R. A. Vreman

Early health technology assessments in pharmacogenomics: a case example in cardiovascular drugs

AIM To assess the required characteristics (cost, sensitivity and specificity) of a pharmacogenomic test for being a cost-effective prevention of angiotensin-converting enzyme inhibitors induced angioedema. Furthermore, we assessed the influence of only testing high-risk populations. MATERIALS & METHODS A decision tree was used. RESULTS With a willingness-to-pay threshold of €20,000 and €80,000 per quality adjusted life year, a 100% sensitive and specific test may have a maximum cost of €1.30 and €1.95, respectively. When only genotyping high-risk populations, the maximum test price would be €5.03 and €7.55, respectively. CONCLUSION This theoretical pharmacogenomic test is only cost-effective at high specificity, high sensitivity and a low price. Only testing high-risk populations yields more realistic maximum test prices for cost-effectiveness of the intervention.

Weighing of evidence by health technology assessment bodies: retrospective study of reimbursement recommendations for conditionally approved drugs

This study assessed whether five Health Technology Assessment (HTA) bodies in Europe were more negative about drugs with a Conditional Marketing Authorization (CMA) that are approved without controlled studies compared to CMA drugs that are approved based on controlled studies. The HTA recommendations were categorized into positive, restricted, and negative. A total of 92 HTA recommendations were available for 27 drugs. Thirty of 62 (48%) and 17 of 30 (57%) of the recommendations were negative for drugs with and without controlled studies, respectively. Overall, only 12 (13%) recommendations were positive. In all jurisdictions, recommendations between drugs with and drugs without controlled data were comparable, which suggests that the presence of controlled data is not decisive in HTA evaluations. The small proportion of unrestricted positive recommendations highlights difficulties with recommending the drugs in this cohort, which may be caused by scientific uncertainty or other factors. Earlier collaboration between stakeholders is advised in order to improve patient access.

1594 – Effects of alcohol hangover on driving performance

Introduction Alcohol hangover is the most commonly experienced next day consequence of heavy drinking. The symptoms experienced during this post-intoxication state develop when blood alcohol concentration (BAC) returns to zero. The feeling of general misery can persist up to 24 h and can significantly affect planned activities and cognitive functioning. Objective To examine the effects of alcohol hangover on driving performance. Methods In N=47 healthy volunteers, driving performance was tested the morning following heavy drinking (alcohol hangover) and on a control day (no alcohol). Subjects performed a standardized 100-km highway driving test in the STISIM driving simulator. Primary outcome measure was the Standard Deviation of Lateral Position (SDLP), i.e. the weaving of the car. In addition, self-reported driving quality and driving style measures were scored. Results Driving performance was significantly worse during alcohol hangover (ΔSDLP = +1.85 cm; p=0.005). Driving impairment during alcohol hangover was supported by subjective measures. During alcohol hangover, driving quality was rated as significantly worse (p=0.0001), less safe, less considerate, less predictable, and less responsible (p=0.001). Subject reported being significantly more tensed during hangover and more effort was needed to perform the driving test (p=0.001). Conclusion Driving is significantly impaired during alcohol hangover. The magnitude of driving impairment is higher than that observed after administering alcohol to achieve a BAC of 0.05% (ΔSDLP = +1.7 cm), i.e. the legal limit for driving in many countries.

ALCOHOL HANGOVER EFFECTS ON STANDARD DEVIATION OF LATERAL POSITION AND LAPSES OF ATTENTION DURING SIMULATED HIGHWAY DRIVING

Abstract presented at the Australasian Professional Society on Alcohol and other Drugs Conference 2013, 24-27 November 2013, Brisbane, Australiapresented at the Australasian Professional Society on Alcohol and other Drugs Conference 2013, 24-27 November 2013, Brisbane, AustraliaAbstract presented at the Australasian Professional Society on Alcohol and other Drugs Conference 2013, 24-27 November 2013, Brisbane, AustraliaAbstract presented at the Australasian Professional Society on Alcohol and other Drugs Conference 2013, 24-27 November 2013, Brisbane, AustraliaAbstract presented at the Australasian Professional Society on Alcohol and other Drugs Conference 2013, 24-27 November 2013, Brisbane, Australia

LAPSES OF ATTENTION DURING DRIVING IN THE ALCOHOL HANGOVER STATE

# S14.1 BEHAVIOURAL CONSEQUENCES OF THE ALCOHOL HANGOVER - PRELIMINARY FINDINGS {#article-title-2} Attention and memory appear broadly to be affected by alcohol hangover, but research examining these effects in greater detail, together with executive functioning, is required (Ling et al, 2010). We have recently secured an EU Marie Curie Research Fellowship to allow Dr Lauren to conduct research assessing the cognitive consequences of the alcohol hangover. In this on-going randomised, repeated measures, crossover trial, participants are being recruited from Keele University to take part in a study assessing neurocognitive effects of alcohol hangover in a sample of 200 adults. In order to comprehensively assess the cognitive domains most susceptible to the effects of alcohol hangover a battery of Computerised Mental Performance Assessment (COMPASS) tasks are being used. Cognitive domains assessed include; immediate and delayed declarative memory, working memory, attention and executive function and mood. Participants are tested on 2 occasions following both an evening alcohol consumption and abstention. The Bond Lader Visual Analogue scale revealed significantly reduced feelings of alertness, contentment and a trend for reduced feelings of calmness, following a hangover. Alcohol hangover also resulted in impaired performance on the spatial working memory, and numeric working memory as well as significantly slower reaction times on the attention and response inhibition task. Alcohol hangover also leads to greater number of errors during Rapid Visual Information Processing. The present results suggest that tasks, which rely heavily on medial temporal and frontal processing, appear to be most greatly affected. Furthermore overall speed of information processing appears to be impeded. # S14.2 PROSPECTIVE MEMORY DEFICITS ASSOCIATED WITH A STATE OF ALCOHOL HANGOVER {#article-title-3} Background. Alcohol hangover leads to deficits on a range higher order cognitive processes, including executive functions. The current study attempts to extend this focus to observe whether alcohol hangover impedes everyday prospective memory (PM: memory for future events). Methods. An existing groups design was used to compare a group of students who were recovering from alcohol hangover the day after a heavy drinking session, with a group who were hangover-free. A hangover rating scale was used to measure hangover effects; a drug-use questionnaire measured alcohol and other drug use; the Hospital Anxiety and Depression Scale measured mood and the Prospective Remembering Video Procedure (PRVP) measured objective PM. Anyone who reported using an illegal substance or suffering from a psychiatric illness (such as depression) were excluded from the study. Results. After observing no significant between-group differences on age, weekly alcohol use, weekly cigarette use, anxiety or depression scores, the alcohol hangover group recalled significantly fewer items on the PRVP than the hangover-free control group. Conclusion. Impaired Everyday PM should be added to the list of cognitive deficits associated with a state of alcohol hangover. # S14.3 LAPSES OF ATTENTION DURING DRIVING IN THE ALCOHOL HANGOVER STATE {#article-title-4} Background. The morning after a drinking session, i.e. during the alcohol hangover state, people commonly report reduced alertness and ability to concentrate. Thus, it is likely that lapses of attention may occur. These lapses may compromise safety in potentially dangerous activities such as driving a car. The purpose of this study was to examine the presence of lapses of attention during driving in the hangover state. Methods. In N = 47 healthy volunteers, driving performance was tested the morning following an evening of consuming on average 10.2 (4.2) alcoholic drinks (alcohol hangover) and on a control day (no alcohol consumed). Subjects performed a standardized 100-km highway driving test in the STISIM driving simulator when BAC was zero. Lapses of attention were examined, defined as a continuous change of lateral position >100 cm for at least 8 seconds. The number of lapses, maximum lateral deviation, and total time of lapses were computed. Results were compared with subjective assessments of driving quality and driving style. Hangover severity was scored with a visual analog scale ranging from 0 (absent) to 10 (extreme). Δlapses (hangover – control) was related to subjective outcome measures. Results. Data from 4 subjects were excluded as they reported that they had no hangover. Another subject was excluded because he scored positively (6out of 10) on the hangover scale on the control day. Data from N = 42 subjects are presented. During hangover, a significantly increased number of lapses relative to the control day (7.7 versus 5.3 lapses, p = 0.019), and an increased total lapse time (182.7 versus 127.3 seconds, p = 0.040) were observed. The maximum lapse deviation did not differ between hangover and control sessions (p = 0.130). Δlapses was significantly correlated to difference scores on subjective driving quality (p = 0.025) and mental effort to perform the test (p = 0.042). Δlapses was not significantly related to subjective assessments of driving style, sleep quality, or sleepiness scores obtained before or after driving. Driving impairment was significantly related to hangover severity scores. A significant positive relationship was found between difference scores on hangover severity and number of lapses (r = 0.373, p = 0.015) and total lapse time (r = 0.380, p = 0.013). There was no relationship with the number of consumed alcoholic drinks the night before. Conclusions. Driving is significantly impaired during alcohol hangover. Funding: This study was funded by Utrecht University. # S14.4 BIOLOGICAL, PSYCHOLOGICAL, AND BEHAVIORAL CORRELATES OF THE ALCOHOL HANGOVER {#article-title-5} Background. Alcohol intake is a necessary precondition for a hangover. However the amount of alcohol consumed is not proportionally related to the presence and/or severity of the hangover symptoms. Although increased research attention has provided some knowledge regarding its contributory factors, the etiology of the hangover remains merely unknown. Methods. A naturalistic study consisting of an alcohol and a control (alcohol-free) condition was set up, in order to investigate several biological, psychological and behavioral correlates of alcohol hangovers in social drinkers. The day following an evening of alcohol consumption, participants completed a survey and saliva samples were collected. The same procedure was followed after an evening on which no alcohol was consumed. Results. Psychological complaints, smoking, sleeping time, age and sex do not seem to play a decisive role in hangover etiology. Hangover severity and binge drinking were accompanied by a significantly suppressed immune effect compared to the control condition. Hangover severity could be predicted for 36% by blood alcohol concentration estimates, dancing activity, hangover frequency and changes in IFN-γ and TNF-α levels. Conclusions. The day after an evening of alcohol consumption, a suppression of both pro-inflammatory and anti-inflammatory cytokines was observed. More research is needed to investigate how and to what extent changes of cytokine concentrations, psychological and personality characteristics, and other biomarkers are related to the presence and severity of alcohol hangover. Funding: This study was funded by Utrecht University.

S14THE HEALTH AND BEHAVIOURAL CONSEQUENCES OF ALCOHOL HANGOVER

# S14.1 BEHAVIOURAL CONSEQUENCES OF THE ALCOHOL HANGOVER - PRELIMINARY FINDINGS {#article-title-2} Attention and memory appear broadly to be affected by alcohol hangover, but research examining these effects in greater detail, together with executive functioning, is required (Ling et al, 2010). We have recently secured an EU Marie Curie Research Fellowship to allow Dr Lauren to conduct research assessing the cognitive consequences of the alcohol hangover. In this on-going randomised, repeated measures, crossover trial, participants are being recruited from Keele University to take part in a study assessing neurocognitive effects of alcohol hangover in a sample of 200 adults. In order to comprehensively assess the cognitive domains most susceptible to the effects of alcohol hangover a battery of Computerised Mental Performance Assessment (COMPASS) tasks are being used. Cognitive domains assessed include; immediate and delayed declarative memory, working memory, attention and executive function and mood. Participants are tested on 2 occasions following both an evening alcohol consumption and abstention. The Bond Lader Visual Analogue scale revealed significantly reduced feelings of alertness, contentment and a trend for reduced feelings of calmness, following a hangover. Alcohol hangover also resulted in impaired performance on the spatial working memory, and numeric working memory as well as significantly slower reaction times on the attention and response inhibition task. Alcohol hangover also leads to greater number of errors during Rapid Visual Information Processing. The present results suggest that tasks, which rely heavily on medial temporal and frontal processing, appear to be most greatly affected. Furthermore overall speed of information processing appears to be impeded. # S14.2 PROSPECTIVE MEMORY DEFICITS ASSOCIATED WITH A STATE OF ALCOHOL HANGOVER {#article-title-3} Background. Alcohol hangover leads to deficits on a range higher order cognitive processes, including executive functions. The current study attempts to extend this focus to observe whether alcohol hangover impedes everyday prospective memory (PM: memory for future events). Methods. An existing groups design was used to compare a group of students who were recovering from alcohol hangover the day after a heavy drinking session, with a group who were hangover-free. A hangover rating scale was used to measure hangover effects; a drug-use questionnaire measured alcohol and other drug use; the Hospital Anxiety and Depression Scale measured mood and the Prospective Remembering Video Procedure (PRVP) measured objective PM. Anyone who reported using an illegal substance or suffering from a psychiatric illness (such as depression) were excluded from the study. Results. After observing no significant between-group differences on age, weekly alcohol use, weekly cigarette use, anxiety or depression scores, the alcohol hangover group recalled significantly fewer items on the PRVP than the hangover-free control group. Conclusion. Impaired Everyday PM should be added to the list of cognitive deficits associated with a state of alcohol hangover. # S14.3 LAPSES OF ATTENTION DURING DRIVING IN THE ALCOHOL HANGOVER STATE {#article-title-4} Background. The morning after a drinking session, i.e. during the alcohol hangover state, people commonly report reduced alertness and ability to concentrate. Thus, it is likely that lapses of attention may occur. These lapses may compromise safety in potentially dangerous activities such as driving a car. The purpose of this study was to examine the presence of lapses of attention during driving in the hangover state. Methods. In N = 47 healthy volunteers, driving performance was tested the morning following an evening of consuming on average 10.2 (4.2) alcoholic drinks (alcohol hangover) and on a control day (no alcohol consumed). Subjects performed a standardized 100-km highway driving test in the STISIM driving simulator when BAC was zero. Lapses of attention were examined, defined as a continuous change of lateral position >100 cm for at least 8 seconds. The number of lapses, maximum lateral deviation, and total time of lapses were computed. Results were compared with subjective assessments of driving quality and driving style. Hangover severity was scored with a visual analog scale ranging from 0 (absent) to 10 (extreme). Δlapses (hangover – control) was related to subjective outcome measures. Results. Data from 4 subjects were excluded as they reported that they had no hangover. Another subject was excluded because he scored positively (6out of 10) on the hangover scale on the control day. Data from N = 42 subjects are presented. During hangover, a significantly increased number of lapses relative to the control day (7.7 versus 5.3 lapses, p = 0.019), and an increased total lapse time (182.7 versus 127.3 seconds, p = 0.040) were observed. The maximum lapse deviation did not differ between hangover and control sessions (p = 0.130). Δlapses was significantly correlated to difference scores on subjective driving quality (p = 0.025) and mental effort to perform the test (p = 0.042). Δlapses was not significantly related to subjective assessments of driving style, sleep quality, or sleepiness scores obtained before or after driving. Driving impairment was significantly related to hangover severity scores. A significant positive relationship was found between difference scores on hangover severity and number of lapses (r = 0.373, p = 0.015) and total lapse time (r = 0.380, p = 0.013). There was no relationship with the number of consumed alcoholic drinks the night before. Conclusions. Driving is significantly impaired during alcohol hangover. Funding: This study was funded by Utrecht University. # S14.4 BIOLOGICAL, PSYCHOLOGICAL, AND BEHAVIORAL CORRELATES OF THE ALCOHOL HANGOVER {#article-title-5} Background. Alcohol intake is a necessary precondition for a hangover. However the amount of alcohol consumed is not proportionally related to the presence and/or severity of the hangover symptoms. Although increased research attention has provided some knowledge regarding its contributory factors, the etiology of the hangover remains merely unknown. Methods. A naturalistic study consisting of an alcohol and a control (alcohol-free) condition was set up, in order to investigate several biological, psychological and behavioral correlates of alcohol hangovers in social drinkers. The day following an evening of alcohol consumption, participants completed a survey and saliva samples were collected. The same procedure was followed after an evening on which no alcohol was consumed. Results. Psychological complaints, smoking, sleeping time, age and sex do not seem to play a decisive role in hangover etiology. Hangover severity and binge drinking were accompanied by a significantly suppressed immune effect compared to the control condition. Hangover severity could be predicted for 36% by blood alcohol concentration estimates, dancing activity, hangover frequency and changes in IFN-γ and TNF-α levels. Conclusions. The day after an evening of alcohol consumption, a suppression of both pro-inflammatory and anti-inflammatory cytokines was observed. More research is needed to investigate how and to what extent changes of cytokine concentrations, psychological and personality characteristics, and other biomarkers are related to the presence and severity of alcohol hangover. Funding: This study was funded by Utrecht University.

S14THE HEALTH AND BEHAVIOURAL CONSEQUENCES OF ALCOHOL HANGOVERS14.1BEHAVIOURAL CONSEQUENCES OF THE ALCOHOL HANGOVER - PRELIMINARY FINDINGSS14.2PROSPECTIVE MEMORY DEFICITS ASSOCIATED WITH A STATE OF ALCOHOL HANGOVERS14.3LAPSES OF ATTENTION DURING DRIVING IN THE ALCOHOL HANGOVER STATES14.4BIOLOGICAL, PSYCHOLOGICAL, AND BEHAVIORAL CORRELATES OF THE ALCOHOL HANGOVER

# S14.1 BEHAVIOURAL CONSEQUENCES OF THE ALCOHOL HANGOVER - PRELIMINARY FINDINGS {#article-title-2} Attention and memory appear broadly to be affected by alcohol hangover, but research examining these effects in greater detail, together with executive functioning, is required (Ling et al, 2010). We have recently secured an EU Marie Curie Research Fellowship to allow Dr Lauren to conduct research assessing the cognitive consequences of the alcohol hangover. In this on-going randomised, repeated measures, crossover trial, participants are being recruited from Keele University to take part in a study assessing neurocognitive effects of alcohol hangover in a sample of 200 adults. In order to comprehensively assess the cognitive domains most susceptible to the effects of alcohol hangover a battery of Computerised Mental Performance Assessment (COMPASS) tasks are being used. Cognitive domains assessed include; immediate and delayed declarative memory, working memory, attention and executive function and mood. Participants are tested on 2 occasions following both an evening alcohol consumption and abstention. The Bond Lader Visual Analogue scale revealed significantly reduced feelings of alertness, contentment and a trend for reduced feelings of calmness, following a hangover. Alcohol hangover also resulted in impaired performance on the spatial working memory, and numeric working memory as well as significantly slower reaction times on the attention and response inhibition task. Alcohol hangover also leads to greater number of errors during Rapid Visual Information Processing. The present results suggest that tasks, which rely heavily on medial temporal and frontal processing, appear to be most greatly affected. Furthermore overall speed of information processing appears to be impeded. # S14.2 PROSPECTIVE MEMORY DEFICITS ASSOCIATED WITH A STATE OF ALCOHOL HANGOVER {#article-title-3} Background. Alcohol hangover leads to deficits on a range higher order cognitive processes, including executive functions. The current study attempts to extend this focus to observe whether alcohol hangover impedes everyday prospective memory (PM: memory for future events). Methods. An existing groups design was used to compare a group of students who were recovering from alcohol hangover the day after a heavy drinking session, with a group who were hangover-free. A hangover rating scale was used to measure hangover effects; a drug-use questionnaire measured alcohol and other drug use; the Hospital Anxiety and Depression Scale measured mood and the Prospective Remembering Video Procedure (PRVP) measured objective PM. Anyone who reported using an illegal substance or suffering from a psychiatric illness (such as depression) were excluded from the study. Results. After observing no significant between-group differences on age, weekly alcohol use, weekly cigarette use, anxiety or depression scores, the alcohol hangover group recalled significantly fewer items on the PRVP than the hangover-free control group. Conclusion. Impaired Everyday PM should be added to the list of cognitive deficits associated with a state of alcohol hangover. # S14.3 LAPSES OF ATTENTION DURING DRIVING IN THE ALCOHOL HANGOVER STATE {#article-title-4} Background. The morning after a drinking session, i.e. during the alcohol hangover state, people commonly report reduced alertness and ability to concentrate. Thus, it is likely that lapses of attention may occur. These lapses may compromise safety in potentially dangerous activities such as driving a car. The purpose of this study was to examine the presence of lapses of attention during driving in the hangover state. Methods. In N = 47 healthy volunteers, driving performance was tested the morning following an evening of consuming on average 10.2 (4.2) alcoholic drinks (alcohol hangover) and on a control day (no alcohol consumed). Subjects performed a standardized 100-km highway driving test in the STISIM driving simulator when BAC was zero. Lapses of attention were examined, defined as a continuous change of lateral position >100 cm for at least 8 seconds. The number of lapses, maximum lateral deviation, and total time of lapses were computed. Results were compared with subjective assessments of driving quality and driving style. Hangover severity was scored with a visual analog scale ranging from 0 (absent) to 10 (extreme). Δlapses (hangover – control) was related to subjective outcome measures. Results. Data from 4 subjects were excluded as they reported that they had no hangover. Another subject was excluded because he scored positively (6out of 10) on the hangover scale on the control day. Data from N = 42 subjects are presented. During hangover, a significantly increased number of lapses relative to the control day (7.7 versus 5.3 lapses, p = 0.019), and an increased total lapse time (182.7 versus 127.3 seconds, p = 0.040) were observed. The maximum lapse deviation did not differ between hangover and control sessions (p = 0.130). Δlapses was significantly correlated to difference scores on subjective driving quality (p = 0.025) and mental effort to perform the test (p = 0.042). Δlapses was not significantly related to subjective assessments of driving style, sleep quality, or sleepiness scores obtained before or after driving. Driving impairment was significantly related to hangover severity scores. A significant positive relationship was found between difference scores on hangover severity and number of lapses (r = 0.373, p = 0.015) and total lapse time (r = 0.380, p = 0.013). There was no relationship with the number of consumed alcoholic drinks the night before. Conclusions. Driving is significantly impaired during alcohol hangover. Funding: This study was funded by Utrecht University. # S14.4 BIOLOGICAL, PSYCHOLOGICAL, AND BEHAVIORAL CORRELATES OF THE ALCOHOL HANGOVER {#article-title-5} Background. Alcohol intake is a necessary precondition for a hangover. However the amount of alcohol consumed is not proportionally related to the presence and/or severity of the hangover symptoms. Although increased research attention has provided some knowledge regarding its contributory factors, the etiology of the hangover remains merely unknown. Methods. A naturalistic study consisting of an alcohol and a control (alcohol-free) condition was set up, in order to investigate several biological, psychological and behavioral correlates of alcohol hangovers in social drinkers. The day following an evening of alcohol consumption, participants completed a survey and saliva samples were collected. The same procedure was followed after an evening on which no alcohol was consumed. Results. Psychological complaints, smoking, sleeping time, age and sex do not seem to play a decisive role in hangover etiology. Hangover severity and binge drinking were accompanied by a significantly suppressed immune effect compared to the control condition. Hangover severity could be predicted for 36% by blood alcohol concentration estimates, dancing activity, hangover frequency and changes in IFN-γ and TNF-α levels. Conclusions. The day after an evening of alcohol consumption, a suppression of both pro-inflammatory and anti-inflammatory cytokines was observed. More research is needed to investigate how and to what extent changes of cytokine concentrations, psychological and personality characteristics, and other biomarkers are related to the presence and severity of alcohol hangover. Funding: This study was funded by Utrecht University.