Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical trials

TY - JOUR

T1 - Use of clinical staging in amyotrophic lateral sclerosis for phase 3 clinical trials

AU - Balendra, Rubika

AU - Jones, Ashley

AU - Jivraj, Naheed

AU - Steen, I Nick

AU - Young, Carolyn A

AU - Shaw, Pamela J

AU - Turner, Martin R

AU - Leigh, P Nigel

AU - Al-Chalabi, Ammar

AU - UK-MND LiCALS Study Group, Mito Target ALS Study Group

PY - 2015/1

Y1 - 2015/1

N2 - Objectives: The use of clinical staging in the fatal neurodegenerative disease amyotrophic lateral sclerosis would have value in optimising future therapeutic trials. We aimed to use previous clinical trial data to determine the length of time patients spend in each of four proposed stages, its range and transition patterns to subsequent stages.Methods: Using databases from two multicentre clinical trials, patients were retrospectively staged through the trial course. At each stage we assessed whether patients then progressed to an earlier, consecutive or later stage or death. Duration spent in each stage before progression to a later stage was calculated.Results: There were 725 patients. No patients moved to an earlier stage. More patients at stages 1, 2 and 3 progressed to the consecutive stage rather than skipping a stage. 59.3% of patients at Stage 1 progressed to Stage 2, 54.0% of patients at Stage 2 progressed to Stage 3, 42.3% of patients at Stage 3 progressed to Stage 4 and 47.0% of Stage 4 patients progressed to death. Transition times between stages had a median duration of 3 to 7 months for stages 2 to 4.Discussion: We have shown using trial data that transition times between stages are short. Use of stage duration as an endpoint might allow a shorter trial duration. We have shown face validity in this system as most patients progress through consecutive stages, and none revert to earlier stages. Furthermore, we have shown the system is reliable across populations and therefore has content validity.

AB - Objectives: The use of clinical staging in the fatal neurodegenerative disease amyotrophic lateral sclerosis would have value in optimising future therapeutic trials. We aimed to use previous clinical trial data to determine the length of time patients spend in each of four proposed stages, its range and transition patterns to subsequent stages.Methods: Using databases from two multicentre clinical trials, patients were retrospectively staged through the trial course. At each stage we assessed whether patients then progressed to an earlier, consecutive or later stage or death. Duration spent in each stage before progression to a later stage was calculated.Results: There were 725 patients. No patients moved to an earlier stage. More patients at stages 1, 2 and 3 progressed to the consecutive stage rather than skipping a stage. 59.3% of patients at Stage 1 progressed to Stage 2, 54.0% of patients at Stage 2 progressed to Stage 3, 42.3% of patients at Stage 3 progressed to Stage 4 and 47.0% of Stage 4 patients progressed to death. Transition times between stages had a median duration of 3 to 7 months for stages 2 to 4.Discussion: We have shown using trial data that transition times between stages are short. Use of stage duration as an endpoint might allow a shorter trial duration. We have shown face validity in this system as most patients progress through consecutive stages, and none revert to earlier stages. Furthermore, we have shown the system is reliable across populations and therefore has content validity.

KW - Acknowledged-BRC

KW - Acknowledged-BRU

KW - Acknowledged-BRU-13/14

U2 - 10.1136/jnnp-2013-306865

DO - 10.1136/jnnp-2013-306865

M3 - Article

C2 - 24463480

SN - 0022-3050

VL - 86

SP - 45

EP - 49

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

IS - 1

ER -