Participation in a single-blinded pediatric therapeutic strategy study for juvenile idiopathic arthritis: are parents and patient-participants in equipoise?

BACKGROUND: Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials (RCT) need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. METHODS: We compared preferences of parents/patients at enrolment, documented by a questionnaire (phase 1), with preferences developed during follow-up by an interview-study (phase 2) to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study (NTR 1574). This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug (DMARD), currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. RESULTS: Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority (n = 19) stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. CONCLUSIONS: Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians' research question is in line with preferences of the patient-group. By exploring so-called 'informed patient-group'-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms.

Improved nitrogen nutrition enhances root uptake, root-to-shoot translocation and remobilization of zinc ((65) Zn) in wheat.

This study focussed on the effect of increasing nitrogen (N) supply on root uptake and root-to-shoot translocation of zinc (Zn) as well as retranslocation of foliar-applied Zn in durum wheat (Triticum durum). Nutrient solution experiments were conducted to examine the root uptake and root-to-shoot translocation of (65) Zn in seedlings precultured with different N supplies. In additional experiments, the effect of varied N nutrition on retranslocation of foliar-applied (65) Zn was tested at both the vegetative and generative stages. When N supply was increased, the (65) Zn uptake by roots was enhanced by up to threefold and the (65) Zn translocation from roots to shoots increased by up to eightfold, while plant growth was affected to a much smaller degree. Retranslocation of (65) Zn from old into young leaves and from flag leaves to grains also showed marked positive responses to increasing N supply. The results demonstrate that the N-nutritional status of wheat affects major steps in the route of Zn from the growth medium to the grain, including its uptake, xylem transport and remobilization via phloem. Thus, N is a critical player in the uptake and accumulation of Zn in plants, which deserves special attention in biofortification of food crops with Zn.