[The budget control function of the Drug Reimbursement System]. / De budgetbeheersende functie van het Geneesmiddelenvergoedingssysteem.

We now have 10 years of experience with the Dutch Price Reference System (Dutch acronym GVS), which was instituted in order to reduce the growth of extramural pharmaceutical costs to 4.1% annually, assuming no loss of medical quality. The system focussed mainly on budget control rather than on increasing cost-effectiveness by substitution. The budget-control aims were not achieved. As epidemiological and demographic developments would account for about 3% annual budget growth given an unchanged individual consumption of pharmaceuticals, the 4.1% criterion left only 1% room for autonomous growth (price, volume). The current 8% average annual growth rate indicates 5% autonomous growth. This rate is low, however, compared to other European countries, where a number of autonomous growth factors are not systematically counterbalanced at the product level by substitution incentives and control over prices and indication by health-care authorities and health-insurance companies. The GVS and related administrative measures have therefore most likely exerted a significant budget-controlling influence. The current policy of the Dutch Ministry of Health, Welfare and Sports in terms of goals, actors' roles and incentives fits well with the GVS, which should therefore be continued.

[Class substitution as an instrument of efficiency in the supply of medicines: possibilities and limitations]. / Klassensubstitutie als doelmatigheidsinstrument in de geneesmiddelenvoorziening: mogelijkheden en beperkingen.

Class substitution is the substitution of a drug by another cheaper drug from the same pharmacological drug class to save costs. This principle is applied in drug formularies and reference-based drug-pricing systems. Class substitution should not only consider similarities in pharmacological mechanisms of action but should also assess whether the different drugs within the class are equivalent at a population level with respect to efficacy, effectiveness, applicability, and safety. The implementation of class substitution requires protocols as well as a monitoring system to evaluate compliance with the protocols and their effects on drug costs. In addition, specific studies are needed to establish whether undesirable effects occur at the patient level.

Introduction to the pharmacoeconomics of herbal medicines.

This article explores the need to perform pharmacoeconomic evaluations of herbal medicines and assesses the extent to which this approach has been applied so far to these products. There seems to be no compelling need for pharmacoeconomic analyses of herbal over-the-counter medicines, but such analyses are certainly warranted for herbal prescription medicines that have a high level of reimbursement. Such preparations are used in Germany, in particular, where physicians prescribed ginkgo, hawthorn, St John's wort, horse-chestnut and saw palmetto to a value of more than DM50 million each in 1996. In our survey, only a single pharmacoeconomic study, of uncertain quality, was found on these 5 herbs, whereas several pharmacoeconomic reports on synthetic competitors were retrieved. The time has come to submit highly reimbursed herbal prescription medicines to the same rigorous pharmacoeconomic evaluations as their synthetic competitors. At present, such studies are particularly important for Germany, but in the future they may also become relevant for other countries, inside as well as outside Europe.

Reporting format for economic evaluation. Part II: Focus on modelling studies.

This article presents the first version of a reporting format for modelling studies which is based on a general reporting format by our taskforce, which was published in the previous issue of this journal. The use of decision-analytical models for economic evaluations is increasing because, in practice, it is not always possible to derive information from prospective studies. However, the acceptance of modelling studies is generally lower than prospective studies not only because of the use of secondary data, but also because the reports of modelling studies do not always have sufficient transparency. Hence, a standardised reporting format may improve the transparency and, consequently, the acceptance of modelling studies. This article presents an example of a reporting format for economic evaluation based on modelling studies, which may facilitate the development of future guidelines for modelling studies. The format consists of a number of headings, which are followed by a brief recommendation on the content. This format does not deal with methodology and data management, but especially addresses validation and quality assurance, which may increase the transparency of the report.

Reporting format for economic evaluation. Part I: Application to the Dutch healthcare system.

This article presents the first version of the reporting format for economic valuation that was created in 1995 by a multidisciplinary taskforce. The members of this taskforce come from a broad spectrum of backgrounds within the healthcare field and participated in the exercise voluntarily. The format presented should be understood as the preferred Dutch structure for the reporting of any study on economic evaluation. In view of the many areas of contention that exist within the field, this format only gives normative directions in those areas in which consensus exists, as evidenced by the current published international guidelines. A regular review and adaptation of this format will be needed to reflect advances in the field.

[Evaluation of drugs: efficacy, applicability, effectiveness and efficiency]. / Waardebepaling van geneesmiddelen: werkzaamheid, toepasbaarheid, doeltreffendheid en doelmatigheid.

In view of rising costs of drugs and the limited budget, government, institutes, researchers, prescribers, pharmacists and pharmaceutical industries should have a standardized assessment system at their disposal on which to base their pharmacotherapeutic policy. Evaluation can be achieved in four successive steps, taking into account both therapeutical and financial aspects. The first two steps, determining efficacy and applicability, represent the current system of evaluating drugs before allowance to the market. Steps 3 and 4 describe the ways in which effectiveness and efficiency can be involved in the evaluation by means of (cost) effectiveness analysis. Achieving optimal results from this stepwise approach requires speedy acceptance of the currently available guidelines for effective and efficient research.

Hypnotics. Drug selection by means of the System of Objectified Judgement Analysis (SOJA) method.

Selection of hypnotics for drug formularies in The Netherlands, France and the UK is made by means of the System of Objectified Judgement Analysis (SOJA) method. The following criteria are included in the method: clinical efficacy (maximal 300 points), adverse effects (250 points), clinical documentation (150 points), cost (120 points), pharmacokinetic properties (80 points), toxicity (50 points), drug interactions (30 points) and the number of tablet strengths available (20 points). In all 3 countries, zolpidem, zopiclone and temazepam showed the highest score, followed by lormetazepam. High scores favour inclusion in formularies. Nitrazepam and loprazolam scored 75 to 130 points less than the top 3, and flunitrazepam shows the lowest score (119 to 183 points less than zolpidem, zopiclone and temazepam). Therefore, the first 3 (or 4) hypnotics are most suitable for formulary inclusion while the others are not.

Aluminum hydroxide, calcium carbonate and calcium acetate in chronic intermittent hemodialysis patients.

BACKGROUND AND METHODS: Prevention of secondary hyperparathyroidism in uremia necessitates correction of hyperphosphatemia and hypocalcemia. In order to avoid aluminum toxicity, calcium containing phosphate binders are used increasingly, instead of aluminium hydroxide. Recent studies have shown that calcium acetate has many characteristics of an ideal phosphate binder. It is, for instance, a more readily soluble salt compared with calcium carbonate. This advantage might, however, disappear if calcium carbonate is taken on an empty stomach, a few minutes before meals. We examined the efficacy of three different phosphate binding agents in a randomized prospective study of 53 patients on regular hemodialysis. Bicarbonate dialyses were performed with a dialysate calcium concentration of 1.75 mmol/l. After a three-week wash-out period, patients received either aluminum hydroxide (control group), calcium acetate, or calcium carbonate as their phosphate binder. Patients were instructed to take the calcium salts a few minutes before meals on an empty stomach, and aluminum hydroxide during meals. Serum calcium, phosphate, intact parathormone, and alkaline phosphatase levels were determined every month. Patient compliance was estimated every month by asking the patients which phosphate binder and what daily dose they had used. RESULTS: Aluminum hydroxide tended to be the most effective phosphate binder. The mean +/- SEM required daily dose of calcium acetate at 12 months was 5.04 +/- 0.60 g, corresponding to 10.1 +/- 1.20 tablets of 500 mg. Co-medication with aluminum hydroxide, however, was needed (1.29 +/- 0.54 g per day, corresponding to 2.6 +/- 1.08 tablets of 500 mg). The required daily calcium carbonate dose appeared to be 2.71 +/- 0.48 g, corresponding to 5.4 +/- 0.95 capsules of 500 mg, with an adjuvant daily aluminum hydroxide dose of 0.69 +/- 0.27 g, corresponding to 1.4 +/- 0.55 tablets of 500 mg (p = 0.0055). Thus, the mean daily doses of elemental calcium were comparable between the calcium acetate and calcium carbonate-treated patients (1.28 +/- 0.15 g versus 1.09 +/- 0.19 g; n.s.). The incidence of hypercalcemic episodes (albumin-corrected serum calcium levels above 2.80 mmol/l) in the calcium acetate-treated group was 18% versus 31% in the calcium carbonate-treated group (p < 0.005). None of the aluminum hydroxide-treated patients experienced hypercalcemic episodes. Mean serum concentrations of alkaline phosphatase, intact parathormone, and aluminum did not differ between the groups. CONCLUSIONS: In chronic intermittent hemodialysis patients, per gram administered elemental calcium phosphate binding with either calcium acetate or calcium carbonate is equivalent, provided that calcium carbonate is taken on an empty stomach a few minutes before meals. The number of capsules calcium carbonate, but also the total amount in grams, necessary to keep serum phosphate and intact parathormone levels into an acceptable range then is significantly less. This might improve patient compliance.

Future developments in the pharmacotherapy of lung disease.

Future advances in the pharmacotherapy of lung disease will occur mainly in the treatment of asthma, and will include the development of new long-acting beta 2-agonists, long-acting parasympatholytics, phosphodiesterase inhibitors, corticosteroids with fewer systemic side-effects, and other antiinflammatory drugs. Free radicals play an important role in most lung diseases, including asthma, emphysema, fibrosis, and adult respiratory distress syndrome. The search for free radical scavengers is now in progress. Replacement therapy with alpha 1-antitrypsin and surfactant is now possible. Progress in this area stems principally from a better understanding of the pathogenesis of lung disease.