Bias in reporting of endpoints of efficacy and toxicity in randomized clinical trials (RCTs) for women with breast cancer (BC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6043-6043
Author(s):  
Francisco Emilio Vera Badillo ◽  
Roman Shapiro ◽  
Alberto Ocana ◽  
Eitan Amir ◽  
Ian Tannock
Keyword(s):  
Randomized Clinical Trials ◽  
Phase Iii ◽  
Funding Source ◽  
Industry Funding ◽  
Quality Of Reporting ◽  
Rational Therapy ◽  
Secondary Endpoints ◽  
Background Phase ◽  
Completeness Of Reporting

6043 Background: Phase III RCTs are designed to assess clinically important differences in endpoints that reflect benefit to patients. Accurate and unbiased reporting is essential to guide rational therapy. Here we evaluate the quality of reporting of the primary endpoint (PE) and of toxicity in RCTs for BC. Methods: PUBMED was searched from 1995-2011 to identify RCTs for BC. Scales for assessing bias in reporting of the PE and of toxicity were developed. For the PE, scales assessed whether the concluding statement of the abstract (CSAbs) was (a) based on the PE, (b) described appropriately a statistically positive or negative result for the PE, or (c) was based on secondary endpoints. Bias and completeness of reporting of toxicity was assessed using a hierarchy scale of whether reporting occurred in the CSAbs, elsewhere in the abstract, in the discussion of the article or only in the results. Association of bias with Journal Impact Factor (JIF); changes in the PE compared to protocol information in clinicaltrials.gov and funding source was also evaluated. Results: 164 trials were evaluated; 33% showed bias in reporting of the PE. The PE was more likely to be reported in the CSAbs if statistically significant [OR 5.2, 95% CI 1.9-14.3, p=0.001]. A statistically negative PE was not reported in the CSAbs in 27% of trials. Of the 30 trials where protocol information was available in clinicaltrials.gov, there were non-significant associations for the PE to show a positive result if had been changed, and for greater bias in reporting the PE if it was unchanged. 67% of studies showed bias in reporting of toxicity. Only 14% mentioned toxicity in CSAbs. When the PE was positive, bias in reporting of toxicity was more common [OR 2.0, 95% CI 1.0-3.9, p=0.04]. There was no apparent association between bias in reporting of either the PE or toxicity and JIF or funding source, but a non-significant association between change in the PE and industry funding. Conclusions: Bias in reporting of the PE is common especially for studies with a negative PE. Reporting of toxicity is poor especially for studies with a positive PE. Changing of the PE appears to be a strategy to increase the likelihood of observing a statistically significant result.

Does quality of treatment-related harms reporting affect conclusions about superiority of treatment?

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6607-6607
Author(s):  
R. S. Mhaskar ◽  
A. Kumar ◽  
H. Soares ◽  
M. Schell ◽  
B. Djulbegovic
Keyword(s):  
Randomized Clinical Trials ◽  
Standard Treatment ◽  
Reporting Quality ◽  
Phase Iii ◽  
Quality Of Reporting ◽  
Chi Square ◽  
Outcome Reporting Bias ◽  
Quality Of Treatment ◽  
Experimental Treatments

6607 Background: It is often not known if harms were considered in the overall benefit-risk evaluation in deciding about the superiority of treatments. Here we present a study examining the relationship between researchers’ conclusions about the superiority of treatment with quality of treatment-related harms reporting. Methods: We reviewed all consecutive phase III randomized clinical trials (RCTs) conducted by Southwest Oncology Group from 1960 to 2003 (117 RCTs involving 139 comparisons enrolling 58,908 patients). We extracted data on primary outcomes [overall survival (OS), event free survival (EFS)], and treatment-related mortality (TRM). We classified the quality of reporting as good, intermediate or poor. Association of superiority of treatment and harms reporting was evaluated using chi-square test and meta-analytic techniques. Results: 76% of studies (106/139) reported TRM. Of these, the quality of reporting of harms was considered as “good” in 36% (38/106) of studies, “intermediate” in 55% (58/106), and “poor” in 9% (10/106). Investigators judged experimental treatments to be superior in 34% of trials (48/139) while standard treatment was superior in 66% (91/139). TRM data was reported in 75% (36/48) of results favoring experimental treatments and 78% (70/91) of results favoring standard treatments. There was no association between superiority of a treatment and TRM reporting (p = 0.80) or quality of harms reporting (p = 0.83). The pooled hazard ratio (HR) for OS in RCTs reporting TRM was 0.94 (95% CI: 0.90, 0.99) and for RCTs not reporting TRM was 0.99 (95% CI: 0.89, 1.09) (test of heterogeneity p = 0.06). The pooled HR for EFS among RCTs reporting TRM was 0.88 (95% CI: 0.83, 0.94) and for RCTs not reporting TRM it was 1.01 (95% CI: 0.79, 1.29) (test of heterogeneity p = 0.07). Additionally, the pooled HR for OS and EFS did not show any bias in reporting of harms according to harms reporting quality. Conclusions: Investigators’ conclusion regarding the superiority of experimental or standard treatment does not appear to be associated with outcome reporting bias for harms. Investigators judge both harms and benefits when they draw conclusions about treatment superiority. No significant financial relationships to disclose.

Phase III randomized clinical trials global distribution and funding: Trends and disparities.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18563-e18563
Author(s):  
Karina Pinheiro ◽  
Mauricio Ribeiro ◽  
Luiza Lara Gadotti ◽  
Fabiane Marson ◽  
Carlos Diego Holanda Lopes ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Phase Iii ◽  
Funding Source ◽  
Pharmacological Interventions ◽  
World Region ◽  
Funding Sources ◽  
Phase Iii Clinical Trials ◽  
Disease Site ◽  
Background Phase

e18563 Background: Phase III clinical trials (PIIICT) constitute the cornerstone of the progress and development of new therapeutic strategies. However, their complexity and costs in a scenario of limited funding sources impose important limitations in their scope and reach. Methods: We searched in clinicaltrials.gov to identify PIIICT evaluating pharmacological interventions in adjuvant, neoadjuvant and metastatic settings between 2010-2020 in breast, cervix, colorectal cancer (CRC), lung, melanoma, prostate and penile cancer. Trials identified were categorized according to disease site, funding source and world region/country (R/C). Case incidence in 2020 was collected from the IARC website. Results: Of 825 clinical trials, 72.7% were industry-sponsored (IS). Trials by R/C, not including multicentric studies (61.8%): (A) USA 76 trials, 53.9% non-industry sponsored (NIS); (B) Europe/UK 112, 59.8% NIS; (C) Asia (excluding China) 62, 27.4% NIS and (D) China 183, 43.7% NIS. There was a statistically significant association between location and funding source (p= 0.0003). NIS source was detected in higher proportion of trials ongoing in regions A and B (59%). IS was statistically less frequent in uterine cervix/penis (42.8%) and CRC (49.6%) IS was significantly higher in lung and prostate trials (both 81%) (p<0.0001). Table summarizes our results by tumor sites. We also found a statistically significant association between the incidence of malignancies in the selected primary sites and the amount of registered clinical trials, overall (p<0.0001) and IS as well (p<0.0001). The database is under expansion to include other disease sites as well as other geographic areas separately (Africa, Russia, South America, India, and Oceania). Cervix and penile results were combined given their biological and epidemiological similarities. Conclusions: There is a significant disparity between the number of clinical trials and tumor prevalences as well as among the distribution of IS trials funding.[Table: see text]

scholarly journals CTNI-01. EFFECT OF STEREOTACTIC RADIOSURGERY COMPARED TO WHOLE-BRAIN RADIOTHERAPY FOR LIMITED BRAIN METASTASIS ON LONG TERM COGNITION AND QUALITY OF LIFE: A POOLED ANALYSIS OF RANDOMIZED CLINICAL TRIALS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii40-ii41
Author(s):  
Joshua Palmer ◽  
Brett Klamer ◽  
Karla Ballman ◽  
Paul Brown ◽  
Jane Cerhan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Randomized Clinical Trials ◽  
Whole Brain Radiotherapy ◽  
Pooled Analysis ◽  
Cognitive Outcomes ◽  
Phase Iii ◽  
Brain Radiotherapy ◽  
Over Time

Abstract PURPOSE We investigated the long term impact of SRS and WBRT in two large prospective phase III trials. METHODS Patients with 1–4 BMs +/- resection were randomized to SRS or WBRT. Cognitive deterioration was a drop of &gt;1 standard deviation from baseline in &gt;2/6 cognitive measures (CM). Quality of life (QOL) scores were scored 0–100 point scale. CM and QOL scores were modeled using baseline adjusted Linear Mixed Models (LMM) with uncorrelated random intercept for subject and random slopes for time. Differences over time between groups and the effect of &gt;2 cognitive scores with &gt;2 SD change from baseline were assessed. RESULTS 88 patients were included with median follow up of 24 months. We observed decreasing CM over time (SRS: 4/6; WBRT: 5/6). Mean CM was significantly higher in SRS for Total recall and Delayed Recall at 3, 6, 9, 12 months. More patients in WBRT arm declined 1 SD in &gt;1 and &gt;2 CM at the 3, 6, 9, and 12 months. A 1 SD decline in &gt;3 CM at 1 year was 21% SRS vs 47% WBRT (p=0.02). SRS had fewer patients with a 2 SD decline in &gt;1 CM at every time point. SRS had fewer patients with a 2 SD decline at &gt;2 and &gt;3 CM. WBRT had lower QOL at 3 months, but switched to SRS having lower QOL at 24 months for PWB, EWB, FWB, FactG, BR, and FactBR (p&lt; 0.05). A 2 SD decline in cognition decreased mean FWB by 6.4 units (95% CI: -11, -1.75; p=0.007) and decreased QOL by 5.1 units (95% CI: -7.7, -2.5; p&lt; 0.001). CONCLUSIONS We report the first pooled prospective study demonstrating the long term outcomes of patients with BMs after cranial radiation. WBRT was associated with worse cognitive outcomes. Impaired cognition is associated with worse QOL.

scholarly journals Brain Metastases Research 1990–2010: Pattern of Citation and Systematic Review of Highly Cited Articles

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Carsten Nieder ◽  
Anca L. Grosu ◽  
Minesh P. Mehta
Keyword(s):  
Clinical Trials ◽  
Brain Metastases ◽  
Randomized Clinical Trials ◽  
Citation Rate ◽  
Prognostic Score ◽  
Median Number ◽  
Research Activity ◽  
Secondary Endpoints ◽  
Number Of Citations

Background. High and continuously increasing research activity related to different aspects of prevention, prediction, diagnosis and treatment of brain metastases has been performed between 1990 and 2010. One of the major databases contains 2695 scientific articles that were published during this time period. Different measures of impact, visibility, and quality of published research are available, each with its own pros and cons. For this overview, article citation rate was chosen.Results. Among the 10 most cited articles, 7 reported on randomized clinical trials. Nine covered surgical or radiosurgical approaches and the remaining one a widely adopted prognostic score. Overall, 30 randomized clinical trials were published between 1990 and 2010, including those with phase II design and excluding duplicate publications, for example, after longer followup or with focus on secondary endpoints. Twenty of these randomized clinical trials were published before 2008. Their median number of citations was 110, range 13–1013, compared to 5-6 citations for all types of publications. Annual citation rate appeared to gradually increase during the first 2-3 years after publication before reaching high levels.Conclusions. A large variety of preclinical and clinical topics achieved high numbers of citations. However, areas such as quality of life, side effects, and end-of-life care were underrepresented. Efforts to increase their visibility might be warranted.

scholarly journals Comparing quality of reporting between preprints and peer-reviewed articles in the biomedical literature

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Clarissa F. D. Carneiro ◽  
Victor G. S. Queiroz ◽  
Thiago C. Moulin ◽  
Carlos A. M. Carvalho ◽  
Clarissa B. Haas ◽  
...  
Keyword(s):  
Time Lag ◽  
Life Sciences ◽  
Biomedical Literature ◽  
Quality Of Reporting ◽  
Journal Publication ◽  
Similar Range ◽  
The Difference ◽  
The Impact ◽  
Completeness Of Reporting

Abstract Background Preprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the reader’s ability to independently interpret data and reproduce findings. Methods In this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire. After that, we performed paired comparisons between preprints from bioRxiv to their own peer-reviewed versions in journals. Results Peer-reviewed articles had, on average, higher quality of reporting than preprints, although the difference was small, with absolute differences of 5.0% [95% CI 1.4, 8.6] and 4.7% [95% CI 2.4, 7.0] of reported items in the independent samples and paired sample comparison, respectively. There were larger differences favoring peer-reviewed articles in subjective ratings of how clearly titles and abstracts presented the main findings and how easy it was to locate relevant reporting information. Changes in reporting from preprints to peer-reviewed versions did not correlate with the impact factor of the publication venue or with the time lag from bioRxiv to journal publication. Conclusions Our results suggest that, on average, publication in a peer-reviewed journal is associated with improvement in quality of reporting. They also show that quality of reporting in preprints in the life sciences is within a similar range as that of peer-reviewed articles, albeit slightly lower on average, supporting the idea that preprints should be considered valid scientific contributions.

Phase III randomized trial of definitive chemoradiotherapy (CRT) with FOLFOX or cisplatin and fluorouracil in esophageal cancer (EC): Final results of the PRODIGE 5/ACCORD 17 trial.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA4003-LBA4003 ◽  
Author(s):  
Thierry Conroy ◽  
Marie-Pierre Galais ◽  
Jean Luc Raoul ◽  
Olivier Bouche ◽  
Sophie Gourgou-Bourgade ◽  
...  
Keyword(s):  
Squamous Cell ◽  
Treatment Options ◽  
Complete Response ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
Ecog Ps

LBA4003 Background: CRT is one of the best treatment options for localized EC. As new combinations are required to improve safety and survival, we launched a randomized phase II study to assess the complete response (CR) rate of CRT with FOLFOX versus 5FU/cisplatin in 97 pts with localized EC (Conroy 2010). The trial having met its objectives, it has been pursued as a phase III trial. Stratified randomization was performed centrally in a 1:1 ratio according to histological type, pretreatment weight loss in the prior 6 months (<10% vs ≥10%), ECOG PS (0 vs 1 vs 2), and center. Methods: Pts with technically unresectable cancer or those with surgical contraindications or who refused to undergo surgery were eligible. Eligibility criteria also included age >18 years (y), PS ≤ 2, previously untreated adenocarcinoma or squamous cell EC (any T, N0 or N1, M0 or M1a). The radiation dose was 50 Gy (2Gy/fr) 5 d/wk for 5 wks in both arms. In Arm A, pts received 6 bimonthly cycles (cy): oxaliplatin 85 mg/m2 d1 and leucovorin 200 mg/m2 followed by 5-FU 400 mg/m2 bolus d1 then 1,600 mg/m2 46h continuous infusion (ci) ; the first 3 cy were delivered during RT, the 3 other after. In Arm B, pts received 4 cy: cisplatin 75 mg/m2 d1 followed by 5FU 1,000 mg/m2/d ci d1-4, the first 2 cy during RT and 2 other after. The primary endpoint was PFS. Main secondary endpoints were OS, grade 3-4 toxicities, and quality of life. A total of 266 pts would provide 90% power to detect a 20% 3y-PFS difference (α=0.05). Results: 267 pts were enrolled between 10/2004 and 08/2011. Treatment cohorts were well balanced: male 81%; median age 61 y; PS 0 53%, squamous cell 85.8%, stage III 52%, IVA 6.0% and IVB 3.0%. Full treatment was delivered to 67.9% and 72.2% of pts in arms A/B, respectively. 7 toxic deaths occurred in each arm. Grade 3/4 toxicities per pt (%) in arms A/B were neutropenia 30.6/31.3, febrile neutropenia 5.3/7.0, anemia 5.4/11.0, asthenia 17.6/10.2, respectively. The median FU time was 25.3 mos. 3y-PFS was 18.2/17.4 % (HR=1.07; 95%CI =0.80-1.43) and median OS was 20.2 /17.5 m (HR=1.06; 95%CI =0.77-1.46). Conclusions: CRT with FOLFOX does not improve PFS compared to cisplatin and 5-FU and has similar toxicities.

Randomized Clinical Trials Presented at the World Congress of Endourology: How Is the Quality of Reporting?

2010 ◽  
Vol 24 (12) ◽  
pp. 2067-2073 ◽  
Author(s):  
Riccardo Autorino ◽  
Claudio Borges ◽  
Michael A. White ◽  
Fatih Altunrende ◽  
Sisto Perdoná ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
World Congress ◽  
Quality Of Reporting ◽  
The World

Abstract reporting in randomized clinical trials of acute lung injury: An audit and assessment of a quality of reporting score*

2005 ◽  
Vol 33 (9) ◽  
pp. 1937-1945 ◽  
Author(s):  
Karen E. A. Burns ◽  
Neill K. J. Adhikari ◽  
Michelle Kho ◽  
Maureen O. Meade ◽  
Rakesh V. Patel ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Randomized Clinical Trials ◽  
Quality Of Reporting ◽  
Abstract Reporting

A phase III study comparing amrubicin and cisplatin (AP) with irinotecan and cisplatin (IP) for the treatment of extended-stage small cell lung cancer (ED-SCLC): JCOG0509.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7003-7003 ◽  
Author(s):  
Yoshikazu Kotani ◽  
Miyako Satouchi ◽  
Masahiko Ando ◽  
Kazuhiko Nakagawa ◽  
Nobuyuki Yamamoto ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Severe Diarrhea ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Ecog Ps ◽  
To Receive

7003 Background: IP is the standard treatment for ED-SCLC, however often cause severe diarrhea. AP have shown promising activity in SCLC with fewer diarrhea. We conducted a phase III trial comparing AP with IP. Methods: Eligibility criteria included patients (pts) with chemotherapy-naïve, ED-SCLC, aged 20 to 70, and ECOG PS 0-1. Pts were randomized to receive either IP or AP, balancing for site, sex, and PS. IP comprised administration of I (60 mg/m2) iv on days 1, 8, and 15, and P (60 mg/m2) iv on day1,every 4 weeks. AP comprised administration of A (40 mg/m2) iv on day 1-3, and P (60 mg/m2) iv on day1, every 3 weeks. The planned sample size was 141 pts in each arm with a one-sided alpha of 5% and power of 70% and a non-inferiority margin of hazard ratio (HR) as 1.31. The primary endpoint was overall survival (OS). The secondary endpoints were response rate (RR), progression-free survival (PFS), adverse events (AEs), and quality of life (QOL). We evaluated pts’ QOL twice: at the baseline and after completion of the second course. Results: 284 pts were randomized to IP (n=142) and AP (n=142). Median age was 63, 84% were male, and 56% had PS 0. When 191pts enrolled, more febrile neutropenia (FN) was observed in AP than anticipated, and the initial dose of A was decreased from 40 mg/m2 to 35 mg/m2. At the second interim analysis conducted after the completion of patient accrual, the median OS of AP (15.0 m) was much worse than that of IP (18.3 m) and the HR (1.41; 96.3% CI, 1.03-1.93) exceeds even the non-inferiority margin, so the Data and Safety Monitoring Committee recommended early publication of the results. Median PFS was 5.7 (IP) vs. 5.2 months (AP) (HR 1.43, 95% CI, 1.13-1.82). RR was 69.5% (IP) vs. 77.9% (AP) (p=0.14). AEs in IP and AP arm were Grade 4 neutropenia (22.5% vs. 78.6%), G3-4 FN (10.7% vs. 32.1%), and G3-4 diarrhea (7.1% vs.1.4%). Proportion of improvement in physical status of QOL was 37.1%(IP) vs. 31.7%(AP), (odds ratio 0.72; 95%CI, 0.43-1.22; P=0.227). Conclusions: AP showed more bone marrow suppression than expected although it caused less diarrhea. The non-inferiority of AP to IP was not demonstrated and IP remains the standard treatment for ED-SCLC.

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