Published on: January 1, 2018
by Women’s Brain Health Initiative:
Volunteers Urgently Needed for Alzheimer’s Disease Clinical Trials.
The prevalence of dementia is expanding rapidly. According to Alzheimer’s Disease International (ADI), someone in the world develops dementia every three seconds. In 2015, there were an estimated 46.8 million individuals worldwide living with dementia and this figure is believed to be close to 50 million people in 2017. The ADI reports that this number will almost double every 20 years, reaching 75 million in 2030 and 131.5 million in 2050.
There is currently no cure for dementia or treatment to stop its progression or reverse the symptoms. To date, five drugs have been approved for the treatment of Alzheimer’s disease – the most common type of dementia. Many of these medications are aimed at slowing the rate at which symptoms worsen. The benefit from these drugs is generally modest, and many patients and their families may not even notice any benefit at all. Indeed, drug development for Alzheimer’s disease has proven to be very difficult. No new drugs have been approved for Alzheimer’s disease since 2003.
With so many individuals facing this devastating disease globally, and very limited treatment options available, the need to identify new drugs for Alzheimer’s disease is urgent. Fortunately, a variety of clinical trials are underway around the world assessing ways to prevent, delay the onset, slow the progression, or cure the disease, and to impact symptoms more substantially than the currently-approved medications.
What is a Clinical Trial?
Clinical trials are a critical stage in the research process in which the effects of a health-related intervention (including drugs and non-drug treatments) are evaluated. During clinical trials, the medical strategy, treatment, or device is tested on humans to determine its safety and efficacy. According to ADI, the entire drug development process takes an average of 13 years.
Before clinical trials commence, preclinical testing is conducted in a laboratory using tissue cultures and animals to see whether a given treatment has the potential to treat the disease or illness. If an approach seems promising, clinical trials begin and proceed through three phases:
If a drug proves successful in phase 3, health regulatory authorities review the results and decide whether to approve the drug. Even after a drug is approved and is being used as a treatment, it often continues to be studied in Phase 4 trials to examine whether any uncommon side effects surface as the drug is administered in greater numbers of people.
Sometimes, when a drug is being “repurposed”(meaning that its safety has already been established in association with a different disease), the drug development process can be shortened – in some instances skipping phase 1 trials and in rare instances skipping phase 2 trials.
Clinical Trials Depend on Volunteers
Unlike the preclinical phases of research, clinical trials rely entirely on volunteer participation. As Dr. Knebl and Dr. Patki emphasize, “medical research would grind to a halt without volunteer subjects.”
Vast Numbers of Volunteers are Required
At the world’s first G8 Summit on Dementia in December 2013, ministers from each of the participating countries agreed to set a goal to identify a cure or disease-modifying therapy for dementia by 2025. In order to reach this target, a great amount of research – proceeding at a quick pace – is necessary. In turn, vast numbers of volunteers will be needed for clinical trials.
In a recent article entitled “Alzheimer’s disease drug development pipeline: 2017,” published in Alzheimer’s & Dementia, Dr. Jeffrey Cummings and his colleagues reported that a total of 54,073 participants are required to take part in the 139 clinical trials that are already in the pipeline. These figures are based on the number of studies that are currently in various phases of testing, as registered on clinicaltrials.gov (a U.S. government website that includes nearly all U.S. clinical trials, as well as most international studies).
While the clinicaltrials.gov database is fairly comprehensive, it is not exhaustive, and this study only examined active trials of drugs and did not include non-drug or biomarker studies, which also require participants. Consequently, the actual number of trials underway and participants needed is even higher than these researchers stated. A 2016 article published on the BrightFocus Foundation website indicates that “more than 400 clinical trials are currently looking at new treatments for Alzheimer’s disease and many of them are actively recruiting.”
Making matters even more difficult, typically only between 10% and 50% of interested volunteers are eligible to participate in clinical trials. Using the conservative rule of thumb of ten people screened for each enrolled participant, researchers will need to recruit upward of 540,000 potential volunteers to find the number of participants noted by Dr. Jeffrey Cummings and his team.
The Challenges of Finding Enough Volunteers
Not surprisingly, then, recruiting volunteers will be a massive undertaking. Volunteer recruitment is frequently described as the slowest and most expensive part of clinical trials. In fact, recruitment periods are often longer than the treatment component of the study. Pharmaceutical Research and Manufacturers of America (PhRMA), in its 2013 report on Alzheimer’s drug development, noted that recruiting and retaining clinical trial participants is “currently the greatest obstacle to developing new Alzheimer’s treatments.”
A 2013 Research!America poll found that the majority of Americans (72%) indicate that they would likely participate in clinical trials if recommended by their doctor. However, many researchers struggle to find sufficient numbers of individuals to partake in their clinical trials. There are a variety of explanations to account for this gap between interest in participation and actual enrollment. According to the ADI, some of the major factors impeding sufficient enrollment in dementia trials include the following:
Lack of awareness of opportunities is one of the biggest challenges to dementia trial recruitment. Many individuals affected by dementia do not know that they can participate in clinical trials or where to find information on studies in their areas. Even those who do learn about research opportunities may not fully understand the clinical trial process.
Most individuals with concerns about their memory or cognitive function will first visit their primary care physicians, who are often thought of as a trusted source of health-related information. Primary care physicians are therefore in a strong position to inform patients about research they might want to participate in. However, like individuals living with dementia and their families, low physician awareness of clinical trials is a significant barrier to trial enrollment.
The ADI reports that a survey across five European countries found that only 19% of physicians, on average, were aware of a single clinical trial recruiting in their areas. Only 22% of respondents in the 2013 Research!America poll indicated that their doctors or other health care professionals had ever spoken to them about medical research. Similarly, a poll conducted by Imperial Clinical Research Services found that physicians were even less likely to bring up the topic of medical research with their patients (88% of respondents indicated that their primary care physician had never mentioned a study). Reasons for this include concerns about risks for their patients and long distance to a research site.
For many individuals living with dementia, the lack of a study partner is another hurdle to participation. A study partner is often mandatory in most dementia studies as they assist in the consent process, transport participants to and from trial sites, help the Alzheimer’s patient comply with all research requirements (such as taking medication in the right dosage at the right time(s)), and provide feedback to the researchers on trial outcomes (such as assessing any improvements in cognitive performance, memory, and daily functioning).
Consequently, some individuals may be excluded from enrollment because they do not have access to a study partner or the study partner may not have the time or resources to provide the support needed for trial participation. Participating is often challenging, if not impossible, for those caregivers who work full-time and are not available to attend numerous lengthy appointments during the typical 9-to-5 clinic hours. Caregivers may also feel burnt-out from providing the usual everyday support and therefore perceive research participation as too significant of an undertaking.the lack of a study partner is another hurdle to participation. A study partner is often mandatory in most dementia studies as they assist in the consent process, transport participants to and from trial sites, help the Alzheimer’s patient comply with all research requirements (such as taking medication in the right dosage at the right time(s)), and provide feedback to the researchers on trial outcomes (such as assessing any improvements in cognitive performance, memory, and daily functioning).
Additionally, clinical trials are designed with specific inclusion criteria for enrollment, which limits the number of volunteers who qualify for participation by trial design. Many Alzheimer’s and dementia studies require volunteers to undergo diagnostic tests such as lumbar punctures or magnetic resonance imaging (MRI) scans, which may be viewed as intrusive or time consuming. Cultural and linguistic challenges can also hinder participation as individuals from diverse communities may be skeptical or suspicious of research and institutional settings, or the volunteers may not speak the same language as the clinicians.
Many clinical trials test interventions for a specific disease, thereby limiting the number of potential participants to those without coexisting conditions. Further, individuals taking medications for dementia symptoms or other health conditions may involuntarily exclude themselves from trial participation.
Prevention trials must also overcome the unique challenge of some individuals not wanting to undergo testing to see whether they are at risk of developing Alzheimer’s disease (which is a key part of determining eligibility to participate in this type of research). In spite of this, though, more and more individuals are interested in understanding their dementia risk when they realize that they might be able to mitigate that risk through participating in a clinical trial.
Who Can Participate in Clinical Trials?
People with varying stages of Alzheimer’s disease and those at risk of developing Alzheimer’s disease are needed for clinical trials. If you think that you may be experiencing early symptoms of cognitive impairment, research is an option to consider. Cognitively healthy individuals are also needed for Phase 1 trials.
The Need for Greater Diversity Among Volunteers
For study findings to be applicable beyond the laboratory environment, participants must be representative of the general population of individuals with or at risk of developing Alzheimer’s disease. Unfortunately, however, this is usually not the case. According to a 2014 article entitled “Facilitating Alzheimer’s Disease Research Recruitment” by Dr. Joshua D. Grill and Dr. James E. Galvin, Alzheimer’s disease trial participants “tend to be younger, more educated, and more often Caucasian than is typical for the general AD population.”
Researchers struggle to find volunteers from diverse racial and ethnic backgrounds. For instance, a 2007 review found that more than 90% of participants in the U.S. National Institutes of Health Alzheimer’s studies and 97% of participants in industry-funded Alzheimer’s studies were non-Latino Caucasians. Yet, in 2006, 19% of adults aged 65 or older in the U.S. were non-Caucasian. Even more concerning, many of the racial and ethnic groups that are underrepresented in clinical trials are actually at higher risk of developing dementia.
Likewise, study participants have historically been unrepresentative of the Alzheimer’s population when it comes to education level. While there has been an overrepresentation of highly-educated participants in Alzheimer’s clinical trials, epidemiological studies show that less-educated individuals (those with less than 12 years of schooling) are at higher risk for developing Alzheimer’s disease.
Reasons People Volunteer
People volunteer to participate in Alzheimer’s research for multiple reasons, both personal and altruistic. Two of the most common reasons are (i) that the individual with or at risk of developing Alzheimer’s disease hopes to benefit personally from a new treatment and (ii) that the individual wants to help find treatments or a cure for future generations.
What to Expect if You Volunteer
Clinical trials typically proceed as follows:
Length of Clinical Trials
Clinical trials typically vary in length from three months to five years. The duration of the trial largely depends upon the time that it takes to recruit sufficient volunteers. Dr. Jeffrey Cummings and his colleagues reported that, on average, the duration of a trial (including recruitment and treatment period) was the shortest for phase 1 trials (at 755 days). Phase 2 trials took an average of 1,140 days to complete, while phase 3 trials averaged 1,677 days.
How to Volunteer for a Study
Hopefully, going forward, primary care physicians will be more likely to provide their Alzheimer’s patients (or those at risk) with information about clinical trials. Doctor referrals have great potential to increase the number of volunteers.
If your doctor does not mention clinical trial opportunities to you, be proactive and ask about them. Your inquiry may prompt your doctor to learn more and get back to you with information. Even better, ask your doctor to refer you to a clinical trial site where you will be able to receive information first hand.
There are also a variety of online tools that may be helpful in identifying a clinical trial of interest. Clinicaltrials.gov is one of the most comprehensive among this group of online resources.
Two websites that provide Canadian-specific information are:
Some examples of online resources that are dementia-specific and mainly geared towards U.S. residents include:
If you are in the Toronto area, consider volunteering for a study at Toronto Memory Program, Canada’s largest clinical trial site for testing drugs to prevent and treat Alzheimer’s disease. Dr. Sharon Cohen, Neurologist and Medical Director at Toronto Memory Program, notes that “most individuals with or at risk for Alzheimer’s disease are completely unaware of clinical trial opportunities and are grateful to find a centre that offers the latest treatment approaches and options. At any given time, Toronto Memory Program is participating in 15 to 20 international trials and is actively recruiting participants for half of these trials.”
Toronto Memory Program has been internationally recognized for its excellence in clinical research and for providing research opportunities to thousands of Canadians. For more information on trials at Toronto Memory Program, visit https://www.torontomemoryprogram.com/ or contact the Clinical Trial Educators at 416-386-9606. You may also wish to attend one of Dr. Cohen’s presentations about Alzheimer’s prevention and treatment. Details about upcoming dates and locations can be found in the “Events” section of the website.
As Dr. Cohen observes, “Clinical trials are the hope for the future and volunteers are key. Researchers cannot achieve the urgently needed breakthroughs in Alzheimer’s disease without the assistance of volunteers willing to pioneer with them. The faster we complete recruitment for clinical trials, the sooner we will put an end to Alzheimer’s disease. It is not a matter of ‘if’ we will beat this disease but ‘when.’ As the number of individuals affected with Alzheimer’s disease rises, the call to action in clinical trials has never been greater.”
Questions to Ask Before Enrolling in Clinical Research
To help you make an informed decision about participating in a clinical trial, consider asking the researchers the following questions:
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