Industry-sponsored Trials Research Articles

Intersectionality Between Country, Gender and Funding in Authorship for Phase III Trials Presented at the ASCO Annual Meeting 2022.

Multiple disparities have been recognized in the area of location, gender, and funding for leadership in oncology clinical trials. Understanding their intersectionality is crucial to be able to formulate policies and actions, to ensure research is representative of the global oncology community. Here, data from phase III trials presented at the ASCO Annual Meeting of 2022 (ASCO22) were analyzed. The location of institution, gender of lead and senior authors, and funding source for solid tumor phase III trial abstracts presented at the ASCO22 were analyzed. World Bank analytical grouping version 2021-2022 was used to describe regions and countries as high (HIC), upper-middle (UMIC), lower-middle (LoMIC), and low-income (LIC). Across 239 phase III abstracts, lead and senior authors respectively represented HIC institutions in 83% and 85%, UMIC in 13% and 12%, and LoMIC in 4% and 3%. No authors worked in LICs or sub-Saharan Africa. Women accounted for 29% of lead and 23% of senior authors. This distribution persisted across regions, with women as lead authors ranging from 19% (UMIC) to 31% (HIC), and as senior authors from 7% (UMIC) to 25% (HIC). Industry funded 62% of trials, academia 17%, and others 15%; 6% lacked funding. Industry funding was highest in HIC trials (66% for lead and senior authors), followed by UMICs (55% lead, 53% senior) and LoMICs (11% lead, 0% senior). Industry-sponsored trials were proportionally equally represented among female and male senior authors (63% each). There is marked intersectionality in leadership of oncology clinical trials presented at the world's largest oncology conference.

Postapproval Innovation For Oncology Drugs And The Inflation Reduction Act.

The Inflation Reduction Act's Drug Price Negotiation Program (DPNP) will affect incentives for biopharmaceutical investment by reducing prices and expected profits. Discussion has focused on the program's potential impact on the number of new drugs, but postapproval activity, which is common in oncology, will also be affected. If the history we describe is representative, postapproval exposure to DPNP eligibility dates would be high for oncology drugs. For 155 oncology drugs approved during the period 2000-21 (112 small molecules and 43 biologics), 57percent of labeled indications approved by the Food and Drug Administration and 68percent of industry-sponsored clinical trials occurred postapproval, often near or after DPNP selection dates. Compared with biologics, exposure to DPNP eligibility dates is more than twice as high for small molecules; although expected durations from drug approval to trial end are shorter, DPNP eligibility dates occur much sooner. Areas of potential postapproval impact include additional tumor types; rare diseases, particularly for drugs with multiple orphan indications; and pediatric indications, of which two-thirds occurred postapproval.

Comparison of Industry-Sponsored Trials (IST) and Investigator-Initiated Trials (IIT) in Advanced Genitourinary Cancers in the United States, Canada, United Kingdom and France

Comparison of Industry-Sponsored Trials (IST) and Investigator-Initiated Trials (IIT) in Advanced Genitourinary Cancers in the United States, Canada, United Kingdom and France

Patient Enrollment per Month (Accrual) in Clinical Trials Leading to the FDA Approval of New Cancer Drugs.

Insufficient patient enrollment per month (=accrual) is the leading cause of cancer trial termination. To identify and quantify factors associated with patient accrual in trials leading to the US Food and Drug Administration (FDA) approval of new cancer drugs. All anti-cancer drugs with FDA approval were identified in the Drugs@FDA database (2000-2022). Data on drug indication's background-, treatment-, disease-, and trial-related factors were collected from FDA labels, clinicaltrials.gov, and the Global Burden of Disease study. The association between patient accrual and collected variables was assessed in Poisson regression models reporting adjusted rate ratios (aRR). We identified 170 drugs with approval in 455 cancer indications on the basis of 292 randomized and 163 single-arm trials. Among randomized trials, median enrollment per month was 38 patients (interquartile range [IQR]: 26-54) for non-orphan, 21 (IQR: 15-38, aRR 0.88, p = 0.361) for common orphan, 20 (IQR: 10-35, aRR 0.73, p <0.001) for rare orphan, and 8 (IQR 6-12, aRR 0.30, p < 0.001) for ultra-rare orphan indications. Patient enrollment was positively associated with disease burden [aRR: 1.0003 per disability-adjusted life year (DALY), p < 0.001), trial sites (aRR: 1.001 per site, p < 0.001), participating countries (aRR: 1.02 per country, p < 0.001), and phase 3 vs. 1/2 trials (aRR: 1.64, p = 0.037). Enrollment was negatively associated with advanced-line vs. first-line treatments (aRR: 0.81, p = 0.010) and monotherapy vs. combination treatments (aRR: 0.80, p = 0.007). Patient enrollment per month was similar between indications with and without a biomarker (median: 27 vs. 32, aRR 0.80, p = 0.117). Patient enrollment per month was substantially lower in government-sponsored than industry-sponsored trials (median: 14 vs. 32, aRR 0.80, p = 0.209). Enrollment was not associated with randomization ratios, crossover, and study blinding. Disease incidence and disease burden alongside the number of study sites and participating countries are the main drivers of patient enrollment in clinical trials. For rare disease trials, greater financial incentives could help expedite patient enrollment. Novel trial design features, including skewed randomization, crossover, or open-label masking, did not entice patient enrollment.

Evolution of the Innovative Therapies for Children With Cancer Consortium Trial Portfolio for Drug Development for Children With Cancer.

The aim of the Innovative Therapies for Children with Cancer (ITCC) consortium is to improve access to novel therapies for children and adolescents with cancer. The evolution of the ITCC clinical trial portfolio since 2003 was reviewed. All ITCC-labeled phase I/II trials opened between January 1, 2003 and February 3, 2018 were analyzed in two periods (2003-2010 and 2011-2018), and data were extracted from the ITCC database, regulatory agencies' registries, and publications. Sixty-one trials (62% industry-sponsored) enrolled 3,198 patients. The number of trials in the second period increased by almost 300% (16 v 45). All biomarker-driven trials (n = 14) were conducted in the second period. The use of rolling six and model-based designs increased (1 of 9, 11% v 21 of 31, 68%), and that of 3 + 3 designs decreased (5 of 9, 55% v 5 of 31, 16%; P = .014). The proportion of studies evaluating chemotherapeutics only decreased (5 of 16, 31% v 4 of 45, 9%), the proportion of single-agent targeted therapies did not change (9 of 16, 56.2% v 24 of 45, 53.3%), the proportion of combination targeted therapies trials increased (2 of 16, 12%, v 17 of 45, 38%), the proportion of randomized phase II trials increased (1 of 7, 14% v 8 of 14, 57%). More trials were part of a pediatric investigation plan in the second period (4 of 16, 25% v 21 of 45, 46%). The median time for Ethics Committees' approvals was 1.7 times longer for academic compared with industry-sponsored trials. This study reports a shift in the paradigm of early drug development for childhood cancers, with more biologically relevant targets evaluated in biomarker-driven trials or in combination with other therapies and with more model-based or randomized designs and a greater focus on fulfilling regulatory requirements. Improvement of trial setup and recruitment could increase the number of patients benefiting from novel agents.

Diversity, Equity, and Inclusion in Urolithiasis Clinical Trials: Representative Enrollment by Race, Ethnicity, and Sex.

We sought to assess whether participant enrollment is appropriately representative of the overall urolithiasis population in published urolithiasis clinical trials. PubMed was queried for urolithiasis US clinical trials published from 2000 to 2022. Trials were evaluated for reporting patient race/ethnicity and sex data. These were then compared to the stone prevalence reported by the National Health and Nutrition Examination Survey from 2015 to 2018. We calculated a representation quotient (RQ) to describe enrollment of patients and then stratified by geographic location, study type, and funding source. Of the 180 urolithiasis trials performed in the US, we identified 40 trials (22%) reporting race or ethnicity and 104 trials (58%) reporting sex. Male and female participants are well represented (RQ 0.97 and 1.02, respectively). Overall, the RQ of Black, Asian American and Pacific Islander, White, Hispanic, and mixed/other participants is 1.84, 1.06, 1.04, 0.46, and 0.34, respectively. Trials completed in the Western Section and multi-institutional trials have the most proportional enrollment, while trials in the South Central and Southeastern Sections have underrepresentation of mixed/other and Hispanic patients. Enrollment was similar among all trial subtypes. Government- and industry-funded trials had more diverse enrollment than academic-funded trials. Only 1 in 4 published US urolithiasis trials report race or ethnicity enrollment. Mixed race and Hispanic participants are consistently underrepresented, while Black participants are overrepresented. Government- and industry-sponsored multi-institutional trials have the most proportional representation. Investigators should prioritize inclusive recruitment and improve reporting practices to accurately reflect the diversity of the urolithiasis population.

Principal Features of Industry-Funded Trials that Posted Informed Consent Forms on ClinicalTrials.gov: a Cross-Sectional Analysis.

We aim to characterize industry-funded trials that have posted the informed consent forms (ICFs), and to assess whether the role played by industry as 'sponsor' or 'collaborator' could impact several relevant variables. A cross-sectional study wasconducted on ClinicalTrials.gov on all industry-funded trials registered on or before 25 February 2023. We registered types of intervention, current recruitment status, design, enrollment, and countries involved. For trials with special interest to potential participants and investigators and/or clinicians an analysis of the role played by industry as 'sponsor' or 'collaborator' was performed. Of 116,281 industry-funded trials registered, 741 (0.6%) had posted ICFs. Most of these trials were categorized as 'completed' (n = 408) or 'terminated' (n = 107). The review of a sample of 359 trials showed that most were on drugs and/or biologics (59%), were randomized (51%), conducted exclusively in the USA (72%), and had posted results (79%), protocols (92%), and statistical analysis plans (SAPs) (89%). Trials in which industry participated as 'collaborator' were significantly more likely to post ICFs when trials were in the 'active, not recruiting' phase (OR 4.70, 99.71% CI 1.59-13.9, p < 0.001) than industry-sponsored trials. This was also the case when assessing drugs/biologics (OR 2.64, 99.71% CI 1.25-5.58, p < 0.001). Conversely, companies acting as 'sponsors' were significantly more likely to post ICFs with trials assessing devices, radiation interventions and/or diagnostic tests (OR 0.37, 99.71% CI 0.17-0.79, p < 0.001) than when participating as 'collaborators'. While industry-funded trials rarely post ICFs, when they do, they are highly compliant with transparency requirements. Regulations and ethics codes should consider requiring posting of protocols, SAPs, and ICFs for all clinical trials, regardless the type of sponsor.

Temporal trends and characteristics associated with racial, ethnic, and sex representation in COVID-19 clinical trials: A systematic review and meta-analysis

BackgroundEarly in the pandemic, extensive attention was cast on limited inclusion of historically underrepresented patient populations in COVID-19 clinical trials. How diverse representation improved following these initial reports remains unclear. MethodsPubMed, Embase and the Cochrane Library were searched (through April 2024) for US-based COVID-19 trials. Utilizing random-effects, we compared expected proportions of trial participants from racial and ethnic groups and of female sex between trials enrolling primarily in 2020 versus primarily 2021–2022. Meta-regression was performed to assess associations between trial characteristics and group representation. ResultsWe retrieved 157 studies comprising 198,012 participants. White (2020: 63.1% [95% CI, 60.8%–67.3%]; 2021–2022: 73.8% [95% CI, 71.5%–76.0%]) and female representation (2020: 46.1% [95% CI, 44.7%–47.4%)]; 2021–2022: 51.1% [95% CI, 49.3%–52.8%) increased across enrollment periods. Industry-sponsored trials were associated with higher White (coefficient, 0.10 [95% CI, 0.03–0.18]) and Hispanic or Latinx representation (coefficient, 0.16 [95% CI, 0.08–0.25]) and lower Asian (coefficient, −0.03 [95% CI, −0.06– –0.003]) and female representation (coefficient, −0.03 [95% CI, −0.07– –0.002]). Outpatient trials were associated with higher White (coefficient, 0.20 [95% CI, 0.13–0.26]) and female representation (coefficient, 0.16 [95% CI, 0.13–0.18]), and lower Black representation (coefficient, −0.10 [95% CI, −0.10– –0.08]). ConclusionsDespite improved female representation in COVID-19 trials over time, there was no clear increase in non-White representation. Trial characteristics such as primary sponsor, clinical setting, and intervention type correlate with representation of specific demographic groups and should be considered in future efforts to improve participant diversity.

Abstract PO5-26-11: The Breast Cancer Research Foundation Drug Research Collaborative – A unique and innovative model for industry-funded, academically driven research to advance the field of breast cancer

Abstract The Breast Cancer Research Foundation (BCRF) is committed to preventing and curing breast cancer through groundbreaking research. In pursuit of this mission, the BCRF launched the Drug Research Collaborative (DRC) in 2016—a pioneering program designed to bridge the gap between academic investigators and access to investigational therapies, thereby fostering greater academic-driven research in breast cancer. The DRC's primary objective is to fund independent, innovative, and high-quality investigator-initiated trials (IITs) and pre-clinical/translational research projects. In conventional drug development, industry-sponsored registration trials play a crucial role, leaving limited resources and scope for exploratory and translational IITs that fall outside the industry's drug approval strategy. Additionally, industry-funded IIT research faces challenges such as reputational risks, perceived influence during internal review processes, intellectual property (IP) concerns, and logistics/program management burdens. The BCRF-DRC program addresses these challenges by issuing requests for proposals to generate creative and unbiased ideas, which are then vetted through an academic review process involving leading breast cancer experts. The most promising research projects are selected for further advancement. The BCRF-DRC program is facilitated by the BCRF research staff, providing project management, while the Translational Breast Cancer Research Consortium (TBCRC), founded by the BCRF and also supported by Susan G. Komen, supports the clinical trial aspects of the program. Since its inception, the BCRF-DRC has expanded from one to three industry partners, securing a total funding of $25 million for 15 projects, including seven clinical trials and eight pre-clinical projects. This abstract reports on the ongoing progress and outcomes achieved by these three programs. The BCRF-DRC represents a revolutionary paradigm in research funding and collaboration by harnessing the collective power of industry partners, philanthropic organizations, and academic institutions. Through this collaborative effort, the BCRF-DRC provides a unique platform for researchers to accelerate the translation of scientific discoveries into effective clinical interventions, thus making significant strides in the field of breast cancer in the coming decades. By empowering academic investigators, fostering unbiased research, and addressing the limitations of industry-funded IITs, the BCRF-DRC is revolutionizing breast cancer research and driving the development of novel interventions. This abstract highlights the transformative potential of the BCRF-DRC program and its contribution to advancing breast cancer treatments and ultimately improving patient outcomes. The success of this collaborative model serves as a testament to the power of multi-sector partnerships and the pivotal role they play in shaping the future of breast cancer research. Citation Format: Unnati Jariwala, Dorraya El-Ashry, Judy Garber, Larry Norton. The Breast Cancer Research Foundation Drug Research Collaborative – A unique and innovative model for industry-funded, academically driven research to advance the field of breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-26-11.

Comparing the Real-World and Clinical Trial Bleeding Rates Associated with Oral Anticoagulation Treatment for Atrial Fibrillation.

Background The prevention of stroke in patients with atrial fibrillation (AF) involves the use of oral anticoagulation, commonly in the form of direct oral anticoagulants (DOACs). However, it comes with an increased risk of bleeding, and therefore, counselling patients on their individual risks is important. Although the majority of patients initiated on DOACs have been represented within the clinical trials, some cohorts are under-represented in whom clinicians cannot practice evidence-based medicine. Methods Utilising the pooled clinical trial (CT) data sourced from Medidata Enterprise Data Store, five recent open-label industry-sponsored AF trials were compared with real-world data (RWD) sourced from the HealthVerity™ Marketplace with the occurrence of bleeding events as the primary outcome of interest. Results A total of 64,421 patients were included in the analysis, with 3207 patients from the clinical DOAC trials and 61,214 patients from the RWD cohort. Overall, the patients from the RWD cohort had more co-morbidities, were older (72.2 ± 11.9 vs. 65.3 ± 10.7 years old, p < 0.001), had higher mean CHA2DS2VASc (3.98 ± 1.9 vs. 2.87 ± 1.73, p < 0.001), and HAD-BLED scores (2.13 ± 1.02 vs. 1/04 ± 0.93, p < 0.001) when compared to the trial data. When comparing the incidence of the first major bleed at 12 months post-treatment initiation, rates in the RWD cohort were significantly higher (10.69 vs. 18.97 per 100 person-years). The impact of co-morbidities such as age, CHA2DS2VASc, and HAD-BLED scores was similar in both cohorts; however, there was an under-representation of older females and more co-morbid patients within the clinical trial cohort. Conclusions DOAC-treated patients have a higher bleeding incidence rate in the RWD cohort than in clinical trials. This can be explained by the older patient age group with more complex medical h istories and higher HAS-BLED scores. The under-representation of higher-risk patients and lower proportion of females within clinical trials should be addressed to better translate clinical trial data into real-world clinical practice.

Abstract CT224: Preliminary efficacy and safety results from the (TATCIST) trial: A PSMA-directed targeted alpha therapy with FPI-2265 (225Ac-PSMA-I&amp;T) for the treatment of metastatic castration-resistant prostate cancer (mCRPC)

Abstract INTRODUCTION: Targeted α therapy (TAT) in mCRPC is a rapidly advancing class of radiotherapeutics that can effectively deliver potent and local radiation selectively to cancer cells while sparing the surrounding normal cells. Retrospective studies of 225Ac PSMA-RLT (radioligand therapy), have shown promise in pts with mCRPC, where activity correlates with disease characteristics and prior therapies. FPI-2265 (225Ac-PSMA-I&amp;T) consists of a small-molecule PSMA-targeting ligand coupled with a 225Ac radionuclide. Here we present the initial results from TATCIST, an ongoing, open-label, single-arm study (NCT05219500) to evaluate the efficacy and safety of FPI-2265 in pts with mCRPC that was initiated as an investigator-sponsored study then converted into an industry-sponsored trial with more stringent eligibility criteria. METHODS: Eligible pts are required to have progressive mCRPC with PSMA-positive PET. Prior radioligand therapy is permitted. Pts with skeletal metastases presenting as a superscan were excluded upon protocol amendment and excluded from this analysis. Four doses of FPI-2265 at 100 kBq/kg (±10%) are administered at 8-week intervals; de-escalation in cycle 2 and beyond is allowed. Proportion of pts with PSA ≤50%, maximum %PSA decrease, and safety and tolerability of FPI-2265 were assessed. RESULTS: At the time of the data cut (30Jan2024) 30 pts have received ≥1 dose FPI-2265, with 25 pts having ≥12 weeks follow up. For this analysis, 21 pts were evaluable for safety and 20 pts were evaluable for PSA response: 4 pts with superscan were excluded and 1 pt was excluded due to uninterpretable PSA data. In general, pts were heavily pretreated in terms of prior lines of therapy. Most pts (17/21 [81%]) had received a prior taxane, including 8 pts who received ≥2 lines of taxanes. Eight pts received prior 177Lu PSMA-RLT (Lu). PSA50 was achieved in 10/20 pts (50%); In a subset of pts with the baseline PSMA SUVmean &amp;gt;6 (n=13 overall; post-Lu, n=6), PSA50 was achieved in 9 pts (69%). Treatment-related adverse events (TRAEs) included dry mouth (18/21 [86%]), fatigue (10/21 [48%]) dry eye (6/21 [28%]), and anemia (6/21 [28%]). All were Grade 1-2 in severity, expect anemia Grade 3 which was observed in (5/21 [24%]). Other Grade 3 TRAEs included decreased platelet count (3/21 [14%]). No Grade 4 or 5 TRAEs were reported. Dry mouth was primarily Grade 1 (13/21 [62%]) with only 5 patients (24%) experiencing Grade 2 dry mouth; there were no related discontinuations. CONCLUSION: Preliminary efficacy and safety data as of 30Jan24 suggest that FPI-2265 is active in heavily pretreated pts with progressive mCRPC, including pts who received prior Lu therapy. Higher PSMA SUVmean was associated with improved PSA responses, Safety and tolerability were consistent with other published studies of 225Ac-PSMA-RLTs. These initial results support further investigation of FPI-2265 and a new phase 2/3 trial will begin enrolling soon. Citation Format: Ebrahim S. Delpassand, Mohammad Jawed Hashmi, Julia Kazakin, Omer Nawaz, Gabriella Garufi, Joanne Schindler, Luke Nordquist. Preliminary efficacy and safety results from the (TATCIST) trial: A PSMA-directed targeted alpha therapy with FPI-2265 (225Ac-PSMA-I&amp;T) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT224.

109 Age-Friendly Research Tools to Enhance Inclusion of Older Adults in Research

OBJECTIVES/GOALS: Older adults are often underrepresented in research due to recruitment and retention barriers, among others. Frameworks have been developed to address these barriers but have not been disseminated to research teams without aging expertise. We aimed to test Age-Friendly tools among non-aging-trained research teams. METHODS/STUDY POPULATION: Our team developed and/or adapted seven Age-Friendly research tools to improve inclusion of older adults in research. Tools included a communication guide, Age-Friendly research checklist, knowledge consent check, and condolence card template, among others. Non-aging-trained research team members (n= 21) were invited to pilot test them and share strengths, limitations, and areas for improvement for each tool. Feedback was collected for up to 4 months using REDCap surveys and analyzed for common themes. Participants provided written informed consent and received a stipend of $1000 upon the completion of the surveys. RESULTS/ANTICIPATED RESULTS: Sixteen participants (76%) from primarily cancer and neurology departments completed at least one survey. The communication guide, research checklist, and knowledge check were implemented the most within the participants' study populations. Participants shared that the tools were user-friendly, easy to access, and well-explained through webinar trainings (offered separately) or instruction sheets. The most frequently reported barriers were lack of time, industry-sponsored trial restrictions, and lack of age-appropriate study populations. DISCUSSION/SIGNIFICANCE: Age-Friendly tools were acceptable and valuable among non-aging-trained research members. Dissemination of these tools could improve the experience for research teams and older adults and help align demographics of enrolled study populations with demographics of the condition being studied.

Abstract P122: A Semi-Automated Tool Can Increase Stroke Clinical Trial Recruitment

Introduction: Stroke is a major public health problem, and stroke-related research is crucial. However, enrollment in randomized controlled stroke trials of acute therapies is challenging, leading to missed patients during the screening phase. The current screening process is person-dependent and can be highly variable across stroke team members, time of the day, and hospitals. High-volume stroke centers participate in more than 15 simultaneous NIH and industry-sponsored stroke trials. We hypothesize that a HIPAA-compliant screening tool can optimize screening and increase trial enrollment. Methods: This tool is a HIPAA-compliant application, developed by the Power Team at the University of Pittsburgh Medical Center, using Microsoft Power Apps. It has three purposes: screening, maintaining the database, and reporting. The screening process begins with patient demographics, and basic stroke-related data, followed by acute ischemic, subacute ischemic, and hemorrhagic stroke trial groups. Users can select their preferred subgroup of studies and continue filling in the rest of the form by answering pertinent questions. Upon form submission, the tool calculates the patient’s eligibility status for each trial in that group. The database is immediately available on the opening page or on the cloud. After submission, this can be edited, e.g., refusal for enrollment, or change in the patient’s condition. Reporting can be automated by using Power tools or it can be done manually. For manual reporting, the database gives filtering options based on time frames, patients, trials, and more. Results: The tool is in the testing phase, and we expect to have enrollment data by the time of the meeting. Conclusions: This tool has several advantages over manual screening. First, it reduces the orientation time for new research team members. Second, it mitigates the risk of overlooking potentially eligible patients in time-sensitive scenarios. Third, it is highly customizable by editing the codebook and can be adjusted per research site. This can be particularly helpful for smaller hospitals surrounded by underserved areas and can decrease health disparities by extending the chance of clinical trial participation. Fourth, it automatically maintains an up-to-date data log, which can be extracted at various intervals, such as monthly or per study. This not only streamlines the data recording but also simplifies reporting to study sponsors. Lastly, it expedites trial completion by accelerating the enrollment process. In conclusion, this tool can have significant benefits for research teams and for the broader public.

Diversity of US participants in AstraZeneca-sponsored clinical trials

BackgroundTo develop medicines that are safe and efficacious to all patients, clinical trials must enroll appropriate target populations, but imbalances related to race, ethnicity and sex have been reported. A comprehensive analysis and improvement in understanding representativeness of patient enrollment in industry-sponsored trials are key public health needs. MethodsWe assessed race/ethnicity and sex representation in AstraZeneca (AZ)-sponsored clinical trials in the United States (US) from 2010 to 2022, compared with the 2019 US Census. ResultsIn total, 246 trials representing 95,372 patients with complete race/ethnicity and sex records were analyzed. The proportions of different race/ethnicity subgroups in AZ-sponsored clinical trials and the US Census were similar (White: 69.5% vs 60.1%, Black or African American: 13.3% vs 12.5%, Asian: 1.8% vs 5.8%, Hispanic: 14.4% vs 18.5%). We also observed parity in the proportions of males and females between AZ clinical trials and US Census (males: 52.4% vs 49.2%, females: 47.6% vs 50.8%). Comparisons of four distinct therapy areas within AZ (Respiratory and Immunology [R&I]; Cardiovascular, Renal, and Metabolism [CVRM]; Solid Tumors; and Hematological Malignancies), including by trial phases, revealed greater variability, with proportions observed above and below US Census levels. ConclusionThis analysis provides the first detailed insights into the representativeness of AZ trials. Overall, the proportions of different race/ethnicity and sex subgroups in AZ-sponsored clinical trials were broadly aligned with the US Census. We outline some of AZ's planned health equity initiatives that are intended to continue to improve equitable patient enrollment.

Registered trials on novel therapies for myasthenia gravis: a cross-sectional study on ClinicalTrials.gov

Novel biologics in MG therapy research is on the rise. This research aimed to investigate the characteristics of registered trials on novel therapies for myasthenia gravis on ClinicalTrials.gov. This cross-sectional study used a descriptive approach to assess the features of the included trials on ClinicalTrials.gov. We found 62 registered trials from 2007 to 2023 on ClinicalTrials.gov. The results showed a yearly rise in the number of registered trials (r = 0.76, p < 0.001). Following 2017, more industry-sponsored trials were conducted (91.5% [43] vs. 60% [9], p = 0.009), fewer results were released (10.6% [5] vs. 60% [9], p = 0.001), and more trials entered phase 3 (67.4% [31] vs. 20% [2], p = 0.001). The most researched novel medications were neonatal Fc receptor inhibitors (51.2% [21]), complement inhibitors (39.0% [16]), and B cell depletors (14.6% [6]). According to the website’s data, the neonatal Fc receptor inhibitors and complement inhibitors were effective in treating myasthenia gravis patients in three trials (NCT03315130, NCT03669588, and NCT00727194). This study provides valuable insights into the profile of registered trials on novel therapies for myasthenia gravis. More clinical studies are needed in the future to prove the value of its application.

Differences and Common Ground in 177Lu-PSMA Radioligand Therapy Practice Patterns: International Survey of 95 Theranostic Centers.

177Lu-labeled prostate-specific membrane antigen (PSMA) radioligand therapy effectively treats metastatic castration-resistant prostate cancer. Patients requiring treatment, and consequently the number of theranostic centers, are expected to increase significantly after Food and Drug Administration and European Medicines Agency approval. This requires standardization or harmonization among theranostic centers. The aim of this study was to assess operational differences and similarities among 177Lu-PSMA treatment centers. Methods: A questionnaire comprising 62 items, designed by a core team of 5 physicians and externally reviewed by international experts, was developed. Study participants were asked to provide answers about their center, patient selection, radiopharmaceuticals, clinical assessment before and after 177Lu-PSMA treatments, laboratory values, treatment discontinuation, posttreatment imaging, and general information. An invitation e-mail to participate in the study was sent in June 2022. Duplicates were removed to allow for only one valid response per center. Results: Ninety-five of 211 (45%) contacted centers completed the questionnaire. Most participating centers were in Europe (51%), followed by America (22%) and Asia (22%). During the 12 mo before this study, a total of 5,906 patients received 177Lu-PSMA therapy at the 95 participating centers. Most of these patients were treated in Europe (2,840/5,906; 48%), followed by Asia (1,313/5,906; 22%) and Oceania (1,225/5,906; 21%). PSMA PET eligibility for 177Lu-PSMA was determined most frequently using 68Ga-PSMA-11 (77%). Additional pretherapy imaging included 18F-FDG PET/CT, CT, renal scintigraphy, and bone scintigraphy at 41 (49%), 27 (32%), 25 (30%), and 13 (15%), respectively, of the 84 centers for clinical standard of care, compassionate care, or local research protocols and 11 (26%), 25 (60%), 9 (21%), and 28 (67%), respectively, of the 42 centers for industry-sponsored trials. PSMA PET eligibility criteria included subjective qualitative assessment of PSMA positivity at 33% of centers, VISION criteria at 23%, and TheraP criteria at 13%. The mean standard injected activity per cycle was 7.3 GBq (range, 5.5-11.1 GBq). Sixty-two (65%) centers applied standardized response assessment criteria, and PSMA PET Progression Criteria were the most applied (37%). Conclusion: Results from this international survey revealed interinstitutional differences in several aspects of 177Lu-PSMA radionuclide therapy, including patient selection, administered activity, and the response assessment strategy. Standardization or harmonization of protocols and dedicated training are desirable in anticipation of increasing numbers of patients and theranostic centers.

Accessibility of clinical study reports supporting medicine approvals: a cross-sectional evaluation

ObjectivesClinical study reports (CSRs) are highly detailed documents that play a pivotal role in medicine approval processes. Though not historically publicly available, in recent years, major entities including the European Medicines Agency (EMA), Health Canada, and the US Food and Drug Administration (FDA) have highlighted the importance of CSR accessibility. The primary objective herein was to determine the proportion of CSRs that support medicine approvals available for public download as well as the proportion eligible for independent researcher request via the study sponsor. Study Design and SettingThis cross-sectional study examined the accessibility of CSRs from industry-sponsored clinical trials whose results were reported in the FDA-authorized drug labels of the top 30 highest-revenue medicines of 2021. We determined (1) whether the CSRs were available for download from a public repository, and (2) whether the CSRs were eligible for request by independent researchers based on trial sponsors’ data sharing policies. ResultsThere were 316 industry-sponsored clinical trials with results presented in the FDA-authorized drug labels of the 30 sampled medicines. Of these trials, CSRs were available for public download from 70 (22%), with 37 available at EMA and 40 at Health Canada repositories. While pharmaceutical company platforms offered no direct downloads of CSRs, sponsors confirmed that CSRs from 183 (58%) of the 316 clinical trials were eligible for independent researcher request via the submission of a research proposal. Overall, 218 (69%) of the sampled clinical trials had CSRs available for public download and/or were eligible for request from the trial sponsor. ConclusionCSRs were available from 69% of the clinical trials supporting regulatory approval of the 30 medicines sampled. However, only 22% of the CSRs were directly downloadable from regulatory agencies, the remaining required a formal application process to request access to the CSR from the study sponsor.

Recent landscape and trends for industry-sponsored pediatric clinical trials in China from 2013 to 2022.

Pediatric medication is a challenging issue globally. Promoting trials of medications for children and implementing measures to encourage innovation for addressing unmet medical and health needs are important. To explore the recent landscape of pediatric clinical trials of new investigational drugs conducted by pharmaceutical enterprises in China from 2013 to 2022 to provide insight into pediatric drug development in the pharmaceutical industry and regulatory policy formulation. We performed a cross-sectional observational investigation of pediatric clinical trials registered from January 1, 2013, to December 31, 2022, on the Registration and Information Disclosure Platform for Drug Clinical Trials, the official registration platform established in 2013 for trials of new investigational drugs initiated by biopharmaceutical enterprises. Trials that included pediatric participants (under 18 years old) were retrieved, and their relevant characteristics were extracted and analyzed. In total, 895 pediatric clinical trials were collected, accounting for 5.1% of the total registered clinical trials initiated prior to January 1, 2023. The overall average annual growth rate for the number of pediatric clinical trials was 12% (P < 0.001). Phase III trials accounted for the highest proportion (49.1%, 439). Of the 895 trials included, 736 (82.2%) were domestic trials, and 159 (17.8%) were international multicenter trials. In terms of tested drugs, investigations of biological products accounted for the largest proportion of trials (67.4%, 603). Among pediatric clinical trials, studies of vaccines accounted for the largest proportion of trials (41.0%, 367), followed by trials for rare diseases (17.2%, 154). Furthermore, geographical distribution analysis revealed that the largest and smallest numbers of trials were conducted in North China (35.7%, 320) and Northeast China (0.8%, 7), respectively. The growth trends for industry-sponsored clinical trials involving children illustrate the progress and increasing capability of pediatric drug development achieved in China since 2013. Current challenges and potential areas of focus for policymakers and stakeholders include investigating orphan drugs for rare diseases according to the unique epidemiological characteristics of Chinese children, expanding the scope of pediatric clinical trials, and improving the uneven geographical distribution of leading research centers.

Current status and future perspective of clinical trials for patients with multiple myeloma

There are two main types of clinical trials: industry-sponsored trials and investigator-initiated trials. Both of these, like the two sets of wheels on a car, are essential to development of treatments. Numerous clinical trials have been conducted in multiple myeloma, contributing to the development of new drugs and the current treatment landscape. Highly effective novel immunotherapies, such as bispecific antibodies and chimeric antigen receptor T-cell therapy, have emerged, and could be incorporated into the treatment landscape in the near future. However, given the improved performance of current standard therapies, the drawbacks (e.g., toxicity) of immunotherapy can be expected to outweigh the benefits (efficacy) in some patients. Therefore, clinical trials are designed to evaluate treatments stratified based on factors such as post-treatment efficacy and disease risk, and stratified treatment approaches are increasingly being considered as well as one-size-fits-all approaches to treatment development. In addition, the use of real-world data is being explored to make clinical trials more efficient. These approaches are expected to further improve the individualization and efficiency of multiple myeloma treatment.

From Research to Application of Wearable-Derived Digital Health Measures—A Perspective From ActiGraph

ActiGraph counts were first conceptualized in 1996 to provide an accelerometer-derived metric that can quantify physical activity based on intensity. ActiGraph incorporated this metric into its product suite, enabling its wide adoption in research studies. Over the last 20 years, ActiGraph activity counts have become one of the most common metrics and building blocks of health outcome measures used in wearable research, with &gt;24,000 journal articles published (based on Google Scholar search in 2023). Recently, this field of research is increasingly moving toward clinical application where wearable-derived metrics are growing in industry-sponsored clinical trials, including several use cases endorsed by the regulatory authorities. We celebrate this emerging trend as these patient-generated measures help reduce trial burden and enhance the meaningfulness of developed medical products to the patients. However, true adoption of digital measures in industry research is only in its infancy and still faces many challenges. As a digital health technology provider, ActiGraph has launched several strategic initiatives to support the research community to overcome these challenges and accelerate the translation of research to clinical application. The open-source release of the ActiGraph count algorithm was one of those initiatives. In this commentary, we take the opportunity to share our perspective in supporting the research community with this metric over the last 20 years, the motivation for making this open source, and what we are building to accelerate clinical adoption and realize the promise of better patient care.