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. 2025 Feb;21(2):e14436.
doi: 10.1002/alz.14436. Epub 2024 Dec 18.

Appropriate use of meaningful within-patient change (MWPC) thresholds in Alzheimer's disease

Claire J Lansdall  1 , Jeffrey L Cummings  2 , Jeffrey Scott Andrews  3
Affiliations

Appropriate use of meaningful within-patient change (MWPC) thresholds in Alzheimer's disease

Claire J Lansdall et al. Alzheimers Dement. 2025 Feb.
No abstract available

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Conflict of interest statement

Claire J. Lansdall (C.J.L.) is an employee of F. Hoffmann‐La Roche Ltd and owns stock options in F. Hoffmann‐La Roche Ltd. Jeffrey L. Cummings (J.L.C.) has provided consultation to Acadia, Actinogen, Acumen, AlphaCognition, ALZpath, Aprinoia, AriBio, Artery, Biogen, Biohaven, BioVie, BioXcel, Bristol‐Myers Squibb, Cassava, Cerecin, Diadem, Eisai, Global Alzheimer's Platform (GAP) Foundation, GemVax, Janssen, Jocasta, Karuna, Lighthouse, Lilly, Lundbeck, EQT Life Sciences (formerly LSP), Mangrove Therapeutics, Merck, NervGen, New Amsterdam, Novo Nordisk, Oligomerix, Ono, Optoceutics, Otsuka, Oxford Brain Diagnostics, Prothena, reMYND, Roche, Sage Therapeutics, Signant Health, Simcere, Sinaptica, Suven, TrueBinding, Vaxxinity, and Wren pharmaceutical, assessment, and investment companies. J.L.C. owns the copyright of the Neuropsychiatric Inventory. J.L.C. has stocks/options in Artery, Vaxxinity, Behrens, Alzheon, MedAvante‐Prophase, and Acumen. J.L.C. has received the following grants: National Institute of General Medical Sciences (NIGMS) grant P20GM109025; National Institute of Neurological Disorders and Stroke (NINDS) grant U01NS093334; National Institute on Aging (NIA) grant R01AG053798; NIA grant P30AG072959; NIA grant R35AG71476; NIA R25 AG083721‐01; Alzheimer's Disease Drug Discovery Foundation (ADDF); Ted and Maria Quirk Endowment; Joy Chambers‐Grundy Endowment. Jeffrey Scott Andrews (J.S.A.) is an employee of Takeda Pharmaceutical Company Limited and a minor shareholder of Takeda Pharmaceutical Company Limited. Author disclosures are available in the Supporting Information.

Figures

FIGURE 1
FIGURE 1
Hypothetical examples of analyses and outputs using MWPC thresholds to define meaningful within‐patient progression on the CDR‐SB. These outputs are for illustrative purposes only and reflect hypothetical trial data. (A) A hypothetical hazard ratio graph displaying the risk of meaningful within‐patient progression by treatment arm. Here, meaningful progression can be defined by MWPC thresholds that are considered appropriate for the enrolled trial population (i.e., it may be appropriate to select a 1‐point threshold for MCI and a 2‐point threshold for mild AD patients, based on existing estimates in early AD 7 , 8 , 9 ). (B) A hypothetical eCDF plot, reporting the proportion of patients who meet or exceed established MWPC thresholds (denoted by Threshold X, Threshold Y) by the treatment arm in the table insert. eCDF plots can be useful graphical outputs to display the cumulative proportion of patients who experience a given score change on the CDR‐SB from baseline to the primary analysis timepoint. The curve for an effective treatment should be shifted to the left, indicating that individuals receiving treatment are less likely to experience greater levels of progression on the CDR‐SB. Graphs can be annotated with a range of MWPC thresholds that are considered appropriate for the enrolled trial population and the proportion of patients in each arm whose change‐from‐baseline meets or exceeds these thresholds can be reported as indicated in the table insert. AD, Alzheimer's disease; CDR‐SB, Clinical Dementia Rating—Sum of Boxes; eCDF, empirical cumulative distribution function; MCI, mild cognitive impairment; MWPC, meaningful within‐patient change.
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References

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