Newborn Screening Has Moved Way Beyond PKU.

Nurses need to understand how clinical genetic and genomic applications affect newborn screening and advocate for parents and newborns.

Effectiveness of Community-Engaged Research Strategies in Increasing COVID-19 Vaccinations in Targeted Communities: The Community Engagement Alliance (CEAL) Regional Teams.

Objectives. To explore a key outcome of interest for the Community Engagement Alliance (CEAL) Regional Teams by examining COVID-19 vaccinations over time in US counties where CEAL teams operated and comparing them to demographically similar counties in the same state. Methods. Our evaluation used a nonequivalent control group design. Each county where a CEAL team operated was matched to a unique non-CEAL county in the same state. Components of the Centers for Disease Control and Prevention's Social Vulnerability Index were used as the matching criteria. COVID-19 vaccinations (county-level percentage of residents aged 18 years or older who are fully vaccinated) for CEAL and matched counties were analyzed over time. Results. The mean percentage of vaccinated adults was significantly higher in CEAL counties than in matched non-CEAL counties. Sensitivity analyses confirmed conclusions did not change depending on the CEAL cohort or closeness of matches. Conclusions. Our findings support CEAL team efforts to increase COVID-19 vaccinations in target communities and employ community-engaged research more broadly within public health contexts. (Am J Public Health. 2024;114(S1):S124-S127. https://doi.org/10.2105/AJPH.2023.307517).

COVID-19 Information, Trust, and Risk Perception Across Diverse Communities in the United States: Initial Findings from a Multistate Community Engagement Alliance (CEAL).

Objectives. To provide initial findings from Community Engagement Alliance (CEAL), a multistate effort funded by the National Institutes of Health, to conduct urgent community-engaged research and outreach focused on COVID-19 awareness, education, and evidence-based response. Methods. We collected survey data (November 2020-November 2022) from 21 CEAL teams from 29 state and regional CEAL sites spanning 19 US states, the District of Columbia, and Puerto Rico, which covered priority populations served and trusted sources of information about COVID-19, including prevention behaviors, vaccination, and clinical trials. Results. A disproportionate number of respondents were Latino (45%) or Black (40%). There was considerable variability between CEAL sites regarding trusted sources of information, COVID-19 prevention, and COVID-19 vaccination. For example, more respondents (70%) reported health care providers as a trusted source of COVID-19 information than any other source (ranging from 6% to 87% by site). Conclusions. CEAL rapidly developed novel infrastructure to engage academic, public health, and community organizations to address COVID-19's impacts on underserved communities. CEAL provides an example of how to respond in future public health emergencies to quickly promote trustworthy, evidence-based information in ways that advance health equity. (Am J Public Health. 2024;114(S1):S112-S123. https://doi.org/10.2105/AJPH.2023.307504).

Patients' attitudes and preferences toward delayed disease progression in the absence of improved survival.

BACKGROUND: Cancer patients' attitudes toward progression-free survival (PFS) gains offered by treatment are not well understood, particularly in the absence of overall survival (OS) gains. The objectives were to describe patients' willingness to accept treatment that offers PFS gains without OS gains, to compare these findings with treatments offering OS gains, and to qualitatively summarize patients' reasons for their preferences. METHODS: A multicenter, cross-sectional, convergent mixed-methods study design recruited patients who had received at least 3 months of systemic therapy for incurable solid tumors. A treatment trade-off exercise determined the gains in imaging PFS that patients require to prefer additional systemic treatment for a scenario of a newly diagnosed, asymptomatic, incurable abdominal tumor. A qualitative, descriptive, thematic analysis explored factors influencing patients' decisions, and a narrative method integrated the quantitative and qualitative findings. RESULTS: In total, 100 patients participated (63% were older than 60 years of age). If additional treatment with added toxicity offered no OS advantage, 17% would prefer it for no PFS benefit; 26% for some PFS benefit (range, 3-9 months), whereas 51% would decline it regardless of PFS benefit. Similarly, 71% preferred additional treatment offering a 6-month OS advantage dependent on described toxicity levels (P = .03). A spectrum of reasons for these preferences reflected the complexity of participants' attitudes and values. CONCLUSIONS: Prolongation of time to progression was not universally valued. Most patients did not prefer treatments that negatively affect quality of life for PFS gains alone. Implications for individual decision making, policy, and trials research are discussed.

Characterizing Variability in Lung Cancer Outcomes and Influence of a Lung Diagnostic Assessment Program in Southeastern Ontario, Canada.

INTRODUCTION: Regional variability in lung cancer (LC) outcomes exists across Canada, including in the province of Ontario. The Lung Diagnostic Assessment Program (LDAP) in southeastern (SE) Ontario is a rapid-assessment clinic that expedites the management of patients with suspected LC. We evaluated the association of LDAP management with LC outcomes, including survival, and characterized the variability in LC outcomes across SE Ontario. METHODS: We conducted a population-based retrospective cohort study by identifying patients with newly diagnosed LC through the Ontario Cancer Registry (January 2017-December 2019) and linked to the LDAP database to identify LDAP-managed patients. Descriptive data were collected. Using a Cox model approach, we compared 2-year survival for patients managed through LDAP vs. non-LDAP. RESULTS: We identified 1832 patients, 1742 of whom met the inclusion criteria (47% LDAP-managed and 53% non-LDAP). LDAP management was associated with a lower probability of dying at 2 years (HR 0.76 vs. non-LDAP, p < 0.0001). Increasing distance from the LDAP was associated with a lower likelihood of LDAP management (OR 0.78 for every 20 km increase, p < 0.0001). LDAP-managed patients were more likely to receive specialist assessment and undergo treatments. CONCLUSIONS: In SE Ontario, initial diagnostic care provided via LDAP was independently associated with improved survival in patients with LC.

Defining the role of real-world data in cancer clinical research: The position of the European Organisation for Research and Treatment of Cancer.

The emergence of the precision medicine paradigm in oncology has led to increasing interest in the integration of real-world data (RWD) into cancer clinical research. As sources of real-world evidence (RWE), such data could potentially help address the uncertainties that surround the adoption of novel anticancer therapies into the clinic following their investigation in clinical trials. At present, RWE-generating studies which investigate antitumour interventions seem to primarily focus on collecting and analysing observational RWD, typically forgoing the use of randomisation despite its methodological benefits. This is appropriate in situations where randomised controlled trials (RCTs) are not feasible and non-randomised RWD analyses can offer valuable insights. Nevertheless, depending on how they are designed, RCTs have the potential to produce strong and actionable RWE themselves. The choice of which methodology to employ for RWD studies should be guided by the nature of the research question they are intended to answer. Here, we attempt to define some of the questions that do not necessarily require the conduct of RCTs. Moreover, we outline the strategy of the European Organisation for Research and Treatment of Cancer (EORTC) to contribute to the generation of robust and high-quality RWE by prioritising the execution of pragmatic trials and studies set up according to the trials-within-cohorts approach. If treatment allocation cannot be left up to random chance due to practical or ethical concerns, the EORTC will consider undertaking observational RWD research based on the target trial principle. New EORTC-sponsored RCTs may also feature concurrent prospective cohorts composed of off-trial patients.

Thoughts on Writing High-Quality Review Articles.

The Associate Editor provides useful suggestions for authors on writing review articles.

Characterizing Regional Variability in Lung Cancer Outcomes across Ontario-A Population-Based Analysis.

Background: Lung cancer (LC) is the leading cause of cancer-related mortality. In Ontario, Canada, there are significant survival differences for patients with newly diagnosed LC across the 14 provincial regions. Methods: A population-based retrospective cohort study using ICES databases from 01/2007-12/2017 identified patients with newly diagnosed LC through the Ontario Cancer Registry and those with LC as the cause of death. Descriptive data included patient, disease, and system characteristics. The primary outcome was 5-year survival by region. Results: 178,202 patient records were identified; 101,263 met inclusion criteria. LC incidence varied by region (5.6-14.6/10,000), as did histologic subtype (adenocarcinoma: 27.3-46.1%). Five-year cancer-specific survival was impacted by age, rurality, pathologic subtype, stage at diagnosis, and income quintile. Timely care was inversely related to survival (fastest quintile: HR 3.22, p < 0.0001). Adjusted 5-year cancer-specific survival varied across regions (24.1%, HR 1.12; 34.0%, HR 0.89, p < 0.001). Conclusions: When adjusting for confounders, differences in survival by health region persisted, suggesting a complex interplay between patient, disease, and system factors. A single approach to improving patient care is likely to be ineffective across different systems. Quality improvement initiatives to improve patient outcomes require different approaches amongst health regions to address local disparities in care.

Association of Quality-of-Life Outcomes in Cancer Drug Trials With Survival Outcomes and Drug Class.

Importance: Although quality of life (QOL) is an important clinical end point, cancer drugs are often approved based on overall survival (OS) or putative surrogate end points such as progression-free survival (PFS) without QOL data. Objective: To ascertain whether cancer drug trials that show improvement in OS or PFS also improve global QOL of patients with cancer compared with the control treatment, as well as to assess how unchanged or detrimental QOL outcomes are reported in trial publications. Design, Setting, and Participants: This retrospective cohort study included all patients with cancer in the advanced setting who were enrolled into phase 3 randomized clinical trials (RCTs) of cancer drugs reporting QOL data and published in English language in a PubMed-indexed journal in the calendar year 2019. The systematic search of PubMed was conducted in July 2020. Main Outcomes and Measures: Association of QOL outcomes with OS and PFS, framing of unchanged QOL outcomes in trial publications, and the association of favorable framing with industry funding of the trials. Results: A total of 45 phase 3 RCTs enrolling 24 806 participants (13 368 in the experimental arm and 11 438 in the control arm) met the inclusion criteria and were included in the study analyses. Improvement in global QOL with the experimental agent was reported in 11 (24%) RCTs. The RCTs with improved QOL were more likely to also show improved OS vs trials with unimproved QOL (7 of 11 [64%] trials vs 10 of 34 [29%] trials; χ2 = 4.13; P = .04); there was no such association observed for PFS (6 of 11 [55%] trials vs 17 of 34 [50%] trials, χ2 = 0.03; P = .87). Six trials reported worsening QOL, of which 3 (50%) were trials of targeted drugs, and 11 trials reported improvement in QOL, of which 6 (55%) were trials of immunotherapy drugs. Of the 34 trials in which QOL was not improved compared with controls, 16 (47%) reported these results in a positive frame, an observation statistically significantly associated with industry funding (χ2 = 6.35; P = .01). Conclusions and Relevance: In this cohort study, a small proportion of RCTs of cancer drugs showed benefit in global QOL with the experimental agent. These results showed an association between QOL benefit and OS benefit but no such association with PFS benefit. Trials that failed to show improved QOL often reported their QOL outcomes more favorably. Non-immunotherapy-targeted drugs led to worse QOL more often than did cytotoxic agents.

Perspective on Cancer Control: Whither the Tobacco Endgame for Canada?

Aims: In 2014, in response to evidence that Canada's tobacco use would lead, inexorably, to substantial morbidity and mortality for the foreseeable future, a group of experts convened to consider the development of a "Tobacco Endgame" for Canada. The "Tobacco Endgame" defines a time frame in which to eliminate structural, political, and social dynamics that sustain tobacco use, leading to improved population health. Strategies: A series of Background Papers describing possible measures that could contribute to the creation of a comprehensive endgame strategy for Canada was prepared in advance of the National Tobacco Endgame Summit hosted at Queen's University in 2016. At the summit, agreement was reached to work together to achieve <5% tobacco use by 2035 (<5 by '35). A report of the proceedings was shared widely. Achievements: Progress since 2016 has been mixed. The Summit report was followed by a national forum convened by Health Canada in March 2017, and in 2018, the Canadian Government adopted "<5 × '35" tobacco use target in a renewed Canadian tobacco reduction strategy. Tobacco use has declined in the last 5 years, but at a rate slower than that which will be needed to achieve the <5 by '35 goal. There remain > 5 million smokers in Canada, signaling that smoking-related diseases will continue to be an enormous health burden. Furthermore, the landscape of new products (e-cigarettes and cannabis) has created additional risks and opportunities. Future directions: A bold, reinvigorated tobacco control strategy is needed that significantly advances ongoing policy developments, including full implementation of the key demand-reduction policies of the WHO Framework Convention on Tobacco Control. Formidable, new disruptive policies and regulations will be needed to achieve Canada's Endgame goal.

Do Editorialists With Industry-Related Conflicts of Interest Write Unduly Favorable Editorials for Cancer Drugs in Top Journals?

BACKGROUND: Editorials accompanying the publication of trials in major oncology journals can have a substantial influence on clinical practice. We describe the prevalence of financial conflicts of interest (FCOIs) of authors writing such editorials and the extent to which FCOIs may shape the interpretation of clinical trials. METHODS: We examined editorials published in 2018 alongside trial reports in the top 5 journals that publish cancer drug trials (New England Journal of Medicine, Lancet, Lancet Oncology, JAMA Oncology, and Journal of Clinical Oncology). An editorial was considered to have an FCOI if at least one of the editorialists had any disclosed FCOI. An FCOI with the same company whose drug was being discussed in the editorial was classified as a direct FCOI. Editorials were reviewed for their content and classified as being unduly favorable (defined as the presence of a positive spin without discussion of limitations) or not. Association of an FCOI and a direct FCOI with writing an unduly favorable editorial was assessed. RESULTS: Of the 90 editorials assessed, 74% (n=67) were classified as having an FCOI with the pharmaceutical industry, and 39% (n=35) had an FCOI with the same company whose product was being discussed in the editorial (direct FCOI). Editorials were classified as being unduly favorable toward the study drug in 12% (8 of 67) and 13% (3 of 23) (P=1.0) of those with and without FCOIs, respectively; corresponding rates with and without direct FCOI were 23% (8 of 35) and 5% (3 of 55), respectively (P=.009). CONCLUSIONS: Editorials in top oncology journals were frequently authored by experts with FCOIs, including direct FCOIs. Authoring an unduly favorable editorial for a new cancer drug was significantly associated with the author having a direct FCOI with the same company. These findings support the call for journals to ensure that authors of editorials have no direct FCOIs.