Murdoch Childrens Research Institute and The Royal Children s Hospital Centre for Community Child Health

Size: px

Start display at page:

Download "Murdoch Childrens Research Institute and The Royal Children s Hospital Centre for Community Child Health"

Melina Matthews
5 years ago
Views:

1 Is Lactobacillus reuteri DSM effective for the treatment of infant colic? Results from an international individual participant data meta-analysis (IPDMA) Murdoch Childrens Research Institute and The Royal Children s Hospital Centre for Community Child Health

2 Aberdeen 2014 Group #2 Turku 2016 Group #1 Michael Cabana, Francesco Savino, Flavia Indrio, Daniel Tancredi, Frank d Amico Anna Partty, Valerie Sung, Kim Chau, Hania Szajewska 2

3 Background: probiotics and infant colic Infant colic / excessive crying of unknown cause in <3m old Common, burdensome Aetiology elusive Management options limited Link between infant gut microbiota and colic Conflicting RCTs of Lactobacillus reuteri DSM in treating colic Centre for Community Child Health

4 4

5 5

6 6

7 7

8 What is an IPDMA? Specific type of Meta Analysis Individual Patient Data from each study is obtained Patient data is statistically modeled Unit of analysis is the individual patient (not the summary statistic) Require collaborative effort with the authors of studies

9 Traditional Meta-analysis Data simulation courtesy of Professor Frank D Amico

10 Control = 8.0 (6.7) Treatment = 7.2 (5.2) = 0.84 (1.9) Control = 14.5 (9.7) Treatment = 9.1 (10.1) = 5.33 (1.8) In Traditional Meta-analysis the unit of analysis is the individual study Control = 19.0 (13.3) Treatment = 8.8 (12.0) Control = 20.3 (10.8) Treatment = 8.5 (11.6) Control = 18.5 (12.2) Treatment = 13.5 (9.2) = (3.6) = 11.8 (2.5) = 5.0 (7.8) 10

11 Control = 8.0 (6.7) Treatment = 7.2 (5.2) = 0.84 (1.9) Control = 14.5 (9.7) Treatment = 9.1 (10.1) = 5.33 (1.8) In IPDMA the unit of analysis is the individual patient Control = 19.0 (13.3) Treatment = 8.8 (12.0) Control = 20.3 (10.8) Treatment = 8.5 (11.6) Control = 18.5 (12.2) Treatment = 13.5 (9.2) = (3.6) = 11.8 (2.5) = 5.0 (7.8) 11

12 Individual patient level data Data simulation courtesy of Professor Frank D Amico

13 IPDMA Dataset More powerful instrument for synthesizing evidence from studies with disparate results Statistically adjust for patient characteristics at the finest resolution E.g. delivery type, enrollment age, family history of allergy Better assess subgroups of patients who may or may not benefit from a probiotic intervention 13

14 Centre for Community Child Health

15 IPDMA Aims 1. To determine whether L. reuteri DSM is effective in managing infants with colic less than 3 months old 2. To determine whether the effects of L. reuteri DSM on infants with colic differ according to 1. Feeding method (breast vs formula) 2. Delivery type (vaginal vs caesarian) 3. Age group ( 6 weeks vs > 6 weeks chronological age) 4. Atopic risk (family history of allergy) Centre for Community Child Health

16 Statistical Analysis Mixed-effects generalized linear models for longitudinal data to estimate treatment effects Treatment Success ( 50% reduction in crying/fussing) log-poisson regression, to estimate incidence ratios Cry/fuss duration (minutes per day) linear regression, to estimate mean (between-group) difference in changes from baseline At Day 21 (primary outcome) At Days 7, 14 (secondary outcomes) Centre for Community Child Health

17 Characteristics of included trials Study n Feeding method Median infant age (wks) Caesarian delivery (%) Family history of atopy (%) Male (%) Measure of cry/fuss duration Italy 46 Breast & no dairy Poland 80 Breast Diary of parental recall at end of each day Australia 167 Breast & formula Baby Day Diary (prospective record) Modified Baby Day Canada 52 Breast Diary Centre for Community Child Health

Results and Discussion Treatment effect size estimates relatively similar across the studies Incidence ratio (for treatment success) Mean changes in crying time from baseline Statistically

18 Results and Discussion Treatment effect size estimates relatively similar across the studies Incidence ratio (for treatment success) Mean changes in crying time from baseline Statistically significant effects on both outcomes at all three follow-up time-points Strong evidence for treatment effects in the breastfed infants Significant differences by feeding type when heterogeneity in treatment effects explored No evidence for treatment effect in formula fed infants Centre for Community Child Health

19 Conclusion L. reuteri DSM is effective in treating breastfed infants with colic Insufficient evidence for use of L. reuteri DSM in formula-fed infants with colic Centre for Community Child Health

20 Important lessons International collaboration would not have been possible without ISAPP facilitating its members meeting Now established a framework for collaboration for future IPDMAs as an effective way of resolving conflicting study results, especially in the era of expensive clinical trials Centre for Community Child Health

21 THANK YOU! Centre for Community Child Health

Probiotics for management of infantile colic: a systematic review of randomized controlled trials

Systematic review/meta-analysis Probiotics for management of infantile colic: a systematic review of randomized controlled trials Department of Paediatrics, Medical University of Warsaw, Warsaw, Poland