Eight-year experience of using HTA in drug reimbursement: South Korea.

This study describes the process and results of drug reimbursement decision-making in South Korea and evaluates its performance from the perspectives of the various stakeholders involved. Data were retrieved from the evaluation report posted on the Health Insurance Review and Assessment Service (HIRA) website. As of 2014, 253 new drugs had been submitted to the HIRA for appraisal. Of these, 175 (69.2%) were recommended in favor of listing and 78 (30.8%) were rejected. Furthermore, 68 of these drugs were deemed clinically improved relative to existing drugs. For those drugs that did not demonstrate clinical superiority (which was most of them), a simple price comparison to the existing drug was utilized as a gate toward listing. On top of the base-line analysis, 104 stakeholders from the industry, academia, public office, and civic society responded to a questionnaire designed to obtain their opinions on the South Korean positive list system (PLS). Stakeholders agreed that the consistency of reimbursement decision-making has improved since 2007, while accessibility to new drugs has apparently decreased. Respondents also indicated a preference toward improved public access to decision-making information. This examination of reimbursement decisions in South Korea will illuminate critical issues for countries that are considering the introduction of similar policies.

Price cuts and drug spending in South Korea: the case of antihyperlipidemic agents.

OBJECTIVE: To identify the effect of price control policies on drug expenditure in South Korea. METHODS: We retrospectively examined the effects of price-reduction policies on drug expenditures, in particular regarding anti-hyperlipidemic drugs. The National Health Insurance claims data for a 60-month period between 2006 and 2010 were analysed. A segmented regression analysis was conducted with three intervention variables: July 2008, April 2009, and January 2010. RESULTS: Despite three rounds of price cuts, monthly drug expenditures increased by KRW 599.67 million (USD 523,726) after the third intervention (p=0.0781). The trend in volume increased consistently, but not significantly. The unit prices showed a steady downward trend over time, but rebounded after the third price cut. The number of patients with hyperlipidemia more than doubled to 3729 (p=0.0801) per month after the entry of generics for atorvastatin in July 2008. CONCLUSION: Extensive price controls did not effectively suppress the growth of pharmaceutical expenditures. The increased number of patients, attributable to the newly launched generic drug atorvastatin, and the increased use of expensive drugs were major factors affecting the increase in drug spending. Policies that regulate both drug prices and utilisation, and that reduce financial burdens via enhanced use of generics need to be introduced.

Cost-utility analysis for platinum-sensitive recurrent ovarian cancer therapy in South Korea: results of the polyethylene glycolated liposomal doxorubicin/carboplatin sequencing model.

OBJECTIVE: We performed a cost-utility analysis to assess the cost-effectiveness of a chemotherapy sequence including a combination of polyethylene glycolated liposomal doxorubicin (PLD)/carboplatin versus paclitaxel/carboplatin as a second-line treatment in women with platinum-sensitive ovarian cancer. METHODS: A Markov model was constructed with a 10-year time horizon. The treatment sequence consisted of first- to sixth-line chemotherapies and best supportive care (BSC) before death. Cycle length, a time interval for efficacy evaluation of chemotherapy, was 9 weeks. The model consisted of four health states: responsive, progressive, clinical remission, and death. At any given time, a patient may have remained on a current therapy or made a transition to the next therapy or death. Median time to progressions and overall survivals data were obtained through a systematic literature review and were pooled using a meta-analytical approach. If unavailable, this was elicited from an expert panel (eg, BSC). These outcomes were converted to transition probabilities using an appropriate formula. Direct costs included drug-acquisition costs for chemotherapies, premedication, adverse-event treatment and monitoring, efficacy evaluation, BSC, drug administration, and follow-up tests during remission. Indirect costs were transportation expenses. Utilities were also derived from the literature. Costs and utilities were discounted at an annual rate of 5% per cycle. RESULTS: PLD/carboplatin combination as the second line in the sequence is more effective and costly than paclitaxel/carboplatin combination, showing an additional US$21,658 per quality-adjusted life years. This result was robust in a deterministic sensitivity analysis except when median time to progression of second-line therapies and administration cost of PLD/carboplatin per administration cycle were varied. The probability of cost-effectiveness for PLD/carboplatin combination was 49.4% at a willingness to pay $20,000. CONCLUSION: A PLD/carboplatin combination is an economically valuable option as second-line chemotherapy for the treatment of platinum-sensitive ovarian cancer in South Korea.

Injectable and biodegradable poly(organophosphazene) hydrogel as a delivery system of docetaxel for cancer treatment.

Although docetaxel (DTX) is an advanced taxoid, further augmentation of its properties is still required, such as improvement in its low aqueous solubility. Herein, we report the development of biodegradable/injectable poly(organophosphazene) (PPZ) hydrogels for the delivery of DTX without the use of organic solvents. An aqueous solution of PPZ containing α-amino-ω-methoxy-poly(ethylene glycol) (AMPEG) 750 instead of AMPEG 550 was prepared, thereby increasing the erosion capacity of the hydrogel by judicious balance of the hydrophobic/hydrophilic moieties. The safety of the hydrogel was demonstrated using a biocompatibility test. The PPZ aqueous solution (8 wt%) containing DTX exhibited a thermosensitive sol-gel-sol transition that was independent of the concentration of DTX (1-3 mg/mL). The in vitro release study indicated that the dominant release mechanism was either erosion or diffusion/erosion-controlled release depending on the DTX content of the hydrogel. The in vivo anticancer effect of the intratumorally injected PPZ system in human gastric cancer cell-xenografted mice was evaluated, which demonstrated a significantly (p < 0.01) enhanced effect of the DTX-PPZ hydrogel system compared to the control (DTX solution, i.v.). In conclusion, the PPZ hydrogel may be a promising candidate for DTX delivery, affecting a decrease in the size of tumors with little toxicity prior to exeresis.

Thermosensitive/magnetic poly(organophosphazene) hydrogel as a long-term magnetic resonance contrast platform.

A thermosensitive/magnetic poly(organophosphazene) hydrogel (a magnetic hydrogel) was designed and synthesized for long-term magnetic resonance (MR) imaging. To turn a thermosensitive poly(organophosphazene) hydrogel (an original hydrogel) into a long-term MR contrast platform, cobalt ferrite (CoFe(2)O(4)) nanoparticles, which have hydrophobic surfaces, were bound to the original hydrogel via interactions between the hydrophobic surfaces of the nanoparticles and the (L)-isoleucine ethyl esters of the polymer. The magnetic hydrogel showed extremely low cytotoxicity and adequate magnetic properties for use in long-term MR imaging, in addition to possessing the same properties of the original hydrogel, such as viscosity, thermosensitivity, biodegradability, biocompatibility, a reversible sol-to-gel phase transition near body temperature, and injectability. The magnetic hydrogel was injected into a rat brain using stereotactic surgery. After the injection, the applicable potentiality as a long-term MR contrast platform was successfully estimated over 4-5 weeks. Consequently, it was shown that a magnetic hydrogel as a long-term MR contrast platform has the potential to be applied in a long-term theranostic hydrogel system. Furthermore, it is expected that this platform can be useful in the clinical field of incurable diseases due to either surgical difficulties or lethality, such as with brain tumors, when the platform is combined with therapeutic drugs for long-term MR theragnosis in further studies.