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Enrollment of children into pediatric clinical trials remains challenging. More effective strategies to improve recruitment of children into trials are needed. This study used in-depth qualitative interviews with parents who were approached to enroll their children in a clinical trial in order to gain an understanding of the barriers to pediatric clinical trial participation.Twenty-four parents whose children had been offered the opportunity to participate in a clinical trial were interviewed: 19 whose children had participated in at least 1 clinical trial and 5 who had declined participation in any trial. Each study aspect, from the initial explanation of the study to the end of the study, can affect the willingness of parents to consent to the proposed study and future studies. Establishing trust, appropriate timing, a transparent discussion of risks and benefits oriented to the layperson, and providing motivation for children to participate were key factors that impacted parents' decisions.In order for clinical trial accrual to be successful, parents' priorities and considerations must be a central focus, beginning with initial trial design. The recommendations from the parents who participated in this study can be used to support budget allocations that ensure adequate training of study staff and improved staffing on nights and weekends. Studies of parent responses in outpatient settings and additional inpatient settings will provide valuable information on the consent process from the child's and parent's perspectives. Further studies are needed to explore whether implementation of such strategies will result in improved recruitment for pediatric clinical trials.

Exposure of the roots of Alnus glutinosa (L.) Gaertn. to white light stimulated within 5 days a substantial increase in the content of quercetin and kaempferol, two major flavonols in acid hydrolysates of both roots and root exudates. Both compounds were detected also in hydrolysates of root extracts of Myrica gale and Casuarina equisetifolia, the latter a species not nodulated by Frankia strains effective on Alnus. A 7-fold reduction in nodulation of seedlings 12 days after inoculation with Frankia preincubated for 24 h with kaempferol supported the possibility that flavonols might be involved in the regulation of nodulation. Nodulation of seedling roots that were inoculated with Frankia and then exposed to light was inhibited by 50% after 11 days compared with seedlings with darkened roots. This effect of light treatment was preceded by a 30-fold increase in quercetin and kaempferol. The inhibitory effects on nodulation of preincubation of Frankia with kaempferol persisted for 18 days after inoculation, but there was no significant effect on nodulation after prolonging exposure of the root system to light for 40 days. The data support indirectly the suggestion that the balance between stimulatory and inhibitory flavonoids in roots and root exudates may contribute to the regulation of nodulation of actinorhizal plants.Résumé : L'exposition à la lumière blanche pendant 5 jours des racines de l'Alnus glutinosa (L.) Gaertn. stimule une augmentation substantielle de la teneur en quercétine et en kampférol, deux flavonols majeurs qu'on retrouve dans les hydrolysats des racines ainsi que des exsudats. On retrouve également ces deux composés dans les hydrolysats d'extraits racinaires du Myrica gale et du Casuarina equisetifolia, cette dernière espèce de formant pas de nodules avec les souches de Frankia actives sur Alnus. Une réduction de sept fois dans la nodulation de plantules âgées de 12 jours après inoculation avec du Frankia, pré-incubé pendant 24 h dans du kampférol, supporte la possibilité que des flavonols pourraient être impliqués dans la régulation de la nodulation. La nodulation de racines de plantules, inoculées avec du Frankia et exposées par la suite à la lumière, a été inhibée à 50% après 11 jours, comparativement à des racines maintenues à l'obscurité. Cet effet du traitement à la lumière est précédé d'une augmention de 30 fois de la quercétine et du kamférol. Les effets inhibiteurs sur la nodulation, d'une pré-incubation des Frankia avec le kampférol, persistent pendant 18 jours après l'inoculation, mais il n'y a pas d'effet significatif sur la nodulation lorsqu'on prolonge l'exposition à la lumière du système racinaire pendant 40 jours. Les données supportent indirectement la suggestion que la balance entre les flavonoïdes stimulateurs et inhibiteurs, dans les racines et les exsudats racinaires, pourrait contribuer à la régulation de la nodulation chez les plantes actinorhiziennes.

Despite legislation to stimulate pediatric drug development through clinical trials, enrolling children in trials continues to be challenging. Non-investigator (those who have never served as a clinical trial investigator) providers are essential to recruitment of pediatric patients, but little is known regarding the specific barriers that limit pediatric providers from participating in and referring their patients to clinical trials. We conducted an online survey of pediatric providers from a wide variety of practice types across the United States to evaluate their attitudes and awareness of pediatric clinical trials. Using a 4-point Likert scale, providers described their perception of potential barriers to their practice serving as a site for pediatric clinical trials.Of the 136 providers surveyed, 52/136 (38%) had previously referred a pediatric patient to a trial, and only 17/136 (12%) had ever been an investigator for a pediatric trial. Lack of awareness of existing pediatric trials was a major barrier to patient referral by providers, in addition to consideration of trial risks, distance to the site, and time needed to discuss trial participation with parents. Overall, providers perceived greater challenges related to parental concerns and parent or child logistical barriers than study implementation and ethics or regulatory barriers as barriers to their practice serving as a trial site. Providers who had previously been an investigator for a pediatric trial were less likely to be concerned with potential barriers than non-investigators. Understanding the barriers that limit pediatric providers from collaboration or inhibit their participation is key to designing effective interventions to optimize pediatric trial participation.

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