Sadly Inadequate Cochrane Review of Renal Colic

With little fanfare (probably because this Tamiflu document was published the same week), the Cochrane Collaboration published a review of the efficacy of alpha-blockers for stone expulsion.  The authors strongly approve of this therapy.  They also grievously downplay the tragic disutility of the data reviewed.

Only 7 of 32 included studies had adequate blinding to treatment for physicians and patients.  Only 6 studies report a blinded mechanism for randomization.  8 studies did not report outcomes matching the methods.  They are, frankly, a catastrophic mix of tiny samples, non-peer-reviewed abstracts, and low-quality study design:

• Abdel-Meguid 2010 – 150 patients from Saudi Arabia, could not access.
• Agrawal 2009a – 102 patients from India, multiple interventions, no disclosures statement.
• Al Ansari 2010 – 100 patients from Qatar, no disclosures statement.
• Aldemir 2011 – 90 patients from Turkey, multiple interventions, no disclosures statement.
• Autorino 2005 – 96 patients in Italy, no disclosures statement.
• Ayubov 2007 – Only published as conference abstract.
• Cervenakov 2002 – 104 patients in Slovak Republic, could not access.
• Dong 2009 – Korean Journal of Urology not indexed in PubMed.
• Erturhan 2007 – 120 patients from Turkey, multiple interventions, no disclosures statement.
• Ferre 2009 – 77 patients from USA, funded by academic grant.
• Han 2006 – Korean Journal of Urology not indexed in PubMed.
• Hermanns 2009 – 90 patients from Switzerland, authors state no COI.
• Hong 2008 – Only published as conference abstract, ”furosemide-based expulsive therapy”.
• Kaneko 2010 – 71 patients from Japan, no disclosures statement.
• Kim 2007b – Only published as conference abstract.
• Kupeli 2004 – 78 patients from Turkey, multiple interventions, no disclosures statement.
• Liatsikos 2007 – 73 patients from Greece, multiple interventions, no disclosures statement.
• Lojanapiwat 2008 – 75 patients from Thailand, multiple interventions, Astellas supplied tamulosin.
• Mukhtarov 2007 – Only published as conference abstract, multiple interventions.
• Pedro 2008 – 76 patients from Minnesota, supported by Sanofi-Aventis.
• Porpiglia 2004 – 86 patients from Italy, multiple interventions, no disclosures statement.
• Porpiglia 2009 – 91 patients from Italy, multiple interventions, authors state no COI.
• Sayed 2008 – 90 patients from Egypt, could not access.
• Sun 2009 – 60 patients from China, no disclosures statement.
• Taghavi 2005 – Only published as conference abstract, multiple interventions.
• Vincendeau 2010 – 129 patients from France, multiple pharma COI.
• Wang 2008 – 95 patients from Taiwan, multiple interventions, could not access.
• Ye 2011 – 3,189 patients from China, multiple interventions, supported by Astellas.
• Yencilek 2010 – 92 patients from Turkey, no disclosures statement.
• Yilmaz 2005 – 114 patients from Turkey, multiple interventions, no disclosures statement.
• Zehri 2010 – 65 patients from Pakistan, no disclosures statement.
• Zhang 2009b – 314 patients from China, multiple interventions, no disclosures statement.

This is a classic case of “Garbage In, Garbage Out”, where pooling studies for statistical power in a systematic review obfuscates the heterogeneity and poor underlying data quality.  From what I can gather, only two of these trials – Pedro 2008 and Vincendeau 2010 – registered as clinical trials and subscribed to methods and follow-up of sufficient integrity.  Both of these studies showed no or minimal benefit to alpha-blockers.

Patients will have adverse effects from these medications.  They may, however, also derive some stone passage and symptomatic benefit – although the magnitude of benefit cannot be reliably known.  Ultimately, the evidence collated by this systematic review is not of sufficient quality to support the authors’ conclusion:

“The use of alpha-blockers in patients with ureteral stones results in a higher stone-free rate and a shorter time to stone expulsion.”  

This statement ought to be significantly tempered by a declaration of the limitations of the underlying data.  It is probably still reasonable to offer a generic alpha-blocker to patients, but the expectation of ever knowing the true value of the therapy is basically nil.

“Alpha-blockers as medical expulsive therapy for ureteral stones (Review)”