estimates vary, dementia affects more than 5 million people in the US and nearly 10 million people in Europe. Nearly 60% of people with dementia live in countries with emerging clinical trial markets. Asia accounts for nearly 50% of new dementia cases, due mostly to the increase in the elderly population taking place in China, India, and in south Asian and western Pacific countries. Trials that seek treatment naïve patients need to look beyond major markets and include regions which offer large and diverse patient populations.

In global Alzheimer’s disease clinical trials, you have to expect some heterogeneity even under the most controlled circumstances. Diagnosis, treatment, and care differ between countries. For example, US may have a higher number of concomitant medications than a country in Eastern Europe. Multinational trials need to be large enough to account for potentially increased variance.

Patient outreach and caregiver support. To reach Alzheimer’s patients, you need to employ targeting strategies and messaging that resonate with caregivers. Caregivers may be family members, friends or health professionals. Trial designs needs to consider caregiver support, as caring for a person with Alzheimer’s disease can have high physical, emotional, and financial costs. Spouses are often primary caregivers. In general, they will also be elderly and may suffer from their own health issues. The spouse may no longer be driving, which will make attending study visits difficult. In many trials, providing a car service to assist with clinic and lab visits will significantly improve trial acceptance. Retention support, in form of visit and medication reminders can also alleviate caregiver burden. Facility convenience is important to caregivers. Small amenities go a long way. Is the waiting room comfortable? Is wi-fi available? It is not uncommon for study visits to take hours.

Site Selection. Site selection needs to go beyond typical assessment criteria. Do staff have experience and proven compliance or certification with the rating scales that will be used in a specific trial? How recent is the certification, or how often is the methodology refreshed? Rater drift is common, requiring on-going rater monitoring and remedial training.

What is the availability and qualification of the facility and staff performing, PET, MRI and lumbar punctures? Compliance with imaging is better when imaging facilities are on site or adjacent to the study site. If not on site, how is the site aligned with PET centers and other imaging centers?

Also, look at the turnover rate of patient-facing staff. Considering the importance of minimizing patient agitation and caregiver stress, consistency of staff and staff familiarization will go a long way in patient retention.

Patient-friendly trials. Other considerations to incorporate patient-friendly principles into Alzheimer’s disease clinical trials include:

  • Use patient-friendly language. At the outset of a trial, face-to-face communication is important. Taking extra time to explain the purpose of the clinical trial, what to expect in study visits, and why certain procedures are important can boost participation and patient retention. How will risks and benefits be explained? Consider terms such as “treatment arm” “greater than minimal risk” “randomization” how well do these terms resonate with patients and caregivers? (Probably not as well as you think.)
  • Find out (ask patients and caregivers upfront) about their communication preferences during the trial. Many prefer email; while others opt for SMS messaging. And some will prefer postcards.
  • Study websites are a popular way of providing the information to the extended network of caregivers and family members. If well informed, they are more likely to allow the patient to participate.
  • We’ve learned from patient and caregiver research that trial acceptance can be improved by incorporating relatively simple changes: such as reducing waiting times at sites, offsetting travel and parking, and providing feedback on medical tests and trial results.

Alzheimer’s disease clinical trials are challenging. But patients and caregivers are willing, if the conditions of participation are acceptable. Clinical trial success is possible with comprehensive feasibility, informed site selection, knowledge (and support) of patient and caregiver preferences, and patient-friendly trials. For more information on this topic, watch our webinar or read our white paper.

Additional sources: Bairu, M; Weiner, M. Global Clinical Trials for Alzheimer’s Disease, 2014. Clariness research.

This post, originally written in March 2016, was updated in August 2016 with references to recent Alzheimer’s disease research news

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