Study Design Bias Research Articles

The Oncology QCARD Initiative: Fostering efficient evaluation of initial real-world data proposals.

The oncology quality, characterization, and assessment of real-world data (Oncology QCARD) Initiative was formed to develop a set of minimum study design and data elements needed to evaluate the fitness of the real-world data (RWD) source(s) proposed in an initial study concept as part of early interaction with scientific reviewers. A multidisciplinary executive committee (EC) was established to guide the Oncology QCARD Initiative. The EC conducted a landscape review of published literature, guidances, and guidelines to evaluate relevant dimensions of data quality measurement. Guided by the review and informed by expert feedback, the Oncology QCARD Initial Protocol Characterization (IPC) provides a summary of minimum elements needed to adequately describe an initial clinical study concept that involves RWD and is intended to support decision-making. Fit-for-use data and fit-for-purpose design emerged as themes from the landscape analysis. Data that are fit-for-use are both relevant (sufficiently capturing exposure, outcomes, and covariates) and reliable (understanding data accrual and quality control and whether the data represent the underlying concepts they are intended to represent) to answer a specific research question. A fit-for-purpose design takes appropriate steps to ensure internal and external validity and allows for transparency in reporting. The QCARD-IPC focuses on high-level characteristics of RWD sources and study design domains including data temporality, population, medical product exposure, comparators, and covariates, endpoints, statistical analysis, and data quality assurance plans. Evaluation of studies including RWD requires understanding the data source, study design, and potential biases to preliminarily evaluate whether selected RWD are fit-for-use for the research question. The Oncology QCARD-IPC provides a structured, transparent approach to facilitate early review and enhanced communication between study sponsors and scientific reviewers of initial study proposals including RWD.

Variations in the association between polygyny and experience of intimate partner violence by husband’s alcohol consumption: a cross-sectional study among postpartum women in Thailand

BackgroundIntimate partner violence is more common in polygynous couples than monogamous couples, but the extent that this association is modified by the husband’s alcohol consumption is unknown. The objectives of this study are: (1) To describe the extent to which polygyny is associated with self-reported experience of intimate partner violence among women receiving postpartum care; (2) To describe the extent to which the mentioned association is modified by the husband’s alcohol consumption.MethodsWe conducted a hospital-based cross-sectional study among women age 18 years or older receiving postpartum care at 8 public hospitals in 3 provinces in Northern and Northeastern Thailand using self-administered questionnaires. We analyzed data using descriptive statistics, logistic regression, and stratified analyses.ResultsA total of 1207 women agreed to participate in the study, 8% of whom reported that their husbands practiced polygyny. Women in a polygynous relationship were more likely than women in monogamous relationships to experience intimate partner violence (11.7% vs. 3.6%, Adjusted OR = 2.23; 95% CI = 0.94, 5.26). The prevalence of intimate partner violence was relatively low in both groups among women whose husbands did not drink (2.9% vs. 0%, Adjusted OR = N/A), and very high in both groups among those whose husbands binge-drank (46.2% vs. 20.8%, Adjusted OR = 9.54; 95% CI = 1.10, 82.54). However, the Breslow-Day Test of Homogeneity suggested that there was no statistically significant effect modification (p-value = 0.259).ConclusionStakeholders in intimate partner violence should consider both alcohol use (particularly binge-drinking) and polygyny as risk factors for intimate partner violence. However, caveats regarding study design, misclassification and potential information bias, and lack of generalizability should be considered in the interpretation of the study findings.

Assessing the Certainty of the Evidence in Systematic Reviews: Importance, Process, and Use.

When interpreting results and drawing conclusions, authors of systematic reviews should consider the limitations of the evidence included in their review. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach provides a framework for the explicit consideration of the limitations of the evidence included in a systematic review, and for incorporating this assessment into the conclusions. Assessments of certainty of evidence are a methodological expectation of systematic reviews. The certainty of the evidence is specific to each outcome in a systematic review, and can be rated as high, moderate, low, or very low. Because it will have an important impact, before conducting certainty of evidence, reviewers must clarify the intent of their question: are they interested in causation or association. Serious concerns regarding limitations in the study design, inconsistency, imprecision, indirectness, and publication bias can decrease the certainty of the evidence. Using an example, this article describes and illustrates the importance and the steps for assessing the certainty of evidence and drawing accurate conclusions in a systematic review.

Conflicting Results and Statistical Malleability: Embracing Pluralism of Empirical Results

Abstract Conflicting results undermine making inferences from the empirical literature. So far, the replication crisis is mainly seen as resulting from honest errors and questionable research practices such as p-hacking or the base-rate fallacy. I discuss the malleability (researcher degrees of freedom) of quantitative research and argue that conflicting results can emerge from two studies using different but plausible designs (e.g., eligibility criteria, operationalization of concepts, outcome measures) and statistical methods. I also explore how the choices regarding study design and statistical techniques bias results in a way that makes them more or less relevant for a given policy or clinical question.

The relationship between haemoglobin concentrations and obstructive sleep apnea syndrome: A systematic review and meta-analysis

BackgroundThis systematic review and meta-analysis investigates the relationship between haemoglobin (Hb) concentrations and obstructive sleep apnea syndrome (OSAS). MethodsFollowing PRISMA guidelines, we searched PubMed, EMBASE, and Cochrane Library from inception to March 8, 2024. Eligible studies included cross-sectional, cohort, and case-control designs comparing Hb concentrations in OSAS patients and healthy controls. Two reviewers independently screened records and extracted data. The risk of bias was assessed using the Joanna Briggs Institute checklist. ResultsA total of 27 studies involving 6499 OSAS subjects and 5199 controls were included. Hb concentrations were significantly higher in OSAS patients compared to controls (SMD: 0.28; 95 % CI: 0.18 to 0.39; I2 = 84.4 %). Subgroup analysis by OSAS severity showed that severe OSAS patients had higher Hb concentrations than those with mild/moderate OSAS. Sensitivity analyses confirmed the robustness of the findings. However, 7 studies reported opposite results, indicating possible regional or methodological differences. ConclusionHb concentrations are elevated in OSAS patients, with higher levels observed in severe cases. The significant heterogeneity and the predominance of studies from Turkey highlight the need for further research in diverse populations. Limitations include potential publication bias and variability in study designs.

Adipose-derived stem cells in diabetic foot care: Bridging clinical trials and practical application.

Diabetic foot ulcers (DFUs) pose a critical medical challenge, significantly im-pairing the quality of life of patients. Adipose-derived stem cells (ADSCs) have been identified as a promising therapeutic approach for improving wound healing in DFUs. Despite extensive exploration of the mechanical aspects of ADSC therapy against DFU, its clinical applications remain elusive. In this review, we aimed to bridge this gap by evaluating the use and advancements of ADSCs in the clinical management of DFUs. The review begins with a discussion of the classification and clinical management of diabetic foot conditions. It then discusses the current landscape of clinical trials, focusing on their geographic distribution, reported efficacy, safety profiles, treatment timing, administration techniques, and dosing considerations. Finally, the review discusses the preclinical strategies to enhance ADSC efficacy. This review shows that many trials exhibit biases in study design, unclear inclusion criteria, and intervention protocols. In conclusion, this review underscores the potential of ADSCs in DFU treatment and emphasizes the critical need for further research and refinement of therapeutic approaches, with a focus on improving the quality of future clinical trials to enhance treatment outcomes and advance the field of diabetic wound care.

Diagnostic and therapeutic considerations in patients with bilateral diffuse uveal melanocytic proliferation.

This review aims to summarize the current knowledge concerning the clinical features, diagnostic work-up, and therapeutic approach of bilateral diffuse uveal melanocytic proliferation (BDUMP). A meticulous literature search was performed in the PubMed database. A supplementary search was made in Google Scholar to complete the collected items. Our search strategy utilized the following keywords: "bilateral diffuse uveal melanocytic proliferation", "BDUMP", and "Paraneoplastic Syndrome". Articles were considered based on their relevance, with the search spanning publications up to 2023. Studies were excluded if they did not contribute pertinent information or lacked methodological rigor. A critical appraisal of included studies was conducted, assessing study design, sample size, methodology, and potential bias, ensuring a thorough and transparent review process. BDUMP is a rare and potentially sight-threatening condition characterized by the bilateral proliferation of melanocytes within the uvea. BDUMP is typically observed in middle-aged or elderly individuals and is often associated with an underlying malignancy, most commonly of gastrointestinal origin. BDUMP is frequently misdiagnosed as a benign nevus or choroidal metastasis, leading to delayed diagnosis and treatment. The ophthalmic symptoms and signs typically precede the diagnosis of a systemic malignancy, emphasizing the crucial role of ophthalmologists in the recognition of BDUMP. Several diagnostic modalities can aid in the diagnosis of BDUMP, including ophthalmic examination, imaging studies such as optical coherence tomography, fluorescein angiography, and indocyanine green angiography, and biopsy of the uveal tissue. Treatment of BDUMP is directed towards the underlying malignancy and may include chemotherapy, radiotherapy, or surgical resection. Additionally, strict monitoring with regular follow-ups may contribute to the detection of new lesions and the reduction in the size of existing ones. BDUMP can be considered a potential biomarker in the management of malignancies, especially when the primary underlying tumor has not been detected. Further research is needed to better understand the pathogenesis of BDUMP and its association with malignancy.

Risk factors associated with severe dengue in Latin America: A systematic review and meta-analysis.

Severe dengue is a significant health problem in Latin America, with children being the most affected. Understanding risk factors for severe dengue is crucial for enhancing patient care. Therefore, this study aims to systematically review the literature to identify the risk factors associated with severe dengue in Latin America through systematic review and meta-analysis. PubMed, SciELO, LILACS and EMBASE databases were used to search for eligible scientific articles for the review. The outcomes considered were symptoms of severe dengue, hospitalisation and death. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the quality of the studies. Data analysis was performed using STATA v 13.0 software. The degree of heterogeneity between studies was quantified using the I2 measure, and statistically significant results were defined as those with p values <0.05. Of the 1876 articles screened, 47 articles were included in the systematic review and 45 articles were analysed through meta-analysis. Identified risk factors associated with severe dengue included secondary dengue infection, female sex, white or Caucasian ethnicity and specific signs and symptoms such as headache, myalgia and/or arthralgia, vomiting/nausea, abdominal pain or tenderness, diarrhoea, prostration, lethargy, fatigue or similar. For the death outcome, respiratory symptoms and age <18 years were identified as risk factors. On the other hand, in women, the diagnosis of positive tourniquet test, platelet count <100,000 per μL and symptoms of capillary fragility were associated with a lower probability of death. These data highlight the importance of early screening of patients, to identify possible haemorrhagic signs and reduce deaths from dengue. This study has limitations, including possible publication bias, heterogeneity of results and study design biases. These findings are significant for shaping strategies, management approaches and identifying high-risk groups, which will help establish future guidelines.

Pitfalls and biases in neuroepidemiological studies of COVID-19 and the nervous system: a critical appraisal of the current evidence and future directions.

Neurological manifestations frequently occur in individuals with COVID-19, manifesting during the acute phase, persisting beyond the resolution of acute symptoms, and appearing days or weeks after the initial onset of COVID-19 symptoms. However, predicting the incidence, course, and outcome of these neurological manifestations at the individual patient level remains challenging. Biases in study design and limitations in data collection may contribute to the inconsistency and limited validity of the reported findings. Herein, we focused on critically appraising pitfalls and biases of prior reports and provide guidance for improving the quality and standardization of future research. Patients with COVID-19 exhibit diverse demographic features, sociocultural backgrounds, lifestyle habits, and comorbidities, all of which can influence the severity and progression of the infection and its impact on other organ systems. Overlooked or undocumented comorbidities and related treatments may contribute to neurological sequelae, which may not solely be attributable to COVID-19. It is crucial to consider the potential side effects of vaccines in relation to neurological manifestations. To investigate neurological manifestations of COVID-19, it is essential to employ valid and reliable diagnostic criteria and standard definitions of the factors of interest. Although population-based studies are lacking, well-defined inception cohorts, including hospitalized individuals, outpatients, and community residents, can serve as valuable compromises. These cohorts should be evaluated for the presence of common comorbidities, alongside documenting the primary non-neurological manifestations of the infectious disease. Lastly, patients with COVID-19 should be followed beyond the acute phase to assess the persistence, duration, and severity of neurological symptoms, signs, or diseases.

Cardiac Magnetic Resonance Findings of Coronavirus Disease 2019 (COVID-19) Vaccine-Associated Myopericarditis at Intermediate Follow-Up: A Comparison with Classic Myocarditis

To report intermediate cardiac magnetic resonance (CMR) findings of coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis (C-VAM) and compare with classic myocarditis. Retrospective cohort study including children diagnosed with C-VAM from May 2021 through December 2021 with early and intermediate CMR. Patients with classic myocarditis from January 2015 through December 2021 and intermediate CMR were included for comparison. There were 8 patients with C-VAM and 20 with classic myocarditis. Among those with C-VAM, CMR performed at a median 3days (IQR 3, 7) revealed 2 of 8 patients with left ventricular ejection fraction <55%, 7 of 7 patients receiving contrast with late gadolinium enhancement (LGE), and 5 of 8 patients with elevated native T1 values. Borderline T2 values suggestive of myocardial edema were present in 6 of 8 patients. Follow-up CMRs performed at a median 107days (IQR 97, 177) showed normal ventricular systolic function, T1, and T2 values; 3 of 7 patients had LGE. At intermediate follow-up, patients with C-VAM had fewer myocardial segments with LGE than patients with classic myocarditis (4/119 vs 42/340, P=.004). Patients with C-VAM also had a lower frequency of LGE (42.9 vs 75.0%) and lower percentage of left ventricular ejection fraction <55% compared with classic myocarditis (0.0 vs 30.0%), although these differences were not statistically significant. Five patients with classic myocarditis did not receive an early CMR, leading to some selection bias in study design. Patients with C-VAM had no evidence of active inflammation or ventricular dysfunction on intermediate CMR, although a minority had persistent LGE. Intermediate findings in C-VAM revealed less LGE burden compared with classic myocarditis.

Quality of observational studies of clinical interventions: a meta-epidemiological review

BackgroundThis meta-epidemiological study aimed to assess methodological quality of a sample of contemporary non-randomised clinical studies of clinical interventions.MethodsThis was a cross-sectional study of observational studies published between January 1, 2012 and December 31, 2018. Studies were identified in PubMed using search terms ‘association’, ‘observational,’ ‘non-randomised’ ‘comparative effectiveness’ within titles or abstracts. Each study was appraised against 35 quality criteria by two authors independently, with each criterion rated fully, partially or not satisfied. These quality criteria were grouped into 6 categories: justification for observational design (n = 2); minimisation of bias in study design and data collection (n = 11); use of appropriate methods to create comparable groups (n = 6); appropriate adjustment of observed effects (n = 5); validation of observed effects (n = 9); and authors interpretations (n = 2).ResultsOf 50 unique studies, 49 (98%) were published in two US general medical journals. No study fully satisfied all applicable criteria; the mean (+/−SD) proportion of applicable criteria fully satisfied across all studies was 72% (+/− 10%). The categories of quality criteria demonstrating the lowest proportions of fully satisfied criteria were measures used to adjust observed effects (criteria 20, 23, 24) and validate observed effects (criteria 25, 27, 33). Criteria associated with ≤50% of full satisfaction across studies, where applicable, comprised: imputation methods to account for missing data (50%); justification for not performing an RCT (42%); interaction analyses in identifying independent prognostic factors potentially influencing intervention effects (42%); use of statistical correction to minimise type 1 error in multiple outcome analyses (33%); clinically significant effect sizes (30%); residual bias analyses for unmeasured or unknown confounders (14%); and falsification tests for residual confounding (8%). The proportions of fully satisfied criteria did not change over time.ConclusionsRecently published observational studies fail to fully satisfy more than one in four quality criteria. Criteria that were not or only partially satisfied were identified which serve as remediable targets for researchers and journal editors.

Utilization of real-world data in assessing treatment effectiveness for diffuse large B-cell lymphoma.

Direct comparisons of the effectiveness of the numerous novel therapies in the diffuse large B-cell lymphoma (DLBCL) treatment landscape in a range of head-to-head randomized phase 3 trials would be time-consuming and costly. Comparative effectiveness studies using real-world data (RWD) represent a complementary approach. Recently, several studies of relapsed/refractory (R/R) DLBCL have used RWD to create observational cohorts to compare patient outcomes with cohorts derived from single-arm phase 2 trials. Using propensity score methods to balance clinically and prognostically relevant baseline covariates, closely matched patient-level cohorts can be generated. By incorporating appropriate measures to assess covariate balance and address potential bias in comparative effectiveness study designs, robust comparative analyses can be performed. Results from such studies have been used to supplement regulatory approval of therapies assessed in single-arm trials. While RWD studies have a greater susceptibility to bias compared to randomized controlled trials, well-designed and appropriately analyzed studies can provide complementary real-world evidence on treatment effectiveness.

Empirical evidence of study design biases in nutrition randomised controlled trials: a meta-epidemiological study

BackgroundInstruments to critically appraise randomised controlled trials (RCTs) are based on evidence from meta-epidemiological studies. We aim to conduct a meta-epidemiological study on the average bias associated with reported methodological trial characteristics such as random sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and compliance of RCTs in nutrition research.MethodsWe searched the Cochrane Database of Systematic Reviews, for systematic reviews of RCTs, published between 01 January 2010 and 31 December 2019. We combined the estimates of the average bias (e.g. ratio of risk ratios [RRR] or differences in standardised mean differences) in meta-analyses using the random-effects model. Subgroup analyses were conducted to investigate the potential differences among the RCTs with low versus high/unclear risk of bias with respect to the different types of interventions (e.g. micronutrients, fatty acids, dietary approach), outcomes (e.g. mortality, pregnancy outcomes), and type of outcome (objective, subjective). Heterogeneity was assessed through I2 and τ2, and prediction intervals were calculated.ResultsWe included 27 Cochrane nutrition reviews with 77 meta-analyses (n = 927 RCTs). The available evidence suggests that intervention effect estimates may not be exaggerated in RCTs with high/unclear risk of bias (versus low) judgement for sequence generation (RRR 0.97, 95% CI 0.93 to 1.02; I2 = 28%; τ2 = 0.002), allocation concealment (RRR 1.00, 95% CI 0.96 to 1.04; I2 = 27%; τ2 = 0.001), blinding of participants and personnel (RRR 0.95, 95% CI 0.91 to 1.00; I2 = 23%; τ2 = 0), selective reporting (RRR 0.97, 95% CI 0.92 to 1.02; I2 = 24%; τ2 = 0), and compliance (RRR 0.95, 95% CI 0.89 to 1.02; I2 = 0%; τ2 = 0). Intervention effect estimates seemed to be exaggerated in RCTs with a high/unclear risk of bias judgement for blinding of outcome assessment (RRR 0.81, 95% CI 0.70 to 0.94; I2 = 26%; τ2 = 0.03), which was predominately driven by subjective outcomes, and incomplete outcome data (RRR 0.92, 95% CI 0.88 to 0.97; I2 = 22%; τ2 = 0.001). For continuous outcomes, no differences were observed, except for selective reporting.ConclusionsOn average, most characteristics of nutrition RCTs may not exaggerate intervention effect estimates, but the average bias appears to be greatest in trials of subjective outcomes. Replication of this study is suggested in this field to keep this conclusion updated.

Impact of reproductive factors on major cardiovascular disease risk in women: a Mendelian randomization study

Abstract Background Cardiovascular disease is a major cause of morbidity and mortality in women. Multiple observational studies have explored the role of female reproductive history on the risk of cardiovascular disease and suggested that factors such as high parity and early menarche are associated with higher rates of cardiovascular disease later in life. However, effect estimates derived from observational studies are liable to influence by residual confounding and bias in study design. We utilise Mendelian randomisation to explore causal pathways underlying this association by leveraging genetic variability in reproductive factors using instrumental variable analysis. Methods Uncorrelated single nucleotide polymorphisms (r2&amp;lt;0.001) were extracted from summary statistics of published sex-specific genome wide association studies (GWAS) for the exposures of age at first birth (n=131,987, unit = years), number of live births (n=193,953, coded into three categories of &amp;lt;2, 2 or &amp;gt;2 live births), age at menarche (n=329,345, unit = years) and age at menopause (n=106,048, unit = years). Genetic association estimates for the outcomes of coronary artery disease, ischaemic stroke, stroke of any type, heart failure and atrial fibrillation were extracted from GWAS analyses on respectively 122,733 cases, 34,217 cases, 40,585 cases, 47,309 cases and 60,620 cases. All GWAS studies were on populations of predominantly European ancestry. Inverse-variance weighted MR was utilised for primary analyses; sensitivity analyses using MR-Egger and weighted median MR were carried out. Results Earlier age at first birth was associated with increased risk of coronary artery disease (OR per 1-year lower age = 1.49, 95% CI 1.28–1.74, p&amp;lt;0.001). Lower age at menarche was also associated with increased risk of coronary artery disease (OR per 1-year lower age = 1.10, 95% CI 1.06–1.14, p&amp;lt;0.001) and increased risk of heart failure (OR 1.12, 95% CI 1.07–1.17, p&amp;lt;0.001). Finally, higher number of live births was associated with increased risk of atrial fibrillation (OR per increase in category of &amp;lt;2, 2 or &amp;gt;2 live births = 2.91, 95% CI 1.16–7.29, p=0.023), increased risk of heart failure (OR 1.90, 95% CI 1.28–2.82, p=0.001), increased risk of ischaemic stroke (OR 2.07, 95% CI 1.22–3.52, p=0.007) and of stroke of any type (OR 1.86, 95% CI 1.03–3.37, p=0.039). Conclusion The results of this study support the emerging evidence of female-specific risk factors for cardiovascular disease, by demonstrating that that earlier age at first birth, higher number of live births, and earlier menarche are all associated with increased cardiovascular morbidity in women. The results notably highlight parity as a major sex-specific risk factor of likely causal relevance. These findings support the inclusion of reproductive history in the routine evaluation of cardiovascular risk in females and identify key markers of risk that may be used to target primary prevention measures. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council GEPSI 946647 for EAWSBritish Heart Foundation RG/16/3/32175 for FSN

Proton pump inhibitors and the risk of cardiovascular events and cardiovascular mortality: A systematic review and meta-analysis of observational studies

Background and AimsObservational research has indicated that proton pump inhibitors (PPIs) might increase the long-term risk of cardiovascular events. This study evaluated the evidence from observational studies for an effect of PPI monotherapy on the risk of incident cardiovascular events and cardiovascular mortality. MethodsThe databases MEDLINE, EMBASE, and Scopus were systematically searched up to September 2021. The primary outcome was first cardiovascular event, i.e. first myocardial infarction or first ischaemic stroke. The secondary outcome was cardiovascular mortality. Studies were included following a detailed risk of bias assessment with the ROBINS-I tool. Sensitivity and bias analyses adjusted for potential publication bias, immortal time bias, and unmeasured confounding. ResultsWe included ten studies with 75,371 first cardiovascular events, as well as seven studies on cardiovascular mortality with 50,329 cardiovascular deaths in total. The pooled hazard ratios (HRs) for PPI use and cardiovascular events were 1.05 with a 95% confidence interval of (0.96; 1.15) before and 0.99 (0.93; 1.04) after adjusting for observational study design bias. The pooled HRs for PPI use and cardiovascular mortality were 1.27 (1.11; 1.44) before and 1.06 (0.96; 1.16) after adjusting for publication bias and observational study design bias. ConclusionIt is questionable, whether PPI monotherapy constitutes a cardiovascular risk factor.

Radiomic Analysis: Study Design, Statistical Analysis, and Other Bias Mitigation Strategies.

Rapid advances in automated methods for extracting large numbers of quantitative features from medical images have led to tremendous growth of publications reporting on radiomic analyses. Translation of these research studies into clinical practice can be hindered by biases introduced during the design, analysis, or reporting of the studies. Herein, the authors review biases, sources of variability, and pitfalls that frequently arise in radiomic research, with an emphasis on study design and statistical analysis considerations. Drawing on existing work in the statistical, radiologic, and machine learning literature, approaches for avoiding these pitfalls are described.

Molecular Subtypes as a Basis for Stratified Use of Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer-A Narrative Review.

Simple SummaryAlthough it is one disease, cancer of the urinary bladder occurs in several molecular subtypes that can be identified by laboratory tests. Tumors of advanced stages are treated with surgical removal of the urinary bladder with or without addition of chemotherapy. About 50% of patients are cured by surgery and this proportion is increased slightly by the addition of chemotherapy. Still, many patients do not benefit from chemotherapy, which also comes with significant toxicity. Recent advances in the field suggest that molecular subtypes can help identify patient categories that do or do not benefit from adding chemotherapy to surgery. In this article, we review the literature and conclude that molecular subtypes are likely to have such a role in the future but that there are differences between studies that make them challenging to compare. The current evidence is insufficient to guide clinical practice.There are no established biomarkers to guide patient selection for neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer. Recent studies suggest that molecular subtype classification holds promise for predicting chemotherapy response and/or survival benefit in this setting. Here, we summarize and discuss the scientific literature examining transcriptomic or panel-based molecular subtyping applied to neoadjuvant chemotherapy-treated patient cohorts. We find that there is not sufficient evidence to conclude that the basal subtype of muscle-invasive bladder cancer responds well to chemotherapy, since only a minority of studies support this conclusion. More evidence indicates that luminal-like subtypes may have the most improved outcomes after neoadjuvant chemotherapy. There are also conflicting data concerning the association between biopsy stromal content and response. Subtypes indicative of high stromal infiltration responded well in some studies and poorly in others. Uncertainties when interpreting the current literature include a lack of reporting both response and survival outcomes and the inherent risk of bias in retrospective study designs. Taken together, available studies suggest a role for molecular subtyping in stratifying patients for receiving neoadjuvant chemotherapy. The precise classification system that best captures such a predictive effect, and the exact subtypes for which other treatment options are more beneficial remains to be established, preferably in prospective studies.

Health-Related Quality of Life, Psychosocial Distress and Unmet Needs in Older Patients With Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is the most common cancer involving the mucosal surfaces of the head and neck and is associated with a number of etiological factors, including cigarette smoking, alcohol and betel nut consumption and exposure to high-risk human papillomavirus. The risk of HNSCC increases with age, peaking in the seventh and eighth decade, but this varies by anatomical and histological subtype. While several advancements have been made in the treatment of head and neck cancer (HNC) in recent decades, undertaking curative treatment still subjects the majority of HNSCC patients to substantial treatment-related toxicity requiring patients to tolerate a gamut of physical, psychological, and emotional demands on their reserves. In conjunction with other patient-related factors, clinicians involved in treating patients with HNSCC may incorporate advancing chronological age into their decision-making process when determining treatment recommendations. While advancing chronological age may be associated with increased concerns regarding physical treatment tolerability, clinicians may also be concerned about heightened vulnerability in various health and wellbeing outcomes. The available literature, however, does not provide evidence of this vulnerability in patients with advancing age, and, in many instances, older patients self-report greater resilience compared to their younger counterparts. While this data is reassuring it is limited by selection bias and heterogeneity in trial and study design and the absence of a consistent definition of the elderly patient with HNSCC. This narrative review article also includes a review of the measures used to assess HRQL, psychosocial outcomes and unmet needs in elderly or older patients with HNSCC.

Diagnostic Accuracy Studies in Radiology: How to Recognize and Address Potential Sources of Bias.

Accuracy is an important parameter of a diagnostic test. Studies that attempt to determine a test's accuracy can suffer from various forms of bias. As radiology is a diagnostic specialty, many radiologists may design a diagnostic accuracy study or review one to understand how it may apply to their practice. Radiologists also frequently serve as consultants to other physicians regarding the selection of the most appropriate diagnostic exams. In these roles, understanding how to critically appraise the literature is important for all radiologists. The purpose of this review is to provide a framework for evaluating potential sources of study design biases that are found in diagnostic accuracy studies and to explain their impact on sensitivity and specificity estimates. To help the reader understand these biases, we also present examples from the radiology literature.

Investigating Applications of Prognostic Scores to Balancing Weights: Evidence from an Evaluation of Accountable Care Organizations

Research ObjectivePropensity score methods, based on the predicted probability of treatment, are ubiquitous in health services research. Over the past decade, an increasing amount of research has investigated applications of prognostic scores: the predicted probability of the study outcome of interest (e.g., illness, mortality). However, this research has focused on the use of prognostic scores in matching, either in conjunction with, or in place of, more commonly‐implemented propensity score matching approaches. There has been little, if any, research focused on the use of prognostic scores with other analytic strategies such as weighting or subclassification typically associated with propensity scores. Prior research has also focused on prognostic scores for binary outcomes. This study presents several analytic strategies based on a continuous pseudo‐prognostic score (P‐PS) and assesses their practical value relative to a public evaluation of a Medicare value‐based payment model.Study DesignWe used Medicare claims and enrollment data covering all 41 Medicare accountable care organizations (ACOs) that participated in the ACO Investment Model (AIM): the same data used to evaluate the first AIM performance year. The evaluation's primary outcome of interest was total Medicare spending, per‐beneficiary‐per‐month. We estimated a regression model for total spending using each ACO's comparison group and predicted the P‐PS (i.e., predicted spending) for intervention and comparison beneficiaries using the model's parameters.While the original evaluation used entropy‐balancing weights to balance all covariates between intervention and comparison beneficiaries within each ACO, we calculated three types of enhanced entropy‐balance weights based on the P‐PS. We balanced intervention and comparison beneficiaries on all covariates and P‐PS, and then incorporated a quadratic P‐PS as well. Lastly, we classified beneficiaries into five quintiles of P‐PS, and separately balanced covariates within each quintile.We assessed the effect of the enhanced weights on the magnitude and precision of corresponding impact estimates, as well as the validity of the parallel trend assumption underlying the difference‐in‐differences (DID) evaluation design, relative to the original weights.Population StudiedBeneficiaries with fee‐for‐service Medicare attributed to ACOs in AIM and corresponding comparison beneficiaries eligible for attribution in 2013–2016.Principal FindingsIncorporating P‐PS directly into the weights did not meaningfully affect estimated differences in baseline parallel trends or impact estimates. However, across the 41 ACOs, weighting by covariates within PPS quintiles reduced average absolute baseline differences by 14.7% at the mean and 21.2% at the median. These differences shifted the mean impact estimate by 6.7%, while increasing the mean standard error of the impact estimates by 2.3%.ConclusionsBalancing covariates within P‐PS quintiles improved the validity of DID estimates by substantially reducing differences in baseline trends, and meaningfully reduced bias in the subsequent impact estimates. Bias reduction was greater than the loss in precision. Incorporating P‐PS directly into the weights did not meaningfully affect baseline or impact estimates.Implications for Policy or PracticeBalancing covariates within prognostic score quintiles shows promise for reducing bias in observational study designs. Unlike matching‐based prognostic score approaches, this method can be implemented when outcomes of interest are continuous, and does not require discarding unmatched data.Primary Funding SourceCenters for Medicare and Medicaid Services.