Diagnostic performance of the ABC score in the PROPPR trial.

INTRODUCTION: The Assessment of Blood Consumption (ABC) score is used to predict massive transfusions (MT). However, its diagnostic performance has not been widely examined, especially when used as an objective tool to enroll patients in multi-center clinical trials. The purpose of this study was to evaluate the performance of the ABC score in enrolling patients in the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial. We hypothesized the ABC score would have a similar diagnostic performance to predict the need for massive transfusion as previous studies. METHODS: This is a retrospective analysis of the PROPPR trial. Patients were enrolled either on the basis of an ABC score ≥2, or by Physician Gestalt, when the ABC score was <2. We calculated the sensitivity, specificity, positive (PPV) and negative (NPV) predictive values and likelihood ratios of the ABC score (≥2) for predicting MT (>10 units of red blood cells/24 h or transfusion of >3 units of red blood cells within the first hour). RESULTS: Of the 680 patients, 438 patients (64 %) had an ABC score of ≥2 and 242 (36 %) had an ABC score of <2. An ABC score of ≥2 had 66.8 % sensitivity and 37.0 % specificity for predicting the need for MT, with a PPV of 88.2 % and NPV of 13.1 %. Similarly, an ABC≥2 had 65.6 % sensitivity and 44.6 % specificity for predicting the need for >3 units RBCs in 1 hour, with a PPV of 89.5 % and NPV of 15.3 %. CONCLUSION: The ABC score had lower performance than previously reported for predicting MT, when applied to PROPPR trial patients. The performance for predicting the need for a 3-unit red blood cell transfusion (or more) in the first hour was slightly higher. LEVEL OF EVIDENCE: Level III, Prognostic.

Benchmarking Site Activation and Patient Enrollment.

Clinical trial conduct poses numerous challenges, many pertaining to patient recruitment. The primary objectives of this study were to update benchmarks on site activation and patient enrollment gathered in previous Tufts CSDD studies and examine current usage of recruitment and retention tactics. The data collection focused on site activation and patient enrollment metrics used for studies. Analyses were conducted comparing results from 2012, 2019 and 2023. The results indicate that actual enrollments exceeded planned enrollments for a majority of studies and timelines were shorter than expected. In addition, differences were found for enrollment achievement by global region and site type. Further investigation into studies conducted during a later time frame and post-pandemic could be compared with current benchmarks to examine differences.

Consensus recommendations for improving the cancer clinical trial matching environment.

Enrollment in cancer clinical trials cannot occur without first successfully identifying trials for which patients are a match based on their clinical characteristics. A lack of onsite matching trials has been identified as the single largest barrier preventing patients from participating in clinical trials. The site-agnostic cancer clinical trial matching environment is a mix of public and private tools and infrastructure that are not designed to work together to facilitate trial matching in an efficient manner. To identify policy and infrastructure solutions that could enable more effective and more frequent use of third-party site-agnostic matching, the American Cancer Society Cancer Action Network held a summit to examine challenges and propose consensus recommendations that could address those challenges. At this 2019 summit, stakeholders in this field examined these barriers and challenges and made a number of policy and infrastructure recommendations to improve the ability of this environment to work in a more coordinated and efficient manner.

Provider motivations and barriers to cancer clinical trial screening, referral, and operations: Findings from a survey.

BACKGROUND: Provider and institutional practices have been shown to have a large impact on cancer clinical trial enrollment. Understanding provider perspectives on screening for trial eligibility is necessary to improve enrollment. METHODS: A questionnaire about incentives, barriers, process tools, and infrastructure related to opening trials and referring patients to onsite and offsite trials was administered to diverse stakeholders, including professional societies, advocacy organizations, and industry networks. Descriptive statistics were used to summarize findings. RESULTS: Overall, 693 responses were received, primarily from physicians (42.7%) and nurses (35.6%) employed at hospital health systems (43.7%) and academic centers (36.5%). Approximately half (49.2%) screened all patients for onsite clinical trials with screening typically done by manual chart review (81.9%). The greatest incentive reported for offering trials was providing the best treatment options for patients (67.7%). Contracting and paperwork (48.5%) were the greatest barriers to opening more onsite trials. Offsite referrals were rare. CONCLUSIONS: Screening for trial eligibility is a largely manual and ad hoc process, with screening and referral to offsite trials occurring infrequently. Administrative and infrastructure barriers commonly prevent sites from opening more onsite trials. These findings suggest that automated trial screening tools built into workflows that screen in a site-agnostic manner could result in more frequent trial eligibility screening, especially for offsite trials. With recent momentum, in part in response to the COVID-19 pandemic, to improve clinical trial efficiencies and broaden access and participant diversity, implementing tools to improve screening and referral processes is timely and essential. PLAIN LANGUAGE SUMMARY: There are many factors that contribute to low adult enrollment in cancer clinical trials, but previous research has indicated that provider and institutional barriers are the largest contributors to low cancer clinical trial enrollment. In this survey, we sought to gain insight into cancer clinical trial enrollment practices from the perspective of health care providers such as physicians and nurses. We found that only approximately half of respondents indicated their institution systematically screens their patients for clinical trials and this process is manual and time consuming. Furthermore, we found that providers infrequently search for and refer patients to clinical trials at other sites. Creating better screening methods could improve enrollment in clinical trials.

Prospective preference assessment for the Comparison of Analgesic Regimen Effectiveness and Safety in Surgery (CARES) trial.

BACKGROUND: Clinical trials face major barriers such as under-enrollment and selective enrollment, which threaten study completion and undermine validity and generalizability. Thus, we conducted a prospective preference assessment (PPA) prior to commencing the Comparison of Analgesic Regimen Effectiveness and Safety in Surgery (CARES) trial-a randomized controlled study comparing the outcomes of managing acute postoperative pain between opioid-sparing and opioid-based therapies. This PPA aimed to (1) determine the patients' willingness to participate in the CARES trial, (2) identify the areas for improvement, and (3) assess the differences between willing and unwilling patients. METHODS: Patients undergoing elective laparoscopic cholecystectomy were recruited between August 2019 and February 2020 from two academic hospitals. A survey was administered to each patient consisting of (1) a vignette describing the trial, (2) an assessment of the patients' understanding of the trial, (3) open-ended questions assessing the attitudes towards the trial, and (4) patient-completed questionnaires. Data were analyzed qualitatively with thematic analysis and quantitatively with the Wilcoxon signed-rank and chi-square tests. RESULTS: Forty-two patients were enrolled and grouped based on the 6-point Likert scale into willing (4-6, 71%) and not willing (1-3, 29%) to participate in the CARES trial. There were no significant differences with respect to all variables: age, education, sex, visible minority status, previous research, previous surgery, regular use of pain medications, surgical concerns, previous discussions on pain management, significant pain within the past 3 months, and significant use of pain medication within the past month. Factors that motivated participation were contributing to scientific research (45%), altruism (29%), and improving personal pain (24%). Common discouraging factors were negative perceptions of opioids (29%), side effects (21%), being blinded to the study medication (21%), and poor pain management (19%). CONCLUSIONS: This PPA revealed that two key discouraging factors for patients were being blinded to the type of pain medication being taken and the potential for poor pain management as a consequence of participation. Modifications to improve patient acceptance of the CARES trial include ensuring sufficient rescue medicine and follow-up visits consistent with current standards of care for all patients, as well as patient education surrounding safe administration and side effects of the study medications.

Home-Based Palliative Care Team Perspectives on Challenges in Patient Referral and Enrollment.

CONTEXT: As funding for home-based palliative care continues to expand, there is an increasing need to understand barriers to patient referral to and acceptance of home-based palliative care. OBJECTIVES: The aim of this study was to elicit perspectives of home-based palliative care administrators and providers on barriers encountered in identification, referral, and enrollment of patients eligible for home-based palliative care. METHODS: We conducted a qualitative study employing focus groups of nine home-based palliative care agencies across California. Focus groups were audio-recorded and transcribed. Using thematic analysis, researchers independently coded the transcripts and identified themes from the codes. RESULTS: A total of 25 HBPC staff participated in the nine focus groups. Participants included both clinicians (n = 17) and administrators (n = 8). Our analysis revealed 13 themes that fit under four major thematic categories: 1) lack of formal payment structures (few HBPC payors and variation in payment and services among payors), 2) agency structure barriers (limitations of electronic medical records and multiple lines of business), 3) patient- and family-level barriers (misconceptions and/or lack of palliative care knowledge, uninformed of the referral and/or no warm hand-off, reluctance to have strangers in the home, overwhelmed with health issues and related services, HBPC service refusal/unresponsive to outreach), and 4) physician-level barriers (misconceptions and/or lack of palliative care knowledge, variability in HBPC payment and services, lack of time, patient ownership). CONCLUSION: HBPC providers identified a myriad of barriers that preclude patient access to HBPC. With growing provision of HBPC services, greater efforts to overcome these barriers are needed.

Factors Associated With the Acceleration of Patient Enrollment in Clinical Studies: A Cross-Sectional Study.

Under-recruitment in clinical trials is an issue worldwide. If the number of patients enrolled is lower than expected, based on the required sample size, then the reliability of the study results and their validation tend to be impaired. The current study therefore evaluated factors associated with accelerating patient enrollment using data from an ongoing multicenter prospective cohort study. The researchers encouraged research institutions to accelerate patient enrollment via e-mail, newsletters, telephone calls, and site visits. We analyzed the relationship between several potential factors associated with acceleration of patient enrollment including site visits and patient enrollment in a real clinical study. Data were collected from 106 research institutions that participated in a multicenter prospective cohort study. Results showed that the following parameters differed in terms of patient enrollment and non-enrollment: urban area (47.2 vs. 67.6%, p = 0.04), clinical research coordinator (CRC) participation in data input to electronic data capture (EDC) (41.7 vs. 11.8%, p < 0.01), and site visit (38.9 vs. 11.8%, p < 0.01). A multivariate analysis revealed that patient enrollment was significantly associated with urban area (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.12-0.86, p = 0.02), CRC participation in data input to EDC (OR 5.02; 95% CI 1.49-16.8; p < 0.01), and site visit (OR 4.54, 95% CI 1.31-15.7, p = 0.01). In conclusion, site visits and CRC participation in data input to EDC had a significant effect on patient enrollment promotion. Moreover, hospitals in rural areas were more effective in promoting patient enrollment than those in urban areas.

Achieving higher performing primary care through patient registration: A review of twelve high-income countries.

BACKGROUND: Patient registration with a primary care providers supports continuity in the patient-provider relationship. This paper develops a framework for analysing the characteristics of patient registration across countries; applies this framework to a selection of countries; and identifies challenges and ongoing reform efforts. METHODS: 12 jurisdictions (Denmark, France, Germany, Ireland, Israel, Italy, Netherlands, Norway, Ontario [Canada], Sweden, Switzerland, United Kingdom) were selected for analysis. Information was collected by national researchers who reviewed relevant literature and policy documents to report on the establishment and evolution of patient registration, the requirements and benefits for patients, providers and payers, and its connection to primary care reforms. RESULTS: Patient registration emerged as part of major macro-level health reforms linked to the introduction of universal health coverage. Recent reforms introduced registration with the aim of improving quality through better coordination and efficiency through reductions in unnecessary referrals. Patient registration is mandatory only in three countries. Several countries achieve high levels of registration by using strong incentives for patients and physicians (capitation payments). CONCLUSION: Patient registration means different things in different countries and policy-makers and researchers need to take into consideration: the history and characteristics of the registration system; the use of incentives for patients and providers; and the potential for more explicit use of patient-provider agreements as a policy to achieve more timely, appropriate, continuous and integrated care.

Development of a Digital Research Assistant for the Management of Patients' Enrollment in Oncology Clinical Trials within a Research Hospital.

Clinical trials in cancer treatment are imperative in enhancing patients' survival and quality of life outcomes. The lack of communication among professionals may produce a non-optimization of patients' accrual in clinical trials. We developed a specific platform, called "Digital Research Assistant" (DRA), to report real-time every available clinical trial and support clinician. Healthcare professionals involved in breast cancer working group agreed nine minimal fields of interest to preliminarily classify the characteristics of patients' records (including omic data, such as genomic mutations). A progressive web app (PWA) was developed to implement a cross-platform software that was scalable on several electronic devices to share the patients' records and clinical trials. A specialist is able to use and populate the platform. An AI algorithm helps in the matchmaking between patient's data and clinical trial's inclusion criteria to personalize patient enrollment. At the same time, an easy configuration allows the application of the DRA in different oncology working groups (from breast cancer to lung cancer). The DRA might represent a valid research tool supporting clinicians and scientists, in order to optimize the enrollment of patients in clinical trials. User Experience and Technology The acceptance of participants using the DRA is topic of a future analysis.

Payment models in primary health care: A driver of the quantity and quality of medical laboratory utilization.

Physician payment models' incentives regarding many aspects of primary health care are not well understood. We focus on the case of medical laboratory utilization and examine how physicians' laboratory test ordering patterns change following a switch to a blended capitation payment model from one with fee for service enhanced with pay for performance. Also, within blended capitation, we examine differences between traditional staffing and interdisciplinary teams. Using a propensity score weighted fixed-effects specification to address selection, it is estimated that the switch to capitation leads to a short-run average of 3% fewer laboratory requisitions per patient. Patients' laboratory utilization also becomes more concentrated with the rostering physician. More importantly, using diabetes-related laboratory tests as a case study, after joining the blended model, physicians order 3% fewer inappropriate/redundant tests, and the addition of an interdisciplinary care team makes the reduction about 9%. Advances in both continuity and quality seem to be associated with blended capitation.

Drug Registries and Approval of Drugs: Promises, Placebo, or a Real Success?

PURPOSE: As part of the approval process, regulatory authorities often require postauthorization studies that involve patient registries; it is unknown, however, whether such registry studies are adequately completed. We investigated whether registry studies for new drugs were performed as agreed at time of approval. METHODS: This study reviewed protocols and follow-up reports for 73 registry studies that were proposed for 43 drugs approved by the Committee for Medicinal Products for Human Use in Europe in the period 2007 to 2010. RESULTS: The data lock point of January 1, 2016, was taken to allow a 5-year follow-up period for each drug after approval. At that time, 2 studies (3%) in registries had been finalized, 19 registries (26%) had not enrolled any patients, and 52 studies (71%) were ongoing. The median enrollment was 31% (interquartile range [IQR], 6-104) of the required number of patients for 41 registry studies that had a predefined sample size, 30% (IQR, 2-101) for nonimposed registries, and 61% (IQR, 18-144) for imposed registries. IMPLICATIONS: Enrollment of patients into postapproval registries is poor, although the results for imposed registries seem better. Currently, registries only have a limited impact on resolving gaps in the knowledge of a drug's benefits and risks at time of marketing authorization.

Breast cancer screening utilization among women from Muslim majority countries in Ontario, Canada.

Breast cancer screening disparities continue to prevail with immigrant women being at the forefront of the under screened population. There is a paucity of knowledge about the role of religious affiliation or cultural orientation on immigrant women's cancer screening uptake. This study examined differences in uptake of breast cancer screening among women from Muslim and non- Muslim majority countries in Ontario, Canada. A cohort of 1,851,834 screening-eligible women living in Ontario during April 1, 2013 to March 31, 2015 was created using linked health and social administrative databases. The study found that being born in a Muslim majority country was associated with lower breast cancer screening uptake after adjusting for region of origin, neighbourhood income, and primary care-related factors. However, screening uptake in Muslim majority countries varied by world region with the greatest differences found in Sub-Saharan Africa and South Asia. Screening uptake was lower for women who had no primary care provider, were in a traditional fee-for service model of primary care, had a male physician, had an internationally trained physician, resided in a low income neighbourhood, and entered Canada under the family class of immigration. Religion may play a role in screening uptake, however, the variation in rates by regions of origin, immigration class, and access to primary care providers alludes to confluence of socio-demographic, cultural beliefs and practices, immigration trajectories and system level factors. Facilitating access for immigrant women to regular primary care providers, particularly female providers and enrollment in primary care models could enhance screening uptake.

Knowledge and Perception about Clinical Research Shapes Behavior: Face to Face Survey in Korean General Public.

Considering general public as potential patients, identifying factors that hinder public participation poses great importance, especially in a research environment where demands for clinical trial participants outpace the supply. Hence, the aim of this study was to evaluate knowledge and perception about clinical research in general public. A total of 400 Seoul residents with no previous experience of clinical trial participation were selected, as representative of population in Seoul in terms of age and sex. To minimize selection bias, every fifth passer-by was invited to interview, and if in a cluster, person on the very right side was asked. To ensure the uniform use of survey, written instructions have been added to the questionnaire. Followed by pilot test in 40 subjects, the survey was administered face-to-face in December 2014. To investigate how perception shapes behavior, we compared perception scores in those who expressed willingness to participate and those who did not. Remarkably higher percentage of responders stated that they have heard of clinical research, and knew someone who participated (both, P < 0.001) compared to India. Yet, the percentage of responders expressed willingness to participate was 39.3%, a significantly lower rate than the result of the India (58.9% vs. 39.3%, P < 0.001). Treatment benefit was the single most influential reason for participation, followed by financial gain. Concern about safety was the main reason for refusal, succeeded by fear and lack of trust. Public awareness and educational programs addressing these negative perceptions and lack of knowledge will be effective in enhancing public engaged in clinical research.

Breast cancer screening disparities among immigrant women by world region of origin: a population-based study in Ontario, Canada.

Rates of mammography screening for breast cancer are disproportionately low in certain subgroups including low-income and immigrant women. The purpose of the study was to examine differences in rates of appropriate breast cancer screening (i.e., screening mammography every 2 years) among Ontario immigrant women by world region of origin and explore the association between appropriate breast cancer screening among these women groups and individual and structural factors. A cohort of 183,332 screening-eligible immigrant women living in Ontario between 2010 and 2012 was created from linked databases and classified into eight world regions of origin. Appropriate screening rates were calculated for each region by age group and selected sociodemographic, immigration, and healthcare-related characteristics. The association between appropriate screening across the eight regions of origin and selected sociodemographic, immigration, and health-related characteristics was explored using multivariate Poisson regression. Screening varied by region of origin, with South Asian women (48.5%) having the lowest and Caribbean and Latin American women (63.7%) the highest cancer screening rates. Factors significantly associated with lower screening across the world regions of origin included living in the lowest income neighborhoods, having a refugee status, being a new immigrant, not having a regular physical examination, not being enrolled in a primary care patient enrollment model, having a male physician, and having an internationally trained physician. Multiple interventions entailing cross-sector collaboration, promotion of patient enrollment models, community engagement, comprehensive and intensive outreach to women, and knowledge translation and transfer to physicians should be considered to address screening disparities among immigrant population. Consideration should be given to design and delivery of culturally appropriate and easily accessible cancer screening programs targeted at high- risk immigrant subgroups, such as women of South Asian origin, refugees, and new immigrants.

Accrual Patterns for Clinical Studies Involving Quantitative Imaging: Results of an NCI Quantitative Imaging Network (QIN) Survey.

Patient accrual is essential for the success of oncology clinical trials. Recruitment for trials involving the development of quantitative imaging biomarkers may face different challenges than treatment trials. This study surveyed investigators and study personnel for evaluating accrual performance and perceived barriers to accrual and for soliciting solutions to these accrual challenges that are specific to quantitative imaging-based trials. Responses for 25 prospective studies were received from 12 sites. The median percent annual accrual attained was 94.5% (range, 3%-350%). The most commonly selected barrier to recruitment (n = 11/25, 44%) was that "patients decline participation," followed by "too few eligible patients" (n = 10/25, 40%). In a forced choice for the single greatest recruitment challenge, "too few eligible patients" was the most common response (n = 8/25, 32%). Quantitative analysis and qualitative responses suggested that interactions among institutional, physician, and patient factors contributed to accrual success and challenges. Multidisciplinary collaboration in trial design and execution is essential to accrual success, with attention paid to ensuring and communicating potential trial benefits to enrolled and future patients.

Recruitment experience for a pragmatic randomized controlled trial: Using EMR initiatives and minimizing research infrastructure.

CONTEXT: Modernized approaches to multisite randomized controlled trials (RCT) include the use of electronic medical records (EMR) for recruitment, remote data capture (RDC) for multisite data collection, and strategies to reduce the need for research infrastructure. These features facilitate the conduct of pragmatic trials, or trials conducted in "real life" settings. OBJECTIVE: We describe the recruitment experience of an RCT to evaluate a clinic-based intervention targeting urban youth with asthma. MATERIALS AND METHODS: Using encounter and prescription databases, a list of potentially-eligible patients was linked to the Epic appointment scheduling system. Patients were enrolled during a scheduled visit and then electronically randomized to a tailored versus generic online intervention. RESULTS AND DISCUSSION: 1146 appointments for 580 eligible patients visiting 5 clinics were identified, of which 45.9% (266/580) were randomized to reach targeted enrollment (n=250). RDC facilitated multisite enrollment. Intervention content was further personalized through real- time entry of asthma medications prescribed at the clinic visit. EMR monitoring helped with recruitment trouble-shooting. Systemic challenges included a system-wide EMR transition and a system-wide reorganization of clinic staffing. CONCLUSIONS: Modernized RCTs can accelerate translation of research findings. Electronic initiatives facilitated implementation of this RCT; however, adaptations to recruitment strategies resulted in a more "explanatory" framework. .

Knowledge and Perception about Clinical Research Shapes Behavior: Face to Face Survey in Korean General Public

Considering general public as potential patients, identifying factors that hinder public participation poses great importance, especially in a research environment where demands for clinical trial participants outpace the supply. Hence, the aim of this study was to evaluate knowledge and perception about clinical research in general public. A total of 400 Seoul residents with no previous experience of clinical trial participation were selected, as representative of population in Seoul in terms of age and sex. To minimize selection bias, every fifth passer-by was invited to interview, and if in a cluster, person on the very right side was asked. To ensure the uniform use of survey, written instructions have been added to the questionnaire. Followed by pilot test in 40 subjects, the survey was administered face-to-face in December 2014. To investigate how perception shapes behavior, we compared perception scores in those who expressed willingness to participate and those who did not. Remarkably higher percentage of responders stated that they have heard of clinical research, and knew someone who participated (both, P < 0.001) compared to India. Yet, the percentage of responders expressed willingness to participate was 39.3%, a significantly lower rate than the result of the India (58.9% vs. 39.3%, P < 0.001). Treatment benefit was the single most influential reason for participation, followed by financial gain. Concern about safety was the main reason for refusal, succeeded by fear and lack of trust. Public awareness and educational programs addressing these negative perceptions and lack of knowledge will be effective in enhancing public engaged in clinical research.

Personalized medicine for pathological circadian dysfunctions.

The recent approval of a therapeutic for a circadian disorder has increased interest in developing additional medicines for disorders characterized by circadian disruption. However, previous experience demonstrates that drug development for central nervous system (CNS) disorders has a high failure rate. Personalized medicine, or the approach to identifying the right treatment for the right patient, has recently become the standard for drug development in the oncology field. In addition to utilizing Companion Diagnostics (CDx) that identify specific genetic biomarkers to prescribe certain targeted therapies, patient profiling is regularly used to enrich for a responsive patient population during clinical trials, resulting in fewer patients required for statistical significance and a higher rate of success for demonstrating efficacy and hence receiving approval for the drug. This personalized medicine approach may be one mechanism that could reduce the high clinical trial failure rate in the development of CNS drugs. This review will discuss current circadian trials, the history of personalized medicine in oncology, lessons learned from a recently approved circadian therapeutic, and how personalized medicine can be tailored for use in future clinical trials for circadian disorders to ultimately lead to the approval of more therapeutics for patients suffering from circadian abnormalities.