How to Capitalize on the Retest Effect in Future Trials on Huntington’s Disease.
PLoS ONE. 2015-12-29; 10(12): e0145842
DOI: 10.1371/journal.pone.0145842
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1. PLoS One. 2015 Dec 29;10(12):e0145842. doi: 10.1371/journal.pone.0145842.
eCollection 2015.
How to Capitalize on the Retest Effect in Future Trials on Huntington’s Disease.
Schramm C(1)(2)(3)(4), Katsahian S(2)(5), Youssov K(1)(3)(4)(6), Démonet JF(7),
Krystkowiak P(8)(9)(10), Supiot F(11), Verny C(12), Cleret de Langavant
L(1)(3)(4)(6), Bachoud-Lévi AC(1)(3)(4)(6); European Huntington’s Disease
Initiative Study Group and the Multicentre Intracerebral Grafting in Huntington’s
Disease Group.
Collaborators: Bachoud-Lévi AC, Boissé MF, Lemoine L, Verny C, Aubin G, Demonet
JF, Calvas F, Krystkowiak P, Simonin C, Delliaux M, Damier P, Renou P, Supiot F,
Slama H, Bachoud-Lévi AC, Guillamo J, Boissé MF, Dürr A, Bloch F, Messouak O,
Tallaksen C, Dubois B, Engles A, Krystkowiak P, Destee A, Memin A,
Thibaut-Tanchou S, Pasquier F, Galitzky M, Rascol O, Mollion H, Broussolle E,
Madigand M, Lallement F, Goizet C, Tison F, Arguillère S, Bakchine S, Khoris J,
Camu W, Resch F, Hannequin D, Durif F, Saudeau D, Autret A.
Author information:
(1)INSERM U955 E01, Neuropsychologie interventionnelle, Institut Mondor de
Recherche Biomédicale, Créteil, France.
(2)INSERM UMRS1138 E22, Science de l’information au service de la médecine
personnalisée, Centre de Recherche des Cordeliers, Université Paris 5, Université
Paris 6, Paris, France.
(3)Université Paris Est, Faculté de Médecine, Créteil, France.
(4)Ecole Normale Supérieure, Institut d’Etude de la Cognition, Paris, France.
(5)Assistance Publique-Hôpitaux de Paris, Service d’informatique et statistiques,
Hôpital Européen Georges Pompidou, Paris, France.
(6)Assistance Publique-Hôpitaux de Paris, Centre National de Référence pour la
Maladie de Huntington, Hôpital Henri Mondor, Créteil, France.
(7)Leenaards Memory Centre, Clinical Neurosciences Department, CHUV Lausanne,
Lausanne, Switzerland.
(8)Centre Hospitalier Universitaire d’Amiens, Service de neurologie, Amiens,
France.
(9)EA 4559 – Laboratoire de Neurosciences Fonctionnelles et Pathologie (LNFP),
Université de Picardie Jules Verne (UPJV), Amiens, France.
(10)SFR CAP-Santé (FED 4231), Amiens, France.
(11)Hôpital Erasme ULB, Service de Neurologie, Bruxelles, Belgium.
(12)CHU d’Angers, Centre de Référence des Maladies Neurogénétiques, Service de
Neurologie, Angers, France.
The retest effect-improvement of performance on second exposure to a task-may
impede the detection of cognitive decline in clinical trials for
neurodegenerative diseases. We assessed the impact of the retest effect in
Huntington’s disease trials, and investigated its possible neutralization. We
enrolled 54 patients in the Multicentric Intracerebral Grafting in Huntington’s
Disease (MIG-HD) trial and 39 in the placebo arm of the Riluzole trial in
Huntington’s Disease (RIL-HD). All were assessed with the Unified Huntington’s
Disease Rating Scale (UHDRS) plus additional cognitive tasks at baseline (A1),
shortly after baseline (A2) and one year later (A3). We used paired t-tests to
analyze the retest effect between A1 and A2. For each task of the MIG-HD study,
we used a stepwise algorithm to design models predictive of patient performance
at A3, which we applied to the RIL-HD trial for external validation. We observed
a retest effect in most cognitive tasks. A decline in performance at one year was
detected in 3 of the 15 cognitive tasks with A1 as the baseline, and 9 of the 15
cognitive tasks with A2 as the baseline. We also included the retest effect in
performance modeling and showed that it facilitated performance prediction one
year later for 14 of the 15 cognitive tasks. The retest effect may mask cognitive
decline in patients with neurodegenerative diseases. The dual baseline can
improve clinical trial design, and better prediction should homogenize patient
groups, resulting in smaller numbers of participants being required.
DOI: 10.1371/journal.pone.0145842
PMCID: PMC4703129
PMID: 26714284 [Indexed for MEDLINE]