Clinical Trials: A Practical Approach

Objective: T o de v elop a North American Society for Pediatric Ga str oen te rol og y , He pat olo gy , and Nut ri tio n (N ASP GH AN) and Eu rop ea n Soc ie ty fo r Pe di atr ic Gas tr oen te ro log y , Hep at ol og y , and Nut rit io n (ES PGH AN ) int er nat io nal con se ns us on th e di agn os is an d ma nag em ent of gas tr oes op hag eal refl ux and gas tr oes op hag eal re flu x di sea se in th e ped ia tr ic po pu la tio n. Methods: An international panel of 9 pediatric gastroenterologists and 2 epidemiologists were selected by both societies, which de v eloped these guidelines based on the Delphi principle. Statements were based on systematic literature searches using the best-av ailable e vidence from PubMed, Cumulati ve Index to Nursing and Allied Health Literature, and bibliographies. The committee con v ened in face-to-face meetings 3 times. Consensus was achie v ed for all recommendations through nominal group technique, a structured, quantitati v e method. Articles were e v aluated using the Oxford Centre for Evidence-based Medicine Le vels of Evidence. Using the Oxford Grades of Recommendation, the quality of e vidence of each of the recommendations made by the committee was determined and is summarized in appendices. Results: More than 600 articles were re vie wed for this work. The document provides e vidence-based guidelines for the diagnosis and management of gastroesophageal reflux and gastroesophageal reflux disease in the pediatric population. Conclusions: Th is do cum ent is int end ed to be us ed in dai ly pra cti ce fo r th e de v el op me nt of fut ure cli ni cal pra ct ic e gu ide lin es and as a bas is for cli ni cal tr ia ls . JP GN 49 :49 8 – 54 7, 20 09 . Ke y Wo rd s: Cli nic al pra ct ic e gu id el ine s — Di agn os tic te sts — Ga str oes op hag ea l refl ux (GE R) — Ga str oes op hag ea l refl ux di sea se (GE RD ) — The rap eut ic mod al iti es. # 20 09 by Eu rop ea n Soc ie ty fo r Pe di atr ic Gas tr oen te ro log y , Hep at ol og y , and Nut rit io n and No rt h Am er ica n So ci ety for Pe dia tri c Ga str oen te rol og y , Hep at ol og y , an d Nu tr iti on

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Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN)

Gastroesophageal reflux (GER), defined as passage of gastric contents into the esophagus, and GER disease (GERD), defined as symptoms or complications of GER, are common pediatric problems encountered by both primary and specialty medical providers. Clinical manifestations of GERD in children include vomiting, poor weight gain, dysphagia, abdominal or substernal pain, esophagitis and respiratory disorders. The GER Guideline Committee of the North American Society for Pediatric Gastroenterology and Nutrition has formulated a clinical practice guideline for the management of pediatric GER. The GER Guideline Committee, consisting of a primary care pediatrician, two clinical epidemiologists (who also practice primary care pediatrics) and five pediatric gastroenterologists, based its recommendations on an integration of a comprehensive and systematic review of the medical literature combined with expert opinion. Consensus was achieved through Nominal Group Technique, a structured quantitative method. The Committee examined the value of diagnostic tests and treatment modalities commonly used for the management of GERD, and how those interventions can be applied to clinical situations in the infant and older child. The guideline provides recommendations for management by the primary care provider, including evaluation, initial treatment, follow-up management and indications for consultation by a specialist. The guideline also provides recommendations for management by the pediatric gastroenterologist. This document represents the official recommendations of the North American Society for Pediatric Gastroenterology and Nutrition on the evaluation and treatment of gastroesophageal reflux in infants and children. The American Academy of Pediatrics has also endorsed these recommendations. The recommendations are summarized in a synopsis within the article. This review and recommendations are a general guideline and are not intended as a substitute for clinical judgment or as a protocol for the management of all patients with this problem.

Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children: recommendations of the North American Society for Pediatric Gastroenterology and Nutrition.

https://www.espen.org/files/ESPEN-Guidelines/2__ESPEN-ESPGHAN-ECFS_guidelines_on_nutrition_care_for_infants_children_and_adults_with_cystic_fibrosis.pdf

ESPEN-ESPGHAN-ECFS guidelines on nutrition care for infants, children, and adults with cystic fibrosis

Guidelines for evaluation and treatment of gastroesophageal reflux in infants and children

Background

Sequential methods are particularly interesting when recruitment is difficult because they may allow a study to be stopped early while maintaining type I and II error rates.



Methods

This placebo-controlled, randomized double-blind study was aimed at assessing the efficacy of metoclopramide (0.2 mg/kg three times daily during 14 days) on gastroesophageal reflux in infancy. The main end point was the relative variation of the percentage of time at pH <4 between inclusion (day 0) and evaluation (day 14) assessed on two 24-hour esophageal pH recordings. Statistical analysis was performed with use of a sequential method, the triangular test.



Results

The study was stopped after the seventh analysis (39 infants evaluated: 20 placebo and 19 metoclopramide) without showing the expected benefit. Improvement on the main end point was 30% ± 48% (mean ± SD). Corresponding unbiased median estimates were 22% for placebo and 39% for metoclopramide (p = 0.28, sequential analysis). On day 14, the percentage of time at pH 5 minutes was 3.0 ± 3.5 for placebo and 1.9 ± 3.0 for metoclopramide (p = 0.33, t test).



Conclusion

If a tendency for a superior improvement with metoclopramide than with placebo was observed on the main end point, it was lower than expected and the difference was not significant. Compared with the corresponding single-stage design, the triangular test allowed to stop the study with a 15% reduction in sample size.



Clinical Pharmacology & Therapeutics (1997) 61, 377–384; doi:

The triangular test to assess the efficacy of metoclopramide in gastroesophageal reflux.

https://www.cysticfibrosisjournal.com/article/S1569-1993(08)00112-4/pdf

Pancreatic enzyme replacement therapy for young cystic fibrosis patients

La survenue de douleurs abdominales chroniques localisees en fosse iliaque droite, associees a la palpation d'une masse en fosse iliaque droite, doit faire evoquer la possibilite d'une mucocele appendiculaire. Cinq observations illustrent cette situation. Le diagnostic est evoque a l'echographie: l'appendice augmente de volume comporte en son sein, une image kystique, confirmee par le lavement baryte qui montre une empreinte du bas-fond caecal. Le traitement chirurgical comporte une appendicectomie completee ou non par l'ablation d'une collerette du bas-fond caecal. Les douleurs abdominales sont frequentes au cours de la mucoviscidose et peuvent poser de veritables problemes diagnostiques (11). Les etiologies les plus frequemment evoquees sont le syndrome d'obstruction intestinale distal (SOID), la constipation et le syndrome de malabsorption (5). D'autres causes plus rares, et pour certaines moins bien connues, doivent etre evoquees. Une douleur en fosse iliaque droite doit toujours faire redouter une appendicite aigue, souvent tardivement reconnue du fait du passe de douleurs abdominales chroniques et de l'utilisation d'antibiotiques (3). La survenue d'accidents d'invaginations a repetition, avec au lavement radiologique une image d'empreinte du bas-fond caecal, doit faire evoquer la possibilite d'une mucocele appendiculaire.

M. Guillot

Papers

The triangular test to assess the efficacy of metoclopramide in gastroesophageal reflux.

Pancreatic enzyme replacement therapy for young cystic fibrosis patients

Mucocèle appendiculaire : une étiologie aux douleurs abdominales chroniques de l'enfant