Oncology Randomized Controlled Trials Research Articles

Use of Placebo in Urologic Oncology Randomized Controlled Trials.

Use of placebo in oncology randomized controlled trials (RCT) is ethically controversial. Placebo may introduce bias, as toxicity profiles of treatment arms can inadvertently unblind subjects and investigators. We investigated the use of placebo in urologic oncology RCTs, hypothesizing that most placebo-controlled trials are effectively unblinded, either explicitly with open-label design or implicitly due to large differences in adverse events (AE) or oncologic outcomes. Urologic oncology RCTs utilizing placebo were identified via ClinicalTrials.gov. Interventional prostate, bladder/urothelial, and renal cancer trials from 2014 to 2024 were included. Subject incompletion, all-cause mortality, AE rates, and serious AE (SAE) rates were identified and compared between placebo and active arms using χ2 and Fisher's exact tests. Sixty studies met inclusion criteria and included 66 placebo arms with 12,918 subjects and 81 active arms with 16,098 subjects. There was no significant difference in incompletion rates between placebo and active arms. Subjects enrolled in active arms reported statistically significant higher SAE and AE rates compared to those in placebo arms across the majority of physiological domains, including 18/24 domains for SAEs and 13/24 for AEs. This relationship persisted in sensitivity analyses where unblinded trials were excluded. In urologic oncology placebo-controlled RCTs, active arms are associated with significantly higher rates of AEs and SAEs compared with placebo arms. These findings indicate a strong possibility that true blinding is not possible in oncology RCTs, even with optimal study design, and serve to better inform future clinical trial design and implementation challenges in employing placebo control.

Analysis of Health-Related Quality of Life Reporting in Phase III RCTs of Advanced Genitourinary Tumors

Background: As recommended in the European Society for Medical Oncology (ESMO) guidelines, assessment of health-related quality of life (HRQoL) should be a relevant endpoint in randomized controlled trials (RCTs) testing new anticancer therapies. However, previous publications by our group and others revealed a frequent underestimation and underreporting of HRQoL results in publication of RCTs in oncology. Herein, we systematically reviewed HRQoL reporting in RCTs testing new treatments in advanced prostate, kidney and urothelial cancers and published between 2010 and 2022. Methods: We searched PubMed RCTs testing novel therapies in genitourinary (GU) cancers and published in fifteen selected journals (Annals of Oncology, BMC Cancer, British Journal of Cancer, Cancer Discovery, Clinical Cancer Research, Clinical Genitourinary cancer, European Journal of Cancer, European Urology, European Urology Oncology, JAMA, JAMA Oncology, Journal of clinical Oncology, Lancet, Lancet Oncology and The New England Journal of Medicine). We excluded trials investigating exclusively best supportive care or behavioral intervention, as well as subgroup or post hoc analyses of previously published trials. For each RCT, we investigated whether HRQoL assessment was performed by protocol and if results were reported in the primary manuscript or in a secondary publication. Results: We found 85 eligible trials published between 2010 and 2022. Only 1/85 RCTs (1.2%) included HRQoL among primary endpoints. Of note, 25/85 (29.4%) RCTs did not include HRQoL among study endpoints. HRQoL results were non-disclosed in 56/85 (65.9%) primary publications. Only 18/85 (21.2%) publications fulfilled at least one item of the CONSORT-PRO checklist. Furthermore, 14/46 (30.4%) RCTs in prostate cancer, 12/25 (48%) in kidney cancer and 3/14 (21.4%) in urothelial cancer reported HRQoL data in primary publications. Next, HRQoL data were disclosed in primary manuscripts of 12/32 (37.5%), 5/13 (38.5%), 5/16 (31.3%) and 5/15 (33.3%) trials evaluating target therapies, chemotherapy, immunotherapy and new hormonal agents, respectively. Next, we found that HRQoL data were reported in 16/42 (38%) and in 13/43 (30.2%) positive and negative trials, respectively. Finally, the rate of RCTs reporting HRQoL results in primary or secondary publications was 55.3% (n = 47/85). Conclusions: Our analysis revealed a relevant underreporting of HRQoL in RCTs in advanced GU cancers. These results highlight the need to dedicate more attention to HRQoL in RCTs to fully assess the value of new anticancer treatments.

Allocation of authorship and patient enrollment among global clinical trials in oncology.

Oncology randomized controlled trials (RCTs) are increasingly global in scope. Whether authorship is equitably shared between investigators from high-income countries (HIC) and low-middle/upper-middle incomes countries (LMIC/UMIC) is not well described. The authors conducted this study to understand the allocation of authorship and patient enrollment across all oncology RCTs conducted globally. A cross-sectional retrospective cohort study of phase 3 RCTs (published 2014-2017) that were led by investigators in HIC and recruited patients in LMIC/UMIC. During 2014-2017, 694 oncology RCTs were published; 636 (92%) were led by investigators from HIC. Among these HIC-led trials, 186 (29%) enrolled patients in LMIC/UMIC. One-third (33%, 62 of 186) of RCTs had no authors from LMIC/UMIC. Forty percent (74 of 186) of RCTs reported patient enrollment by country; in 50% (37 of 74) of these trials, LMIC/UMIC contributed <15% of patients. The relationship between enrollment and authorship proportion is very strong and is comparable between LMIC/UMIC and HIC (Spearman's ρ LMIC/UMIC 0.824, p<.001; HIC 0.823, p<.001). Among the 74 trials that report country enrollment, 34% (25 of 74) have no authors from LMIC/UMIC. Among trials that enroll patients in HIC and LMIC/UMIC, authorship appears to be proportional to patient enrollment. This finding is limited by the fact that more than half of RCTs do not report enrollment by country. Moreover, there are important outliers as a significant proportion of RCTs had no authors from LMIC/UMIC despite enrolling patients in these countries. The findings in this study reflect a complex global RCT ecosystem that still underserves cancer control outside high-income settings.

The Aetion Coalition to Advance Real-World Evidence through Randomized Controlled Trial Emulation Initiative: Oncology.

Legislative and technological advancements over the past decade have given rise to the proliferation of healthcare data generated from routine clinical practice, often referred to as real-world data (RWD). These data have piqued the interest of healthcare stakeholders due to their potential utility in generating evidence to support clinical and regulatory decision making. In the oncology setting, studies leveraging RWD offer distinct advantages that are complementary to randomized controlled trials (RCTs). They also permit the conduct of investigations that may not be possible through prospective designs due to ethics or feasibility. Despite its promise, the use of RWD for the generation of clinical evidence remains controversial due to concerns of unmeasured confounding and other sources of bias that must be carefully addressed in the study design and analysis. To facilitate a better understanding of when RWD can provide reliable conclusions on drug effectiveness, we seek to conduct 10 RWD-based studies that emulate RCTs in oncology using a systematic, protocol-driven approach described herein. Results of this investigation will help inform clinical, scientific, and regulatory stakeholders on the applications of RWD in the context of product labeling expansion, drug safety, and comparative effectiveness in oncology.

Globalization of oncology clinical trials: Which lower-middle and upper-middle income countries are participating?

e13512 Background: With globalization of cancer research, many randomized controlled trials (RCTs) led by high income countries (HICs) are now enrolling patients from lower- and upper-middle income countries (LMICs/UMICs). While enrolling diverse global populations promotes research collaborations, there are unanswered questions about which countries participate in RCTs and how this may contribute to global research capacity. Here we describe which UMICs/LMICs participate in RCTs led by HICs. Methods: The study cohort was identified from a database of all oncology RCTs (systemic/surgery/RT) published globally during 2014-2017. The study cohort was restricted to RCTs led by HICs which enrolled participants from LMIC/UMICs. We used a bibliometric approach to explore whether the participation of UMICs/LMICs in RCTs led by HICs was as expected based on other measures of cancer research activity. Country-level bibliometric output for 2007-2017 was identified in the Web of Science database. We compared RCT participation (i.e. % of RCTs in our cohort that each LMIC/UMIC participated in) with country-level cancer research bibliometric output (i.e. % of total cancer research bibliometric output from the same group of countries that came from a specific LMIC/UMIC). Results: The global cohort included 694 RCTs; 636 (92%) of which were led by HICs. Among the HIC-led trials, 187 (29%) enrolled patients in LMICs (n=84) and/or UMICs (n=182); this formed the study cohort. The most common participating LMICs were India (50% of trials, 42/84), Ukraine (46%, 39/84), Philippines (25%, 21/84), and Egypt (14%, 12/84). The most common participating UMICs were Russian Federation (63% of trials, 115/182), Brazil (50%, 91/182), Romania (34%, 61/182), China (31%, 56/182), Mexico (31%,56/182) and South Africa (30%, 54/182). Several LMICs are over-represented in our cohort of RCTs based on proportional cancer research bibliometric output: Ukraine (46% of RCTs but 2% of cancer research bibliometric output), Philippines (25% RCTs, 1% output), Georgia (8% RCTs, 0.2% output). Several UMICs are also over-represented in the study cohort of RCTs including Russia (63% RCTs, 2% output), Romania (34% RCTs, 2% output), Mexico (31% RCTs, 2% output) and South Africa (30% RCTs, 1% output). The inverse relationship was seen for China (31% RCTs, 69% output). Conclusions: A substantial proportion of RCTs led by HICs enroll patients in LMICs/UMICs. The LMICs/UMICs which participate in these trials are not as one would expected based on overall cancer bibliometric output as a surrogate for research ecosystem maturity. Reasons for this apparent discordance and how these data may inform future capacity strengthening activities require further study.

Informative censoring due to missing data in quality of life was inadequately assessed in most oncology randomized controlled trials

Objective We aimed to systematically characterize reporting missing quality of life (QoL) data in oncology randomized controlled trials (RCTs) and to estimate prevalence of adequate reporting according to existing guidelines.Study Design and Setting This cross-sectional analysis includes all articles on anti-cancer drugs tested in RCTs in six high impact medical/oncology journals, published between January 2015 and May 2020, that reported QoL outcomes. From 1942 identified articles, 215 (11%) met inclusion criteria. Data abstracted included whether compliance for QoL assessment were reported, whether results from a missing data statistical analysis were reported, whether articles met current recommendations for reporting missing data in QoL assessments.Results The results from a missing data statistical analysis were available in 22 trials (10.2%). Overall, 16 trials (7.4%) met current recommendations for reporting missing data in QoL assessments. Articles specifically reporting on QoL or patient reported outcomes were more likely to meet recommendations than other reports (P < 0.0001).Conclusion This systematic cross-sectional study found that most oncology RCTs reporting on QoL do not report adequately on missing data in QoL, with only 7.4% of trials meeting current reporting guidelines. The possibility of informative censoring, therefore, cannot be assessed in most of trials.

Lack of pre-planned financial outcomes evaluation in phase 3 cancer trials.

e18826 Background: New cancer treatments have the potential to cause economic stress at the personal and societal level. Little is known on the evaluation of financial outcomes in clinical trials. We hypothesized that randomized controlled trials (RCTs) are unlikely to have pre-planned analyses to look at economic outcomes that address financial toxicity to patients and cost-effectiveness to society. Methods: Interventional therapeutic-intent phase 3 cancer-specific RCTs were identified through ClinicalTrials.gov. Pre-planned economic outcomes addressing financial toxicity or cost-effectiveness were identified. Results: We identified 1,069 interventional phase 3 oncology RCTs. Overall, 101 (9.4%) had pre-planned to evaluate quality of life using the European Organization for Research and Treatment of Cancer Quality of Life (QOL) Questionnaire (EORTC QLQ-C30) instrument, of which a single question (Q28) relates to financial toxicity. However, only ten (0.94%) trials included pre-planned financial/economic endpoints; all were secondary endpoints. Among those planning to evaluate economic outcomes, 6/10 planned to collect data and report on financial distress using Q28 on EORTC QLQ-C30 and 3/10 pre-planned performing cost-effectiveness analyses. One study planned to perform an economic evaluation, including health utilities, as measured by the EuroQol-Five Dimension (EQ-5D) Questionnaire. All ten trials were industry–sponsored, and two were co-sponsored by a National Cancer Institute (NCI) cooperative group. The majority (8/10) were superiority-designed trials, and 6/10 included progression-free survival as the primary endpoint. The majority (6/10) assessed targeted therapy as the primary intervention. Multinational enrollment was predominant (8/10). Of the 10 trials, nine had a published manuscript. One was closed because of accrual issues. Among the six trials that had pre-specified reporting on financial distress, two published on financial toxicity. Of the two trials that had a priori planned to do a cost-effective analysis, one was published. However, overall 3/9 had published a cost-effective analysis. Conclusions: Less than one percent of oncology RCTs have pre-specified plans to evaluate economic outcomes associated with personal financial distress or cost-effectiveness. For the trials that had pre-planned reporting on financial toxicity, the instrument used to evaluate financial toxicity is a single question which has not been validated as a standalone assessment. Cost-effectiveness analyses were more likely to be published than on financial toxicity and were often completed as a post-hoc analysis. Given that many newly investigated therapies increase the financial burden on patients and add cost to the healthcare system more broadly, pre-planned evaluation of economic outcomes in RCTs is imperative in order to create a value-based framework in assessing new therapies.

The validity of progression-free survival (PFS) 2 as a surrogate endpoint for overall survival (OS) in randomized controlled trials (RCTs) of advanced solid tumors.

1516 Background: OS is the gold-standard endpoint for treatment efficacy in oncology RCTs. However, prolonged follow-up is required to obtain mature data, which impedes regulatory approval of potentially beneficial therapies. Furthermore, increasing therapeutic options including cross over to investigational agents at disease progression often confound OS findings. PFS-2, defined as time from randomization to progression on second-line therapy, has been proposed as a potential surrogate endpoint for OS. Using a meta-analytic approach, we aimed to assess the association between OS and PFS-2, and its validity compared with other surrogate endpoints. Methods: We performed an electronic literature search to identify RCTs of systemic therapies that reported PFS-2 as a pre-specified endpoint with defined follow up protocols. Articles were screened for eligibility and outcome data were extracted. Correlations in the relative treatment difference between treatment arms for OS vs PFS-2, PFS-1, and objective response rate (ORR) were assessed as the comparison of hazard ratios (HR) and odds ratio (OR) respectively. Results: 38 eligible RCTs comprising of 44 analysis units, with 19,031 patients across 8 unique tumor types were identified. The majority received targeted therapies (72.2%), followed by immunotherapy (IO; 26.3%). The correlations of HR-OS/HR-PFS-2, HR-OS/HR-PFS-1 and HR-OS/OR-ORR were r = 0.67 (95% CI 0.08-0.69), r = 0.12 (95% CI 0.00-0.13) and r = 0.21 (95% CI 0.00-0.33) respectively. Correlations between OS with surrogates was assessed in different subgroups according to post-progression survival times (SPP), types of treatment agents and rate of subsequent therapy after progression (table). Conclusions: Across diverse tumors and therapies, treatment effect on PFS-2 has modest to strong correlation with OS, but poor correlations were observed between OS-PFS-1 and OS-ORR respectively. Across all subgroups, PFS-2 performs consistently better than traditional surrogates of PFS-1 and ORR, validating and providing support for use in future RCTs.[Table: see text]

Methodology, results, and publication of oncology clinical trials: Insights from all the world’s randomized controlled trials (RCTs) 2014-2017.

2019 Background: Clinical cancer research is now a global effort. Most published overviews of oncology trials are restricted to a specific disease site or cohort of high-profile journals. Here we describe authorship, trial characteristics, design, and results of all oncology RCTs published globally during 2014-2017. Methods: A structured literature search was designed using PUBMED to identify all RCTs evaluating anti-cancer therapies published during 2014-2017. Data were captured regarding authorship, participants, study characteristics, design, and results. Among superiority RCTs that met the primary endpoint (i.e. statistically “positive”), we calculated the ESMO-MCBS to identify trials with substantial clinical benefit (MCBS scores 4/5 or A/B). Outcomes were compared with Chi Square or Fisher’s Exact tests. Results: The study cohort included 694 RCTs. The most common cancers evaluated were breast (17%, 121/694), lung (15%, 104/694) and colorectal (8%, 58/694). Treatment intent was curative, adjuvant/neoadjuvant, and palliative in 10% (68/694), 25% (176/694), and 65% (448/694) of trials respectively. Median sample size was 443 (IQR 246-718). Seventy percent (488/694) of RCTs were supported by industry; 87% (601/694) of experimental arms tested systemic therapy. Ninety-two percent (636/694) of RCTs were led by investigators in 28 high-income countries; the most common countries leading these trials were US (27%, 174/636), France (10%, 64/636), Germany (10%, 62/636), Japan (9%, 59/636), and UK (9%, 57/636). The most common primary endpoints were PFS (32%, 220/694), OS (31%, 215/694), and DFS (11%, 79/694); Forty-six percent of all trials (318/694) met their primary endpoint. Among superiority trials with “positive” results, 33% met ESMO-MCBS threshold for substantial clinical benefit. The median impact factor (IF) of journals which published the overall study cohort of trials was 21 (IQR 7-27); trials meeting their primary endpoint were published in higher profile journals (median IF 25 vs 18, p &lt; 0.001). Conclusions: At the global level, oncology clinical trials are dominated by high-income countries and study diseases which do not necessarily reflect the global burden of cancer. The vast majority of trials are funded by industry and only one third of “positive” trials meet ESMO-MCBS threshold for substantial clinical benefit.

Age disparities among cancer clinical trial participants: The role of industry sponsorship.

11527 Background: Randomized controlled trials (RCTs) in oncology, which often establish the standard of care for cancer patients, do not necessarily enroll trial participants representative of the broader patient population. We sought to characterize age disparities for cancer patients enrolled on RCTs, and asked whether certain trial-related factors (such as industry sponsorship) predispose trials to larger age disparities between trial enrollees and the general population. Methods: All phase 3 RCTs in clinical oncology with results available were identified through ClinicalTrials.gov. Only randomized multi-arm trials assessing a therapeutic intervention for cancer patients were included. The scope of trials was limited to breast, colorectal, lung, and prostate disease sites. Trial participant median ages were compared to national SEER data for population median ages by disease site. Results: Three-hundred and two trials met inclusion criteria. For all trials, the trial median age was an average 6.23 years younger than the population median age (95% CI: -5.55 to -6.91 years, p &lt; 0.001). Trials with industry sponsorship had significantly younger trial patient populations compared with non-industry-sponsored trials (mean difference from population -6.57 vs -4.48 years, p = 0.02). Younger patients were enrolled on trials evaluating targeted agents (p = 0.04), superiority-design trials (p = 0.02), and trials utilizing a surrogate primary endpoint (p = 0.03). By disease site, lung cancer trials enrolled the youngest patients relative to the population median (-8.98 years), followed by breast (-7.76 years), colorectal (-6.96 years), and prostate (+2.66 years, p &lt; 0.001). Conclusions: Industry-funded clinical trials are associated with larger age disparities among trial participants; we believe this represents a novel finding both in clinical oncology and academic medicine more broadly. Underrepresentation of older patients on RCTs has major ramifications for the generalizability of results as well as equity of access to care; future efforts to address trial participant age disparities may focus on those trials at greatest risk for disparities based on the identified risk factors, including industry sponsorship.

A Systematic Review and Recommendation for Reporting of Surrogate Endpoint Evaluation Using Meta-analyses.

BackgroundMeta-analysis of randomized controlled trials (RCTs) has been widely conducted for the evaluation of surrogate endpoints in oncology, but little attention has been given to the adequacy of reporting and interpretation. This review evaluated the reporting quality of published meta-analyses on surrogacy evaluation and developed recommendations for future reporting.MethodsWe searched PubMed through August 2017 to identify studies that evaluated surrogate endpoints using the meta-analyses of RCTs in oncology. Both individual patient data (IPD) and aggregate data (AD) meta-analyses were included for the review.ResultsEighty meta-analyses were identified: 22 used IPD and 58 used AD from multiple RCTs. We observed variability and reporting deficiencies in both IPD and AD meta-analyses, especially on reporting of trial selection, endpoint definition, study and patient characteristics for included RCTs, and important statistical methods and results. Based on these findings, we proposed a checklist and recommendations to improve completeness, consistency, and transparency of reports of meta-analytic surrogacy evaluation. We highlighted key aspects of the design and analysis of surrogate endpoints and presented explanations and rationale why these items should be clearly reported in surrogacy evaluation.ConclusionsOur reporting of surrogate endpoint evaluation using meta-analyses (ReSEEM) guidelines and recommendations will improve the quality in reporting and facilitate the interpretation and reproducibility of meta-analytic surrogacy evaluation. Also, they should help promote greater methodological consistency and could also serve as an evaluation tool in the peer review process for assessing surrogacy research.

Improving recruitment in 11 challenging oncology RCTs using the QuinteT Recruitment Intervention.

e18635Background: Randomized controlled trials (RCTs) are the most rigorous approach for evaluating healthcare interventions, but many fail to recruit to target. Few interventions to improve recrui...

Examining the adherence to CONSORT guidelines and the reporting of the enrollment process in clinical oncology randomized controlled trials: A review of trials published between 2013 and 2015.

e14026 Background: Due to eligibility criteria, most, if not all, randomized controlled trials (RCTs) exclude patients at the outset, before randomization. Understanding which patients are excluded is important to evaluate the external validity of the results. The proportion of trials that report the entire flow diagram of patient enrollment, in accordance with the CONSORT 2010 statement, is unknown. Failure to do so makes it more difficult to discuss the generalizability of the trial findings. Methods: We performed the systematic retrieval and analysis of all phases II and III RCTs published in paper form between 2013 and 2015, in four high impact factor journals, in the field of clinical oncology. Our main objective was to determine the proportion of trials that report the number of patients assessed for eligibility before randomization. We further aimed to identify the variables that affect this reporting as well as the reasons for patient exclusion, to calculate the recruitment fraction and the number needed to screen and to determine the proportion of trials that include a discussion on the generalizability of the trial findings. Results: 462 RCTs were reviewed. Among them, 426 (92.2%) included the flow diagram in the article and 224 (48.5%) reported the number of patients assessed for eligibility. This proportion varied significantly between the journals studied, but it did not increase over time. A total of 116 (25.1%) included a discussion of generalizability. Among the trials that reported the entire enrollment process, the reason for patient exclusion could not be found in 50 (22.3%). Conclusions: There is still room for improvement in the reporting of the determinants of external validity in clinical oncology RCTs. Increasing the reporting of the enrollment process could help clinicians and health policy makers establish to whom the results of a trial apply.

Low Adequacy Between Severe Adverse Events Reporting in Oncology Phase III Trials and Expectations of the Eortc Members

ABSTRACT Aim: Reports of randomized controlled trials (RCTs) published in oncology literature are generally poorly conform to the 2004 Consolidated Standards of Reporting Trials (CONSORT ) extension for harms. We assessed the consistency in between expectations of a panel of EORTC experts regarding reporting of AEs and the actual quality of publication of RCTs. Methods: Reporting of severe-AEs, AEs related outcomes and composite AEs outcomes were reviewed in 325 oncology RCTs reports published between 2007 and 2011. An online survey was sent to the network of EORTC investigators to evaluate their expectation concerning the AE reporting. Then we compared AE reporting in phase III reports with EORTC member expectations. The characteristics of the article associated with better quality in AEs related outcomes reporting were also investigated. Results: A total of 211 EORTC members have responded to the survey. Among them, 99% thought that all lethal AEs (LAEs) should be reported and 95% thought that all AE leading to withdrawal should also be reported. Clearly described LAEs were found in 190 out of 325 RCTs (58%) and AEs leading to withdrawal were correctly reported in 53 out of 325 RCTs (16%). LAEs were more correctly reported in North-America / Intercontinental trials (p = 0.0004) and in trials testing a molecular targeted therapy (p = 0.016). AEs leading to withdrawals were more correctly reported in RCTs funded by industry (p = 0,001). Composite AEs such as “dermatologic AEs” or “neurologic AEs” were used in 95 out of 325 RCTs (29%); 25% of them were clearly described. Conclusions: There are important discrepancies between the expectations of EORTC network investigators and the reporting quality of AE reporting in oncology phase III reports. Recommendations able to improve the reporting of severe-AE reporting in oncology phase III reports are discussed. Disclosure: All authors have declared no conflicts of interest.

Involvement of low- and middle-income countries (LMCs) in oncology randomized controlled trials (RCTs).

6087 Background: Lower costs and fewer regulatory barriers make clinical trials in LMCs attractive, but little is known about characteristics of such trials and roles of investigators from LMCs. We describe trends in participation of investigators from LMCs in oncology RCTs over a decade. Methods: We used Medline to identify all RCTs published in English between January 1 1998 and December 31 2008 evaluating treatment in five solid tumours (lung, breast, colorectal, stomach, liver) with high mortality in LMCs as per GLOBOCAN 2002. Data on author affiliations and roles (first, middle or corresponding author), trial characteristics, funding and study interventions were abstracted using an electronic form. Countries were stratified into low-, middle- and high-income using World Bank data. Interventions were categorized as requiring basic, limited, enhanced or maximal resources as per the Breast Health Global Initiative classification. Logistic regression identified factors associated with investigator participation from LMCs. Results: 454 trials were identified: lung (n=177), breast (n=165), colorectal (n=82), stomach (n=29), liver (n=7). The annual number of trials published increased from 10 trials in 1998 to 86 in 2008. The proportion of trials with at least one LMC author also increased over time from 20% in 1998 to 29% in 2008 (p=0.01), but almost all LMC authors were from middle-income countries. In 17% of trials involving LMC authors, they were first or corresponding authors. 67% of trials involving LMC investigators evaluated interventions requiring enhanced or maximal resources for implementation. Factors associated with LMC participation included industry funding (OR=3.57, p&lt;0.0001), use of placebo arm (OR=2.59, p=0.02) and metastatic setting (OR=3.87, p=0.0003). Conclusions: An increasing number of oncology RCTs involve LMC investigators primarily in non-leadership roles. These trials are commonly industry-funded and often test interventions that require at least enhanced resources for implementation. To minimize concerns of exploitation and facilitate future collaboration it is crucial that interventions are locally feasible and investigators receive appropriate authorship.

Quality of the supportive and palliative oncology literature: a focused analysis on randomized controlled trials

The quality of the supportive and palliative oncology literature is unclear. We examined five indicators of study quality in the supportive and palliative oncology literature. We systematically searched MEDLINE, PsychInfo, EMBASE, ISI Web of Science, and CINAHL for original studies related to "palliative care" and "cancer" during the first 6 months of 2004 and 2009. For each study, we extracted the study size, the sample size calculation, and other study characteristics. We also determined the Consolidated Standards of Reporting Trials (CONSORT) overall quality score, the key methodologic index, and the Jadad score for randomized controlled trials (RCTs). A total of 840 studies were included for sample size analysis, and 44 RCTs were identified for quality of reporting analysis. The median sample size was 70 for RCTs, 112 for cohort studies, and 200 for cross-sectional studies. Sample size calculations were most frequently reported in RCTs; however, 29/44 (66%) RCTs had no reporting, 5/44 (11%) had partial reporting, and 10/44 (23%) had full reporting. The median CONSORT overall quality score was 9 (interquartile range 7-11), key methodologic index was 0.50 (interquartile range 0-1.75), and Jadad score was 2 (interquartile range 1-3), suggesting low quality of reporting. We found no differences in the quality scores between 2004 and 2009. Key methodologic index score ≥ 2 was associated with the presence of funding from any source (10/25 vs. 1/19, P = 0.013) and funding from pharmaceutical industry (5/9 vs. 6/35, P = 0.03). We identified deficiencies in the quality of supportive and palliative oncology RCTs.

Quality of safety reporting in oncology-randomized controlled trials (RCTs).

e13037 Background: Clinical trial reports often emphasize the efficacy of an investigational agent. Inadequate reporting of harms in published reports of RCTs may cause a misinterpretation of the risk to benefit ratio associated with new therapies. Our aim was to evaluate the quality of reporting of safety results in RCTs in oncology. Methods: We searched Medline to identify all RCTs with a sample size of at least 200 patients evaluating experimental medical therapies in breast and colorectal cancer published from 2000 to 2007. Each article was reviewed by a single investigator using a standardized data extraction form based on the harm reporting criteria developed by the CONSORT group. A random sample of articles was reviewed by a second investigator for quality assurance. Results: A total of 98 RCTs were identified through our search (breast n =68, colorectal n =30). The level of agreement between investigators performing data abstraction was high (kappa=0.737). Of these, 95.9% reported adverse events (AEs) in the body of the manuscript while only 39.8% of studies described AEs in the abstract. Information on only common and severe AEs was provided in 23.4% and 40.4% of reports respectively. The population group used for safety analysis was not identified in 19.4% of trials. No information on treatment discontinuation or dose reductions was provided in 24.5% and 53.1% of reports. Date of publication (before vs. after publication of the CONSORT harm reporting criteria), tumor site (breast vs colorectal), and treatment setting (early vs advanced disease) were not associated with quality of reporting severe adverse events, treatment discontinuation, and dose reduction. RCTs of advanced disease were more likely to report common adverse events than RCTs of early disease (41.3% vs 10.6% p=0.001). Conclusions: Most oncology RCTs fail to adequately report harm-related results. Adherence to reporting guidelines for adverse events is particularly important in oncology trials, where therapies often have a narrow therapeutic window.

Adequacy of Published Oncology Randomized Controlled Trials to Provide Therapeutic Details Needed for Clinical Application

Randomized controlled trials (RCTs) improve clinical care through evidence-based results. Guidelines exist for RCT result reporting, but specific details of therapeutic administration promote clinical application and reproduction of the trial design. We assess the reporting methodology in RCTs published in major oncology journals. Ten essential elements of RCT reporting were identified and included drug name, dose, route, cycle length, maximum number of cycles, premedication, growth factor support, patient monitoring parameters, and dosing adjustments for hematologic and organ-specific toxicity. All therapy-based oncology RCTs published between 2005 and 2008 in the New England Journal of Medicine (NEJM), Journal of Clinical Oncology (JCO), Journal of the National Cancer Institute (JNCI), Blood, and Cancer were analyzed for inclusion of these 10 elements. Of 339 identified articles, 262 were included in the final analysis (165 from JCO, 31 from NEJM, 27 from Cancer, 20 from JNCI, and 19 from Blood). Premedication, growth factor support, and dose adjustments for toxicities were each reported less than half of the time. Only 30 articles (11%) met the main objective of complete data reporting (ie, all 10 essential elements) and was highest in JNCI (5/20; 25%), followed by Cancer (5/27; 18%), JCO (18/165; 11%), Blood (1/19; 5%), and NEJM (1/31; 3%). The presence of an online appendix did not substantially improve complete reporting. RCTs published in major oncology journals do not consistently report essential therapeutic details necessary for translation of the trial findings to clinical practice. Potential solutions to improve reporting include modification of submission guidelines, use of online appendices, and providing open access to trial protocols.

Adequacy of published oncology randomized controlled trials to provide details needed for clinical application

6536 Background: Randomized control trials (RCTs) provide evidence for life-saving and supportive therapies. Although manuscript submissions follow a standard scientific format, major oncology journals have minimal standards for reporting treatment administration. Published data investigating chemo and biologic therapy often lack details needed for effective and safe clinical application. Methods: All therapy-based phase III oncology RCTs published between 2005–2008 in the Journal of Clinical Oncology (JCO), The New England Journal of Medicine (NEJM), Journal of the National Cancer Institute (JNCI), Blood, and Cancer were eligible for inclusion. Physicians and oncology pharmacists were surveyed for details needed for clinical practice. Each article was evaluated for these mandatory elements ( Table ). Differences were calculated using the Chi-squared test. Results: Literature search identified 339 eligible articles, 77 were reviews or meta-analyses. 262 were included in the final analysis (165 JCO; 31 NEJM; 27 Cancer; 20 JNCI; 19 Blood). Only 31 (12%; median score 7.3) met the main objective of complete data reporting. The most consistently reported and missing elements are described in Table 1. Premedications, growth factor support, and dose adjustments for hematologic or organ toxicity were reported less than half the time (p&lt;0.0001). The presence of an online appendix did not significantly improve the results (data not shown). Conclusions: RCTs published in top tier oncology journals fail to consistently report full details needed for clinical application. Manuscript submission guidelines should be modified to promote consistent reporting with potential use of online appendices. Standardized editorial policy may allow safe and effective translation of trial drug findings into clinical practice. [Table: see text] No significant financial relationships to disclose.