5) Downgrading fatigue post-treatment to low-quality evidence
From a publicly released email exchange, we know that the previous Cochrane Editor in chief David Tovey strongly objected to the results for fatigue post-treatment to be rated as moderate quality. He wrote: “the conclusion that this is moderate certainty evidence seems indefensible to me.” Tovey argued that it could be further downgraded for inconsistency (because of considerable heterogeneity reflected by a I2 of 80%) or imprecision (because the confidence interval of the effect crosses the line of no longer being clinically significant). The authors – represented by officials of the Norwegian Institute of Public Health (NIPH) – argued that heterogeneity was mostly due to the study by Powell et al.: when it was removed, the heterogeneity became acceptable while the effect size remained moderate. Regarding imprecision, they argued that GRADE only advises downgrading when the confidence interval crosses the line of no effect, not the line of a clinically significant effect. In the email correspondence, the authors did seem to agree that these were both borderline cases and open to interpretation. They, therefore, proposed the following compromise, as explained by Atle Fretheim from the NIPH: “I proposed a compromise: We simply grade the evidence for this outcome as Low-moderate. The authors have accepted to use the term ‘may’ (usually indicating low certainty evidence) when describing the certainty of the evidence, rather than the term ‘probably’ (usually indicating moderate certainty). They have also accepted not to use any categorization of the effect size.” An alternative solution proposed was to use the term “low to moderate quality evidence”. The 2019 amendment, however, uses the words “probably” and “moderate-certainty evidence”.
