Assessing the efficiency of eligibility criteria for low-dose computed tomography lung screening in China according to current guidelines.

BACKGROUND: Evidence from observational studies indicates that lung cancer screening (LCS) guidelines with high rates of lung cancer (LC) underdiagnosis, and although current screening guidelines have been updated and eligibility criteria for screening have been expanded, there are no studies comparing the efficiency of LCS guidelines in Chinese population. METHODS: Between 2005 and 2022, 31,394 asymptomatic individuals were screened using low-dose computed tomography (LDCT) at our institution. Demographic data and relevant LC risk factors were collected. The efficiency of the LCS for each guideline criteria was expressed as the efficiency ratio (ER). The inclusion rates, eligibility rates, LC detection rates, and ER based on the different eligibility criteria of the four guidelines were comparatively analyzed. The four guidelines were as follows: China guideline for the screening and early detection of lung cancer (CGSL), the National Comprehensive Cancer Network (NCCN), the United States Preventive Services Task Force (USPSTF), and International Early Lung Cancer Action Program (I-ELCAP). RESULTS: Of 31,394 participants, 298 (155 women, 143 men) were diagnosed with LC. For CGSL, NCCN, USPSTF, and I-ELCAP guidelines, the eligibility rates for guidelines were 13.92%, 6.97%, 6.81%, and 53.46%; ERe for eligibility criteria were 1.46%, 1.64%, 1.51%, and 1.13%, respectively; and for the inclusion rates, they were 19.0%, 9.5%, 9.3%, and 73.0%, respectively. LCs which met the screening criteria of CGSL, NCCN, USPSTF, and I-ELCAP guidelines were 29.2%, 16.4%, 14.8%, and 86.6%, respectively. The age and smoking criteria for CGSL were stricter, hence resulting in lower rates of LC meeting the screening criteria. The CGSL, NCCN, and USPSTF guidelines showed the highest underdiagnosis in the 45-49 age group (17.4%), while the I-ELCAP guideline displayed the highest missed diagnosis rate (3.0%) in the 35-39 age group. Males and females significantly differed in eligibility based on the criteria of the four guidelines (P < 0.001). CONCLUSIONS: The I-ELCAP guideline has the highest eligibility rate for both males and females. But its actual efficiency ratio for those deemed eligible by the guideline was the lowest. Whereas the NCCN guideline has the highest ERe value for those deemed eligible by the guideline.

Exclusion of older adults from randomized controlled trials in rheumatoid arthritis.

OBJECTIVES: To assess eligibility criteria that either explicitly or implicitly exclude older patients from randomized controlled trials (RCTs) in RA. METHODS: Our analysis included RCTs of pharmacological interventions registered with ClinicalTrials.gov and started between 2013 and 2022. Co-primary outcomes were proportions of trials with an upper age limit and the eligibility criteria indirectly increasing risk of the exclusion of older adults. RESULTS: A total of 143/290 (49%) trials had an upper age limit of 85 years or less. Multivariable analysis showed that the odds of an upper age limit were significantly lower in trials performed in the USA [adjusted odds ratio (aOR), 0.34; CI, 0.12-0.99; P = 0.04] and intercontinental trials (aOR, 0.4; CI, 0.18-0.87; P = 0.02). In total, 154/290 (53%) trials had at least one eligibility criterion implicitly excluding older adults. These included specific comorbidities (n = 114; 39%), compliance concerns (n = 67; 23%), and broad and vague exclusion criteria (n = 57; 20%); however, we found no significant associations between these criteria and trial characteristics. Overall, 217 (75%) trials either explicitly or implicitly excluded older patients; we also noted a trend towards increasing proportion of these trials over time. Only one trial (0.3%) enrolled solely patients aged 65 and older. CONCLUSION: Older adults are commonly excluded from RCTs in RA based on both age limits and other eligibility criteria. This seriously limits the evidence base for the treatment of older patients in clinical practice. Given the growing prevalence of RA in older adults, relevant RCTs should be more inclusive to them.

Transparency in Cognitive Training Meta-analyses: A Meta-review.

Meta-analyses often present flexibility regarding their inclusion criteria, outcomes of interest, statistical analyses, and assessments of the primary studies. For this reason, it is necessary to transparently report all the information that could impact the results. In this meta-review, we aimed to assess the transparency of meta-analyses that examined the benefits of cognitive training, given the ongoing controversy that exists in this field. Ninety-seven meta-analytic reviews were included, which examined a wide range of populations with different clinical conditions and ages. Regarding the reporting, information about the search of the studies, screening procedure, or data collection was detailed by most reviews. However, authors usually failed to report other aspects such as the specific meta-analytic parameters, the formula used to compute the effect sizes, or the data from primary studies that were used to compute the effect sizes. Although some of these practices have improved over the years, others remained the same. Moreover, examining the eligibility criteria of the reviews revealed a great heterogeneity in aspects such as the training duration, age cut-offs, or study designs that were considered. Preregistered meta-analyses often specified poorly how they would deal with the multiplicity of data or assess publication bias in their protocols, and some contained non-disclosed deviations in their eligibility criteria or outcomes of interests. The findings shown here, although they do not question the benefits of cognitive training, illustrate important aspects that future reviews must consider.

Assessment of eligibility criteria in renal cell carcinoma trials evaluating systemic therapy.

OBJECTIVES: To characterise the restrictiveness of eligibility criteria in contemporary renal cell carcinoma (RCC) trials, using recommendations from the American Society of Clinical Oncology (ASCO)-Friends of Cancer Research (FCR) initiative. METHODS: vPhase I-III trials assessing systemic therapies in patients with RCC starting between 30 June 2012 and 30 June 2022 were identified. Eligibility criteria regarding brain metastases, prior or concurrent malignancies, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, and human immunodeficiency virus (HIV) infection were identified and stratified into three groups: exclusion, conditional inclusion, and not reported. Descriptive statistics were used to determine the frequency of eligibility criteria. Fisher's exact test or chi-square test were used to calculate their associations with certain trial characteristics. RESULTS: A total of 423 RCC trials were initially identified of which 112 (26.5%) had sufficient accessible information. Exclusion of patients with HIV infection, HBV/HCV infection, brain metastases, and prior or concurrent malignancies were reported in 74.1%, 53.6%, 33.0%, and 8.0% of trials, respectively. In the context of HIV and HBV/HCV infection, patients were largely excluded from trials evaluating immunotherapy (94.4% and 77.8%, respectively). In addition, brain metastases were excluded in trials assessing targeted therapy (36.4%), combined therapy (33.3%), and immunotherapy (22.2%). Exclusion of patients with prior or concurrent malignancies was less frequently reported, accounting for 9.1%, 8.3%, and 5.6% targeted therapy, combined therapy and immunotherapy trials, respectively. CONCLUSION: A substantial proportion of RCC trials utilise restrictive eligibility criteria, excluding patients with fairly prevalent comorbidities. Implementing the ASCO-FCR recommendations will ensure resulting data are more inclusive and aligned with patient populations in the real-world.

Meta-analysis of Pregnancy Events in Biomedical HIV Prevention Trials in Sub-Saharan Africa: Implications for Gender Transformative Trials.

Historically, pregnant and lactating populations (PLP) have been excluded or disenrolled from biomedical HIV prevention trials, despite being more likely to acquire HIV during pregnancy and the post-partum period. We conducted a meta-analysis of pregnancy events in biomedical HIV prevention trials in sub-Saharan Africa to support trialists moving toward more inclusive clinical and implementation studies. We searched peer-reviewed literature reporting pregnancy events and contraceptive requirements in HIV prevention trials between 2001 and 2022. We hypothesized four variables to explain variation: contraceptive requirements, study start year, study product, and sub-region. We fit a meta-analytic model to estimate individual effect sizes and sampling variances, then conducted sub-group analyses to assess moderating effects. We identified 38 references for inclusion, across which the proportion of pregnancy events was 8% (95% confidence interval [CI]: 6-10%) with high heterogeneity (I2 = 99%). Studies not requiring contraceptives (21%, 95%CI: 7-48%) reported a significantly higher proportion of pregnancy events than studies requiring two methods (5%, 95%CI: 2-10%). Studies launched between 2001 and 2007 (11%, 95%CI: 8-16%), microbicide gel trials (12%, 95%CI: 8-18%), and studies conducted in Western Africa (28%, 95%CI: 13-51%) reported higher proportions of pregnancy events than reference groups. Together, these variables have a moderating effect on pregnancy events (p < 0.0001), explaining 63% of heterogeneity in trials. Results describe how, over time, more stringent contraceptive requirements reduced pregnancy events, which ensured necessary statistical power but limited reproductive choice by participants. With the move toward continuing PLP on experimental products, trialists can utilize estimated pregnancy events reported here to inform strategies that accommodate participants' changing fertility preferences.

Absolute neutrophil count clinical trial eligibility criteria for pediatric oncology phase I and phase I/II trials by sponsorship.

Normal absolute neutrophil count (ANC) variations, as seen with Duffy-null associated neutrophil count (DANC), are not accounted for in trial eligibility, which may contribute to racial enrollment disparities. We describe ANC eligibility for pediatric oncology phase I/II clinical trials according to primary sponsorship from 2010 to 2023 using ClinicalTrials.gov. Out of 438 trials, 20% were industry-sponsored. Total 17% of trials required ANC ≥1500 cells/µL for enrollment; however, industry-sponsored trials were significantly more likely to require ANC ≥1500 cells/µL than non-industry-sponsored trials (odds ratio 2.53, 95% confidence interval: 1.39-4.62; p < .001). These data suggest laboratory exclusion criteria are one possible mechanism for pediatric clinical trial enrollment disparities.

Evaluation of Inclusion and Exclusion Criteria for Pyoderma Gangrenosum in Clinical Research: A Systematic Review.

INTRODUCTION: Pyoderma gangrenosum (PG) is a rare, inflammatory dermatologic disease that, as a diagnosis of exclusion with nonspecific histologic features, is difficult to diagnose. As pharmaceutical interest in potential treatments for PG increases, the need for standardized diagnostic criteria to ensure reproducibility, comparability, and external validity of PG research is required. In this study, we aim to characterize the inclusion and exclusion criteria used in the diagnosis of PG in clinical research studies as well as the eligibility of PG in clinical trials. METHODS: A systematic review was conducted to characterize the PG inclusion and exclusion criteria in research studies. An additional search of the USA and international clinical trials databases was conducted as well to capture eligibility criteria for PG trials. RESULTS: Our study revealed a broad range of inclusion and exclusion criteria used to establish the presence or absence of PG. Based on eight distinct categories used to characterize inclusion criteria for research studies, diagnosis by a dermatologist (n = 25, 31.6%), no inclusion criteria listed (n = 21, 26.6%), and clinical and histopathologic features consistent with PG (n = 20, 25.3%) were most common. For current clinical trials, six categories were used to characterize inclusion criteria, of which clinical and histopathologic features consistent with PG (n = 5, 31.3%), identification based on diagnosis of PG (n = 4, 25.0%), and clinical features consistent with PG (n = 3, 18.8%) were the most common. CONCLUSION: This systematic literature review highlights the range of heterogeneity in diagnostic and eligibility criteria used in PG-directed clinical research and current clinical trials and illustrates the need for the development of consensus guidelines and a rigorous framework to enable high-quality future trials for PG.

Defining and quantifying population-level need for children's palliative care: findings from a rapid scoping review.

BACKGROUND: The number of children who require palliative care has been estimated to be as high as 21 million globally. Delivering effective children's palliative care (CPC) services requires accurate population-level information on current and future CPC need, but quantifying need is hampered by challenges in defining the population in need, and by limited available data. The objective of this paper is to summarise how population-level CPC need is defined, and quantified, in the literature. METHODS: Scoping review performed in line with Joanna Briggs Institute methodology for scoping reviews and PRISMA-ScR guidelines. Six online databases (CINAHL, Cochrane Library, EMBASE, Medline, PsycINFO, and Web of Science), and grey literature, were searched. INCLUSION CRITERIA: literature published in English; 2008-2023 (Oct); including children aged 0-19 years; focused on defining and/or quantifying population-level need for palliative care. RESULTS: Three thousand five hundred seventy-eight titles and abstracts initially reviewed, of which, 176 full-text studies were assessed for eligibility. Overall, 51 met the inclusion criteria for this scoping review. No universal agreement identified on how CPC need was defined in population-level policy and planning discussions. In practice, four key definitions of CPC need were found to be commonly applied in quantifying population-level need: (1) ACT/RCPCH (Association for Children with Life-Threatening or Terminal Conditions and their Families, and the Royal College of Paediatrics and Child Health) groups; (2) The 'Directory' of Life-Limiting Conditions; (3) 'List of Life-Limiting Conditions'; and (4) 'Complex Chronic Conditions'. In most cases, variations in data availability drove the methods used to quantify population-level CPC need and only a small proportion of articles incorporated measures of complexity of CPC need. CONCLUSION: Overall, greater consistency in how CPC need is defined for policy and planning at a population-level is important, but with sufficient flexibility to allow for regional variations in epidemiology, demographics, and service availability. Improvements in routine data collection of a wide range of care complexity factors could facilitate estimation of population-level CPC need and ensure greater alignment with how need for CPC is defined at the individual-level in the clinical setting.

Total Joint Arthroplasty Outcomes in Eligible Patients Versus Patients Who Failed to Meet at Least 1 Eligibility Criterion: A Single-Center Retrospective Analysis.

BACKGROUND: This study looks to investigate how not meeting eligibility criteria affects postoperative outcomes following total joint arthroplasty surgery. METHODS: A retrospective review was conducted of total joint arthroplasty patients at a single academic institution. Demographics, laboratory values, and complications were recorded. Continuous and categorical variables were compared using the Student's T-test and the Chi-Square test, respectively. Multivariable analysis was used to control for confounding variables. RESULTS: Our study included 915 total hip and 1,579 total knee arthroplasty patients. For total hip and total knee arthroplasty, there were no significant differences in complications (P = .11 and .87), readmissions (P = .83 and .2), or revision surgeries (P = .3 and 1) when comparing those who met all criteria to those who did not. Total hip arthroplasty patients who did not meet two criteria had 16.1 higher odds (P = .02) of suffering a complication. There were no differences in complications (P = .34 and .41), readmissions (P = 1 and .55), or revision surgeries (P = 1 and .36) between ineligible patients treated by total joint arthroplasty surgeons and those who were not. Multivariable analysis demonstrated no eligibility factors were associated with outcomes for both total hip and knee arthroplasty. CONCLUSIONS: There was no significant difference in outcomes between those who met all eligibility criteria and those who did not. Not meeting two criteria conferred significantly higher odds of suffering a complication for total hip arthroplasty patients. Total joint arthroplasty surgeons had similar outcomes to non-total joint surgeons, although their patient population was more complex. LEVEL OF EVIDENCE: III.

Eligibility criteria in clinical trials in breast cancer: a cohort study.

BACKGROUND: Breast cancer (BC) is the most common cancer type in women. The purpose of this study was to assess the eligibility criteria in recent clinical trials in BC, especially those that can limit the enrollment of older patients as well as those with comorbidities and poor performance status. METHODS: Data on clinical trials in BC were extracted from ClinicalTrials.gov. Co-primary outcomes were proportions of trials with different types of the eligibility criteria. Associations between trial characteristics and the presence of certain types of these criteria (binary variable) were determined with univariate and multivariate logistic regression. RESULTS: Our analysis included 522 trials of systemic anticancer treatments started between 2020 and 2022. Upper age limits, strict exclusion criteria pertaining to comorbidities, and those referring to inadequate performance status of the patient were used in 204 (39%), 404 (77%), and 360 (69%) trials, respectively. Overall, 493 trials (94%) had at least one of these criteria. The odds of the presence of each type of the exclusion criteria were significantly associated with investigational site location and trial phase. We also showed that the odds of the upper age limits and the exclusion criteria involving the performance status were significantly higher in the cohort of recent trials compared with cohort of 309 trials started between 2010 and 2012 (39% vs 19% and 69% vs 46%, respectively; p < 0.001 for univariate and multivariate analysis in both comparisons). The proportion of trials with strict exclusion criteria was comparable between the two cohorts (p > 0.05). Only three of recent trials (1%) enrolled solely patients aged 65 or 70 and older. CONCLUSIONS: Many recent clinical trials in BC exclude large groups of patients, especially older adults, individuals with different comorbidities, and those with poor performance status. Careful modification of some of the eligibility criteria in these trials should be considered to allow investigators to assess the benefits and harms of investigational treatments in participants with characteristics typically encountered in clinical practice.

Clinical Significance of Eligibility Criteria Determined by the SPIRITS Trial in Patients with Advanced Gastric Cancer.

INTRODUCTION: This study aimed to assess the clinical significance of eligibility criteria determined by phase 3 clinical trials in the clinical practice of patients with advanced gastric cancer who underwent chemotherapy. METHODS: Patients with stage IV gastric cancer who received chemotherapy between February 2002 and December 2021 were retrospectively enrolled and divided into two groups (the eligible vs. ineligible group) based on eligibility criteria determined by the SPIRITS (S-1 vs. S-1 plus cisplatin) trial. RESULTS: Among the 207 patients, 103 (49.8%) and 104 (50.2%) patients were classified into eligible and ineligible groups, respectively. Eligibility criteria were significantly correlated with age, the first-line regimen of chemotherapy, the presence or absence of conversion surgery, and tumor response to the first-line chemotherapy (all p < 0.01). The eligible group had a significantly higher induction of post-progression chemotherapy after first- and second-line chemotherapy than did the ineligible group (all p < 0.01). The ineligible group had significantly poorer prognoses than the eligible group (p < 0.0001). Multivariate analysis showed that peritoneal dissemination, tumor response, conversion surgery, and eligibility criteria were independent prognostic factors (all p < 0.05). CONCLUSION: Eligibility criteria determined by the SPIRITS trial may have clinical utility for predicting tumor response, the induction of conversion surgery, and prognosis in patients with advanced gastric cancer who underwent chemotherapy.

Navigating imperfect policies to donate plasma: Survey on plasma donation and a pilot plasma donation program among men who have sex with men in Canada.

BACKGROUND: In 2021, Canada implemented a pilot plasma program allowing some sexually active men who have sex with men (including but not limited to gay and bisexual men; gbMSM) to donate plasma. Changes to plasma donation policy could help address inequities in access to plasma donation and increase Canada's domestically collected plasma supply if more gbMSM donate as a result. We aimed to (1) examine views regarding plasma donation and the pilot program prior to implementation and (2) identify modifiable theory-informed predictors of gbMSM's intention to donate plasma. METHODS: We developed, piloted, and disseminated a questionnaire informed by the Theoretical Domains Framework (TDF). We recruited gbMSM in London (ON) and Calgary (AB) to an anonymous, online cross-sectional survey. RESULTS: A total of 246 gbMSM completed the survey. On scales from 1 (strongly disagree) to 5 (strongly agree), general intention to donate was high (mean = 4.24; SD = 0.94). The pilot program itself was mostly acceptable (mean = 3.71, SD = 1.16), but the intention to donate under the unique requirements of the pilot program was lower than general intention (mean = 3.58; SD = 1.26). Two domains from the theoretical domains framework (TDF) (beliefs about consequences of donating plasma and social influences) were independently associated with general intention to donate. DISCUSSION: The pilot plasma program as an incremental step toward more inclusive policies was mostly viewed as acceptable by the impacted communities. Historical and ongoing exclusions create unique barriers to donation. There are clear opportunities for developing theory-informed interventions to support gbMSM to donate plasma as policies continue to become more inclusive and more become eligible to donate.

Relevance of haemoglobin monitoring in apheresis plasma donors: A retrospective cohort study in Québec, Canada.

BACKGROUND AND OBJECTIVES: Systematically measuring pre-donation haemoglobin (Hb) levels might be overly cautious for apheresis plasma donation, since plasmapheresis entails a small loss of red blood cells. We explored the association between the frequency of apheresis plasma donation and capillary blood Hb levels. MATERIALS AND METHODS: This retrospective cohort study included donors who gave apheresis plasma at least twice between 24 October 2020 and 23 October 2022 in Québec, Canada. Results were stratified by sex and analysed with linear repeated-measure mixed models with random intercepts. RESULTS: In total, 9535 men (mean age = 46.7 years) and 9409 women (mean age = 41.1 years) made ≥2, but no more than 16 apheresis plasma donations. Over an average of 9.2 months of observation, men maintained Hb levels well above the Hb deferral threshold, and their Hb levels decreased by only 0.17 g/dL between the 1st and 15th donation return (p < 0.0001). Over an average of 9.0 months of observation, women also maintained adequate Hb levels, and their Hb levels decreased by 0.08 g/dL between the 1st and 15th donation return. CONCLUSION: The frequency of apheresis plasma donation was not associated with clinically meaningful changes in Hb levels, neither in men nor in women. This evidence questions the relevance of systematically monitoring Hb for apheresis plasma donation, at least for donation frequencies of ≤7-8 times per year. However, an adverse impact of plasmapheresis on Hb levels cannot be ruled out for individuals donating more frequently or for longer than ~9 months.

Insights into the diversity of blood donation practice across Asia: How blood collection agencies adapt donor criteria and processes to their population.

BACKGROUND AND OBJECTIVES: Securing an adequate blood supply relies on accurate knowledge of blood donors and donation practices. As published evidence on Asian populations is sparse, this study aims to gather up-to-date information on blood donors and donation practices in Asia to assist planning and strategy development. MATERIALS AND METHODS: Ten blood collection agencies (BCAs) provided 12 months' data on donors who met eligibility criteria or were deferred, as well as details of their donation practices. Body mass index and blood volumes were calculated and analysed. RESULTS: Data on 9,599,613 donations and 154,834 deferrals from six national and four regional BCAs revealed varied donation eligibility and collection practices. Seven used haemoglobin (Hb) criteria below the World Health Organization anaemia threshold. Seven accepted donors weighing <50 kg. Data collection on the weight and height of donors and on deferrals was inconsistent, often not routine. Deferred donors appear to weigh less, with corresponding lower estimated blood volume. CONCLUSION: The diversity in eligibility criteria and donation practices reflects each BCA's strategy for balancing donor health with securing an adequate blood supply. Use of lower Hb criteria substantiate their appropriateness in Asia and indicate the need to define Hb reference intervals relevant to each population. We encourage routine gathering of donor weight and height data to enable blood volume estimation and local optimization of donation volumes. Blood volume estimation formulae specific for the Asian phenotype is needed. Information from this study would be useful for tailoring donation criteria of Asian donors around the world.

Effective matching of patients to clinical trials using entity extraction and neural re-ranking.

INTRODUCTION: Clinical trials (CTs) often fail due to inadequate patient recruitment. Finding eligible patients involves comparing the patient's information with the CT eligibility criteria. Automated patient matching offers the promise of improving the process, yet the main difficulties of CT retrieval lie in the semantic complexity of matching unstructured patient descriptions with semi-structured, multi-field CT documents and in capturing the meaning of negation coming from the eligibility criteria. OBJECTIVES: This paper tackles the challenges of CT retrieval by presenting an approach that addresses the patient-to-trials paradigm. Our approach involves two key components in a pipeline-based model: (i) a data enrichment technique for enhancing both queries and documents during the first retrieval stage, and (ii) a novel re-ranking schema that uses a Transformer network in a setup adapted to this task by leveraging the structure of the CT documents. METHODS: We use named entity recognition and negation detection in both patient description and the eligibility section of CTs. We further classify patient descriptions and CT eligibility criteria into current, past, and family medical conditions. This extracted information is used to boost the importance of disease and drug mentions in both query and index for lexical retrieval. Furthermore, we propose a two-step training schema for the Transformer network used to re-rank the results from the lexical retrieval. The first step focuses on matching patient information with the descriptive sections of trials, while the second step aims to determine eligibility by matching patient information with the criteria section. RESULTS: Our findings indicate that the inclusion criteria section of the CT has a great influence on the relevance score in lexical models, and that the enrichment techniques for queries and documents improve the retrieval of relevant trials. The re-ranking strategy, based on our training schema, consistently enhances CT retrieval and shows improved performance by 15% in terms of precision at retrieving eligible trials. CONCLUSION: The results of our experiments suggest the benefit of making use of extracted entities. Moreover, our proposed re-ranking schema shows promising effectiveness compared to larger neural models, even with limited training data. These findings offer valuable insights for improving methods for retrieval of clinical documents.

[The correct way to read and understand published clinical trial results].

Correct interpretation of clinical trial results is important. Overall survival was once considered the primary endpoint for neoplastic disease, but surrogate endpoints are increasingly being used for diseases whose prognosis has improved. This is due to the longer trial duration required to obtain conclusions and to poor statistical power. Clinical decision-making in practice is also shifting to using these surrogate endpoints. In clinical trials, eligibility criteria are set to obtain differences between arms. However, this does not mean that results should only be applied to eligible populations, as it is not realistic to conduct a clinical trial in patients with all possible characteristics. Rather, results should be applied to patients who do not meet the eligibility criteria, with careful consideration. A single clinical trial often presents the results of many subgroup analyses, but the main conclusion should not be judged differently by subgroup. The purpose of subgroup analysis is to find potential confounders that interact with the conclusion, and results of subgroup analysis should not be overestimated. Non-inferiority trials have become increasingly common in recent years, and their importance is not limited to demonstrating the non-inferiority of the primary endpoint. Specifically, they are also important for understanding the benefits in the experimental arm outside those in primary analysis. Some secondary endpoints are very important for making conclusions about these benefits.

Exclusion criteria of breast cancer clinical trial protocols: a descriptive analysis.

PURPOSE: 3-8% of US adults with cancer are enrolled in a clinical trial due to various barriers to enrollment. The purpose of this study is to evaluate the variability of eligibility criteria, which currently have no standard guidelines. METHODS: This descriptive analysis utilized all therapeutic breast protocols offered at the University of Alabama at Birmingham between 2004 and 2020. Exclusion criteria were abstracted using OnCore and ClinicalTrials.gov. Laboratory values included liver function tests and hematologic labs. Comorbid conditions included congestive heart failure, cardiovascular disease, central nervous system (CNS) metastases, and prior cancer history. Comorbid conditions were further analyzed by amount of time protocols required participants to be from diagnosis or exacerbation-free. RESULTS: 102 protocols were eligible. Among liver laboratory values, bilirubin (78%) was included in most protocols ranging from institutional upper limit of normal (ULN) (9%) to 3xULN (2%), with 1.5xULN (56%) being most common. Similar variability was observed in alanine transaminase and aspartate transaminase. Among hematological labs, 82% of protocols defined a lower limit of acceptable absolute neutrophil count ranging from 500 µL (1%) to 1800 µL (1%), with 1500 µL (64%) being most common. Of the comorbid conditions, exclusion criteria varied for congestive heart failure (49%), an acute exacerbation of cardiovascular disease (80%), CNS metastases (59%), and a prior cancer (66%). The allowable timeframe varied between protocols for cardiovascular disease and prior cancer. CONCLUSION: Substantial heterogeneity was observed across laboratory values and comorbid variables among protocols. Future research should focus on defining standardized eligibility criteria while allowing for deviation based on drug specificity.

Staff perspectives on barriers and enablers to implementing alternative source plasma eligibility criteria for gay, bisexual, and other men who have sex with men.

BACKGROUND: Canadian Blood Services introduced new eligibility criteria that allows some sexually active gay, bisexual, and other men who have sex with men (gbMSM) to donate source plasma, marking a significant change from time-based deferral criteria. We aimed to identify potential barriers and enablers to implementing the new criteria from the perspective of donor center staff. STUDY DESIGN AND METHODS: We conducted Theoretical Domains Framework-informed interviews with staff from two source plasma donation centers in Canada. RESULTS: We completed 28 interviews between June 2020 and April 2021. Three themes representing eight domains captured key tensions. Valuing inclusive eligibility criteria: staff support inclusive criteria; many were concerned the new criteria remained discriminatory. Investing in positive donor experiences: staff wished to foster positive donor experiences; however, they worried gbMSM donors would express anger and disappointment regarding the new criteria, staff would experience unease over using stigmatizing criteria and convey nonverbal cues of discomfort, and recurring plasma donors may behave inappropriately. Supporting education, training, and transparency of eligibility criteria: participants believed providing in-person training (i.e., to explain criteria rationale, address discomfort, practice responding to donor questions) and ensuring donors and the public were well-informed of the upcoming changes would improve implementation. DISCUSSION: Participant views emphasize the importance of supporting staff through training and transparent communication to optimize the delivery of world-class equitable care for a new cohort of donors who have previously been excluded from plasma donation. Findings inform which staff supports to consider to improve implementation as policies continue to shift internationally.

Awareness of, Willingness to Take PrEP and Its Actual Use Among Belgian MSM at High Risk of HIV Infection: Secondary Analysis of the Belgian European MSM Internet Survey.

We examined PrEP awareness, willingness to take it and early PrEP use among men who have sex with men (MSM) at increased risk of HIV acquisition in Belgium. This analysis of the Belgian EMIS online data of 2017-2018 adopts a cascade approach, with the following steps quantified as conditional probabilities: being eligible for, aware of, willing to take PrEP, and PrEP use. One out of three MSM was eligible to use PrEP according to the operationalized Belgian reimbursement criteria. PrEP awareness was lower among socioeconomically vulnerable MSM, MSM living outside large cities, MSM who were less open about their sexuality and those who did not identify as gay or homosexual. A lack of PrEP knowledge, a higher self-efficacy regarding safe sex, having a steady partner and reporting more symptoms of depression were related to unwillingness to use PrEP. Among those willing to take PrEP, less than one third were actually using PrEP. Not using PrEP was associated with living in small cities and experiencing financial problems.

Randomized clinical trials and real life studies: Comparison of baseline characteristics of patients in oral target therapies for renal cell carcinoma.

INTRODUCTION: Pivotal Randomized Controlled Trials (RCTs) constitute scientific evidence in support of therapeutic choices when a drug is authorized in the market. In RCTs, patients are selected in a rigorous manner, in order to avoid bias that may influence efficacy assessments. Therefore, patients who take the drug in Real Life Studies (RLSs) are not the same as those participating in RCTs, which, in turn, leads to low data transferability from RCTs to RLS. The objective of this study was to evaluate the differences between RCTs and RLS, in terms of patient baseline characteristics. MATERIALS AND METHODS: Our study includes all oral target therapies for RCC (Renal Cell Carcinoma) marketed in Europe before March 31, 2019. For each treatment, we considered both RCTs and RLSs, the former gathered from Summary of Product Characteristics published on the European Medicine Agency (EMA) website, and the latter yielded by our search in relevant literature. For each drug considered, we then compared the baseline characteristics of patients included in the RCT samples with those of the samples included in the RLSs using the Chi-squared and Mann-Whitney tests. RESULTS: We considered six medicines, for a total of 9 pivotal RCTs and 31 RLSs. RCTs reported the same type of patient baseline characteristics, whereas RLSs are more varied in reporting. Some patient baseline characteristics (metastases, previous treatments, etc.) were significantly different between RCTs and RLs. Other characteristics, such as ECOG Performance Status, brain metastases, and comorbidities, liver and kidney failure, are comprised in exclusion criteria of RCTs, though are included in RLS.Discussion and Conclusion: While evaluating equal treatments for the same indications, RCTs and RLSs do not always assess patients with the same characteristics. It would be necessary to produce evidence from RLSs so as to have an idea of treatment effectiveness in patients groups that are not eligible or underrepresented in RCTs.