Evidence strengths and limitations

Evidence strengths and limitations

Given the large heterogeneity in the small studies included in the meta-analyses of the Cochrane systematic review it may not have been wholly appropriate to pool their results statistically. It is of note that because of large variations in study outcomes, follow-up period, and dose, Yiannakopoulou et al. (2012) decided not to combine the results of individual studies into a meta-analysis. The 2 different approaches each have strengths and weaknesses. Both reviews reached similar conclusions.

The conclusions in both systematic reviews about whether botulinum toxin brand and site of injection influenced efficacy of treatment were based on 1 or 2 small RCTs so these conclusions may not be reliable.

The natural history of anal fissures is typically turbulent with temporary periods of complete or partial healing interrupted by periods of recurrence and symptomatic pain. Hence, the length of follow-up may have had a substantial influence on the reported fissure healing rates in the studies.

A major limitation of the studies included in both systematic reviews was their small numbers of participants (usually fewer than 100 participants in each trial) and relatively short and variable follow-up periods to assess fissure healing (typically less than 6 months). Using shorter follow-up periods may have overestimated the effectiveness of non-surgical methods of fissure healing as they would not capture instances of later recurrence.

Shorter follow-up periods are also more susceptible to the random influences of different spontaneous or temporary healing rates in either treatment group leading to spurious findings. This is potentially more problematic in smaller studies.

An important overall limitation of the evidence on botulinum toxin type A injection in chronic anal fissure is that none of the studies identified compared botulinum toxin type A injection with 0.4% GTN ointment, the only licensed treatment for chronic anal fissure in the UK. Also, there were no systematic reviews or RCTs that assessed use of botulinum toxin after treatment failure with 0.4% GTN ointment.