However, among the 51 studies with statistical design there was a notable heterogeneity in the type of design applied.
A notable heterogeneity existed among study methodologies, with different KOH concentrations used for treatment and/or studies lacking a control group.
A three- to eightfold increased risk of drug-related death was found when comparing weeks 1 + 2 with weeks 3 12, with notable heterogeneity between countries: United Kingdom, 7.5 (95% CI: 5.7 9.9); Australia, 4.0 (95% CI: 3.4 4.8); Washington State, USA, 8.4 (95% CI: 5.0 14.2) and New Mexico State, USA, 3.1 (95% CI: 1.3 7.1).
I 2 of less than 30% of the variability in point estimate was considered as mild heterogeneity, more than 50% was notable heterogeneity, whereas in between was considered as moderate heterogeneity.
The clinical heterogeneity of HSP is related to a notable genetic heterogeneity; however, insight into the genetic basis of these disorders is expanding rapidly (Dion et al., 2009; Finsterer et al., 2012) and supports a close genetic link between HSP and other neurodegenerative diseases (Novarino et al., 2014).
Analyses by geographical area demonstrated notable heterogeneity at a regional level, with the majority of the scientific output coming from six areas.
In an attempt to explain the notable heterogeneity, we used effect-modifier analyses.
The H statistic is a complement to the I statistic in assessing study heterogeneity; an H <1.2 indicates little heterogeneity, and an H >1.5 raises caution regarding notable heterogeneity (26).
Heterogeneity was calculated using the χ test and the I. Notable heterogeneity was defined as an I substantially >50% (4).
A random-effects model was applied when there was notable heterogeneity (I index ≥50%), and otherwise, the fixed-effects model was used.
