Clinical Strategies to Optimize Software as a Medical Device to treat Mental Health

Devin Ridgley, PhD, Director, Project Management, Medical Device and Diagnostics Research, ICON

JoAnne Bronikowski, BSCS, RAC, Senior Manager, Regulatory Affairs, ICON

Awareness of mental health disorders has significantly improved in recent decades in the US. Due to this elevated awareness there has been an increase in diagnoses, opening the door to new clinical interventions. According to the National Institute of Health, 22.8% of Americans over the age of 18 experience a diagnosable mental health disorder in any given year. Anxiety disorder affects 19.1%, while 8.3% suffer from depressive illnesses annually. Schizophrenia and psychotic disorders are rarer (0.25%-0.64%), however they can have an outsized impact on society. Schizophrenia is one of the top 15 leading causes of disability globally. No matter the diagnosis, mental health disorders affect the quality of life of the patient and their families.

Opportunities of SaMD use to treat mental health

In parallel with greater awareness and diagnoses, there have been major technological advances resulting in increased processing power in smaller devices. Digital health is transforming the healthcare industry, with software aiding the diagnosis and treatment of illnesses. Software as a medical device (SaMD) enhances patient and healthcare provider access to real-time health information, enabling earlier diagnosis and access to a broader range of treatment options. Treating mental health disorders using SaMD is being studied in controlled research environments for indications including major depressive disorders and schizophrenia. The development of smartphone applications is an encouraging new avenue to treat these conditions.

Challenges of integrating SaMD in clinical trials

As with developing any new treatment, there are challenges when integrating these technologies into clinical trials. Any potential risks and benefits must be weighed carefully, as they are in other clinical trials. SaMD as a treatment for mental health disorders has additional challenges related to the target patient population. Issues of consent, ethical considerations and patient recruitment need to be handled with special care due to the vulnerabilities of the patients.

For SaMDs to treat mild mental health disorders the issue of mental capacity and trial informed consent can proceed as in a traditional clinical trial. However, some of the patients who potentially have the most to gain from using SaMD have more severe mental health disorders impacting their mental capacity to provide informed consent. A legally authorized representative may be necessary to provide informed consent for trial participation. Sponsors must implement standardized assessments of patient mental capacity to give consent. There are several acceptable scales which can be used to screen potential trial participants, including the Clinical Global Impression and World Health Organization Disability Assessment Schedule 2.0. Disorder-specific scales can also be employed to assess the risk and benefit of a clinical trial inclusion for each patient. Furthermore, it is important to incorporate scales that assess patient mental stability and safety, such as the Columbia Suicide Severity Rating Scale.

Patients with compromised mental health often have cognitive impairments and may be overwhelmed by SaMD technology. These patients may struggle with adoption and/or adherence to SaMD treatment requirements. Thus, a lack of human factor/usability understanding can negatively impact the value of SaMD technologies to clinical trials affecting patient outcomes and the quality, validity, and reliability of data. During SaMD design and development, the patients’ technological capabilities to comply with the SaMD treatment requirements (abilities to understand and use a smartphone, tablet or laptop application), need to be assessed. This assessment should be strongly considered (at a minimum) during the development of the SaMD as the understanding of human factors and usability risks will directly impact the efficacy of the treatment. For trials incorporating already available SaMDs, prior to enrolment and randomization, standardized assessments can provide a uniform evaluation across multiple sites to mitigate the risk of the impact of technology adoption and adherence on trial success.

Technical considerations

Data is essential to the success of any clinical trial. When performing clinical trials of SaMD digital therapeutics, the device used must be capable of tracking user data per patient to ensure protocol compliance. The data gathered by the trial application version is likely to be more comprehensive than the original product design specifications to meet trial primary end points. Equally importantly, the developer must take extra measures to ensure that patient protected health information is safeguarded. This can be done with a comprehensive review of SaMD access restrictions, access reviews, and retention term across the sponsor’s integrated systems for data storage and processing.

Sponsors need a multifaceted approach to training and technical support for the SaMD trial. No one team can be responsible for both the training and technical support required for a clinical trial of the SaMD digital therapeutic. A collaborative, proactive approach by the sponsor and clinical research organization (CRO) will ensure that all sites and patients are appropriately trained. A common avoidable mistake is expecting the clinical team to troubleshoot technical issues with the SaMD when they occur. Appropriate expert technical support should be available to the CRO, sites, investigators, and/or patients. The sponsor and CRO should proactively anticipate potential risks and put mitigation measures in place.

Patient recruitment

In all clinical trials the ability to optimize and predict enrolment by the target patient population is a critical factor. SaMD studies introduce additional variables which are not present in other studies. Collaboration between the sponsor and a CRO to identify multiple potential sites and principal investigators (PI) is an important first step to addressing this issue. Targeting a single site “type” for a given SaMD protocol places an unnecessary risk if the target site/PI criteria are wrong for this patient pool. Sponsor and CRO collaboration to evaluate a diverse set of sites for inclusion can mitigate this risk. Seamless, clear communication between site staff, sponsor, and the CRO will ensure that feedback and recommendations are actioned. To prevent patient dropout and the risk of timeline extensions, stipends for participation and reimbursement of transport costs should be considered.

Regulatory considerations

The level of regulatory control is dependent on the risk level associated with the healthcare decisions made in response to the data provided by the software application. The FDA regulates an app as SaMD when it makes claims regarding the diagnosis or treatment of a mental health condition. Clinical data will likely be required to support the safety and effectiveness of these SaMDs. The clinical evaluation will closely examine SaMD inputs, algorithms, and outputs via clinical association validation, analytical/technical validation, and clinical validation. Sponsors must provide evidence demonstrating the SaMD’s ability to deliver clinically meaningful and accurate results relevant to its intended use. Clinical validation should confirm that the SaMD fulfils its intended purpose within the target population and the specific clinical care context for which it was designed.

Conclusion

SaMDs have the potential to improve the lives of patients managing mental health disorders, by providing accessible, scalable, patient-centered treatment options. Clinical trials will always have unexpected challenges and SaMD trials are no exception. These studies require additional measures to address ethical and consent considerations due to a vulnerable patient population. Additional technical and regulatory support through partnerships with a CRO allows sponsors greater adaptability to changing circumstances. Close collaboration between the sponsor and CRO can optimize patient recruitment, study budget, study timelines, and pathway to market for a new or enhanced SaMD.

Devin Ridgley, PhD, director, project management, medical device and diagnostics research; and JoAnne Bronikowski, BSCS, RAC, senior manager, regulatory affairs; both with ICON