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Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour.

ABSTRACT: OBJECTIVE:Unbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments. DESIGN:Literature review, pooling analysis and correlation analysis. DATA SOURCES:PubMed, from 1 January 2010 to 30 June 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES:Eligible articles are phase III RCTs comparing anticancer agents for advanced solid tumours. Additionally, the articles should report objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) or time to progression (TTP); the treatment effect of these endpoints, OR or HR, should be based on central and local assessments. RESULTS:Of 76 included trials involving 45?688 patients, 17 (22%) trials reported their endpoints with statistically inconsistent inferences (p value lower/higher than the probability of type I error) between central and local assessments; among them, 9 (53%) trials had statistically significant inference based on central assessment. Pooling analysis presented no systematic bias when comparing treatment effects of both assessments (ORR: OR=1.02 (95% CI 0.97 to 1.07), p=0.42, I2=0%; DCR: OR=0.97 (95% CI 0.92 to 1.03), p=0.32, I2=0%); PFS: HR=1.01 (95% CI 0.99 to 1.02), p=0.32, I2=0%; TTP: HR=1.04 (95% CI 0.95 to 1.14), p=0.37, I2=0%), regardless of funding source, mask, region, tumour type, study design, number of enrolled patients, response assessment criteria, primary endpoint and trials with statistically consistent/inconsistent inferences. Correlation analysis also presented no sign of systematic bias between central and local assessments (ORR, DCR, PFS: r>0.90, p<0.01; TTP: r=0.90, p=0.29). CONCLUSIONS:No systematic bias could be found between local and central assessments in phase III RCTs on solid tumours. However, statistically inconsistent inferences could be made in many trials between both assessments.

SUBMITTER: Zhang J

PROVIDER: S-EPMC6144327 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour.

Zhang Jianrong J Zhang Yiyin Y Tang Shiyan S Jiang Long L He Qihua Q Hamblin Lindsey Tristine LT He Jiaxi J Xu Zhiheng Z Wu Jieyu J Chen Yaoqi Y Liang Hengrui H Chen Difei D Huang Yu Y Wang Xinyu X Deng Kexin K Jiang Shuhan S Zhou Jiaqing J Xu Jiaxuan J Chen Xuanzuo X Liang Wenhua W He Jianxing J

BMJ open 20180910 9

<h4>Objective</h4>Unbiased assessment of tumour response is crucial in randomised controlled trials (RCTs). Blinded independent central review is usually used as a supplemental or monitor to local assessment but is costly. The aim of this study is to investigate whether systematic bias existed in RCTs by comparing the treatment effects of efficacy endpoints between central and local assessments.<h4>Design</h4>Literature review, pooling analysis and correlation analysis.<h4>Data sources</h4>PubMe ...[more]

PMID: 30206071

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Project description:Background:In previous studies, complete-case implementation of blind independent central review has been considered unnecessary based on no sign of systematic bias between central and local assessments. In order to further evaluate its value, this study investigated evaluation status between both assessments in phase III trials of anti-cancer drugs for non-hematologic solid tumors. Methods:Eligible trials were searched in PubMed with the date of Jan 1, 2010 to Jun 30, 2017. We compared objective response rate (ORR) and disease control rate (DCR) between central and local assessments by study-level pooled analysis and correlation analysis. In pooled analysis, direct comparison was measured by the odds ratio (OR) of central-assessed response status to local-assessed response status; to investigate evaluation bias between central and local assessments, the above calculated OR between experimental (exp-) and control (con-) arms were compared, measured by the ratio of OR. Results:A total of 28 included trials involving 17,466 patients were included (28 with ORR, 16 with DCR). Pooled analysis showed central assessment reported lower ORR and DCR than local assessment, especially in trials with open-label design, central-assessed primary endpoint, and positive primary endpoint outcome, respectively. However, this finding could be found in both experimental [exp-ORR: OR=0.81 (95% CI: 0.76-0.87), P<0.01, I2=11%; exp-DCR: OR=0.90 (0.81-1.01), P=0.07, I2=42%] and control arms [con-ORR: OR=0.79 (0.72-0.85), P<0.01, I2=17%; con-DCR: OR=0.94 (0.86-1.02), P=0.14, I2=12%]. No sign of evaluation bias between two assessments was indicated through further analysis [ORR: ratio of OR=1.02 (0.97-1.07), P=0.42, I2=0%; DCR: ratio of OR=0.98 (0.93-1.03), P=0.37, I2=0%], regardless of mask (open/blind), sample size, tumor type, primary endpoint (central-assessed/local-assessed), and primary endpoint outcome (positive/negative). Correlation analysis demonstrated a high-degree concordance between central and local assessments (exp-ORR, con-ORR, exp-DCR, con-DCR: r>0.90, P<0.01). Conclusions:Blind independent central review remained irreplaceable to monitor local assessment, but its complete-case implementation may be unnecessary.

Project description:BackgroundAutomatic processes, such as attentional biases or interpretative biases, have been purported to be responsible for several psychiatric disorders. Recent reviews have highlighted that cognitive biases may be modifiable. Advances in eHealth and mHealth have been harnessed for the delivery of cognitive bias modification. While several studies have evaluated mHealth-based bias modification intervention, no review, to our knowledge, has synthesized the evidence for it. In addition, no review has looked at commercial apps and their functionalities and methods of bias modification. A review is essential in determining whether scientifically validated apps are available commercially and the proportion of commercial apps that have been evaluated scientifically.ObjectiveThe objective of this review was primarily to determine the proportion of attention or cognitive bias modification apps that have been evaluated scientifically and secondarily to determine whether the scientifically evaluated apps were commercially available. We also sought to identify commercially available bias modification apps and determine the functionalities of these apps, the methods used for attention or cognitive bias modification, and whether these apps had been evaluated scientifically.MethodsTo identify apps in the published literature, we searched PubMed, MEDLINE, PsycINFO, and Scopus for studies published from 2000 to April 17, 2018. The search terms used were "attention bias" OR "cognitive bias" AND "smartphone" OR "smartphone application" OR "smartphone app" OR "mobile phones" OR "mobile application" OR mobile app" OR "personal digital assistant." To identify commercial apps, we conducted a manual cross-sectional search between September 15 and 25, 2017 in the Apple iTunes and Google Play app stores. The search terms used to identify the apps were "attention bias\" and "cognitive bias." We also conducted a manual search on the apps with published evaluations.ResultsThe effectiveness of bias modification was reported in 7 of 8 trials that we identified in the published literature. Only 1 of the 8 previously evaluated apps was commercially available. The 17 commercial apps we identified tended to use either an attention visual search or gamified task. Only 1 commercial app had been evaluated in the published literature.ConclusionsThis is perhaps the first review to synthesize the evidence for published mHealth attention bias apps. Our review demonstrated that evidence for mHealth attention bias apps is inconclusive, and quite a few commercial apps have not been validated scientifically.

Project description:BACKGROUND:The current coronavirus disease (COVID-19) pandemic is holding the world in its grip. Epidemiologists have shown that the mortality risks are higher when the health care system is subjected to pressure from COVID-19. It is therefore of great importance to maintain the health of health care providers and prevent contamination. An important group who will be required to treat patients with COVID-19 are health care providers during semiacute surgery. There are concerns that laparoscopic surgery increases the risk of contamination more than open surgery; therefore, balancing the safety of health care providers with the benefit of laparoscopic surgery for the patient is vital. OBJECTIVE:We aimed to provide an overview of potential contamination routes and possible risks for health care providers; we also aimed to propose research questions based on current literature and expert opinions about performing laparoscopic surgery on patients with COVID-19. METHODS:We performed a scoping review, adding five additional questions concerning possible contaminating routes. A systematic search was performed on the PubMed, CINAHL, and Embase databases, adding results from gray literature as well. The search not only included COVID-19 but was extended to virus contamination in general. We excluded society and professional association statements about COVID-19 if they did not add new insights to the available literature. RESULTS:The initial search provided 2007 records, after which 267 full-text papers were considered. Finally, we used 84 papers, of which 14 discussed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Eight papers discussed the added value of performing intubation in a low-pressure operating room, mainly based on the SARS outbreak experience in 2003. Thirteen papers elaborated on the risks of intubation for health care providers and SARS-CoV-2, and 19 papers discussed this situation with other viruses. They conclude that there is significant evidence that intubation and extubation is a high-risk aerosol-producing procedure. No papers were found on the risk of SARS-CoV-2 and surgical smoke, although 25 papers did provide conflicting evidence on the infection risk of human papillomavirus, hepatitis B, polio, and rabies. No papers were found discussing tissue extraction or the deflation risk of the pneumoperitoneum after laparoscopic surgery. CONCLUSIONS:There seems to be consensus in the literature that intubation and extubation are high-risk procedures for health care providers and that maximum protective equipment is needed. On the other hand, minimal evidence is available of the actual risk of contamination of health care providers during laparoscopy itself, nor of operating room pressure, surgical smoke, tissue extraction, or CO2 deflation. However, new studies are being published daily from current experiences, and society statements are continuously updated. There seems to be no reason to abandon laparoscopic surgery in favor of open surgery. However, the risks should not be underestimated, surgery should be performed on patients with COVID-19 only when necessary, and health care providers should use logic and common sense to protect themselves and others by performing surgery in a safe and protected environment.

Project description:Wilms tumour (WT) patients with a localised completely necrotic nephroblastoma after preoperative chemotherapy are a favourable outcome group. Since the introduction of the SIOP 2001 protocol, the SIOP- Renal Tumour Study Group (SIOP-RTSG) has omitted radiotherapy for such patients with low-risk, local stage III in an attempt to reduce treatment burden. However, for metastatic patients with local stage III, completely necrotic WT, the recommendations led to ambiguous use. The purpose of this descriptive study is to demonstrate the outcomes of patients with metastatic, completely necrotic and local stage III WT in relation to the application of radiotherapy or not. all metastatic patients with local stage III, completely necrotic WT after 6 weeks of preoperative chemotherapy who were registered in the SIOP 2001 study were included in this analysis. The pattern of recurrence according to the usage of radiation treatment and 5 year event-free survival (EFS) and overall survival (OS) was analysed. seven hundred and three metastatic WT patients were registered in the SIOP 2001 database. Of them, 47 patients had a completely necrotic, local stage III WT: 45 lung metastases (11 combined localisations), 1 liver/peritoneal, and 1 tumour thrombus in the renal vein and the inferior vena cava with bilateral pulmonary arterial embolism. Abdominal radiotherapy was administered in 29 patients (62%; 29 flank/abdominal irradiation and 9 combined with lung irradiation). Eighteen patients did not receive radiotherapy. Median follow-up was 6.6 years (range 1-151 months). Two of the 47 patients (4%) developed disease recurrence in the lung (one combined with abdominal relapse) and eventually died of the disease. Both patients had received abdominal radiotherapy, one of them combined with lung irradiation. Five-year EFS and OS were 95% and 95%, respectively. the outcome of patients with stage IV, local stage III, completely necrotic Wilms tumours is excellent. Our results suggest that abdominal irradiation in this patient category may not be of added value in first-line treatment, consistent with the current recommendation in the SIOP-RTSG 2016 UMBRELLA protocol.

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Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour.

Publications

Systematic bias between blinded independent central review and local assessment: literature review and analyses of 76 phase III randomised controlled trials in 45 688 patients with advanced solid tumour.

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