Page 64 - 16Neonatal Jaundice_compressed

Introduction

than English were not appraised. Both generic and specially developed methodological search
filters were used appropriately.
There was no systematic attempt to search grey literature (conferences, abstracts, theses and
unpublished trials). Hand searching of journals not indexed on the databases was not
undertaken.

Towards the end of the guideline development process, searches were updated and re-executed,
thereby including evidence published and included in the databases up to June 2009. Studies
identified after this date could only be included if they were specifically requested during the
consultation process. Evidence published after this date has not been included in the guideline.
This date should be considered the starting point for searching for new evidence for future
updates to this guideline.
Further details of the search strategies, including the methodological filters employed, are
presented in Appendix I.

Appraisal and synthesis of clinical effectiveness evidence
Evidence relating to clinical effectiveness was reviewed using established guides 3-7;8 and
classified using the established hierarchical system presented in Table 2.2
(www.nice.org.uk/guidelinesmanual). This system reflects the susceptibility to bias that is
inherent in particular study designs.

The type of clinical question dictates the highest level of evidence that may be sought. In
assessing the quality of the evidence, each study receives a quality rating coded as ‘++’, ‘+’ or
‘−’. For issues of therapy or treatment, the highest possible evidence level (EL) is a well-
conducted systematic review or meta-analysis of randomised controlled trials (RCTs; EL 1++)
or an individual RCT (EL 1+). Studies of poor quality are rated as ‘−’. Usually, studies rated as
‘−’ should not be used as a basis for making a recommendation, but they can be used to inform
recommendations. For issues of prognosis, the highest possible level of evidence is a cohort
study (EL 2). A level of evidence was assigned to each study, and to the body of evidence for
each question.

Table 2.2 Levels of evidence for intervention studies

Level Source of evidence
1++ High-quality meta-analyses, systematic reviews of randomised controlled trials (RCTs), or RCTs
with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias
1− Meta-analyses, systematic reviews of RCTs, or RCTs with a high risk of bias
2++ High-quality systematic reviews of case–control or cohort studies; high-quality case–control or
cohort studies with a very low risk of confounding, bias or chance and a high probability that
the relationship is causal
2+ Well-conducted case–control or cohort studies with a low risk of confounding , bias or chance
and a moderate probability that the relationship is causal
2− Case–control or cohort studies with a high risk of confounding, bias or chance and a significant
risk that the relationship is not causal
3 Non-analytical studies (e.g. case reports, case series)
4 Expert opinion, formal consensus

For each clinical question, the highest available level of evidence was selected. Where
appropriate, for example, if a systematic review, meta-analysis or RCT existed in relation to a
question, studies of a weaker design were not considered. Where systematic reviews, meta-
analyses and RCTs did not exist, other appropriate experimental or observational studies were
sought. For diagnostic tests, test evaluation studies examining the performance of the test were
used if the efficacy (accuracy) of the test was required, but where an evaluation of the
effectiveness of the test in the clinical management of patients and the outcome of disease was
required, evidence from RCTs or cohort studies was optimal. For studies evaluating the accuracy

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