In short
- Running clinical trials in neurology isn’t easy. Patients present with diverse deficits, endpoints are subjective (requiring specialist training), and enrolling the right patients is a constant challenge
- Collaborating with a specialized neuroscience CRO is the difference between success and failure.
- PSI’s expert guidance helped bring treatments for life-changing neurology conditions to market
- Case study 1: Cervical dystonia
- For patients with cervical dystonia, PSI’s innovative training program and follow-up helped keep potentially challenging endpoint results consistent and accurate, ensuring the sponsor’s therapy was approved well within projected timelines
- Case study 2: Stroke
- PSI’s stroke expertise, coupled with a focus on quality and compliance, meant rapid global approval of the sponsor’s treatment for upper limb spasticity
Clinical trials in neurology: Complexity from the onset
Running a trial in neurology is filled with complexity, and finding a CRO with the experience needed to help you reach your milestones on time isn’t straightforward. Neurology studies are highly specialized, heterogeneous, and difficult.
- Patients can have multiple neurological deficits (motor, cognitive, sensory, and speech)
A CRO with experience in neurology can aid the sponsor in designing the optimal inclusion/exclusion criteria that balance the needs of the sponsor (scientific rigor) and the needs of the patient (avoiding overly restrictive or impractical recruitment goals) - Patients with neurological conditions have long disease trajectories, slow recovery, and variable response to therapy
CROs experienced in neurology can guide the sponsor in choosing clinically meaningful and regulator acceptable endpoints and comparators - Neurology endpoints often require trained and capable assessors
For example, the gold standard for measuring improvement in spasticity post-stroke requires manual assessment using established clinician-rated spasticity scales, and therefore is subject to differences in physician raters [1]. An experienced CRO can provide and coordinate the needed training and cohesion to ensure measurement of endpoints is scientifically valid and comparable - As endpoints can be subjective, regulatory authorities pay particularly close attention to neurology trials, and require more deliberation and discussion with review boards
A CRO with a track record in neurology adds credibility to the sponsor, and can help demonstrate to regulators and indeed investigators that the trial will be of the highest scientific and ethical standards, especially regarding informed consent - These patients have more comorbidities and are on more medications than those from other therapeutic areas
It is important that the CRO understands this – finding and retaining patients using knowledge of care pathways and referral networks, and then handling adverse events through monitoring and effectively manage comorbidities and polypharmacy is critical - Specialist sites are frequently required to get the right patients for the trial
Your CRO must have an established, global network to be able to select the right sites, KOLs, and PIs to ensure on-time enrollment
Finding the right CRO to match with is the difference between success and failure.
Read on for two case studies across distinct neurology indications for different sponsors, focussing on cervical dystonia and stroke.
Mini case study 1: Cervical dystonia
The challenge
Cervical dystonia is a neurological movement disorder characterized by abnormal head postures due to aberrant neck musculature contractions. The most common form of adult-onset focal dystonia, cervical dystonia is mainly caused by a series of genetic and environmental factors [2]. The wide variation in clinical presentation, coupled with a lack of clear diagnostic criteria, often lead to delays in diagnosis (and treatment) [3]. A relatively small patient population and narrow eligibility criteria can impact enrollment.
Despite cervical dystonia being a new indication for PSI at time of award, the sponsor felt confident in PSI’s capabilities and neurology expertise.
The solution: Collaboration and innovation
The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is used to rate severity, disability and pain in patients with cervical dystonia. Obstacles to proper TWSTRS use include complexity and standardization, and subjectivity. PSI held training sessions (in-person, and virtual) to ensure all investigators would be able to provide the same evaluations, to the same standard, to ensure accurate and consistent data. The pioneering TWSTRS training included:
- Role-playing for simulated (and real) patient interviews to establish baselines for Disability and Pain subscales – including training in neutral interview techniques to avoid biasing responses
- Hands-on workshops with trained movement disorder specialists
- Certification testing (rating standardized videos) so investigators can meet reliability thresholds
- Ongoing quality control through periodic retraining, and frequent data audits
The outcome
The trial was completed on time, and the sponsor’s treatment was approved globally within approximately 3 years from study award to PSI.
Mini case study 2: Ensuring quality in a trial for post-stroke upper limb spasticity
The challenge
Stroke (impaired blood flow to the brain, either due to ischemia or hemorrhage) disrupts proper brain function [4], and survivors often face long-term complications [5]. Post-stroke spasticity is generally defined as velocity-dependent muscle overactivity [6]. Spasticity is relatively common, affecting 19%–92% of stroke survivors [6], and patients experience involuntary muscle contractions that severely compromise their ability to move [5].
Reducing the stiffness associated with post-stroke spasticity can help patients regain some level of control over their lives; locally administered neuromodulating therapies are the most commonly used non-surgical treatment [7]. Heterogeneity of the disease, combined with concomitant patient medications, comorbidities, strict inclusion criteria, and a general lack of awareness are notable challenges for running clinical trials in these patients.
The sponsor selected PSI to run their trial based on CNS experience.
The solution: Quality and compliance
Neurology is a broad specialty, often with little crossover between disciplines. Rehabilitation medicine specialists (physiatrists) treat these patients by focusing on the management of their condition through medications, procedures, or physical therapy.
- For the sponsor and PSI, developing, maintaining, and training a network of rehabilitation medicine specialists was essential. Access to the right physicians at the right centers built credibility and trust for patients
- One risk with the use of relaxant therapies is asphyxia from systemic spread effects. While the sponsor’s therapy is for limb spasticity, careful training in the specialized administration procedures required for the therapy is still required, both pre- and post-administration. Investigator variability can exist in examiner-driven assessment parameter [1]
- PSI ran complex, multidisciplinary, in-person investigator meetings involving CRAs, regional leads, MMs, PIs, and other KOLs to deliver training in (a) administration procedures and (b) consistent evaluation of the treatment effect. Up to 500 people attended each meeting, and the team organized them into small groups of five to seven people per station, which proved challenging. PSI’s expertise enabled these meetings, some of the most complex ever conducted by PSI, to run smoothly, ensuring high-quality data collection during the trial itself
The outcome
Again, the trial met its milestones on time, and the sponsor’s product was approved for use around the world in multiple patient populations, including more challenging subgroups.
Today, PSI continues to collaborate with the same biopharma sponsors and is currently enrolling on new trials.
Our PSI meetings team did an excellent job, and the clinical team—including our CRAs, managers, co-managers, and regional leads—handled everything exceptionally well. The client was very pleased with the outcome, and their feedback reflected how strongly they felt about the quality of our work. We have more investigator meetings planned in different parts of the world in the coming months, we look forward to continuing this successful collaboration.
Key takeaways
Conducting neurology clinical trials is complex, due to the diverse and specialized nature of the studies, and the variability of patients. Collaborating with an experienced CRO is the difference between success and costly setbacks. PSI is your guide: Providing practical advice on trial design, performing feasibility assessments to troubleshoot enrollment, and navigating training, regulation, and compliance challenges.
From start to finish, partnering with an experienced CRO is what turns complexity into clarity. Contact PSI to make sure your neurology trial runs on time, and produces the data you need for approval.
Enroll your pivotal neurology trial on schedule with PSI
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Abbreviations
CRA, Clinical Research Associate;
CNS, central nervous system;
CRO, Contract Research Organization;
KOL, Key Opinion Leader;
MM, Medical Monitor;
PI, Principal Investigators.
References
1. Zurawski, E., et al., Interrater Reliability of the Modified Ashworth Scale with Standardized Movement Speeds: A Pilot Study. Physiother Can, 2019. 71(4): p. 348–354.
2. Defazio, G., et al., Descriptive epidemiology of cervical dystonia. Tremor Other Hyperkinet Mov (N Y), 2013. 3.
3. Jog, M., et al., Causes for treatment delays in dystonia and hemifacial spasm: a Canadian survey. Can J Neurol Sci, 2011. 38(5): p. 704–11.
4. Hilkens, N.A., et al., Stroke. Lancet, 2024. 403(10446): p. 2820–2836.
5. Chohan, S.A., P.K. Venkatesh, and C.H. How, Long-term complications of stroke and secondary prevention: an overview for primary care physicians. Singapore Med J, 2019. 60(12): p. 616–620.
6. Francisco, G.E., et al., Post-Stroke Spasticity, in Clinical Pathways in Stroke Rehabilitation: Evidence-based Clinical Practice Recommendations, T. Platz, Editor. 2021, Springer Copyright 2021, The Author(s). Cham (CH). p. 149–73.
7. Li, H.X., et al., Current techniques for the treatment of spasticity and their effectiveness. EFORT Open Rev, 2025. 10(5): p. 237–249.
