Accounting for repeat enrollments during an emergency clinical trial: the Rapid Anticonvulsant Medications Prior to Arrival Trial (RAMPART).

Abstract

OBJECTIVES:

The objectives were to describe the frequency of repeat enrollment within a specific exception from informed consent trial testing benzodiazepine treatment of prehospital status epilepticus and to estimate the effect of repeat enrollments on the analysis of the primary outcome.

METHODS:

This was a secondary analysis of data collected as part of the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), a study comparing intramuscular midazolam to intravenous lorazepam given by paramedics to patients with prehospital status epilepticus. Subjects in RAMPART achieved a successful primary outcome if they had cessation of seizures by the time of emergency department arrival. Data were collected on all subjects, but only the first enrollment for each individual was used in the primary analysis. The patterns of repeat enrollment are described, along with the demographics of these subjects. In addition, an intraclass correlation coefficient (ICC) was estimated to assess the amount of within-subject correlation and its effect on the estimated treatment effect when all enrollments are included in the analysis.

RESULTS:

A total of 1,023 enrollments occurred in RAMPART among 893 unique individuals (range of repeat enrollment observed = two to 14). The ICC for seizure cessation within individual was low at 0.119; when excluding subjects with benzodiazepine crossover, the ICC was 0.094.

CONCLUSIONS:

In clinical trials of emergency conditions with interval complete resolution, accounting for repeat enrollments is feasible. The RAMPART experience demonstrated that in this setting the within-subject correlation is low and can be accounted for at relatively low statistical cost.

• Authors: William J Meurer, Robert Silbergleit, Katherine S Nicholas, James F Burke, Valerie Durkalski
• Journal: Academic emergency medicine : official journal of the Society for Academic Emergency Medicine (Acad Emerg Med) Vol. 22 Issue 3 Pg. 373-7 (Mar 2015) ISSN: 1553-2712 [Electronic] United States
• PMID: 25715865 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2015 by the Society for Academic Emergency Medicine.

Chemical References

• Anticonvulsants
• Lorazepam
• Midazolam

Topics

• Adult
• Aged
• Allied Health Personnel
• Anticonvulsants (administration & dosage, therapeutic use)
• Double-Blind Method
• Female
• Humans
• Injections, Intramuscular
• Injections, Intravenous
• Lorazepam (administration & dosage, therapeutic use)
• Male
• Midazolam (administration & dosage, therapeutic use)
• Middle Aged
• Racial Groups
• Research Design
• Status Epilepticus (drug therapy)