Minimal clinically important differences in six-minute walking distance in late-onset Pompe disease
Abstract Background The minimal clinically important difference (MCID) is the smallest change in outcome that physicians or patients would consider meaningful and is relevant when evaluating disease progression or the efficacy of interventions. Studies of patients with late-onset Pompe disease (LOPD...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-04-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-024-03156-3 |
| _version_ | 1797209035706990592 |
|---|---|
| author | Kristl G. Claeys Hani Kushlaf Syed Raza Noemi Hummel Simon Shohet Ian Keyzor Agnieszka Kopiec Ryan Graham Brian Fox Benedikt Schoser |
| author_facet | Kristl G. Claeys Hani Kushlaf Syed Raza Noemi Hummel Simon Shohet Ian Keyzor Agnieszka Kopiec Ryan Graham Brian Fox Benedikt Schoser |
| author_sort | Kristl G. Claeys |
| collection | DOAJ |
| description | Abstract Background The minimal clinically important difference (MCID) is the smallest change in outcome that physicians or patients would consider meaningful and is relevant when evaluating disease progression or the efficacy of interventions. Studies of patients with late-onset Pompe disease (LOPD) have used the 6-min walk distance (6MWD) as an endpoint to assess motor function. However, an MCID for 6MWD (% predicted and meters) has yet to be established in LOPD. The objective of the study was to derive 6MWD MCID (% predicted and meters) with different analysis methods and for subgroups of different disease severity for LOPD. Methods Data from the PROPEL trial were used to calculate 6MWD MCID in the overall PROPEL population and subgroups of baseline severity as assessed by walking distance and body mass index (BMI), using anchor- and distribution-based approaches. Results The 6MWD MCIDs varied widely, depending on the method and subgroup, ranging from 2.27%-8.11% predicted for the overall LOPD population (23.7 m-57.2 m). For patients with baseline 6MWD < 150 m, MCIDs ranged from -0.74%-3.37% (-2.1 m-11.3 m). MCIDs increased with distance walked at baseline until a plateau was reached. For BMI subgroups, the MCIDs were generally lowest in obese patients. Conclusion Our analysis shows that MCID depends on the chosen method and disease severity. The findings suggest that applying a single MCID to all patients can be misleading; consequently, a range of possible MCIDs should be considered. This may also be highly relevant for other neuromuscular diseases. This study provides a range of 6MWD MCIDs for LOPD, with lower MCIDs for more severe patients. |
| first_indexed | 2024-04-24T09:48:18Z |
| format | Article |
| id | doaj.art-038589708d914771b4227aa70fd5c9b8 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-24T09:48:18Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-038589708d914771b4227aa70fd5c9b82024-04-14T11:29:08ZengBMCOrphanet Journal of Rare Diseases1750-11722024-04-0119111010.1186/s13023-024-03156-3Minimal clinically important differences in six-minute walking distance in late-onset Pompe diseaseKristl G. Claeys0Hani Kushlaf1Syed Raza2Noemi Hummel3Simon Shohet4Ian Keyzor5Agnieszka KopiecRyan Graham6Brian Fox7Benedikt Schoser8Department of Neurology, University Hospitals LeuvenUniversity of Cincinnati College of MedicineAmicus Therapeutics, Ltd.Certara GmbHAmicus Therapeutics, Ltd.Amicus Therapeutics, Ltd.Amicus Therapeutics, Inc.Amicus Therapeutics, Inc.Department of Neurology, Friedrich-Baur-Institute, Ludwig-Maximilians-UniversityAbstract Background The minimal clinically important difference (MCID) is the smallest change in outcome that physicians or patients would consider meaningful and is relevant when evaluating disease progression or the efficacy of interventions. Studies of patients with late-onset Pompe disease (LOPD) have used the 6-min walk distance (6MWD) as an endpoint to assess motor function. However, an MCID for 6MWD (% predicted and meters) has yet to be established in LOPD. The objective of the study was to derive 6MWD MCID (% predicted and meters) with different analysis methods and for subgroups of different disease severity for LOPD. Methods Data from the PROPEL trial were used to calculate 6MWD MCID in the overall PROPEL population and subgroups of baseline severity as assessed by walking distance and body mass index (BMI), using anchor- and distribution-based approaches. Results The 6MWD MCIDs varied widely, depending on the method and subgroup, ranging from 2.27%-8.11% predicted for the overall LOPD population (23.7 m-57.2 m). For patients with baseline 6MWD < 150 m, MCIDs ranged from -0.74%-3.37% (-2.1 m-11.3 m). MCIDs increased with distance walked at baseline until a plateau was reached. For BMI subgroups, the MCIDs were generally lowest in obese patients. Conclusion Our analysis shows that MCID depends on the chosen method and disease severity. The findings suggest that applying a single MCID to all patients can be misleading; consequently, a range of possible MCIDs should be considered. This may also be highly relevant for other neuromuscular diseases. This study provides a range of 6MWD MCIDs for LOPD, with lower MCIDs for more severe patients.https://doi.org/10.1186/s13023-024-03156-3Minimal clinically important differenceMCIDSix-minute walk distance6MWDLate-onset Pompe diseaseDisease severity |
| spellingShingle | Kristl G. Claeys Hani Kushlaf Syed Raza Noemi Hummel Simon Shohet Ian Keyzor Agnieszka Kopiec Ryan Graham Brian Fox Benedikt Schoser Minimal clinically important differences in six-minute walking distance in late-onset Pompe disease Orphanet Journal of Rare Diseases Minimal clinically important difference MCID Six-minute walk distance 6MWD Late-onset Pompe disease Disease severity |
| title | Minimal clinically important differences in six-minute walking distance in late-onset Pompe disease |
| title_full | Minimal clinically important differences in six-minute walking distance in late-onset Pompe disease |
| title_fullStr | Minimal clinically important differences in six-minute walking distance in late-onset Pompe disease |
| title_full_unstemmed | Minimal clinically important differences in six-minute walking distance in late-onset Pompe disease |
| title_short | Minimal clinically important differences in six-minute walking distance in late-onset Pompe disease |
| title_sort | minimal clinically important differences in six minute walking distance in late onset pompe disease |
| topic | Minimal clinically important difference MCID Six-minute walk distance 6MWD Late-onset Pompe disease Disease severity |
| url | https://doi.org/10.1186/s13023-024-03156-3 |
| work_keys_str_mv | AT kristlgclaeys minimalclinicallyimportantdifferencesinsixminutewalkingdistanceinlateonsetpompedisease AT hanikushlaf minimalclinicallyimportantdifferencesinsixminutewalkingdistanceinlateonsetpompedisease AT syedraza minimalclinicallyimportantdifferencesinsixminutewalkingdistanceinlateonsetpompedisease AT noemihummel minimalclinicallyimportantdifferencesinsixminutewalkingdistanceinlateonsetpompedisease AT simonshohet minimalclinicallyimportantdifferencesinsixminutewalkingdistanceinlateonsetpompedisease AT iankeyzor minimalclinicallyimportantdifferencesinsixminutewalkingdistanceinlateonsetpompedisease AT agnieszkakopiec minimalclinicallyimportantdifferencesinsixminutewalkingdistanceinlateonsetpompedisease AT ryangraham minimalclinicallyimportantdifferencesinsixminutewalkingdistanceinlateonsetpompedisease AT brianfox minimalclinicallyimportantdifferencesinsixminutewalkingdistanceinlateonsetpompedisease AT benediktschoser minimalclinicallyimportantdifferencesinsixminutewalkingdistanceinlateonsetpompedisease |