Evidence Report Narcolepsy (with and without Cataplexy) and Commercial Motor Vehicle Driver Safety Presented to The Federal Motor Carrier Safety Administration October 6, 2009 MANILA Consulting Group, Inc. 1420 Beverly Road, Suite 220 McLean, VA 22101 Evidence reports are independently reviewed by the Agency's Medical Review Board (MRB) and Medical Expert Panel (MEP). FMCSA considers MRB recommendations, MEP opinions and other data; however, all proposed changes to current standards and guidelines will be subject to public notice and comment and relevant rulemaking processes. Narcolepsy and CMV Driver Safety October 2009 Authorship Michelle Bieber-Tregear, PhD MANILA Consulting Group Jessica Roberts Williams, PhD, MSN, MPH MANILA Consulting Group Stephen Tregear, DPhil MANILA Consulting Group Policy Statement This report was prepared by MANILA Consulting Group, Inc. under contract GS-10F-0177N/DTMC75-06- F-00039 with the Department of Transportation’s Federal Motor Carrier Safety Administration. i Narcolepsy and CMV Driver Safety October 2009 Table of Contents Executive Summary ....................................................................................................................................... 1 Purpose of Evidence Report ...................................................................................................................... 1 Identification of Evidence Bases ............................................................................................................... 2 Grading the Strength of Evidence ............................................................................................................. 2 Analytic Methods ...................................................................................................................................... 3 Presentation of Findings ........................................................................................................................... 3 Evidence-Based Conclusions ..................................................................................................................... 3 Key Question 1: Are individuals with narcolepsy (with or without cataplexy) at an increased risk for a motor vehicle crash when compared to comparable individuals without the disorder? ............ 3 Key Question 2: Do currently recommended treatments for narcolepsy reduce the risk for a motor vehicle crash? ............................................................................................................................. 4 Preface ........................................................................................................................................................ 13 Organization of Report ............................................................................................................................ 13 Scope ....................................................................................................................................................... 13 Background ................................................................................................................................................. 15 Normal Sleep, Disruptions to Sleep, and Circadian Rhythms ................................................................. 15 Stages of Sleep .................................................................................................................................... 16 Circadian Rhythm ................................................................................................................................ 17 Narcolepsy .............................................................................................................................................. 18 Causes of Narcolepsy .......................................................................................................................... 19 Diagnostic criteria ............................................................................................................................... 20 Prevalence ........................................................................................................................................... 22 Impact of Narcolepsy .......................................................................................................................... 22 Treatment ............................................................................................................................................... 23 Medications ........................................................................................................................................ 23 Lifestyle Modifications ........................................................................................................................ 24 Crash Statistics, Sleep-related Crash Data, and Relevant Regulations ....................................................... 26 Highway-related Occupational Injuries and Fatalities ............................................................................ 26 Large Truck Crash Statistics ..................................................................................................................... 26 Impact of Fatigue, Sleepiness, and Sleep-related Disorders on Driving Ability .................................. 29 Current Relevant Medical Fitness Standards and Guidelines for CMV Drivers in the United States ..... 30 Relevant Medical Fitness Standards for Medical Examiners .............................................................. 30 Regulatory Medical Fitness Standards and Guidelines in Other Countries ........................................ 31 ii Narcolepsy and CMV Driver Safety October 2009 Medical Fitness Standards and Guidelines for Individuals Performing Transportation Safety in the United States ................................................................................................................................ 34 Methods ...................................................................................................................................................... 36 Key Questions ......................................................................................................................................... 36 Identification of Evidence Bases ............................................................................................................. 37 Searches .............................................................................................................................................. 38 Retrieval Criteria ..................................................................................................................................... 39 Inclusion and Exclusion Criteria .......................................................................................................... 39 Evaluation of Quality and Strength of Evidence ..................................................................................... 40 Statistical Methods ................................................................................................................................. 41 Evidence Synthesis ...................................................................................................................................... 43 Key Question 1: Are individuals with narcolepsy (with or without cataplexy) at an increased risk for a motor vehicle crash when compared to comparable individuals without the disorder? ...................... 43 Introduction ........................................................................................................................................ 43 Identification of Evidence Base ........................................................................................................... 43 Evidence Base ..................................................................................................................................... 44 Generalizability of Evidence to Target Population ............................................................................. 49 Findings ............................................................................................................................................... 53 Summary of Findings .......................................................................................................................... 56 Key Question 2: Do currently recommended treatments for narcolepsy reduce the risk for a motor vehicle crash? .......................................................................................................................................... 57 Introduction ........................................................................................................................................ 57 Identification of Evidence Base ........................................................................................................... 58 Key Question 2A: What is the Impact of Treatment with Modafinil or Armodafinil for Narcolepsy on Driver safety? .......................................................................................................................................... 60 Study Design Characteristics ............................................................................................................... 61 Characteristics of Enrollees ................................................................................................................. 65 Quality of Included Studies ................................................................................................................