Levels of evidence and grades of recommendation supporting European society for medical oncology clinical practice guidelines.

Background: The European Society for Medical Oncology (ESMO) guidelines are among the most comprehensive and widely used clinical practice guidelines (CPGs) globally. However, the level of scientific evidence supporting ESMO CPG recommendations has not been systematically investigated. This study assessed ESMO CPG levels of evidence (LOE) and grades of recommendations (GOR), as well as their trends over time across various cancer settings. Methods: We manually extracted every recommendation with the Infectious Diseases Society of America (IDSA) classification from each CPG. We examined the distribution of LOE and GOR in all available ESMO CPG guidelines across different topics and cancer types. Results: Among the 1,823 recommendations in the current CPG, 30% were classified as LOE I, and 43% were classified as GOR A. Overall, there was a slight decrease in LOE I (-2%) and an increase in the proportion of GOR A (+1%) in the current CPG compared to previous versions. The proportion of GOR A recommendations based on higher levels of evidence such as randomized trials (LOE I-II) shows a decrease (71% vs. 63%, p = 0.009) while recommendations based on lower levels of evidence (LOE III-V) show an increase (29% vs. 37%, p = 0.01) between previous and current version. In the current versions, the highest proportion of LOE I (42%) was found in recommendations related to pharmacotherapy, while the highest proportion of GOR A recommendations was found in the areas of pathology (50%) and diagnostic (50%) recommendations. Significant variability in LOE I and GOR A recommendations and their changes over time was observed across different cancer types. Conclusion: One-third of the current ESMO CPG recommendations are supported by the highest level of evidence. More well-designed randomized clinical trials are needed to increase the proportion of LOE I and GOR A recommendations, ultimately leading to improved outcomes for cancer patients.

The effect of PARP inhibitors in homologous recombination proficient ovarian cancer: meta-analysis.

BRCA1/2 mutations and homologous recombination deficiency (HRD) predispose to increased sensitivity to poly(ADP-ribose)polymerase (PARP) inhibitor treatment. Our aim was to evaluate the PARP inhibitors effect on progression free survival (PFS) in a subpopulation with homologous recombination proficient status (HRD-BRCA-). A systematic literature search was performed for all studies reporting on the effect of PARP inhibitors regarding PFS in the HRD-BRCA- subpopulation, in patients with epithelial ovarian, tubal or primary peritoneal cancers (EOC). Five studies were included, enrolling a population of 3413 patients, with 1070 of them being HRD-BRCA-. PARP inhibitors were effective in the treatment of EOC, regardless of HRD and BRCA status or line of therapy. The estimated pooled effect hazard ratio (HR), assessing PFS for PARP inhibitors compared with control, was 0.76 (95% CI: 0.65-0.88, I2 = 46%) in the HRD-BRCA- subpopulation. Comparing both subpopulations with HRD positive status (HRD+ BRCA+, HRD+ BRCA-) versus the HRD-BRCA-subpopulation, we have found statistically significant differences in the effect on PFS (P < 0.05 for every interaction test) favouring HRD positive subpopulations (HRD+ BRCA+, HRD+ BRCA-). In the HRD-BRCA- subpopulation of patients, PARP inhibitors used as the second- or later-line of therapy showed more pronounced effect then when given as first line treatment (P = 0.04). Treatment of EOC with PARP inhibitors showed a significant effect regarding PFS in the HRD-BRCA- subpopulation, although a much higher benefit was evident for patients with HRD+ status (HRD+ BRCA+ and HRD+ BRCA-). In the HRD- subpopulation second line PARP inhibitor treatment showed greater benefit compared to first line PARP inhibitor treatment.

Comparison of media and academic attention of recently published positive and neutral or negative randomized cardiovascular clinical trials.

BACKGROUND: Citations are used to assess the importance of authors, articles and journals in the scientific community, but do not examine how they affect general public journal readership. The Altmetric Attention Score (AAS) is a new metric for measuring media attention of the published paper. METHODS: We examined cardiovascular (CV) randomized clinical trials (RCTs), published in the 3 highest Web of Science Impact Factor journals (Journal Citation Reports 2019: category "Medicine, General & Internal") and in the 3 highest Web of Science Impact Factor CV journals (Journal Citation Reports 2019: category "Cardiac & Cardiovascular Systems"), through the calendar year of 2017, 2018 and 2019. The primary outcomes were the assessment of the difference between number of citations and AAS among positive and negative CV RCTs. RESULTS: Among the included 262 RCTs, more positive CV RCTs were published (p = 0.002). There was no significant statistical difference between the positive and negative trials, considering the number of citations (p = 0.61). Interestingly, positive trials had a tendency towards a higher AAS (p = 0.058). The correlation between the AAS and the number of citations was moderate positively correlated (ρ = 0.47, p < 0.001). CONCLUSION: We did not find any differences between CV RCTs with positive vs CV RCTs with negative results considering the number of their citations. A tendency towards a higher AAS among positive CV RCTs could indicate higher activity on social media regarding CV trials with positive results. A higher number of published positive CV RCTs among all published CV RCTs could indicate the presence of publication bias but further investigation of unpublished RCTs in trial registries (e.g., clinicaltrials.gov) is needed.