The human brain is probably the most complex structure in the universe. It is therefore not surprising that clinical trials for central nervous system (CNS) diseases such as Parkinson’s disease pose various challenges.

The underlying pathophysiology of the human brain is understood more and more, but by far not fully. This is in contrast to more singular models such as infectious diseases or oncology, where the outcome can often get measured and observed in single cell lines ex vivo. Steadily growing computer processing power does help with some modelling in CNS research, but will most probably never allow for a full explanation of the expected outcome. 

Additionally, the vast majority of neurological disorders are considered chronic conditions needing long-term treatment. Therefore, the duration of clinical trials has to be sufficiently long to assess efficacy and safety for chronic use. To develop new drugs for neurological disorders, chemical entities and/or large molecules have to be able to penetrate or by-pass the blood brain barrier, adding another level of complexity. This means that development timelines for neurological drugs are usually long.

Patient enrolment and retention can also be a challenge. The ability to use technology as a novel digital endpoint becomes especially important in diseases such as Parkinson’s disease where mobility is impaired, because patients are limited in their ability to travel to study centres. Novel digital (wearable) technologies as alternative study endpoints facilitate this approach.

For research in areas such as Parkinson’s disease, digital endpoints may soon be used as primary endpoints, allowing for in-home clinical trials to be conducted over longer periods of time. Fewer activities at the sites and more assessments at the patient’s home are an appropriate approach to limit patient burden. 

In the near future, these ‘digital’ endpoints will be adequately valid to be used as primary endpoints, allowing the assessment of Parkinson’s disease symptoms over longer periods of time and a more naturalistic (patient’s home) environment. That should improve the sensitivity of the assessments and as a consequence also study power. 

Over the past 5 years ICON has conducted phase II & III studies in a range of CNS indications. To speak with one of our CNS experts, please contact us.


This blog is an edited version of “Parkinson’s disease clinical trials: Challenges, advancements, and the role of technology” which appeared in Outsourcing Pharma on 9 Jan 2019. To view the full article, please visit