Clinical study reports (CSRs) are documents submitted to regulators to obtain marketing licenses for drugs and biologics. They are a key source of detailed trial information, providing much more information than other sources, particularly adverse event data. CSRs can be long (up to 10,000s of pages), but they are generally highly structured, and they are likely to be the most comprehensive and complete single source of information about a trial.  

• Using clinical study reports in Cochrane reviews starter pack [PDF] 

Pain is a common primary or secondary outcome in systematic reviews of perioperative anaesthesia and postoperative care. How methods are applied and outcomes are managed varies substantially across published reviews and this can create problems when trying to interpret their findings. Indeed, while it can appear to be simple, managing pain as an outcome presents us with a number of interesting challenges.

The Cochrane Pain, Palliative and Supportive Care Review Group have developed the resources presented here to help to guide review authors and people who are using systematic reviews in this field towards optimal methods in this field. This project was supported by a Cochrane Network Innovation Fund, and the resources were developed in consultation with the Cochrane Musculoskeletal, Oral, Skin and Sensory Network and other key contacts in this topic area.

They established an expert group of editors and authors to distil and synthesize evidence-based best practice guidance on the management of pain as an outcome in systematic review of perioperative anaesthesia and postoperative care. They reviewed the evidence to support best practice, elucidated examples, and provide some recommendations and considerations (see resources below). Discussion is presented on areas of uncertainty where further research is needed, how to incorporate this practice into systemic reviews, and on transferable learnings to systematic review practice in general.

This project has provided resources to drive improvement in the standard of systematic reviews in this field, and also a useful guide for those seeking to use systematic reviews to guide clinical decisions. 

• A checklist of some critical elements for pain reporting and analysis [Doc]
• Introduction to acute postoperative pain [PPT] and accompanying reference list 1 [Doc]
• Measuring postoperative pain [PPT] and accompanying reference list 2 [Doc]
• Looking at outcomes [PPT] and accompanying reference list 3 [Doc]
• Some fundamentals of acute pain studies [PPT] and accompanying reference list 4 [Doc]
• Considerations of study size [PPT] and accompanying reference list 5 [Doc]
• Dealing with publication bias [PPT] and accompanying reference list 6 [Doc]
• Applying lessons in practice [PPT] and accompanying reference list 7 [Doc]

Members of Cochrane and others have developed techniques to manage Type I and II errors that can occur over time by updating and repeating meta-analyses. Cochrane has provided funding for a review of these techniques undertaken by Mark Simmonds at York University and other members of the Statistical Methods Group.  

Two principle techniques emerge as controlling for these errors: Trials Sequential Analysis and Sequential Meta-analysis. Further detailed information is available (see full statement below]). Some review authors have used these techniques, we do not currently encourage or discourage their use at this point.

Recommendation

In July 2017, it was determined that further technical examination of these two approaches is required before the Committee can decide whether there is a preferred approach or whether the methods provide added value to managing random error. An expert panel was to discuss further and report back. See full statement, July 2017.

In December 2018 the Expert Panel recommended against the use of sequential methods for updated meta-analyses in most circumstances within the Cochrane context. They should not be used for the main analyses, or to draw main conclusions. See full statement, December 2018.