Mr. Pickwick and his child went on a field trip and returned empty handed: the widening gap between non-randomised studies and evidence for circadian rhythm sleep disorders management in a paediatric population

Article type
Authors
Khan S1, Heussler H2, McGuire T3, Pache D3, Dakin C2, Cooper D2, Norris R4, Flenady V5, Charles B1
1School of Pharmacy, The University of Queensland, Brisbane, Australia
2Sleep and Respiratory Unit, Mater Children Hospital, Brisbane, Australia
3Pharmacy- Practice and Development, Mater Health Services, Brisbane, Australia
4Australian Centre for Paediatric Pharmacokinetics, Mater Children Hospital, Brisbane, Australia
5Translation Research into Practice (TRIP), Mater Medical Research Institute, Mater Health Services, Brisbane, Australia
Abstract
Background: Therapeutic protocols in the management of circadian rhythm sleep disorders (CRSDs) in the paediatric population are currently inadequate. There is a lack of randomised controlled trials (RCTs) and an ever increasing number of non-RCTs in this specialised niche. However, including information from non-randomised studies may adversely affect therapeutic recommendations. Such concerns have led the Cochrane collaboration to focus on evaluation of results from RCTs, to the virtual exclusion of other forms of evidence.

Objectives: To determine the number of excluded studies on melatonin for the management of CRSDs in visually impaired children and to describe a general framework by which information from non- randomised studies might be integrated into evidence.

Methods: 1) A retrospective, observational study for determining the number of RCTs and non-RCTs/observational studies for melatonin in the management of CRSDs in visually impaired children through the Cochrane Collaboration [Cochrane Developmental, Psychosocial and Learning Problem Group (CDPLG)] was conducted. 2) A framework was developed to include non-randomised studies into evidence: (a) Conceptualisation of question under study (determining the internal and external validity; differentiating the efficacy and effectiveness trials); (b) Developing a conceptual model (based on CRSDs therapeutic outcome measures); (c) Recommendation of proposed for inclusion of non-RCTs / Observational studies.

Results: A total of 9 studies of various designs were evaluated (3 case series; 3 non-RCTs; 2 randomised, but design-flawed studies and 1 N-of-1 trial). None met the Cochrane inclusion criteria. A framework for potential inclusion of such studies is provided.

Conclusions: A null evidence report, based on inclusion criteria, runs the ethical risk of excluding potentially relevant practice-changing evidence. It thus unfairly evaluates the current practice as lacking a sufficient evidence basis. The proposed framework may assist to strengthen the quality and documentation of evidence from non-randomised studies in highly specialized therapeutic areas.