New Dutch guidelines for pharmacoeconomic research

Doc. MUDr. Tomáš Sechser, CSc.

IKEM, Praha

Předkládáme text, jehož publikace v českém písemnictví je poměrně ojedinělá. Je to dáno jednak tím, že je psaný anglicky, jednak tématem samotným.

Volba angličtiny jako jazyka nejhojněji mezinárodně používaného nejen ve farmakoekonomice, ale v odborné komunikaci vůbec pomohla předejít řadě terminologických problémů spojených s užitím češtiny.

Jde o doporučené postupy používané nizozemským regulátorem k návodu, jak odborně, kompetentně, transparentně, ale i reprodukovatelně prezentovat podání výrobce především pro kategorizaci léčivého přípravku. Jedná se o naprosto konkrétní formu zlepšování komunikace mezi zdrojem informace a tím, kdo informaci má použít při rozhodování. Jde o akcentaci metodologické standardizace postupu při neskrývané snaze zlepšit „receptor“ regulátora ke zpracování informace. Tak, aby se obsah farmakoekonomické informace poskytované výrobcem stal přesvědčivější pro ty, kteří přijímají rozhodnutí.

Nejde o principy u nás nové, ale mohou být dobrým příkladem pro naši farmakoekonomickou odbornou veřejnost při relevantních formulacích v našich podmínkách. Proto doufáme, že tato nová farmakoekonomická doporučení pomohou kultivovat tyto postupy i u nás.

Introduction

In The Netherlands, in 1999, the Dutch Health Care Insurance Board (advisory body on the reimbursement of new drugs) presented the guidelines for pharmaco-economic research [1]. The advanced me-thods, such as Bayesian analyses and Value-of-Information analyses are not yet in the guidelines, up to date.

Since January 2005, the Ministry of Health in The Netherlands implemented the use of pharmacoeconomics as a sup-plementary aspect in the evaluation for drug reimbursement. Pharmacoeconomic evaluation was optional in the past, but obligatory since then, to be included in all applications when new drug with proven therapeutic added value claims reimbursement [2].

This policy was already in practice for many years in other countries, such as the UK, Australia and Canada [3].

The Dutch guidelines for pharmaco-economic research consisted initially of 19 recommendations with some of a methodological nature (# 2, 6, 8, 9, 10, 12, 15, 16, 17) and some merely of a procedural nature. Currently, methodological and procedural ones are being separated in distinct booklets [4].

Methods

In 1999, Dutch Health Care Insurance Board presented Dutch guidelines for pharmacoeconomic research. New version of guidelines was actualized since October 27th 2005 and assessed 1st April 2006 by CVZ College Voor Zorgverzekeringen (Health Care Insurance Board). In this review search was performed using the CVZ data base.

Results

Guidelines for pharmacoeconomic research, actualized version by the Ministry of Public Health, Well-being and Sport. These are recommendations how pharmacoeconomic studies should be performed and which aspects should be taken into account. By help of guidelines optimal use of new therapeutic alternatives is applied. With the aim of better application of guidelines in practice The Ministry of Health, Well-being and Sport actualized the pharmacoeconomic guidelines in two phases. The final responsibility was taken by the group of experts for methodology of economic evaluations.

The directives are not for The Netherlands specifically, but form a reflection of the current score of methodology for the implementation of economic evaluation.

There is no difference in interpretation of the contents of the directives between the CVZ and the manufacturers. There are however differences in the appraisal and application of the directives. The new guidelines were assessed 1st April 2006. Commencing date up to 1 April 2006 CVZ assess the pharmaco-economic evaluations which are part of a compensation file still by means of the original directives from 1999. After this date the actualized directives became effective [5].

Reasons for actualization

1. ‑The guideline must be actualized on the basis of the current (international) methodology concerning the implementation of economic evaluations.

2. ‑The guideline to add to other guideline(s) and needs in particularly textual reconsiderations that becomes a univocal interpretation of the guidelines.

3. ‑The guideline is in nature procedural and it is related to information which supplies the manufacturer for the appraisal of mutual substitution and therapeutic value of medicine the guideline is moved to CVZ-publishing of the “procedure application compensation medicines”.

All pharmacoeconomic evaluations, submitted for the support for a compensation application, must be carried out according to these directives. Only when in the file with arguments it is found the reason why the evaluation is not in accordance with the directives, it has been carried out or will be carried out, deviates from the directives permitted.

Guidelines overview

There are now only 11 pharmacoeconomic guidelines (tab. 1):

Guideline #1 (The perspective of the evaluation), states that the societal perspective should be applied and that the most important characteristic of this perspective is the inclusion of the indirect costs from production losses. It is related to the allocation of financial resources and the consequences on the public health.

Guideline #2 (Choice of comparing treat- ment/indication), states that new medici-nes must be compared with the standard treatment, or (if not present) with the usual treatment for compensation, and for a certain indication. Primarily the treatment of which the effectiveness has been proved is considered to be a comparator treatment. Indication must be specified which narrower indication for registration procedure.

Guideline #3 (Analysis technique), states that for the implementation of an pharmacoeconomic evaluation can be chosen from three analysis techniques:

1. cost-utility analyses (CUA) involving the difference costs (incremental costs) compared to the difference in consequences on health are measured life years corrected for quality of life (QALY´s),

2. cost-effectiveness analysis (CEA) involving the difference in costs (incremental costs) become compared to the difference impact (incremental impact), or

3. cost-minimization analyses (CMA) involving comparison of only costs of two treatments and it is applicable when the clinical outcomes of treatments are same.

Guideline #4 (Analysis period), states that the impact and costs of the treatment to compare must be measured over the same period. It concerns both impact and costs but also including cost of side effects, as a result of therapy, for treatment to compare.

Guideline #5 (Cost identification, measuring and appreciation) states that the identification of cost is carried out from social perspective, the measuring and the appreciation of costs must, wherever possible use the National Guide for cost research, with the aim of the uniformity and standardizing of cost measuring is and appreciations in pharmacoeconomic evaluations. Types of cost involved are: direct medical and non-medical costs, indirect medical and non-medical cost, with importance of involving productivity cost, as well. For calculating the costs as a result of productivity losses are two methods applied: Human capital approach and the friction cost method. All cost categories must be mentioned separately and measured in monetary entities.

Guideline #6 (Appreciation of quality of life and QALY´s), states that for the improvement of the quality of life cost utility analyses (CUA) must be performed. Appreciations for the medical condition of patients are stipulated for the number of quality adjusted life years (QALY) to calculate. Both the appreciations and the survival data must be reported separately. The combination from these two elements to QALY must be made transparent.

Guideline #7 (Modeling), states that the model used in pharmacoeconomic ana-lyses must be transparent in supporting decision-making process and preferably connected to clinical research. There are 3 main reasons for implementation of modeling:

– ‑the impact and costs during a time horizon longer than those of clinical research,

– ‑obtained for the clinical data translation to estimates of the effectiveness in daily practice,

– ‑and to compare the effectiveness and costs between resources which have not been compared directly in empirical study.

The validity of the model (face validity, internal and external validity) must be examined and described. Also the results must be compared with study for other countries and with results of other available pharmacoeconomic models for the same medicine.

Guideline #8 (Incremental analysis), states that incremental analysis must be performed on the basis of the incremental differences in impact and costs between the treatment to compare.

Guideline #9 (Discounting of future impact and costs), states that for data concerning the impact and costs collected over a period longer than one year must the impact and costs generated after the first year be discounted. Primary analysis use constant cost discounting at rate of 4%, and future impact is discounted with a constant rate of 1.5%.

Guideline #10 (Uncertainty analysis), states that the sensitivity analysis must be carried out to examine how the results depend on made assumptions. Sensitivity analyses used are: univariate in case of uncertainty of deterministic variables, and probabilistic sensitivity analysis in case of stochastic variables modeling. Cost, impact and cost-effectiveness ratio are methodologically presented and valued. Sensitivity analysis examines parameters in lower and upper limits and to what extended cost, impact and cost-effectiveness ratio changes when assumption is changed.

Guideline #11 (Use of an expert panel), states that if research data are lacking and as a result for obtaining data for input in a model or forming a model for pharmacoeconomic evaluation. To be scientifically described and accepted must be applied an evaluation from expert panel which is composed of experts and is an independent body [6].

Conclusions

The translation of the guidelines is still in progress, above given guidelines are working version of translation. In the nearest future new Dutch guidelines with detailed description will be available on the CVZ website in English. Guidelines were actualized due to many reasons but those highlighted are new trends in pharmacoeconomic research as modeling, due to previous experiences from research as different discounting rate needed for money and for health, and need for formation of independent bodies for evaluation. We hope that obligatory use of pharmacoeconomics and outcomes research as a tool in the evaluation for drug reimbursement will be applied in the near future in the Czech Republic as well as in many other European countries. In October 2010, the 13th Annual European Congress of ISPOR (International Society for Pharmacoeconomics and Outcomes Research) will take place in Prague, and we hope that Czech Republic will make some improvement in application of pharmacoeconomics in decision making process.