Skip to main content

Table 1 Analysis of number of case reports showing improvement or impairment associated with ERT in a specific outcome, based on the strong confirmatory method

From: Agreement between results of meta-analyses from case reports and clinical studies, regarding efficacy and safety of idursulfase therapy in patients with mucopolysaccharidosis type II (MPS-II). A new tool for evidence-based medicine in rare diseases

RANK Outcomes & (SOE score*) Nr. [+] / Total cases p-value** FDR 10% Critical value*** Evidence group****
1 uGAGs (Moderate) 20/44 < 0.0001 0.009 Acceptable
2 Liver V (Moderate) 8/44 0.001 0.018 Acceptable
3 Antibodies (Moderate) 6/44 0.022 0.027 Acceptable
4 6MWT (Low) 4/44 0.177 > 0.036 Unacceptable
4 JROM (Insufficient) 4/44 0.177 > 0.036 Unacceptable
5 Growth height (Low) 3/44 0.379 > 0.045 Unacceptable
6 IRR (Low) 2/44 0.653 > 0.055 Unacceptable
7 Pulmonary function (Low) 1/44 0.895 > 0.064 Unacceptable
8 Cardiac (Insufficient) 0/44 1 > 0.073 Unacceptable
8 QoL (Insufficient) 0/44 1 > 0.073 Unacceptable
8 Sleep apnea (Insufficient) 0/44 1 > 0.073 Unacceptable
  1. Legend:The improvement is defined in accordance with the strong confirmatory method. The impairment was declared when an Infusion Related Reaction (IRR) caused a change in ERT dose.
  2. 6MWT 6-min walk test, FDR False discovery rate (Benjamini-Hochberg procedure), IRR infusion-related reaction, JROM Joint range of motion, Nr. [+] Number of case reports showing improvement or impairment in IRR with ERT in a specific outcome, QoL Quality of life, SOE Strength of evidence, uGAGs Urinary glycosaminoglycans.
  3. *The SOE classification has been previously published in Bradley et .al [12]
  4. ** The analysis assessed whether the percentage of case reports showing a modification in a specific outcome was statistically higher than 5% (null hypothesis, H0). The p-value was performed with one-sided binomial test
  5. *** FDR critical value: Outcomes with p-values lower than FDR critical value are considered as modified by ERT (Multiplicity adjustment). The FDR critical value is calculated ranking the outcomes analyzed from lowest to highest p-value. The rank (r) is divided by number of outcomes and multiplied by the accepted 10% rate of false discoveries. The lowest rank of tied p-values is used because the critical value computed is lower, and it is more conservative to declare a specific outcome as modified by ERT. However, the same outcomes were classified as modified by ERT when the highest or mean rank was used for ties
  6. **** The outcomes that showed a p-value lower than the FDR 10% critical value were classified in the acceptable evidence group (shadow rows). The outcomes that showed a p-value higher than the FDR 10% critical value were classified in an unacceptable evidence group (white rows). In bold: Moderate to high SOE categories