Considerations for using potential surrogate endpoints in cancer screening trials.

The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Review aims to highlight the issues underlying the choice and use of surrogate endpoints for cancer screening trials, to propose criteria for when and how we might use such endpoints, and to suggest possible candidates. We present the current landscape and challenges, and discuss lessons and shortcomings from the therapeutic trial setting. It is hugely challenging to validate a surrogate endpoint, even with carefully designed clinical studies. Nevertheless, we consider whether there are candidates that might satisfy the requirements defined by research and regulatory bodies.

Protocol to measure validity and reliability of colorectal, breast, cervical and lung cancer screening questions from the 2021 National Health Interview Survey: Methodology and design.

Previous studies demonstrate that self-reports of mammography screening for breast cancer and colonoscopy screening for colorectal cancer demonstrate concordance, based on adherence to screening guidelines, with electronic medical records (EMRs) in over 90% of those interviewed, as well as high sensitivity and specificity, and can be used for monitoring our Healthy People goals. However, for screening tests for cervical and lung cancers, and for various sub-populations, concordance between self-report and EMRs has been noticeably lower with poor sensitivity or specificity. This study aims to test the validity and reliability of lung, colorectal, cervical, and breast cancer screening questions from the 2021 and 2022 National Health Interview Survey (NHIS). We present the protocol for a study designed to measure the validity and reliability of the NHIS cancer screening questions compared to EMRs from four US-based healthcare systems. We planned a randomized trial of a phone- vs web-based survey with NHIS questions that were previously revised based on extensive cognitive interviewing. Our planned sample size will be 1576 validity interviews, and 1260 interviews randomly assigned at 1 or 3 months after the initial interview. We are enrolling people eligible for cancer screening based on age, sex, and smoking history per US Preventive Services Task Force recommendations. We will evaluate question validity using concordance, sensitivity, specificity, positive predictive value, negative predictive value, and report-to-records ratio. We further are randomizing participants to complete a second survey 1 vs 3 months later to assess question reliability. We suggest that typical measures of concordance may need to be reconsidered in evaluating cancer screening questions.

Critical lessons from a pragmatic randomized trial of home-based COVID-19 testing in rural Native American and Latino communities.

PURPOSE: Native Americans and Latinos have higher COVID-19 infection and mortality rates and may have limited access to diagnostic testing. Home-based testing may improve access to care in rural and underserved populations. This study tests the effect of community health worker (CHW) support on accessibility, feasibility, and completion of COVID-19 home testing among Native American and Latino adults living on the Flathead Reservation in Montana and in Yakima Valley, Washington. METHODS: A two-arm, multisite, pragmatic randomized controlled trial was conducted using block randomization stratified by site and participant age. Active arm participants received CHW assistance with online COVID-19 test kit registration and virtual swabbing support. The passive arm participants received standard-of-care support from the kit vendor. Logistic regression modeled the association between study arm and test completion (primary outcome) and between study arm and test completion with return of valid test results (secondary outcome). Responses to posttest surveys and interviews were summarized using deductive thematic analysis. FINDINGS: Overall, 63% of participants (n = 268) completed COVID-19 tests, and 50% completed tests yielding a valid result. Active arm participants had higher odds of test completion (odds ratio: 1.66, 95% confidence interval [1.01, 2.75]). Differences were most pronounced among adults ≥60 years. Participants cited ease of use and not having to leave home as positive aspects, and transportation and mailing issues as negative aspects of home-based testing. CONCLUSIONS: CHW support led to higher COVID-19 test completion rates, particularly among older adults. Significant testing barriers included language, educational level, rurality, and test kit issues.

Interruptions in bladder cancer care during the COVID-19 public health emergency.

BACKGROUND: Academic and community urology centers participating in a pragmatic clinical trial in non-muscle-invasive bladder cancer completed monthly surveys assessing restrictions in aspects of bladder cancer care due to the COVID-19 Public Health Emergency. Our objective was to describe pandemic-related restrictions on bladder cancer care. METHODS: We invited 32 sites participating in a multicenter pragmatic bladder cancer trial to complete monthly surveys distributed through REDCap beginning in May 2020. These surveys queried sites on whether they were experiencing restrictions in the use of elective surgery, transurethral resection of bladder tumors (TURBT), radical cystectomy, office cystoscopy, and intravesical bacillus Calmette-Guerin (BCG) availability. Responses were collated with descriptive statistics. RESULTS: Of 32 eligible sites, 21 sites had at least a 50% monthly response rate over the study period and were included in the analysis. Elective surgery was paused at 76% of sites in May 2020, 48% of sites in January 2021, and 52% of sites in January 2022. Over those same periods, coinciding with COVID-19 incidence waves, TURBT was restricted at 10%, 14%, and 14% of sites, respectively, radical cystectomy was restricted at 10%, 14%, and 19% of sites, respectively, and cystoscopy was restricted at 33%, 0%, and 10% of sites, respectively. CONCLUSIONS: Bladder cancer care was minimally restricted compared with more pronounced restrictions seen in general elective surgeries during the COVID-19 pandemic.

The cost of simplifying treatments for cystic fibrosis: Implications of the SIMPLIFY trial.

BACKGROUND: Dornase alfa and hypertonic saline are mucoactive therapies that can improve respiratory symptoms in people with cystic fibrosis (CF). A recent randomized control trial showed that participants with well-preserved pulmonary function taking elexacaftor + tezacaftor + ivacaftor (ETI) who discontinued dornase alfa or hypertonic saline for 6 weeks had no clinically meaningful decline in lung function. This may prompt discussions with care providers regarding ongoing use of these medications. OBJECTIVE: To compare the costs of outpatient medications between people taking ETI who continued or discontinued (1) dornase alfa or (2) hypertonic saline from 2 clinical trials and project cost differences in the US CF population if these 2 medications were used only intermittently for symptom relief instead of chronically. METHODS: The SIMPLIFY study was 2 parallel multicenter trials that randomized participants 1:1 to either continue or discontinue therapy. To estimate costs, we used data from the Merative MarketScan Databases to identify people with CF from 2020 to 2021. Our primary outcomes were differences in costs of outpatient prescription drugs among those who continued vs discontinued dornase alfa and, separately, hypertonic saline. We obtained adjusted differences in median costs. To estimate the annual cost savings if the population of people with CF taking ETI used these medications only intermittently, we multiplied the proportion of people in MarketScan with CF diagnoses who were taking each of these medications by the median cost savings per year and subtracted the cost of "rescue" use. RESULTS: A total of 392 participants from the dornase alfa trial and 273 from the hypertonic saline trial were included in analyses. The adjusted difference in median medication costs was not significant for the hypertonic saline trial, but we observed a significantly decreased 6-week cost of medications in the dornase alfa trial (adjusted median difference in costs between discontinue and continue of $5,860 (95% CI = $4,870-$6,850); P < 0.0001). We estimated that two-thirds of people with CF use ETI and dornase alfa in the United States; if they discontinued dornase alfa except for intermittent use, the resulting annual savings would be $1.21 billion. CONCLUSIONS: Although the costs of dornase alfa and hypertonic saline are smaller compared with ETI, reduction in use would lead to substantial prescription drug cost savings and reduce the treatment burden. However, individual benefits of these therapies should be considered, and decisions regarding changes in therapy remain an important discussion between people with CF and their providers. Study registration number: NCT04378153.

A Call to Improve Usability, Accuracy, and Equity of Self-Testing for COVID-19 and Other Rapid Diagnostic Tests.

The increasing availability of rapid diagnostic self-tests (RDSTs) for COVID-19 has played an important and increasing role during the pandemic. However, for many underserved communities, RDSTs potential benefits are offset by problems with usability, accuracy, and equity. Given the increased need for and interest in home testing for acute and chronic diseases, including COVID-19, this piece offers ways that regulatory agencies, federal public health agencies, and test developers should engage with diverse communities to ensure equity throughout test development, implementation, and evaluation. Such engagement will ensure maximum personal and public health benefits for current and future RDSTs under real-world conditions.

Protocol of the Comparison of Intravesical Therapy and Surgery as Treatment Options (CISTO) study: a pragmatic, prospective multicenter observational cohort study of recurrent high-grade non-muscle invasive bladder cancer.

BACKGROUND: Bladder cancer poses a significant public health burden, with high recurrence and progression rates in patients with non-muscle-invasive bladder cancer (NMIBC). Current treatment options include bladder-sparing therapies (BST) and radical cystectomy, both with associated risks and benefits. However, evidence supporting optimal management decisions for patients with recurrent high-grade NMIBC remains limited, leading to uncertainty for patients and clinicians. The CISTO (Comparison of Intravesical Therapy and Surgery as Treatment Options) Study aims to address this critical knowledge gap by comparing outcomes between patients undergoing BST and radical cystectomy. METHODS: The CISTO Study is a pragmatic, prospective observational cohort trial across 36 academic and community urology practices in the US. The study will enroll 572 patients with a diagnosis of recurrent high-grade NMIBC who select management with either BST or radical cystectomy. The primary outcome is health-related quality of life (QOL) at 12 months as measured with the EORTC-QLQ-C30. Secondary outcomes include bladder cancer-specific QOL, progression-free survival, cancer-specific survival, and financial toxicity. The study will also assess patient preferences for treatment outcomes. Statistical analyses will employ targeted maximum likelihood estimation (TMLE) to address treatment selection bias and confounding by indication. DISCUSSION: The CISTO Study is powered to detect clinically important differences in QOL and cancer-specific survival between the two treatment approaches. By including a diverse patient population, the study also aims to assess outcomes across the following patient characteristics: age, gender, race, burden of comorbid health conditions, cancer severity, caregiver status, social determinants of health, and rurality. Treatment outcomes may also vary by patient preferences, health literacy, and baseline QOL. The CISTO Study will fill a crucial evidence gap in the management of recurrent high-grade NMIBC, providing evidence-based guidance for patients and clinicians in choosing between BST and radical cystectomy. The CISTO study will provide an evidence-based approach to identifying the right treatment for the right patient at the right time in the challenging clinical setting of recurrent high-grade NMIBC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03933826. Registered on May 1, 2019.

Characteristics associated with cystic fibrosis-related pulmonary exacerbation treatment location.

Previous studies indicate that hospital rather than home treatment of pulmonary exacerbations (PEx) in people with cystic fibrosis (CF) can improve outcomes. We evaluated characteristics of adult participants from the Standardized Treatment of Pulmonary Exacerbations (STOP2) trial with two separate comparisons: (1) those who were treated initially in hospital (N = 768) to those treated initially at home (N = 214) and (2) those treated only in hospital (N = 328) to those who were treated only at home or both at home and in hospital (N = 654). Participants who had Medicaid insurance, were treated for shorter duration, and traveled longer to reach treatment centers were more likely to have been treated initially in the hospital. Having Medicaid insurance, being treated for a shorter duration, and being male were associated with being treated only in the hospital. This analysis suggests decisions about the location of treatment are based on pragmatic factors rather than on clinical characteristics.

Trial Participation and Outcomes Among English-Speaking and Spanish-Speaking Patients With Appendicitis Randomized to Antibiotics: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: Spanish-speaking participants are underrepresented in clinical trials, limiting study generalizability and contributing to ongoing health inequity. The Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial intentionally included Spanish-speaking participants. Objective: To describe trial participation and compare clinical and patient-reported outcomes among Spanish-speaking and English-speaking participants with acute appendicitis randomized to antibiotics. Design, Setting, and Participants: This study is a secondary analysis of the CODA trial, a pragmatic randomized trial comparing antibiotic therapy with appendectomy in adult patients with imaging-confirmed appendicitis enrolled at 25 centers across the US from May 1, 2016, to February 28, 2020. The trial was conducted in English and Spanish. All 776 participants randomized to antibiotics are included in this analysis. The data were analyzed from November 15, 2021, through August 24, 2022. Intervention: Randomization to a 10-day course of antibiotics or appendectomy. Main Outcomes and Measures: Trial participation, European Quality of Life-5 Dimensions (EQ-5D) questionnaire scores (higher scores indicating a better health status), rate of appendectomy, treatment satisfaction, decisional regret, and days of work missed. Outcomes are also reported for a subset of participants that were recruited from the 5 sites with a large proportion of Spanish-speaking participants. Results: Among eligible patients 476 of 1050 Spanish speakers (45%) and 1076 of 3982 of English speakers (27%) consented, comprising the 1552 participants who underwent 1:1 randomization (mean age, 38.0 years; 976 male [63%]). Of the 776 participants randomized to antibiotics, 238 were Spanish speaking (31%). Among Spanish speakers randomized to antibiotics, the rate of appendectomy was 22% (95% CI, 17%-28%) at 30 days and 45% (95% CI, 38%-52%) at 1 year, while in English speakers, these rates were 20% (95% CI, 16%-23%) at 30 days and 42% (95% CI 38%-47%) at 1 year. Mean EQ-5D scores were 0.93 (95% CI, 0.92-0.95) among Spanish speakers and 0.92 (95% CI, 0.91-0.93) among English speakers. Symptom resolution at 30 days was reported by 68% (95% CI, 61%-74%) of Spanish speakers and 69% (95% CI, 64%-73%) of English speakers. Spanish speakers missed 6.69 (95% CI, 5.51-7.87) days of work on average, while English speakers missed 3.76 (95% CI, 3.20-4.32) days. Presentation to the emergency department or urgent care, hospitalization, treatment dissatisfaction, and decisional regret were low for both groups. Conclusions and Relevance: A high proportion of Spanish speakers participated in the CODA trial. Clinical and most patient-reported outcomes were similar for English- and Spanish-speaking participants treated with antibiotics. Spanish speakers reported more days of missed work. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Association of Weight Loss in Ambulatory Care Settings With First Diagnosis of Lung Cancer in the US.

Importance: Lung cancer, the US's leading cause of cancer death, is often diagnosed following presentation to health care settings with symptoms, and many patients present with late-stage disease. Objective: To investigate the association between weight loss and subsequent diagnosis of incident lung cancer in an ambulatory care population and to assess whether recorded weight change had higher odds of lung cancer diagnosis than objective measurements. Design, Setting, and Participants: This case-control study included patients visiting a US academic medical center between January 1, 2012, and December 31, 2019. Data were derived from US ambulatory care electronic health records from the University of Washington Medical Center linked to the local Surveillance, Epidemiology, and End Results cancer registry. Cases were identified from patients who had a primary lung cancer diagnosis between 2012 and 2019; controls were matched on age, sex, smoking status, and presenting to the same type of ambulatory clinic as cases. Data were analyzed from March 2022 through January 2023. Exposure: Continuous and categorical weight change were assessed. Main Outcomes and Measures: Odds ratios estimating the likelihood of a diagnosis of lung cancer were calculated using univariable and multivariable conditional logistic regression. Results: A total of 625 patients aged 40 years or older with a first primary lung cancer diagnosis and 4606 matched controls were included (1915 [36.6%] ages 60 to 69 years; 418 [8.0%] Asian, 389 [7.4%] Black, 4092 [78.2%] White). In unadjusted analyses, participants with weight loss of 1% to 3% (odds ratio [OR], 1.12; 95% CI, 0.88-1.41), 3% to 5% (OR, 1.36; 95% CI, 0.99-1.88), or 5% to 10% (OR, 1.23; 95% CI, 0.82-1.85) over a 2-year period did not have statistically significantly increased risk of lung cancer diagnosis compared with those who maintained a steady weight. However, participants with weight loss of 10% to 50% had more than twice the odds of a lung cancer diagnosis (OR, 2.27; 95% CI, 1.27-4.05). Most categories of weight loss showed significant associations with an increased risk of lung cancer diagnosis for at least 6 months prior to diagnosis. Patients who had weight loss both recorded in clinicians' notes and measured had higher odds of lung cancer compared with patients who had only recorded (OR, 1.26; odds; 95% CI, 1.04-1.52) or measured (OR, 8.53; 95% CI, 6.99-10.40) weight loss. Conclusions and Relevance: In this case-control study, weight loss in the prior 6 months was associated with incident lung cancer diagnosis and was present whether weight loss was recorded as a symptom by the clinician or based on changes in routinely measured weight, demonstrating a potential opportunity for early diagnosis. The association between measured and recorded weight loss by clinicians presents novel results for the US.

Evaluation of an experiential training program in patient-centered outcomes and comparative effectiveness research for diverse researcher communities and health care organizations.

Background/Objective: The goal of the Patient-Centered Outcomes Research Partnership was to prepare health care professionals and researchers to conduct patient-centered outcomes and comparative effectiveness research (CER). Substantial evidence gaps, heterogeneous health care systems, and decision-making challenges in the USA underscore the need for evidence-based strategies. Methods: We engaged five community-based health care organizations that serve diverse and underrepresented patient populations from Hawai'i to Minnesota. Each partner nominated two in-house scholars to participate in the 2-year program. The program focused on seven competencies pertinent to patient-centered outcomes and CER. It combined in-person and experiential learning with asynchronous, online education, and created adaptive, pragmatic learning opportunities and a Summer Institute. Metrics included the Clinical Research Appraisal Inventory (CRAI), a tool designed to assess research self-efficacy and clinical research skills across 10 domains. Results: We trained 31 scholars in 3 cohorts. Mean scores in nine domains of the CRAI improved; greater improvement was observed from the beginning to the midpoint than from the midpoint to conclusion of the program. Across all three cohorts, mean scores on 52 items (100%) increased (p ≤ 0.01), and 91% of scholars reported the program improved their skills moderately/significantly. Satisfaction with the program was high (91%). Conclusions: Investigators that conduct patient-centered outcomes and CER must know how to collaborate with regional health care systems to identify priorities; pose questions; design, conduct, and disseminate observational and experimental research; and transform knowledge into practical clinical applications. Training programs such as ours can facilitate such collaborations.

Symptoms and signs of lung cancer prior to diagnosis: case-control study using electronic health records from ambulatory care within a large US-based tertiary care centre.

OBJECTIVE: Lung cancer is the most common cause of cancer-related death in the USA. While most patients are diagnosed following symptomatic presentation, no studies have compared symptoms and physical examination signs at or prior to diagnosis from electronic health records (EHRs) in the USA. We aimed to identify symptoms and signs in patients prior to diagnosis in EHR data. DESIGN: Case-control study. SETTING: Ambulatory care clinics at a large tertiary care academic health centre in the USA. PARTICIPANTS, OUTCOMES: We studied 698 primary lung cancer cases in adults diagnosed between 1 January 2012 and 31 December 2019, and 6841 controls matched by age, sex, smoking status and type of clinic. Coded and free-text data from the EHR were extracted from 2 years prior to diagnosis date for cases and index date for controls. Univariate and multivariable conditional logistic regression were used to identify symptoms and signs associated with lung cancer at time of diagnosis, and 1, 3, 6 and 12 months before the diagnosis/index dates. RESULTS: Eleven symptoms and signs recorded during the study period were associated with a significantly higher chance of being a lung cancer case in multivariable analyses. Of these, seven were significantly associated with lung cancer 6 months prior to diagnosis: haemoptysis (OR 3.2, 95% CI 1.9 to 5.3), cough (OR 3.1, 95% CI 2.4 to 4.0), chest crackles or wheeze (OR 3.1, 95% CI 2.3 to 4.1), bone pain (OR 2.7, 95% CI 2.1 to 3.6), back pain (OR 2.5, 95% CI 1.9 to 3.2), weight loss (OR 2.1, 95% CI 1.5 to 2.8) and fatigue (OR 1.6, 95% CI 1.3 to 2.1). CONCLUSIONS: Patients diagnosed with lung cancer appear to have symptoms and signs recorded in the EHR that distinguish them from similar matched patients in ambulatory care, often 6 months or more before diagnosis. These findings suggest opportunities to improve the diagnostic process for lung cancer.

Early Pregnancy Loss Management in the Emergency Department vs Outpatient Setting.

Importance: Early pregnancy loss (EPL), or miscarriage, is the most common complication of early pregnancy, and many patients experiencing EPL present to the emergency department (ED). Little is known about how patients who present to the ED with EPL differ from those who present to outpatient clinics and how their management and outcomes differ. Objective: To compare the management and outcomes of patients with EPL who present to the ED vs outpatient clinics. Design, Setting, and Participants: This retrospective cohort study used the IBM MarketScan Research Database, a national insurance claims database. Participants were pregnant people aged 15 to 49 years in the US who presented to either an ED or outpatient clinic for initial diagnosis of EPL from October 2015 through December 2019. Data analysis was performed from May 2021 to March 2022. Exposures: The primary exposure was location of service (ED vs outpatient clinic). Other exposures of interest included demographic characteristics, current pregnancy history, and comorbidities. Main Outcomes and Measures: The primary outcome was EPL management type (surgical, medication, or expectant management). Complications, including blood transfusion and hospitalization, and characteristics associated with location of service were also evaluated. Bivariable analyses and multivariable logistic regression were used for data analysis. Results: A total of 117 749 patients with EPL diagnoses were identified, with a mean (SD) age of 31.8 (6.1) years. Of these patients, 20 826 (17.7%) initially presented to the ED, and 96 923 (82.3%) presented to outpatient clinics. Compared with the outpatient setting, patients in the ED were less likely to receive surgical (2925 patients [14.0%] vs 23 588 patients [24.3%]) or medication (1116 patients [5.4%] vs 10 878 patients [11.2%]) management. In the adjusted analysis, characteristics associated with decreased odds of active (surgical or medication) vs expectant management included ED (vs outpatient) presentation (adjusted odds ratio [aOR], 0.46; 95% CI, 0.44-0.47), urban location (aOR, 0.87; 95% CI, 0.82-0.91), and being a dependent on an insurance policy (vs primary policy holder) (aOR, 0.71; 95% CI, 0.67-0.74); whereas older age (aOR per 1-year increase 1.01; 95% CI, 1.01-1.01), established prenatal care (aOR, 2.35; 95% CI, 2.29-2.42), and medical comorbidities (aOR, 1.05; 95% CI, 1.02-1.09) were associated with increased odds of receiving active management. Patients in the ED were more likely than those in outpatient clinics to need a blood transfusion (287 patients [1.4%] vs 202 patients [0.2%]) or hospitalization (463 patients [2.2%] vs 472 patients [0.5%]), but complications were low regardless of location of service. Conclusions and Relevance: In this cohort study of privately insured patients with EPL, differences in management between the ED vs outpatient setting may reflect barriers to accessing comprehensive EPL management options. More research is needed to understand these significant differences in management approaches by practice setting, and to what extent EPL management reflects patient preferences in both outpatient and ED settings.

Understanding the effect of new U.S. cervical cancer screening guidelines and modalities on patients' comprehension and reporting of their cervical cancer screening behavior.

With recent shifts in guideline-recommended cervical cancer screening in the U.S., it is important to accurately measure screening behavior. Previous studies have indicated the U.S. National Health Interview Survey (NHIS), a resource for measuring self-reported screening adherence, has lower validity among non-White racial/ethnic groups and non-English speakers. Further, measuring diverse population groups' comprehension of items and attitudes toward HPV self-sampling merits investigation as it is a modality likely to be recommended in the U.S. soon. This study cognitively tested NHIS items assessing recency of and reasons for receiving cervical cancer screening and attitudes toward HPV self-sampling. We conducted cognitive interviews between April 2021 - April 2022 in English and Spanish with individuals screened in the past two years by either a medical center in metropolitan Seattle, Washington or a safety-net healthcare system in Dallas, Texas. Interviews probed understanding of reasons for screening, experiences with abnormal results, and interest in HPV self-sampling. We completed 32 interviews in Seattle and 42 interviews in Dallas. A majority of participants were unaware that two different tests for cervical cancer screening exist (Pap and HPV). Many did not know which type(s) of test they received. Dallas participants had more limited and inaccurate knowledge of HPV compared to Seattle participants, and fewer responded favorably toward HPV self-sampling (32% vs. 55%). To improve comprehension and accurate reporting of cervical cancer screening, we suggest specific refinements to currently used survey questions. Attitudes toward self-sampling should be explored further as differences may exist by region and/or sociodemographic factors.

Perception of Treatment Success and Impact on Function with Antibiotics or Appendectomy for Appendicitis: A Randomized Clinical Trial with an Observational Cohort.

OBJECTIVE: To compare secondary patient reported outcomes of perceptions of treatment success and function for patients treated for appendicitis with appendectomy vs. antibiotics at 30 days. SUMMARY BACKGROUND DATA: The Comparison of Outcomes of antibiotic Drugs and Appendectomy trial found antibiotics noninferior to appendectomy based on 30-day health status. To address questions about outcomes among participants with lower socioeconomic status, we explored the relationship of sociodemographic and clinical factors and outcomes. METHODS: We focused on 4 patient reported outcomes at 30 days: high decisional regret, dissatisfaction with treatment, problems performing usual activities, and missing >10 days of work. The randomized (RCT) and observational cohorts were pooled for exploration of baseline factors. The RCT cohort alone was used for comparison of treatments. Logistic regression was used to assess associations. RESULTS: The pooled cohort contained 2062 participants; 1552 from the RCT. Overall, regret and dissatisfaction were low whereas problems with usual activities and prolonged missed work occurred more frequently. In the RCT, those assigned to antibiotics had more regret (Odd ratios (OR) 2.97, 95% Confidence intervals (CI) 2.05-4.31) and dissatisfaction (OR 1.98, 95%CI 1.25-3.12), and reported less missed work (OR 0.39, 95%CI 0.27-0.56). Factors associated with function outcomes included sociodemographic and clinical variables for both treatment arms. Fewer factors were associated with dissatisfaction and regret. CONCLUSIONS: Overall, participants reported high satisfaction, low regret, and were frequently able to resume usual activities and return to work. When comparing treatments for appendicitis, no single measure defines success or failure for all people. The reported data may inform discussions regarding the most appropriate treatment for individuals. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02800785.

How Timely Is Diagnosis of Lung Cancer? Cohort Study of Individuals with Lung Cancer Presenting in Ambulatory Care in the United States.

The diagnosis of lung cancer in ambulatory settings is often challenging due to non-specific clinical presentation, but there are currently no clinical quality measures (CQMs) in the United States used to identify areas for practice improvement in diagnosis. We describe the pre-diagnostic time intervals among a retrospective cohort of 711 patients identified with primary lung cancer from 2012-2019 from ambulatory care clinics in Seattle, Washington USA. Electronic health record data were extracted for two years prior to diagnosis, and Natural Language Processing (NLP) applied to identify symptoms/signs from free text clinical fields. Time points were defined for initial symptomatic presentation, chest imaging, specialist consultation, diagnostic confirmation, and treatment initiation. Median and interquartile ranges (IQR) were calculated for intervals spanning these time points. The mean age of the cohort was 67.3 years, 54.1% had Stage III or IV disease and the majority were diagnosed after clinical presentation (94.5%) rather than screening (5.5%). Median intervals from first recorded symptoms/signs to diagnosis was 570 days (IQR 273-691), from chest CT or chest X-ray imaging to diagnosis 43 days (IQR 11-240), specialist consultation to diagnosis 72 days (IQR 13-456), and from diagnosis to treatment initiation 7 days (IQR 0-36). Symptoms/signs associated with lung cancer can be identified over a year prior to diagnosis using NLP, highlighting the need for CQMs to improve timeliness of diagnosis.

Association of Patient Belief About Success of Antibiotics for Appendicitis and Outcomes: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials. Objective: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial. Design, Setting, and Participants: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive antibiotics in the CODA trial. After informed consent but before randomization, participants who were assigned to receive antibiotics responded to a baseline survey including a question about how successful they believed antibiotics could be in treating their appendicitis. Interventions: Participants were categorized based on baseline survey responses into 1 of 3 belief groups: unsuccessful/unsure, intermediate, and completely successful. Main Outcomes and Measures: Three outcomes were assigned at 30 days: (1) appendectomy, (2) high decisional regret or dissatisfaction with treatment, and (3) persistent signs and symptoms (abdominal pain, tenderness, fever, or chills). Outcomes were compared across groups using adjusted risk differences (aRDs), with propensity score adjustment for sociodemographic and clinical factors. Results: Of the 776 study participants who were assigned antibiotic treatment in CODA, a total of 425 (mean [SD] age, 38.5 [13.6] years; 277 male [65%]) completed the baseline belief survey before knowing their treatment assignment. Baseline beliefs were as follows: 22% of participants (92 of 415) had an unsuccessful/unsure response, 51% (212 of 415) had an intermediate response, and 27% (111 of 415) had a completely successful response. Compared with the unsuccessful/unsure group, those who believed antibiotics could be completely successful had a 13-percentage point lower risk of appendectomy (aRD, -13.49; 95% CI, -24.57 to -2.40). The aRD between those with intermediate vs unsuccessful/unsure beliefs was -5.68 (95% CI, -16.57 to 5.20). Compared with the unsuccessful/unsure group, those with intermediate beliefs had a lower risk of persistent signs and symptoms (aRD, -15.72; 95% CI, -29.71 to -1.72), with directionally similar results for the completely successful group (aRD, -15.14; 95% CI, -30.56 to 0.28). Conclusions and Relevance: Positive patient beliefs about the likely success of antibiotics for appendicitis were associated with a lower risk of appendectomy and with resolution of signs and symptoms by 30 days. Pathways relating beliefs to outcomes and the potential modifiability of beliefs to improve outcomes merit further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

A History of Health Economics and Healthcare Delivery Research at the National Cancer Institute.

With increased attention to the financing and structure of healthcare, dramatic increases in the cost of diagnosing and treating cancer, and corresponding disparities in access, the study of healthcare economics and delivery has become increasingly important. The Healthcare Delivery Research Program (HDRP) in the Division of Cancer Control and Population Sciences at the National Cancer Institute (NCI) was formed in 2015 to provide a hub for cancer-related healthcare delivery and economics research. However, the roots of this program trace back much farther, at least to the formation of the NCI Division of Cancer Prevention and Control in 1983. The creation of a division focused on understanding and explaining trends in cancer morbidity and mortality was instrumental in setting the direction of cancer-related healthcare delivery and health economics research over the subsequent decades. In this commentary, we provide a brief history of health economics and healthcare delivery research at NCI, describing the organizational structure and highlighting key initiatives developed by the division, and also briefly discuss future directions. HDRP and its predecessors have supported the growth and evolution of these fields through the funding of grants and contracts; the development of data, tools, and other research resources; and thought leadership including stimulation of research on previously understudied topics. As the availability of new data, methods, and computing capacity to evaluate cancer-related healthcare delivery and economics expand, HDRP aims to continue to support this growth and evolution.