Trial Sponsorship Research Articles

A comprehensive analysis of patient demographics and disparities in contemporary oncology clinical trials (2022-2023).

e13748 Background: Overcoming disparities in cancer research is a major challenge that needs to be prioritized in clinical trials in oncology. In this study, we aimed to assess the current representation of patient demographics in phase 2 and 3 clinical trials in oncology to illuminate healthcare inequities during clinical trial recruitment. Methods: We identified published phase 2 and phase 3 oncology studies in five medical journals (New England Journal of Medicine, Journal of Clinical Oncology, Lancet, Lancet Oncology, and JAMA Oncology). We extracted data on patient demographics including sex, age, race, and ethnicity. We also extracted information on trial sponsorship (industry vs investigator initiated). Results: We included 381 articles published between 2022 and 2023 (108 investigator-initiated; 273 industry-sponsored). Details on age groups (<65 vs >65) were available in 149 studies (n=78,523 patients) including 47,192 (60.1%) < 65; and 31,331 (39.9%) >65. Data on gender were available in 373 studies (n=159,836 patients) including 73,308 (45.9%) males and 86,526 (54.1%) females (2 patients were listed as other). Race was reported in 214 studies (n=92,562) including 65,876 Caucasian (71.2%), 3,428 (3.7%) Black, 18,235 (19.7%) Asian, and 5,023 (5.4%) other/missing. Ethnicity data were available in 52 studies including 2,570 Hispanics (12.4%) and 18,234 non-Hispanics or unknown (87.6%). Conclusions: While there are efforts being made to diversify the recruitment of clinical trials, inequities in trial recruitment remains a major issue. Caucasian and younger patients represented the majority of patients, which may not be reflective of real-world practice. There is an important need to focus on increasing enrollment of underrepresented populations and understanding barriers to enrollment.

Public reporting of black participation in anti-hypertensive drug clinical trials

Non-Hispanic Black people in the United States have the highest prevalence of essential hypertension. Unfortunately, clinical trials often underrepresent Black patients. We aim to understand whether trial sponsorship type is associated with representation of Black participants in anti-hypertensive drug clinical trials. Then, we contextualize our findings amongst current efforts to improve diversity in clinical research populations. We searched ClinicalTrials.gov in May 2022 for antihypertensive drug trials. Of n=408 trials in our initial search, n=97 (23.77%) met inclusion criteria and were stratified by sponsorship type (industry vs non-industry). Standardized tests of difference were employed to compare characteristics of these trials, and linear regression was used to model change over time. Of 97 trials reporting results from 2010 to 2020, there were minimal differences in the percent of Black patients enrolled in anti-hypertensive clinical trials by sponsorship type. Both industry and non-industry sponsored studies had high rates of non-reporting, with slightly more non-reporting for industry (73.2%) vs non-industry (66.67%) studies. Industry funded studies reported results to ClinicalTrials.gov within 23.3 ± 15.0 months from completing studies, while non-industry funded trials reported within 18.9 ± 10.8 months. Despite Black Americans carrying the highest burden of disease for essential hypertension, they are underrepresented in anti-hypertension clinical trials and their overall participation has decreased between 2010 and 2020. In addition, there is major underreporting of trial participant race. We implore researchers and funders to establish clear, meaningful targets for anti-hypertensive drug trial diversity, and improve transparency in reporting of study characteristics.

Tvt CAR7: Phase 1 Clinical Trial of Base-Edited "Universal” CAR7 T Cells for Paediatric Relapsed/Refractory T-ALL

Background Genome editing can overcome HLA barriers to generate 'off-the-shelf’ CAR T cell therapies. Despite the success of CAR-T cell therapies in B-cell malignancies, the expression of shared T cell antigens has constrained the development of CAR T cells targeting T-cell malignancies, due to T cell fratricide. Targeted base editing using CRISPR guided cytidine deamination mediates highly precise C→U→T conversion which can directly disrupt gene expression without DNA breaks. This Phase I study will investigate the feasibility and safety of base edited (BE) allogeneic CAR T cells against CD7, disrupted for TCR, CD7 and CD52. The cells are used to secure remission ahead of allogeneic stem cell transplantation (allo-SCT). Investigational medicinal product (IMP) Two allogeneic healthy donor derived BE-CAR7 T cell banks were manufactured from steady state apheresis harvests using a semi-automated process under compliant conditions. Cells were activated with an anti-CD3/CD28 reagent (Transact) and electroporated with codon optimised base editor (coBE) mRNA and three single guide RNAs targeting TRBC, CD52 and CD7. Subsequent lentiviral transduction delivered CAR7 (59-62% efficiency) and magnetic bead processing depleted residual TCRαβ+ T cells (residual 0.1-0.3%). Highly efficient disruption of CD7 and CD52 (98-99%) was confirmed by sequencing. Cells were cryopreserved and QC tested by flow cytometry, ddPCR for copy number (3.1-3.6) and replication competent lentivirus was excluded. Anti-leukemic potency was confirmed in vitro and in human:murine chimera experiments. Trial sponsorship & approvals The TvT CAR7 study (ISRCTN15323014) is an open label, single centre, single arm and non-randomised clinical trial. The trial is sponsored by Great Ormond Street Hospital NHS trust and is supported by MRC, Wellcome Trust and NIHR. Clinical trial authorisation was provided by MHRA and ethical approval by a gene therapy advisory committee (GTAC) ahead of site initiation. Study aims and Objectives The study aims to establish the safety and feasibility of BE-CAR7 to induce molecular remission in children with relapsed/refractory (r/r) CD7-positive T-ALL, ahead of a planned allo-SCT. Assessments include incidence of adverse events, duration of remission, disease-free survival and overall survival. Expansion, persistence and elimination of BE-CAR7 cells and immune recovery after allo-SCT are monitored. Eligibility, treatment and recruitment The study opened on 14th April 2022 at Great Ormond Street Hospital recruiting children across the UK aged between 6 months and 16 years with r/r CD7+ T-cell malignancies quantifiable in bone marrow (>10-4 by flow or PCR). Exclusions include active uncontrolled infections, pre-existing GvHD or the detection of anti-HLA antibodies against the IMP. Eligible patients receive lymphodepletion with fludarabine (150 mg/sqm), cyclophosphamide (120 mg/kg) and alemtuzumab (1 mg/kg), followed by infusion of 0.2-2.0x106 BE-CAR7 T cells (maximum 5x104/kg TCRαβ T cells). Patients in molecular remission at day +28 proceed to allo-SCT, to remove BE-CAR 7 cells and promote immune reconstitution. The first subject was infused on 4th May 2022. Grade 2 CRS and grade 1 ICANS were observed, but no GvHD. Bone marrow assessment at d+28 revealed morphological remission without count recovery and with PCR-MRD <10-4 and the patient proceeded to reduced intensity allo-SCT as planned. This Phase 1 study aims to treat 10 children in the UK. Conclusion The study has demonstrated the feasibility of manufacturing "off-the-shelf” GMP-compliant base edited CAR7 T cells and is investigating their safety and efficacy against paediatric r/r T-ALL.

Information Disclosure in the Presence of Competition: Evidence from the Pharmaceutical Industry

This paper studies how competition impacts firms' voluntary disclosure of product quality information. Our empirical context is the pharmaceutical industry, where firms must decide whether to disclose drug quality information that is acquired in clinical trials. Leveraging variation in clinical trial sponsorship and a difference-in-differences design, we show that firms in competitive markets are less likely to publicly disclose clinical trial results. In exploring mechanisms, we find evidence for a decline in product quality as driving these findings. These results suggest that market structure plays an important role in shaping the production and provision of product quality information.

Vitamin D supplementation for chronic liver diseases in adults.

Vitamin D deficiency is often reported in people with chronic liver diseases. Improving vitamin D status could therefore be beneficial for people with chronic liver diseases. To assess the beneficial and harmful effects of vitamin D supplementation in adults with chronic liver diseases. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE Ovid, Embase Ovid, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We scanned bibliographies of relevant publications and enquired experts and pharmaceutical companies as to additional trials. All searches were up to November 2020. Randomised clinical trials that compared vitamin D at any dose, duration, and route of administration versus placebo or no intervention in adults with chronic liver diseases. Vitamin D could have been administered as supplemental vitamin D (vitamin D3 (cholecalciferol) or vitamin D2 (ergocalciferol)), or an active form of vitamin D (1α-hydroxyvitamin D (alfacalcidol), 25-hydroxyvitamin D (calcidiol), or 1,25-dihydroxyvitamin D (calcitriol)). We used standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of evidence. We included 27 randomised clinical trials with 1979 adult participants. This review update added 12 trials with 945 participants. We assessed all trials as at high risk of bias. All trials had a parallel-group design. Eleven trials were conducted in high-income countries and 16 trials in middle-income countries. Ten trials included participants with chronic hepatitis C, five trials participants with liver cirrhosis, 11 trials participants with non-alcoholic fatty liver disease, and one trial liver transplant recipients. All of the included trials reported the baseline vitamin D status of participants. Participants in nine trials had baseline serum 25-hydroxyvitamin D levels at or above vitamin D adequacy (20 ng/mL), whilst participants in the remaining 18 trials were vitamin D insufficient (less than 20 ng/mL). Twenty-four trials administered vitamin D orally, two trials intramuscularly, and one trial intramuscularly and orally. In all 27 trials, the mean duration of vitamin D supplementation was 6 months, and the mean follow-up of participants from randomisation was 7 months. Twenty trials (1592 participants; 44% women; mean age 48 years) tested vitamin D3 (cholecalciferol); three trials (156 participants; 28% women; mean age 54 years) tested vitamin D2; four trials (291 participants; 60% women; mean age 52 years) tested 1,25-dihydroxyvitamin D; and one trial (18 participants; 0% women; mean age 52 years) tested 25-hydroxyvitamin D. One trial did not report the form of vitamin D. Twelve trials used a placebo, whilst the other 15 trials used no intervention in the control group. Fourteen trials appeared to be free of vested interest. Eleven trials did not provide any information on clinical trial support or sponsorship. Two trials were funded by industry. We are very uncertain regarding the effect of vitamin D versus placebo or no intervention on all-cause mortality (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.51 to 1.45; 27 trials; 1979 participants). The mean follow-up was 7 months (range 1 to 18 months). We are very uncertain regarding the effect of vitamin D versus placebo or no intervention on liver-related mortality (RR 1.62, 95% CI 0.08 to 34.66; 1 trial; 18 participants) (follow-up: 12 months); serious adverse events such as hypercalcaemia (RR 5.00, 95% CI 0.25 to 100.8; 1 trial; 76 participants); myocardial infarction (RR 0.75, 95% CI 0.08 to 6.81; 2 trials; 86 participants); thyroiditis (RR 0.33, 95% CI 0.01 to 7.91; 1 trial; 68 participants); circular haemorrhoidal prolapse (RR 3.00, 95% CI 0.14 to 65.9; 1 trial; 20 participants); bronchopneumonia (RR 0.33, 95% CI 0.02 to 7.32; 1 trial 20 participants); and non-serious adverse events. The certainty of evidence for all outcomes is very low. We found no data on liver-related morbidity such as gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, ascites, or liver cancer. There were also no data on health-related quality of life. The evidence is also very uncertain regarding the effect of vitamin D versus placebo or no intervention on rapid, early, and sustained virological response in people with chronic hepatitis C. Given the high risk of bias and insufficient power of the included trials and the very low certainty of the available evidence, vitamin D supplementation versus placebo or no intervention may increase or reduce all-cause mortality, liver-related mortality, serious adverse events, or non-serious adverse events in adults with chronic liver diseases. There is a lack of data on liver-related morbidity and health-related quality of life. Further evidence on clinically important outcomes analysed in this review is needed.

Innovations in infertility: a comprehensive analysis of the ClinicalTrials.gov database

To characterize the interventional clinical trials in infertility and to assess whether trial location or industry sponsorship was associated with trial noncompletion. Retrospective review of trials registered with ClinicalTrials.gov. None. None. None. Descriptive statistics characterizing the attributes of the clinical trials including intervention type, topic, population, completion status, size, location, sponsor, and results. The effects of the sponsor and trial location on trial noncompletion were assessed via logistic regression. In total, 505 trials initiated between 2010 and 2020 were included in our analysis. Drug interventions were the most commonly studied (45%); ovarian stimulation trials accounted for 27% of the studies. Live birth was tracked as an outcome by 20% of the studies; 3% of the trials included mental health outcomes. Few trials (15%) enrolled male participants. Only 11% of the trials reported results, and 4% of the trials reported the race or ethnicity of the participants. Most trials (82%) were conducted outside the United States. Overall, 18% of the trials were not completed, most often because of lack of accrual (47%). United States trials had over twice the odds of noncompletion in univariate analysis (odds ratio = 2.48, 95% confidence interval = [1.47, 4.17]); however, this relationship lost significance after adjusting for potential confounders (odds ratio = 0.95, 95% confidence interval = [0.42, 2.14]). Trial sponsorship was not associated with trial noncompletion. Infertility trials predominantly investigated drug interventions, particularly ovarian stimulation. Live birth was an infrequent outcome despite its relevance to patients. Clinical trials should aim to address the unmet needs in fertility care and be inclusive of underserved populations affected by infertility.

Characteristics of dermatology clinical trials 2007-2018: Insights from a systematic analysis of ClinicalTrials.gov

Characteristics of dermatology clinical trials 2007-2018: Insights from a systematic analysis of ClinicalTrials.gov

Trial Sponsorship and Time to Reporting for Phase 3 Randomized Cancer Clinical Trials.

Simple SummaryTimely execution and reporting of cancer clinical trials is important to patients and clinical researchers. Looking at a group of over three hundred cancer clinical trials with published results, we studied what factors influenced how quickly they reported their results in scientific journals. We found that trials sponsored by cooperative groups tended to report more slowly on average, while industry-funded trials reported more quickly. Additionally, we found that even after accounting for other variables that might affect timely reporting—such as whether a trial was successful, the type of cancer studied, or what type of intervention was studied—industry-funded trials still reported more quickly on average than non-industry funded trials. The reasons for these differences in reporting times are important to understand because trial results affect patient care and ongoing clinical research endeavors.The pace of clinical trial data generation and publication is an area of interest within clinical oncology; however, little is known about the dynamics and covariates of time to reporting (TTR) of trial results. To assess these, ClinicalTrials.gov was queried for phase three clinical trials for patients with metastatic solid tumors, and the factors associated with TTR from enrollment completion to publication were analyzed. Based on the 319 included trials, cooperative-group-sponsored trials were reported at a slower rate than non-cooperative-group trials (median 37.5 vs. 31.0 months; p < 0.001), while industry-funded studies were reported at a faster rate than non-industry-supported trials (31.0 vs. 40.0 months; p = 0.005). Furthermore, successful trials (those meeting their primary endpoint) were reported at a faster rate than unsuccessful studies (27.5 vs. 36.0 months; p < 0.001). Multivariable analysis confirmed that industry funding was independently associated with a shorter TTR (p = 0.006), while cooperative group sponsorship was not associated with a statistically significant difference in TTR (p = 0.18). These data underscore an opportunity to improve cooperative group trial efficiency by reducing TTR.

Characteristics of Contemporary Randomized Clinical Trials and Their Association With the Trial Funding Source in Invasive Cardiovascular Interventions

Changes in evidence-based practice and guideline recommendations depend on high-quality randomized clinical trials (RCTs). Commercial device and pharmaceutical manufacturers are frequently involved in the funding, design, conduct, and reporting of trials, the implications of which have not been recently analyzed. To evaluate the design, outcomes, and reporting of contemporary randomized clinical trials of invasive cardiovascular interventions and their association with the funding source. This cross-sectional study analyzed published RCTs between January 1, 2008, to May 31, 2019. The trials included those involving coronary, vascular and structural interventional cardiology, and vascular and cardiac surgical procedures. We assessed (1) trial characteristics, (2) finding of a statistically significant difference in the primary end point favoring the experimental intervention, (3) reporting of implied treatment advantage in trials without significant differences in primary end point, (4) existence of major discrepancies between registered and published primary outcomes, (5) number of patients whose outcomes would need to switch from a nonevent to an event to convert a significant difference in primary end point to nonsignificant, and (6) association with funding source. Of the 216 RCTs analyzed, 115 (53.2%) reported having commercial sponsorship. Most trials had 80% power to detect an estimated treatment effect of 30%, and 128 trials (59.3%) used composite primary end points. The median (interquartile range [IQR]) sample size was 502 (204-1702) patients, and the median (IQR) follow-up duration was 12 (1.0-14.4) months. Overall, 123 trials (57.0%) reported a statistically significant difference in the primary outcome favoring the experimental intervention; reporting strategies that implied an advantage were identified in 55 (65.5%) of 84 trials that reported nonsignificant differences. Commercial sponsorship was associated with a statistically significantly greater likelihood of favorable outcomes reporting (exponent of regression coefficient β, 2.80; 95% CI, 1.09-7.18; P = .03) and with the reporting of findings that are inconsistent with the trial results. Discrepancies between the registered and published primary outcomes were found in 82 trials (38.0%), without differences in trial sponsorship. A median (IQR) number of 5 (2.8-12.5) patients experiencing a different outcome would have change statistically significant results to nonsignificant. Commercial sponsorship was associated with a greater number of patients (exponent of regression coefficient β, 1.29; 95% CI, 1.00-1.66; P = .04). These results suggest that contemporary RCTs of invasive cardiovascular interventions are relatively small and fragile, have short follow-up, and have limited power to detect large treatment effects. Commercial support appeared to be associated with differences in trial design, results, and reporting.

Sponsorship of oncology clinical trials in the United States according to age of eligibility.

BackgroundThe sponsorship mix of trials relevant to young people with cancer has not been reported. Understanding this sponsorship mix may have implications for policies and regulations related to pediatric cancer drug development.MethodsWe analyzed sponsorship of interventional trials first opened in the United States from 2007 to 2018 using the ClinicalTrials.gov registry. A total of 51 781 trials across non‐oncology disciplines and 18 431 oncology trials were classified according to lower age of eligibility (≥18 years vs < 18 years). Studies were stratified according to sponsorship (industry vs non‐industry). Trial characteristics were compared by sponsorship category. Trends in sponsorship were tracked over time.ResultsWithin oncology trials for patients ≥ 18 years, sponsorship was 33% industry and 67% non‐industry. Among oncology trials that included patients < 18 years, sponsorship was 16.6% industry and 83.4% non‐industry (P < .001). 15.5% of industry‐sponsored trials in non‐oncology disciplines included patients < 18 years, whereas only 5.2% of industry‐sponsored oncology trials were open to patients < 18 years (P < .001). Relative to trials with non‐industry sponsors, there was a statistically significant increase in industry sponsorship of oncology trials that included patients < 18 years over time (P < .001). Trial characteristics differed significantly according to sponsor type regardless of age of eligibility.ConclusionsInterventional oncology trials that include patients < 18 years are less likely to be industry‐sponsored compared to oncology trials exclusively in patients ≥ 18 years. Compared to other medical disciplines, a smaller proportion of industry‐sponsored oncology trials included patients < 18 years. Trial sponsorship is associated with differential trial characteristics, such as trial duration and number of patients enrolled, regardless of age.

Reporting of financial conflicts of interest in meta-analyses of drug trials published in high-impact medical journals: comparison of results from 2017 to 2018 and 2009

BackgroundA previous study found that 2 of 29 (6.9%) meta-analyses published in high-impact journals in 2009 reported included drug trials’ funding sources, and none reported trial authors’ financial conflicts of interest (FCOIs) or industry employment. It is not known if reporting has improved since 2009. Our objectives were to (1) investigate the extent to which pharmaceutical industry funding and author-industry FCOIs and employment from included drug trials are reported in meta-analyses published in high-impact journals and (2) compare current reporting with results from 2009.MethodsWe searched PubMed (January 2017–October 2018) for systematic reviews with meta-analyses including ≥ 2 randomized controlled trials (RCTs) of patented drugs. We included 3 meta-analyses published January 2017–October 2018 from each of 4 high-impact general medicine journals, high-impact journals from 5 specialty areas, and the Cochrane Database of Systematic Reviews, as in the previous study.ResultsAmong 29 meta-analyses reviewed, 13 of 29 (44.8%) reported the funding source of included trials compared to 2 of 29 (6.9%) in 2009, a difference of 37.9% (95% confidence interval, 15.7 to 56.3%); this included 7 of 11 (63.6%) from general medicine journals, 3 of 15 (20.0%) from specialty medicine journals, and 3 of 3 (100%) Cochrane reviews. Only 2 of 29 meta-analyses (6.9%) reported trial author FCOIs, and none reported trial author-industry employment.Protocol PublicationA protocol was uploaded to the Open Science Framework prior to initiating the study. https://osf.io/8xt5p/LimitationsWe examined only a relatively small number of meta-analyses from selected high-impact journals and compared results to a similarly small sample from an earlier time period.ConclusionsReporting of drug trial sponsorship and author FCOIs in meta-analyses published in high-impact journals has increased since 2009 but is still suboptimal. Standards on reporting of trial funding described in the forthcoming revised PRISMA statement should be adapted and enforced by journals to improve reporting.

Under Reporting of Patient Reported Outcomes (PROs) in Myeloproliferative Neoplasm (MPN) Clinical Trials

Introduction Improvements in overall survival (OS) and quality of life (QoL) are clinically relevant outcomes that should guide clinical decision-making. Patients with MPNs can live with their disease for a long period of time, which increases the importance of understanding the impact of treatment in regards to a patients' Health-Related QoL. Therefore, including PROs in clinical trials has become paramount in facilitating informed treatment decisions made by health care providers and patients. Furthermore, the FDA encourages the implementation of patient-centric measures in clinical trials. Objective We aimed to evaluate the frequency at which PRO measures are utilized as study endpoints and are made publicly available when trial results are published. Methods A review was conducted to characterize studies that have evaluated PRO in patients undergoing treatment for myeloproliferative neoplasms. We searched Citeline® Trialtrove database, a registry of clinical trials, for randomized clinical trials including patients with all myeloproliferative neoplasms, initiated between the years 2006-2016, utilizing at least 1 PRO. We excluded trials that evaluated supportive care and studies with no publications. For included trials, we recorded the following data: indication, treatment and comparator, clinical development phase, endpoints, trial sponsorship, and type of scale or questionnaire used for PRO endpoint. We then identified all available publications associated with the trial, and recorded type of publication (abstract or full text), year, number of randomized patients, and reported outcomes. Results Thirty-five MPN trials were obtained through our search. Trials included patients with chronic myelogenous leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis, and mastocytosis. Of these 35 trials, 16 were excluded; two studies were classified as supportive care, three studies did not have a publication or were terminated without results, and 11 studies did not have at least one PRO. 19 trials (19/30; 63%) included at least one PRO assessment as an endpoint and were included in the analysis. Among these 19 trials, the commonly used PRO assessments were EQ-5D, EORTC-QLQ C30, Total Symptom Score (TSS), FACT-Leu, FACT-G, MPN-SAF, and Patient Global Impression of Change (PGIC). Three of the 19 trials (15.8%) utilized at least one PRO as a primary endpoint. Among the 19 trials, thirteen (68.4%) were sponsored by industry, three (15.8%) were sponsored by industry-academic collaborations, and three (15.8%) were sponsored solely by academic institutions. 12 studies (63.2%) reported PRO results within their publications. Six studies (31.6%) reported PRO data within their initial publication. Nine of the19 trials (47.4%) included a comprehensive report of PRO data within their publications, while three (15.8%) only partially reported PRO data. Of the 12 trials with published PRO data, four of 12 (33.3%) reported the PRO more than six months after the initial full publication. Most of the included trials focused on disease control outcome and overall survival benefit was not shown. Conclusions: Despite a growing emphasis on QoL and the inclusion of PROs in oncology clinical trials, a significant number of the observed MPN randomized trials did not include a PRO measure. Of those trials that included a PRO measurement, many lacked the comprehensive reporting needed to inform the assessment of clinical benefit and respective decisions. Early and timely reporting of PRO data should be valued, especially in this indication; however, the publication of PRO data along with other critical trial endpoints was not seen in many of the initial trial reports. The collection of PRO data should result in routine, timely, and appropriate reporting as part of the trial outcome publication, to allow for a thorough assessment of investigational clinically relevant treatment effects. If the primary trial publication does not include the PRO results, there should be a reference or acknowledgment to the impending PRO publication. Future research in this field may evaluate the reasons why PROs are not implemented more often in clinical trials and what causal factors have influenced the under-reporting of PRO data in trial publications. Table Disclosures No relevant conflicts of interest to declare.

2.34 TRENDS IN THE SPONSORSHIP, CLINICAL FOCUS, INTERVENTION TYPE, AND TRIAL RIGOR IN PEDIATRIC MENTAL HEALTH CLINICAL RESEARCH: A COMPREHENSIVE REVIEW AND ANALYSIS OF CLINICALTRIALS.GOV

Multiple fields of medicine have analyzed the ClinicalTrials.gov database to provide seminal reviews of their fields’ clinical research. These studies have identified important trends in trial sponsorship, intervention type, clinical focus, and predictors of trial design rigor. Such analyses have not been performed in pediatric mental health clinical trials, which is the aim of this study.

Sponsorship of pediatric oncology interventional trials.

10044 Background: The sponsor of a clinical trial is the single entity responsible for the overall conduct and oversight of the trial. Sponsors may be pharmaceutical/biotech companies (“industry”), government agencies (e.g. NIH), or other entities such as academic institutions. Trial sponsorship may have important regulatory and financial implications for the trial intervention under investigation. We sought to compare oncology trial sponsorship based upon age of eligibility. Methods: We used the clinicaltrials.gov database to evaluate all interventional trials from September 1, 2009 to December 1, 2018. We included all trials regardless of indication and then separately analyzed only oncology trials. We analyzed sponsor status as “industry”, “government”, or “other”. Results: Sponsorship data were available for 59,582 interventional trials across all disciplines (n = 15,564 oncology trials). Across all disciplines and ages of eligibility, lead trial sponsorship was 34% industry, 5% government, and 61% other. Across all oncology trials, sponsorship mix was similar: 31% industry; 6% government, and 62% other. Among adult oncology trials (age of eligibility starting at age 18 years), trial sponsorship was 33% industry, 6% government, and 61% other. Among pediatric-only oncology trials (age of eligibility capped &lt; 18 years), trial sponsorship was 25% industry, 1% government, and 74% other. 5% of industry sponsored trials across all indications were pediatric-only compared to 0.63% of industry-sponsored trials in oncology. 95% of industry sponsored pediatric-only oncology trials were phase 1 or 2 trials, compared to 90% in adults. Conclusions: Pediatric-only interventional oncology trials are less likely to be industry sponsored compared to adult oncology trials or trials across all disciplines. Less than 1% of industry sponsored interventional trials in oncology focus on children &lt; 18 years of age.

Association of Industry and Academic Sponsorship With Negative Phase 3 Oncology Trials and Reported Outcomes on Participant Survival

Only 3.4% of cancer drugs evaluated in phase 1 trials are approved by the US Food and Drug Administration, with most failing in phase 3 trials. To investigate whether an association exists between the sponsorship and conduct of a negative phase 3 randomized clinical trial (RCT) investigating a cancer drug that lacked supporting phase 2 trial evidence for that drug, and to evaluate the association with overall survival among patients randomized to the experimental arm of such phase 3 trials. Articles in the Lancet, Lancet Oncology, JAMA, JAMA Oncology, and Journal of Clinical Oncology published between January 2016 and June 2018 were searched. Phase 3 RCTs of cancer drugs that failed to improve the primary end point were selected and any prior phase 2 trial of the same drug that supported the phase 3 trial was selected without any date or journal restrictions. Percentages of negative phase 3 RCTs of cancer drugs that lacked any phase 2 evidence, had a negative phase 2 trial, or had a positive phase 2 study were extracted. Associations were assessed using the Fisher exact test. Pooled hazard ratios and 95% CIs for the overall survival of patients enrolled in these negative phase 3 RCTs were estimated using a random-effects model. Negative phase 3 RCTs with a lack of a phase 2 trial or the presence of a negative phase 2 trial and overall survival of enrolled patients in the phase 3 RCTs. In this meta-epidemiological study, 67 negative phase 3 RCTs on cancer drugs, which included 64 600 patients, met the criteria of being sponsored by industry or academic groups, of which 42 RCTs (63%) were industry sponsored and the remaining 25 RCTs (37%) were academic. A phase 2 trial was not available for 28 of these trials (42%). Of 29 trials (43%) with a phase 2 trial available, 8 trials (28%) failed to meet their primary end points and 5 of those were industry sponsored. There was no association with overall survival for patients participating in these negative phase 3 RCTs (pooled hazard ratio, 0.99; 95% CI, 0.96-1.02). When the pooled analysis was limited to the 27 RCTs with a hazard ratio above 1.00, the overall pooled hazard ratio for overall survival was 1.11 (95% CI, 1.06-1.16). No association between having a negative or undefined phase 2 trial and trial sponsorship was found using the Fisher exact test. More than 40% of the negative phase 3 RCTs in oncology published in these 5 journals were conducted without a supporting phase 2 trial and were sponsored by both academia and industry. Running such trials not only may risk loss of resources owing to a failed trial but also may be associated with decreased patient survival. Further research and regulations in this area appear warranted.

The relationship of study and authorship characteristics on trial sponsorship and self-reported conflicts of interest among neuro-oncology clinical trials.

To examine the association between trial sponsorship sources, self-reported conflicts of interest (COI), and study and author characteristics in central nervous system (CNS) oncology clinical trials (CT). MEDLINE search was performed for original CT on "Central Nervous System Neoplasms"[Mesh]. The investigators assessed for relationships between funding source (industry, academic or cooperative, none, not described), COI (presented, none, or not reported), CT, and author characteristics. From 2010 to 2015, 319 CT were considered eligible. The majority of the studies involved primary gliomas (55.2%) and were Phase II CT (59.2%). Drug therapy was investigated in 83.0% of the CT. The remaining studies investigated surgery or radiotherapy. A minority of papers were published in journals with impact factor (IF) higher than > 10 (16%) or in regions other than North America and Europe (20.4%). Overall, 83.1% of studies disclosed funding sources: 32.6% from industry alone, 33.9% from an academic or cooperative group, and 10.7% from a mixed funding model. COI data was reported by 85.9% of trials, of which 56.2% reported no COI and 43.8% reported a related COI. Significant predictors for sponsorship (industry and/or academia) on univariate analysis were study design, type of intervention, journal impact factor, study conclusion, transparency of COI and presence of COI. On multivariate analysis, type of intervention, (P < 0.001), journal impact factor (IF) (P = 0.003), presence of COI (P < 0.001) and study conclusion (P = 0.003) remained significant predictors of sponsorship. For predicting COI, significant variables on univariate analysis were disease type, type of intervention, journal IF, funding source, and intervention arm being related to sponsor. On multivariate analysis, disease type (P = 0.003), journal IF (P < 0.001), type of intervention (P = 0.001), and funding source (P = 0.008) remained significant. The majority of CNS CT reported some external funding sources and non-related COI. We identified that drug trials, higher IF, presence of COI, and a neutral or negative study conclusion are associated with external funding. Likewise drug trials, higher IF, and glioma trials are associated with presence of COI.

Differences in Funding Sources of Phase III Oncology Clinical Trials by Treatment Modality and Cancer Type.

Given the limited resources available to conduct clinical trials, it is important to understand how trial sponsorship differs among different therapeutic modalities and cancer types and to consider the ramifications of these differences. We searched clinicaltrials.gov for a cross-sectional register of active, phase III, randomized controlled trials (RCTs) studying treatment-related endpoints such as survival and recurrence for the 24 most prevalent malignancies. We classified the RCTs into 7 categories of therapeutic modality: (1) chemotherapy/other cancer-directed drugs, (2) targeted therapy, (3) surgery, (4) radiation therapy (RT), (5) RT with other modalities, (6) multimodality therapy without RT, and (7) other. RCTs were categorized as being funded by one or more of the following groups: (1) government, (2) hospital/university, (3) industry, and (4) other. χ analysis was performed to detect differences in funding source distribution between modalities and cancer types. The percentage of multimodality trials (5%) and radiation RCTs (4%) funded by industry was less than that for chemotherapy (32%, P<0.01) or targeted therapy (48%, P<0.01). Trials studying targeted therapy were less likely to have hospital/university funding than any of the other modalities (P<0.01 in each comparison). Trials of chemotherapy were more likely to be funded by industry if they also studied targeted therapy (P<0.01). RCTs studying targeted therapies are more likely to be funded by industry than trials studying multimodality therapy or radiation. The impact of industry funding versus institutional or governmental sources of funding for cancer research is unclear and requires further study.

Trial sponsorship and self-reported conflicts of interest in breast cancer radiation therapy: An analysis of prospective clinical trials

PurposeWe aim to assess any association between study and self-reported conflict of interest (COI) or trial sponsorship in breast cancer radiation clinical trials. Materials and methodsWe searched PubMed for all clinical trials (CTs) published between 09/2004 and 09/2014 related to breast cancer. We included only radiotherapy CTs with primary clinical endpoints. We classified eligible trials according to the funding source, presence or absence of conflict of interest, study conclusion and impact factor (IF). Results1,603 CTs were retrieved. 72 randomized clinical trials were included for analysis. For-profit (PO), not for profit organization (nPO), none and not reported sponsorship rates were 9/72 (12.5%), 35/72 (48.6%), 1/72 (1.4%), 27/72 (37.5%), respectively. Present, absent or not reported COI were found in 6/72 (8.3%), 43/72 (59.7%) and 23/72 (32%) of the CTs, respectively. Conclusion was positive, neutral and negative in 57/72 (79.1%), 9/72 (12.5%) and 6/72 (8.4%) of the trials, respectively. Positive conclusion was reported in 33/44 (75%) funded trials (PO and nPO) and 5/6 (83.3%) CTs with reported COI. On univariate analysis no association with funding source (P=0.178), COI (P=0.678) or trial region (P=0.567) and trial positive conclusion was found. Sponsored trials (HR 4.50, 95CI-0.1.23-16.53;P=0.0023) and positive trials (HR 4.78, 95CI- 1.16-19.63;P=0.030) were more likely to be published in higher impact factor journals in the multivariate analysis. ConclusionsnPO funding was reported in almost 50% of the evaluated CTs. No significant association between study conclusion and funding source, COI or trial region was identified. Sponsored trials and positive trials were more likely to be published in higher impact factor journals.

Trial Sponsorship and Self-Reported Conflicts of Interest in Clinical Trials of Central Nervous System Malignancies

Trial Sponsorship and Self-Reported Conflicts of Interest in Clinical Trials of Central Nervous System Malignancies

Trends in Consent for Clinical Trials in Cardiovascular Disease.

BackgroundCardiovascular clinical trials depend on patient enrollment. Enrollment rates appear inadequate, but little is known about how frequently patients accept or decline offers of enrollment. The objective of this study was to assess trends and predictors of patient acceptance of offers to enroll in clinical trials for cardiovascular disease.Methods and ResultsWe utilized an established database containing all randomized, controlled trials (n=1224) in cardiovascular disease published between 2001 and 2012 in the 8 highest‐impact general medical and cardiology journals. Studies were eligible if the number of patients approached and number of patients declining enrollment could be ascertained from published materials. All studies were screened for eligibility. Each eligible study was reviewed by 3 co‐authors. All discrepancies were resolved by the group. The main outcome was acceptance rate, defined as the number of patients enrolled divided by the number patients who were eligible and approached. Only 21.7% (n=266) of studies provided information sufficient to assess patient enrollment and refusals. The median acceptance rate across trials was 83.2%. Significant predictors of higher enrollment included: enrollment in the acute setting (P=0.031); geographical region (P<0.001 for group); and trial sponsorship (P=0.006 for group).ConclusionsRates of reporting data sufficient to calculate acceptance rates are low. This compromises the ability to identify drivers of low enrollment and assess trial generalizability. However, the high rates of acceptance observed suggest that factors other than patients’ decisions may be the primary drivers of declining rates of trial enrollment.