Commercial Trials Research Articles

Early Performance of Selected Citrus Rootstocks Grafted with ‘Valencia’ Sweet Orange in Commercial Settings within a Citrus Greening Endemic Environment

Citrus greening or Huanglongbing (HLB) has caused sweet orange (Citrus sinensis) yield in Florida to decrease by 55% since the disease was first discovered in 2005. As a consequence, the profitability and sustainability of citrus (Citrus sp.) production in Florida have been jeopardized, as evidenced by the 62% reduction in the number of citrus growers statewide. Because there is still no effective treatment or management strategy to cure the disease, it is crucial to optimize grove practices and management. The use of improved rootstocks could increase the tolerance of citrus scions to biotic and abiotic stresses, thereby allowing growers to cope better with the impact of HLB in the field. We used yield data collected from commercial trials over the course of multiple seasons to assess the side-by-side performance of various commercially available rootstocks developed by the two major breeding programs in Florida in HLB-endemic field conditions. We found that some of the rootstocks attained not only statistically significant differences in yield relative to the control but also meaningful differences in revenue. Those estimates provide evidence regarding the effect of rootstock during the first few seasons after planting. Our findings are useful to improve growers’ decision-making processes regarding rootstock selection for new groves.

COMPLETE RECORDING OF COURT BY TECHNICAL MEANS: LEGAL REGULATION, CONTENT AND FUNCTIONS

The article is devoted to the study of the principle of full fixation of the trial by technical means in the procedural legislation of Ukraine using an interdisciplinary approach. It was found that with the exception of the Code of Ukraine on Administrative Offenses, all current procedural codes of Ukraine contain provisions which establishes the obligation of means using the full recording of the trial court including those of the product of the recording – record the court hearing made by technical means. In the commercial, administrative and civil proceedings kinds trial recording can take place not only in court but also outside the court session, the Criminal Procedure Code of Ukraine stipulates that full recording of court hearings and procedural actions with the help of audio and video recording equipment is provided not only during the trial, but also in the cases provided for by this Code during the pre-trial investigation. As a result it is justified that the concept of “litigation” is much broader than the concept of “court hearing” and in the context of the constitutional principle of justice – “completeness of fixation by technical means” – to correctly use the concept of “litigation” and not “court hearing or proceedings”. With international experience analysis of the interaction principles of transparency, openness and publicity of the principle of full trial recording by technical means. It is proved that the consolidation at the level of the Constitution of Ukraine and the procedural legislation of Ukraine of the obligatory recording by technical means of the course of the court session is a necessary addition to the principle of publicity. In order to ensure the openness of the content of the court hearing to the participants of the relevant process and the general public. It is determined that further digitalization of court activities and litigation will lead to a new reading of the traditional principles of litigation. It is substantiated that the completeness of recording the trial by technical means should be ensured by all available means to fully reflect information about events that are recorded to ensure awareness of information that is important for assessment not only by the court in making court decisions but also participants and the public. It is determined that the functions of full recording of the trial by technical means are: fixing, information, technical and modernization, educational, preventive and procedural economy.

Effects of Revalor-XH, Revalor-200, and combination Revalor-IH/Revalor-200 on yearling beef heifer growth performance and carcass characteristics for 138 days on feed

The objective was to evaluate finishing heifer implant programs including a single noncoated implant (Revalor-200; REV-200); an initial noncoated implant (Revalor-IH) followed by another noncoated implant (Revalor-200; REV-IH/200) 80 d before slaughter; or a partially coated, delayed-release implant (Revalor-XH; REV-XH) on growth performance and carcass characteristics when heifers were fed for 138 d. A commercial feedlot trial used 1,728 crossbred heifers (initial BW = 412 kg; SD = 28.2 kg) to examine the 3 implant strategies. Only heifers implanted with REV-IH/200 were removed from their pen at re-implantation. Heifers implanted with REV-IH/200 had greater (P ≤ 0.05) carcass-adjusted final BW, calculated as hot carcass weight/DP, and G:F compared with heifers implanted with REV-200 or REV-XH. Treatment did not affect (P ≥ 0.24) final BW or ADG on a live basis. Heifers implanted with REV-IH/200 had greater (P ≤ 0.05) hot carcass weight and LM area compared with heifers implanted with REV-200 or REV-XH. Marbling score and 12th-rib fat thickness were not different (P ≥ 0.12) among implant treatments. Calculated YG were decreased (P = 0.05) for heifers implanted with REV-IH/200 compared with heifers implanted with REV-200, with a significant (P < 0.01) shift to a lower calculated YG distribution for heifers implanted with REV-IH/200 compared with REV-200 or REV-XH. Greater concentrations of trenbolone acetate and estradiol-17β improved carcass-adjusted G:F and hot carcass weight but did not significantly decrease marbling despite heifers having a lower calculated YG.

Evaluation of Avian Reovirus S1133 Vaccine Strain in Neonatal Broiler Chickens in Gastrointestinal Integrity and Performance in a Large-Scale Commercial Field Trial

Avian reovirus (ARV) is the principal cause of several diseases. The vaccination of breeders allows for the control of viral arthritis and delivery of maternal-derived antibodies to the progeny. The vaccination of broiler chickens with ARV strain S1133 is used to prevent viral arthritis. However, the post-vaccination enteric effects have not been well-characterized. The purpose of this study was to evaluate the effect of vaccination with the S1133 strain on the weight gain and feed conversion of broiler chickens and to characterize the gastric, enteric, and pancreatic lesions that the strain could induce. A total of 672,000 chickens were divided into two groups: a group vaccinated with ARV strain S1133 (S1133ARV) and a control group (not vaccinated). Upon histological analysis, the vaccine group showed less proventricular glandular tissue and atrophy of the pancreas and duodenal villi, as well as having a lower average daily profit. The conclusion based on the results of this investigation is that neonatal vaccination with S1133ARV causes atrophy of the pancreatic acini, proventricular glands, and intestinal villi, leading to an increased diameter of the glandular lumen and atrophy of the enteric villous, as well as weight loss, in broiler chickens.

A guide to eliminating baggy webs

Slack or baggy webs can cause misregistration, wrinkles, and breaks in printing and converting operations. Bagginess appears as non-uniform tautness in the cross direction (CD) of a paper web. The underlying cause is uneven CD tension profiles, for which there are few remedies once the paper is made. Precision measurements of CD tension profiles combined with trials on commercial paper machines have shown that uniform CD distribution of moisture, basis weight, and caliper profiles at the reel are key to avoiding bagginess. However, the most important but infrequently measured factor is the CD moisture profile entering the dryer section. Wetter areas entering the dryers are permanently elongated more than dry areas, leading to greater slackness in the finished paper. In storage, wound-in tension can amplify baggy streaks in paper near the surface of a roll and adjacent to the core. Unwrapped or poorly wrapped rolls exposed to low humidity environments may have baggy centers caused by moisture loss from the roll edges. All of the factors that impact bagginess have been incorporated in a mathematical model that was used to interpret the observations from commercial trials and can be used as a guide to solve future problems.

Molecular Profiling of Relapsed and Refractory Myeloma Identifies Frequent Bi-Allelic Driver Events — Interim Results of the ‘Myeloma UK Seven’ Biomarker Trial

IntroductionPomalidomide and low-dose dexamethasone (PomDex) are approved for relapsed and refractory myeloma (RRMM) with Overall Response Rates of about 30%, including durable remissions. Combining PomDex with biologic agents can improve response, but there are currently no markers to predict which patients benefit from the addition of drugs to PomDex alone. Myeloma UK (MUK) seven is a multi-center UK phase II trial that is designed to generate evidence for improved outcomes and treatment stratification in RRMM by: 1) building a bio-repository for molecular characterization of RRMM and discovery of predictive markers for response 2) patient randomisation to Cyclophosphamide-PomDex (CyPomDex) or PomDex to investigate if the cost-effective CyPomDex combination increases progression free survival compared to PomDex 3) a flexible design that allows addition of trial arms with other promising PomDex combinations. We report high patient and investigator bio-sampling adherence and first comprehensive genetic profiling results in RRMM using a novel molecular assay platform.MethodsMUKseven (NCT02406222) will in total recruit 250 RRMM patients who are currently randomised 1:1 to CyPomDex or PomDex therapy. Registered patients undergo bone marrow sampling at screening, Cycle 1 Day 14, Cycle 4 Day 14 and at disease progression, and peripheral blood sampling on Cycle 1 Day 1. Patient consent includes mandatory bio-sampling at screening. Material is shipped to central laboratories for processing and storage of CD138-purified (>95%) MM tumor and non-tumor bone marrow microenvironment cells. Participants are currently recruited from over 30 NHS Hospitals in the MUK Early Phase Clinical Network.Digital multiplex ligation-dependent probe amplification (dMLPA®; MRC Holland) is a novel assay for high-throughput genome-wide copy number aberration (CNA) profiling. The MM specific D006 assay contains 160 probes that interrogate regions frequently affected by CNA in MM, including hotspots CDKN2C, CKS1B, MYC and regions encoding for therapeutic targets such as MCL1 or SLAMF7. In addition, 219 probes are distributed over all chromosomal arms and inform a virtual karyogram. The targeted design allows for analysis of over 80 patient samples in a single MiSeq (Illumina) run, using 10-20 ng DNA input material.ResultsBetween March 2016 and July 2017 a total of 83 patients were randomised to MUKseven with a median follow up of 6 cycles (1-13). Bone marrow material was received by central laboratories for all patients (100%) at screening, 69/79 (87.3%) at Cycle 1 day 14, 47/54 (87.0%) at Cycle 4 day 14 and 13/29 (44.8%) at disease progression. Peripheral blood was received for 73/79 (92.4%) on Cycle 1 Day 1. These return rates are higher than those reported for recent commercial trials. Of importance, for 52% of patients, matched bone marrow samples from earlier disease stages collected as part of UK academic research studies were available.We profiled the first 81 RRMM samples from trial entry with dMLPA and compared CNA frequency to a recently published newly diagnosed MM (NDMM) cohort which was assessed with MLPA (Shah V, Leukemia 2017). We found significantly more focal bi-allelic CNA of driver lesions in RRMM than in NDMM (P = 0.002). These included homozygous deletions of CDKN2C (6.2 vs 1.9%) and RB1 (3.7 vs 0.8%), amplifications of MYC (8.6 vs 2.3%), and heterozygous losses of TP53 (16.0 vs 9.6%). There were significantly more RRMM patients with one or more of the following bi-allelic changes: CDKN2C, RB1 or CYLD homozygous loss, or 1q amplification (18.5 vs 8.2%; P = 0.007), and 3.7% of patients in the RRMM cohort showed more than one bi-allelic change. We identified frequent homozygous deletions in NFκB pathway genes such as CYLD (4.9%), and recurrent amplifications of therapeutic targets like MCL1 and SLAMF7 on chromosome 1 (8.6% amplifications). The trial is recruiting and profiling of additional cases as well as longitudinal profiling of cases with material from earlier disease stages is ongoing.ConclusionWe demonstrate highly successful conduct of a multi-center biomarker discovery trial by the Myeloma UK Clinical Trial Network and the UK Myeloma Research Alliance. Our results demonstrate that bi-allelic CNA increase significantly in RRMM and some of these may help guide therapy. Recruitment and analyses of additional cases enrolled into MUKseven are ongoing and updated data will be presented at the meeting. DisclosuresPawlyn:Takeda: Honoraria, Other: Travel support; Janssen: Other: Travel support; Celgene: Honoraria, Other: Travel support. Atanesyan:MRC-Holland: Employment. Savola:MRC-Holland: Employment. Thakurta:Celgene Corporation: Employment, Equity Ownership. Garg:Janssen: Other: travel support, Research Funding, Speakers Bureau; Takeda: Other: travel support; Novartis: Other: travel support, Research Funding. Cook:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetcs: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau. Boyd:Janssen: Honoraria, Other: Travel support; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Kaiser:Takeda: Consultancy; BMS: Consultancy, Other: Travel expenses; Janssen: Honoraria; Chugai: Consultancy; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding.

Patient-Reported Outcomes After Treatment Discontinuation: Commercial Clinical Trial Data From Four Cancer Types

ObjectivesHow frequently patient-reported outcome (PRO) data are collected in commercial cancer clinical trials after treatment discontinuation and the quality of that data are poorly understood. We reviewed treatment discontinuation follow-up PRO data collection to learn about trials collecting these data and understand data quality. The review included 4 cancer types representing potential for long- (prostate cancer), medium-/long- (breast cancer), and short-term (pancreatic cancer and hepatocellular carcinoma) follow-up owing to disease trajectory. MethodsWe reviewed registration trials in US Food and Drug Administration databases between January 2010 and January 2019. Protocols were reviewed to determine whether PROs were collected and, if so, whether these included the follow-up phase. Clinical study reports were reviewed when follow-up PROs were collected to determine completion rates. Results were summarized using descriptive analyses. ResultsOf the 46 trials containing PRO data, 46% had at least 1 follow-up PRO assessment. Follow-up schedules of assessment were wide ranging; the first assessment occurred between 30 days and 6 months after stopping treatment with follow-up for as long as 3 years. PRO completion rates were reported in 57% of 21 trials; at the first follow-up assessment, completion rates for the treatment arm ranged from 38% to 91% and from 41% to 100% in the control arm. ConclusionsThe quality of the follow-up PRO data, based on completion rates, was variable, as was the duration of follow-up. A clear research objective should be developed for follow-up PRO data, accounting for patient burden. If PRO data are collected, monitoring should be implemented to improve completion because poor completion limits data use in the benefit-risk assessment.

Assessment of Novel Water Applied Prebiotic to Evaluate Gut Barrier Failure and Performance in Two Commercial Trials in Brazil. A Pilot Study With an Economic Perspective.

The present study evaluated the effect of administration of a water applied prebiotic on gut barrier failure (Experiment 1) and performance in broiler chickens under commercial conditions (Experiment 2). Experiment 1, one thousand four hundred and forty day-of-hatch Ross broiler chickens were assigned to one of two experimental groups (n = 30 replicate pens/treatment; n = 24 chicks/pen). Birds in the treated group received the prebiotic orally in the drinking water (0.2ml/bird) on days 3 and 17 of age. The second group served as the untreated control group. On d 18, intestinal samples were analyzed by qRT-PCR to determine the expression of MUC2, IL-8, TGF-β4, and ZO-1. On d 17, d 28, and d 35 blood samples were collected to determine circulating endotoxin levels. On d 28, mucosal intestinal scrapping was collected to measure relative total sIgA levels. At d 42, liver samples were collected to evaluate liver bacterial translocation. In Experiment 2, the prebiotic was evaluated in two commercial trials. Chickens were raised under normal production conditions and fed a 3-phase commercial basal diet with enramycin (7 g/ton). In Trial 1, 8,974,237 broiler chickens were treated with the prebiotic. The prebiotic was administered in the drinking water (0.2 mL/bird) following the manufacture label instructions at day three and seventeen of life. Production parameters were compared to historical information from the company over the same broiler operation and production cycles. For trial 2, 921,411 broiler chickens were treated with the prebiotic as in Trial 1. In Experiment 1, treated chickens showed a significant (P < 0.05) increase in mRNA expression of MUC2, TGF-β4, IL-8, ZO-1, and sIgA, but a significant reduction of serum endotoxin levels and incidence of liver lactose positive bacterial translocation when compared to non-treated chickens. In both trials of Experiment 2, a significant reduction in total mortality was observed in the treated chickens when compared with the historical farm data. Economic analysis utilizing the total percent of mortality revealed a $1: $2.50 USD and $1: $4.17 USD return for Trial 1 and Trial 2, respectively. The results suggest that the prebiotic positively influences gastrointestinal integrity and performance.

Institutionally chartered Data and Safety Monitoring Boards: structured approaches to assuring participant safety in clinical research

Data and Safety Monitoring Boards (DSMBs) derived from the need to monitor large federally funded multi-center clinical trials and evolved to include commercial and other large and complex trials. Eventually,...

PCN210 Patient-Reported Outcomes in Commercial Pediatric Oncology Clinical Trials

Pediatric patient-reported outcome (PRO) data can complement existing safety and efficacy data by quantifying symptom and functional outcomes from the patient’s perspective. This information can help inform FDA’s benefit-risk assessment of cancer therapeutics. This study assessed use of PROs in pediatric oncology registrational trials submitted for FDA review.

Fed-Batch System for Propagation of Brewer’s Yeast

A novel high-density yeast propagation system has been developed, which produced yeast that performed as well as cropped yeast in commercial brewery trials. This process is capable of producing yeast concentrations 13 times greater than traditional yeast propagation approaches used in breweries to date. The system is based on a controlled fed-batch yeast fermentation, which can produce pitching yeast in as little as 24 h. A demonstrator plant was installed in a regional brewery and yeast produced from the test-platform was used to pitch commercial brews. Plant-scale trials have shown that the yeast propagated using this new system had the same fermentation profile compared to control fermentations that used cropped yeast. Volatile analysis showed no significant difference between the control and experimental beers. The experimental beers tasted true-to-type and were released to trade. The new process allows for smaller pitching volumes while maintaining overall beer quality.

Effects of dietary supplementation of heat-killed Lactobacillus plantarum L-137 on growth performance and immune response of bighead catfish (Clarias macrocephalus)

The aim of this study was to determine the effects of heat-killed Lactobacillus plantarum L-137 (HK L-137) on the growth performances and immune response of juvenile bighead catfish (Clarias macrocephalus). The experiment was conducted with four iso-nitrogenous (44.8 % crude protein) and iso-caloric (20.17 KJ g−1) diets supplemented with different levels (0, 10, 20, and 50 mg kg−1) of HK L-137. The bighead catfish (n = 1800, average body weight: 9.69 ± 0.24 g) were randomly introduced to 200-L composite tanks (filled with 150 L of fresh water) and stocked at 150 fish tank−1 in triplicates per dietary treatment for 60 days. The results showed that the diets supplemented with 10, 20, and 50 mg kg−1 of HK L-137 significantly increased the growth, protein efficiency ratio, feed conversion ratio, survival rate, and lysozyme activity compared to the control. Furthermore, the diets supplemented with 20 and 50 mg kg−1 or 10 and 20 mg kg−1 of HK L-137 significantly enhanced the total white blood cell count or apparent digestibility coefficient of the fish, respectively. The fish fed the HK L-137 diets (at 10, 20, and 50 mg kg−1) revealed lower cumulative mortality than the control after challenge with Aeromonas hydrophila. Our results suggested that dietary supplementation of 10 mg kg−1 HK L-137 is the most efficient in improving the performance and immunity of bighead catfish; however, this should be confirmed in further study under full-scale commercial trials.

Frailty in relapsed/ refractory multiple myeloma registration trials.

e20017 Background: Multiple Myeloma (MM) is predominantly a disease of older adults with a median age of onset at 70 years. There is growing interest in using criterion other than chronological age, like frailty, to determine fitness for treatment and ultimately improve clinical outcomes in MM. Frailty is the accumulation of aging-associated diseases and disabilities, making patients more vulnerable to adverse outcomes when exposed to stressors like anti-cancer treatment. MM frailty measures have primarily been developed and tested in newly diagnosed patients. MM patients typically relapse, but there is limited knowledge regarding the prevalence of frailty in the relapsed/refractory (RRMM) setting. The aim of this research was to determine the prevalence of frailty in RRMM commercial clinical trials, at the time of trial enrollment, using the International Myeloma Working Group (IMWG) Frailty Index. Methods: We pooled baseline data from 6 RRMM clinical trials submitted for FDA regulatory review between 2010 and 2020. The IMWG Frailty Index was calculated for each patient based on 4 variables: age (≤75, 75–80, &gt;80 years, score 0, 1, 2, respectively), Charlson Comorbidity Index (CCI; ≤1 or ≥2, score 0 or 1), and (Instrumental) Activities Daily Living (ADL &gt;4 or ≤4, score 0 or 1; IADL &gt;5 or ≤5, score 0 or 1). As ADLs and IADLs are not routinely collected in clinical trials, we substituted this information with corresponding EQ-5D items on self-care and usual activities. Fit, Intermediate-fit, and Frail patients received IMWG scores of 0, 1, and ≥2 respectively. Descriptive statistics for frailty were summarized by age. Results: 2766 RRMM patients were aggregated from six clinical trials. 1502 (54%) patients were Fit, 780 (28%) were Intermediate-fit, and 484 (18%) were Frail. The median age of patients across trials was 65 [range 30-91]. The median CCI was 0 [range 0-7] out of 37. IMWG frailty scores have been presented by age category in Table. Prevalence of frailty at baseline by age in RRMM registration trials. Conclusions: Most patients in RRMM registration trials were classified as Fit at baseline, using the IMWG Frailty Index. This was expected due to stringent trial enrollment criteria which exclude patients with severe comorbidities, as reflected in the low average CCI. The IMWG index heavily weights patient age. As such, there were no Fit patients in the 75 – 80 year old cohort and only Frail patients in the 80+ year old cohort. This is despite the fact that these older patients met stringent trial enrollment criteria and had CCI scores &lt; 7. Chronologic age alone should not be used as an absolute exclusion for treatment, whether in the trial or real-world setting. Future research into frailty indices that do not heavily weight age is warranted.[Table: see text]

275 Comparison of Revalor-xh with a revalor-ih/revalor-h/revalor-200 Re-implant Program on Feedlot Cattle

Abstract A commercial feedlot trial evaluated a 3-implant re-implant program using Revalor-IH/Revalor-H/Revalor-200 compared to a single Revalor-XH (200 mg TBA and 20 mg E2 partially coated) implant strategy on feedlot performance and carcass characteristics of calf fed heifers. Heifer calves (n = 1356) were purchased through time and blocked by source and arrival date, assigned randomly to pen within block, and pen assigned randomly to one of the two implant treatments. Heifers who received the 3-implant re-implant treatment were re-implanted on d67 with Revalor-H and on d137 with Revalor-200. Each block of cattle were harvested on the same study day, which averaged 215 days on feed. Performance data were analyzed as a randomized block design, with the blocking factor as source/arrival time being considered random. Implant strategy was analyzed as a fixed effect with pen (n = 20) as the experimental unit. On a live basis, heifers implanted with Revalor-XH had a tendency for a greater gain efficiency (P = 0.06) though there were no significant differences between implant treatments for final body weight, gain or intake (P ≥ 0.15). There were no significant differences between implant treatments for hot carcass weight, gain, or gain efficiency (P ≥ 0.29) on a carcass-adjust basis. Marbling score and 12th rib fat thickness were not impacted by implant treatment (P ≥ 0.80); however, there was an increase in LM area (P = 0.02) for heifers on the 3-implant re-implant treatment compared to the Revalor-XH implanted heifers. There was also a tendency for a greater calculated YG in heifers who received Revalor-XH (P = 0.07). Heifers fed for approximately 215 d with a single Revalor-XH implant performed similarly to heifers fed the same amount of days receiving a 3-implant re-implant strategy using Revalor-IH/H/200 combination.

Commercial herbicides trial against Alocasia sp. (wild yam) at oil palm plantation, Borneo, Malaysia

Weeds in oil palm plantations include any plant or vegetation that in any way interferes with the production of palms, resulting in a reduction in yield or quality. Alocasia sp. (wild yam) is a common weed at oil palm plantation in Borneo, Malaysia. This study was conducted to evaluate commercial herbicides’ effectiveness (amine, ally, glyphosate, and paraquat) against Alocasia sarawakensis, Alocasia robusta, and A. macrorrhizos. Cocktail herbicide showed faster wilting, scorching and rotten and least/late regeneration within 30 days of monitoring. Combination of two chemicals reacted better and potentially long-lasting, and further observation can provide info on the difference between (systemic+contact), (contact+contact) and (systemic+systemic). Cost-effectiveness analysis showed herbicides cocktails Treatment 9 (amine + ally + surfactant), Treatment 11 (amine + paraquat + surfactant), and Treatment 12 (ally + paraquat + surfactant) were the most cost-effective (±RM0.58 cent/16 L) to control Alocasia sp. This study’s finding would give an alternative solution for oil palm plantation to control weed, especially Alocasia sp.

Patient-Reported Outcomes in Pediatric Cancer Registration Trials: A US Food and Drug Administration Perspective.

Pediatric patient-reported outcome (PRO) data can help inform the U.S. Food and Drug Administration's (FDA) benefit-risk assessment of cancer therapeutics by quantifying symptom and functional outcomes from the patient's perspective. This study assessed use of PROs in commercial pediatric oncology trials submitted to FDA for regulatory review. FDA databases were searched to identify pediatric oncology product applications approved between 1997 and 2020. Sponsor-submitted documents were reviewed to determine whether PRO data were collected, which instruments were used, and the quality of collected data (sample size, completion rates, and use of fit-for-purpose instruments). The role of PROs in each trial (endpoint hierarchy) was also recorded, along with whether any PRO endpoints were included in product labeling. Seventeen pediatric oncology applications were reviewed, 4 included PRO data: Denosumab, Tisagenlecleucel, Larotrectinib, and Selumetinib. In these 4 instances, PROs served as exploratory endpoints and were not incorporated in product labeling. Trials collecting PRO data were Phase II or Phase I/II single-arm studies with sample sizes of 28 to 88 patients. Symptomatic Adverse Events were characterized using clinician-reported Common Terminology Criteria for Adverse Events (CTCAE) without additional patient self-report. PROs were infrequently utilized in pediatric cancer registration trials. When used, PRO data were limited by lack of a clear research objective and corresponding prospective statistical analysis plan. Contemporary PRO symptom libraries such as the National Cancer Institute's Pediatric PRO-CTCAE may provide an opportunity to better evaluate the occurrence and impact of symptomatic Adverse Events, from the patient's perspective, in pediatric oncology trials.

Algal Extracts as Plant Growth Biostimulants

The review summarizes and systematizesthe data accumulated in recent years as a result of research and commercial trials of seaweed extracts (SE). The results of the assessment of SE as a special class of biostimulants and the key problems of the manufacturing process of SE biostimulants are presented. The chemical composition of SE and a range of their positive effects on plants, such as accelerating seed germination and rooting of cuttings, stimulating the growth of shoots and roots, increasing the efficiency of nutrient uptake and plant yield are described. Evidence is given for the ability of SE to alleviate plant stress caused by various abiotic or biotic factors. Possible involved mechanisms at metabolic and genetic level are discussed. Examples of the influence of SE on plant rhizosphere are considered. The priority tasks are stated, the solution of which should determine the prospects for the use of SE in agriculture in the coming years.

Soybean (Glycine max) cropping in Sweden – influence of row distance, seeding date and suitable cultivars

ABSTRACT Field trials were conducted 2010–2012 in soybeans (Glycine max (L.) Merr.) to investigate cultivar choice, suitable seeding dates and row distances for cropping in Sweden. The cultivar trials showed that commercially available varieties of the 000-group can be used for cropping in Sweden. Yield typically amounted to 1500–2500 kg ha−1 of dry marketable seeds. Cultivars introduced to Sweden should be tested in the field before large-scale production as the 000-classification not fully is valid for Swedish conditions. Row distance (12.5; 25 and 50 cm) had no overall statistically significant impact on yield, but 25 or 50 cm are recommended as these distances are suitable for physical weed control such as row cultivation or torsion weeding. Seeding in the period May 15–30th is recommended to secure germination and yield. The outcome of the trials was supported by results from field demonstrations and commercial cultivar trials in 2013–2014.

Abstract PD12-12: Floor and ceiling effects in the EORTC QLQ-C30 physical functioning subscale among patients with breast cancer enrolled in commercial clinical trials vs. a community trial

Abstract Background: The EORTC QLQ-C30 Physical Functioning (PF) subscale is a widely used patient-reported outcome (PRO) measure that quantifies cancer patients’ physical function. Responsiveness, the degree to which a scale can assess clinical deterioration and improvement, is an important measurement characteristic that can be assessed by looking at floor and ceiling effects. A floor effect is defined as a high proportion of study participants reporting the lowest possible score in the variable of interest, while a ceiling effect is the opposite. We characterized floor and ceiling effects of the PF subscale in patients with breast cancer enrolled in commercial clinical trials vs. a community-based trial.Objectives: (1) Determine floor/ceiling effects of the QLQ-C30 PF items and subscale among patients receiving treatment for breast cancer (2) Compare floor/ceiling effects among patients enrolled in randomized clinical trials vs. those treated in a community care trial.Methods: PF data from 5 breast cancer commercial clinical trials submitted to the FDA for review were pooled (Clinical Trial or CT Cohort). A subgroup of breast cancer patients from the Alliance PRO-TECT trial was also analyzed (Community Cohort). Descriptive statistics were used to assess floor/ceiling effects, distributions of PF items, and the summed PF score at baseline and follow-up, for both cohorts. Results: The CT Cohort and Community Cohort consisted of 5,975 and 178 patients, respectively. Most patients in both cohorts were female, over the age of 50, and White. They were from varied treatment settings (adjuvant, 1st line, and 2nd line). 78% of CT patients had a baseline ECOG score of 0 (fully active), vs. only 44% in the Community Cohort. Baseline and follow-up floor effects (i.e. % of patients with the lowest response option - “not at all”) are presented in Table 1. Floor effects were more pronounced in the CT Cohort, with 43 to 94% of CT patients responding “not at all” to items in the PF subscale at baseline vs. 24 to 89% in the Community Cohort. Additionally, smaller proportions of CT patients responded “not at all” at Cycle 3 follow up compared to baseline. Meanwhile, floor effects in the Community Cohort were similar at baseline and month 3 follow up.Ceiling effects (i.e. % of patients with the highest domain response) were also observed in both cohorts. Over 54% of CT patients scored ≥93/100 on the 100-point PF subscale, at baseline. This proportion decreased to 30% at Cycle 3 follow up. On the other hand, 26% of community patients scored ≥93/100 on the PF subscale, at baseline. This proportion increased to 30% at Month 3. Conclusion: We observed high floor/ceiling effects in the PF domain of the QLQ-C30 among patients in commercial clinical trials, more so than in the community. Inclusion of patient advocacy groups in the item selection process may increase the relevancy and sensitivity of the PF domain to the population being studied. Stakeholders in clinical trial and clinical practice settings may consider adding additional high functioning items from the EORTC’s item library, to more accurately determine the impact of anti-cancer treatment on patients’ physical functioning. Table 1: Baseline and Follow Up Floor Effects - % of patients responding “not at all”Clinical Trial CohortCommunity CohortBaselineCycle 3BaselineMonth 3ItemQuestion% (n)% (n)% (n)% (n)1Do you have any trouble doing strenuous activities, like carrying a heavy shopping bag or a suitcase?43% (2,540)27% (573)24% (42)27% (43)2Do you have any trouble taking a long walk?60% (3,554)28% (585)24% (42)30% (47)3Do you have any trouble taking a short walk outside of the house?88% (5,256)68% (1,395)58% (104)64% (101)4Do you need to stay in bed or a chair during the day?73% (4,364)57% (1,181)46% (82)51% (81)5Do you need help with eating?94% (5,599)93% (1,904)89% (159)91% (145) Citation Format: Meena N Murugappan, Bellinda King-Kallimanis, Christina Mangir, Lynn Howie, Vishal Bhatnagar, Julia A Beaver, Ethan Basch, Paul G Kluetz. Floor and ceiling effects in the EORTC QLQ-C30 physical functioning subscale among patients with breast cancer enrolled in commercial clinical trials vs. a community trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD12-12.

Multi-omics-based prediction of hybrid performance in canola

Key messageComplementing or replacing genetic markers with transcriptomic data and use of reproducing kernel Hilbert space regression based on Gaussian kernels increases hybrid predictionaccuracies for complex agronomic traits in canola.In plant breeding, hybrids gained particular importance due to heterosis, the superior performance of offspring compared to their inbred parents. Since the development of new top performing hybrids requires labour-intensive and costly breeding programmes, including testing of large numbers of experimental hybrids, the prediction of hybrid performance is of utmost interest to plant breeders. In this study, we tested the effectiveness of hybrid prediction models in spring-type oilseed rape (Brassica napus L./canola) employing different omics profiles, individually and in combination. To this end, a population of 950 F1 hybrids was evaluated for seed yield and six other agronomically relevant traits in commercial field trials at several locations throughout Europe. A subset of these hybrids was also evaluated in a climatized glasshouse regarding early biomass production. For each of the 477 parental rapeseed lines, 13,201 single nucleotide polymorphisms (SNPs), 154 primary metabolites, and 19,479 transcripts were determined and used as predictive variables. Both, SNP markers and transcripts, effectively predict hybrid performance using (genomic) best linear unbiased prediction models (gBLUP). Compared to models using pure genetic markers, models incorporating transcriptome data resulted in significantly higher prediction accuracies for five out of seven agronomic traits, indicating that transcripts carry important information beyond genomic data. Notably, reproducing kernel Hilbert space regression based on Gaussian kernels significantly exceeded the predictive abilities of gBLUP models for six of the seven agronomic traits, demonstrating its potential for implementation in future canola breeding programmes.