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N Otten

Publications and source records attributed to N Otten.

15 recordsLinked to original sources
PubMed1999

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.

Canada↗
PubMed1998

Use of economic evaluation guidelines: 2 years' experience in Canada.

Considerable effort has been expended in recent years in the development of methodology guidelines for economic evaluation of pharmaceutical products, driven in part by the desire to improve the rigour and quality of economic evaluations and to help decision making. Canada was one of the first countries to develop such guidelines and to encourage their use. This paper examines the extent to which the economic evaluations that were submitted to the Canadian Coordinating Office for Health Technology Assessment in the last two years adhered to Canadian guidelines. The analytic technique employed by twelve studies as well as the comparator used, the perspective taken, the outcome measure selected, the cost items that were taken into consideration and the extent of sensitivity analyses that were performed are reviewed in this paper. It can be concluded that although studies have been of variable quality, the majority of them were well presented, complete and transparent, due in part to the guidelines. Except for the perspective of the analysis, guidelines were, in many respects, adhered to and did not restrict investigators to specific methodologies or specific techniques. They were also instrumental in ensuring a minimum set of standards.

Canada↗
PubMed1998

A Canadian perspective.

Although the healthcare program in Canada is in many ways universal, there are several differences between the provinces. Two key federal bodies (the Health Protection Branch of Health Canada and the Patented Medicine Prices Review Board) are involved in the drug review process. In addition, the Canadian Coordinating Office for Health Technology Assessment (CCOHTA), an organization funded jointly by provinces and the federal government, reviews new or existing drugs at the request of provinces. Each province or territory and the federal government has its own drug plan or plans. The 10 Canadian provinces require a notice of compliance, information on pricing, and clinical and comparative information for submission of a new drug. Over the last 3 years, 8 of the 10 provinces have required pharmacoeconomic analyses to be added to the submissions. Four of the eight provinces requiring pharmacoeconomic evaluations have specified that these evaluations should be made according to the Canadian Coordinating Office for Health Technology Assessment guidelines. A review of the utilization patterns of lipid-lowering therapies is presented in this Canadian context. Statins comprised 80% of the lipid-lowering drug market in 1995. Prescribers use statins available in Canada interchangeably for all approved and nonapproved indications. The newest statin, atorvastatin, has attained a market share for new prescriptions equivalent to simvastatin and pravastatin, despite the lack of clinical outcome studies. CCOHTA reviewed the evidence of efficacy and effectiveness of statins, evaluated whether significant differences existed between statins, and analyzed published economic evaluations. It found that treatment of higher-risk patients with statins is more cost-effective than that of lower-risk subjects. The evaluation also concluded that the statins, as a class, probably act in reducing LDL and raising HDL, resulting in beneficial clinical outcomes.

Journal Article↗
PubMed1997

Health economics of gastroesophageal reflux disease.

The present study provides an overview of the current state of health economics studies of gastroesophageal reflux disease (GERD). It indicates the strengths and weaknesses of individual studies, and the state of health economics analysis in general as they apply to GERD. Specifically, this study adopts a pharmacoeconomic perspective, which is a subsection of health economics analytical methods, to provide a comparative analysis of alternative courses of action based on cost and consequence. The pharmacoeconomic outlook is most effective when it considers a comprehensive societal perspective, with special consideration given to other relevant viewpoints, such as the payer, the primary provider and, most important, the patient. Pharmacoeconomics provides several specific analytical techniques for GERD-related health economics analysis. The Canadian Association of Gastroenterology consensus conference on GERD in 1996 thought that a cost effective analysis was the most appropriate technique to assess the pharmacoeconomics of GERD. Six previous studies on GERD health economics have been performed comparing omeprazole with H2 receptor antagonists. These studies vary in cost data collected and in analytical techniques. In general, the existing outcome measurements of these previous health economics studies are not ideal. Namely, they combine various GERD grades, use randomized controls, are endoscopically based, assess pharmaceutical therapy only and are short term. More appropriate health economic trials in GERD, which focus on GERD management strategies and therapeutic treatment of GERD, need to be designed and conducted. These economic assessments, however, should not replace detailed thinking, careful observation, good judgement and common sense.

Canada↗
PubMed1996

An economic evaluation of finasteride for treatment of benign prostatic hyperplasia.

This evaluation was conducted at the request of a Canadian provincial government considering finasteride for formulary inclusion. The comparator therapies, in accordance with Canadian pharmacoeconomic guidelines, were the most prevalent treatment [transurethral resection of the prostate (TURP)] and the lowest cost treatment (watchful waiting). All costs were measured in 1994 Canadian dollars ($Can), and both costs and outcomes were discounted at 5% per annum. Cost-effectiveness and cost-utility ratios were calculated, and were found to be dependent on initial symptom severity and the anticipated duration of treatment with finasteride. The drug was shown to be the dominant alternative compared with both TURP and watchful waiting for patients with moderate symptoms, when the duration of drug therapy is 3 years or less. However, finasteride is a weak alternative for patients with severe symptoms who are treated for 4 years or more. For other groups of patients (i.e. moderate symptoms and on finasteride for 4 years or more; severe symptoms and on treatment for 3 years or less), the drug can improve health-related quality of life, but at a cost of between $Can3000 and $Can97,000 per incremental quality-adjusted life year (1994 dollars). Our study also indicated that it would cost between $Can2.7 million and $Can5.6 million, depending on the severity mix of the patients, to treat cohort of 10,000 men aged 60 years or older with finasteride.

Aged↗
PubMed1994

Experimental treatment of equine sarcoid using a xanthate compound and recombinant human tumour necrosis factor alpha.

A xanthate compound with antiviral and antitumoural activities, tricyclodecan-9-yl-xanthogenate (D609) in combination with the potassium salt of the lauric acid (KC12) and, in a further investigation, the above-mentioned substances together with recombinant human TNF alpha (rh-TNF alpha), were tested on equine sarcoid tumours for therapeutic efficacy. A pilot investigation on 5 healthy horses showed that the compounds were well-tolerated; apart from a local, temporary oedema at the injection site, no other clinical symptoms were observed after subcutaneous administration of volumes from 0.1 to 10 ml per injection. The tested concentrations of D609 and KC12 (5 mg/ml solution) and of rh-TNF alpha (50 micrograms/ml) were used for the treatment experiments. The repeated injections of the compounds to 11 sarcoid affected horses were also well-tolerated, except by one horse. In this case the treatment had to be interrupted after two injections because of severe reaction, i.e. fever and lameness due to oedemas. Five horses (n = 6 sarcoids) were treated by local, subcutaneous injection of D609 and KC12 under the tumour at intervals of 3 weeks. On one periocular sarcoid the compounds were applied as an ointment. After a follow-up period of 18 months, 5 tumours did completely regress and one remained unchanged. The periocular tumour showed a reduction in size. Five horses (n = 9 sarcoids) were then treated with a combination of D609, KC12 and rh-TNF alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

DNA of bovine papillomavirus type 1 and 2 in equine sarcoids: PCR detection and direct sequencing.

Nucleotide sequences of bovine papillomavirus (BPV) DNA amplified by the polymerase chain reaction (PCR) from samples of equine sarcoid skin tumours were determined. All naturally occurring sarcoids (n = 58 tumours from 32 horses and 2 donkeys) contained BPV-DNA. All but 3 of the genome fragments belonged to the BPV type 1 strain (BPV-1); the remaining were BPV type 2. Similar results were obtained with cutaneous bovine papillomas used as controls (n = 20). One of the horses, carrying 2 sarcoids, was particularly interesting; one tumour contained BPV-1 DNA whilst the other sarcoid yielded BPV-2 DNA, suggesting that horses are not immune to super-infection. BPV-DNA was even amplified from the sarcoid samples which had yielded negative results in previous investigations when DNA isolated from the lesions was used in Southern blot hybridization with BPV probes. In addition, there was no detectable BPV-DNA in any equine or bovine tissue examined other than sarcoids or cutaneous bovine papillomas. Biopsies of normal skin surrounding lesions yielded exclusively negative results. The described nucleotide differences represent a natural genomic variation of this BPV type between geographically distant locations. The identical variations recovered from cattle and horses in Switzerland, a finding of great epidemiological interest, strongly suggest that a uniform variant of BPV-1 is one of the etiologic agents of equine sarcoid and bovine papilloma in a given region.

Animals↗
PubMed1984

Free valproic acid: steady-state pharmacokinetics in patients with intractable epilepsy.

Free and total valproic acid (VPA) pharmacokinetic evaluation was carried out at steady state in six young epileptics who were also receiving other anticonvulsants. Subjects received their usual morning dose of VPA after an overnight fast. Blood samples for free and total VPA were taken prior to the dose and frequently thereafter for 12 hours. The calculated pharmacokinetic parameters for total VPA and free VPA were: half-lives of 7.5 +/- 1.6 hours and 5.0 +/- 1.5 hours, volumes of distribution of 0.189 +/- 0.038 l/kg and 1.51 +/- 0.98 l/kg, and clearances of 0.30 +/- 0.06 and 3.6 +/- 2.0 ml/min/kg., respectively. There was a strong correlation between percent free VPA and total VPA (r = 0.81) but marked inter- and intra-subject variations were seen. Studies attempting to correlate VPA levels to clinical response must take such data into account.

Adolescent↗
PubMed1981

Use of cimetidine in hospital patients.

The use of cimetidine in 137 patients in a large Canadian teaching hospital was assessed prospectively. About 80% of the patients received the drug for treatment and 20% received it for prophylaxis. All of the prophylactic indications as well as some of the treatment indications have not been approved by the health protection branch of the Department of National Health and Welfare, nor do most have adequate literature documentation. The duration of therapy varied from less than 3 days to more than 2 months. The average cost of cimetidine therapy was $40.71. The dosage was not adjusted in over 50% of the patients in whom impairment of renal function was serious enough to warrant consideration of a dosage reduction. Approximately half of the patients received concurrent antacid therapy. Although cimetidine is relatively safe, its use in this institution was less than optimal.

Cimetidine↗
PubMed1981

Comparison of gas-liquid chromatography and EMIT assay for serum valproic acid.

We describe a simple direct extraction method for the gas-liquid chromatography determination of serum valproic acid. The working range for the assay is 2-180 mg/L and our within-run precision was 5.8 and 4.3% at the 40 and 90 mg/L concentrations respectively. Hemolyzed and lipemic sera as well as samples from patients with hyperbilirubinemia and from patients with decreased renal function were put through the assay and no interfering peaks were noted. Interference occurred when teflon-lined screw caps were used during the extraction step. The method was proven to be accurate by linear regression analysis of samples containing weighed-in amounts of valproic acid. The above assay was compared to an enzyme immunoassay technique (EMIT). The working range for the latter is 10-150 mg/L and the with-run precision was 10.8 and 5.9% and 90 mg/L concentration respectively. Samples were run by both the gas-liquid chromatograph and enzyme immunoassay methods and gave very similar results over the range 16-139 mg/L.

Bilirubin↗
PubMedDate not supplied

A multivariable analysis of factors governing the steady-state pharmacokinetics of valproic acid in 52 young epileptics.

A number of factors have been implicated in the interpatient variability of valproic acid (VPA) pharmacokinetics. These include patient age, concurrent anticonvulsant therapy, and dosage of VPA. In the clinical setting, it is important to determine which of these variables exert a major effect on the observed differences in VPA disposition. Accordingly, we analyzed the data from 52 young epileptic patients using multivariate statistical methods. Concurrent anticonvulsant therapy was the major determinant of VPA clearance in this patient population. The half-life of VPA was significantly related to age, but volume of distribution and clearance were not. The dosage of VPA affected the volume of distribution of VPA but not the half-life or clearance of this drug. These results provide a more rational understanding of VPA pharmacokinetics in the clinical setting and have implications for the monitoring and manipulation of VPA therapy in the epileptic population.

Adolescent↗
PubMedDate not supplied

First-dose and steady-state pharmacokinetics of valproic acid in children with seizures.

The serum concentration-time curve of valproic acid was followed in 25 children after single oral doses of the drug and at steady-state. Total body clearance (CL), half-life (t 1/2), and apparent volume of distribution (Vd) were calculated from the terminal portion of the curve and from the area under the serum concentration-time curve (AUC). The CL and Vd were significantly greater at steady-state (0.42 +/- 0.20 ml/min/kg and 0.231 +/- 0.067 L/kg, respectively) than after a single dose (0.32 +/- 0.13 ml/min/kg and 0.191 +/- 0.055 L/kg, respectively). This difference was most pronounced in patients with valproic acid dosage increases in excess of 20% and no change in their concurrent anticonvulsant therapy between the single-dose and steady-state study periods. The t 1/2 was not significantly different between the 2 study periods. There was a significant correlation between age and both CL and Vd after single doses and at steady-state. The t 1/2 did not appear to be age related. These results suggest that the adequacy of the dosage regimen must be determined during maintenance therapy rather than extrapolated from data obtained after a single dose. Re-evaluation of therapy as the child grows older may also be necessary in view of the age-related differences in valproic acid pharmacokinetics which this study has demonstrated.

Adolescent↗