Efficiency of multivariate tests in trials in progressive supranuclear palsy.
Clinical trials
Item response theory
Multiple endpoints
Multivariate tests
Progressive supranuclear palsy
Simulation study
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
26 Oct 2024
26 Oct 2024
Historique:
received:
12
12
2023
accepted:
15
10
2024
medline:
27
10
2024
pubmed:
27
10
2024
entrez:
27
10
2024
Statut:
epublish
Résumé
Measuring disease progression in clinical trials for testing novel treatments for multifaceted diseases as progressive supranuclear palsy (PSP), remains challenging. In this study we assess a range of statistical approaches to compare outcomes as measured by the items of the progressive supranuclear palsy rating scale (PSPRS). We consider several statistical approaches, including sum scores, a modified PSPRS rating scale that had been recommended by FDA in a pre-IND meeting, multivariate tests, and analysis approaches based on multiple comparisons of the individual items. In addition, we propose two novel approaches which measure disease status based on Item Response Theory models. We assess the performance of these tests under various scenarios in an extensive simulation study and illustrate their use with a re-analysis of the ABBV-8E12 clinical trial. Furthermore, we discuss the impact of the FDA-recommended scoring of item scores on the power of the statistical tests. We find that classical approaches as the PSPRS sum score demonstrate moderate to high power when treatment effects are consistent across the individual items. The tests based on Item Response Theory (IRT) models yield the highest power when the simulated data are generated from an IRT model. The multiple testing based approaches have a higher power in settings where the treatment effect is limited to certain domains or items. The study demonstrates that there is no one-size-fits-all testing procedure for evaluating treatment effects using PSPRS items; the optimal method varies based on the specific effect size patterns. The efficiency of the PSPRS sum score, while generally robust and straightforward to apply, varies depending on the specific patterns of effect sizes encountered and more powerful alternatives are available in specific settings. These findings can have important implications for the design of future clinical trials in PSP and similar multifaceted diseases.
Identifiants
pubmed: 39462124
doi: 10.1038/s41598-024-76668-4
pii: 10.1038/s41598-024-76668-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
25581Subventions
Organisme : European Joint Programme on Rare Diseases
ID : Improve-PSP
Organisme : German Federal Ministry of Education and Research
ID : BMBF: 01KU1403A EpiPD
Organisme : German Federal Ministry of Education and Research
ID : 01EK1605A HitTau
Organisme : Deutsche Forschungsgemeinschaft
ID : EXC 2145 SyNergy - ID 390857198
Organisme : DFG grants
ID : HO2402/6-2
Organisme : DFG grants
ID : HO2402/18-1 MSAomics
Informations de copyright
© 2024. The Author(s).
Références
U.S. Department of Health and Human Services Food and Drug Administration, “Multiple endpoints in clinical trials guidance for industry draft guidance,” (2017). https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm536750.pdf .
Golbe, L. I. & Ohman-Strickland, P. A. A clinical rating scale for progressive supranuclear palsy. Brain 130(6), 1552–1565 (2007).
doi: 10.1093/brain/awm032
pubmed: 17405767
Boxer, A. L. et al. Davunetide in patients with progressive supranuclear palsy: A randomised, double-blind, placebo-controlled phase 2/3 trial. Lancet Neurol. 13(7), 676–685 (2014).
doi: 10.1016/S1474-4422(14)70088-2
pubmed: 24873720
pmcid: 4129545
Tolosa, E. et al. A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy. Mov. Disord. 29(4), 470–478 (2014).
doi: 10.1002/mds.25824
pubmed: 24532007
Nuebling, G. et al. Prospera: A randomized, controlled trial evaluating rasagiline in progressive supranuclear palsy. J. Neurol. 263(8), 1565–1574 (2016).
doi: 10.1007/s00415-016-8169-1
pubmed: 27230855
Dam, T. et al. Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: A phase 2, randomized, placebo-controlled trial. Nat. Med. 27(8), 1451–1457 (2021).
doi: 10.1038/s41591-021-01455-x
pubmed: 34385707
Höglinger, G. U. et al. Safety and efficacy of tilavonemab in progressive supranuclear palsy: A phase 2, randomised, placebo-controlled trial. Lancet Neurol. 20(3), 182–192 (2021).
doi: 10.1016/S1474-4422(20)30489-0
pubmed: 33609476
Roesler, T. W. et al. Four-repeat tauopathies. Prog. Neurobiol. 180, 101644 (2019).
doi: 10.1016/j.pneurobio.2019.101644
Levin, J., Kurz, A., Arzberger, T., Giese, A. & Höglinger, G. U. The differential diagnosis and treatment of atypical parkinsonism. Deutsches Ä rzteblatt Int. 113(5), 61 (2016).
O’Brien, P. C. Procedures for comparing samples with multiple endpoints. Biometrics 40(4), 1079–1087 (1984).
doi: 10.2307/2531158
pubmed: 6534410
Reitmeir, P. & Wassmer, G. One-sided multiple endpoint testing in two-sample comparisons. Commun. Stat.-Simul. Comput. 25(1), 99–117 (1996).
doi: 10.1080/03610919608813301
Ristl, R., Urach, S., Rosenkranz, G. & Posch, M. Methods for the analysis of multiple endpoints in small populations: A review. J. Biopharm. Stat. 29(1), 1–29 (2019).
doi: 10.1080/10543406.2018.1489402
pubmed: 29985752
Rasch, G. Studies in Mathematical Psychology: I. Probabilistic Models for Some Intelligence and Attainment tests (1960).
Gewily, M. et al. Quantitative comparisons of progressive supranuclear palsy rating scale versions using item response theory. Mov. Disord.[SPACE] https://doi.org/10.1002/mds.30001 (2024).
doi: 10.1002/mds.30001
pubmed: 39206961
Senn, S. Change from baseline and analysis of covariance revisited. Stat. Med. 25(24), 4334–4344 (2006).
doi: 10.1002/sim.2682
pubmed: 16921578
Siemons, L. & Krishnan, E. A short tutorial on item response theory in rheumatology. Clin. Exp. Rheumatol. 32(4), 581–586 (2014).
pubmed: 25065775
Ueckert, S. Modeling composite assessment data using item response theory. CPT: Pharmacomet. Syst. Pharmacol. 7(4), 205–218 (2018).
Thissen, D., Pommerich, M., Billeaud, K. & Williams, V. S. Item response theory for scores on tests including polytomous items with ordered responses. Appl. Psychol. Measurement 19(1), 39–49 (1995).
doi: 10.1177/014662169501900105
Chalmers, R. P. Mirt: A multidimensional item response theory package for the r environment. J. Stat. Softw. 48, 1–29 (2012).
doi: 10.18637/jss.v048.i06
Pipper, C. B., Ritz, C. & Bisgaard, H. A versatile method for confirmatory evaluation of the effects of a covariate in multiple models. J. R. Stat. Soc. Ser. C: Appl. Stat. 61(2), 315–326 (2012).
doi: 10.1111/j.1467-9876.2011.01005.x
Dallow, N. S., Leonov, S. L. & Roger, J. H. Practical usage of O’Brien’s OLS and GLS statistics in clinical trials. Pharm. Stat. 7(1), 53–68 (2008).
doi: 10.1002/pst.268
pubmed: 17390306
Dmitrienko, A., Tamhane, A. C. & Bretz, F. Multiple Testing Problems in Pharmaceutical Statistics (CRC Press, 2009).
doi: 10.1201/9781584889854
Logan, B. R. & Tamhane, A. C. On O’Brien’s OLS and GLS tests for multiple endpoints. Lect. Notes-Monogr. Ser. 47, 76–88 (2004).
Simes, R. J. An improved bonferroni procedure for multiple tests of significance. Biometrika 73(3), 751–754 (1986).
doi: 10.1093/biomet/73.3.751
Hommel, G. A stagewise rejective multiple test procedure based on a modified Bonferroni test. Biometrika 75(2), 383–386 (1988).
doi: 10.1093/biomet/75.2.383
Futschik, A., Taus, T. & Zehetmayer, S. An omnibus test for the global null hypothesis. Stat. Methods Med. Res. 28(8), 2292–2304 (2019).
doi: 10.1177/0962280218768326
pubmed: 29635962
Vickerstaff, V., Ambler, G. & Omar, R. Z. A comparison of methods for analysing multiple outcome measures in randomised controlled trials using a simulation study. Biometr. J. 63(3), 599–615 (2021).
doi: 10.1002/bimj.201900040
Smith, K. W. Forming composite scales and estimating their validity through factor analysis. Soc. Forces 53(2), 168–180 (1974).
doi: 10.2307/2576010
Stamelou, M. & Höglinger, G. A review of treatment options for progressive supranuclear palsy. CNS Drugs 30, 629–636 (2016).
doi: 10.1007/s40263-016-0347-2
pubmed: 27222018