Reasons For Screen Failure Research Articles

Screen Failures in Clinical Trials in Retina

PurposeDisparities in clinical trials are a major problem due to significant underrepresentation of certain gender, racial and ethnic groups. Several factors including stringent eligibility criteria and recruitment strategies hinder our understanding of retinal disease. Thus, we aimed to study the various reasons of screen failures and specific patient and study characteristics among screen failures. DesignThis is a cross-sectional retrospective study MethodsScreening data of 87 trials from 6 centers were analyzed. Study characteristics (disease studied, phase of trial, route of drug administration) and patient demographics (age, gender, race, ethnicity, and employment status) were compared among different causes of screen failures. Screen failures were broadly classified into six categories: exclusion due to vision-based criteria, exclusion due to imaging findings, exclusion due to other factors, patient-related criteria, physician related criteria and miscellaneous. Descriptive statistics, Pearson Chi-square test and ANOVA were used for statistical analysis. Main outcome measuresDetermine the prevalence of various reasons for screen failures in multiple trials and its trend among different study and patient characteristics. ResultsAmong 87 trials and 962 patients, 465(48.2%) patients were successfully randomized and 497(51.8%) patients were classified as screen failures. The trials were conducted for various retinal diseases. Mean age was 76.50 ±10.45 years and 59.4% were females. Predominantly whites(93.4%) and unemployed/retired patients(66.6%) were screened. Of the 497 screen failures, most were due to patients not meeting inclusion criteria of imaging findings (n=221[44.5%]) followed by inclusion of vision-based criteria (n=73 [14.7%]), exclusion due to other factors (n=75[15.1%]), patient-related (n=34[6.8%]), physician-related (n=28[5.6%]) and miscellaneous reasons (n= 39[17.8%]). Reason for screen failure was not available for 27(5.4%) patients. A higher proportion of patients screened for surgical trials (15%) declined to participate in the study compared to non-invasive trials involving topical drugs and photobiomodulation (0%).(p=0.02) ConclusionPatients not meeting the imaging and vision-cased criteria were the most common reasons for screen failures. Whites and unemployed patients predominantly participated in clinical trials. Patients are more inclined to continue participation in non-invasive clinical trials compared to surgical trials. Better recruitment strategies and careful consideration of study criteria can aid in decreasing the rate of screen failures.

Slow and Steady Wins the Race: Optimization of Older Adult Allogeneic Hematopoietic Cell Transplant (Allo-HCT) Candidates

Background: Allo-HCT is the only potentially curative therapy available for many hematologic malignancies, but due to its intensity and associated toxicities, is infrequently offered to older adults. This study explored the feasibility and efficacy of individualized, geriatric assessment (GA)-guided intervention among older adult candidates for allo-HCT. Methods: Patients ≥ 60 years old that were candidates for allo-HCT were recruited between June 11, 2021 and July 1, 2022. Exclusion criteria included inability to speak English, diagnosis of dementia, and planned allo-HCT in < 1 month or > 6 months. Baseline GA was completed at time of enrollment. Subjects were prescribed multi-domain personalized geriatric intervention based on results of their individual GA. Patients were continued on geriatric intervention for up to 6 months or until transplant. A post-intervention GA was conducted after 6 months or at time of admission for allo-HCT, whichever occurred first. Metrics included in GA are defined in table 1. Subjects were provided wearable accelerometer device for activity tracking. Primary outcome of interest was change in 6-minute walk test (6MWT) and secondary outcomes included improved or maintained short physical performance battery (SPPB), receipt of allo-HCT, and overall survival (OS). Wilcoxon signed rank test was used to compare GA metrics pre- and post-intervention, and OS was estimated using the Kaplan-Meier method. Exploratory analyses included univariable modeling of association of baseline GA metrics with receipt of allo-HCT and OS. Results: A total of 63 allo-HCT eligible patients were approached, 30 consented and were evaluable. Of 33 not enrolled, 17 declined (7 due to requirement to wear accelerometer device), 7 were planned for allo-HCT in < 1 month, 4 were not interested in allo-HCT, 3 had virtual appointments with incomplete GA, 1 had dementia and 1 with anticipated allo-HCT date > 6 months. The majority of enrolled subjects were male (80%) and all were non-Hispanic, white. Median age at enrollment was 68.9 years (range: 60.8-79.2). Half (n=15) were diagnosed with acute myeloid leukemia, 40% (n=12) with myelodysplastic syndrome, and one each with chronic myelomonocytic leukemia, myelofibrosis, and non-Hodgkin lymphoma. The median time from allo-HCT-eligible diagnosis to baseline GA was 4.1 months (range: 1.2-118.9). More than half (n=16, 53.3%) of subjects received allo-HCT. Median time to allo-HCT from diagnosis was 13.8 months (range: 3.3-122.1) and from baseline GA was 4.6 months (range: 0.5-10.8). No one baseline GA metric was associated with receipt of allo-HCT (table 2). Median OS from study enrollment for all subjects was not reached (95% CI: 9.8 month-NR) with median follow-up of 14.8 months (range: 10.7-19.3). At baseline, better gait speed on 6MWT (HR: 0.72; 95% CI: 0.59-0.89, p=0.0018), SPPB (HR: 0.76; 95% CI: 0.60-0.97; p=0.02), and Montreal Cognitive Assessment (MOCA; HR: 0.72; 95% CI: 0.55-0.95; p = 0.02) scores were all associated with improved OS in univariable analysis (table 2). Pre and post-intervention GA metrics are presented in table 1. Only 14 subjects completed at least partial post-intervention GA, 12 of whom received allo-HCT. Reasons for not completing post-intervention GA included subjects declining to schedule (n=6), issues of care coordination (e.g.: frequent or prolonged hospital admissions, changes to allo-HCT admission plan; n=6), and death (n=4). Twelve subjects had both pre and post-intervention 6MWT data, 83.3% (n=10) improved by at least 50 feet. Ten subjects had both pre and post-intervention SPPB and all improved by at least 1 point or maintained a normal score (>9). Discussion: Improvement in or maintenance of 6MWT and SPPB were demonstrated in the majority of subjects with measured pre and post-intervention GA. Unfortunately, attrition was a major limitation of the study. Patterns of loss to follow-up, as well as reasons for screen failure, will be important areas for further exploration and potential targets for intervention at institutional and provider levels. Importantly, age was not associated with OS. Early education about allo-HCT paired with patient-centered goals of care conversations may be useful in identifying older adults most motivated and likely to benefit from GA-guided intervention.

Analysis of Clinical Trial Screen Failures in Inflammatory Bowel Diseases [IBD]: Real World Results from the International Organization for the study of IBD.

Recruitment for randomized controlled trials [RCTs] in inflammatory bowel diseases [IBD] has substantially dropped over time. This study aimed to assess reasons why IBD patients are not included in sponsored multicentre phase IIb-III RCTs. All IOIBD members [n = 58] were invited to participate. We divided barriers to participation as follows: [1] reasons patients with active IBD were not deemed appropriate for an RCT; [2] reasons qualified patients did not wish to participate; and [3] reasons for screen failure [SF] in patients agreeing to participate. We assess these in a 4-week prospective study including, consecutively, all patients with symptomatic disease for whom a treatment change was required. In addition, we performed a 6-month retrospective study to further evaluate reasons for SF. A total of 106 patients (60 male [56.6%], 63 Crohn's disease [CD] [59.4%]), from ten centres across the world, were included in the prospective study. An RCT has not been proposed to 65 of them [mainly due to eligibility criteria]. Of the 41 patients to whom an RCT was offered, eight refused [mainly due to reluctance to receive placebo] and 28 agreed to participate. Among these 28 patients, five failed their screening and 23 were finally included in an RCT. A total of 107 patients (61 male [57%], 67 CD [62.6%]), from 13 centres worldwide, were included in our retrospective study of SFs. The main reason was insufficient disease activity. This first multicentre study analysing reasons for non-enrolment in IBD RCTs shows that we lose patients at each step. Eligibility criteria, the risk of placebo assignment, and insufficient disease activity were part of the main barriers.

P664 Analysis of Clinical Trial Screen Failures in IBD: Real World Results from the IOIBD

Abstract Background Recruitment rates for phase 2b/3 randomized controlled trials (RCTs) in IBD have substantially dropped over time. Several steps are required prior to successful patient randomization. Initially the physician must propose a trial to a potentially eligible patient during a pre-screening process (step 1). This is followed by patient’s acceptance or refusal (step 2). Finally, after informed consent the patient undergoes trial screening to ensure they meet all eligibility criteria (step 3). Evaluating each step separately, this study aims to assess reasons why IBD patients are not included in RCT and patients’ outcome after screen failure (SF). Methods All IOIBD member physicians (n=58) were invited to participate. To assess steps 1 and 2, consecutive IBD patients in relapse for whom a treatment change was required were prospectively included over a 4-week period. Reasons that prevented the IBD physician offering a sponsored multicenter phase 2b/3 RCT (step 1) and reasons why the patient accepted or refused to participate (step 2) were assessed through a physician and a patient survey, respectively. Reasons for SF (step 3) from the last 6 months, including the 4 weeks of steps 1-2, were collected retrospectively. Results A total of 104 (59 male, 62 CD, mean age of 37.2 years) and 102 patients (58 male, 63 CD, mean age of 40.6 years) from 12 centers were included in steps 1-2 and 3, respectively (Tables 1 and 2). Among 104 patients in relapse for whom a treatment change was required, 41 (39.4%) were offered a RCT. Of the 28 who consented to RCT, 5 failed their screening (SF rate of 17.9%) and 23 were included. Main reason that prevent IBD physicians from offering an RCT (step 1) are shown in Figure 1. After receiving information about RCT, major reasons why patients accepted or refused to participate included the trust they had in their IBD specialist and the risk of being assigned to a placebo, respectively (step 2). Regarding 102 patients included in step 3, main reasons of SF were insufficient disease activity (n=37), concurrent infection (n=15) and dropout (n=12) (Figure 2). Half of SFs could have been avoided by thorough prescreening. After SF, 51 patients were treated with commercially available therapy, 14 were rescreened for the same RCT (after resolution of the issue leading to SF), no treatment was required for 14, 10 were referred to surgery and 6 were screened for another RCT (the outcome was unknown for 7). Conclusion This first multicentric study reported a SF rate of 17.9%. Insufficient disease activity and the risk of assigning the patient to a placebo seem to be barriers to inclusion. Half of SFs could have been avoided by better pre-screening. After SF, most of patients were treated with commercially available therapy.

S1400 The Complexity of NASH Cirrhosis Clinical Trials: Screen Failure Reasons and Baseline Patient Characteristics

Introduction: Patients with NASH cirrhosis has the highest likelihood of developing major adverse liver related events and an unmet need in terms of therapeutic options. Several drugs are being tested in patients with NASH cirrhosis in phase 2 trials. Screen failure (SF) reasons in non-cirrhotic NASH trials have been described; however, limited data exists on the reason for screen failure reasons in NASH cirrhosis trials. The aim of this study was to understand the reasons for screen failure in 5 NASH cirrhosis trials and to describe the patient's characteristics of both screens failed subjects and those who randomised. Methods: Data on patients who were presented for screening visits for five phase 2 NASH cirrhosis trials at one research site were analysed. The reasons for screen failure were divided into 4 major categories: 1. Biopsy, 2. Laboratory tests, 3. Imaging tests, 4. Other. Baseline characteristics including demographics, clinical history, lab values, findings from imaging tests and biopsy were collected. Characteristics of patients that screen failed were compared to those who randomised using 2-sided t-test, p value < 0.05 was considered statistically significant. Results: 68 patients were included in the analysis. 23 randomised (33.8%) and 45 screen failed (66.17%). The mean age was 57.98 years with 45% (31) of the population being male. Mean BMI in the whole population was 38.38 Kg/m2. 51.47% (35) of the patients were found to have type 2 diabetes. The reasons for screen failure were as follows: 4 (8.8%) on biopsy, 12 (26.6%) on labs, 11 (24.4%) in imaging tests, 15 (33.3%) for other reasons. The top 4 causes included in the other category were patients outside of the screening window, using prohibited medications, subject dropping out and presence of esophageal varices. There was no significant difference between the screen failure group and the randomised group in terms of platelet count, INR, bilirubin, FIB4 score and AGILE4 score (p > 0.05 for all). (Figure) Conclusion: NASH cirrhosis trials have similar screen failure rates compared to non-cirrhotic trials; however, the reasons for screen failure are different. In NASH cirrhosis trials, fewer patients screen failed because of not meeting histologic criteria on liver biopsy which has been the major reason for screen failure in non-cirrhotic trials. Baseline laboratory and imaging tests were not different between patients who screen failed and those who randomised. (Table)Figure 1.: Minor causes of screen failure Table 1. - Comparison chart showing basic characteristics of randomised and screen failure population 2 sided T Test Mean Mean Mean Total Population Randomised population Screen Failure population T-Test Age 58.31 60.95 56.88 BMI 37.38 39.88 37.05 Hba1C 6.42 6.43 6.46 % Diabetes 52.90% 48.50% 51.40% Platelets 177.23 159.26 187.30 0.13 Bilirubin 0.795 0.83 0.76 0.52 INR 1.13 1.15 1.12 0.24 kPa 23.31 24.03 22.24 0.79 Agile 4 0.44 0.518 0.42 0.23 CAP score 302.35 310.33 297.57 0.59 Fib 4 3.12 2.95 3.41 0.53

The Clinical Profile and Natural History of Patients Who Fail Screening for Transcatheter Mitral Valve Replacement: Rationale and Design of the Prospective Multicenter Mitral Valve Screening Survey (MVSS)

Mitral valve disease is insidious and associated with a decreased quality of life and survival over time. Despite surgery being the standard of care, many patients are at prohibitive surgical risk. Furthermore, a substantial proportion of patients with symptomatic mitral valve disease fail stringent screening criteria for transcatheter mitral valve replacement (TMVR). The natural history of patients who fail screening is not well-characterized, and data are limited on the reasons for screen failure in this population. The Mitral Valve Screening Survey (MVSS) seeks to detail the clinical profile and natural history of patients who fail screening for TMVR. The MVSS is a prospective, multicenter registry enrolling up to 1000 consecutive subjects who, after screening for TMVR, are deemed not to be candidates. Subjects will be followed for 30 days after failing screening for TMVR and annually for up to 5 years with clinical evaluations. The primary study endpoint of the MVSS registry is all-cause mortality at 1 year. Additional secondary endpoints include all-cause mortality, hospitalizations, subsequent mitral valve intervention (transcatheter or surgical), reason for screen failure, and quality-of-life assessments at 30 days and annually up to 5 years of follow-up. The MVSS registry is the first prospective multicenter study to characterize the clinical and anatomical profile of patients who fail screening for TMVR while providing longitudinal clarification on the natural history and outcomes of these patients. Clinical trial registrationMitral Valve Screening Survey (MVSS), https://clinicaltrials.gov/ct2/show/NCT04736667, NCT04736667

994-P: DINAMO—Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents with Type 2 Diabetes (T2D) : Innovative Study Design and Baseline Characteristics

T2D in youth remains challenging to manage and there is need for an expanded treatment armamentarium. The DINAMO study was designed to overcome recruitment difficulties that plagued previous T2D studies in youth. Within 3 years, DINAMO enrolled 158 patients aged to &amp;lt;18 years at 64 sites in 12 countries with HbA1c 6.5-10.5% on metformin and/or insulin. Unique to this study, participants with a modifiable exclusion initially could be re-screened up to 5 times. Patients were randomized to linagliptin (5 mg) , empagliflozin (mg) , or placebo (1:1:1) . At week 12, 50% of empagliflozin patients who could not attain HbA1c &amp;lt;7.0% were re-randomized to either remain on mg or increase to 25 mg. HbA1c change from baseline to week 26 was the primary efficacy endpoint and safety was evaluated over 52 weeks. The main reason for screen failure was HbA1c out of range (57%) . Baseline characteristics of participants are shown below. The study will be completed in fall 2022. Innovative approaches (e.g., testing multiple agents against a single placebo, re-screening patients with modifiable exclusion criteria, using a consortium model to consolidate efforts of several centers, and creating a Steering Committee to adjust study design) can successfully overcome the challenges of conducting clinical trials in youth with T2D. Disclosure L.M. Laffel: Advisory Panel; Medtronic, Roche Diabetes Care. Consultant; Boehringer Ingelheim International GmbH, Dexcom, Inc., Dompé, Insulet Corporation, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk, Provention Bio, Inc. T. Danne: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG. Research Support; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG. Stock/Shareholder; DreaMed Diabetes, Ltd. W.V. Tamborlane: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Medtronic, Novo Nordisk, Sanofi, Takeda Pharmaceutical Company Limited. G.J. Klingensmith: Research Support; AstraZeneca, Novo Nordisk, Takeda Pharmaceutical Company Limited. Stock/Shareholder; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. C. Schroeder: Employee; Boehringer Ingelheim Inc. D. Neubacher: Employee; Boehringer Ingelheim International GmbH. N. Soleymanlou: Employee; Boehringer Ingelheim Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc. J. Marquard: Employee; Boehringer Ingelheim Inc. P. Zeitler: Consultant; Boehringer Ingelheim International GmbH, Daiichi Sankyo, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk, Takeda Pharmaceutical Company Limited. S.M. Willi: Advisory Panel; Boehringer Ingelheim International GmbH, Medtronic. Research Support; Jaeb Center for Health Research, Provention Bio, Inc. Other Relationship; National Institute of Diabetes and Digestive and Kidney Diseases. Funding Boehringer Ingelheim

658. Diagnostic Testing Among Patients with Suspected Recurrent Clostridioides difficile Infection (rCDI) in ECOSPOR III a Phase 3 Clinical Trial: Implications for Clinical Practice vs Clinical Trials

BackgroundAccurate diagnosis of rCDI is challenging because of limitations in test performance and alternative causes of recurrent diarrhea, such as post-infectious irritable bowel syndrome (IBS). Stool enzyme immunoassay (EIA) toxin testing (TOX) is the best predictor of active disease, but may miss cases of CDI when toxins are below the limit of detection. In contrast, glutamate dehydrogenase (GDH) or PCR have high sensitivity but cannot differentiate colonization from infection, leading to possible overdiagnosis due to low specificity. In ECOSPOR III, SER-109, an investigational purified microbiome therapeutic, was superior to placebo in reducing rCDI (12.4% vs 39.8%, respectively; p-value < 0.001). We examined diagnostic testing patterns among screened subjects. MethodsPatients with ≥2 prior episodes and ≥3 unformed bowel movements over 48 hours were screened. To ensure enrollment of patients with active CDI, toxin testing was required at entry via a local certified or central lab (Eurofins; Framingham, MA). Subjects with discordant GDH+/TOX- tests at the central lab had reflex confirmatory testing with a cell cytotoxicity neutralization assay (CCNA), considered the “gold standard” for toxin testing.ResultsThe leading reason for screen failure among 281 subjects screened was a negative toxin test (50/99; 50.5%). Of 182 patients enrolled, 59 (32.4%) qualified with EIA TOX+ at the local lab (33 TOX+; 25 GDH+/TOX+) and 122 (67.0%) qualified by the central lab (Table 1). Of these 122 subjects, 87 qualified by GDH+/TOX+ but 35 required additional reflex testing by CCNA due to discordant GDH+/TOX-results; all 35 were positive. Diagnostic Testing for Qualifying C. difficile Episode in ITT Population ConclusionThese diagnostic testing patterns suggest a subset of patients with suspected rCDI have toxin concentrations below the EIA threshold for detection or may have an alternative cause of diarrhea, such as post-infectious IBS. Thus, the limitations of EIA toxin testing need to be considered in clinical practice when evaluating patients with compatible symptoms of rCDI and a high prior probability of infection. In contrast, in trials of investigational agents, toxin testing assures enrollment of patients with active disease and accurate estimates of efficacy. Disclosures Matthew Sims, MD, PhD, FACP, FIDSA, Astra Zeneca (Independent Contractor)Diasorin Molecular (Independent Contractor)Epigenomics Inc (Independent Contractor)Finch (Independent Contractor)Genentech (Independent Contractor)Janssen Pharmaceuticals NV (Independent Contractor)Kinevant Sciences gmBH (Independent Contractor)Leonard-Meron Biosciences (Independent Contractor)Merck and Co (Independent Contractor)OpGen (Independent Contractor)Prenosis (Independent Contractor)Regeneron Pharmaceuticals Inc (Independent Contractor)Seres Therapeutics Inc (Independent Contractor)Shire (Independent Contractor)Summit Therapeutics (Independent Contractor) Sahil Khanna, MBBS, MS, Seres (Grant/Research Support) Darrell Pardi, MD, seres (Consultant)Vedanta (Consultant) Paul Feuerstadt, MD, FACG, Ferring/Rebiotix Pharmaceuticals (Consultant, Scientific Research Study Investigator, Speaker's Bureau)Finch Pharmaceuticals (Scientific Research Study Investigator)Merck and Co (Speaker's Bureau)SERES Therapeutics (Consultant, Scientific Research Study Investigator)Takeda Pharmaceuticals (Consultant) Elaine E. Wang, MD, Seres Therapeutics (Employee) Elaine E. Wang, MD, Seres Therapeutics (Employee, Shareholder) Barbara McGovern, MD, Seres Therapeutics (Employee, Shareholder) Lisa von Moltke, MD, Seres Therapeutics (Employee, Shareholder)

Disparities by Race and Ethnicity Among Adults Recruited for a Preclinical Alzheimer Disease Trial

Underrepresentation of many racial/ethnic groups in Alzheimer disease (AD) clinical trials limits generalizability of results and hinders opportunities to examine potential effect modification of candidate treatments. To examine racial and ethnic differences in recruitment methods and trial eligibility in a multisite preclinical AD trial. This cross-sectional study analyzed screening data from the Anti-Amyloid in Asymptomatic AD study, collected from April 2014 to December 2017. Participants were categorized into 5 mutually exclusive ethnic/racial groups (ie, Hispanic, Black, White, Asian, and other) using participant self-report. Data were analyzed from May through December 2020 and included 5945 cognitively unimpaired older adults between the ages of 65 and 85 years screened at North American study sites. Primary outcomes included recruitment sources, study eligibility, and ineligibility reasons. To assess the probability of trial eligibility, regression analyses were performed for the likelihood of being eligible after the first screening visit involving clinical and cognitive assessments. Screening data were included for 5945 participants at North American sites (mean [SD] age, 71.7 [4.9] years; 3524 women [59.3%]; 5107 White [85.9%], 323 Black [5.4%], 261 Hispanic [4.4%], 112 Asian [1.9%], and 142 [2.4%] who reported race or ethnicity as other). Recruitment sources differed by race and ethnicity. While White participants were recruited through a variety of sources, site local recruitment efforts resulted in the majority of Black (218 [69.2%]), Hispanic (154 [59.7%]), and Asian (61 [55.5%]) participants. Participants from underrepresented groups had lower mean years of education (eg, mean [SD] years: Hispanic participants, 15.5 [3.2] years vs White participants, 16.7 [2.8] years) and more frequently were women (226 [70.0%] Black participants vs 1364 [58.5%] White participants), were unmarried (184 [56.9%] Black participants vs 1364 [26.7%] White participants), and had nonspousal study partners (237 [73.4%] Black participants vs 2147 [42.0%] White participants). They were more frequently excluded for failure to meet cognitive inclusion criteria (eg, screen failures by specific inclusion criteria: 147 [45.5%] Black participants vs 1338 [26.2%] White participants). Compared with White participants, Black (odds ratio [OR], 0.43; 95% CI, 0.34-0.54; P < .001), Hispanic (OR, 0.53; 95% CI, 0.41-0.69; P < .001), and Asian participants (OR, 0.56; 95% CI, 0.38-0.82; P = .003) were less likely to be eligible after screening visit 1. Racial/ethnic groups differed in sources of recruitment, reasons for screen failure, and overall probability of eligibility in a preclinical AD trial. These results highlight the need for improved recruitment strategies and careful consideration of eligibility criteria when planning preclinical AD clinical trials.

Reasons for Screen Failure for Transcatheter Mitral Valve Repair and Replacement

Despite an expanding armamentarium of devices, many patients with mitral regurgitation referred for transcatheter mitral valve repair (TMVr) or replacement (TMVR) do not meet strict clinical trial inclusion and exclusion criteria. We sought to understand the rates that patients were excluded from transcatheter mitral valve therapies and reasons why. We retrospectively analyzed the medical charts and correspondence related to patients referred to our tertiary valve center for TMVr or TMVR between June 2016 and September 2019. Patients were screened for eligibility by our structural Heart Team for either TMVr or TMVR. If TMVr or TMVR was not offered, the reason for screen failure was recorded and categorized. Over the 3-year period, 564 patients were referred for TMVr and orTMVR. Out of these, 15.9% were determined to be eligible for, and underwent, surgical repair or replacement. Ninety-two patients (16.3%) underwent TMVr or TMVR. The majority of patients (343 of 564, 60.8%) ultimately did not undergo intervention. The primary reason for exclusion was clinical in 38.5%, issues related to patient preference of care delivery in 38.8%, anatomical in 13.7%, and futility in 9.0%. In contemporary real-world practice, the majority of patients with mitral regurgitation referred for transcatheter therapies are excluded. Clinical trials testing new transcatheter devices should be encouraged to record and report reasons for screen failure and follow these patients to better understand optimal timing of intervention, address challenging anatomies, and, ultimately, improve penetrance of these novel therapies.

Abstract 16677: Real World Screen Failure Rates for Transcatheter Mitral Valve Repair and Replacement for Mitral Regurgitation

Background: Despite an expanding armamentarium of devices, many patients with mitral regurgitation referred for transcatheter mitral valve repair or replacement are not eligible to participate in the clinical trials or receive a commercially available device. We sought to understand the reasons why patients were excluded from receiving therapy. Methods: We retrospectively analyzed the medical charts, and correspondence related to patients referred to our tertiary valve center for transcatheter mitral valve replacement (TMVR) or transcatheter mitral valve repair (TMVr) between June 2016 to September 2019. Patients were screened for eligibility by our structural Heart Team for either TMVR or TMVr. If TMVR or TMVr was not offered the reason for screen failure was recorded and categorized. Results: Over the 3-year period, 564 patients were referred for TMVR/TMVr. Of these, 15.9% were determined to be eligible for and underwent surgical repair or replacement. 440 patients (78.0%) were considered for TMVR/TMVr. 92 patients (16.3%) underwent TMVR/TMVr. The majority of patients (348/564, 61.7%) ultimately did not undergo intervention (Panel A). The reasons for exclusion were clinical in 78%, issues related to patient preference of care delivery in 49% of patients, anatomical in 37% and futility in 25% of patients (Panel B). Conclusions: The majority of patients with mitral regurgitation referred for transcatheter mitral therapy are excluded for a variety of reasons. Clinical trials testing new transcatheter mitral valve devices should be encouraged to follow patients who are excluded to better understand optimal timing of intervention, address challenging anatomies, and ultimately improve penetrance of these novel therapies.

FDA Analysis of Screen Failures By Race in Clinical Trials of Acute Myeloid Leukemia

Background: Ethnic and racial minorities are underrepresented in oncologic clinical trials. One potential barrier to participation may be narrow eligibility criteria which contribute to an increased rate of screen failure among minorities. Prior work in multiple myeloma demonstrated a higher rate of screen failure among black or African-American (AA) patients and lower rate of screen failure among Asian patients compared with white patients (1). Here, we examine screen failure rates by race in patients screened for participation in clinical trials of acute myeloid leukemia (AML). Methods: Trials submitted to the U.S. Food and Drug Administration (FDA) to support approval of new treatments for AML between 2016-2019 were examined. Trials which included information on screen failures and race were included. Trial, screen failure status, basic demographic information (age, gender, race, and ethnicity), country of participant, and reason for screen failure (if relevant) were abstracted from the trials. Screen failure rates were calculated based on this information. Results: Twenty-one trials of AML therapies were identified, of which screen failure and race information were available in fourteen. Of these, information on reason for screen failure was available in nine. A total of 6,471 patients were identified across fourteen trials (Table 1). Race was recorded as unknown for 2,934 (46%) of patients. A total of 3,372 (52%) screen failures occurred. Minorities were more likely to be screen failures at 201/603 (33%) compared to whites at 27%. Of minorities, screen failures occurred in 29% of black/AA patients, 36% of Asians, and 36% of patients of any other race. A total of 579 patients were included in the nine trials that included data on reasons for screen failures (Table 2). Lack of appropriate mutation (i.e. IDH1/2, FLT3) was the most common reason for screen failure overall and was more common in black/AA (41%) and Asian patients (66%) compared to white patients (29%). Other issues related to the disease course (e.g. not at the appropriate point in treatment, not treated within the time limit set in the protocol) led to screen failure in 28% black/AA patients versus 9-22% for other races (19% overall). White patients were more likely than patients of other races to be screen failures due to cardiac issues (4%) and laboratory abnormalities (6%). Conclusions: Minority patients were numerically more likely to be screen failures compared to whites in trials of AML therapeutics, which exemplifies the known issue of lower minority recruitment in clinical trials. Minority patients were more likely to be screen failures due to lack of appropriate mutation and less likely due to lab abnormalities or cardiac issues. The significance of this finding is uncertain given the limited information on reasons for screen failure and the small number of minority patients in the database. Further investigation into screen failures in minority patients with AML is indicated. These results underscore the importance of including racial and ethnic minorities in all phases of translational and clinical research to further precision oncology for all patients since oncogenic driver mutation frequencies may vary among different populations. (1) Kanapuru B, Fernandes L FDA analysis of multiple myeloma trials supporting approval; Presented at FDA-AACR workshop to examine under-representation of African Americans in multiple myeloma clinical trials 2/13/20 Disclosures No relevant conflicts of interest to declare.

Abstract 26: A novel electronic platform to improve clinical trial workflow and screening

Abstract Background: Early-phase clinical trials are increasingly complex, with “seamless” phase I/II trial designs that include multiple parallel disease and/or biomarker-selected expansion cohorts. Challenges for participating sites in phase 1 (P1) trials include rapid identification of patients for available trial slots, high screen failure (SF) rates, and workload distribution among nurses and data coordinators. The Princess Margaret (PM) Cancer Centre Solid Tumor P1 program is the largest early-phase clinical trial program in Canada. There are currently 53 actively recruiting clinical trials, and approximately 250-300 patients are enrolled annually. To improve operational efficiency at the point of care, we designed a novel electronic platform, termed Phase One Spot Tracker (POST). Methods: An electronic, password-restricted, web-based tracker and smartphone-enabled app was created using PHP Laravel, JavaScript (iOS), and Java (Android). The intention was to replace the two previously used Excel spreadsheets, where one listed the trial information and the other included available slot allocations by trial. These spreadsheets were cumbersome to use in clinic, without the ability to search or filter. POST enabled all users to access the data from any computer or phone, increased the ease of updating information in real time, and functioned as a search engine to locate available spots more quickly. It contains specific information including brief trial description, key eligibility criteria, biopsy requirements, status of trial slots (e.g., screening, available, pending, etc.). The data security of POST is ensured by Amazon Web Services. Results: Prior to launching POST, three time-measured simulations showed that it reduced the coordinators’ workload to update trial information by 30 minutes. Currently POST is used by 65 users, including 7 physicians, 14 nurses, and 29 coordinators at the PM Cancer Centre. POST is used by investigators during a weekly P1 new patient consultation clinic to identify trial candidates as well as in weekly P1 team meetings to review all patients enrolled and approached for clinical trials. We are enhancing the POST platform to enable tracking of SF (patients who undergo study-specific screening procedures but are not enrolled in a clinical trial), timeline for replacing patients who screen fail, and reasons for SF. Conclusions: POST is an electronic, smart phone-enabled platform that can be implemented at the point of care for early-phase clinical trials. POST can also provide real-time tracking data about operational metrics (startup time, screening time, enrollment data, nursing and data coordinator workload, and screen failures) that can be used to drive quality improvement. POST can be extended to other disease site groups as well as to other institutions. This will eventually lead to an increase in work efficiency and provide a better quality of care for cancer patients. Citation Format: Ramy R. Saleh, Olivia Chan, Silvi Kuld, Patrick Marban, Anna Spreafico, Aaron Hansen, Albiruni Razak, Lillian L. Siu, Philippe L. Bedard. A novel electronic platform to improve clinical trial workflow and screening [abstract]. In: Proceedings of the AACR Special Conference on Advancing Precision Medicine Drug Development: Incorporation of Real-World Data and Other Novel Strategies; Jan 9-12, 2020; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(12_Suppl_1):Abstract nr 26.

Abstract WMP106: Why Are Women Less Represented in ICH Trials?

Background: Fewer women than men tend to be enrolled in clinical trials of intracerebral hemorrhage (ICH). It is unclear whether this reflects lower prevalence of ICH in women, selection bias, poor recruitment efforts, or other factors. We undertook this study to examine differences between women and men in the reasons for exclusion from the iDEF (Intracerebral hemorrhage Deferoxamine) trial. Methods: The screen failure log included 29 different reasons for exclusion. Chi square statistics and p-values were used to evaluate whether women and men differed with regard to reason for screen failure. Findings: The iDEF trial enrolled 294 subjects; 38.5% were women. A total of 8776 subjects were screen failures. Sex was missing in 58. The remaining 8718 were included in this analysis; 3982 women (45.7%) and 4736 men (54.3%) (p&lt;0.0001). The enrollment rates were 2.8% in women vs. 3.7% in men (p=0.01). We were unable to obtain consent in 1.3% of women vs 1.7% of men (p=0.1), and patients/families declined participation in 1.3% of women vs. 1.3% of men (p=0.9). More women than men failed screening because of age &gt;80 (22.4% vs 12.6%) and pre-existing DNR/DNI (3.7% vs. 2.8%). Conversely, fewer women than men failed screening because inability to administer study drug within 24 hour due to late presentation (6.6% vs 7.8%), admission NIHSS score &lt;6 (10.2% vs 13.2%), coagulopathy (5.3% vs 7.5%), inability to comply with the protocol (0.7% vs 1.3%), abnormal renal function (1.9% vs 2.9%), drug/alcohol abuse (1.7% vs 3.7%), and presentation with confirmed aspiration or pneumonia (1.1% vs 1.8%).These differences were statistically significant. Interpretation: Results from this multi-center, prospective, ICH trial indicate that lower rates of women enrollment may be attributed to older age and higher rates of pre-existing DNR/DNI orders. Inability to obtain consent or declining participation was similar between women and men, arguing against selection bias. Our findings should be confirmed in other ICH trials to determine if additional efforts are needed to improve women’s participation in future studies. Funding: US National Institutes of Health and US National Institute of Neurological Disorders and Stroke (U01NS074425)

A Phase II Trial of Topical Sodium Nitrite in Patients with Sickle Cell Disease and Leg Ulcers

Background Leg ulcerations are a serious and debilitating complication of sickle cell disease (SCD). Patients with SCD and leg ulcers have biomarkers of severe hemolytic anemia, a state associated with low bioavailability of nitric oxide (NO). Therapies directed at restoring NO bioavailability might prove beneficial. We selected topical sodium nitrite for clinical development due to its safety profile and vascular, anti-microbial, antiplatelet, and pro-keratinocyte functions. The nitrite anion is a vasodilator in vivo by generating NO in tissues with low oxygen tension and pH, conditions that are likely present in chronic wounds. Data from our successful phase 1 study showed improved regional blood flow, decreased ulcer pain, and appeared to improve ulcer healing. The dosing data informed the concentration of active ingredient to be used and suggested sodium nitrite efficacy in SCD patients with leg ulcers (Minniti, CP et al, Lancet Haematol 1, e95-e103). Study Design and Methods This is a multicenter, phase 2, prospective, randomized, placebo-controlled study of topical sodium nitrite in patients with SCD and leg ulcers. Primary aim is to determine the safety, tolerability, and effectiveness of twice a week topical application of study ointment for 10 weeks. We hypothesize that sodium nitrite will 1) accelerate wound healing (&gt;25% improvement over placebo arm); and/or 2) decrease pain at the wound site (&gt;20% over placebo). Ulcers measured by ImageJ planimetry software to increase accuracy. The secondary aims are to: a) evaluate the effect of hydroxyurea (HU) on leg ulcer healing in combination with topical sodium nitrite or placebo; b) assess changes in ulcer microbiome after application of sodium nitrite or placebo and how these changes may relate to healing; c) evaluate the dermal composition and microvascular structure in the ulcer beds. We plan to enroll 50 adults with all SCD genotypes and leg ulcers not individually &gt;100 cm2, such that, after an expected 20% dropout, 40 subjects will complete &gt; 8 weeks of treatment. Exclusion criteria: use of PDE5 inhibitors, NO, L-arginine, nitroprusside, nitroglycerine; acute bacterial infection; pre-existing methemoglobinemia (&gt;3.5% on two different occasions); G6PD deficiency. Randomization is stratified by HU use to minimize potential confounding effects on study outcomes. Funded by the Food and Drug Administration (FDA) Division of Orphan Drug Development (# FD-R-0005729); active at two sites (ClinicalTrials.gov NCT02863068). Results We have screened 68 subjects with known history of leg ulcer: 46% were not eligible as the ulcer was closed at the time of screening. Of the 30 eligible, 13 subjects enrolled (12 at Montefiore Medical Center, 1 at the University of Pittsburgh), with 9 subjects randomized. Reasons for screen failure, other than ulcer closed, are depicted in fig 1. Three subjects experienced ulcer decrease &gt;25% in the run-in period and did not have ointment application as per protocol. One subject withdrew due to lack of adherence. Therefore the overall dropout rate at this time is 33%, higher than the 20% anticipated. No study ointment SAEs have been noted, AEs have been minor and non-ointment related. Most SAEs have been VOCs, expected in this patient population and wound infections. Discussion As expected, enrollment of subjects with a rare complication of a rare disease is challenging. The recurrent pattern of ulcers in SCD was the reason why the majority of patients were not able to enroll, as the ulcer was closed at the time of screening. We monitor them closely for possible re-opening. Simplification of protocol-related procedures, such as decrease in number of required visits from twice to once a week by packaging dose-specific blister packs that the patient takes home for self-administration of ointment, has facilitated enrollment. Travel to the center is being addressed. A close relationship between the subjects and study team is essential. Co-location of the wound specialist in the sickle cell clinic and training the research nurse for wound care has helped with recruitment. Disclosures Ogu: Vertex Pharmaceuticals: Consultancy. Kato:Novartis, Global Blood Therapeutics: Consultancy, Research Funding; Bayer: Research Funding. Minniti:Doris Duke Foundation: Research Funding.

2037P - A challenging task – Identifying carcinoma of unknown primary (CUP) patients according to ESMO guidelines: The CUPISCO trial experience

BackgroundThe CUPISCO trial (NCT03498521) is an ongoing, phase II, randomised, multicentre study comparing molecularly-guided therapy with standard platinum-based chemotherapy in newly diagnosed poor-risk CUP patients. MethodsEligible patients have poor-risk adeno- or undifferentiated CUP as defined by ESMO 2015 guidelines and tissue for molecular sequencing. Local sites initiate the screening process with potentially eligible patients. Patients then undergo central Eligibility Review (ER), a cooperative effort between a central pathology laboratory, external referent oncologists and each site’s investigator and pathology laboratory to confirm the diagnosis. Patients with favourable prognostic subsets or with a strong suspicion of an existing primary site of origin based on immunohistochemistry (IHC) signature and clinical picture are excluded. ResultsAs of 19 March 2019, 157 patients had been screened, of whom 91 (58%) failed screening. Three patients were successfully re-screened. Of the 88 patients who permanently failed screening, 23 were due to technical reasons (e.g. insufficient quality/quantity of tissue for sequencing), 20 for failure to meet inclusion/exclusion criteria not directly related to CUP diagnosis, and 14 for other reasons (e.g. declining health status). A set of 31 patients were not enrolled because the CUP diagnosis could not be confirmed at the IHC level, 19 of those after ER review. Central IHC review results included pathological signatures more typical of specific primary tumours (e.g. prostate cancer or melanoma), or marker combinations typically positive in favourable CUP subsets or rare tumour entities. ConclusionsExperience with the CUPISCO study has highlighted challenges with standardised screening and diagnostic processes in an international clinical trial and the difficulties inherent in accurate diagnosis of poor-risk CUP. Confirming a CUP diagnosis for a clinical trial with multiple review checkpoints can result in many reasons for screen failures. By sharing this experience, we aim to foster understanding and to improve diagnostic algorithms for CUP. Clinical trial identificationNCT03498521. Editorial acknowledgementMedical writing assistance was provided by Ian Leighton, PhD, Nspm Ltd, Meggen, Switzerland, and supported by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Legal entity responsible for the studyF. Hoffmann-La Roche Ltd. FundingF. Hoffmann-La Roche Ltd. DisclosureC. Pauli: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche. T. Bochtler: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche. L. Mileshkin: Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Beigene. G. Baciarello: Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen Oncology; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas-Pharma; Advisory / Consultancy: Roche; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Ipsen. F. Losa: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Research grant / Funding (institution): Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy: Servier. J.S. Ross: Shareholder / Stockholder / Stock options, Full / Part-time employment: Foundation Medicine Inc. S. Yalcin: Honoraria (self): Roche; Honoraria (self): Sanofi; Honoraria (self): Amgen; Honoraria (self): Novartis; Honoraria (self): Lilly; Honoraria (self): MSD; Honoraria (self): Merck Serono. A. Beringer: Full / Part-time employment: F. Hoffmann-La Roche Ltd.. S. Foser: Full / Part-time employment: F. Hoffmann-La Roche Ltd. J. Scarato: Full / Part-time employment: F. Hoffmann-La Roche Ltd.. M. Mueller-Ohldach: Full / Part-time employment: Hoffmann-La Roche Ltd. H. Moch: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche. A. Krämer: Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche. All other authors have declared no conflicts of interest.

550P - Effect of reasons for screen failure (RFSF) on standard of care in cancer patients screened for clinical trials

550P - Effect of reasons for screen failure (RFSF) on standard of care in cancer patients screened for clinical trials

Abstract TP17: Patients Treated With Endovascular Treatment Outside Guidelines

Backgroud: The number of Endovascular treatments (EVT) in stroke is increasing rapidly after the publication of the positive trials. Generally, EVT is recommended in anterior circulation large vessel stroke in a 6 hour time window in patients who are independent (modified Rankin scale 2 or less) and if the infarct is not too large (ASPECTS &gt; 4 or diffusion weighted imaging lesion volume &lt;70 cc). Methods: GOLIATH (General Or Local anesthesia in Intra Arterial THerapy) is a study which is testing whether conscious sedation (CS) or general anesthesia (GA) should be recommended during EVT. The inclusion criteria for GOLIATH include those mentioned above and also, patients must have an MRI scan because the primary outcome measure is infarct growth from baseline to 48-72 hours after EVT as measured on diffusion weighted imaging. Included patients are randomized between GA and CS. We have also captured screen failures (i.e., patients who did not fulfil inclusion criteria but who underwent EVT anyway). We compared the number of patients treated in GOLIATH with the number of screen failures from study initiation in March 2015 to August 2016. Results: Eighty-seven patients have been enrolled in GOLIATH. In the same period, 85 patients have been treated with EVT outside of GOLIATH. The reasons for screen failure were: Posterior circulation stroke: 20 patients NIHSS &lt;10: 18 patients Groin puncture &gt; 6 hours: 16 patients CT scan: 16 patients. (Pacemaker, vomiting, metallic foreign bodies or implants) Intubated at arrival: 5 patients Infarct &gt; 70 cc: 3 patients Baseline mRS &gt;2: 2 patients Age &lt;18 years: 2 patients Withdrew consent: 1 patient Deemed unsafe by anesthesiologist: 2 patients Discussion: Among the first 69 patients in GOLIATH, 45 (65%) achieved a good outcome and 6 (9%) were dead at 90 days. Among the first 58 screen failures, 21 (36%) achieved a good outcome and 16 (28%) were dead at 90 days (p=0.002 for good outcome and p=0.01 for death, Chi-square test). Conclusion: A high number of patients are treated outside the general guidelines. Trials are needed to demonstrate effect is these subgroups. (Posterior circulation stroke, NIHSS &lt;10 and groin puncture &gt;6 hours.)

A Case-Control Study Brings to Light the Causes of Screen Failures in Phase 1 Cancer Clinical Trials

IntroductionEnrolling cancer patients in phase I clinical trials (P1s) requires that they fulfill specific criteria. Between the time they sign the consent form and the 1st administration of the experimental drug, some patients may be excluded and considered as screen failures (SFs). Our objective was to assess SF patients profiles and the reasons and risk factors for SFs.Materials and MethodsAll patients included in P1s at Gustave Roussy from 2008 to 2013 were reviewed retrospectively. SFs were matched with control P1 patients who were successfully enrolled. Patient and tumor characteristics, P1 types and the reasons for SF were analyzed.ResultsAmong 1,293 patients, 192 (15%) were SF cases; 182 SF cases were matched with 182 controls: median age was 57 (48–64) and 55 (47–63), median home-cancer center distance was 69 vs 55 km, 45% vs 34% had more than 2 metastatic sites, median screening period was 14 vs 11 days, median progression-free survival during the previous line was 12 vs 14 weeks, 37% vs 29% of LDH values were above the upper limit of normal, 42% vs 36% of albumin values were < 35 g/L, respectively. Reasons for SFs were cancer progression (44%), sponsor decision unrelated to a clinical reason (25%), patient retrieval (13.5%), relevant comorbidity (13.5%). Multivariate analysis revealed that a high Royal Marsden Hospital (RMH) prognostic score was potentially associated with higher risk of SFs (OR = 2.3; 95% CI [1.0–5.7], p = 0.06).ConclusionCancer progression led to half of the SFs in P1s. Physicians should pay attention to the RMH score at the time of patient inclusion to avoid further SFs.

Screen failure rates in contemporary phase II/III therapeutic trials in genitourinary malignancies.

176 Background: Screen failures cost effort, time and resources estimated at about $2000 per patient (Bienkowski RS et al 2008). There is little published data about the frequency or causes of screen failures in genitourinary (GU) cancer clinical trials. Methods: We reviewed published articles and contacted study investigators on 42 key phase 2 and 3 trials in advanced GU cancer run from 1999 to 2015. We sought data on the numbers and causes of screen failures. Screen failures were defined as individuals who underwent screening but were not enrolled in the trial. Results: Among all 11 phase 3 trials in prostate cancer, the mean screen failure rate was 25% (17.9%-30.3%). In 4 recent trials evaluating novel androgen receptor pathway targeted agents, abiraterone and enzalutamide before or after chemotherapy for castration-resistant disease, the mean screen failure rate was 28% (range 22% to 30%). Only 2 of 3 prostate cancer chemotherapy trials completed after 2008 collected screen failure data with screen failure rates of 18 and 21%. The main reason for screen failures among all prostate cancer clinical trials was ineligibility. Among 14 phase 3 trials in kidney cancer, 5 reported rates and the mean screen failure rate was 24% (range 21%-27%). The main reasons again were ineligibility, with a very small percentage due to patient refusal. Among 17 phase 2 or 3 trials in bladder cancer, 6 reported rates and the mean screen failure rate was 13% (range 2.04% - 22.8%). The main reasons were primarily ineligibility and patient refusal to a lesser extent. Only (16/42) 38% of the trials published screen failure rates-73% of those in prostate cancer (all completed after 2008), 29% in kidney cancer, and 24% in bladder cancer. Conclusions: Contemporary trials in GU cancer that collected screen failure data had fairly consistent failure rates of 20-30% in prostate and kidney cancer. Many trials did not collect data on the numbers of and reasons for screen failures. Greater standardization of definitions, methods and reporting are needed to better understand and improve screen failure rates in GU cancer trials.