Obstructive Sleep Apnea and Commercial Motor Vehicle Driver Safety

1. Obstructive Sleep Apnea and Commercial Motor Vehicle Driver Safety Update on the 2007 Evidence Report PREPARED FOR: Federal Motor Carrier Safety Administration Medical Review Board Meeting, June 30, 2011 Prepared By: Stephen Tregear, DPhil Program Director Division of Evidence-based Decision and Policy Making Manila Consulting Group

2. The Driving Task

3. Sleep Apnea: Associated Problems • Excessive daytime sleepiness • Cognitive function reduced • Psychomotor performance impaired • Comorbid conditions • Hypertension • Cardiovascular Disease • Diabetes

4. Evidence Report Background • Original evidence report presented to FMCSA in July 2007 • http://www.fmcsa.dot.gov/rules-regulations/TOPICS/mep/report/Sleep-Apnea-Final-Executive-Summary-prot.pdf • MEP held in August 2007 • MEP recommendations presented to MRB and FMCSA in January 2008 • http://www.fmcsa.dot.gov/rules-regulations/TOPICS/mep/report/Sleep-MEP-Panel-Recommendations-508.pdf

5. Evidence Report Background • Article published in the Journal of Clinical Sleep Medicine in 2009 • Obstructive Sleep Apnea and Risk of Motor Vehicle Crash: Systematic Review and Meta-Analysis. Tregear et al. JCSM 2009; 5:573-81 . • Article published in Sleep in 2010 • Continuous Positive Airway Pressure Reduces Risk of Motor Vehicle Crash among Drivers with Obstructive Sleep Apnea: Systematic Review and Meta-analysis. Tregear et al. SLEEP 2010;33:1373-1380. • New searches requested by FMCSA in late April 2011 • This presentation summarizes all of this work

6. Original Key Questions • Key Question 1: Are individuals with obstructive sleep apnea (OSA) at an increased risk for a motor vehicle crash when compared to comparable individuals who do not have OSA? • Key Question 2: What disease-related factors are associated with an increased motor vehicle crash risk among individuals with OSA? • Key Question 3: Given the findings of Key Question 2, are individuals with OSA unaware of the presence of the factors that appear to be associated with an increased motor vehicle crash risk?

7. Original Key Questions • Key Question 4: Are there screening/diagnostic tests available that will enable examiners to identify those individuals with OSA who are at an increased risk for a motor vehicle crash? • Key Question 5: Which treatments have been shown to effectively reduce crash risk among individuals with OSA? • Key Question 6: What is the length of time required following initiation of an effective treatment for individuals with OSA to reach a degree of improvement that would permit safe driving?

8. Original Key Questions • Key Question 7: How soon, following cessation of treatment (i.e., as a consequence of non-compliance), will individuals with OSA demonstrate reduced driver safety?

9. Key Question 1: Crash Risk Original 2007 Report • 17 studies included • 2 studies - CMV drivers • All case-control • Quality = Low/moderate

10. Key Question 1: Crash Risk Among CMV Drivers • Howard et al. 2004 (Quality = Low) • Australia • 2,342 of 3,268 (72%) responded • CMV drivers with sleep apnea syndrome (symptom diagnosis [MAPS] ≥ 5 + ESS ≥ 11) vs. CMV drivers not diagnosed with sleep apnea syndrome (controls) • Drivers diagnosed with sleep apnea syndrome (MAP Score ≥ 0.5 and ESS Score ≥ 11) found to be at an increased risk for crash (OR = 1.3, 95% CI: 1.00-1.69)

11. Key Question 1: Crash Risk Among CMV Drivers • Stoohs et al. 1994 (Quality = Moderate) • A cross-sectional population of 90 CMV drivers 20-64 years of age who agreed to undergo overnight recordings (Mesam IV) • Recordings consisted of: • Oxygen saturation • Heart rate • Snoring sounds • Body position/movement • Crash data – self reported via questionnaire • Main outcome measures included: • Crash rate over previous 5 years • ODI • Total sleep time

12. Key Question 1: Crash Risk Among CMV Drivers

13. Key Question 1: Crash Risk Among CMV Drivers

14. Key Question 1: Crash Risk • CMV drivers with OSA are at an increased risk for a crash when compared to their counterparts who do not have the disorder (SoE: Minimally Acceptable) • A precise estimate of magnitude of this increased risk cannot be determined at this time

15. Key Question 1: Crash Risk: Findings of Rate Ratio (RR) Studies • 15 studies • RR studies = crash rate among individuals with OSA vs. crash rate among comparable individuals without OSA • Overall quality = Low • We wished to pool data from studies • 6 studies not pooled because not enough data was presented to determine the crash rate ratio and 95% confidence intervals • Crash data from 9 studies pooled

16. Key Question 1: Crash Risk (Random-Effects Meta-Analysis)

17. Key Question 1: Crash Risk: Findings of Rate Ratio (RR) Studies • Findings of remaining 6 studies not included in MA do not contradict findings of MA • Sensitivity analyses did not overturn findings of MA • No evidence of publication bias found • Findings robust

18. Key Question 1: Crash Risk • As a group, drivers with obstructive sleep apnea are at an increased risk for a motor vehicle crash when compared with comparable drivers who do not have the disorder (SoE: Strong) • Precise estimate of magnitude of this increased risk not calculated • Crash Risk Rate in region of 1.30 to 5.72 • Crash risk among individuals with a diagnosis of OSA is between 30% and 572% higher than comparable individuals without the disorder

19. Key Question 1: Crash Risk: Findings of Rate Ratio (RR) Studies - 2009 • 18 studies • 8 studies not pooled because not enough data was presented to determine the crash rate ratio and 95% confidence intervals • Crash data from 10 studies pooled

20. Key Question 1: Crash Risk (Random-Effects Meta-Analysis - 2009)

21. Key Question 1: Crash Risk - 2009 • Findings of previous analysis confirmed • Precise estimate of magnitude of this increased risk not calculated • Crash Risk Rate in region of 1.20 to 4.89 • Crash risk among individuals with a diagnosis of OSA is between 20% and 489% higher than comparable individuals without the disorder

22. Key Question 1: Crash Risk • Another systematic review found similar results: • Ellen 2006 – For studies investigating whether noncommercial drivers with sleep apnea have increased crash rates, the majority (23 of 27 studies and 18 of 19 studies with control groups) found a statistically significant increased risk, with many of the studies finding a 2 to 3 times increased risk. For commercial drivers, only 1 of 3 studies found an increased crash rate, with this association being weak (odds ratio of 1.3).

23. Key Question 1: Updated Search through May 2011 • One new study identified • Komada et al. 2009 – The odds ratio of MVA in the OSAS group compared to a general population was 2.36. • Some new studies of note that examine impact on driving performance: • Pizza et al., 2009 - Simulator • Tippin et al., 2009 – Visual vigilance test • Vaculin et al. 2009 – Simulator • Phillip et al., 2008 – Naturalistic driving • All found that individuals with OSA showed reductions in driving-related performance

24. Key Question 2: Risk Factors and Crash Risk Original 2007 Report • 10 studies included • All case-control studies • One specific to CMV drivers • Overall quality = Low

25. Key Question 2: Risk Factors and Crash Risk

26. Key Question 2: Risk Factors and Crash Risk • Stoohs et al. (Quality = Moderate) examined the relationship between several potential risk factors for crash in CMV drivers • Risk factors assessed included: • Presence of excessive daytime sleepiness (measured using custom instrument) • Severity of sleep disordered breathing (based on ODI – Mesam IV [level 4]) • Body mass index (BMI) • Excessive daytime sleepiness associated with increased crash risk among CMV drivers • Neither the severity of sleep disordered breathing nor BMI were found to be significantly associated with crash risk

27. Key Question 2: Risk Factors and Crash Risk • Four factors have consistently been shown to be associated with crash risk among the general driver population: • Severity of disordered respiration during sleep (as measured by the AHI or the RDI) • Presence and degree of daytime sleepiness (as measured using ESS but not MSLT or MWT) • Blood oxygen saturation levels • Body mass index (BMI)

28. Key Question 2: Updated Search through May 2011 • Several new studies identified • Amra et al., 2011 – High-risk Berlin questionnaire, larger neck circumference, and a history of witnessed apneas were the most important predictors of motor vehicle accident. • Komada et al. 2009 - Subjective excessive daytime sleepiness and severity of OSAS are independently associated with the occurrence of MVA. • Phillip et al., 2008 – The number of inappropriate line crossings correlated with MWT scores, Karolinska Sleepiness Scale scores measured at halfway in total driving distance and Epworth Sleepiness Scale

29. Key Question 3: Awareness of Identified Risk Factors Original 2007 Report • 3 studies • All case-series • Different approaches to same problem

30. Key Question 3: Awareness of Identified Risk Factors • One study found that when individuals with moderate-to-severe OSA re-evaluated the degree of sleepiness they had experienced prior to the onset of treatment (measured via the ESS), the pre-treatment level of sleepiness was reassessed as being much higher than originally reported • One study found no correlation between ESS and MSLT scores, suggesting a disconnect between subjective and objective measures of sleepiness • One study found no difference in ESS scores of individuals with OSA and ESS scores estimated by their partners

31. Key Question 3: Awareness of Identified Risk Factors • Individuals with OSA may not be aware of the extent to which they are affected by daytime sleepiness (SoE: Minimally Acceptable)

32. Key Question 3: Updated Search through May 2011 • No new studies that meet inclusion criteria identified

33. Key Question 4: Diagnosis and Severity Stratification Original 2007 Report • 43 studies • 42 studies assessed the diagnostic performance of a portable sleep monitoring system • 1 study assessed the effectiveness of a clinical model in addition to a portable sleep monitoring system • This was the only study to have enrolled only CMV drivers • Moderate-to-high quality

34. Key Question 4: Diagnosis and Severity Stratification

35. Key Question 4: Diagnosis and Severity Stratification • No model or psychometric instrument has been shown to accurately stratify individuals with OSA by disease severity (a surrogate marker for crash risk) • A number of portable sleep monitoring systems, though not as accurate as the current reference standard (PSG), offer an alternative method for assessing the severity of OSA in a large number of individuals at a relatively low cost • It is not clear whether these systems are accurate enough to be considered acceptable alternatives to PSG for stratifying individuals by OSA severity for the purposes of making decisions about the fitness of an individual to drive a CMV • A formal decision and cost-effectiveness analyses should be performed to fully address this issue

36. Key Question 4: Updated Searchthrough May 2011 • Many new studies (over 10) have been identified • Recommend that FMCSA consider commissioning new set of analyses to include new data

37. Key Question 5: Treatment Effectiveness • 3 separate evidence bases developed • Crash – 9 studies • All CPAP • Simulated driving performance – 10 studies • 8 CPAP • 1 medication (theophylline) • 1 dental appliance (mandibular advancement) • 1 surgery (UPPP) • Indirect measures – 48 studies • 3 Behavioral modification • 32 CPAP • 2 Dental appliances • 8 medication • 6 surgery

38. Key Question 5: Treatment Effectiveness

39. Key Question 5: Treatment Effectiveness % Reduction in Crash Rate Following CPAP *Any non-injurious crash **Any injurious crash

40. Key Question 5: Treatment Effectiveness • Crash risk reduced by approx 72% following CPAP

41. Key Question 5: Updated Search through May 2011 • A systematic review on impact of CPAP on crash risk identified • Antonopoulos et al., 2010 - A statistically significant reduction in real accidents and near miss accidents was observed. Meta-regression analysis suggested that nCPAP more effective among patients entering the studies with higher baseline accident rates. • Many new studies (over 30) have been identified • Recommend that FMCSA consider commissioning new set of analyses to include new data

42. Key Question 5: Treatment Effectiveness • But is this reduction large enough to reduce crash risk to “normal” levels?

43. Key Question 5: Treatment Effectiveness • Indirect measures suggest that not all individuals will attain normal levels of function

44. Key Question 5: Updated Search through May 2011 • No new studies identified by searches performed in 2009 (CPAP only) • Many new studies (k>30) identified by searches performed in May 2011 (all treatment options) • Recommend that FMCSA consider commissioning new set of analyses to include new data

45. Key Question 6: Time to Reach Optimal Effectiveness Original 2007 Report • 24 studies • 12 CPAP • 1 CPAP & Oral Appliances • 1 CPAP and Medication • 9 Medication • 1 Oral Appliances • High quality: 8 • Moderate quality: 14 • Low quality: 2

46. Key Question 6: Time to Reach Optimal Effectiveness • The impact that CPAP has on crash risk reduction among individuals with OSA is seen after as little as one night of treatment (SoE: Minimally Acceptable) • Simulated driving performance, severity of disordered respiration, blood oxygen saturation, and some (but not all) measures of cognitive and psychomotor performance improve significantly following a single night of treatment • Exactly how many nights of treatment are required until CPAP exerts maximum benefit is not known but evidence suggests <2 weeks

47. Key Question 6: Updated Search through May 2011 • No new studies identified

48. Key Question 7: Time to Deteriorate Original 2007 Report • 4 studies • All 4 assessed effects of withdrawal from CPAP

49. Key Question 7: Time to Deteriorate • Cessation of CPAP leads to a decrease in simulated driving ability and increases in both OSA severity and daytime sleepiness (SoE: Minimally Acceptable) • The exact rate at which deterioration occurs cannot be determined; however, this deterioration may occur as soon as 24 hours following cessation of treatment

50. Key Question 7: Updated Search through May 2011 • No new studies identified