The revised Canadian Guidelines for the Economic Evaluation of Pharmaceuticals.

The first edition of the Guidelines for Economic Evaluation of Pharmaceuticals: Canada was published in November 1994. At that time, the Canadian Coordinating Office for Health Technology Assessment (CCOHTA) was assigned the task of maintaining and regularly updating the Canadian Guidelines. Since their introduction, a great deal of experience has been gained with the practical application of the guidelines. Their role has also evolved over time, from being a framework for pharmacoeconomic research to the point where a wide variety of decision-makers use economic evaluations based on the principles set out in the guidelines as a means of facilitating their formulary decisions. In addition, methodologies in certain areas (and the body of related research literature in general) have developed considerably over time. Given these changes in the science and the experience gained, CCOHTA convened a multi-disciplinary committee to address the need for revisions to the guidelines. The underlying principles of the review process were to keep the guidance nature of the document, to focus on the needs of 'doers' (so as to meet the information needs of 'users') and to provide information and advice in areas of controversy, with sound direction in areas of general agreement. The purpose of this review is three-fold: (i) to outline the process which lead to the revision of the Canadian Guidelines; (ii) to describe the major changes made to the second edition of this document; and (iii) to consider the 'next steps' as they relate to the impact of such guidelines and the measurement of outcomes related to economic assessments of pharmaceuticals in general.

Direct and indirect costs of asthma in Canada, 1990.

OBJECTIVE: To calculate the direct and indirect costs of asthma in Canada. DESIGN: Cost-of-illness study. SETTING: Canada. PATIENTS: All Canadians receiving inpatient or outpatient care for asthma in 1990. OUTCOME MEASURES: Direct costs incurred by inpatient care, emergency services, physician and nursing services, ambulance use, drugs and devices, outpatient diagnostic tests, research and education. Indirect costs from productivity loss due to absence from work, inability to to perform housekeeping activities, need to care for children with asthma who were absent from school, time spent travelling and waiting for medical care, and premature death from asthma. All costs are in 1990 Canadian dollars. RESULTS: Depending on assumptions, the total cost of asthma was estimated to be between $504 million and $648 million. Direct costs were $306 million. The single largest component of direct costs was the cost of drugs ($124 million). The largest component of indirect costs was illness-related disability ($76 million). CONCLUSIONS: Annual costs of treating asthma are comparable to the individual cost of infectious diseases, hematological diseases, congenital defects, perinatal illnesses, home care and ambulance services. Asthma costs may increase in the future, given current morbidity and mortality trends. Further evaluation of the effectiveness and cost-effectiveness of available asthma interventions in addition to aggregate cost data are required to determine whether resource allocation for the treatment of asthma can be improved.

Detection of deficits in temporal pattern discrimination using the seashore rhythm test in young children with reading impairments.

A deficiency in temporal pattern discrimination frequently is a distinguishing characteristic of children with dyslexia or learning disabilities (LD). We studied the feasibility of using the Seashore Rhythm Test, a subtest of the Halstead-Reitan neurological assessment battery (Halstead, 1947), with young children to discriminate children with reading impairments from age-matched controls reading at a normal level, in an effort to develop tools to determine readiness to read in young school-age children. Major considerations in test selection were ease of administration and wide use and acceptance. Fifty-nine children in Grades 1 through 3 were administered a battery of tests during the last 3 weeks of the school year by blinded experimenters. Tests administered included the Seashore Rhythm Test, Benton Visual Retention Test, Peabody Picture Vocabulary Test, Blau Torque Test, and the Rod and Frame Test. Children with reading impairments (n = 24) in all age groups were found to exhibit a marked deficit in the ability to discriminate patterned pairs of tones on the Seashore Rhythm Test compared to controls (n = 26). These children also exhibited deficits in right-left orientation, as indicated by their poor performance on the Blau Torque Test. Performance on the Seashore and the Blau by a group of children diagnosed as learning disabled (n = 9) was similar to the group with reading impairments. No significant differences between controls and children with reading impairments or LD were observed in Rod and Frame or Benton performance. The results suggest that the Seashore Rhythm Test may prove to be a useful tool to detect young children who will later show signs of reading impairment.

Neonatal exposure to a high level of ACTH4-10 impairs adult learning performance.

Male offspring of Sprague-Dawley dams were injected with 25 micrograms of ACTH4-10 or the vehicle on days 2 through 7 postpartum. Peptide treated animals exhibited a marked motor response to the peptide injection. Adrenal weights of these animals were consistently heavier than littermate controls in both the developing and adult animals. ACTH4-10 treated neonates exhibited significantly poorer learning performance in the shuttle box and were slower to acquire the reversal learning problem of a visual discrimination task under light shock levels. In addition, these animals also exhibited an exaggerated startle response and a stronger thigmotaxis response in the open field than controls. These results indicate that exposing the developing nervous system to relatively high levels of ACTH4-10 can produce marked long-term effects on behavior.

ACTH 4-9 effects on the human visual event-related potential.

Three oral doses (5, 10 and 20 mg) of an analog of ACTH 4-9 were compared with a vehicle control and d-amphetamine (10 mg). In a double-blind procedure, five men and five women were tested at weekly intervals with each treatment. In each session, four visual event-related potentials (ERPs) were recorded at hourly intervals. Visual ERPs were averaged from the electroencephalogram recorded from the left and right hemisphere. Dosage, time after administration, hemisphere of the brain and sex of the subject influenced the ERP. The ACTH 4-9 analog decreased amplitude of P100 but increased integrated activity of the ERP. This effect peaked at 60 minutes then "recovered." The effects of the peptide were more pronounced with doses of 5 and 10 mg, in the right hemisphere of men and in the left hemisphere of women. The findings indicated that the ACTH 4-9 analog influenced components of ERP commonly related to the perceptual/attentional state of the organism in a sexually dimorphic manner.

Event-related potentials during selective attention to speech sounds.

Event-related potentials (ERPs) were recorded from subjects while they selectively attended to sequences of stop-consonant syllables or sequences of tone pips of different frequencies. The ERP difference waveforms that distinguished attended from unattended speech sounds were highly similar in morphology and scalp distribution to the difference waveforms elicited by the tone pips. These results suggest that the attention mechanisms brought into play when selecting complex phonetic stimuli for further analysis are similar to those engaged when selecting between tones of different frequencies, in contrast with previous theoretical interpretations. Latency differences observed between the attention-related ERPs to simple and complex stimuli were attributed to differences in the duration of processing that makes these stimulus features available to attention mechanisms.