Table 3.

Challenges in adapting systematic review methodology to toxicology

Systematic review step	Challenges specific to toxicology
Planning	Composition of a skilled review team covering all fields of expertise required, especially systematic review experience
	Definition of the role of the systematic review sponsor
Framing the question	Framing of the question in a way that it is amenable to systematic reviews
Developing and publishing of the protocol	Publication of protocols so that they are highly and timely visible to stakeholders and interested parties
Searching for evidence	Identification of sources to be searched, including gray literature sources
	Provision of means to conduct appropriately balanced searches, e.g., by better annotation of the toxicological literature
	Familiarization of information specialists with toxicological evidence and databases
Selecting the evidence	Handling of the possibly vast amount of identified records and appropriate documentation of the selection process
Extracting (the data)	Efficient and transparent data management
Assessing the evidence	Determination of the importance of the various potential quality aspects, e.g., by empirical evidence
	Determination on how to best to integrate quality appraisal results into developing and supporting conclusions
Analyzing data	Exploration of the role of publication bias in toxicology, i.e., the frequency, the direction and the causes
	Exploration of the use of investigating external validity of subgroups
Interpreting the results	Determination of the confidence in a body of evidence
	Exploration of how to integrate bodies of evidence within an evidence stream and across evidence streams
Reporting	Making available all information relevant to allow for independent replication of the review