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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
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Orphanet Journal of Rare Diseases

ISSN: 1750-1172