Active patient engagement (PE) in which patients function as genuine partners in clinical trials – particularly in drug development – has gained enormous importance in recent years. Currently, PE is considered the gold standard in all phases of study design due to the growing awareness of the discrepancy between patient needs and research practice [1]. It is generally accepted that joint action between patient partners and academic researchers is crucial for enhancing the focus on patient-centered healthcare [1]. Zvonareva et al. [2] proposed a framework for conceptualizing the varying degrees of PE in drug research delineating four levels: consultation, involvement, collaboration, and patient-controlled. However, PE remains uncommon in the context of drug research trials. While a variety of disease areas are encompassed by trials that incorporate PE activities, many disease areas remain devoid of such activities in the context of drug research [2]. By actively engaging patient partners in determining how to conduct trials, it is more probable that unmet clinical needs will be addressed and that participant recruitment and adherence will be facilitated.

To the best of our knowledge, PE has not yet been applied in the design of a randomized controlled trial (RCT) investigating the effectiveness and safety of a compound in individuals with mild cognitive impairment (MCI). Mild cognitive impairment is defined as a decline in cognitive abilities that is significantly below what would be expected for an individual’s age and level of education. Frequently regarded as an intermediated phase between normal cognitive aging and dementia, MCI differs from dementia in that it is not accompanied by substantial limitations in activities of daily living (ADL) [3]. Nevertheless, MCI represents a notable alteration in health status and is associated with an elevated risk of progression to dementia with a progression rate of approximately 70% within five years [4]. Moreover, MCI is frequently associated with Alzheimer’s disease (AD), with 40–60% of individuals aged 58 and above diagnosed with MCI also exhibiting underlying AD pathology [5, 6]. A meta-analysis conducted by Jansen and colleagues [7] indicates that the prevalence of AD pathology is 20–30% higher in individuals with MCI compared to those with non-impaired cognition or subjective cognitive impairment, supporting the notion that MCI constitutes a risk condition for AD.

In many cases, direct PE is no longer feasible after the disease progresses and transitions into AD because medical decisions have to be made by patients’ legal representatives on behalf of the individual at this stage [8]. In contrast, people with MCI retain full legal competence. In light of the significant challenges posed by AD to both individuals and society [9], an evidence-based pharmacological treatment for MCI is urgently needed but is currently unavailable [10]. The fact that MCI is easy to diagnose provides the unique chance to implement a treatment that could potentially delay or reduce the probability of progression to AD.

The cannabinoid known as cannabidiol (CBD) has been identified as a promising candidate for slowing down the progression of MCI and therefore delaying the transition to AD due to its neuroprotective and anti-inflammatory properties [11]. In addition, CBD is safe and generally well-tolerated, largely due to its lack of untoward psychoactive sequelae. To date, only a limited number of studies have actively incorporated PE when examining the efficacy and safety of cannabis-based medicines across various indications [12]. Remarkably, approval of highly purified CBD (Epidiolex^®) to treat seizures in two rare forms of epilepsy (Lennox-Gastaut syndrome and Dravet syndrome) in 2018 was significantly initiated by the fact that the mother of Charlotte, a little girl with Dravet syndrome, had self-initiated adjunctive therapy with a high concentration of CBD from the tetrahydrocannabinol (THC) strain of cannabis to reduce the frequency of Charlotte’s seizures [13]. This case study impressively illustrates the benefits of engaging patients and their relatives or caregivers in initiating new pharmacological therapy strategies.

As part of our planned RCT investigating the effectiveness and safety of CBD in individuals with MCI, we aimed to directly involve patient partners in all steps of the study. To this end, we administered an online survey to individuals diagnosed with MCI who had participated in a recent trial at our center [14]. With this approach, we aimed to design an RCT that employs the most pertinent outcomes for participants, offers a more convenient approach to adverse events (AEs), and considers practical aspects such as acceptance of additional and invasive investigations.

Here, we present the results of the first online survey administered to people with MCI exploring their views on matters of convenience and their preferences regarding the setup of a clinical trial.