Acceptable incremental cost effectiveness ratio for use of new drugs, cases in statin therapies.

As it is an urgent issue to contain increasing healthcare expenditures, unlimited reimbursement of pharmaceuticals continues to be controversial. The objective of this study is to identify acceptable incremental cost effectiveness ratios between new and conventional therapies. Clinical study data for five statin therapies were used to indicate treatment effectiveness and incremental costs were indicated by price premiums at price listing. The incremental cost effectiveness ratios to pravastatin were 0 yen/patient with response, 1,475.1 yen/patient with response, 3,033.3 yen/patient with response, and 3,032.4 yen/patient with response. By conducting further analyses in various pharmaceuticals and categorizing acceptable incremental cost effectiveness ratios based on the disease severity and expected level of improvement in disease condition, drug prices that reflect the value of new pharmaceuticals and that are reasonable to be reimbursed can be suggested.

[Patient needs for consultation with pharmacists].

More prescription drugs are dispensed by pharmacists rather than doctors in response to government healthcare reform. However, the results of our preliminary survey suggested a hypothesis that patients were not always satisfied with explanations provided by pharmacists upon dispensing, and therefore patient satisfaction might be enhanced if pharmacists spent more time on consultation services. The survey was conducted in 1,800 people. 321 people (17.8%) answered that pharmacist explanations were not sufficient or that they expected further consultation with pharmacists. The most common reason why they did not ask for consultation was that other patients were waiting (41.7%). If up to 30-minute consultation service was available at a pharmacy where patient privacy was ensured, 898 people (49.9%) answered that they wanted to use the service. The average willingness-to-pay (WTP) for the service was 338 yen and the mean WTP was 400 yen. When those who answered 0 yen were excluded, the average was 386 yen and the mean was 400 yen. The online survey revealed that some patients were not satisfied with pharmacist explanations upon dispensing, and that there was a need for consultation services at pharmacies. Many of the reasons why patients did not ask for consultation although they wanted to were attributable to pharmacies, and the survey results suggested a need for improvement in their services. In view of the WTP for the service, it is considered worthwhile to discuss the introduction of such a system for consultation services into dispensing fee.

Cost-utility analysis of varenicline, an oral smoking-cessation drug, in Japan.

OBJECTIVE: To conduct a cost-utility analysis of two 12-week smoking-cessation interventions in Japan: smoking-cessation counselling by a physician compared with use of varenicline, an oral smoking-cessation drug, in addition to counselling. METHODS: A Markov model was constructed to analyse lifetime medical costs and QALYs from the perspective of the healthcare payer. The cycle length was 5 years. Both costs and QALYs were discounted at 3% annually. The cohort of smokers was classified by sex and age, and we assumed that smokers started smoking at the age of 20 years and received smoking-cessation therapy at the ages of 30, 40, 50, 60 or 70 years (five separate models were run). The healthcare costs and QALYs were calculated throughout the term until the age of 90 years. In the base-case analysis, success rates of varenicline plus counselling and counselling alone were assumed to be 37.9% and 25.5%, respectively, in male smokers, and 22.2% and 16.1%, respectively, in female smokers, based on a randomized controlled trial conducted in Japan. Both univariate and probabilistic sensitivity analyses were conducted. RESULTS: Prescribed varenicline was shown to be more effective and less costly than smoking-cessation counselling alone. Varenicline would save direct medical costs of Japanese Yen (yen)43 846 ($US381; $US1 = yen115; Oct 2007) and generate an increase of 0.094 QALYs in male smokers. In females the incremental cost-effectiveness ratio was yen346 143 per QALY gained. Varenicline is estimated to save yen23.7 billion ($US206 million) of the medical costs for tobacco-associated diseases for the whole population. Overall savings are yen9.5 billion. Sensitivity analyses suggested the robustness of the results. CONCLUSIONS: As with any data of this nature, there is some uncertainty in the results and further research is warranted. However, based on the results of this pharmacoeconomic evaluation, varenicline, the first non-nicotine, oral treatment developed for smoking cessation, appears to be cost effective and may contribute to future medical cost savings in Japan.

[Regulatory sciences in herbal medicines and dietary supplements].

Regulatory science began in the late 1980's in the pharmaceutical area in Japan. It aimed not only at vertical, top-down regulation but also horizontal regulation to suit the social value system. Herbal medicines and dietary supplements are two areas where regulatory science is still not well developed and used. Risk perception, risk assessment and risk management in these areas are often neglected by regulators, academicians and the public. Since the risk of using herbal medicines and dietary supplements is a global concern, development of a global regulatory system is needed. In this paper, we introduce the current situation of several projects which deal with regulatory science in herbal medicines and dietary supplements, namely: (1) Herbal ATC (HATC) classification project initiated by Uppsala Monitoring Centre (UMC) which led to the development of the provisional HATC code of 228 Kampo formulae and Standard Kampo Formula Nomenclature (SKFN) in Japan, (2) WHO/WPRO International Standardization of Terminology (IST) which resulted in the publication of "WHO Internal Standard Terminologies on Traditional Medicine in the Western Pacific Region Forum for Herbal Harmonization", (3) Forum for the Harmonization of Herbal Medicines (FHH), (4) CONSORT extension for herbal medicines, (5) ICH M5 (Data elements and standards for drug dictionaries), and (6) activities on nomenclature at the International Organization for Standardization (ISO). However, there is a lack of coordination among these projects. Therefore, harmonization of all projects aimed at harmonizing and standardizing all aspects of regulatory science for herbal medicines and dietary supplements is recommended. However, careful consideration should be given to each unique local situation.

Crystal structure of activated ribulose-1,5-bisphosphate carboxylase/oxygenase from green alga Chlamydomonas reinhardtii complexed with 2-carboxyarabinitol-1,5-bisphosphate.

Ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) catalyzes the initial steps of photosynthetic carbon reduction and photorespiratory carbon oxidation cycles by combining CO(2) and O(2), respectively, with ribulose-1,5-bisphosphate. Many photosynthetic organisms have form I rubiscos comprised of eight large (L) and eight small (S) subunits. The crystal structure of the complex of activated rubisco from the green alga Chlamydomonas reinhardtii and the reaction intermediate analogue 2-carboxyarabinitol-1,5-bisphosphate (2-CABP) has been solved at 1.84 A resolution (R(cryst) of 15.2 % and R(free) of 18.1 %). The subunit arrangement of Chlamydomonas rubisco is the same as those of the previously solved form I rubiscos. Especially, the present structure is very similar to the activated spinach structure complexed with 2-CABP in the L-subunit folding and active-site conformation, but differs in S-subunit folding. The central insertion of the Chlamydomonas S-subunit forms the longer betaA-betaB loop that protrudes deeper into the solvent channel of rubisco than higher plant, cyanobacterial, and red algal (red-like) betaA-betaB loops. The C-terminal extension of the Chlamydomonas S-subunit does not protrude into the solvent channel, unlike that of the red algal S-subunit, but lies on the protein surface anchored by interactions with the N-terminal region of the S-subunit. Further, the present high-resolution structure has revealed novel post-translational modifications. Residue 1 of the S-subunit is N(alpha)-methylmethionine, residues 104 and 151 of the L-subunit are 4-hydroxyproline, and residues 256 and 369 of the L-subunit are S(gamma)-methylcysteine. Furthermore, the unusual electron density of residue 471 of the L-subunit, which has been deduced to be threonine from the genomic DNA sequence, suggests that the residue is isoleucine produced by RNA editing or O(gamma)-methylthreonine.