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While Case Report Forms are a main contributor to collected data, non-CRF data such as core laboratory data and central imaging can be critical to any clinical study.

Establishing Metrics and Standardization for Non-CRF Data in EDC

Video interview with Sepehr Shojaei, VP, Design Solutions, Lightship

Lightship's Approach to Accessible, Representative, and Impactful Clinical Trials

Lightship prioritizes patient accessibility and centricity in clinical trials, ensuring a seamless and positive experience for every participant. Learn more about:

Lightship's mission and core purpose as a company

How Lightship’s mobile nursing teams and home visits enhance study participation and retention

The role of mobile research units in the community and how they enhance participant education, accessibility, and convenience

Sepehr Shojaei, VP of Design Solutions at Lightship, talks about how the company works with pharma and contract research organization (CRO) partners to support clinical trials that are patient-first and accessible.

Latest Conference Coverage

Lightship’s Approach to Accessible, Representative, and Impactful Clinical Trials

Video interview with David MacMurchy, CEO of Lightship

Accelerate Inclusive Enrollment and Delivery with Lightship

Lightship focuses on patient accessibility and centricity in clinical trials, ensuring the patient experience is a positive one. Learn more about:

Lightship's impact on achieving diversity in clinical trials by engaging underrepresented patient populations

How Lightship utilizes hybrid and decentralized trial designs to reduce patient burden

The impact a patient centric model has on clinical trial participation and outcomes

David MacMurchy, Chief Executive Officer at Lightship, offers some insights into the company's mission toward improving equity and diversity in clinical trials. 

Boehringer Ingelheim has announced the start of the JADE Phase II clinical trial (NCT06769048), evaluating the efficacy and safety of BI 1584862 as a potential first-in-class treatment for geographic atrophy (GA). BI 1584862, a phospholipid modulator, was discovered and developed in-house by Boehringer. It intends to limit the growth of GA by targeting inflammation and preserving vascular function.

In a press release, Karl Csaky, MD, PhD, principal investigator of the Phase II trial and chief executive and medical officer, Retina Foundation of the Southwest, said: “Vision loss associated with geographic atrophy profoundly affects the lives of those impacted, particularly older adults, making daily activities more difficult. The loss of independence has a significant burden for patients, caregivers and society overall. I’m excited to see that Boehringer Ingelheim is exploring treatment options aimed at reducing the treatment and visit burden for patients and their caregivers. An oral treatment could alleviate the burden of existing treatment regimens and offer the opportunity to address both eyes simultaneously in patients with bilaterial disease.”

The JADE study is open to adults aged 55 years and older with GA that was diagnosed by imaging of the retina. It has four treatment groups comprised of multiple BI 1584862 doses and a placebo arm. The primary endpoint of the study is slope of change from baseline in square root transformed GA area as measured by fundus autofluorescence over a treatment period of up to 50 weeks. Participants will be in the study for one year.

In the press release, Patrick Bussfeld, MD, PhD, global head of medicine, eye health at Boehringer Ingelheim, added: “At Boehringer Ingelheim, we recognize the need for treatments that address the diverse needs of GA patients and of the medical community. Our commitment is reflected in our Phase II clinical trials investigating two distinct compounds, BI 1584862 and BI 771716, each targeting different pathways. This approach highlights our dedication to providing tailored solutions that support the individual needs of people living with the condition. By exploring multiple avenues, we are seeking to offer more individualized treatment options and, ultimately, improve the quality of life for people living with geographic atrophy."

As Bussfeld mentioned, Boehringer is evaluating another potential GA treatment in BI 771716. The investigational antibody fragment was developed by Boehringer along with technology licensed from CDR-Life. In September 2024, Boehringer announced plans to further advance the potential therapy following positive Phase I results. In the study (NCT06006585), BI 771716 achieved its primary safety endpoint following intravitreal administration of single and multiple doses.

In a press release from the time, Heiko Niessen, PhD, global therapeutic area head translational medicine & clinical pharmacology retinal health at Boehringer Ingelheim, said: “We are delighted to have achieved a critical milestone in our development of BI 771716, and are now preparing a Phase II clinical study to investigate efficacy and dosing. BI 771716 is part of our comprehensive retinal portfolio demonstrating our long-term commitment to preserving both eyesight and quality of life in people with retinal diseases.”

Charles C. Wykoff, MD, PhD, principal investigator of the Phase I trial, director of research at Retina Consultants of Texas; chair of research, Retina Consultants of America; and deputy chair of ophthalmology for the Blanton Eye Institute, Houston Methodist Hospital, added: “The development of new therapies for geographic atrophy remains one of the most important needs in the age related macular degeneration space. Achieving the Phase I safety endpoint is a meaningful step forward for this potential new treatment for people with this sight-threatening and life-affecting condition.”

1. ​​Boehringer Ingelheim starts Phase II study of its potential first-in-class oral compound as a treatment for Geographic Atrophy. News release. Boehringer Ingelheim. May 6, 2025. Accessed May 8, 2025. 

https://www.boehringer-ingelheim.com/science-innovation/human-health-innovation/phase-ii-start-oral-treatment-geographic-atrophy

2. A Study to Test Different Doses of BI 1584862 in People With a Distinct Form of Age-related Macular Degeneration (AMD) Called Geographic Atrophy. ClinicalTrials.gov. Accessed May 8, 2025. 

https://clinicaltrials.gov/study/NCT06769048?cond=BI%201584862&rank=5

3. Boehringer Ingelheim announces plans to advance potential new treatment for Geographic Atrophy, following positive Phase I results. News release. Boehringer Ingelheim. September 5, 2024. Accessed May 8, 2025. 

https://www.boehringer-ingelheim.com/science-innovation/human-health-innovation/geographic-atrophy-treatment-move-phase-ii

The JADE study will be evaluating BI 1584862, an investigational oral compound that targets inflammation and preserves vascular function.

Boehringer Announces Start of Phase II Geographic Atrophy Trial of Potential First-in-Class Therapy

In this video interview, Rob Jones product manager, TMF practice area, Pharmalex, discusses challenges the TMF space is currently facing and how it can utilize collaboration in making advancements. 

Battling Outdated Regulations in the Trial Master File Space

, Rob Jones, product manager, TMF practice area, Pharmalex, discussed challenges in the trial master file (TMF) space, highlighting outdated regulations such as ICH E6(R3). When it comes to innovation and compliance in the space, he stressed the importance of a risk-based approach, focusing on critical records and leveraging artificial intelligence for big data analysis. Moving forward, Jones believes the TMF community's collaborative nature can be viewed as a strength in navigating regulatory changes and technological advancements.

ACT: What are some challenges the TMF space is currently facing? How do you think they can be addressed?

It's a nice, broad question. I think really the biggest challenge is keeping up. I think right now we've got new regulations coming in, things like ICH E6(R3) have finally come in this year, after being delayed for a little bit because of other things that were going on in the early 2020s. We've got new proposed standards from the reference model with V4 and all of this while trying to balance that desire for innovation, cost effective solutions, just an ever-changing landscape. I think one of the things that we have to look at and admit is regulations have been a little out of step for a while. We were expecting ICH E6(R3) months, if not years ago, but again, due to things that got delayed. That's fine, but a lot of things have already passed it by. The EMA has already put in new guidelines around their perception of the TMF. They had a brilliant new guideline around computerized system validation, which included things like the electronic TMF. The MHRA have been giving us more and more feedback on their current public forums and Q&As and things like that. It's kind of a little too late in some ways, ICH E6(R2) came out in 2016, and even then it was only a small look there in the grand scheme of things, realistically, it was written back in 1996. I don't need to tell you how much has changed since 1996. My marker for a lot of these things when I talk with people, is the first iPhone came out in 2007, so anything post-2007, you have had constant satellite communication world in your pocket. We're an industry that's built on stability, order, organization, we're managing clinical trial documents, but this new world hasn't been that for a long time, it's messy in a lot of ways.

The challenge really is, what do we do when the regulations are a little bit too old and outdated? How do we manage when other industries, especially outside of clinical trials, are just flying by, and what can we do to keep up without jeopardizing people's comfort, without jeopardizing all of the hard work that's gone into it? I think the nice thing really, with the TMF, and this shows every single time I go to a conference. It is one of the very few parts of clinical trials where it's an open book. There is a real community behind everything. Everyone's talking to each other. You go and talk with people, and they will tell you that TMF stands for “too much fun.” They'll tell you that TMF stands for “too many friends.” There is really this idea of everyone's in it together. I think the nice thing with that is that's been built from the beginning. The reference model when it came up was sponsors, CROs, vendors, consultants, all working together, sharing what they were doing. Nothing was secret. Nothing was hidden behind closed doors. I think, really, that is the biggest strength, and that's how we can address this ever-changing landscape, if we all come to get together and make a bit of a collective decision and say, “We as a group are going to make an interpretation of this, and this is how we're going to take it forwards.” There's a little bit where perception becomes reality, and if we're all pushing in that same direction, that really helps with how we can address all of this. I think, again, just for the TMF world, that's really how we're going to get by with these things changing at such a rate. It's one of the biggest strengths of our little, niche part of the industry.

In this video interview, Rob Jones, product manager, TMF practice area, Pharmalex, discusses challenges the TMF space is currently facing and how it can utilize collaboration in making advancements. 

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.

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.

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.

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.

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.

, PhD, director, project management, medical device and diagnostics research; and 

, BSCS, RAC, senior manager, regulatory affairs; both with ICON

With close collaboration between sponsors, CROs, and regulators, this emerging technology has the potential to greatly improve the lives of patients.

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

View the Applied Clinical Trials April 2025 issue in an interactive format.

Pratibha Potare

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