It’s one of the tenets of the evidence-based practice process that questions are framed as ‘PICO’: patient, intervention, comparison and outcome. But what happens when the question is bigger than PICO?
For example, your patients may be a children needing chemotherapy (that’s the ‘P’ sorted) and you’re trying to decide which antiemetics to prescribe to stop them feeling sick (which is very unpleasant) and being sick (which is a bit less unpleasant) and preferably not having dystonic reactions (which are very very unpleasant), or constipation. (So that’s your ‘O’. Or ‘OOOO’, actually.) Now your job is to come up with the range of interventions that might make a difference, and try to compare them all in terms of their probable benefit for the patient’s primary outcomes. You might start with ondansetron, dexamethasone, metoclopromide, cyclizine, domperidone, granisitron and aprepitant, all needing to be compared. (And that would give you PIIICCCOOOO …. shout it out ….).
Or you may have a ‘simpler’ list – for patients with nocturnal enuresis does an alarm system, desmopressin, oxybutinin, or reward charts have a better chance of improving dryness in the short term with reduced relapse and few side effects? (PIICCOOO?)
The answer you seek may come from a series of systematic reviews, comparing A-B, B-C, B-D etc etc, which would be OK, but what would be even better would be an overarching ‘review of reviews’ or ‘network meta-analysis’ that drew all the studies together to give a truly comparative answer. Such studies do exist (there’s one for enuresis  and another for medical management of anxiety disorders[2}) and are an increasingly useful part of the EBMing clinician’s armoury. A less ‘methodological’ version of this may be to examine a clinical guideline, or the BMJ Publication ‘Clinical Evidence’  which seeks to provide an overview of treatments for a number of paediatric conditions.
Of course, some questions remain too big for even one review-of-reviews to cover (“How should preterm birth be prevented?”, or “What is the best way to manage asthma?”) and you may need to break up the question into slightly smaller ones. For many others though, it may now be well worth thinking of a new pinnacle to the hierarchy of evidence; an umbrella.
Acknowledgement: The lovley umbrella is from CathyLWood’s blog here
 Russell, K. & Kiddoo, D. The Cochrane Library and nocturnal enuresis: an umbrella review. Evidence-based child health: a Cochrane review journal. 2006;1:5-8: see here
 Uthman OA, Abdulmalik J. Comparative efficacy and acceptability of pharmacotherapeutic agents for anxiety disorders in children and adolescents: a mixed treatment comparison meta-analysis. Curr Med Res Opin [Internet]. 2010 Jan [cited 2009 Dec 19];26(1):53-59: see here
 Clinical Evidence (BMJ Publications, London): see here