Driving tests with patients

Transcription

1 Br. J. clin. Pharmac. (1984), 18, 103S-108S Driving tests with patients J. J. de GIER Department of Pharmacotherapy, Subfaculty of Pharmacy, Drugs and Driving Research Group, State University of Utrecht, Vondellaan 14, 3521 GE Utrecht, The Netherlands 1 Mental illness and the use of psychotropic drugs are considered to influence driving skills of patients. However, studies which indicate the relative contributions of these factors are rare. 2 It is emphasized that for measuring the effects of psychotropic drugs on driving performance of patients, real driving tests are needed. 3 Actual driving and psychomotor performance of patients receiving diazepam, and patients and healthy volunteers receiving mebhydrolin were measured to illustrate the use of real driving tests. 4 The results of both studies are discussed in terms of problems associated with the application of these tests. Patient recruitment is considered to be a major problem. To draw conclusions under these circumstances is extremely difficult, but still acceptable in comparison with the limitations and methodological difficulties of the more commonly used laboratory tests. 5 Some guidelines for driving tests with patients are given. Keywords driving tests psychotropic drugs Introduction Present epidemiological data suggest that the use of psychotropic drugs is associated with an increased involvement in traffic accidents (Maki & Linnoila, 1976; Warren et al., 1981). However, the relative contributions of mental illness and psychotropic drug use have not been identified out in these epidemiological studies. With respect to the drug use it is possible that some patients with mental disturbances would be more hazardous drivers if they were not taking their medication. But still, it is also possible that after taking their drugs in normal therapeutic dosages, these patients remain unsafe drivers. Laboratory studies on the effects of psychotropic drugs on driving-related skills of chronically treated outpatients are rare. Yet, these patients are the drivers of interest in the epidemiological studies. A major limitation of most laboratory studies is the use of short duration laboratory tests, hardly related to the complex skill of real driving and yet frequently assumed to be valid indicators of real driving performance. It has been demonstrated that tests should be prolonged and monotonous to minimise 'the pulling together' effect which is a handicap of the commonly used batteries of attractive and entertaining short duration tests (Hart et al., 1976; Seppala et al., 1979). 103S

2 104S J. J. de Gier During the last 5 years simulated driving and low speed vehicle handling tests have been important tools to reveal the overall effects of drugs on driving. However, this does not reflect actual driving since the situation lacks the essential environment, i.e. other traffic (Silverstone, 1974). Subjects' motivation for reactions under simulated conditions is mostly lower than when really driving in traffic situations. At least in simulated driving the test lasts long enough to be boring and monotonous. For overcoming most of the limitations and methodological difficulties mentioned above we decided to perform our studies with patients, using a driving test for the measurement of real driving performance. Since we felt that real driving tests and validated laboratory tests (including simulated driving) are both needed to study the drugs and driving problem as such, we compared the patients' performance in a laboratory task with their real driving performance. In order to study patient compliance and to detect a possible drug level - response relationship, levels of psychotropic drugs (and their pharmacologically active metabolites) in body fluids, in particular saliva, are measured. General practitioners, mainly in the Province of Utrecht, collaborate in our studies for the recruitment of patients. Methods and Results Driving test During the driving test, skills were related by a trained observer in the front seat of the car using a 110-item checklist. The observer was an employee of the Traffic Department of the Royal Dutch Tourist Association (ANWB) who normally acts as examiner for the Advanced Drivers Test ot this association. The items of the checklist reflect behavioural components and cognitive skills involved in driving. Items are rated on a three point scale as 'satisfactory', 'moderate' and 'insufficient'. A final driving ability score is assessed by calculating the total number of items scored as 'insufficient' in a selection of 22 so called important items. The importance of an item is indexed regarding the fundamental contribution of respective items to traffic safety. Driving tests take place on the city streets of Utrecht and surroundings between and Traffic conditions during each test vary enough to ensure a good basis for measuring driving skills. The approximate distance is 60 km and average driving time is 86 min. The vehicle used is a small station wagon equipped with dual controls. Normally, the first 20 min of actual driving are not rated to allow patients to become familiar with the vehicle. In order to decide which score on the 22 items would characterize the subject as an unsafe driver, the driving scores of 20 learner drivers were used to set this criterion. These drivers performed the driving test within 7 days after they failed the practical examinations by the Dutch Licensing Authorities for a licence. In particular the items concerning 'visual perception' and 'anticipation of events' were scored as 'insufficient'. Laboratory test In our experiments we use attention-demanding tasks that have been described in full elsewhere (de gier et al., 1981). These tasks are based on visual vigilance and are designed to be protracted and boring. A high-attention demanding task (A) and a low-attention demanding task (B) are performed for 1 h each (without an interval in between) in a soundproof room. In task A the subject has to detect randomly introduced irregularities in the sequence in which a moving dot (speed 900 ms/movement) lights up in a 10 x 10 stationary pattern of small open circles on a colour CRT. Normally, the dot moves continuously from left to right and top to bottom by skipping two circles or no circle at all. An irregularity is said to occur if the moving dot skips one circle. The latter detected by the subject is recorded as a 'hit'. Incorrect responses are recorded as 'false alarms' or 'misses'. In task B the subject has to keep the joystick controlled cursor within the boundaries of a slowly moving (0.5 cm/s) CRT displayed square (dimension 70/ 30 mm). Changes of direction of movement (horizontal movement only) are randomly introduced and the subject's performance is measured by the number of seconds that the centre of the cursor is outside the boundaries of the square. Experimental design During each day of experimentation two subjects are tested individually on driving and laboratory tests (09.00 or 14.00); one subject starting the driving test, the other the laboratory test. Lunches are standardized (milk, orange juice and sandwiches). Subjects are instructed not to drink alcoholic beverages within 24 h preceding

3 their tests and not to take any other drugs than the one under investigation and prescribed by their physician. They are allowed to smoke between the sessions and to have one cup of coffee at lunch. Furthermore they are instructed not to speak about their drug use, if any, to the observer in the car. Drugs and driving performance * Mean score (%) of hits (task A) * - IVlean number of false alarms (task A) o = Mean number of seconds out (taskb) 105S NS P < 0.01 P < 0.05 Study I Seventeen male subjects, under normal medical control by the same physician, took part in this study. Nine subjects (45.6 ± 9.6 years of age) were outpatients receiving diazepam for the relief of anxiety (orally twice or three times daily 5 mg by prescription). Their driving experience was 23.3 ± 8.2 years. Eight subjects served as controls (42.5 ± 8.1 years of age) and their driving experience was 19.8 ± 5.4 years. In this particular study all subjects completed a driving test 1 day preceding the experiment in order to become familiar with the vehicle and the driving area. The results of the driving test are given in Table 1 and Figure 3a. The patients scored significantly (P < 0.05, Mann-Whitney U-test) more often 'insufficient' on the 22 most important items. The patients showed impaired visual perception and anticipation of dangerous events during driving to an extent that there were more unsafe drivers among them (5/9) compared with the control subjects (1/8). The results of the laboratory test are given in Figure 1. The patients showed significantly less (P < 0.01, Student's t-test) false alarms in task A and significantly more (P < 0.05) seconds out in task B. Figure 2 shows the latter results where the Table 1 Number of important items scored as 'insufficient' in the driving test. Subject Patients on Control diazepam subjects 1 0(0) 0(0) 2 1 (0) 6(1) 3 11(5)* 1(0) 4 13 (5)* 12 (5)* 5 7(3) 0 (0) 6 8 (4)* 4(2) 7 11(6)* 6(3) 8 8(3) 0 (0) 9 10(4)* o Number of items scored as 'insufficient' out of six items reflecting 'visual perception' and 'anticipation of events' *, four items scored as 'insufficient' constitutes unsafe driving Figure 1 Aw 0 15 X E co 'a 10 S a to 5 ẹ 0 I HUFF1 l I Patients Control subjects The results of the laboratory test in Study I. seconds out are presented as periods of sustained seconds out. Furthermore, there was a correlation between performance in task B (total number of seconds out) and driving performance (number of items scored as insufficient) (Spearman coefficient of correlation 0.52). Although good correlation existed between saliva (or pharmacologically active levels) and plasma levels of diazepam (r = 0.901), no correlations were found between blood levels of the drug and/or its major metabolite (N-desmethyldiazepam) and performance measurements. Study II The purpose of this study was to evaluate the extent of impairment of driving performance caused by mebhydrolin, a widely used HI-receptor antagonist in the Netherlands. During the first 6 weeks of the hay fever season in 1982 only six patients (all male) were recruited by the general practitioners in the Province of Utrecht. Therefore it was decided to extend the total number of subjects by including healthy volunteers employing the same design as indicated for the patients, i.e. first day of experimentation during treatment and a second day after the treatment had ceased (after a washout period of at least 7 days). z

4 106S J. J. de Gier 40 a) l Patients 2 20 LL * Control subjects Periods of sustained seconds out (task B) Figure 2 The results of task B presented as periods of sustained seconds. Twenty male subjects were divided into two groups (I + II) each of 10 subjects. Both groups were assessed on the tests twice, i.e. with and without administration of mebhydrolin 50 mg three times daily for a period of 7 days. For group I the medication started after a base-line measurement, for the other group (II) the assessments were made for the first time after drug treatment (wash-out period of 7 days). Table 2 presents the mean values of age, weight and driving experience of the subjects (patients indicated as Group III). The results of the driving test are given in Figure 3b. It shows the mean number of items scored as 'insufficient' out of 22 items indicated as most important regarding their fundamental contribution to unsafe driving. Statistical evaluation revealed no significant (5% level of significance for a two-tailed test) differences in real car driving performance within (Wilcoxon matchedpairs signed-ranks test) and between (Mann- Whitney U-test) the three groups of subjects. In group I only two subjects under mebhydrolin and in group II only one subject in the base-line condition showed unsafe driving. The results of the laboratory test are given in Figure 4. There was only one significant drug effect in group III. The patients showed significantly more (P < 0.05) false alarms during treatment with mebhydrolin. Again no betweengroup differences were noticed. Discussion It has been demonstrated before that the driving test used in these studies is able to show differences in driving performance after the use of moderate quantities of alcohol (0.45 g/kg) (de Gier, 1979). In study I it is demonstrated that patients receiving diazepam perform worse, showing impaired visual perception and anticipation of dangerous events during driving. Since the performance of patients without their medication was unknown, it is not possible to blame the drug alone for impairment of performance. However, it was the combination of 'patient and drug' that showed unsafe driving. The results of the driving test in Study II indicate that mebhydrolin 50 mg three times daily did not significantly impair car driving. The results also indicate a slight tendency for an impairment in scores on the second day compared to the first day regardless of treatment given. There is no sign of any practice or session effect. Since driving performance in two of the three groups was measured on the second day without administration of the drug, this tendency is probably due to the subjects' lack of motivation to show their best. In Figure 3a and 3b the results of driving tests with patients are given to compare the results of the two studies presented in this paper. Since the observer in study II is the same person as one of the two observers used in study I it is concluded Table 2 The mean values (± s.d.) of age, weight and driving experience of patients and healthy volunteers. Group I (n = 10) Age (years) 25.3 ± 4.6 Weight (kg) 72.5 ± 5.3 Driving experience mean length (years) 5.9 ± 4.8 km x 103 year ± 19.8 Group II Group III (n = 10) (n = 6) 24.8± ± ± ± ± ± ± ± 12.0

5 Drugs and driving performance 107S (n E cc c 0). iq E X.- 0) v._c E Loo n a * Study I 0* ux a,) E 0) o t c en m D C o C,) 0)0 o n0' C, b Study II DZ o DZ C ND M M 1st 2nd 1st DZ = Patients on diazepam (n = 9) C = Control subiects * P < 0.05 (n - 8) v Group I (n = 10) A Group II (n = 10) A Group III (n = 6) ND = no drug M = Mebhydrolin (50 mg three times daily) Figure 3 The results of the driving tests in both studies presented as the mean number of important items scored as insuffcient. ND 2nd Task A r = Mean score (%) of hits = Mean number of false alarms Task B = Mean number of seconds out * P < 0.05 Group I T Group II T r (n = 10) (n = 10) Figure 4. I.. L L No drug Mebhydrolin Mebhydrolin No drug Mebhydrolin No drug 50 mg three 50 mg three 50 mg three times daily times daily times daily The results of the laboratory test in Study II.

6 108S J. J. de Gier that patients under the influence of diazepam seem to be driving worse than patients under the influence of mebhydrolin. Regarding the proportions of 'unsafe drivers' in the respective groups, this difference in driving performance is also illustrated. However, due to the small number of subjects in studies, it is hard to draw any definite conclusions. The results of the laboratory tests need some discussion. In both studies it seems that patients perform differently from the control subjects. In study I patients receiving diazepam performed better in task A (lower false alarm rate) and worse in task B (more seconds out). In study II patients receiving mebhydrolin performed worse in task A (higher false alarm rate) and showed no difference in task B. The following question needs to be answered: How much of the impairment of performance observed among patient groups is due to their treatment, their underlying disease, their motivation and to group differences (i.e. in age, profession, etc.)? However, it is emphasized that the total number of patients in both groups is probably too small for any questioning or any definite answers. These small groups of patients also illustrate the fact that patient recruitment is a major problem in performing tests with patients. Patients have to fulfill the inclusion criteria of the protocols, physicians have to be motivated to ask the patients and researchers have to cope with the stress of a study that runs for years before the data analysis begin and the results are obtained. In the meantime a new drug with fewer side effects than the drug under investigation may be available on the market. In conclusion, referring to the results of the two studies discussed in this paper, real driving tests are feasible tools in studying impaired driving performance in patients. For future research some guidelines for driving tests with patients can be given: (a) Parallel studies (e.g. with laboratory tests or simulator tests) need to be included in the experimental design in order to investigate correlations in results between these tests. This may lead to standardization of methods which is badly needed. (b) Patients must be studied before and after treatment with the drug. In these situations the influence of mental illness or the drug itself needs to be partialed out. (c) Drug level measurements are important tools in order to check on 'patient compliance' and to investigate drug levelresponse relationships. Studies in which these efforts are made are scarce. (d) Patient recruitment is a major problem. Unfortunately, the only solution to this problem is persistency. References Gier, J. J. de (1979). A subjective measurement of the influence of ethyl alcohol in moderate levels on real driving performance. Blutalkohol, 16, Gier, J. J. de, Hart, B. J. 't, Nelemans, F. A & Bergman, H. (1981). Psychomotor performance and real driving performance of outpatients receiving diazepam, Psychopharmacology, 73, Hart, J., Hill, H. M., Bye, C. E., Wilkinson, R. T. & Peck, A. W. (1976). The effects of low doses of amylobarbitone sodium and diazepam on human performance. Br. J. clin. Pharmac., 3, Miaki, M. & Linnoila, M. (1976). Characteristics of driving in relation to the drug and alcohol use of Finnish outpatients. Mod. Probl. Pharmacopsychiat., 11, Seppala, T., Linnoila, M. & Mattila, M. J. (1979). Drugs, alcohol and driving. Drugs, 17, Silverstone, T. (1974). Drugs and driving. Br. J. clin. Pharmac., 1, Warren, R., Simpson, H., Hilchie, J., Cimbura, G., Lucas, D. & Bennet, R. (1981). Drugs detected in fatally injured drivers in the province of Ontario. In Alcohol, Drugs and Traffic Safety, ed Goldberg, L. Vol 1, pp Stockholm: Almqvist & Wiksell.