Allied Market Research expects the schizophrenia drugs market to exceed $12 billion by 2031, citing factors like expanding prevalence, an aging population and increases in R&D activities. While this increased investment is good news for drug developers and patients alike, there are complexities and challenges unique to schizophrenia that biomedical companies should consider as they plan and conduct clinical trials.

Assessment overload
Assessments are the measures used to determine the effectiveness of a therapy that is being investigated, and these assessments can be particularly daunting when studying schizophrenia.

If a research team is using a questionnaire, the process might require 10 or more assessments and scales being administered with overlapping topics and questions. A large number of assessments is challenging for both patients and administrators, and it can have a direct impact on data quality. In fact, a 2019 study found that conducting a high number of evaluations in a single day with small time intervals between evaluations was associated with lower compliance.

To reduce the number of questionnaires and ease the burden on trial participants, it is best to split up intense screening periods over two or three days and plan breaks between assessments so patients can remain fully focused and comfortable.

Due to the large volume of assessment data acquired in most schizophrenia studies, data transfers from vendors to data management may be delayed or the data may be incomplete, emphasizing the need to set clear data transfer agreements at the beginning of each study. Rater materials and assessment equipment, such as PDF copies of the scales and/or ePROs (electronic patient-reported outcomes), should also be on site prior to administering assessments and scales.

Strong training leads to strong data
Clinical trial raters and study coordinators are the evaluators who work directly with patients to assess the effectiveness of new medical treatments. These site personnel play a crucial role in maintaining patient interest in a study, making it crucial for them to get to know each patient on a personal level. This is particularly important for patients with schizophrenia, who often feel afraid or unable to trust others due to characteristics of the disease like paranoia, delusions, and hallucinations.

All raters should undergo training to understand outcome requirements, learn how to pose unbiased questions, and ensure consistency with their messaging and delivery. Principal investigators should take the lead in ensuring fellow staff are trained in a timely manner, attend refresher trainings, where required, and accurately report completion of those trainings. They should also perform at least one dry run for all raters and study coordinators.

As a result of COVID, decentralized clinical trials grew in popularity, along with the practice of at-home assessments and ePROs. While these methods have improved patient retention, the absence of on-site administration, accuracy and completion remains a concern. Open communication and responsiveness are key, and depending on the number of assessments being administered, it may be beneficial to activate multiple raters for a study (at least two unique raters per assessment).

Tapping the right experts
Selecting the right vendor to manage patient logistics (travel, hotels, transportation) is one worthwhile retention strategy, and some companies also find success offering minimal financial compensation (e.g. $10 per week) to ensure study adherence and consistent completion of all ePRO assessments at home. Contract research organizations (CROs) can also help biomedical companies avoid roadblocks that could impact a participant’s willingness to proceed with an assessment.

Effective retention is also closely connected to effective recruitment. Implementing recruitment strategies early in trial design can have a significant impact on enrollment. For example, a Phase 2a schizophrenia study conducted in 2018 resulted in over-enrollment of 23 participants, three months ahead of schedule, due to effective recruitment initiatives. The cost savings achieved by reaching these milestones offsets the additional costs of incentivizing patients for assessment completion, screen fail completions or communication efforts with the sites.

Tying it together 
As biomedical companies begin to plan schizophrenia studies, they should carefully consider and anticipate the challenges they may face. By aligning the right strategy with the right expertise, teams can more effectively advance novel treatments for schizophrenia through the regulatory process.

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Anne Waugh is a senior project manager at Rho, a global contract research organization (CRO) that provides a full range of drug development services. She has 12+ years of experience in clinical research, including CNS indications, with a focus on schizophrenia for the past 4.5 years. In a Phase 2a schizophrenia study, her team completed enrollment three months early and received a perfect score on their final client satisfaction survey. She is familiar with common scales and assessments, including PANSS, NAS-16, AIMS, MADRAS, among others, has overcome common delivery challenges in this complex indication, and maintains strong relationships with high-performing sites.