15 years of patient-reported outcomes in clinical trials leading to GU cancer drug approvals: a systematic review on the quality of data reporting and analysis.

Background: Standardized, high-quality PRO data reporting is crucial for patient centered care in the field of oncology, especially in clinical trials that establish standard of care. This study evaluated PRO endpoint design, conduct and reporting methods in FDA approved drugs for GU malignancies. Methods: A systematic review of the FDA archives identified GU cancer drug approvals from Feb 2007 to July 2022. ClinicalTrials.gov and PubMed were used to retrieve relevant data. PRO data was screened, and analytic tools, interpretation methods in the published papers and study protocols were reviewed. Compliance with PRO reporting standards were assessed using PRO Endpoint Analysis Score (PROEAS), a 24-point scoring scale from Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium (SISAQOL). Findings: We assessed 40 trial protocols with 27,011 participants, resulting in 14 renal cell cancer (RCC), 16 prostate cancer (PC), and 10 urothelial cancer (UC) approvals. PRO data was published for 27 trials, with 23 PRO publications (85%) focusing solely on PRO data, while 4 (15%) included PRO data in the original paper. Median time between primary clinical and secondary paper with PRO data was 10.5 months (range: 9-25 months). PROs were not planned as primary endpoints for any study but 14 (52%) reported them as secondary, 10 (37%) as exploratory outcomes, and 3 (11%) lacked any clarity on PRO data as endpoint. Mean PROEAS score of all GU cancers was 11.10 (range: 6-15), RCC (11.86, range: 6-15), UC (11.50, range: 9-14), and PC (10.56, range: 6-15). None met all the SISAQOL recommendations. Interpretation: Low overall PROEAS score and delays in PRO data publication in GU cancer drug trials conducted in the past decade emphasize the need for improvement in quality of design and conduct of PRO endpoint in future trials and accelerated publication of PRO endpoints, using standardized analysis, and prespecified hypothesis driven endpoint. These improvements are essential for facilitating interpretation and application of PRO study findings to define patient care. Funding: None.

Evaluation of Patient-Reported Outcomes (PROs) Protocol Content and Reporting for Clinical Trials that Lead to the approval of frontline Immune Checkpoint Blockade Combination for Patients with Advanced Renal Cell Carcinoma - The Patients' Voice or a Missed Opportunity.

INTRODUCTION: Immune checkpoint blockade (ICB) is a rapidly emerging field of oncology that has revolutionized the metastatic renal cell carcinoma (mRCC) treatment. Four recent treatment regimens Nivolumab-Ipilimumab, Pembrolizumab-Axitinib, Nivolumab-Cabozantinib, and Pembrolizumab-Lenvatinib-have demonstrated improved clinical endpoints compared to standard of care and are endorsed by NCCN (2021). However, data on patient-reported outcomes (PROs) for patients receiving these regimens are limited. We conducted a comparative assessment of the quality and standardization of PROs endpoints and data reported for these randomized controlled trials (RCTs). PATIENTS AND METHODS: We systematically identified all RCTs evaluating combination ICB for ccRCC. PROs-specific data were abstracted from the final version of 4 RCT protocols, as well as clinical and PROs specific manuscripts published between April 2018 and April 2021. We used 3 previously published guides standardizing PROs research to objectively score the data: (i) 24-point PROEAS; (ii) 12-point SPIRIT-PRO; and (iii) 14-point CONSORT-PRO. RESULTS: The CheckMate 214, KEYNOTE 426, CheckMate 9ER, and CLEAR studies had PROEAS scores of 88% (21/24), 37% (9/24), 83% (20/24), and 16% (4/24), respectively, and SPIRIT-PRO scores of 50% (6/12), 75% (9/12), 66% (8/12), and 41% (5/12) respectively. The CONSORT-PRO scores were 86% (12/14) for CheckMate 214 and 43% (6/14) for CheckMate 9ER, but scores were not available for the CLEAR and KEYNOTE 426 studies because of a lack of sufficient data. The average SPIRIT-PRO score across the 4 RCTs was 58%, indicating a reasonable adoption of PROs research in data management and analysis. The CheckMate 214 trial had the longest follow-up and most comprehensive published PROs data. CONCLUSION: Our analysis identified the limitations of current PROs data in combination ICB approved for mRCC. This analysis will enable clinicians to better interpret the current PROs results and emphasize the importance of better incorporation of PROs endpoints in future mRCC trial design.

Patient-Reported Outcomes in Clinical Trials Leading to Cancer Immunotherapy Drug Approvals From 2011 to 2018: A Systematic Review.

BACKGROUND: Patient-reported outcomes (PROs) promote patient centeredness in clinical trials; however, in the field of rapidly emerging and clinically impressive immunotherapy, data on PROs are limited. METHODS: We systematically identified all immunotherapy approvals from 2011 through 2018 and assessed the analytic tools and reporting quality of associated PRO reports. For randomized clinical trials (RCTs), we developed a novel 24-point scoring scale: the PRO Endpoints Analysis Score based on 24 criteria derived from the recommendations of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium. RESULTS: We assessed 44 trial publications supporting 42 immunotherapy approvals. PROs were published for 21 of the 44 (47.7%) trial publications. Twenty-three trials (52.3%) were RCTs and 21 (47.7%) pertained to single-arm trials. The median time between primary clinical outcomes publications and their corresponding secondary PRO publications was 19 months (interquartile range = 9-29 months). Of the 21 PRO reports, 4 (19.0%) reported a specific hypothesis, and most (85.7%) used descriptive statistics. Three (3 of 21 [14.3%]) studies performed a control for type I error. As for RCTs, 14 of 23 (60.9%) published PRO data, including 13 (56.5%) that published a secondary dedicated manuscript. One-half of these 14 trials scored less than 13 points on the 24-point PRO Endpoints Analysis Score. The mean score was 12.71 (range = 5-17, SD = 3.71), and none met all the recommendations of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium. CONCLUSIONS: Suboptimal reporting of PROs occurs regularly in cancer immunotherapy trials. Increased efforts are needed to maximize the value of these data in cancer immunotherapy development and approval.

Collaborative Learning in the Texas Medicaid 1115 Waiver Program.

The Texas Medicaid 1115 Transformation Waiver reforms the state's safety net systems by creating a Delivery System Reform Incentive Payment incentive pool for innovative healthcare delivery. The Waiver supports the design and implementation of transformative projects. As part of the Waiver requirements, regions created Learning Collaboratives to collaborate on project implementation and outcomes. This paper describes the experience of one region in adapting the Institute for Healthcare Improvement Breakthrough Series (IHI BTS) model, as a framework for their Learning Collaborative. Implementation of the Learning Collaborative was systematic, multidimensional, and regularly evaluated. Some features of the IHI model were adapted, specifically longer Plan-Do-Check-Act cycles and the lack of a single clinical focus. This experience demonstrates the ability of a region to improve health from a more diverse perspective than the traditional IHI BTS Collaboratives. Within the region, organizations are connecting, agencies are building continuums of care, and stakeholders are involved in healthcare delivery. The initial stages show a remarkable increase in communication and enhanced relationships between providers. At the end of the 5-year Waiver, evaluation of the impact of the regional and cohort Learning Collaboratives will determine how well the adapted IHI BTS model facilitated improvements in the community's health.

Wealth, Health Expenditure, and Cancer: A National Perspective.

BACKGROUND: The US health care system is characterized by high health expenditures with penultimate outcomes. This ecological study evaluates the associations between wealth, health expenditure, and cancer outcomes at the state level. METHODS: We extracted gross domestic product (GDP) and health expenditure per capita from the 2009 Bureau of Economic Analysis and the Centers for Medicare & Medicaid Services, respectively. Using data from the NCI, we retrieved colorectal cancer (CRC), breast cancer, and all-cancer age-adjusted rates and computed mortality/incidence (M/I) ratios. We used the Spearman's rank correlation to determine the association between the financial indicators and cancer outcomes, and we constructed geographic distribution maps to describe these associations. RESULTS: GDP per capita significantly correlated with lower M/I ratios for all cancers, breast cancer, and CRC. As for health expenditure per capita, preliminary analysis highlighted a rift between the Northeastern and Southern states, which translated into worse breast and all-cancer outcomes in Southern states. Further analysis showed that higher health expenditure significantly correlated with decreased breast cancer M/I ratio. However, CRC outcomes were not significantly affected by health expenditure, nor were all-cancer outcomes. CONCLUSIONS: All cancers, breast cancer, and CRC outcomes significantly correlated with wealth, whereas only breast cancer correlated with higher health expenditure. Future research is needed to evaluate the potential role of policies in optimizing resource allocation in the states' efforts against CRC and minimizing disparities in interstate cancer outcomes.

Association Between ß-Genus Human Papillomavirus and Cutaneous Squamous Cell Carcinoma in Immunocompetent Individuals-A Meta-analysis.

Importance: Existing epidemiological evidence remains controversial regarding the association between ß-genus human papillomavirus (ß-HPV) and cutaneous squamous cell carcinoma (cSCC) in immunocompetent individuals. Objective: We aimed to clarify this association and evaluate type-specific ß-HPV involvement. Data Sources: We performed a systematic literature search of MEDLINE and EMBASE for studies in humans through June 18, 2014, with no restriction on publication date or language. The following search terms were used: "human papillomavirus" and "cutaneous squamous cell carcinoma or skin squamous cell carcinoma or cSCC or nonmelanoma skin neoplasms." Study Selection: Articles were independently assessed by 2 reviewers. We only included case-control or cohort studies, in immunocompetent individuals, that calculated the odds ratio (OR) for cSCC associated with overall and type-specific ß-HPV. Data Extraction and Synthesis: We first assessed the heterogeneity among study-specific ORs using the Q statistic and I2 statistic. Then, we used the random-effects model to obtain the overall OR and its 95% CI for all studies as well as for each type of HPV. We also tested and corrected for publication bias by 3 funnel plot-based methods. The quality of each study was assessed with the Newcastle Ottawa Scale. Main Outcomes and Measures: Pooled ORs and 95% CIs for overall ß-HPV and HPV types 5, 8, 15, 17, 20, 24, 36, and 38 association with skin biopsy proven cSCC. Results: Seventy-nine articles were assessed for eligibility; 14 studies met inclusion criteria for the meta-analysis and included 3112 adult immunocompetent study participants with cSCC and 6020 controls. For all detection methods, the overall association between ß-HPV and cSCC was significant with an adjusted pooled OR (95% CI) of 1.42 (1.18-1.72). As for the type-specific analysis, types 5, 8, 15, 17, 20, 24, 36, and 38 showed a significant association with adjusted pooled ORs (95% CIs) of 1.4 (1.18-1.66), 1.39 (1.16-1.66), 1.25 (1.04-1.50), 1.34 (1.19-1.52), 1.38 (1.21-1.59), 1.26 (1.09-1.44), 1.23 (1.01-1.50), and 1.37 (1.13-1.67) respectively. Our subgroup analysis in studies using only serology for HPV detection showed a significant association between overall ß-HPV and HPV subtypes 5, 8, 17, 20, 24, and 38 with an increased risk of cSCC development. Conclusions and Relevance: This study serves as added evidence supporting ß-HPV as a risk factor for cSCC in healthy individuals. The subgroup analysis highlights this significant association for HPV 5, 8, 17, 20, and 38, which may help to direct future prevention efforts.

PREVALENCE OF DIABETES MELLITUS AMONG PATIENTS WITH ESSENTIAL ARTERIAL HYPERTENSION.

OBJECTIVES: This study evaluates the prevalence of diabetes mellitus (DM) among patients with arterial hypertension, and indirectly, the crucial impact of adopting screening for diabetes as a standard procedure for all patients diagnosed with arterial hypertension. MATERIALS & METHODS: This cross-sectional study was performed on a sample of hypertensive patients recruited from three different university hospitals in Lebanon. Blood pressure and glycemic blood measurements were determined in all subjects. In addition, a complete clinical history and physical exam were performed. Data was entered and analyzed using SPSS 19.0. Frequencies for the different variables were calculated, and the chi-square and independent sample t-tests were conducted. RESULTS: This study included 294 patients. Prevalence of diabetes was 27%, and 23% of diabetic patients were newly diagnosed. More than half of the subjects suffering from DM had uncontrolled blood pressure, contrasted with only one third of the non-diabetic subjects with uncontrolled hypertension. CONCLUSION: The prevalence of DM in patients with essential hypertension was more than double that of the general population. Therefore, major recommendations would be to adopt strictly the diabetes screening requirements and aggressive management among hypertensive patients to minimize both the health and cost burdens associated with undetected DM.

Ventilator-associated events prevention, learning lessons from the past: A systematic review.

BACKGROUND: Preventing Ventilator-associated events (VAE) is a major challenge. Strictly monitoring for ventilator-associated pneumonia (VAP) is not sufficient to ensure positive outcomes. Therefore, the surveillance definition was updated and a change to the broader VAE was advocated. OBJECTIVE: This paper summarizes the scientific efforts assessing VAP preventive bundles and the recent transition in surveillance methods. METHODS: We conducted a systematic review to identify lessons from past clinical studies assessing VAP prevention bundles. We then performed a thorough literature review on the recent VAE surveillance algorithm, highlighting its advantages and limitations. CONCLUSION: VAP prevention bundles have historically proven their efficacy and the introduction of the new VAE definition aimed at refining and objectivizing surveillance methods. Randomized controlled trials remain vital to determine the effect of VAE prevention on patient outcomes. We recommend expanding beyond limited VAP prevention strategies towards VAE prevention bundles.

Strategic planning processes and financial performance among hospitals in Lebanon.

BACKGROUND: Strategic planning has been presented as a valuable management tool. However, evidence of its deployment in healthcare and its effect on organizational performance is limited in low-income and middle-income countries (LMICs). The study aimed to explore the use of strategic planning processes in Lebanese hospitals and to investigate its association with financial performance. METHODS: The study comprised 79 hospitals and assessed occupancy rate (OR) and revenue-per-bed (RPB) as performance measures. The strategic planning process included six domains: having a plan, plan development, plan implementation, responsibility of planning activities, governing board involvement, and physicians' involvement. RESULTS: Approximately 90% of hospitals have strategic plans that are moderately developed (mean score of 4.9 on a 1-7 scale) and implemented (score of 4.8). In 46% of the hospitals, the CEO has the responsibility for the plan. The level of governing board involvement in the process is moderate to high (score of 5.1), whereas physician involvement is lower (score of 4.1). The OR and RPB amounted to respectively 70% and 59 304 among hospitals with a strategic plan as compared with 62% and 33 564 for those lacking such a plan. No statistical association between having a strategic plan and either of the two measures was detected. However, the findings revealed that among hospitals that had a strategic plan, higher implementation levels were associated with lower OR (p < 0.05). CONCLUSIONS: In an LMIC healthcare environment characterized by resource limitation, complexity, and political and economic volatility, flexibility rather than rigid plans allow organizations to better cope with environmental turbulence.