Providing Guidance in the Dark: Rare Renal Diseases and the Challenge to Improve the Quality of Evidence

Davide Bolignano; Evi V. Nagler; Wim Van Biesen; Carmine Zoccali


Nephrol Dial Transplant. 2014;29(9):1628-1632. 

In This Article

Can we Provide Acceptable Guidance in Rare Renal Diseases?

Clinical practice guidelines are built up on the basis of evidence-based medicine but available scientific knowledge and available good quality studies are ranked according to an accepted 'evidence ladder' for studies related to intended effects of therapy:

  1. Systematic reviews of reliable RCTs including meta-analyses with low-heterogeneity between the results.

  2. Other meta-analyses of RCTs.

  3. Single RCT(s).

  4. Meta-analyses of observational studies (cohorts and case–control).

  5. Single observational studies (cohorts and case–control).

  6. Published case series/case-reports.

  7. Anecdotal case-reports.

  8. Expert opinion.

In rare renal diseases, the basis of evidence for treatments is generally weak and, in very rare diseases, the combined evaluation of single-case studies is often the only evidence that can be obtained. Can principles of clinical guidance applied to common diseases be appropriate also for rare diseases? A systematic search by the German Institute for Quality and Efficiency in Health Care (IQWiG) revealed no different methodological approaches for the development of clinical practice recommendations in rare diseases when compared with guidelines for common disorders.[12] This document underlined that the issue of 'scarce evidence' is a limitation pertaining also guidelines on common diseases. Therefore, in principle, there is no reason to adopt a different approach or pose different requirements for rare diseases. A position document by the European Medicines Agency (EMEA)[13] supports the concept that rules for the production of guidelines on common diseases are also applicable to rare diseases. EMEA emphasizes that all forms of evidence, even anecdotal case-reports, may provide relevant information and should then be taken into consideration.