Clinical Trial Infrastructure Research Articles

Association of Community-Level Social Vulnerability With Clinical Trial Discussion and Participation Among Cancer Survivors.

Community factors and structural barriers may contribute to disparities and underrepresentation in cancer clinical trials. We evaluate the influence of community-level social determinants of health, as measured by the Centers for Disease Control and Prevention Social Vulnerability Index (SVI), on disparities in cancer clinical trial discussion and participation. We performed a cross-sectional analysis of the 2021 Health Information National Trends Survey-SEER, a representative survey of cancer survivors sampled from three SEER registries. The primary outcomes included patient-reported clinical trial discussion and participation. The primary exposure was county-level SVI, linked to each survey respondent by ZIP code of residence and categorized into quintiles. Survey-weighted bivariate comparisons and multivariable logistic regression were performed to evaluate the association between SVI and clinical trial discussion and participation, adjusting for age, sex, race and ethnicity, education, income, and cancer stage. We identified 1,220 respondents residing in 153 counties with a median SVI of 0.41 (IQR, 0.27-0.62), representing a population of over 400,000 cancer survivors on weighted analysis. Of the cohort, 15.1% reported clinical trial discussion and 7.7% reported clinical trial participation. Patients who are most socially vulnerable (fifth quintile of SVI) had significantly lower odds of clinical trial discussion (odds ratio [OR], 0.36 [95% CI, 0.15 to 0.87]; P = .02) and clinical trial participation (OR, 0.15 [95% CI, 0.03 to 0.75]; P = .02) compared with patients who are least socially vulnerable (first quintile of SVI). These findings suggest interventions to identify socially vulnerable communities for expansion of clinical trial opportunities and infrastructure may be an impactful strategy toward improving diversity and representation in cancer clinical trials.

How Immunocompromised Hosts Were Left Behind in the Quest to Control the Covid-19 Pandemic.

The immunocompromised population was disproportionately affected by the SARS-CoV-2 pandemic. However, these individuals were largely excluded from clinical trials of vaccines, monoclonal antibodies, and small molecule antivirals. While the community of scientists, clinical researchers, and funding agencies have proven that these therapeutics can be made and tested in record time, extending this progress to vulnerable and medically complex individuals from the start has been a missed opportunity. Here we advocate that it is paramount to plan for future pandemics by investing in specific clinical trial infrastructure for the immunocompromised population to be prepared when the need arises.

Abstract 919: Veterans Health Administration: Decentralized clinical trials

Abstract Purpose: The Veterans Health Administration (VA) created National TeleOncology (NTO) service in 2019 to provide telehealth cancer care to Veterans and to augment care provided at VA facilities through a hub and spoke model. More recently, VA established a Decentralized Clinical Trials (DCTs) infrastructure to support clinical trials (CTs) that rely on telehealth, where research staff are at different locations, and/or where a single IRB provides oversight even when subjects are at different locations. Brief Description: Research support and infrastructure is variable across VA facilities resulting in uneven access to cancer CTs in the VA system. Veterans often live in rural areas or have transportation challenges, which are barriers to participate in CTs. The COVID-19 pandemic resulted in increased telehealth use in clinical care and in CTs, providing the rationale for a focused effort in DCTs. DCTs have the potential to reduce barriers to CT involvement at the facility- and patient-level and may be more representative of real-world clinical scenarios. Summary of Data: Since its inception, NTO has provided hematology and oncology telehealth care to over 10,000 Veterans, of which 47.5% live in rural or highly rural areas, 76.5% are white and 13.2% are black or African American. Because the NTO program provides clinical care via telehealth modalities, patients who receive care through NTO may be more comfortable with participating in CTs that use telehealth, and thus are part of a pool of potentially eligible subjects.Since creation of the DCT program, three cancer DCTs have been conducted in the VA (1) BNT001 Digital Therapeutic Feasibility Pilot Study, (2) Cemiplimab Survivorship Epidemiology (CASE) Study, and (3) Proof-Of-ConcepT DEcentralized CliNical TrIAL (POTENTIAL) study. The BNT study enrolled 24 Veterans, 19 were male, 22 were white, 13 lived in rural areas, and the median age at enrollment was 68 years, including numerous cancer diagnoses. Veterans enrolled in the BNT study received cancer care at seven VA facilities. The CASE study has enrolled 24 male Veterans, 23 were white, 5 lived in rural areas, and the median age at enrollment was 74 years. The POTENTIAL study enrolled 4 male Veterans, 3 were white, 2 lived in rural areas, and the median age at enrollment was 72 years. Upcoming DCTs will focus on the following disease types: metastatic non-small cell lung cancer, multiple myeloma, and relapsed/refractory diffuse large B-cell lymphoma. Conclusions: The VA provides clinical cancer care to Veterans through the NTO program. The DCT program builds upon the existing clinical infrastructure to conduct CTs on a national scale. The NOP DCT team is a component of the VA’s Enhance Equity and Access to Clinical Trials (ENACT) initiative, which is part of Cancer Moonshot. The DCT program intends to expand CT opportunities to Veterans with cancer, minimize barriers to CT activation and enrollment, and improve access to cancer CTs for all Veterans. Citation Format: Ashlyn Press, Jennifer Ordman, Jacqueline Boreland, Zachary Burningham, Shelby Schoenborn, Tiffany Stewart, Bethany Oberg, Perri Pepperman, Holly Morris, Sarah Bloemers, Nawshin Kutub, Shannon Elam, Michael J. Kelley, Daphne Friedman. Veterans Health Administration: Decentralized clinical trials [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 919.

Towards advancing Out-of-Hospital cardiac arrest (OHCA) registries globally: Considerations from the global OHCA registry (GOHCAR) collaborative

A growing number out-of-hospital cardiac arrest (OHCA) registries have been developed across the globe. A few of these are national, while others cover larger geographical regions. These registries have common objectives; continuous quality improvement, epidemiological research and providing infrastructure for clinical trials. OHCA registries make performance comparison across Emergency Medical Services systems possible for benchmarking, hypothesis generation and further research. Changes in OHCA incidence and outcomes provide insights about the effects of secular trends or health services interventions. These registries, therefore, have become a mainstay of OHCA management and research. However, developing and maintaining these registries is challenging. Coordination of different service providers to support data collection, sustainable resourcing, data quality and data security are the key challenges faced by these registries.Despite all these challenges, noteworthy progress has been made and further standardization and co-ordination across registries can result in great international benefit. In this paper we present a ‘why’ and ‘how to’ model for setting up OHCA registries, and suggestions for better international co-ordination through a Global OHCA Registries Collaborative (GOHCAR). We draw together the knowledge of a cohort of international researchers, with experience and expertise in OHCA registry development, management, and data synthesis.

Abstract 993: Comprehensive immunophenotypic strategies to enable equity in remote settings for improved cancer prognosis

Abstract Improved cancer prognosis begins with insights obtained from high quality data during clinical trials. Execution of longitudinal clinical trials in flow cytometry is complex, primarily due to logistical challenges in high quality sample collection. For instance, highly remote indigenous population centers are both disadvantaged in access to healthcare and often underrepresented in clinical trials. This paradox is highlighted in the case of Australian First Nations communities, for which lung cancer prevalence peaks in males at twice the magnitude of the general population. Our group has developed a novel blood “immune signature” that robustly predicts failure to make a clinical response to checkpoint therapies targeting the PD-1/PD-L1 pathway. Encouraged by these groundbreaking findings, which were achieved through applying a comprehensive 38-plex immunophenotyping CyTOF panel to biobanked cancer samples, recent advances in CyTOF technology now give us the opportunity to expand our clinical implementation to remote settings, with a further expanded panel to 50+ markers. CyTOF is the only technology that allows easily implemented remote asynchronous sample collection and the largest immunophenotyping panel that yields reproducible results. Asynchronous collection is uniquely enabled using a stable lyophilized large-scale staining panel and achieving comprehensive marker coverage in one panel minimizes blood sample required. Furthermore, the new technology enables a highly simplified workflow including blood collection and processing in remote locations to enable the simplest clinical trial infrastructure complexity and cost, easily implemented in current hospital lab environments. As such, this study is designed to ultimately demonstrate both clinical impact of the large panel and utility of CyTOF technology for highly simplified and robust workflow for multi-site clinical trials. This project has 3 phases; i) implementation and evaluation of the collection, analysis technique and data management of this new approach across multiple sites, ii) collection of samples for analysis both pre- and post- initiation of therapy to establish efficacy and optimize as necessary, and iii) blinded clinical trial. We will report on the first phase of this project which is implementing new workflow across clinical collection site, data integration and analysis. This workflow would enable highly simplified collection to access indigenous and under-served populations spread across remote sites in Australia. Citation Format: Natalie J. Smith, Michael Cohen, Julie Alipaz, Christina Loh, David King, Barbara Fazekas de St Groth, Helen M. McGuire. Comprehensive immunophenotypic strategies to enable equity in remote settings for improved cancer prognosis [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 993.

Comparison of efficiency and safety of open surgery, hybrid surgery and endovascular repair for the treatment of thoracoabdominal aneurysms: a systemic review and network meta-analysis.

The objective of this study was to perform a network meta-analysis (NMA) to assess the efficacy and safety of three different surgical interventions- open surgical repair (OSR), hybrid surgical repair (HSR), and endovascular repair (EVAR)- for the treatment of thoracoabdominal aortic aneurysms (TAAAs). Electronic repositories like PubMed, Embase, Web of Science, Scopus, ScienceDirect, the Cochrane library, Clinical trial, and China National Knowledge Infrastructure (CNKI) were systematically searched to identify studies that compared the efficacy of OSR, HSR, and EVAR with endografts for the treatment of TAAAs until December 24th, 2022. Random-effects and fixed-effects models were employed to analyze the data gathered in a network meta-analysis. The study's primary outcomes of interest encompassed in-hospital mortality, long-term survival rate, and postoperative complications. Eleven comparative studies meet inclusion criterias. There were 2,222 patients in OSR, 1,574 patients in EVAR and 537 patients in HSR. EVAR has lower one-month mortality than OSR (RR: 0.31; 95% CI: 0.17-0.70) and HSR (RR: 0.37; 95% CI: 0.22-0.71), and lower incident rate of renal complications than HSR (RR: 0.20; 95% CI: 0.08-0.43) and OSR (RR: 0.34; 95% CI: 0.16-0.65). Nonetheless, there was no noteworthy discrepancy identified in the long-term survival rates of these procedures. As compared with OSR, HSR, and EVAR, EVER has lower one-month mortality, and lower incident rates of complications. PROSPERO (CRD42022313829).

Development and validation of a caregiver‐reported outcome measure for Alzheimer’s disease: the Alzheimer’s Disease Caregiver Reported‐Health Index (ADCR‐HI), a fully validated tool to bolster clinical trial and research infrastructure

AbstractBackgroundAs therapeutic advancements are made in the field of Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI), it is important to have a fully validated, sensitive, and reliable, disease‐specific outcome measures that can accurately measure changes in AD and MCI symptomatic disease burden. The U.S. Food and Drug Administration has encouraged the use of caregiver reported outcome measures (CRO) to measure therapeutic benefit of new treatments on patient populations when a patient is unable to report on themselves. This research describes the creation, testing, and validation of a novel, multifactorial CRO: The Alzheimer’s Disease Caregiver Reported‐Health Index (ADCR‐HI).MethodsWe conducted interviews and a large cross‐sectional study involving individuals with AD and MCI and their caregivers to determine what symptoms and issues are most important to patients (Figure 1). Questions were selected for the ADCR‐HI based on their importance to patients with MCI and AD, potential to respond to therapeutic intervention, and generalizability. We beta tested the ADCR‐HI with caregivers of individuals with MCI and AD to determine its clarity, ease of use, and relevance to those with MCI and AD. We performed test‐retest reliability, known groups validity, internal consistency, and area under the curve analyses of the ADCR‐HI to assess the statistical characteristics, performance, and clinical meaningfulness of the outcome measure.ResultsThe content of the ADCR‐HI was validated using a cross‐sectional study of 329 caregivers. The ADCR‐HI contains 8 subscales that measure disease burden in the following areas: 1. Memory, 2. Cognitive health, 3. Social Health, 4. Physical Health, 5. Communication, 6. Fatigue, 7. Sleep, and 8. Emotional Health. The ADCR‐HI was identified as easy to use, relevant to the patient population, responsive, and clear during beta testing. The ADCR‐HI was shown to be reliable during test‐retest reliability testing with 34 caregivers and able to distinguish between patient cohorts with different disease severities.ConclusionThe ADCR‐HI is a valid, sensitive, and reliable marker of disease burden in AD. This disease‐specific outcome measure is available for use by researchers, clinicians, patient organizations, and companies to measure changes in disease burden during therapeutic trials.

Development of a patient‐reported outcome measure for Alzheimer’s disease: the Alzheimer’s Disease‐Health Index (AD‐HI), a fully validated tool to bolster clinical trial and research infrastructure

AbstractBackgroundAs therapeutic advancements are made in Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI), it is important to have a fully validated, sensitive, and reliable disease‐specific patient‐reported outcome measure (PRO) to accurately measure changes in AD and MCI symptomatic disease burden. The U.S. Food and Drug Administration has encouraged the use of PROs to measure therapeutic benefit of potential new treatments. This research describes the development, testing, and validation of a novel, multifactorial PRO: The Alzheimer’s Disease‐Health Index (AD‐HI).MethodsWe conducted interviews and a large cross‐sectional study involving individuals with AD and MCI and their caregivers to determine what symptoms and issues are most important to patients (Figure 1). Questions were selected for the AD‐HI based on their importance to patients with MCI and AD, potential to respond to therapeutic intervention, and generalizability to the broader MCI and AD patient population as determined through qualitative interviews and a cross‐sectional study. We beta tested the initial version of the AD‐HI with individuals with MCI and AD to determine its clarity, ease of use, and relevance to those with MCI and AD. We performed test‐retest reliability, known groups validity, internal consistency, and area under the curve analyses of the AD‐HI to assess the statistical characteristics, performance, and clinical meaningfulness of the outcome measure.ResultsThe content of the AD‐HI was validated using a cross‐sectional study of 104 patients. The final version of the AD‐HI contains 9 subscales that measure disease burden in the following areas: 1) Memory, 2) Cognitive health, 3) Fatigue, 4) Sleep, 5) Social health, 6) Communication, 7) Emotional health, 8) Physical health, and 9) Pain. The AD‐HI was identified as easy to use, relevant to the patient population, responsive, and clear during beta testing. The ADCR‐HI was shown to be reliable during test‐retest reliability testing with 22 individuals and able to distinguish between patient cohorts with different disease severities.ConclusionThe AD‐HI is a is a valid, sensitive, and reliable marker of disease burden in AD This disease‐specific outcome measure is available for use by researchers, clinicians, patient organizations, and companies to measure changes in disease burden during therapeutic trials.

Abstract IA031: Equitable access to clinical trials: The role of community healthcare systems

Abstract Approximately 85% of US cancer care is delivered in community healthcare systems, most of which have no formal affiliation with academic programs and do not identify the research mission as a core responsibility. Therefore, most community-based cancer programs are research deserts. Yet there is strong evidence to support the oft-cited statement: 'the best treatment is a clinical trial.' In this age of rapid-fire discovery and clinical trials driven by deep knowledge of cancer biology and drug chemistry, coupled with close regulatory oversight, clinical trials carry much smaller risk for participants than ever before. In the end, clinical trials provide access to tomorrow's treatment, today. The socio-ecological model of healthcare recognizes that most problems and solutions reside at the levels of the individual, clinician, organization and social policy. As the number of actors sequentially diminishes from the individual to the social policy levels, the potential enduring impact of interventions sequentially rises. Interventions directly targeting the individual level are least efficient, those that target key social policies have the greatest enduring impact. So with the wicked challenge of inequitable clinical trials access. We will focus on the institutional level in my solutions-oriented discussion of equitable access to clinical trials. Using the NCI's Minority-Underserved NCORP progam and the Baptist Memorial Health Care Corporation as living examples, we will review intervention frameworks, objectively analyze the barriers to clinical trials access, and provide a pragmatic discussion of stakeholder-centered approaches to building clincial trials infrastructure in the places where people routinely seek care. We propose approaches to integrate clincal research as a core component of cancer care delivery in community healthcare systems and make the case that key external stakeholders, including patient advocacy groups, sponsors of research and healthcare policymakers must meet the target population where they reside. That connection can only happen by building clinical trials infrastructure and manpower within community healthcare systems. Citation Format: Ray U. Osarogiagbon. Equitable access to clinical trials: The role of community healthcare systems [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 IA031.

Global platform trial design for tau (MAPT) mutation carriers

AbstractBackgroundPathogenic mutations in the MAPT (tau) gene cause familial frontotemporal lobar degeneration (f‐FTLD). No disease‐modifying treatments exist. Tau therapeutics being tested in other tauopathies may be suitable candidates, but the small number of identified mutation carriers prohibits traditional clinical trial designs from achieving adequate power. Platform trial designs permit multiple therapies to be tested in parallel and improve power by sharing placebo groups across treatment arms. We evaluate whether a platform design could improve the likelihood of identifying an effective treatment for MAPT mutation carriers.MethodALLFTD and GENFI observational data were used to simulate MAPT prevention and early symptomatic clinical trials (CDR®+NACC‐FTLD≤1). Only presymptomatic participants (CDR®+NACC‐FTLD = 0) within 2.5 years of expected symptom onset based on disease progression models (DPM) were included. First, we evaluated the time and sample size required to test five treatments using a platform design compared to sequential randomized control trials. Platform designs assumed a max of three treatment arms at any time, with new arms enrolling upon completion of prior arms. Each arm randomized 60 mutations carriers 3:1 treatment to placebo, with a placebo group shared across arms. Minimum follow up was 1.5 years with common close. Sequential trials assumed 90 participants allocated 1:1 treatment to placebo, with three‐month intervals between trials. Using a platform design, we compared a novel method for testing therapeutic effects using DPMs to account for differential rates of expected progression compared to traditional mixed models for repeated measures (MMRM) tests controlling for baseline CDR®+NACC‐FTLD.ResultFive treatments could be tested in a platform design using 300 participants (75% treated) over five years, compared to 450 participants (50% treated) over 13 years using traditional, sequential trials. Platform trial simulations indicated that with 80% power, DPM‐based analytic approach could detect a 25% treatment effect, whereas traditional MMRM could only detect a 40% effect.ConclusionPlatform designs combined with DPM‐based analyses provide a path to testing more treatments with fewer participants. Adequately powered MAPT platform trials are feasible but require a global clinical trial infrastructure.

HIV vaccines: Lessons from basic research, clinical trials, and public policy

Forty years since its discovery in 1983, HIV/AIDS still lacks a cure, despite advances in biomedicine that have dramatically improved global understanding of the virus’s biology. Decades of research and improvements to clinical trial infrastructure have promoted the development of novel vaccines for HIV, but these vaccines have shown limited efficacy. The landmark clinical trial “RV144” in Thailand (2003) showed modest efficacy of an HIV vaccine for the first time ever, sparking the formation of public-private partnerships and a wave of other HIV vaccine clinical trials. Around two decades later, the COVID-19 pandemic provided an impetus to move vaccine technology forward and exposed areas for improvement in vaccine and clinical-trial infrastructure. Looking at historical examples from both HIV and COVID-19 research, vaccine trials, and global statistics, it is clear that a successful vaccination campaign will require generous funding, collaboration, clinical trial infrastructure, sharing of data and resources amongst researchers, and policy based on scientific evidence and ethics. Such a successful campaign will also require overcoming several hurdles, such as delivering vaccines to individuals in countries with underdeveloped health care systems and both demographic and geographic disparities in access to care. The perspectives in this article are apropos given the recent development of HIV vaccines that have entered clinical trials.

Towards a national equitable and sustainable clinical research infrastructure for Aotearoa New Zealand.

Clinical trials are a critical element of a modern, high-functioning, learning healthcare system. Clinical trials provide access to novel, as yet unfunded treatments, and deliver cutting-edge healthcare. Evidence from clinical trials ensures appropriateness of healthcare, allows disinvestment from practices that are found not to improve outcomes or be cost-effective, and supports the introduction of new approaches, all of which leads to improvement in health outcomes. In 2020, Manatū Hauora - Ministry of Health and The Health Research Council of New Zealand funded a project to understand the current state of clinical trial activity in Aotearoa New Zealand and to propose the infrastructure required to support equitable clinical trial activity, in order to ensure that trials benefiting from publicly funded infrastructure are responsive to the needs of New Zealanders and ultimately enable equitable delivery of the best healthcare we can achieve to all New Zealanders. This viewpoint reports the process that was undertaken to develop the final proposed infrastructure and the rationale for the approach. The restructuring of the Aotearoa New Zealand health system into Te Whatu Ora - Health New Zealand and Te Aka Whai Ora - Māori Health Authority that will both operate hospital services and commission primary and community healthcare at a national level provides the ideal opportunity to integrate and embed research into Aotearoa New Zealand's healthcare system. Integration of clinical trials and research more broadly into the public healthcare system will require a significant shift in the culture within our healthcare system. Research must be recognised and promoted as a core activity for clinical staff at all levels of the healthcare system, rather than something to be tolerated or even hindered. Strong leadership will be required from the top of Te Whatu Ora - Health New Zealand down to ensure the required cultural shift to recognise the value of clinical trials to all aspects of the healthcare system, and to grow capability and capacity of the health research workforce. The investment required by the Government to implement the proposed clinical trial infrastructure will be substantial, but now is the ideal time for investment in clinical trials infrastructure in Aotearoa New Zealand. We urge the Government to be bold and invest now to ensure the benefits can be reaped for all New Zealanders in years to come.

Data transparency and demographic representation in approval packages of FDA-approved oncology drugs from 2012-2021.

1594 Background: Over the past decade, the U.S. Food and Drug Administration (FDA) has leveraged regulations and guidance documents to accelerate improvements in demographic reporting and encourage adequate representation of minorities in clinical trials. This cross-sectional study aims to assess the impact of these interventions by characterizing demographic data reporting and representation by sex, age, and racial and ethnic identity in pivotal trials supporting novel cancer therapeutics approved by the FDA from 2012 through 2021. Methods: Study demographic data were abstracted from FDA drug approval packages and US cancer population demographic data was abstracted from US Cancer Statistics. The percentages of trials reporting sex, age, racial and ethnic identity of participants in drug approval packages were calculated and participation to prevalence ratios (PPRs) were calculated by dividing the percentage of participants in each demographic by the percentage of the US cancer population in each group. PPRs were constructed for each pivotal trial by cancer type. Adequate representation was defined as PPR 0.8-1.2 and the proportion of trials which were adequately representative of each demographic was calculated and trended over time. Results: From 2012 through 2021, the FDA approved 118 cancer therapeutics, based on 131 pivotal trials. For drugs approved 2012-2016, the majority of associated pivotal trials reported participation based on sex (100% of trials), age (100%) and White (98%), Black (75%) or Asian (84%) racial identity, but not American Indian or Alaskan Native racial identity (18%) or Hispanic ethnic identity (41%). For drugs approved 2017-2021, there were no significant improvements in demographic data reporting, although there was a trend towards increased reporting on Hispanic ethnic identity from 2012-2016 (41%) to 2017-2021 (65%) (p= 0.06). For drugs approved 2012-2016, most pivotal trials adequately represented female participants (78% of trials) and participants identifying as White (87%), but few pivotal trials adequately represented older adults (7%), participants identifying as Black (11%), American Indian or Alaskan Native (0%), Asian (18%) or Hispanic (5%). Representation in pivotal trials did not significantly improve for any demographic for drugs approved 2017-2021 (p>0.05). Conclusions: This study found that the last decade’s efforts to improve demographic data transparency and representation in clinical trials have not yet borne fruit for novel cancer therapeutics. More consequential FDA regulations may be necessary. Beyond the FDA, demographic data transparency and adequate minority representation in oncology clinical trials is an all-stakeholder responsibility. A more just clinical trial infrastructure requires greater collaboration between the FDA, sponsors, enrollers, contract research organizations and cooperative groups.

NCCN Highlights Best Practices for Challenges in Oncology

NCCN Highlights Best Practices for Challenges in Oncology

Abstract 4383: Development and validation of the Lung Cancer-Health Index (LC-HI), a clinically-relevant, disease-specific patient-reported outcome measure

Abstract Study Aim: The goal of this research is to develop and validate a novel, disease-specific patient-reported outcome measure (PRO) for use in clinical monitoring and therapeutic trials in Lung Cancer (LC). Methods: LC currently accounts for the greatest number of cancer deaths worldwide, driving an increased need for novel therapeutic development in LC. To bolster clinical trial infrastructure, it is critical to have a comprehensive, sensitive and reliable PRO that accurately tracks LC multifactorial disease burden. This research describes the development and validation of the Lung Cancer-Health Index (LC-HI) as an efficient mechanism for assessing how patients with LC feel and function in response to therapeutic treatment. We conducted semi-structured, qualitative interviews with 15 individuals diagnosed with LC and collected 653 direct participant quotes to determine the most frequent and important symptoms in LC. Based upon participant responses, we designed a survey that inquired about 162 symptoms from 14 symptomatic themes. This survey was implemented in a cross-sectional study with 139 participants with LC. The collected data was used to generate the first version of the LC-HI, which contained symptom questions showing the highest impact to the population and the potential to respond to therapeutic intervention. Symptom questions were grouped into distinct subscales using factor analysis. We beta-tested the LC-HI with 15 patients with LC to evaluate its usability, clarity, and applicability. Based on patient feedback, we modified the instrument and evaluated its test-retest reliability with 22 individuals with LC. Known groups testing was performed with the final instrument. Results: The final version of the LC-HI contains 45 symptom questions grouped into 10 subscales that measure the following areas of LC health: 1) fatigue, 2) physical function, 3) emotional health, 4) sleep and daytime sleepiness, 5) activity participation, 6) breathing function, 7) gastrointestinal function, 8) cognitive function, 9) social performance, and 10) pain. Total LC disease burden is measured using a weighted composite of these subscale scores. During beta interviews, individuals with LC deemed the instrument to be easy to use, clear, relevant, and comprehensive. Statistical and psychometric analyses confirmed that the LC-HI is reliable, valid, sensitive, specific, of high internal consistency, and able to differentiate between groups with known varying levels of disease burden (based on disability status and smoking history). Conclusions: Our research demonstrates the validity of the LC-HI as a marker of the multifaceted disease burden in LC. This disease-specific PRO provides researchers and clinicians with a reliable tool to use in patient monitoring, clinical trials, and to support FDA drug labeling claims. Citation Format: Anika Varma, Spencer Rosero, Jamison Seabury, Jennifer Weinstein, Charlotte Engebrecht, Christine Zizzi, Nuran Dilek, John Heatwole, Megan Baumgart, Deborah Mulford, Ronald Maggiore, Lainie Conrow, Jennifer King, Jacinta Wiens, Chad Heatwole. Development and validation of the Lung Cancer-Health Index (LC-HI), a clinically-relevant, disease-specific patient-reported outcome measure. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4383.

DEVELOPMENT AND VALIDATION OF A PATIENT-REPORTED OUTCOME MEASURE FOR CROHN’S DISEASE: THE CROHN’S DISEASE-HEALTH INDEX (CD-HI), A FULLY VALIDATED TOOL TO BOLSTER CLINICAL TRIAL AND RESEARCH INFRASTRUCTURE

To bolster Crohn’s disease (CD) clinical trial and research infrastructure through the development and validation of a sensitive, multifactorial, disease-specific, patient-reported outcome measure (PRO) for patient monitoring in therapeutic trials of CD.

DEVELOPMENT AND VALIDATION OF A PATIENT-REPORTED OUTCOME MEASURE FOR CROHN’S DISEASE: THE CROHN’S DISEASE-HEALTH INDEX (CD-HI), A FULLY VALIDATED TOOL TO BOLSTER CLINICAL TRIAL AND RESEARCH INFRASTRUCTURE

Abstract STUDY AIM To bolster Crohn’s disease (CD) clinical trial and research infrastructure through the development and validation of a sensitive, multifactorial, disease-specific, patient-reported outcome measure (PRO) for patient monitoring in therapeutic trials of CD. BACKGROUND As therapeutic advancements are made in the field of CD, it is vital to have a fully validated, sensitive, and reliable, disease-specific PRO to accurately measure changes in disease burden. Importantly, the U.S. Food and Drug Administration has encouraged the use of PROs to measure therapeutic benefit of new treatments on patient populations. This research describes the creation, testing, and validation of a new, multifactorial PRO: The Crohn’s Disease-Health Index (CD-HI). METHODS Questions were selected for the CD-HI based on their importance to patients, potential to respond to therapeutic benefit, reliability, internal consistency, and generalizability (Figure 1). We beta tested the CD-HI to evaluate its clarity, ease of use, and applicability to the CD patient population. We performed test-retest reliability, known groups validity, internal consistency, and area under the curve (AUC) analyses. RESULTS The final version of the CD-HI contains 12 subscales that measure disease burden in the following areas: 1) fatigue, 2) dietary restrictions, 3) gastrointestinal health, 4) sleep and daytime sleepiness, 5) bowel and bladder function, 6) emotional wellbeing, 7) joint health, 8) pain, 9) neck and back health, 10) activity participation, 11) social wellbeing, and 12) skin health. The CD-HI also provides a composite measure of total disease burden. Fifteen participants participated in beta testing and identified the CD-HI as easy to use, clear, relevant, and comprehensive. Twenty-three individuals with CD participated in test-retest reliability testing of the CD-HI, which indicated a high reliability of the individual questions, subscales, and full instrument (intraclass correlation coefficient = 0.84 for the full instrument). The CD-HI and its subscales demonstrated a high internal consistency (Cronbach’s α = 0.98 for the full instrument). The CD-HI total and subscale scores successfully distinguished between patient cohorts with differing disease severity. AUC analysis demonstrated a high sensitivity and specificity of the CD-HI in distinguishing between those with CD on disability vs. not on disability, with an AUC value of 0.9087 (Figure 2). CONCLUSIONS The CD-HI is a fully validated, sensitive, and accurate marker of disease burden in CD. This disease-specific PRO is available for use by researchers, clinicians, patient organizations, and companies to monitor patients and measure disease burden during therapeutic trials

Is the U.S. clinical trial infrastructure optimized to meet the current and growing enrollment needs?

AbstractBackgroundAlzheimer’s disease (AD) clinical development continues to expand with 28 drugs in Phase 3, 74 in Phase 2, and 24 in Phase 1 in 2021. This study seeks to investigate how the U.S. clinical trial infrastructure is prepared to meet the current and growing enrollment needs. We aim to evaluate the overlap between regional density of persons with dementia (PWD) and trial site service areas with attention to how coverage gaps impact the ability to enroll study participants representative of the national population diagnosed with AD.MethodPrevalence of AD by race, gender, socioeconomic status and language was collected using the 2019 US Census Bureau. Data on trial site location was gathered using ClinicalTrials.gov and a third party service. The SiteRx Provider Network, a network of over 1,200 treating neurologists and primary care physicians that refer patients to research across 28 US states, was gathered using ZIP codes from a proprietary database. AD prevalence by ZIP code was compared against ZIP codes of current clinical trials sites that conduct Phase 1‐3 CNS trials across the U.S and SiteRx Provider Network using a radius of approximately 60 miles.ResultThere are gaps between PWD and trial sites locations, which are significantly worse for minority patients. Heat maps were created using Excel and Tableau to visualize data, which indicated key areas of infrastructure misalignment given existing patient populations. Additional analysis was performed to explore how PWD and site location incompatibility impacted potential enrollment based on key demographic domains.ConclusionThe current AD clinical trial site infrastructure is not well equipped to meet the growing need for clinical trial recruitment. SiteRx is positioned to strengthen trial infrastructure through their ability to bridge community‐based care with nearby research sites to optimize enrollment at current sites and identity geographies in need of trial sites given the existing AD patient population.

The Alzheimer’s Disease‐Health Indices (AD‐HI): Development of Two Novel Outcome Measures for Use in Clinical Trials

AbstractBackgroundIn preparation for upcoming clinical trials, there is a clear need for improved clinical trial infrastructure to facilitate therapeutic assessment in Alzheimer’s disease, (AD), mild cognitive impairment (MCI), and related dementias. This research describes the development of a patient‐reported outcome measure, the Alzheimer’s Disease‐Health Index (AD‐HI), and a caregiver‐reported outcome measure, the Alzheimer’s Disease Caregiver‐Health Index (ADCR‐HI). These novel outcome measures were developed using large scale input from patients and caregivers and were designed in accordance with U.S. Food and Drug Administration (FDA) guidelines for use in drug labeling claims.MethodWe first conducted semi‐structured qualitative interviews with individuals with AD, MCI, or dementia and their caregivers to identify potential symptoms of importance to these disease populations. We subsequently performed a cross‐sectional study involving individuals with AD, MCI, or dementia and caregivers to determine the prevalence and relative importance of symptoms identified during preliminary qualitative interviews. Using this data, we developed two outcome measures known as the AD‐HI and the ADCR‐HI. Symptom questions and subscales were selected for the instruments based on their prevalence and importance to the patient populations, their generalizability, and ability to respond to therapeutic intervention. Factor analysis was used to group symptom questions into distinct symptomatic themes of patient health.ResultFifteen individuals with AD, MCI, or dementia and 15 caregivers provided 2,263 quotes regarding the symptomatic burden of AD, MCI, or dementia. One‐hundred and four patients and 329 caregivers participated in a cross‐sectional study to determine the prevalence and relative importance of the most relevant symptoms identified through interviews. The AD‐HI and the ADCR‐HI were developed based on this data and simultaneously measure overall patient disease burden and disease burden in 9 disease specific areas.ConclusionThe AD‐HI provides researchers and clinicians with a valid mechanism to measure disease burden during therapeutic trials involving individuals with AD, MCI, or dementia. Similarly, the ADCR‐HI provides a viable option when a patient can no longer complete a patient‐reported outcome measure on their own behalf. Ongoing steps will further optimize the usability and reliability of these instruments in preparation for upcoming clinical trials.

"If You Don't Trust Your Doctor That Much...You'd Feel Less Confident Doing a Research Study": Factors Influencing Black Patient Participation in Hematology Trials

Background Racial disparities exist in incidence and survival from hematological cancers. These differences are driven by multiple factors, including disease biology and access to high-quality cancer care (e.g., enrollment in a clinical trial). Black persons constitute 5-7% of participants in therapeutic cancer clinical trials (Bhatnagar et al. 2017, S. Al Hadidi et al. 2020, S. Al Hadidi et al. 2022), despite accounting for 14% of the US population. While previous studies have broadly focused on understanding factors that underpin that disparity in clinical trials, very few have focused explicitly on populations with hematological cancers. Further, research evaluating the perspectives of hematologists on factors that influence clinical trial enrollment for the Black population remains limited. The objective of this study was to understand factors that influenced Black participant enrollment in hematology-focused clinical trials by examining the perspectives of Black patients with multiple myeloma and their hematologists. Methods Between August 2021-January 2022, hematologists were recruited to participate in single semi-structured 60-minute virtual interviews, while patients diagnosed with multiple myeloma were asked to participate in focus group discussions (FGDs) lasting up to 90 minutes via videoconferencing. Through the Sort and Sift, Think, and Shift approach (Maietta et al. 2021),analytic memoing and diagramming of key quotations were used to assess topics and identify larger conceptual themes. We tabled and grouped themes, topics, and associated quotations at multiple levels using the National Institute on Minority Health and Health Disparities Research framework. Topics and themes from FGDs and hematologist interviews were then distilled into key claims. Results We conducted 6 FGDs with 23 patients and 13 semi-structured interviews with hematologists. Hematologists perceived trust at multiple levels (e.g., patient-provider, patient-health care system) as an influential determinant of Black patients' enrollment in clinical trials (Table 1). Factors that fostered patient-hematologist trust included the length of the relationship, use of transparent and empathic communication, and shared racial identities of patients and hematologists. For patients, trust in the hematologist, health care system, and proposed trial intervention were determinants of whether Black patients enrolled in a clinical trial. Patients also emphasized the importance of hematologists acknowledging the historical events that led to the intentional harm of Black persons engaged in research-related activities and recommended additional efforts to foster shared medical decision-making. Some hematologists perceived clinical trial discussions as potentially harmful when building trust in their patient relationships. Hematologists also considered patient context--such as geographic location, socioeconomic challenges, and health literacy along with study eligibility criteria--when deciding to offer a clinical trial (Figure 1). Hematologists also viewed lack of time, trial availability, and adequate clinical trial infrastructure as barriers to discussing and enrolling Black patients in clinical trials. Conclusion Black patients and hematologists perceived trust at multiple levels as critical to enhancing the enrollment of Black participants in hematology-focused cancer clinical trials. Additionally, hematologists' perceptions about patients, including the additional burdens associated with clinical trial participation, also impacted whether or not Black patients are given the opportunity to participate in a clinical trial. Addressing disparities in clinical trial enrollment among Black participants requires multilevel interventions such as 1) fostering patient-clinician relationships, 2) increasing clinical trial availability and partners in community-based settings, 3) providing support to overcome logistical barriers, 4) acknowledging and finding strategies to address physician biases. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal