Open Access Highly Accessed Open Badges Protocol

Pharmacologic interventions for painful diabetic neuropathy: an umbrella systematic review and comparative effectiveness network meta-analysis (Protocol)

Marcio L Griebeler1*, Apostolos Tsapas2, Juan P Brito3, Zhen Wang4, Olivia J Phung5, Victor M Montori5 and M Hassan Murad5

Author Affiliations

1 Division of Diabetes, Endocrinology, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA

2 Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece

3 Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, 55905, USA

4 Western University of Health Sciences, College of Pharmacy and Western Diabetes Institute, Rochester, MN, USA

5 Division of Preventive Medicine, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA

For all author emails, please log on.

Systematic Reviews 2012, 1:61  doi:10.1186/2046-4053-1-61

Published: 2 December 2012



Neuropathic pain can reduce the quality of life and independence of 30% to 50% of patients with diabetes. The comparative effectiveness of analgesics for patients with diabetic neuropathy remains unclear. The aim of the current work, therefore, was to summarize the evidence about the analgesic effectiveness of the most common oral and topical agents used for the treatment of peripheral diabetic neuropathy.


We will use an umbrella approach (systematic review of systematic reviews) to identify eligible randomized controlled trials (RCTs) for the most common oral or topical analgesics for painful diabetic neuropathy. Two reviewers will independently determine RCT eligibility. Disagreement will be solved by consensus and arbitrated by a third reviewer. We will extract descriptive, methodological and efficacy data in duplicate. Results will be pooled and analyzed using classic random-effects meta-analyses and network meta-analyses to compute the absolute and relative efficacy of therapeutic options. We will use the I2 statistic and Cochran’s Q test to assess heterogeneity. Risk of bias and publication bias, if appropriate, will be evaluated, as well as overall strength of the evidence.


This network meta-analysis aims to synthesize available direct and indirect evidence of effectiveness of analgesics in the treatment of painful diabetic neuropathy. The network approach will offer the opportunity to generate a ranking based on efficacy and along with known side effects, costs, and administration burdens will enable patients and clinicians to make choices that best reflect their preferences for treatment of painful diabetic neuropathy.

Comparative effectiveness research; Diabetic neuropathy; Network meta-analysis; Systematic review