Role of Pilot Trials in RCT Quality and Feasibility

Large randomized controlled trials are crucial for assessing intervention efficacy but often fail or remain incomplete due to feasibility issues. Pilot trials may increase full-scale trial success but come with methodological challenges, including the debate over estimating efficacy. Design modifications post-pilot are common but their impact on feasibility is not fully understood. Furthermore, the association between pilot trials and the quality of full-scale trials is underexplored. This meta-epidemiological study tackles these challenges by assembling two datasets. We searched PubMed for pilot trials published between 2005 and 2018 and their subsequent full-scale trials. The meta-analysis of the full-scale trials was then used to identify other full-scale trials on the same research topic but without a pilot trial. In Paper 1, we analyzed 248 pairs of pilot and full-scale trials. Full-scale trials with a significant pilot trial were 2.72 times more likely to find a significant result for the primary efficacy outcome than those with a non-significant pilot trial. In 73% of the pairs, the pilot trial yielded a larger point estimate than the full-scale trial, yet in 87% of cases, the pilot's 95% confidence interval encompassed the full-scale point estimate. Paper 2 analyzed 249 pilot and full-scale trial pairs. Using feasibility progression criteria in pilot trials and maintaining the same masking status as the full-scale trial may improve the chances of successful screening, whereas adding extra content to the intervention, changing to active or more frequent control, and altering follow-up lengths and visits may decrease the chances of retaining participants in full-scale trials. In Paper 3, 58 full-scale trials with a pilot trial and 151 full-scale trials without were identified from 47 meta-analyses. A pilot trial's presence was associated with lower risk of bias in full-scale trial random sequence generation, allocation concealment, and participants/researchers masking, but not outcome assessment masking, incomplete outcome data, and selective reporting. Pilot trials can offer early signals on intervention efficacy. Researchers and funders should weigh both the data from pilot trials and proposed design modifications when evaluating full-scale trials. Pilot trials may improve the quality of ensuing full-scale trials and warrant more frequent consideration

Comparing knowledge, accessibility, and use of evidence-based chronic disease prevention processes across four countries

<p>Background: Evidence-based chronic disease prevention (EBCDP) effectively reduces incidence rates of many chronic diseases, but contextual factors influence the implementation of EBCDP worldwide. This study aims to examine the following contextual factors across four countries: knowledge, access, and use of chronic disease prevention processes.</p><p>Methods: In this cross-sectional study, public health practitioners (N = 400) from Australia (n = 121), Brazil (n = 76), China (n = 102), and the United States (n = 101) completed a 26-question survey on EBCDP. One-way ANOVA and Pearson's Chi-Square tests were used to assess differences in contextual factors of interest by country.</p><p>Results: Practitioners in China reported less knowledge of EBCDP processes (p < 0.001) and less use of repositories of evidence-based interventions, than those from other countries (p < 0.001). Academic journals were the most frequently used method for accessing information about evidence-based interventions across countries. When selecting interventions, Brazilian and Chinese practitioners were more likely to consider implementation ease while the Australian and United States practitioners were more likely to consider effectiveness (p < 0.001).</p><p>Conclusions: These findings can help inform and improve within and across country strategies for implementing EBCDP interventions.</p

Predicting peritoneal carcinomatosis of gastric cancer: A simple model to exempt low-risk patients from unnecessary staging laparoscopy

BackgroundPeritoneal carcinomatosis (PC) of gastric cancer indicates a poor outcome and is mainly diagnosed by staging laparoscopy (SL). This study was designed to develop a risk stratification model based on the number of risk factors to exempt low-risk patients from unnecessary SL.MethodsThis was a retrospective cohort study based on a single institution between January 2015 and December 2019. SL is indicated for patients of advanced locoregional stage, and clinicopathologic characteristics of 535 consecutive patients were included. PC-associated variables were identified by logistic regression analysis. A risk stratification model based on the number of risk factors was constructed, and we defined its predictive value with a receiver operating characteristic (ROC) curve and negative predictive value.ResultsIn total, 15.9% of included patients were found to have PC during SL. Borrmann type IV, elevated CA125, and tumour diameter ≥5 cm were independent risk factors of PC. These three factors combined with cT4 were selected as predictive factors, and the number of predictive variables was significantly related to the possibility of PC (2.0%, 12.8%, 20.0%, 54.2%, and 100%, respectively). When the cutoff value is more than one predictive factor, the negative predictive value is 98.0%, with an area under the curve of 0.780. This model could exempt 29.8% of unnecessary SL compared to the indication of the current NCCN guideline.ConclusionsWe constructed a simple model to predict the probability of PC using the number of predictive factors. It is recommended that patients without any of these factors should be exempt from SL

Developing a survey tool to assess implementation of evidence-based chronic disease prevention in public health settings across four countries

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TfR1 binding with H-ferritin nanocarrier achieves prognostic diagnosis and enhances the therapeutic efficacy in clinical gastric cancer

H-ferritin (HFn) nanocarrier is emerging as a promising theranostic platform for tumor diagnosis and therapy, which can specifically target tumor cells via binding transferrin receptor 1 (TfR1). This led us to investigate the therapeutic function of TfR1 in GC. The clinical significance of TfR1 was assessed in 178 GC tissues by using a magneto-HFn nanoparticle-based immunohistochemistry method. The therapeutic effects of doxorubicin-loaded HFn nanocarriers (HFn-Dox) were evaluated on TfR1-positive GC patient-derived xenograft (GC-PDX) models. The biological function of TfR1 was investigated through in vitro and in vivo assays. TfR1 was upregulated (73.03%) in GC tissues, and reversely correlated with patient outcome. TfR1-negative sorted cells exhibited tumor-initiating features, which enhanced tumor formation and migration/invasion, whereas TfR1-positive sorted cells showed significant proliferation ability. Knockout of TfR1 in GC cells also enhanced cell invasion. TfR1-deficient cells displayed immune escape by upregulating PD-L1, CXCL9, and CXCL10, when disposed with IFN-γ. Western blot results demonstrated that TfR1-knockout GC cells upregulated Akt and STAT3 signaling. Moreover, in TfR1-positive GC-PDX models, the HFn-Dox group significantly inhibited tumor growth, and increased mouse survival, compared with that of free-Dox group. TfR1 could be a potential prognostic and therapeutic biomarker for GC: (i) TfR1 reversely correlated with patient outcome, and its negative cells possessed tumor-aggressive features; (ii) TfR1-positive cells can be killed by HFn drug nanocarrier. Given the heterogeneity of GC, HFn drug nanocarrier combined with other therapies toward TfR1-negative cells (such as small molecules or immunotherapy) will be a new option for GC treatment

Laparoscopic versus open gastrectomy for elderly local advanced gastric cancer patients: study protocol of a phase II randomized controlled trial

Abstract Background Gastric cancer is one of the most common malignant tumors worldwide. With the rapid aging of global population, the number of elderly patients with local advanced gastric cancer is increasing. Surgery is the essential treatment for local advanced gastric cancer. However, elderly patients are at high risk of postoperative complications due to reduced functional reserve and increased comorbidities. Laparoscopic gastrectomy may be a promising surgery approach for elderly patients but its benefits remain controversial. We therefore proposed this randomized trial to evaluate the safety and efficacy of laparoscopic versus open gastrectomy for local advanced gastric cancer in patients aged 70 and above. Methods The current study has a randomized, parallel controlled, single-center, open-label, superiority design with two arms. A sample of 180 local advanced gastric cancer patients aged 70 and above will be recruited in Peking University Cancer Hospital and Institute. Participants will be randomized to either receive open or laparoscopic gastrectomy. The primary outcome is surgical safety, including complication rate, reoperation rate, readmission rate, and mortality rate within 30 days after surgery. The secondary endpoints include postoperative rehabilitation status, one-year postoperative life quality, three-year overall and disease-free survival. Assessments will take place at baseline (before random assignment), at 30 days, one-year, and three-year after the surgery. The study has been approved by an ethical review board. Discussion We hypothesized that laparoscopic gastrectomy is superior to open gastrectomy in terms of perioperative safety for local advanced gastric cancer patients aged 70 and above. If this hypothesis is statistically proved, the rational introduction of minimally invasive surgery technique in traditional gastrectomy can help improve the surgical safety for elderly patients, reduce patient financial burden, shorten hospital stay, and improve hospital beds turnover rate. Our research data will also provide high quality clinical evidence and data support for the conduction of multicenter phase III clinical trials. Trial registration The study has been prospectively registered in ClinicalTrial.gov (NCT03564834)

Global burden prediction of gastric cancer during demographic transition from 2020 to 2040

Abstract. Background:. Despite the decline in the incidence and mortality rates of gastric cancer (GC), the impact of demographic transition on the global burden of GC remains unclear. The current study aimed to estimate the global disease burden through 2040 by age, sex, and region. Methods:. GC data for incident cases and deaths by age group and sex were taken from The Global Cancer Observatory (GLOBOCAN) 2020. The incidence and mortality rates were predicted through 2040 by fitting a linear regression model over the most recent trend period with the Cancer Incidence in Five Continents (CI5) data. Results:. The global population will grow to 9.19 billion by 2040, accompanied by increasing population ageing. The incidence and mortality rates of GC will show a persistent decrease, with an annual percent change of –0.57% for males and –0.65% for females. East Asia and North America will have the highest and lowest age standardized rates, respectively. A slowdown in the growth of incident cases and deaths will be observed worldwide. The proportion of young and middle-aged individuals will decline, while the percentage of the elderly will increase, and the number of males will be almost twice the number of females. East Asia and high human development index (HDI) regions will be heavily burdened by GC. East Asia had 59.85% of the new cases and 56.23% of deaths in 2020; these will increase to 66.93% and 64.37% by 2040, respectively. The interaction between population growth, the change in ageing structure and the decline in incidence and mortality rates will lead to an increased burden of GC. Conclusions:. Ageing and population growth will offset the decline in the incidence and mortality rate of GC, resulting in a substantial increase in the number of new cases and deaths. The age structure will continue to change, especially in high HDI regions, requiring more targeted prevention strategies in the future