Physician at work

Why Are Alzheimer’s Disease Clinical Trials So Challenging To Carry Out?

The last Alzheimer’s drug in the US was approved in 2003. Despite billions of dollars poured into Alzheimer’s disease research in the last two decades, most clinical trials have yielded negative results. No less than 146 drug treatments for Alzheimer’s have proven ineffective in clinical trials between 1998 and 2017.

The drugs that have been approved address only symptoms. They do not target the disease’s underlying causes and cannot slow its progression. It’s important to remember that Alzheimer’s disease is the 5th global cause of mortality according to the WHO. The average life expectancy for someone diagnosed with the condition is 7 years.

Adding to the challenge of finding successful treatments for Alzheimer’s disease is the difficulty of running clinical trials. But why is that? Why are Alzheimer’s disease clinical trials so difficult?

The Challenge of Finding Participants for Clinical Trials

People suffering from Alzheimer’s may have the disease in an asymptomatic form for many years before exhibiting symptoms and being accurately diagnosed. Unlike many other major diseases, Alzheimer’s progresses over the course of years, not months.

Many people who are eventually diagnosed with Alzheimer’s do not receive a diagnosis until their cognitive function becomes affected. In many cases, they are not aware of their loss in cognitive function until it becomes severe enough for it to impact their day to day life or for other people to notice it. By that time, the disease is so advanced that new treatments that try to slow or prevent the progression of the disease or alter its course prove ineffective.

In other words, it’s difficult for researchers to find participants for Alzheimer’s disease clinical trials simply because people who have the condition in an early stage don’t know they have it. Early, preventive screening could change this, but awareness and perception about the condition need to be improved too. According to a report, 60% of healthcare providers still believe that dementia is part of normal aging.

At the same time, Alzheimer’s disease is not easy to diagnose. There is no quick test that can determine whether a person suffers from Alzheimer’s or not. In fact, there is no single blood test, scan, exam, or cognitive test that can give a 100% accurate diagnosis.

Instead, healthcare providers use an exclusion process to diagnose dementia. They exclude other diseases that may cause dementia-like symptoms and then they differentiate between different types of dementia to finally reach an Alzheimer’s diagnosis.

The Very High Costs of Alzheimer’s Disease Drug Development

The complexities of developing new drugs for Alzheimer’s disease, coupled with the very high failure rate of past endeavors have increased the costs of Alzheimer’s drug development exponentially.

Biogen, Eisai, Merck, Roche, J&J, and Roche are just some of the big companies that have failed to develop effective Alzheimer’s treatments despite promising leads. The estimated cost of developing new Alzheimer’s disease drugs is a whopping $5.7 billion, which is seven times higher than that for cancer.

While big bucks are being invested into Alzheimer’s research, the very high cost of developing drugs that have the potential to modify the disease’s progression means that relatively few organizations can afford to run large-scale clinical trials.

The vetting process for clinical trial drugs is extremely tough, with most entrants floundering in the first phases. So many promising small-scale studies have met with failure during clinical trials that neither pharmaceutical companies nor research centers are assuming risks lightly.

The Duration of Alzheimer’s Disease Clinical Trials

Another major challenge with clinical trials for Alzheimer’s is the usually slow progression of the condition compared to other diseases. It may take years before short term memory problems in someone with Alzheimer’s escalate into reading problems or object recognition problems. From these, two or more years may pass before signs of poor judgment and short attention appear. These symptoms are not easy to quantify, either.

While the average drug can be developed in as little as 10 years (!), Alzheimer’s disease treatments take years longer because participants in clinical trials have to be carefully monitored over time. All the careful testing and assessments that accurate long-term clinical trials require make these trials even more difficult than they would be if they only suffered from a shortage of participants and high costs.

In the end, the time between an Alzheimer’s disease clinical trial begins and its conclusion can be measured in years. During this time, new findings, changes in funding due to lack of progress, and other variables may take their tolls on the trial. Alzheimer’s trials then carry a lot of risks even for the richest pharmaceutical companies.

A Relentless Search

Despite clinical trials in Alzheimer’s disease being so difficult, there were over 132 agents in clinical trials in 2019. Of these, 96 had the capability to modify the course of the disease. Across all phases of clinical trials, there were more ongoing clinical trials last year than in 2018. This highlights both the resilience of researchers and institutions and the pressing need for developing effective Alzheimer’s treatments.

Alzheimer’s disease is a condition with far-reaching implications. While running clinical trials for it is very challenging and the failure rate of newly proposed treatments is extremely high, the medical world has no choice but to march on in their search for new treatments.

More than motivating researchers to keep trying, all the past Alzheimer’s research failures and setbacks have not been a waste of time. Many failed clinical trials have contributed meaningful information to our understanding of the condition, which is crucial to the continual evolution of new treatment ideas.

High-profile failed trials have challenged assumptions about Alzheimer’s, most notably whether the plaques and tangles that have long been considered the hallmarks of the disease are truly the causes of Alzheimer’s and not merely symptoms that have masked other causes.

By understanding what doesn’t work, researchers could predict more accurately what may work. They may narrow down potential new ideas to focus on the strategies that show the most potential based on existing data. Of course, in the complex world of Alzheimer’s research things are not as straightforward as that. Still, many past trials could prove to be helpful pointers in the right direction. They could provide an indirect solution to one of modern medicine’s greatest quests.

Final Thoughts

It would not be an overstatement to say that Alzheimer’s disease is one of the most difficult diseases to understand and develop new treatments for. Clinical trials for Alzheimer’s are expensive and lengthy and even when funding exists, it can be hard to find participants for them in time to optimize testing results. Also, because they have a traditionally high failure rate, they generate reticence, hesitation, and bias.

But each unsuccessful Alzheimer’s disease clinical trial adds another rung to the long and intricate ladder that researchers need to keep climbing to finally reach the top of the great mountain that effectively treating Alzheimer’s is. But the goal justifies all efforts and expenses—discovering treatments that could save the lives of millions of people around the world.

Researchers may have lost many fights with Alzheimer’s, but the big battle against this neurodegenerative condition that affects millions of people continues. And today, researchers are better prepared than they have ever been.