HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) All Versions of this Article: dc06-2479v1 30/10/2619    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dyck, P. J. Articles by O'Brien, P. C. Search for Related Content PubMed PubMed Citation Articles by Dyck, P. J. Articles by O'Brien, P. C. Social Bookmarking                What's this?

Challenges in Design of Multicenter Trials: Endpoints Assessed Longitudinally for Change and Monotonicity

¹Peripheral Neuropathy Research Laboratories and
²Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, MN
³VIATRIS GambH, Bad Homburg, Germany
⁴Ergomed GmbH, Frankfurt am Main, Germany
⁵German Diabetes Clinic, German Diabetes Center, Leibniz Institute at the Heinrich Heine University, Düsseldorf, Germany
⁶Lilly Research Laboratories, Indianapolis, IN., and
⁷Indiana University School of Medicine, Indianapolis, IN.

dyck.peter{at}mayo.edu

ABSTRACT

OBJECTIVE:Assessing clinimetric performance of polyneuropathy (DSPN) endpoints in single and multicenter trials.

METHODS:Assessed were placebo treated patients with DSPN in the VIATRIS (V) and Lilly (L) trials and an epidemiologic cohort (R).

RESULTS:Test reproducibility in clinical trial cohorts (r_I 0.7 to 0.85) approached that in R (r_I 0.85 to 0.95). Associations between pairs of endpoints explained < 10% of the variability of data (sometimes 15-35%), being higher in R and V than in L. Most endpoints did not show monotonic worsening over 4 years. However, sural nerve amplitude and peroneal motor conduction velocity did. A nerve conduction score ( 5 NC nds) did not show monotonic worsening in established DSPN. In R followed for 9.5 years, monotonic worsening of small magnitude occurred for sural amplitude, vibration detection threshold, and especially for composite quantitative sensation.

CONCLUSIONS:The main reason why it is difficult to demonstrate monotonic worsening of neuropathic endpoints appears to be very slow worsening of DSPN, a placebo effect for symptoms and signs, and measurement noise. Demonstrating disease progression in controlled trials of DSPN is more likely when: 1) patients with developing rather than established DSPN are selected; 2) type 1 DM patients are preferentially recruited; 3) patients are selected who cannot or will not achieve ideal glycemic control; 4) endpoints chosen are known to show monotonic worsening; and 5) a restricted number of centers and expert examiners (trained, certified, using standard approaches and reference values and interactive surveillance of tests) are used.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. J.M. Boulton Whither Clinical Research in Diabetic Sensorimotor Peripheral Neuropathy?: Problems of end point selection for clinical trials Diabetes Care, October 1, 2007; 30(10): 2752 - 2753. [Full Text] [PDF]