Clinical Trial Sponsors Research Articles

Évaluation des dépenses du circuit des produits de santé dans le cadre d’études institutionnelles – Étude de cas au CHU de Toulouse

Clinical research faces complex and unpredictable budgetary challenges, despite its central role in the development of healthcare products. This retrospective study examines the estimated and actual costs of 13 trials managed by the Clinical Trials Coordinating Pharmacy at the University Hospital of Toulouse. It aims to assess the accuracy of estimates, identify trial-influencing events and identify budget adjustment variables. The results show that only two of the 13 studies stay within their initial estimates, with most exceeding their projected margins. Costs vary by area, with shipping and packaging in particular exceeding the initial budget, while distribution costs are more accurately estimated. Several factors influence costs, including study duration, centre locations, number of enrolments, product stability and protocol amendments. Extending the study duration leads to increased costs in all areas, while reducing the number of inclusions tends to be in line with the original budget. In conclusion, budget management in clinical trials is complex due to numerous influencing variables. Careful planning and consideration of the specifics of each trial are crucial for more accurate estimates and budget adherence. This study enhances the understanding of the financial challenges faced by institutional sponsors of clinical trials and contributes to the refinement of budgeting methods for future clinical trials.

A reactogenic "placebo" and the ethics of informed consent in Gardasil HPV vaccine clinical trials: A case study from Denmark.

Medical ethics guidelines require of clinical trial investigators and sponsors to inform prospective trial participants of all known and potential risks associated with investigational medical products, and to obtain their free informed consent. These guidelines also require that clinical research be so designed as to minimize harms and maximize benefits. To examine Merck's scientific rationale for using a reactogenic aluminum-containing "placebo" in Gardasil HPV vaccine pre-licensure clinical trials. We examined the informed consent form and the recruitment brochure for the FUTURE II Gardasil vaccine trial conducted in Denmark; and we interviewed several FUTURE II trial participants and their treating physicians. We also reviewed regulatory documentation related to Gardasil vaccine approval process and the guidelines on evaluation of adjuvants used in human vaccines. It was found that the vaccine manufacturer Merck made several inaccurate statements to trial participants that compromised their right to informed consent. First, even though the study protocol listed safety testing as one of the study's primary objectives, the recruitment brochure emphasized that FUTURE II was not a safety study, and that the vaccine had already been proven safe. Second, the advertising material for the trial and the informed consent forms stated that the placebo was saline or an inactive substance, when, in fact, it contained Merck's proprietary highly reactogenic aluminum adjuvant which does not appear to have been properly evaluated for safety. Several trial participants experienced chronic disabling symptoms, including some randomized to the adjuvant "placebo" group. In our view, the administration of a reactive placebo in Gardasil clinical trials was without any possible benefit, needlessly exposed study subjects to risks, and was therefore a violation of medical ethics. The routine use of aluminum adjuvants as "placebos" in vaccine clinical trials is inappropriate as it hinders the discovery of vaccine-related safety signals.

Legal Regulation оf Insurance оf Clinical Trials оf Medicinal Products іn Ukraine

The article examines the current state and prospects of development of insurance for clinical trials of medicinal products in Ukraine, and also substantiates the need to introduce certain types of insurance in this area. As a result of a systematic analysis of current legislation, scientific literature and international acts, the author classifies persons participating in clinical trials of medicinal products into: 1) clinical trial subjects and 2) participants of such a scientific and medical experiment. In addition, the author outlines the main risks that arise for individual trial participants throughout the entire dynamics of clinical trials of medicines and proposes to minimize them by: changing the regulatory approach to making insurance mandatory by clarifying the subject matter of the insurance contract (insurance of liability of the investigator and sponsor of clinical trials); introduction of property insurance and liability insurance of manufacturers of medicinal products with state support; introduction of professional liability insurance of the investigator/co-investigator of clinical trials of medicinal products; introduction of insurance of investment and financial risks in the field of clinical trials of medicinal products with state support. It is also established that the peculiarities of the legal status of clinical trial participants, the specifics of their interests, and the need to participate in the trial influence the formation of the theory of multiple risks arising in the course of a clinical trial of a medicinal product and can be manifested as cases with negative consequences. The theory of multiple risks makes it possible to group them into different areas depending on the criterion of personalization (status of a person participating in a medical experiment: subject/ participant): 1) personal risks; 2) property risks; 3) liability risks.

519 Strategic Reinvestment of Sponsored Trials Residuals for Research Portfolio Development

OBJECTIVES/GOALS: Academic research is often viewed as a necessary core mission but a financial loss requiring central or clinical funds support. We present cases as evidence of sustaining academic unit research endeavors through strategic planning and reinvestment of sponsored clinical trials residuals. METHODS/STUDY POPULATION: Successful endeavors are presented that demonstrate strategic reinvestment of clinical trials residuals to develop robust academic self-sustaining research programs. A multi-year strategic plan was developed leveraging residuals from sponsored clinical trials to build an academic research infrastructure supporting extramural grant applications, pilot studies, pre- and post-award management, equipment investment, and faculty incentives. RESULTS/ANTICIPATED RESULTS: Example 1, pooling four existing department clinical trials generated yearly profits that expanded clinical trials capacity and used residuals to support a grant coordinator. Over 7 years, trial volume increased to near 50, revenue increased to $2.5 million annually, staffing increased to 20 FTEs, and extramural grant applications increased from 16 to 50. Example 2 started with a department with no infrastructure. Central support was leveraged for 6-months to support a coordinator to initiate a clinical trials program. The initial investment was offset by trials earnings by year 2, breaking even financially, while establishing a nascent yet robust infrastructure to build autonomously without additional central funding requests. DISCUSSION/SIGNIFICANCE: Utilizing sponsored clinical trials as a strategic investment fund, academic units can realize fiscally responsible expansion of research activities and national recognition through acquisition of extramural funding and investigator-initiated investigations.

Abstract 999: Clinical trial matchmaking: Connecting sites to sponsors

Abstract Background: Oncology programs may encounter many challenges engaging in clinical trials. The Association of Community Cancer Center’s (ACCC) Community Oncology Research Institute (ACORI) conducted a survey to gather insights on barriers to clinical trial provision and implementation, patient recruitment, and identifying resources to support cancer programs. Methods: A survey of 29 questions was administered via Qualtrics. The survey focused on research-naïve sites (i.e., sites with little to no clinical research experience). Survey recipients were identified from ACCC’s membership database, and the survey was open from May 5 to October 10, 2023. One survey response was captured per program. Results: Of the 350 respondents, most were physicians, investigators, or oncology fellows (20%), directors/administrators (16%), patient navigators (12%), and APPs (12%). Responding programs were categorized as a comprehensive community cancer program (28%), community practice (26%), or academic medical center (21%). Eighty percent of respondents indicated their program currently conducts clinical research. The most common challenges included: patient recruitment (40%), limited staffing (36%), limited clinician time (32%), and lack of training in research administration and conduct (25%). The top 3 resources desired were communication about clinical research opportunities (65%), connections to clinical trial sponsors (49%), and clinical research coordinator training (41%). Conclusions: Survey results showed a clear need for improved communication regarding clinical research opportunities, connections to clinical trial sponsors, and education around clinical trial implementation. Data from this survey will be used to match sites with trial sponsors, especially sites that serve patients with cancer from under resourced geographic, socioeconomic, racial, and ethnic groups. Future efforts will seek to engage clinical trial sponsors in improving trial engagement and feasibility, workforce support, training, and clinical mentorship. Citation Format: Lyndsey Griffin, Latha Shivakumar, Leigh Boehmer, Savannah Dodson, Elana Plotkin, Sumanta Pal, Al B. Benson. Clinical trial matchmaking: Connecting sites to sponsors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 999.

Exploring the divergence in perspectives on clinical trial operations in South Korea during the COVID-19 pandemic: a comparison of a trial site and sponsors.

During the COVID-19 pandemic, novel clinical trial methods known as decentralized clinical trials (DCTs) were rapidly introduced. The attitude toward operating clinical trials and perspectives on DCTs may differ between clinical trial sites and sponsors. The impact of the COVID-19 pandemic on clinical trials was investigated for a society of sponsors and a trial site in South Korea. The current difficulties and future perspectives on clinical trials were assessed and compared between the site and sponsors. Both the site and sponsors reported on their experiences with the challenges of conducting clinical trials during the pandemic era. While 64% of personnel from the site judged that the difficulties were solved by their own solutions, 67.6% of personnel from sponsors considered cooperation with trial sites as a key solution to overcome the difficulties. While half of the personnel from the site were skeptical of the changes in trial operation methods, the sponsors expected the institutionalization of DCT elements. In conclusion, with varying attitudes, sponsors and sites attempted to overcome the challenges of conducting clinical trials during the pandemic era. To conduct clinical trials effectively, both sponsors and sites must work closely together to find solutions with efficient communication. For the successful implementation of new tools such as DCTs, the government needs to solicit support from sponsors and sites and change regulations.

Operational Differences between Product Development Partnership, Pharmaceutical Industry, and Investigator Initiated Clinical Trials.

Medicine development is a lengthy endeavour. Increasing regulatory stringency and trial complexity might lead to reduced efficiency, dwindled output, and elevated costs. However, alternative models are possible. We compared the operational differences between pharmaceutical industry sponsored trials, product development partnership trials, and investigator-initiated trials to identify key drivers of inefficiency in clinical research. We conducted an exploratory mixed-methods study with stakeholders, including clinical trial sponsors, contract research organisations, and investigators. The qualitative component included 40 semi-structured interviews, document reviews of 12 studies and observations through work shadowing in research institutions in Burkina Faso, Mali, and Switzerland. The findings were triangulated with an online survey polling clinical research professionals. The operational differences were grouped under five categories: (i) trial start-up differences including governance and management structure; (ii) study complexity; (iii) site structural and organisational differences; (iv) study conduct, quality approaches, and standard operating procedures; and (v) site capacity strengthening and collaboration. Early involvement of sites in the planning and tailored quality approaches were considered critical for clinical operations performance. Differences between the types of trials reviewed pertained to planning, operational complexities, quality approaches, and support to the sites. Integration of quality-by-design components has the potential to alleviate unnecessary process burden.

Clinical trials are becoming more complex: a machine learning analysis of data from over 16,000 trials

The past decade has seen substantial innovation in clinical trials, including new trial formats, endpoints, and others. Also there have been regulatory changes, increasing competitive pressures and other external factors which impact clinical trials. In parallel, trial timelines have increased and success rates remain stubbornly low. This has led many observers to question whether clinical trials have become overly complex and if this complexity is always needed. Here we present a large-scale analysis of protocols and other data from over 16,000 trials. Using a machine learning algorithm, we automatically assessed key features of these trials, such as number of endpoints, number of inclusion–exclusion criteria and others. Using a regression analysis we combined these features into a new metric, the Trial Complexity Score, which correlates with overall clinical trial duration. Looking at this score across different clinical phases and therapeutic areas we see substantial increases over time, suggesting that clinical trials are indeed becoming more complex. We discuss drivers of increasing trial complexity, necessary or helpful (‘good’) complexity versus unnecessary (‘bad’) complexity, and we explore mechanisms of how sponsors of clinical trials can reduce trial complexity where appropriate.

Probability of Regulatory Approval Over Time: A Cohort Study of Cancer Therapies.

New cancer therapies are frequently evaluated in multiple disease indications. We evaluated whether the probability of achieving US Food and Drug Administration (FDA) approval for a new cancer therapy changes with time. We identified a cohort of anticancer drugs with a first registered efficacy trial from 2007 to 2011 on ClinicalTrials.gov. We downloaded all clinical trials for each included drug from the initiation of efficacy testing to January 11, 2021. Each trial was categorized by cancer indication and assigned to investigational trajectories on the basis of unique drug-indication pairings. We performed a univariate Cox's proportional hazards regression to assess the probability of a trajectory leading to regulatory approval over time since initiation of the first efficacy trial for a given drug. We included 213 drugs in our cohort, of which 37 (17.4%) received FDA approval in at least one oncology indication. In our primary analysis, we found a 15% decrease in the probability of approval for every year since initiation of the first efficacy trial (hazard ratio [HR], 0.85 [95% CI, 0.73 to 0.99]; P = .032). We found a 45% increase in the probability of approval for the first trajectory launched for a given drug in comparison with all others (HR, 0.55 [95% CI, 0.33 to 0.91]; P = .021). Drug-indication pairings pursued years after initial testing for efficacy have lowered probability of affecting care. Clinical trial investigators, sponsors, and regulatory bodies may benefit from awareness of this trend when considering both early and late trajectory trials in a drug's development.

Abstract A033: Use of a novel healthtech platform to record patient-reported needs in real time

Abstract Background: Financial toxicity refers to the challenges that a patient faces due to the high costs of medical care. BIPOC (Black, Indigenous, and People of Color), rural, and other vulnerable populations often bear a disproportionate burden when diagnosed with a chronic disease. As a result, these populations often experience financial toxicity at higher rates. The estimated annual costs of health disparities in the U.S. are $1.24 trillion. Financial toxicity and logistical barriers that affect daily life, such as transportation, family care, rent, and home maintenance, can negatively affect a patient’s life. Many clinical trial sponsors and patient advocacy groups focus on providing support to patients around these barriers, but services are often generalized and provided in a ‘one-size-fits-all’ format, which may not be beneficial on an individual level for each patient. In 2023, together with health IT provider The WiTT Group, Tigerlily launched the innovative web-based Resources and AssIstance for Support and Empowerment (RAISE) platform, which brings together the best of wedding registry, crowdsourcing, and digital payment concepts and tools to match patients with the non-clinical services they need in real time as they go through treatment. With RAISE, Tigerlily empowers Black women with breast cancer to specify needs in their registry in real time, delineated by the time and urgency of each need. Our research question is, “What is the relationship between patient informed financial and non- financial stressors and patient's geographical location, age, cancer sub type and staging?" Methods: Tigerlily captured the “voice of the patient” using user-generated profiles and patient-identified needs on the RAISE platform. Patient-submitted data during the months of May through July 2023 was analyzed. Results: Patients (n=60) documented current financial and non-financial stressors and challenges, as well as other impacted areas of their daily life. Preliminary results indicate that financial costs associated with groceries, insurance copays, and out-of-pocket medication costs were the most requested needs. Additionally, patients reported rent/mortgage, groceries, and childcare as the most financially necessary needs. Conclusions: RAISE allows breast cancer patients from BIPOC, rural, and other vulnerable populations to specify their needs on an individual basis. The most urgent and frequent patient-reported needs were. This approach will be used to inform community-based organizations, advocacy partners, and healthcare providers about patient-reported needs in their communities in order to guide the development of support programs and services. Future research will compare the impact of meeting patient-reported needs on outcomes such as quality of life and the impact of patient-identified stressors. Citation Format: Katherine Cornish, Mary Stober Murray, Maimah Karmo, Jeanne Regnante, Virginia Leach. Use of a novel healthtech platform to record patient-reported needs in real time [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A033.

Rising pharmaceutical innovation in the Global South: a landscape study

BackgroundThere is growing interest in pharmaceutical innovation in low- and middle-income countries (LMICs), but information on existing activities, capacities, and outcomes is scarce. We mapped available data at the global level, and studied the national pharmaceutical innovation systems of Bangladesh and Colombia to shed light on pharmaceutical research and development (R&D) in the Global South, including challenges and prospects, to help fill existing knowledge gaps.MethodsWe gathered and analyzed data from three types of sources: literature, semi-structured interviews with key informants, and publicly available data on R&D funding, R&D scientific capacity measured by human resources, and clinical trial activities.ResultsPharmaceutical R&D activities are occurring in many LMICs, but 16 countries have emerged as frontrunners. Investment in R&D in LMICs has increased in the past decade, particularly from middle-income countries (MICs). Capacity is also growing, with an increase in the number of research organizations and the amount of funding available from external sources. The total number of clinical trials and the proportion of trials in LMICs increased markedly, and there is also growing activity in the earlier, more innovative and riskier Phase 1 and 2 trials. Non-commercial entities comprise the majority of clinical trial funders and sponsors in LMICs. Finally, investments have borne fruit, as indicated by a number of innovative medicines developed in LMICs. The Bangladesh and Colombia country studies showed that there is still a need for both targeted R&D policies to strengthen capacities in the pharmaceutical sector, and more government support to overcome the challenges of a lack of funding and coordination among different actors.ConclusionsBy triangulating between the data sources, it was possible to paint a broad picture of who was involved in pharmaceutical R&D in LMICs, in which particular countries, for which diseases, in which R&D phases, and with what results—as well as how these trends have changed over time. Prioritizing pharmaceutical R&D is an important strategy for better meeting health needs. The trendlines are promising, but focused attention is still needed to realize the potential for greater innovation in the Global South.

The Lived Experience of Pediatric Gene Therapy: A Scoping Review.

Little is known about patients' and families' lived experiences of participating in pediatric gene therapy (GT) clinical trials. Currently, pediatric GT research targets a broad range of indications--including rare and ultra-rare diseases--which vary in severity and in the availability of alternative therapies. Pediatric GT differs meaningfully from adult GT because the decision to participate involves a dyad of both the child and parent or caregiver/s. It is critical to understand patients' and caregivers' perceptions and experiences of social, emotional, physical, and logistical burdens or benefits of participating in such trials, and how they weigh and prioritize these factors when deciding whether to participate. We conducted a scoping review of the current literature in this subject area with objectives to (1) provide an overview of existing literature, (2) identify gaps and areas for further research, and (3) better understand the lived impact of pediatric GT research on patients and their parents/caregivers. Four themes emerged, including (1) weighing risks and benefits (2) timing of GT trial participation, (3) value of clear communication, and (4) potential impact on quality of life. Notably, our sample surfaced articles about how patients/parents/caregivers were thinking about GT-their understanding of its safety, efficacy, and risks-rather than accounts of their experiences, which was our initial intention. Nevertheless, our findings offer useful insights to improve the informed consent process and promote a more patient- and family-centered approach. Moreover, our findings can contribute to patient advocacy organizations' efforts to develop educational materials tailored to patients' and families' expressed informational needs and perspectives, and can inform more patient- and family-centered policies from GT clinical trial sponsors.

2017-2023: state of the art of gene therapies in rare diseases in Europe: the dynamics of clinical R&D, new approved treatments and expected therapies in the pipelines

Aim: Gene therapies have been tested over the past three decades, and after a first market authorization in 2017, the field is starting to deliver. The study aims to analyze the current development dynamics of gene therapies for rare diseases using the GENOTRIAL database®, which gathers information on gene therapy clinical trials and studies conducted between 2017 and 2023 in Europe. Methods: The study involved extracting and filtering clinical trial data from the EudraCT database. Trials with the keyword "Gene Therapy" were selected and filtered using the "Rare disease" filter. Manual verification was conducted to ensure that the selected trial only concerned gene therapy treatments authorized in Europe for rare diseases in phases I to III. A total of 300 European country-related clinical investigations representing a total of 93 European-specific clinical studies were included in the GENOTRIAL database. The trials were classified by development phases, temporal status, sponsors and investigating countries, rare diseases with their related therapeutic area, and approval regulatory information of the identified gene therapies. Results: Analysis reveals that rare diseases present a promising area for gene therapy development. On average, eight rare disease gene therapy trials are launched each year in Europe. The main sponsors of European clinical trials of gene therapies for rare diseases are from US, followed by the United Kingdom and France. The United Kingdom conducts the highest number of investigations in Europe, followed by France, Italy, Spain, and Germany. Nutritional and metabolic diseases are the most represented therapeutic area, followed by rare oncology, blood and lymphatic diseases, and ocular diseases. The analysis identifies 73 gene therapy medical products covering 35 diseases at various stages of development, with 12 new therapies approved in recent years for 8 rare diseases, while 15 other gene therapies are at an advanced stage of phase III in their development plan for 11 other rare diseases. Conclusion: Gene therapy has shown significant progress and potential in treating rare genetic diseases. Europe has emerged as a promising region for gene therapy clinical trials in rare diseases. Efforts are now required to catch up with the USA and UK regarding the number of clinical trials sponsored by European groups.

Assessing asthma symptoms in children: qualitative research supporting the development of the Pediatric Asthma Diary—Child (PAD-C) and Pediatric Asthma Diary—Observer (PAD-O)

BackgroundPediatric asthma has been identified by regulators, clinicians, clinical trial sponsors, and caregivers as an area in need of novel fit-for-purpose clinical outcome assessments (COAs) developed in accordance with the U.S. Food and Drug Administration’s (FDA’s) regulatory guidance for evaluating clinical benefit in treatment trials. To address this gap, the Patient-Reported Outcome (PRO) Consortium’s Pediatric Asthma Working Group has continued development of 2 COAs to assess asthma signs and symptoms in pediatric asthma clinical trials to support efficacy endpoints: a PRO measure, the Pediatric Asthma Diary—Child (PAD-C) for children 8–11 years old (y.o.) and an observer-reported outcome measure, the Pediatric Asthma Diary-Observer (PAD—O) for caregivers of children 4–11 y.o. This qualitative research aimed to generate evidence regarding the content validity of the PAD-C and PAD-O.MethodsSemi-structured combined concept elicitation and cognitive interviews were conducted with a diverse sample of U.S. participants (15 children 8–11 y.o. and 30 caregivers of children 4–11 y.o.). All children had clinician-diagnosed mild to severe asthma. Interviews explored the experience of pediatric asthma and assessed the understanding and relevance of both measures. Interviews were conducted across 3 iterative rounds to allow for modifications.ResultsConcept elicitation findings demonstrated that the core sign/symptom and impact concepts assessed in the PAD-C (cough, hard to breathe, out of breath, wheezing, chest tightness, and nighttime awakenings/symptoms) and PAD-O (cough, difficulty breathing, short of breath, wheezing, and nighttime awakenings/signs) correspond to those most frequently reported by participants; concept saturation was achieved. All PAD-C and PAD-O instructions and core items were well understood and considered relevant by most participants. Feedback from participants, the Pediatric Asthma Working Group, advisory panel, and FDA supported modifications to the measures, including addition of 1 new item to both measures and removal of 1 caregiver item.ConclusionsFindings provide strong support for the content validity of both measures. The cross-sectional measurement properties of both measures and their user experience and feasibility in electronic format will be assessed in a future quantitative pilot study with qualitative exit interviews, intended to support the reliability, construct validity, final content, and, ultimately, FDA qualification of the measures.

Telemedicine Use, Comfort, and Perceived Effectiveness in the Spinal Muscular Atrophy Community.

Background: Telemedicine may increase access to clinical care, particularly for mobility-limited communities such as the spinal muscular atrophy (SMA) community. However, much of the information on exposure to and attitudes toward telemedicine in neuromuscular diseases generally and SMA specifically is anecdotal or from focus groups. Gaining greater insight into patient perspectives is important, given telemedicine's potential for expanding access to care and growing use of telemedicine as a result of technology advances and the COVID-19 pandemic. Methods: Cure SMA collected information on the SMA community's exposure to, comfort with, and perceived effectiveness of telemedicine through its 2021 Community Update Survey. The final analytic sample represented 463 SMA-affected individuals, resident in the United States. Descriptive analyses, correlations, and ordered logit regression models were used to characterize the sample and identify predictors of exposure, comfort, and perceived effectiveness. Data were analyzed on weighted and unweighted bases to account for differences between the survey sample and the SMA community. Stratified analyses were used to compare self-completed surveys with caregiver-completed surveys. Results: 463 individuals answered questions about telemedicine. Approximately four-fifths of these respondents had used telemedicine previously. Factors predicting greater likelihood of prior telemedicine use included male gender, increasing income, having received drug treatment for SMA, history of mental illness, and having non-neutral views regarding comfort and perceived effectiveness of telemedicine. Several factors were also significant predictors of comfort with and perceived effectiveness of telemedicine. Stratified analyses indicated differences between self-completed and caregiver-completed surveys. Conclusion: These results can provide insight into patient experiences with telemedicine and can inform approaches to its use by health care professionals and clinical trial sponsors.

The evolution of an oncology site network partnership in a COVID era clinical trial environment.

125 Background: As a leader in cancer therapy research, Roche created the immunotherapy Centers of Research Excellence (imCORE) Network, a worldwide research network designed to connect members in an open environment of shared information, expertise, and decisions. This network is dedicated to advancing the comprehension of the underlying science and shared operational challenges in order to accelerate the most promising new treatment options for patients. Pre-pandemic the imCORE network was an established partnership model leader with several years of experience. Relationships between site and sponsor were established and consistent. Regularly cadenced face to face and virtual meetings provided proven pathways for open communication and collaboration opportunities. A pipeline of operational efficiencies, pain point interventions, best practices and strategies were brainstormed, co-created, and implemented across multiple workstreams. COVID arrived in March of 2020 and over the course of the next months to years the world changed. These changes were felt acutely, directly impacted clinical research, and specifically impacted imCORE sites, their patients, the network, and how it operates. Methods: This paper focuses on the Roche Sponsored clinical trial operational excellence aspects of the network. Data is collected from network sites related to pre and "post" COVID priorities and impacts. The data is then analyzed to produce best practice recommendations for oncology research sites and networks. Results: It highlights the direct impacts of COVID to a sponsored trial site network. This includes specific measures the network has taken to evolve to fit the needs of its sites and their patients and presents a pathway forward for site networks to consider in the new reality of COVID era clinical trials. Conclusions: COVID impacted and continues to impact clinical research sites and sponsored trial networks in significant and lasting ways. Site and network operations need to evolve to meet the needs of patients and staff in this new reality.

Driving Diversity and Inclusion in Cancer Drug Development - Industry and Regulatory Perspectives, Current Practices, Opportunities, and Challenges.

In April 2022, the FDA issued draft guidance to help industry develop strategies to improve diversity in clinical trials. Historically, clinical trial sponsors have not systematically incorporated efforts to promote diversity, equity, and inclusion (DEI), particularly during the early design stages of clinical development plans and operational strategies. Unfortunately, a retrospective approach to DEI often results in clinical trial participants not being reflective of the diversity of patients intended to be treated with new therapies. A shift to prospective, intentional DEI strategies for clinical trials, including long-term engagement with diverse patients and communities throughout the development life cycle, is necessary to maximize the benefits and minimize the risks of new drugs and devices for all patients. Sponsors' current practices and opportunities for improving DEI address four major topics: institutional commitment, culture change, and governance; clinical development strategy; setting enrollment goals to ensure trial participant diversity; and development and implementation of the operational strategy. As DEI practices gain wider adoption in clinical trials, shared learning and collaboration among stakeholders on an ongoing and noncompetitive basis will lead to sustainable change. Prioritization of enrollment of diverse populations as an integral part of study start-up planning, clinical trial design, and recruitment capabilities will enhance the clinical development process for oncology therapies. Importantly, these efforts will help provide equitable access to clinical trials and innovative cancer therapies.

1360-P: Health Disparities in Clinical Research among Those Living with Diabetes-Related Retinopathy

Background: Despite the higher rates of diabetes among the Black, Indigenous, and People of Color (BIPOC) population, there is a significant underrepresentation of this population in diabetes-related clinical trials which compromises the generalizability of results and further exacerbates health disparities. Objective: To identify barriers and solutions to BIPOC enrollment in diabetes-related clinical trials. Methods: We reviewed 18 diabetes-related clinical trials at Retina Associates LLC in Kansas City and interviewed recruiting physicians from practices across the US. Results: Fewer BIPOC population (15.6%) and women (40%) were enrolled in the analyzed trials. Men were 1.6 times more likely to be screened despite having a 20% higher screen fail rate than women. The fail rate was lower among Caucasian participants than among Hispanic participants (29.6% vs 37.5%). Based on zip codes, the fail rate was 1.25 times higher for those with an estimated average household income below $70,000 compared to those with an income above $100,000. The interviewed physicians valued a potential clinical trial patient’s ability to understand, commitment to health, reliability, and overall interest. They stressed the immense difficulty of time and travel commitments that clinical trials can pose for patients and agreed that increasing diversity in the staff could prove to be beneficial, especially regarding the language barrier many patients face. Conclusions: Several recommendations from the reviewed trials and interviews to improve BIPOC enrollment. Clinical trial sponsors should provide Informed Consent Forms (ICFs) in multiple languages. There needs to be a level of diversity when hiring healthcare providers and study coordinators. Clinical trials should be designed to be less burdensome and include geographic locations with a higher population percentage of minorities, as well as locations within the neighborhoods where these populations receive their healthcare care. Disclosure L.H.Cooper: None. L.Ainley: None. H.Stevens: None. K.Quinn: None. B.A.Cooper: Advisory Panel; Genentech, Inc., Speaker's Bureau; Regeneron, Optomed.

How Much Evidence Is Enough? Research Sponsor Experiences Seeking Regulatory Acceptance of Digital Health Technology-Derived Endpoints

Introduction: Digital health technologies (DHTs) provide opportunities for real-time data collection and assessment of patient function. However, use of DHT-derived endpoints in clinical trials to support medical product labelling claims is limited. Methods: From November 2020 through March 2021, the Clinical Trials Transformation Initiative (CTTI) conducted a qualitative descriptive study using semi-structured interviews with sponsors of clinical trials that used DHT-derived endpoints. We aimed to learn about their experiences, including their interactions with regulators and the challenges they encountered. Using applied thematic analysis, we identified barriers to and recommendations for using DHT-derived endpoints in pivotal trials. Results: Sponsors identified five key challenges to incorporating DHT-derived endpoints in clinical trials. These included (1) a need for additional regulatory clarity specific to DHT-derived endpoints, (2) the official clinical outcome assessment qualification process being impractical for the biopharmaceutical industry, (3) a lack of comparator clinical endpoints, (4) a lack of validated DHTs and algorithms for concepts of interest, and (5) a lack of operational support from DHT vendors. Discussion/Conclusion: CTTI shared the interview findings with the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and during a multi-stakeholder expert meeting. Based on these discussions, we provide several new and revised tools to aid sponsors in using DHT-derived endpoints in pivotal trials to support labelling claims.

Impact of COVID-19 pandemic mitigation strategies on industry and NCI cancer treatment trials.

1565 Background: The onset of the COVID-19 pandemic resulted in major disruptions in enrollment and conduct of cancer clinical trials. In response, regulators allowed modifications to traditional trial processes to enable clinical research and care to continue. The American Society of Clinical Oncology and Friends of Cancer Research established a task force to evaluate how sponsors perceived the impact of these mitigation strategies on data quality and overall trial conduct. Methods: The study used a survey and live interviews of industry and National Cancer Institute (NCI) cooperative group sponsors of cancer treatment trials. Sponsors with trials active in the United States from January 2015-May 2022 were eligible. We assessed perceived impacts of the pandemic on protocol deviations, types of mitigation strategies, trial closures, dropouts, adverse events (AEs), and data integrity. Descriptive statistics were used for survey data summaries. Key findings from semi-structured interviews were described by theme. Results: Of forty-one eligible sponsors, 20 (49%; 15/36 industry and 5/5 cooperative group) completed the survey; eleven (55%; 7/15 industry and 4/5 cooperative group) were interviewed. Sixty percent of sponsors reported large portfolios (>10 trials) of phase II and/or phase III trials. The most widely adopted mitigation strategies were remote distribution of oral anticancer therapies (70%), remote consenting (65%), and remote symptom monitoring for AEs (65%). The proportion of sponsors reporting a “substantial” increase in protocol deviations compared to the pre-pandemic period dropped from 42% in the initial wave (March-April 2020) to 16% thereafter. Sponsors primarily reported “no change” in trial drop-out rates (77%), the number of trials closed due to low accrual (90%), or rates of AEs (81%) at any point during the pandemic. Overall, most (83%) respondents reported the pandemic had “minimal” (14) or “no” impact (1) on data integrity. In interviews, many sponsors reported persistent time delays in data entry related to labor shortages at sites. Conclusions: This study represents the first systematic evaluation of clinical trial sponsors about the impact of the COVID-19 pandemic on the conduct of cancer clinical trials. Remote clinical trial conduct mitigation strategies were broadly adopted. Despite an observed increase in protocol deviations, most sponsors reported the pandemic had minimal or no impact on data integrity. The COVID-19 pandemic impacted how cancer clinical trials were performed and has likely accelerated a trend towards greater flexibility in trial conduct that was already emerging, with potential benefits of reduced burden and improved access for patients and sites . Future work is planned to further quantify the impact of the pandemic and trial mitigation strategies on the quality of trial data both overall and for historically underrepresented patient groups.