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Validity and utility of the cognitive drug research (CDR) computerised cognitive testing system: A review following fifteen years of usage
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P6 Other topics
[3] Li Y, Wang E, Patten CJ, Chert L, Yang CS. Effects of flavonoids on cytochrome P450-dependant acetaminophen metabolism in rats and human liver microsomas. Drug Metab Dispos 1994; 22:566.
Validity and utility of the cognitive drug research (CDR) computerised cognitive testing system: a review following fifteen years of usage K.A. Wesnes, T. Ward, G. Ayre, C. Pincock. Cognitve Drug Research Ltd., 24 Portman Rd., Reading, RG30 lEA, UK In the seventies and early eighties, the growing realisation that cognitive performance was a major consideration for pharmaceutical development, identified a need for more sensitive and sophisticated instruments following disillusionment with traditional paper and pencil measures. The Cognitive Drug Research computerised cognitive testing system was developed to meet this need (Wesnes et al, 1987, 1997). This system has now been in use since 1984 in which time it has become the most widely used of any such system in the world. It has been used to date in several hundred national and international clinical trials. Given this length of time and the number of studies now accrued, there is now sufficient data to enable firm conclusions to be drawn regarding the validity and utility of the system. This paper sets out to review these issues. The CDR system has now been used to examine the effects of over 100 novel compounds from all major drug categories including those which impair function, such as benzodiazepines and classical antipsychotics, through to those which actually improve human cognitive function e.g. anticholinesterases. Sensitivity to drag induced changes have been reported in over 150 published abstracts and papers. An important feature of the CDR system is that it profiles a range of domains of cognitive function, including attention, information processing, sub-loops of working memory, executive function, reasoning, secondary memory and skilled coordination. Over the years factor analyses have been conducted upon various populations tested with the system, including young, middle aged and elderly volunteers and patients with Alzheimer's disease. Data from these analyses will be presented to illustrate the factor structure of the CDR system. In conclusion, after fifteen years of extensive use, it is clear that the CDR system has high utility as a sensitive set of cognitive measures for use in clinical research. Further, the validity of the CDR system for profiling human cognitive function has now been unequivocally established.
References [1] Wesnes K, Simpson PM and Christmas L (1987), The assessment of human information processing abilities in psychopharmaeology. In: Hindmarch I and Stonier PD (Eds.) Human Psychopharmacology:Measures and Methods Volume 1. Chiehester, Wiley, Pp 79-92. [2] Wesnes K, Simpson PM, Jansson B, Gratmrn A, Weimann H-J, Kfippers H, (1997a) Moxonidine and cognitive function: Interactions with moclobemide and lorazepam. European Journal of Clinical Pharmacology 52:351-358. [3] Wesnes K, F a l e ~ e t t i n g NR, Houben JJG, Jenkins E, Jonkman JHJ, Leonard J, Petrini O, van Lier JJ. (1997b). The cognitive, subjective and physical effects of a Ginkgo biloba/Panax ginseng combination in healthy volunteers with neurasthenic complaints. Psychopharmacology Bulletin 33, 677-683.
Development and validation of a system for evaluating cognitive functioning over the telephone for use in late phase drug development K.A. Wesnes, T. Ward, G. Ayre, C. Pincock. Cognitve Drug Research Ltd., 24 Portman Rd., Reading, RG30 lEA, UK The precise and sensitive measurement of cognitive functioning has long been a concern for psychopharmacologists involved in clinical trials. One now widely established way of ensuring this involves the use of a computers, for example, the Cognitive Drug Research (CDR) system
(Wesnes et al, 1987, 1997a, b), which is the most extensively used system of its type in clinical research. Whilst greatly improved since their advent, there are still limiting factors which prevent the use of computers in trials with patients. These primarily involve the cost of computers as well as the logistics of moving and storing them, which can result in the use paper and pencil tests of doubtful relevance and sensitivity. The recent application of Interactive Voice Response (IVR) telephone technology to the pharmaceutical domain suggests one possible solution to this dilemma. This paper describes the development and validation of telephone versions of core tasks of attention, working and secondary memory from the CDR system. A large cohort of normal volunteers (from 10 to 85 years) were assessed using the telephone testing system, and were also tested on the equivalent computerised tests from the CDR system. The order of assessment on the two systems, i.e. telephone and computer, was counterbalanced across volunteers. Correlation of the two sets of scores indicated that the two ways of assessing cognitive functioning were equivalent. Further, the telephone tasks were found to be sensitive to the impairment produced by a social dose of alcohol, confirming their sensitivity to pharmacological manipulation. This study heralds a new era for the cognitive testing of patients in clinical trials. A system is now available which can automatically test over 100 patients simultaneously from anywhere in Europe and North America. The patients can be assessed at home, at frequent intervals, without the involvement of study personnel or the completion of any paperwork. Further, the data are verified and processed during testing and automatically stored in a central database. This methodology c a n be applied to trials of any size and duration. Cognitive testing will now be feasible in all patient trials of compounds likely to alter cognitive function.
References [1] Wesnes K, Simpson PM and Christmas L (1987). The assessment of human information processing abilities in psychopharmacology. In: Hindmarch I and Stonier PD (Eds.) Human Psychopharmacology:Measures and Methods Volume 1. Chichester, Wiley, Pp 79-92. [2] Wesnes K, Simpson PM, Jansson B, Grahn~n A, Weimann H-J, Kiippers H, (1997a) Moxonidine and cognitive function: Interactions with moclobemide and lorazepam. European Journal of Clinical Pharmacology 52:351-358. [3] Wesnes K, Faleni RA, Herring NR, Houben JJG, Jenkins E, Jonkman JHJ, Leonard J, Petrini O, van Lier JJ. (1997b). The cognitive, subjective and physical effects of a Ginkgo biloba/Panax ginseng combination in healthy volunteers with neurasthenic complaints. Psychopharmacology Bulletin 33, 677-683.
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effects of acute doses of standardised Ginkgo Biloba Extract on memory and psychomotor performance in healthy volunteers
U. Rigney, I. Hindmarch. HPRU Medical Research Unit, University of Surrey, Egerton Road, Guildford, Surrey, GU2 5XP, UK This study investigated the effects of acute doses of ginkgo biloba extract (GBE) on memory and psychomotor performance in a randomised, double-blind and placebo controlled 5 way cross-over design. Thirty one healthy volunteers aged 30--59 received GBE 50 mg and 100 mg t.d.s., GBE 120 mg and 240 mg mane and placebo for two days. Following baseline measures, the medication was administered at 0900 hours for the single doses and at 0900, 1500 and 2100 hours for the multiple doses. The test battery was administered pre-dose (08:30 hours) and then hourly until 2100 hours. It consisted of Steinberg Short Term Memory Scanning Task (STM), Stroop Colour Task (SCT), Word Recall Test (immediate recall WRi and delayed recall WRd), Critical Flicker Fusion (CFF), Choice Reaction Time (CRT), Digit Symbol Substitution Task (DSST), Linear Analogue Rating Scale (LARS), Leeds Sleep Evaluation Questionnaire (LSEQ) and Actigraphy (activity monitoring). When the average change from baseline was examined the reaction time for GBE 120 mg was significantly lower on both days of treatment than placebo and all other treatments (p = 0.016). This effect was most evident in the oldest age group (50-59). Consistent with the finding
P6 Other topics
[3] Li Y, Wang E, Patten CJ, Chert L, Yang CS. Effects of flavonoids on cytochrome P450-dependant acetaminophen metabolism in rats and human liver microsomas. Drug Metab Dispos 1994; 22:566.
Validity and utility of the cognitive drug research (CDR) computerised cognitive testing system: a review following fifteen years of usage K.A. Wesnes, T. Ward, G. Ayre, C. Pincock. Cognitve Drug Research Ltd., 24 Portman Rd., Reading, RG30 lEA, UK In the seventies and early eighties, the growing realisation that cognitive performance was a major consideration for pharmaceutical development, identified a need for more sensitive and sophisticated instruments following disillusionment with traditional paper and pencil measures. The Cognitive Drug Research computerised cognitive testing system was developed to meet this need (Wesnes et al, 1987, 1997). This system has now been in use since 1984 in which time it has become the most widely used of any such system in the world. It has been used to date in several hundred national and international clinical trials. Given this length of time and the number of studies now accrued, there is now sufficient data to enable firm conclusions to be drawn regarding the validity and utility of the system. This paper sets out to review these issues. The CDR system has now been used to examine the effects of over 100 novel compounds from all major drug categories including those which impair function, such as benzodiazepines and classical antipsychotics, through to those which actually improve human cognitive function e.g. anticholinesterases. Sensitivity to drag induced changes have been reported in over 150 published abstracts and papers. An important feature of the CDR system is that it profiles a range of domains of cognitive function, including attention, information processing, sub-loops of working memory, executive function, reasoning, secondary memory and skilled coordination. Over the years factor analyses have been conducted upon various populations tested with the system, including young, middle aged and elderly volunteers and patients with Alzheimer's disease. Data from these analyses will be presented to illustrate the factor structure of the CDR system. In conclusion, after fifteen years of extensive use, it is clear that the CDR system has high utility as a sensitive set of cognitive measures for use in clinical research. Further, the validity of the CDR system for profiling human cognitive function has now been unequivocally established.
References [1] Wesnes K, Simpson PM and Christmas L (1987), The assessment of human information processing abilities in psychopharmaeology. In: Hindmarch I and Stonier PD (Eds.) Human Psychopharmacology:Measures and Methods Volume 1. Chiehester, Wiley, Pp 79-92. [2] Wesnes K, Simpson PM, Jansson B, Gratmrn A, Weimann H-J, Kfippers H, (1997a) Moxonidine and cognitive function: Interactions with moclobemide and lorazepam. European Journal of Clinical Pharmacology 52:351-358. [3] Wesnes K, F a l e ~ e t t i n g NR, Houben JJG, Jenkins E, Jonkman JHJ, Leonard J, Petrini O, van Lier JJ. (1997b). The cognitive, subjective and physical effects of a Ginkgo biloba/Panax ginseng combination in healthy volunteers with neurasthenic complaints. Psychopharmacology Bulletin 33, 677-683.
Development and validation of a system for evaluating cognitive functioning over the telephone for use in late phase drug development K.A. Wesnes, T. Ward, G. Ayre, C. Pincock. Cognitve Drug Research Ltd., 24 Portman Rd., Reading, RG30 lEA, UK The precise and sensitive measurement of cognitive functioning has long been a concern for psychopharmacologists involved in clinical trials. One now widely established way of ensuring this involves the use of a computers, for example, the Cognitive Drug Research (CDR) system
(Wesnes et al, 1987, 1997a, b), which is the most extensively used system of its type in clinical research. Whilst greatly improved since their advent, there are still limiting factors which prevent the use of computers in trials with patients. These primarily involve the cost of computers as well as the logistics of moving and storing them, which can result in the use paper and pencil tests of doubtful relevance and sensitivity. The recent application of Interactive Voice Response (IVR) telephone technology to the pharmaceutical domain suggests one possible solution to this dilemma. This paper describes the development and validation of telephone versions of core tasks of attention, working and secondary memory from the CDR system. A large cohort of normal volunteers (from 10 to 85 years) were assessed using the telephone testing system, and were also tested on the equivalent computerised tests from the CDR system. The order of assessment on the two systems, i.e. telephone and computer, was counterbalanced across volunteers. Correlation of the two sets of scores indicated that the two ways of assessing cognitive functioning were equivalent. Further, the telephone tasks were found to be sensitive to the impairment produced by a social dose of alcohol, confirming their sensitivity to pharmacological manipulation. This study heralds a new era for the cognitive testing of patients in clinical trials. A system is now available which can automatically test over 100 patients simultaneously from anywhere in Europe and North America. The patients can be assessed at home, at frequent intervals, without the involvement of study personnel or the completion of any paperwork. Further, the data are verified and processed during testing and automatically stored in a central database. This methodology c a n be applied to trials of any size and duration. Cognitive testing will now be feasible in all patient trials of compounds likely to alter cognitive function.
References [1] Wesnes K, Simpson PM and Christmas L (1987). The assessment of human information processing abilities in psychopharmacology. In: Hindmarch I and Stonier PD (Eds.) Human Psychopharmacology:Measures and Methods Volume 1. Chichester, Wiley, Pp 79-92. [2] Wesnes K, Simpson PM, Jansson B, Grahn~n A, Weimann H-J, Kiippers H, (1997a) Moxonidine and cognitive function: Interactions with moclobemide and lorazepam. European Journal of Clinical Pharmacology 52:351-358. [3] Wesnes K, Faleni RA, Herring NR, Houben JJG, Jenkins E, Jonkman JHJ, Leonard J, Petrini O, van Lier JJ. (1997b). The cognitive, subjective and physical effects of a Ginkgo biloba/Panax ginseng combination in healthy volunteers with neurasthenic complaints. Psychopharmacology Bulletin 33, 677-683.
~ T h e
effects of acute doses of standardised Ginkgo Biloba Extract on memory and psychomotor performance in healthy volunteers
U. Rigney, I. Hindmarch. HPRU Medical Research Unit, University of Surrey, Egerton Road, Guildford, Surrey, GU2 5XP, UK This study investigated the effects of acute doses of ginkgo biloba extract (GBE) on memory and psychomotor performance in a randomised, double-blind and placebo controlled 5 way cross-over design. Thirty one healthy volunteers aged 30--59 received GBE 50 mg and 100 mg t.d.s., GBE 120 mg and 240 mg mane and placebo for two days. Following baseline measures, the medication was administered at 0900 hours for the single doses and at 0900, 1500 and 2100 hours for the multiple doses. The test battery was administered pre-dose (08:30 hours) and then hourly until 2100 hours. It consisted of Steinberg Short Term Memory Scanning Task (STM), Stroop Colour Task (SCT), Word Recall Test (immediate recall WRi and delayed recall WRd), Critical Flicker Fusion (CFF), Choice Reaction Time (CRT), Digit Symbol Substitution Task (DSST), Linear Analogue Rating Scale (LARS), Leeds Sleep Evaluation Questionnaire (LSEQ) and Actigraphy (activity monitoring). When the average change from baseline was examined the reaction time for GBE 120 mg was significantly lower on both days of treatment than placebo and all other treatments (p = 0.016). This effect was most evident in the oldest age group (50-59). Consistent with the finding