Children’s responses to health care interventions often differ significantly from those of adults. Consequently, systematic review (SR) authors must consider the physiological, developmental and psychosocial aspects of childhood. Guidance for SR authors in this area remains limited.
We identified the following areas as key ones for which SR authors must make decisions:
A key decision at the outset of the review is whether to focus on child data only, or to include both adult and child data. This decision can be based on clinical expertise about the condition and its trajectory at different ages. Urinary tract infections, for example, present very differently in children than in adults. However, for a condition with a typical age of onset in adolescence to mid-adulthood, such as Hodgkin’s lymphoma, the physiological differences between children and adults will likely not be profound enough to warrant a separate review.
If there will likely be plausible physiological or developmental differences along the age span included in the review, we recommend planning a priori subgroup analyses, in order to avoid masking these differences.
· Contopoulos-Ioannidis, DG, Baltogianni MS, Ioannidis JPA, “Comparative Effectiveness of Medical Interventions in Adults Versus Children.” The Journal of Pediatrics, 157:2, 2010.
· Cramer K, Wiebe N, Moyer V, Hartling L, Williams K, Swingler G, Klassen TP, “Children in reviews: Methodological issues in child-relevant evidence-syntheses.” BMC Pediatrics, 5:38, 2008.
Age-based treatment effects
Within the age range of 0-18 years, one can expect differing reactions to interventions. Authors should take into consideration age-based treatment effects, where there may be important similarities or differences in terms of physiological and psychosocial development, when planning a priori subgroup analyses.
The following questions may be useful when planning age-based analyses:
1. Is there any evidence of a different/distinct form of the condition at different ages in childhood?
2. Is there any evidence that different etiological factors might be operating at different ages for that disease?
3. Is the intervention largely behavioural and therefore likely to vary according to age because of different degrees of understanding and participation by the child/family unit?
The selection of a priori outcomes should be based on sound knowledge of the disease trajectory and children’s development. Relevant short-term outcomes may differ for children and adults, and similar outcomes may be assessed using different measurement tools. Recognition that the benefits and harms of treatment for children may unfold across subsequent decades of life may influence the choice of outcomes to be assessed and study designs to be included.
Table 1 presents Clinical areas for which studies have been done that develop or apply methodology for selecting outcome domains or outcomes to be used in clinical trials in children younger than 16 years of age, as of 2008 (Sinha et al 2008).
· Sinha I, Jones L, Smyth RL, Williamson PR, “A Systematic Review of Studies That Aim to Determine Which Outcomes to Measure in Clinical Trials in Children.” PLoS Medicine, 5:4, 2008.
Databases have varying definitions of “child” and other age-based terms, and may be inconsistent in indexing pediatric material. The assistance of a librarian experienced with using pediatric-search filters will help to identify relevant material. As well, the “Recommended precise and sensitive PubMed systematic review and child search strategies” outlined in Table 2 will be of assistance (Boluyt et al 2008).
· Boluyt N, Tjosvold L, Lefebvre C, Klassen TP, Offringa M, “Usefulness of Systematic Review Search Strategies in Finding Child Health Systematic Reviews in MEDLINE.” Arch Pediatr Adolesc Med, 162:2, 2008.
Key stages of carrying out SRs in children are affected by the dynamic nature of childhood. Authors are urged to carefully consider how children’s psychosocial and physiological development along the age span will influence their response to interventions.
We are grateful for the contributions from Drs. Hywel Williams (for suggesting the questions for planning age-based analyses) and Eyal Cohen. The Cochrane Child Health Field is supported by funding from the Canadian Institutes of Health Research (Knowledge Synthesis and Translation by Cochrane Canada, CON-105529).
Infographics were developed to inform high quality trials with children
The Standards for Research in (StaR) Child Health include six evidence-based Standards for the optimal design and conduct of pediatric trials. Recognizing that the format of the Standards was impractical for many trialsts, researchers at the Alberta Research Centre for Health Evidence translated the key messages into six one-page infographics. An end-user survey showed that the infographics appeared credible, contained clear language and relevant images, and would be helpful when designing and conducting a trial.
The infographics can be helpful to you if you are involved with research with children or mentor trainees who are learning about research with children. We encourage you to download a free copy of the infographics and share them among your network.
Below is a sample tweet to share the infographics on social media:
Infographics to help trialists design and conduct research with children #childhealth #knowledgetranslation