Industry-funded Trials Research Articles

As bleak as it sounds? Analysing trends in oncology clinical trial initiation in the UK from 2010 to 2022

ObjectivesThe UK’s withdrawal from the European Union (a political movement known as ‘Brexit’) incited concern both in the public and private sector about the future of drug development and the...

Diversity, Equity, and Inclusion in Urolithiasis Clinical Trials: Representative Enrollment by Race, Ethnicity, and Sex.

We sought to assess whether participant enrollment is appropriately representative of the overall urolithiasis population in published urolithiasis clinical trials. PubMed was queried for urolithiasis US clinical trials published from 2000 to 2022. Trials were evaluated for reporting patient race/ethnicity and sex data. These were then compared to the stone prevalence reported by the National Health and Nutrition Examination Survey from 2015 to 2018. We calculated a representation quotient (RQ) to describe enrollment of patients and then stratified by geographic location, study type, and funding source. Of the 180 urolithiasis trials performed in the US, we identified 40 trials (22%) reporting race or ethnicity and 104 trials (58%) reporting sex. Male and female participants are well represented (RQ 0.97 and 1.02, respectively). Overall, the RQ of Black, Asian American and Pacific Islander, White, Hispanic, and mixed/other participants is 1.84, 1.06, 1.04, 0.46, and 0.34, respectively. Trials completed in the Western Section and multi-institutional trials have the most proportional enrollment, while trials in the South Central and Southeastern Sections have underrepresentation of mixed/other and Hispanic patients. Enrollment was similar among all trial subtypes. Government- and industry-funded trials had more diverse enrollment than academic-funded trials. Only 1 in 4 published US urolithiasis trials report race or ethnicity enrollment. Mixed race and Hispanic participants are consistently underrepresented, while Black participants are overrepresented. Government- and industry-sponsored multi-institutional trials have the most proportional representation. Investigators should prioritize inclusive recruitment and improve reporting practices to accurately reflect the diversity of the urolithiasis population.

Principal Features of Industry-Funded Trials that Posted Informed Consent Forms on ClinicalTrials.gov: a Cross-Sectional Analysis.

We aim to characterize industry-funded trials that have posted the informed consent forms (ICFs), and to assess whether the role played by industry as 'sponsor' or 'collaborator' could impact several relevant variables. A cross-sectional study wasconducted on ClinicalTrials.gov on all industry-funded trials registered on or before 25 February 2023. We registered types of intervention, current recruitment status, design, enrollment, and countries involved. For trials with special interest to potential participants and investigators and/or clinicians an analysis of the role played by industry as 'sponsor' or 'collaborator' was performed. Of 116,281 industry-funded trials registered, 741 (0.6%) had posted ICFs. Most of these trials were categorized as 'completed' (n = 408) or 'terminated' (n = 107). The review of a sample of 359 trials showed that most were on drugs and/or biologics (59%), were randomized (51%), conducted exclusively in the USA (72%), and had posted results (79%), protocols (92%), and statistical analysis plans (SAPs) (89%). Trials in which industry participated as 'collaborator' were significantly more likely to post ICFs when trials were in the 'active, not recruiting' phase (OR 4.70, 99.71% CI 1.59-13.9, p < 0.001) than industry-sponsored trials. This was also the case when assessing drugs/biologics (OR 2.64, 99.71% CI 1.25-5.58, p < 0.001). Conversely, companies acting as 'sponsors' were significantly more likely to post ICFs with trials assessing devices, radiation interventions and/or diagnostic tests (OR 0.37, 99.71% CI 0.17-0.79, p < 0.001) than when participating as 'collaborators'. While industry-funded trials rarely post ICFs, when they do, they are highly compliant with transparency requirements. Regulations and ethics codes should consider requiring posting of protocols, SAPs, and ICFs for all clinical trials, regardless the type of sponsor.

767 Racial and Gender Disparities in Traumatic Brain Injury Clinical Trial Enrollment

INTRODUCTION: Despite the increasing number of women and racial/ethnic minorities sustaining Traumatic Brain Injuries (TBI), they are underrepresented in TBI clinical trials. METHODS: The authors conducted a review of TBI clinical trials with reported results registered in ClinicalTrials.gov between 2008 and 2022. The studies were assessed for the proportion of women and racial/ethnic minorities enrolled as well as their reporting of race and gender-specific characteristics such as Gender Ratio (GR) and Racial Diversity Index (RDI). Furthermore, study parameters including year and duration, phase, trial design, type of funding, and trial completion were included. RESULTS: 135 clinical trials met inclusion criteria, of which 65 and 134 reported race and gender, respectively. 25 trials were found to have existing racial disparity (RDI &lt; 1). Comparatively, industry-funded trials had a 26% more likelihood of racial disparities (p = 0.026), whereas federally-funded trials were 30% less likely (p = 0.031). 66 trials had gender disparities (GR &lt; 0.4) present, with federally-funded trials having 37.1% greater rates of gender disparity (p &lt; 0.001, aOR: 5.47, 95% CI: 2.26-14.25). The impact of funding source on race and gender remained significant despite adjusting for other covariates in the multivariate analyses. Racial disparity was negatively correlated with trial completion rate (p &lt; 0.001). Disparities were not found to improve over the 14-year span. CONCLUSIONS: Racial and gender disparities in TBI clinical trial enrollment persist, and the lack of diversity may lead to biased evidence-based medicine. Efforts should be made to increase the representation of women and racial/ethnic minorities in TBI clinical trials to ensure equitable access to effective treatments for all populations.

Phase IV Drug Trials With a Canadian Site: A Comparison of Industry-Funded and Non-Industry-Funded Trials.

Recent regulatory reforms have favored expedited drug marketing and increased reliance on Phase IV clinical trials for safety and efficacy assurance. This study, utilizing ClinicalTrials.gov, assesses the characteristics of Phase IV trials, with at least one site in Canada, examining those funded by industry sponsors and those lacking industry funding. Additionally, it compares the publication status of industry-funded and non-industry-funded trials through a manual review of the medical literature. Between 2000 and 2022, 864 Phase IV trials were completed, with 480 (55.6%) receiving industry funding and 384 (44.4%) funded solely by non-industry sources. Industry-funded clinical trials were larger (mean 204 enrollees versus 70), more likely to be international (57.7% versus 9.6%) and reported results more promptly (1.21 years after completion versus 1.85 years), yet both types shared similar designs, outcomes, and completion times. Publication rates were 81.8% for industry-funded and 65.8% for non-industry-funded trials. The ClinicalTrials. gov registry displayed 48 inaccuracies in publication associations, raising concerns about its accuracy. Our findings underscore the existing institutional limitations in ensuring comprehensive reporting and publication of Phase IV trial results funded by both industry and non-industry sources.

Post-approval indications and clinical trials for cardiovascular drugs: some implications of the US Inflation Reduction Act

Objective To describe the historical baseline landscape of cardiovascular drug post-approval activity, including the number and timing of post-approval clinical trials and approved indications. The US Inflation Reduction Act of 2022 (IRA) Drug Price Negotiation Program (DPNP) and its Maximum Fair Prices (MFPs) will affect incentives for investment in post-approval activity such as clinical trials for new indications. While three of the first ten drugs selected for the DPNP and MFP-setting are cardiovascular or antithrombotic drugs, limited attention has been paid to potential cardiovascular drug impacts, and to post-approval innovation. Methods For the 65 drugs originally approved by the FDA from 1995 through 2021 for a cardiovascular or antithrombotic indication (60 small molecules and 5 biologics), we develop a novel dataset of industry-sponsored, post-approval clinical trials and FDA-approved label changes for new indications. We analyze their number and timing relative to DPNP drug selection and MFP implementation dates, by drug approval-year cohort. Results We find 49% of indications were awarded and 76% of industry-funded clinical trials were completed post-approval, reaching 98% of trials for drugs in the earliest 1995–99 cohort. For the 60 small molecules, 76% of post-approval trials ended five years or more after original drug approval, 65% ended seven or more years after original drug approval (i.e. after potential DPNP selection), and 53% nine or more years after original drug approval (i.e. after potential MFP implementation). Conclusions Post-approval FDA indication approvals and clinical trial starts and primary completion dates often occurred after or near new DPNP selection and MFP implementation dates. This has economic consequences for future investment incentives. Post-approval trials for small molecules, longer-duration trials, and larger-enrollment trials, and post-approval indications focused on limited patient populations and older patients could face particular economic challenges.

Twenty years of participation of racialised groups in type 2 diabetes randomised clinical trials: a meta-epidemiological review.

Type 2 diabetes mellitus prevalence is increasing globally and the greatest burden is borne by racialised people. However, there are concerns that the enrolment of racialised people into RCTs is limited, resulting in a lack of ethnic and racial diversity. This may differ depending whether an RCT is government funded or industry funded. The aim of this study was to review the proportions of racialised and white participants included in large RCTs of type 2 diabetes pharmacotherapies relative to the disease burden of type 2 diabetes in these groups. The Ovid MEDLINE database was searched from 1 January 2000 to 31 December 2020. English language reports of RCTs of type 2 diabetes pharmacotherapies published in select medical journals were included. Studies were included in this review if they had a sample size of at least 100 participants and all participants were adults with type 2 diabetes. Industry-funded trials must have recruited participants from at least two countries. Government-funded trials were not held to the same standard because they are typically conducted in a single country. Data including the numbers and proportions of participants by ethnicity and race were extracted from trial reports. The participation-to-prevalence ratio (PPR) was calculated for each trial by dividing the percentage of white and racialised participants in each trial by the percentage of white and racialised participants with type 2 diabetes, respectively, for the regions of recruitment. A random-effects meta-analysis was used to generate the pooled PPRs and 95% CIs across study types. A PPR <0.80 indicates under-representation and a PPR >1.20 indicates over-representation. Risk of bias assessments were not conducted for this study as the objective was to examine recruitment of racialised and white participants rather than evaluate the trustworthiness of clinical trial outcomes. A total of 83 trials were included, involving 283,122 participants, of which 15 were government-funded and 68 were industry-funded trials. In government-funded trials, the PPR for white participants was 1.11 (95% CI 0.99, 1.24) and the PPR for racialised participants was 0.72 (95% CI 0.60, 0.86). In industry-funded trials, the PPR for white participants was 1.95 (95% CI 1.74, 2.18) and the PPR for racialised participants was 0.36 (95% CI 0.32, 0.42). The limitations of this study include the reliance on investigator-reported ethnicity and race to classify participants as 'white' or 'racialised', the use of estimates for type 2 diabetes prevalence and demographic data, and the high levels of heterogeneity of pooled estimates. However, despite these limitations, the results were consistent with respect to direction. Racialised participants are under-represented in government- and industry-funded type 2 diabetes trials. Strategies to improve recruitment and enrolment of racialised participants into RCTs should be developed. Open Science Framework registration no. f59mk ( https://osf.io/f59mk ) FUNDING: The authors received no financial support for this research or authorship of the article.

Industry Involvement and Transparency in the Most Cited Clinical Trials, 2019-2022

Industry involvement is prominent in influential clinical trials, and commitments to transparency of trials are highly variable. To evaluate the modes of industry involvement and the transparency features of the most cited recent clinical trials across medicine. This cross-sectional study was a meta-research assessment including randomized and nonrandomized clinical trials published in 2019 or later. The 600 trials of any type of disease or setting that attracted highest number of citations in Scopus as of December 2022 were selected for analysis. Data were analyzed from March to September 2023. Outcomes of interest were industry involvement (sponsor, author, and analyst) and transparency (protocols, statistical analysis plans, and data and code availability). Among 600 trials with a median (IQR) sample size of 415 (124-1046) participants assessed, 409 (68.2%) had industry funding and 303 (50.5%) were exclusively industry-funded. A total of 354 trials (59.0%) had industry authors, with 280 trials (46.6%) involving industry analysts and 125 trials (20.8%) analyzed exclusively by industry analysts. Among industry-funded trials, 364 (89.0%) reached conclusions favoring the sponsor. Most trials (478 trials [79.7%]) provided a data availability statement, and most indicated intention to share the data, but only 16 trials (2.7%) had data already readily available to others. More than three-quarters of trials had full protocols (482 trials [82.0%]) or statistical analysis plans (446 trials [74.3%]) available, but only 27 trials (4.5%) explicitly mentioned sharing analysis code (8 readily available; 19 on request). Randomized trials were more likely than nonrandomized studies to involve only industry analysts (107 trials [22.9%] vs 18 trials [13.6%]; P = .02) and to have full protocols (405 studies [86.5%] vs 87 studies [65.9%]; P < .001) and statistical analysis plans (373 studies [79.7%] vs 73 studies [55.3%]; P < .001) available. Almost all nonrandomized industry-funded studies (90 of 92 studies [97.8%]) favored the sponsor. Among industry-funded trials, exclusive industry funding (odds ratio, 2.9; 95% CI, 1.5-5.4) and industry-affiliated authors (odds ratio, 2.9; 95% CI, 1.5-5.6) were associated with favorable conclusions for the sponsor. This cross-sectional study illustrates how industry involvement in the most influential clinical trials was prominent not only for funding, but also authorship and provision of analysts and was associated with conclusions favoring the sponsor. While most influential trials reported that they planned to share data and make both protocols and statistical analysis plans available, raw data and code were rarely readily available.

QLTI-12. ADULT NEURO-ONCOLOGY TRIAL LANDSCAPE IN THE UNITED STATES OVER FIVE DECADES

Abstract PURPOSE The unmet therapeutic needs in neuro-oncology remain significant due to the biological and clinical challenges. Clinical trials are important to close the gap between therapeutic unmet needs and scientific advances. This study aims at analyzing the landscape of neuro-oncology trials to identify completion and failures and guide strategies for the path forward. METHODS US-registered adult neuro-oncology clinical trials were extracted from www.clinicaltrials.gov (1966-2019) to include funding source, trial type, scope, phase, and subjects’ demographics. Trial failures comprised “terminated,” “withdrawn,” and/or “suspended” trials. Univariate and multivariate analysis were used to detect differences across factors and over time. RESULTS Our search yielded 4522 trials, 1257 eligible for this study. In 25 US States, neuro-oncology trials availability is &amp;lt; 0.85/100,000 population. Over time, completed trials have decreased with a significant increased percentage of trial failures from 22% to 36% (p &amp;lt; 0.001). Overtime, NIH funding decreased from 47% to 24% (p &amp;lt; 0.001). Inclusion of subjects ≥ 65-year-old and women increased in the last decade (p &amp;lt; 0.001) while inclusion of Hispanic subjects has decreased (p &amp;lt; 0.001). The top two reasons for failure included accrual and operational difficulties. Industry-funded trials had a trend toward higher failure rate than NIH-funded. A larger proportion of women (p &amp;lt; 0.001), non-Hispanic subjects (p = 0.001), and older adult (p &amp;lt; 0.001) patients were enrolled in completed trials than in failed trials. CONCLUSION Our study is the first report on the neuro-oncology clinical trial landscape in the US over time. The data support the concept that strategies to further the availability of clinical neuro-oncology trials within the US are necessary. As these are developed, attention is needed to identifying and modifying factors contributing to clinical trial failures.

Abstract 14122: Evaluating Gender Diversity in Principal Investigators of Cardiac Electrophysiology Clinical Trials

Background: Importance of diversity in clinical trial participants has been recently highlighted. Though clinical trials led by women principal investigators (PIs) are more likely to enroll diverse participants, the proportion of trials led by women PIs is unknown. Objective: To evaluate gender distribution among PIs who conduct NIH and industry-funded clinical trials in cardiac electrophysiology (EP). Methods: NIH and industry-funded trials in the clinicaltrials.gov registry completed between 1/1/2002 and 12/31/2021 in atrial fibrillation (AF), implantable cardioverter defibrillators (ICDs), pacemakers (PPMs), sudden cardiac arrest (SCA), and ventricular tachycardia (VT) were included. PI names and associated institutions were used to determine gender pronouns on institutional websites or social media. Trials with unidentifiable PI gender were categorized as unknown. Results: 51 NIH-funded and 429 industry-funded trials in AF, SCA, VT, ICDs, and PPMs and 573 total PIs were identified. 128 trials (26.7%) and 123 PIs (21.5%) had unknown PI gender. 16.4% of all trials in which PI gender was known were led by women. 9/49 (18.4%) NIH and 49/295 (16.6%) industry trials were led by women. VT trials had the lowest proportion women-led (NIH: 0/4, 0%; industry: 3/26, 11.5%), whereas PPM trials had the highest proportion women-led in both NIH (3/5, 60%) and all trials (12/48, 22.2%). Of the group with the largest number of trials (AF), 12.9% were women-led (22/170) (Table). Of 450 PIs across all trials whose gender was identified, 14.4% were women. The proportion of women PIs decreased non-significantly over time. Studies between 2002-2011 were 16% women-led, and in 2012 or later this reduced to 13% X 2 (1, N = 450) = 0.81, p &gt; .05. Conclusion: The proportion of cardiac EP clinical trials led by women PIs remains low and has not increased. Urgent efforts are needed to implement strategies to increase leadership roles in clinical trials for women in cardiac electrophysiology.

Racial and gender disparities in traumatic brain injury clinical trial enrollment

OBJECTIVE Despite the increasing number of women and racial/ethnic minorities sustaining traumatic brain injuries (TBIs), they are underrepresented in TBI clinical trials. This study aimed to evaluate gender and racial diversity in enrolled cohorts of TBI clinical trials to identify trends and predictors of increased disparity over time. METHODS The authors reviewed TBI clinical trials with reported results registered on the website ClinicalTrials.gov between 2008 and 2022. The studies were assessed for the proportion of women and racial/ethnic minorities enrolled as well as their reporting of race- and gender-specific characteristics such as gender ratio (GR) and Racial Diversity Index (RDI). Further study parameters, including year and duration, phase, trial design, type of funding, and trial completion, were also included. RESULTS One hundred thirty-five clinical trials met inclusion criteria, of which 65 and 134 reported race and gender, respectively. Twenty-five trials were found to have existing racial disparity (RDI &lt; 1). Comparatively, industry-funded trials had a 26% greater likelihood of racial disparities (p = 0.026), whereas federally funded trials were 30% less likely to demonstrate racial disparities (p = 0.031). Sixty-six trials had gender disparities (GR &lt; 0.4) present, with federally funded trials showing 37.1% greater rates of gender disparity (p &lt; 0.001, adjusted OR 5.47, 95% CI 2.26–14.25). The impact of funding source on race and gender remained significant despite adjusting for other covariates in the multivariate analyses. Racial disparity was negatively correlated with trial completion rate (p &lt; 0.001). Disparities were not found to improve over the 14-year time span. CONCLUSIONS Racial and gender disparities in TBI clinical trial enrollment persist, and the lack of diversity may lead to biased evidence-based medicine. Efforts should be made to increase the representation of women and racial/ethnic minorities in TBI clinical trials to ensure equitable access to effective treatments for all populations.

Changes in Registration Parameters for Ongoing Clinical Trials in Ukraine After 2022 Russian Invasion

Clinical trial activity in Ukraine was seriously affected by the Russian invasion. However, data are lacking on how this conflict affects clinical trials. To evaluate whether registered changes to trial information reflect war-related disturbances to trials in Ukraine. This cross-sectional study included noncompleted trials conducted in Ukraine from February 24, 2022, to February 24, 2023. Trials conducted in Estonia and Slovakia were also analyzed for comparison. Study records within the ClinicalTrials.gov archive were accessed by using the change history feature in the tabular view for each record. Russian invasion of Ukraine. The frequency of changes to the protocol and results registration parameters before and after the start of the war, February 24, 2022. A total of 888 ongoing trials conducted only in Ukraine (5.2%) or in multiple countries (94.8%), and enrolling a median of 348 participants were analyzed. Almost all sponsors for 775 industry-funded trials were non-Ukrainian (99.6%). On February 24, 2023, 267 trials (30.1%) were without any recorded update in the registry after the war. In 15 (1.7%) multisite trials, Ukraine was removed as a location country after mean (SD) of 9.4 (3.0) postwar months. The rates of changes in 20 parameters 1 year before and after the war started had a mean (SD) absolute difference of 3.0% (2.5%). Besides study status changes in each study record version, the contacts and locations field was the most frequently modified (56.1%), with a higher rate for multisite (58.2%) than in only Ukrainian (17.4%) trials. This finding was consistent for all analyzed registration parameters. In trials conducted solely in Ukraine, the median number of record versions was the year before (95% CI, 0-0) and after February 2022 (95% CI, 0-1), similar to registered trials from Estonia and Slovakia. Results of this study suggest that war-related changes in trial conduct in Ukraine may not be completely visible in the largest public trial registry, which is expected to present accurate and timely information on clinical trials. These findings raise questions regarding the updating practices for registration information, which should be mandatory, especially in times of crises, to ensure the safety and the rights of trial participants in a war zone.

Discontinuation and nonpublication analysis of chronic pain randomized controlled trials.

The primary objective of this cross-sectional analysis is to evaluate rates of discontinuation and nonpublication of Randomized controlled trials (RCTs) of therapeutic interventions to treat chronic pain. Using ClinicalTrials.gov, a sample was obtained which included clinical trials pertaining to chronic pain. Trials were analyzed for publication status and completion status of each trial. If information was unavailable on the trial registry database, or could not be allocated through a systematic search, the corresponding trialist was contacted and data points were gathered. In our final analysis of the 408 RCTs, we found that 281 (68.9%) were published in a peer-reviewed journal and 127 (31.1%) were unpublished trials. Of 112 discontinued trials, 59 (52.7%) reached publication. In addition, 221 of 296 completed trials (74.7%) were published, and 75 (25.3%) remained unpublished after trial completion. The most common listed reason for trial discontinuation was administrative recommendations (41 of 71 trials [57.7%]), while not receiving an email reply to our standardized email from the corresponding trialist was the most common result for trial nonpublication (49 of 88 trials [55.7%]). Clinical trials funded by nonindustry sponsors were more likely to reach publication than industry-funded clinical trials (unadjusted odds ratio 1.86 [95% CI, 1.18-2.95]; adjusted odds ratio 3.01 [95% CI, 1.76-5.14]). The rate of discontinuation of RCTs involving patients with chronic pain is concerning. Chronic pain affects many patients; thus, the importance of having quality data from clinical trials cannot be overstated. Our study indicates that chronic pain RCTs are frequently discontinued and their findings often go unpublished - all of which could provide crucial information to providers and patients regarding the treatment of chronic pain. We offer suggestions to enhance chronic pain RCT completion, thereby reducing the waste of resources in chronic pain research.

Analysis of Female Participant Representation in Registered Oncology Clinical Trials in the United States from 2008 to 2020.

Female underrepresentation in oncology clinical trials can result in outcome disparities. We evaluated female participant representation in US oncology trials by intervention type, cancer site, and funding. Data were extracted from the publicly available Aggregate Analysis of ClinicalTrials.gov database. Initially, 270,172 studies were identified. Following the exclusion of trials using Medical Subject Heading terms, manual review, those with incomplete status, non-US location, sex-specific organ cancers, or lacking participant sex data, 1650 trials consisting of 240,776 participants remained. The primary outcome was participation to prevalence ratio (PPR): percent females among trial participants divided by percent females in the disease population per US Surveillance, Epidemiology, and End Results Program data. PPRs of 0.8-1.2 reflect proportional female representation. Females represented 46.9% of participants (95% CI, 45.4-48.4); mean PPR for all trials was 0.912. Females were underrepresented in surgical (PPR 0.74) and other invasive (PPR 0.69) oncology trials. Among cancer sites, females were underrepresented in bladder (odds ratio [OR] 0.48, 95% CI 0.26-0.91, P = .02), head/neck (OR 0.44, 95% CI 0.29-0.68, P < .01), stomach (OR 0.40, 95% CI 0.23-0.70, P < .01), and esophageal (OR 0.40 95% CI 0.22-0.74, P < .01) trials. Hematologic (OR 1.78, 95% CI 1.09-1.82, P < .01) and pancreatic (OR 2.18, 95% CI 1.46-3.26, P < .01) trials had higher odds of proportional female representation. Industry-funded trials had greater odds of proportional female representation (OR 1.41, 95% CI 1.09-1.82, P = .01) than US government and academic-funded trials. Stakeholders should look to hematologic, pancreatic, and industry-funded cancer trials as exemplars of female participant representation and consider female representation when interpreting trial results.

Publication bias in trials registered in the Australian New Zealand Clinical Trials Registry: Is it a problem? A cross-sectional study.

Timely publication of clinical trials is critical to ensure the dissemination and implementation of high-quality healthcare evidence. This study investigates the publication rate and time to publication of randomized controlled trials (RCTs) registered in the Australian New Zealand Clinical Trials Registry (ANZCTR). We conducted a cross-sectional study of RCTs registered with the ANZCTR in 2007, 2009, and 2011. Multiple bibliographic databases were searched until October 2021 to identify trial publications. We then calculated publication rates, proportions, and the time to publish calculated from the date of first participation enrolment to publication date. Of 1,970 trial registrations, 541 (27%) remained unpublished 10 to 14 years later, and the proportion of trials published decreased by 7% from 2007 to 2011. The average time to publish was 4.63 years. The prospective trial registration rate for 2007, 2009 and 2011 was 48% (952 trials) and over this time there was an increase of 19% (280 prospective trials). Trials funded by non-Industry organizations were more likely to be published (74%, 1204/1625 trials) than the industry-funded trials (61%, 224/345 trials). Larger trials with at least 1000 participants were published at a rate of 88% (85/97 trials) and on average took 5.4 years to be published. Smaller trials with less than 100 participants were published at a lower rate with 67% (687/1024 trials) published and these trials took 4.31 years on average to publish. Just over a quarter of all trials on the ANZCTR for 2007, 2009, and 2011 remain unpublished over a decade later. The average time to publication of nearly five years may reflect the larger trials which will have taken longer to recruit participants. Over half of study sample trials were retrospectively registered, but prospective registration improved over time, highlighting the role of mandating trial registration.

Pharmaceutical industry funding and chemotherapy trials for prostate cancer: A systematic review

IntroductionClinical trials are increasingly supported by industries while previous studies have shown that industry-supported studies have more favorable results than studies with other sources of funding. In the present study, we investigated the association of industrial funding on the results of clinical trials regarding chemotherapy in prostate cancer. MethodsA systematic literature search was performed in the Cochrane Library, MEDLINE, and EMBASE to identify clinical trials comparing chemotherapy with treatments such as hormone therapy, surgery, radiotherapy, and placebo in patients with metastatic or non-metastatic prostate cancer. Data were extracted by two reviewers on the financial resources and the positive or negative results of chemotherapy in each study. The quality of articles was evaluated and compared based on Cochrane Critical Appraisal Tool. The trials were divided into two groups; industry funded and those not funded by industry. Association of industry funding and positive outcome was presented as odds ratio. ResultsIn this study, out of the 91 studies, 80.2% were funded by pharmaceutical companies and 19.8% were funded by government agencies. The end result of 61.6% of the studies funded by pharmaceutical companies was an increase in survival due to chemotherapy, whereas only 27.8% of the studies sponsored by government agencies reported positive results (P-value=0.010). In fact, industry-funded trials more often presented statistically significant positive results for survival (OR: 4.17; CI, 1.34–12.99). In general, there was no significant difference in the degree of bias between the two groups. ConclusionAccording to this study, despite of the similar quality of studies funded by pharmaceutical companies and government agencies, positive results were more common in studies related to pharmaceutical companies. Therefore, this point should be taken into account when making a decision on the best treatment approach.

Trends in Women's Leadership of Oncology Clinical Trials.

It has been widely reported that women are underrepresented in leadership positions within academic medicine. This study aimed to assess trends in women representation as principal investigators (PIs) in oncology clinical trials and to characterize trends in women’s leadership in such trials conducted between 1999 and 2019. The gender of 39,240 PIs leading clinical trials was determined using the gender prediction software Genderize.io. In total, 11,516 (27.7%) women served as PIs. Over the past 20 years, an annual increase of 0.65% in women PIs was observed. Analysis by geographic distribution revealed higher women representation among PIs in North America and Europe compared to Asia. Industry-funded trials were associated with lower women PI representation than academic-funded trials (31.4% vs. 18.8%, p<0.001). Also, women PIs were found to be underrepresented in late-phase as compared to early-phase studies (27.9%, 25.7%, 21.6%, and 22.4% in phase I, II, III, and IV, respectively; Cochran-Armitage test for trend, p<0.001). Furthermore, an association was found between the PI’s gender and enrolment of female subjects (50% vs. 43% female participants led by women vs men PIs, respectively, p<0.001). Taken together, while the gender gap in women’s leadership in oncology trials has been steadily closing, prominent inequalities remain in non-Western countries, advanced study phases, industry-funded trials and appear to be linked to a gender gap in patient accrual. These observations can serve for the development of strategies to increase women’s representation and to monitor progress toward gender equality in PIs of cancer clinical trials.

Evolution of eligibility criteria for non-transplant randomized controlled trials in adults with acute myeloid leukemia.

Eligibility criteria for clinical trials are intended to select suitable study subjects but can limit trial participation and generalization of results. While reported for other cancers, non-enrollment rates and evolution of eligibility criteria over time have so far not been studied for randomized controlled trials (RCTs) involving adults with acute myeloid leukemia (AML). Among 3698 studies published between 2010 and 2020, including 447 involving prospective clinical trials, we identified 75 phase three RCTs testing non-transplant therapies for adults with AML. Only 31 studies (41%) provided information on non-enrollment; in these studies, the median non-enrollment rate was 23%, primarily attributed to restrictive eligibility criteria. In 95% of trials, eligibility criteria were reported with the total number per trial increasing over time (P < 0.001), particularly in industry-funded trials. A total of 27 eligibility criteria were used across trials, mostly concerning comorbidities or performance status, with eight of them becoming more common over time. The concordance with recent ASCO - Friends of Cancer Research eligibility criteria recommendations greatly varied, from 35% to 99%. Together, our analyses suggest that the ability to generalize results from non-transplant RCTs may be increasingly limited because of high non-enrollment rates and increasingly restrictive eligibility criteria.

Early Discontinuation, Results Reporting, and Publication of Gynecology Clinical Trials From 2007 to 2020

OBJECTIVE: To characterize gynecology clinical trials over time, compare gynecology subspecialties, and analyze factors associated with early discontinuation, results reporting, and publication. METHODS: We conducted a cross-sectional analysis of all gynecology trials registered on ClinicalTrials.gov between 2007 and 2020 and their resulting publications. Trials were analyzed with descriptive, multivariable logistic, and Cox regression analyses. Primary exposure variables were trial funding and subspecialty. The three primary outcomes included early discontinuation, results reporting to ClinicalTrials.gov, and publication in a peer-reviewed journal indexed on PubMed. RESULTS: Of 223,690 trials registered on ClinicalTrials.gov between October 2007 and March 2020, only 3.7% focused on gynecology (n=8,174, approximately 3,759,086 participants). Subspecialties included reproductive endocrinology and infertility (n=1,428, 17.5%), gynecologic oncology (n=2,063, 25.2%), urogynecology (n=1,118, 13.7%), family planning (n=648, 7.9%), and other benign gynecology (n=2,917, 35.7%). Only 42.0% of completed trials disseminated results through results reporting and publication. Of all funding types, industry-funded trials were the most likely to be discontinued early (P&lt;.001). Academic-funded trials were the least likely to report results (adjusted odds ratio [aOR] 0.38, 95% CI 0.30–0.50) but the most likely to publish (aOR 1.62, 95% CI 1.24–2.12). The number of reproductive endocrinology and infertility trials increased the most of any subspecialty between 2007 and 2020 (6.4% growth rate). Reproductive endocrinology and infertility and family planning trials were the most likely to be stopped early (reproductive endocrinology and infertility: adjusted hazard ratio [aHR] 2.08, 95% CI 1.59–2.71; family planning: aHR 1.55 95% CI 1.06–2.25). When completed, reproductive endocrinology and infertility trials were the least likely to report results (aOR 0.58, 95% CI 0.38–0.88). No significant differences were seen between subspecialties with respect to publication. CONCLUSION: Gynecology trials comprise only 3.7% of all clinical trials. The paucity of gynecology clinical trials aligns with decades of female underrepresentation in research. When completed, gynecology trials have poor dissemination. Our findings raise concern about bias in the performance, reporting, and publication of gynecology clinical trials.

Methodological Quality and Risk of Bias Assessment of Cardiovascular Disease Research: Analysis of Randomized Controlled Trials Published in 2017.

BackgroundAll randomized-controlled trials (RCTs) are required to follow high methodological standards. In this study, we aimed to assess the methodological quality of published cardiovascular clinical research trials in a representative sample of RCTs published in 2017.MethodsCochrane Central Register of Controlled Trials was used to identify cardiovascular clinical research trials with adult participants published in 2017. Overall, 250 (10%) RCTs were randomly selected from a total of 2,419 studies. Data on general trial characteristics were extracted and the risk of bias (RoB) was determined.ResultsOverall, 86% of RCTs have reported at least one statistically significant result, with the primary outcome significant in 69%, treatment favored in 55%, and adverse events reported in 68%. Less than one-third (29%) of trials were overall low RoB, while the other two-thirds were rated unclear (40%) or with high RoB (31%). Sequence generation, allocation concealment, and selective reporting were the domains most often rated with high RoB. Drug trials were more likely to have low RoB than non-drug trials. Significant differences were found in RoB for the allocation concealment and blinding of participants and personnel between industry-funded and non-industry-funded trials, with industry-funded trials more often rated at low RoB.ConclusionAlmost two-thirds of RCTs in the field of cardiovascular disease (CVD) research, were at high or unclear RoB, indicating a need for more rigorous trial planning and conduct. Prospective trial registration is a factor predicting a lower risk of bias.