Alliance A151945: Accrual and characteristics of adolescent and young adult patients in Alliance trials from 2000 to 2017.

BACKGROUND: Identifying patient- and disease-specific characteristics associated with clinical trial enrollment of adolescents and young adults (AYAs) with cancer may target efforts to improve accrual. METHODS: Alliance for Clinical Trials in Oncology (Alliance) trials opened from January 1, 2000, and closed before January 1, 2018, for common AYA cancers were identified. Proportions of AYAs (aged 18-39 years old) versus non-AYAs (aged ≥40 years old) enrolled by cancer type were summarized by descriptive statistics. Among studies with ≥20 AYAs enrolled, demographic and disease characteristics of AYAs versus non-AYAs were compared with χ2 and Kruskal-Wallis tests. A qualitative review was also conducted of therapeutic trials included in analysis in PubMed through December 31, 2021, that reported AYA-specific survival. RESULTS: Among 188 trials enrolling 40,396 patients, AYAs represented 11% (4468 of 40,396) of accrual. AYA accrual varied by cancer type (leukemia, 23.6%; breast, 9.9%; lymphoma, 14.8%; colorectal, 6.2%; central nervous system, 8.1%; melanoma, 11.8%; sarcoma, 12%). Across ages, the proportion of Black and Hispanic patients enrolled was 1%-10%. Compared to non-AYAs, AYAs in breast and colorectal cancer trials were less likely to be White and more likely to be Hispanic. Disease characteristics differed by age for selected trials. Two trials reported AYA-specific survival, with no significant differences observed by age. CONCLUSIONS: AYA accrual to Alliance trials was comparable to or exceeded population-based, age-specific prevalence estimates for most cancer types. Greater proportional representation of Hispanic and non-White patients among AYAs reflects US demographic trends. The small number of minority patients enrolled across ages underscores the persistent challenge of ensuring equitable access to trials, including for AYAs.

Risk factors for damage accrual in primary antiphospholipid syndrome: A retrospective single-center cohort study.

BACKGROUND: Despite anticoagulant therapy, a antiphospholipid syndrome (APS) has a higher rate of recurrent events, which can lead to damage accrual and a negative impact on life quality. OBJECTIVES: To evaluate the risk factors and APS subsets associated with damage accrual. PATIENTS/METHODS: We conducted a retrospective single-center study. We reviewed the medical records of 282 APS patients, with a median age of 36 (IQR 30-46) years and a median of 195 (IQR 137-272) months. The primary endpoint was damage accrual during follow-up, defined as organ/tissue impairment present for at least six months or causing permanent loss. The secondary endpoints were early organ damage within six months of disease onset and death. RESULTS: Eighty (28.4%) patients presented damage accrual; 52.5% developed damage within six months of APS onset, and 41.3% had more than one organ involved. Neuropsychiatric involvement, affecting 38.8% of the patients, was the most frequent, followed by peripheral vasculopathy and renal involvement, 35% either. Death happened in 7 (2.5 %) patients; damage accrual was associated with a 6-fold risk of death [OR 6.7 (95% CI 1.3-35.1), p = 0.03]. Microangiopathy and non-criteria manifestations were independent risk factors for damage accrual with 5-fold and 4-fold higher risk, respectively [(OR 4.9 (95% CI 2.1-11.7), p < 0.0001 and (OR 3.8 (95% CI 1.5-10.1), p = 0.007]. The cumulative incidence of damage accrual increased by 5.7-fold and 3.6-fold in patients with microangiopathy and non-criteria manifestations. CONCLUSIONS: APS patients had a higher frequency of damage accrual. Microangiopathy and non-criteria manifestations were independent risk factors for damage accrual.

Predictive validity of Lupus Patient-Reported Outcome for damage accrual in patients with systemic lupus erythematosus: the LUNA Registry.

OBJECTIVES: The predictive validity of disease-specific quality of life (QOL) remains unknown in patients with systemic lupus erythematosus (SLE), although disease-specific measures are equally or more responsive to changes than generic QOL. We aimed to examine the predictive validity of the Lupus patient-reported outcome (PRO) for damage accrual. METHODS: Patients with SLE and ≥2 measurements over time were included in Japanese nationwide multicentre registry (LUNA). The Lupus PRO questionnaire contains both health-related (HR) and non-HR-QOL measures. Damage accrual was evaluated using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). We examined the association between the Lupus-PRO score at baseline and longitudinal SDI scores using mixed-effects models adjusted for prognostic factors. RESULTS: Among 1295 patients, those with higher HR-QOL of Lupus PRO at baseline demonstrated a significantly lower increase in SDI (-0.005/year, 95% confidence interval [CI]: -0.007 to - 0.004, p < 0.001). According to the categorisation of HR-QOL based on tertile, a similar dose-dependent effect of HR-QOL on longitudinal SDI was identified (second vs first tertile category: -0.101/year, 95% CI: -0.172 to - 0.030; third tertile category: -0.211/year, 95% CI: -0.281 to - 0.142). Non-HR-QOL was not significantly associated with the SDI scores. Among the HR-QOL domains, cognition, procreation, and physical health were significantly associated with the total SDI scores over time. HR-QOL was associated with corticosteroid-dependent and -independent SDI scores. CONCLUSION: A higher HR-QOL of Lupus PRO was associated with a lower increase in SDI scores. Our findings imply the importance of disease-specific HR-QOL measurements in assessing prognosis.

Organo-organic interactions dominantly drive soil organic carbon accrual.

Organo-mineral interactions have been regarded as the primary mechanism for the stabilization of soil organic carbon (SOC) over decadal to millennial timescales, and the capacity for soil carbon (C) storage has commonly been assessed based on soil mineralogical attributes, particularly mineral surface availability. However, it remains contentious whether soil C sequestration is exclusively governed by mineral vacancies, making it challenging to accurately predict SOC dynamics. Here, through a 400-day incubation experiment using 13 C-labeled organic materials in two contrasting soils (i.e., Mollisol and Ultisol), we show that despite the unsaturation of mineral surfaces in both soils, the newly incorporated C predominantly adheres to "dirty" mineral surfaces coated with native organic matter (OM), demonstrating the crucial role of organo-organic interactions in exogenous C sequestration. Such interactions lead to multilayered C accumulation that is not constrained by mineral vacancies, a process distinct from direct organo-mineral contacts. The coverage of native OM by new C, representing the degree of organo-organic interactions, is noticeably larger in Ultisol (~14.2%) than in Mollisol (~5.8%), amounting to the net retention of exogenous C in Ultisol by 0.2-1.3 g kg-1 and in Mollisol by 0.1-1.0 g kg-1 . Additionally, organo-organic interactions are primarily mediated by polysaccharide-rich microbial necromass. Further evidence indicates that iron oxides can selectively preserve polysaccharide compounds, thereby promoting the organo-organic interactions. Overall, our findings provide direct empirical evidence for an overlooked but critically important pathway of C accumulation, challenging the prevailing "C saturation" concept that emphasizes the overriding role of mineral vacancies. It is estimated that, through organo-organic interactions, global Mollisols and Ultisols might sequester ~0.1-1.0 and ~0.3-1.7 Pg C per year, respectively, corresponding to the neutralization of ca. 0.5%-3.0% of soil C emissions or 5%-30% of fossil fuel combustion globally.

Time to diagnosis in systemic lupus erythematosus: Associated factors and its impact on damage accrual and mortality. Data from a multi-ethnic, multinational Latin American lupus cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. METHODS: Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. RESULTS: Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). CONCLUSIONS: In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).

Accrual Quality Improvement Program for clinical trials.

BACKGROUND: The Early Phase Cancer Prevention Clinical Trials Program (Consortia), led by the Division of Cancer Prevention, National Cancer Institute, supports and conducts trials assessing safety, tolerability, and cancer preventive potential of a variety of interventions. Accrual to cancer prevention trials includes the recruitment of unaffected populations, posing unique challenges related to minimizing participant burden and risk, given the less evident or measurable benefits to individual participants. The Accrual Quality Improvement Program was developed to address these challenges and better understand the multiple determinants of accrual activity throughout the life of the trial. Through continuous monitoring of accrual data, Accrual Quality Improvement Program identifies positive and negative factors in real-time to optimize enrollment rates for ongoing and future trials. METHODS: The Accrual Quality Improvement Program provides a web-based centralized infrastructure for collecting, analyzing, visualizing, and storing qualitative and quantitative participant-, site-, and study-level data. The Accrual Quality Improvement Program approaches cancer prevention clinical trial accrual as multi-factorial, recognizing protocol design, potential participants' characteristics, and individual site as well as study-wide implementation issues. RESULTS: The Accrual Quality Improvement Program was used across 39 Consortia trials from 2014 to 2022 to collect comprehensive trial information. The Accrual Quality Improvement Program captures data at the participant level, including number of charts reviewed, potential participants contacted and reasons why participants were not eligible for contact or did not consent to the trial or start intervention. The Accrual Quality Improvement Program also captures site-level (e.g. staffing issues) and study-level (e.g. when protocol amendments are made) data at each step of the recruitment/enrollment process, from potential participant identification to contact, consent, intervention, and study completion using a Recruitment Journal. Accrual Quality Improvement Program's functionality also includes tracking and visualization of a trial's cumulative accrual rate compared to the projected accrual rate, including a zone-based performance rating with corresponding quality improvement intervention recommendations. CONCLUSION: The challenges associated with recruitment and timely completion of early phase cancer prevention clinical trials necessitate a data collection program capable of continuous collection and quality improvement. The Accrual Quality Improvement Program collects cumulative data across National Cancer Institute, Division of Cancer Prevention early phase clinical trials, providing the opportunity for real-time review of participant-, site-, and study-level data and thereby enables responsive recruitment strategy and protocol modifications for improved recruitment rates to ongoing trials. Of note, Accrual Quality Improvement Program data collected from ongoing trials will inform future trials to optimize protocol design and maximize accrual efficiency.

Optimizing accrual to a large-scale, clinically integrated randomized trial in anesthesiology: A 2-year analysis of recruitment.

BACKGROUND: Performing large randomized trials in anesthesiology is often challenging and costly. The clinically integrated randomized trial is characterized by simplified logistics embedded into routine clinical practice, enabling ease and efficiency of recruitment, offering an opportunity for clinicians to conduct large, high-quality randomized trials under low cost. Our aims were to (1) demonstrate the feasibility of the clinically integrated trial design in a high-volume anesthesiology practice and (2) assess whether trial quality improvement interventions led to more balanced accrual among study arms and improved trial compliance over time. METHODS: This is an interim analysis of recruitment to a cluster-randomized trial investigating three nerve block approaches for mastectomy with immediate implant-based reconstruction: paravertebral block (arm 1), paravertebral plus interpectoral plane blocks (arm 2), and serratus anterior plane plus interpectoral plane blocks (arm 3). We monitored accrual and consent rates, clinician compliance with the randomized treatment, and availability of outcome data. Assessment after the initial year of implementation showed a slight imbalance in study arms suggesting areas for improvement in trial compliance. Specific improvement interventions included increasing the frequency of communication with the consenting staff and providing direct feedback to clinician investigators about their individual recruitment patterns. We assessed overall accrual rates and tested for differences in accrual, consent, and compliance rates pre- and post-improvement interventions. RESULTS: Overall recruitment was extremely high, accruing close to 90% of the eligible population. In the pre-intervention period, there was evidence of bias in the proportion of patients being accrued and receiving the monthly block, with higher rates in arm 3 (90%) compared to arms 1 (81%) and 2 (79%, p = 0.021). In contrast, in the post-intervention period, there was no statistically significant difference between groups (p = 0.8). Eligible for randomization rate increased from 89% in the pre-intervention period to 95% in the post-intervention period (difference 5.7%; 95% confidence interval = 2.2%-9.4%, p = 0.002). Consent rate increased from 95% to 98% (difference of 3.7%; 95% confidence interval = 1.1%-6.3%; p = 0.004). Compliance with the randomized nerve block approach was maintained at close to 100% and availability of primary outcome data was 100%. CONCLUSION: The clinically integrated randomized trial design enables rapid trial accrual with a high participant compliance rate in a high-volume anesthesiology practice. Continuous monitoring of accrual, consent, and compliance rates is necessary to maintain and improve trial conduct and reduce potential biases. This trial methodology serves as a template for the implementation of other large, low-cost randomized trials in anesthesiology.

Determinants of bone mass accrual in transgender and gender diverse youth undergoing pubertal suppression therapy.

INTRODUCTION/BACKGROUND: Gender-affirming care for gender diverse and transgender (GDTG) youth includes puberty suppression with gonadotropin-releasing hormone agonists (GnRHa). Puberty is a critical period of bone mass accrual, and pubertal suppression may impact bone health. Previous studies have shown a decrease in areal bone mineral density (aBMD) Z-score while on puberty suppression. However, the rate of bone mass accrual and its determinants during GnRHa therapy are not known. METHODOLOGY: This is a retrospective chart review of GDTG youth with aBMD assessment within six months of starting GnRHa monotherapy at Cincinnati Children's Hospital Medical Center between 01/2011 and 12/2022. In individuals with follow-up aBMD assessment, we calculated their aBMD velocity and generated Z-scores using reference data from the Bone Mineral Density in Childhood Study. The determinants of baseline height-adjusted aBMD and aBMD velocity Z-scores were assessed with multiple linear regression models. RESULTS: Thirty-six participants (36% assigned female at birth (AFAB), mean age at first aBMD assessment 12 ± 1.1 years) had baseline height-adjusted aBMD Z-score of -0.053 ± 0.79. Among 16 participants with follow-up aBMD assessment, the mean aBMD velocity Z-score was -0.42 ± 1.13 (-0.27 ± 0.79 in AFAB vs -0.52 ± 1.32 in assigned male at birth, p = 0.965). Baseline aBMD Z-scores significantly correlated with age at the first aBMD assessment (adjusted R2 0.124, p = 0.02) with combined modeling including age at first aBMD assessment and BMI Z-score being most significant (adjusted R2 0.21, p = 0.008). Only BMI Z-scores were positively associated with the aBMD-velocity Z-scores (adjusted R2 0.255, p = 0.046). CONCLUSIONS: GDTG youth undergoing GnRHa therapy appeared to have below-average aBMD velocity Z-scores. A lower BMI Z-score was a determinant of lower baseline height-adjusted aBMD and aBMD velocity Z-scores. Building on previous studies, our study highlights aBMD velocity as a novel technique for bone health surveillance in GDTG youth.

The adjusted Global Anti-Phospholipid Syndrome Score as predictor of damage accrual measured by Damage Index for APS: a longitudinal study.

OBJECTIVE: To analyse the association between the average 'adjusted' Global APS Score (aGAPSS) over time, as a surrogate of disease activity, and change in Damage Index for APS (DIAPS) during follow-up in patients with thrombotic and non-thrombotic APS. METHODS: Two hundred APS patients (138 primary, 62 associated to other autoimmune diseases) were included. DIAPS change was calculated as the difference between basal DIAPS and DIAPS at the end of follow-up. The aGAPSS was calculated for each patient at baseline and on a yearly basis for up to 6 years (minimum 3 years). The average score per patient was computed and considered the reference aGAPSS. Linear regression models were designed to analyse the association between mean aGAPSS and DIAPS change. Moreover, factors associated to high (increase of DIAPS ≥1 during follow-up) vs low (increase of DIAPS <1 during follow-up) damage accrual were assessed. RESULTS: A higher mean aGAPSS value was associated to a DIAPS increase during follow-up (b = 0.04, P < 0.001) in the multivariate analysis. Higher mean aGAPSS values were found in patients with a DIAPS increase ≥1 during follow-up compared with patients with an increase of <1 point [9.22 (95% CI 7.58, 10.86) vs 6.72 (95% CI 6.0, 7.43), P = 0.003]. aGAPSS increased the odds a DIAPS increment of ≥1 point during follow-up [OR = 1.12 (95% CI 1.04, 1.21), P = 0.003]. CONCLUSIONS: Our data support the utility of longitudinal assessing of the aGAPSS score in predicting damage accrual, measured by DIAPS, in APS.

Elevated bone turnover markers predict bone mineral density accrual in adolescents with 21-hydroxylase deficiency.

CONTEXT: Prognostic biomarkers for monitoring bone health in adolescents with 21-hydroxylase deficiency (21OHD) are needed. OBJECTIVES: To assess associations between concentrations of baseline bone turnover markers (BTMs) including osteocalcin (OC) and type-I collagen C-terminal telopeptide (CTX) and changes in lumbar spine bone mineral density (LSBMD) in adolescents with classic 21OHD. DESIGNS AND PATIENTS: A retrospective-prospective study of 33 adolescents with classic 21OHD who had baseline data for LSBMD, bone age (BA), and BTM concentrations. METHODS: BTM concentrations were converted into z-scores according to BA. We measured LSBMD at the follow-up study visit and calculated the annual percentage change in LSBMD (%∆LSBMD). RESULTS: At baseline, participants (55% female, 79% Tanner 5) had mean (±SD) age of 14.6 ± 3.6 years, BA 16.7 ± 2.9 years, and average glucocorticoid (GC) dose 17.3 ± 5.6 mg/m2 /day of hydrocortisone equivalent. The mean follow-up duration was 14.4 ± 5.6 months. Median (Q1-Q3) %∆LSBMD was 3.6% (0-8.5)/year. %∆LSBMD was similar among genders or 21OHD subtypes. Prednisolone versus hydrocortisone replacement resulted in lower %∆LSBMD (p = .004). %∆LSBMD was increased across tertiles of CTX z-score (p = .014). %∆LSBMD correlated negatively with GC dose (p = .01) and positively with CTX and OC z-scores (p < .01). In regression analyses, only CTX z-score positively associated with %∆LSBMD (p = .003), adjusting for sex, BA, body mass index, testosterone, 25-hydroxyvitamin D, and GC type and dose. CONCLUSIONS: Higher GC dose and the use of prednisolone were associated with decreased LSBMD accrual in adolescents with 21OHD. CTX z-score independently associated with LSBMD accrual, suggesting its potential for prognostic bone biomarker.

Designing a phase-III time-to-event clinical trial using a modified sample size formula and Poisson-Gamma model for subject accrual that accounts for the lag in site initiation using the PERT distribution.

A priori estimation of sample size and subject accrual in multi-site, time-to-event clinical trials is often challenging. Such trials are powered based on the number of events needed to detect a clinically significant difference. Sample size based on number of events relates to the expected duration of observation time for each subject. Temporal patterns in site initiation and subject enrollment ultimately affect when subjects can be accrued into the study. Lag times are common as the site start-up process optimizes, resulting in delays that may curtail observational follow-up and therefore undermine power. The proposed method introduces a Program Evaluation and Review Technique (PERT) model into the sample size estimation which accounts for the lag in site start-up. Additionally, a PERT model is introduced into a Poisson-Gamma subject accrual model to predict the quantity of study sites needed. The introduction of the PERT model provides greater flexibility in both a priori power assessment and planning the number of sites, as it specifically allows for the inclusion of anticipated delays in site start-up time. This model results in minimal power loss even when PERT distribution inputs are misspecified compared to the traditional assumption of simultaneous start-up for all sites. Together these updated formulations for sample size and subject accrual models offer an improved method for designing a multi-site time-to-event clinical trial that accounts for a flexible site start-up process.

Differential glycosylation of tissue non-specific alkaline phosphatase in mesenchymal stromal cells differentiated into either an osteoblastic or adipocytic phenotype.

It has long been known that tissue non-specific alkaline phosphatase (TNAP) is essential for the correct formation of bone, as altered expression or function of this enzyme results in hypophosphatasia, a disease characterised by compromised bone structure, density and strength. However, recent evidence strongly suggests that the enzyme also has a role in lipid accrual and adipogenesis, a function that seems far removed from bone formation. Given that mesenchymal stromal cells (MSCs) are progenitors of both osteoblasts and adipocytes, the question arises of how TNAP is regulated to potentially have a different function when MSCs undergo either osteogenesis or adipogenesis. As the primary protein sequence is unchanged for the enzyme during both types of differentiation, any differences in function must be attributed to post-translational modification and/or localisation. We therefore examined the location of TNAP in bone- or adipose-derived MSCs differentiated into an adipocytic phenotype and compared the glycosylation state of the enzyme in MSCs differentiated into either osteoblasts or adipocytes. TNAP was found to co-locate with perilipin around lipid droplets in MSCs from bone, subcutaneous- and visceral adipose tissue during adipocytic differentiation. Treatment of TNAP with wheat germ lectin followed by electrophoresis showed minor differences in glycosylation between the phosphatase isolated from cells from these tissues, whereas electrophoresis after neuraminidase digestion highlighted differential glycosylation between cell types and during adipogenesis and osteoblastogenesis. This infers that post-translational modification of TNAP is altered during differentiation and is dependent on the eventual phenotype of the cells.

The value of a two-armed Bayesian response adaptive randomization trial.

We investigate the value of a two-armed Bayesian response adaptive randomization (RAR) design to investigate early preterm birth rates of high versus low dose of docosahexaenoic acid during pregnancy. Unexpectedly, the COVID-19 pandemic forced recruitment to pause at 1100 participants rather than the planned 1355. The difference in power between number of participants at the pause and planned was 87% and 90% respectively. We decided to stop the study. This paper describes how the RAR was used to execute the study. The value of RAR in two-armed studies is quite high and their use in the future is promising.

Direct-to-Consumer Recruitment Methods via Traditional and Social Media to Aid in Research Accrual for Clinical Trials for Rare Diseases: Comparative Analysis Study.

BACKGROUND: Recruitment into clinical trials is a challenging process, with as many as 40% of studies failing to meet their target sample sizes. The principles of direct-to-consumer (DTC) advertising rely upon novel marketing strategies. The ability to reach expansive audiences in the web-based realm presents a unique opportunity for researchers to overcome various barriers to enrollment in clinical trials. Research has investigated the use of individual web-based platforms to aid in recruitment and accrual into trials; however, a gap in the literature exists, whereby multiple mass communication platforms have yet to be investigated across a range of clinical trials. OBJECTIVE: There is a need to better understand how individual factors combine to collectively influence trial recruitment. We aimed to test whether DTC recruitment of potentially eligible study participants via social media platforms (eg, Facebook [Meta Platforms Inc] and Twitter [Twitter Inc]) was an effective strategy or whether this acted as an enhancement to traditional (eg, email via contact registries) recruitment strategies through established clinical research sites. METHODS: This study tested multiple DTC web-based recruitment efforts (Facebook, Twitter, email, and patient advocacy group [PAG] involvement) across 6 national and international research studies from 5 rare disease consortia. Targeted social media messaging, social media management software, and individual study websites with prescreening questions were used in the Protocol for Increasing Accrual Using Social Media (PRISM). RESULTS: In total, 1465 PRISM website referrals occurred across all 6 studies. Organic (unpaid) Facebook posts (676/1465, 46.14%) and Rare Diseases Clinical Research Network patient contact registry emails (461/1465, 31.47%) represented the most successful forms of engagement. PRISM was successful in accumulating a 40.1% (136/339) lead generation (those who screened positive and consented to share their contact information to be contacted by a clinical site coordinator). Despite the large number of leads generated from PRISM recruitment efforts, the number of patients who were subsequently enrolled in studies was low. Across 6 studies, 3 participants were ultimately enrolled, meaning that 97.8% (133/136) of leads dropped off. CONCLUSIONS: The results indicate that although accrual results were low, this is consistent with previously documented challenges of studying populations with rare diseases. Targeted messaging integrated throughout the recruitment process (eg, referral, lead, and accrual) remains an area for further research. Key elements to consider include structuring the communicative workflow in such a way that PAG involvement is central to the process, with clinical site coordinators actively involved after an individual consents to share their contact information. Customized approaches are needed for each population and research study, with observational studies best suited for social media recruitment. As evidenced by lead generation, results suggest that web-based recruitment efforts, coupled with targeted messaging and PAG partnerships, have the potential to supplement clinical trial accrual.

Interventions to increase racial and ethnic minority accrual into cancer clinical trials: A systematic review.

BACKGROUND: Racial and ethnic minorities (REMs) continue to be underrepresented in clinical trials despite the 1993 National Institutes of Health's Revitalization Act mandating the representation of women and underrepresented minority groups in clinical trials. Although Blacks represent 15% and Hispanics 13% of the cancer population, their clinical trial enrollment rates are disproportionately low at 4% to 6% and 3% to 6%, respectively. A systematic review exploring interventions aimed at improving cancer clinical trial (CCT) enrollment for REMs was conducted. METHODS: A systematic search of PubMed, Cochrane CENTRAL, and Ovid PsycINFO was conducted for English-language studies since 1993. Inclusion criteria included peer-reviewed, US-based studies with interventions aimed to recruit underrepresented minority adult patients into cancer clinical trials. REM groups were defined as Black, Hispanic, Asian, American Indian, and Native Hawaiian/other Pacific Islander. RESULTS: The systematic search identified 3123 studies, of which nine met inclusion criteria. Interventions included patient navigation/coaching (n = 4), a clinical trial educational video (n = 2), institutional research infrastructure changes (n = 1), a relationship building and social marketing recruitment model (n = 1), and cultural competency training for providers (n = 1). A statistically significant improvement in accrual was shown in three of the patient navigation interventions, one of the clinical trial educational videos and an institutional research infrastructure change. CONCLUSIONS: This systematic review illustrates several potential mechanisms by which to increase CCT recruitment for patients of REM backgrounds in various clinical settings. More randomized controlled trials are needed to further explore the benefits of these interventions for REMs.

Enrollment of adolescent and young adult patients newly diagnosed with cancer in NCI CTEP-sponsored clinical trials before and after launch of the NCI National Clinical Trials Network.

BACKGROUND: Participation of adolescents and young adults (AYAs) in oncology clinical trials is important to ensure adequate opportunities for AYA patients to contribute to, and benefit from, advances in cancer treatment. METHODS: Accrual data for National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP) cooperative group-led treatment trials were examined to assess enrollment of newly diagnosed AYA patients (15-39 years) during the period 2004-2019, with particular interest in comparing enrollment before launch of the NCI National Clinical Trials Network (NCTN) to after. All phase 2, 2/3, and 3 trials activated during the period between January 1, 2004, and December 31, 2019, were identified (n = 1568) and reduced to a set of 304 that met predetermined criteria to focus on cooperative group-led trials that involved therapy for newly diagnosed cancer and had age eligibility overlapping the AYA range. The proportion of AYA patients relative to total accrual, along with 95% bootstrapped CI was calculated for patients enrolled pre-NCTN and post-NCTN. RESULTS: AYA accrual comprised 9.5% (95% CI, 7.6-11.8) pre-NCTN compared with 14.0% (95% CI, 9.9-18.3) post-NCTN. The mean difference in proportions post-NCTN compared with pre-NCTN was 4.4% (0.7%-8.3%). CONCLUSIONS: These results indicate an increase in AYA participation in trials conducted within the NCTN relative to the pre-NCTN period. This suggests an awareness and utilization of NCTN trials for AYAs with cancer.

Decreased cortical bone density and mechanical strength with associated elevated bone turnover markers at peri-pubertal peak height velocity: a cross-sectional and longitudinal cohort study of 396 girls with adolescent idiopathic scoliosis.

Decreased cortical bone density and bone strength at peak height velocity (PHV) were noted in girls with adolescent idiopathic scoliosis (AIS). These findings could provide the link to the previously reported observation that low bone mineral density (BMD) could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS. INTRODUCTION: As part of the studies related to aetiopathogenesis of AIS, we assessed bone qualities, bone mechanical strength and bone turnover markers (BTMs) focusing at the peri-pubertal period and PHV in AIS girls. METHODS: 396 AIS girls in two separate cohorts were studied. Skeletal maturity was assessed using the validated thumb ossification composite index (TOCI). Bone qualities and strength were evaluated with high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA). RESULTS: Cohort-A included 179 girls (11.95 ± 0.95 years old). Girls at TOCI-4 had numerically the highest height velocity (0.71 ± 0.24 cm/month) corresponding to the PHV. Subjects at TOCI-4 had lower cortical volumetric BMD (672.36 ± 39.07 mg/mm3), cortical thickness (0.68 ± 0.08 mm) and apparent modulus (1601.54 ± 243.75 N/mm2) than: (a) those at TOCI-1-3 (724.99 ± 32.09 mg/mm3 (p < 0.001), 0.79 ± 0.11 mm (p < 0.001) and 1910.88 ± 374.75 N/mm2 (p < 0.001), respectively) and (b) those at TOCI-8 (732.28 ± 53.75 mg/mm3 (p < 0.001), 0.84 ± 0.14 mm (p < 0.001), 1889.11 ± 419.37 N/mm2 (p < 0.001), respectively). Cohort-B included 217 girls (12.22 ± 0.89 years old). Subjects at TOCI-4 had higher levels of C-terminal telopeptide of type 1 collagen (1524.70 ± 271.10 pg/L) and procollagen type 1 N-terminal propeptide (941.12 ± 161.39 µg/L) than those at TOCI-8 (845.71 ± 478.55 pg/L (p < 0.001) and 370.08 ± 197.04 µg/L (p < 0.001), respectively). CONCLUSION: AIS girls had decreased cortical bone density and bone mechanical strength with elevated BTMs at PHV. Coupling of PHV with decreased cortical and FEA parameters could provide the link to the previously reported observation that low BMD could contribute as one of the prognostic factors for curve progression that mostly occurs during PHV in AIS.

Addressing the Barriers to Clinical Trials Accrual in Community Cancer Centres Using a National Clinical Trials Navigator:A Cross-Sectional Analysis.

INTRODUCTION: Clinical trials, although academically accepted as the most effective treatment available for cancer patients, poor accrual to clinical trials remains a significant problem. A clinical trials navigator (CTN) program was piloted where patients and/or their healthcare professionals could request a search and provide a list of potential cancer clinical trials in which a patient may be eligible based on their current status and disease. OBJECTIVES: This study examined the outcomes of a pilot program to try to improve clinical trials accrual with a focus on patients at medium to small sized cancer programs. Outcomes examined included patient disposition (referral to and accrual to interventional trials), patient survival, sites of referral to the CTN program. METHODS: One 0.5 FTE navigator was retained. Stakeholders referred to the CTN through the Canadian Cancer Clinical Trials Network. Demographic and outcomes data were recorded. RESULTS: Between March 2019 and February 2020, 118 patients from across Canada used the program. Seven per cent of patients referred were enrolled onto treatment clinical trials. No available trial excluded 39% patients, and 28% had a decline in their health and died before they could be referred or enrolled onto a clinical trial. The median time from referral to death was 109 days in those that passed. CONCLUSION: This novel navigator pilot has the potential to increase patient accrual to clinical trials. The CTN program services the gap in the clinical trials system, helping patients in medium and small sized cancer centres identify potential clinical trials at larger centres.

Oncologic patients' misconceptions may impede enrollment into clinical trials: a cross-sectional study.

BACKGROUND: Clinical trials are an essential source for advances in oncologic care, yet the enrollment rate is only 2-4%. Patients' reluctance to participate is an important barrier. This study evaluates patients' level of understanding and attitudes towards clinical trials. METHODS: This cross-sectional study was conducted in the oncology department and day care unit at the oncology division Tel Aviv Sourasky Medical Center, Israel. From January 2015 to September 2016. Two-hundred patients' currently receiving active anti-cancer therapy at a large tertiary hospital completed an anonymous questionnaire comprised of demographic information, past experience in clinical research and basic knowledge on clinical trials. RESULTS: The majority of respondents did not meet the minimum knowledge level criteria. In those who replied they would decline to participate in a clinical trial, concern were related to potential assignment to the placebo arm, provision of informed consent and trust issues with their oncologist. Those with sufficient knowledge were significantly more interested in participating. Patients with past experience in clinical trials had a higher level of academic education, were less religious, had a better understanding of medical research and were inclined to participate in future research. CONCLUSIONS: Misperceptions of clinical trials may contribute substantially to the unwillingness to participate in them.

It starts from the womb: maximizing bone health.

The foundation of bone health is established in utero. Bone accrual starts from the developing fetus and continues throughout childhood and adolescence. This process is crucial to achieve peak bone mass. Understanding factors that influence bone accrual before attainment of peak bone mass is thus critical to improve bone health and prevent osteoporosis, thereby reducing the burden of osteoporotic fractures in older women. In this review, we broadly outline factors influencing peak bone mass from pregnancy to infancy, childhood and adolescence with potential diseases and medications that may affect the optimum trajectory to maximizing bone health. It is estimated that a 10% increase in peak bone mass will delay the onset of osteoporosis by 13 years in a woman.