The clinical relevance of outcomes used in late-onset Pompe disease: can we do better?

Lachmann, Robin; Schoser, Benedikt

doi:10.1186/1750-1172-8-160

Orphanet Journal of Rare Diseases

Table 1 Clinical relevance of 6MWD changes in patients with chronic respiratory disease and late-onset Pompe disease

From: The clinical relevance of outcomes used in late-onset Pompe disease: can we do better?

Source	Disease	n	6MWT				Relevance			Authors’ conclusions
Source	Disease	n	Mean ± SD baseline (m)	Timepoint (m)	Absolute diff. (m)	Relative diff. (%)	Absolute MCID* (m)	Relative MCID^†(%)	Patient notice change?^‡	Authors’ conclusions
[22]	COPD	112	371 ± 129				54	15		“Awareness of the smallest difference in walking distance that is noticeable to patients may help clinicians interpret effectiveness of treatments”
[23]	IPF	826	392 ± 109				24–45	6–11		“6MWT is a reliable, valid and responsive measure of exercise tolerance in IPF”
[24]	CAD after ACS	81	~480	Week 8: 553	73 ± 57	15	25	5	“same” to “a little bit better”	“A MCID of 25 m will help practitioners interpret changes in 6MWD in patients with CAD after ACS”
[25]	PAH	405	343 ± 77				~33	10		“The MID of 33 m helps assess treatment responses during trials of specific PAH therapies and sample size calculations”
[26]	COPD	460	361 ± 112				35	10		“The low correlations between 6MWT and patient-reported anchors questions whether a minimal important difference exists”
[27]	DMD	18	357	1 year: 300	−57	16	Above	Above	No	“The 6MWD changes at 1 year confirm the validity of this endpoint and emphasize that preserving ambulation must remain a major goal of DMD therapy”
[28]	DMD	21	366 ± 83	1 week: 364 ± 87	−2	<1	Below	Below	No	“Modified 6MWT is feasible and safe, documents disease-related limitations on ambulation, is reproducible, and offers a new outcome measure for DMD natural history and therapeutic trials”
[29]	PAH	213	330 ± 74	Week 16: 366	36	11	Within	Above	No	“Treatment increased the time to clinical worsening”
[30]	MPS	22	319 ± 131	Week 26: 339 ± 127	20	6	Below	Within	No	“Treatment translated into clinically important improvements in physical capacity (6MWT)”
[18]	Pompe	60	332 ± 127	Week 78: 358 ± 141	Week 78: 25	8	Within	Within	No
[14]	Pompe	5	64	3 years: 184	120	188	Above	Above	“same” to “somewhat better”
[12]	Pompe	58	320 ± 161	1–3 years: 383 ± 178	63	20	Above	Above	“same” to “a little bit better”
[31]	Pompe	22	341 ± 150	1 year: 393 ± 157	52	15	Within	Above	“same” to “a little bit better”
[13]	Pompe	21	312 ± 166	3 years: 326 ± 175	14	5	Below	Within	No
[32]	Pompe	17	117 (median)	3 years: 265	148	126	Above	Above	“same” to “somewhat better”
[19]	Pompe	11	246 ± 185	1.5–2 years: 295 ± 195	49	20	Within	Above	“same” to “a little bit better”
[33]	Pompe	1	320	4 months: 500	180	56	Above	Above	“same” to “much better”
[34]	Pompe	1	~375	32 months: 353	−44	11	Within	Above	No
[35]	Pompe	2	1 pt: 660	6 months: 700	40	6	Within	Within	Maybe “same” to “a little bit better”

*Absolute MCID defined as 24–54 m based on the range described by Redelmeier et al.[22] and du Bois et al.[23].
^†Relative MCID defined as 5–10% based on range described by du Bois et al.[23], Gremeaux et al.[24], Mathai et al.[25], and Puhan et al.[26].
^‡According to the publication by Redelmeier et al.[22] in patients with COPD, patients change their rating from “same” to “a little bit better” with an increase of 40 m in the 6MWT; from “same” to “somewhat better” with an increase of 100 m; and from “same” to “much better” with an increase of approximately 180 m. For a patient to rate the change from “same” to “a little bit worse”, the decrease in the 6MWT needs to be 70 m.
ACS acute coronary syndrome, CAD coronary artery disease, COPD chronic obstructive pulmonary disease, diff. difference, DMD Duchenne muscular dystrophy, IPF idiopathic pulmonary fibrosis, MCID minimal clinically important difference, MPS mucopolysaccharidosis I, 6MWD 6MWT distance, 6MWT 6-minute walking test, PAH pulmonary arterial hypertension, pt patient, SD standard deviation.

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ISSN: 1750-1172

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