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- 2026-05-20 21:57:46
- Policy
- Janssen prepares to close Hyangnam plant, renewing licenses
- by Lee, Tak-Sun Jan 29, 2020 06:27am
- Janssen Korea is to close Hyangnam plant in 2021 and the company is speeding up the process of transferring items manufactured in Hyangnam to other facilities. Apparently some of them would be transferred to other Korean manufacturing companies, whereas some would be manufactured abroad and imported to Korea. As of Jan. 28, Korea’s Ministry of Food and Drugs Safety (MFDS) cleared Janssen Korea’s antipsychotic medicine, Invega (paliperidone) ER tablet in 3 mg, 6 mg, and 9 mg doses. These items are the same items approved back in April 2010. But the newly approved items would be imported to Korea, unlike the previously approved ones manufactured in Hyangnam plant. Janssen Korea has preemptively notified the change to drug distribution channels in Korea and forewarned the drug supply would be suspended until coming May. With the new license in Korea as an imported drug, Invega is expected to be listed for reimbursement from April. UBIST reported Invega has generated 2.3 billion won in Korea for outpatient prescription last year. The drug manufacturing plant is reportedly moving to Italy from Hyangnam, Korea. And the global company would obtain more new drug import licenses, as Janssen has notified Jurnista SR tablet and Topamax springkle capsule would also be manufactured abroad and imported back to Korea. The existing license on Invega has been returned as of passed Jan. 17. Janssen Korea canceling the license and leaving void period in between licenses are inevitable at the moment. Regardless, Invega Sustenna injection would be supplied without a break. Invega Sustenna, unlike the tablet form, was approved as an imported drug in July 2010. Janssen has already registered the injection’s DMF with Irish and Belgian plants as manufacturer of active ingredient paliperidone. Some items are transferring to other Korean manufacturers. Pain reliever Ultracet is transferred to Handok, and gastro-oesophageal reflux disease treatment Pariet is running bioequivalence test for approval to be transferred to Kolmar Korea. And Tyrenol 8-hour ER tablet is highly likely to be transferred to Handok. Janssen’s Hyangnam plant, built in 1983, would stop its production life of 38 years after a year. As it was the center of global drug manufacturing plant in Korea, the Korean pharmaceutical industry is left with bittersweet sentiment of the plant.
- Company
- Breakthrough anticancer Tagrisso makes KRW 29 billion
- by An, Kyung-Jin Jan 29, 2020 06:26am
- Tagrisso AstraZeneca’s new lung cancer treatment Tagrisso has continued to top the prescription drug market. After two years of reimbursement listing, the new drug has generated almost 30 billion won and expanded the overall epidermal growth factor (EGFR) targeted therapy prescription volume. According to pharmaceutical product research firm UBIST on Jan. 23, Tagrisso’s outpatient prescription volume reached 29 billion won last year. The treatment continued to lead the EGFR targeted therapy market as its outpatient prescription volume rose by 33.7 percent than the previous year at 21.7 billion won. Tagrisso (osimertinib) is a third generation tyrosine kinase inhibitor (TKI) developed to inhibit EGFR T790M resistance mutation. The treatment was approved by Korea’s Ministry of Food and Drug Safety (MFDS) in May 2016 as a once-daily treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), whose T790M has been mutated after being treated with other existing EGFR-TKI options like Iressa (gefitinib), Tarceva (erlotinib), and Giotrif (afatinib). In December 2018, the targeted therapy won an expanded indication as a first-line therapy on patients with locally advanced or metastatic NSCLC and an EGFR exon 19 deletion or exon 21 L858R mutation. Growth of Tragrisso outpatient prescription volume by month (Unit: KRW 1 million) Source: UBIST In December 2017, the first month of reimbursement listing, Tagrisso made 1.7 billion won and teased its future success from early on. From April 2018, its prescription volume soared as Hanmi Pharmaceutical’s Olita (olmutinib) that received reimbursement on the same day as Tagrisso was suspended from development and sales, and Tagrisso became the only third generation EGFR-TKI in the market. The prescription volume steeply peaked at 2.8 billion won in last July, and it has plateaued at around 2.7 billion won since then. But, the overall sales volume is estimated to be even higher as its inpatient prescription is significant. Due to Tagrisso’s exceptional performance, the overall EGFR targeted therapy’s outpatient prescription volume has increased up to 60.4 billion won. The figure has increased by 15.6 percent from the year before, and by 41.5 percent compared to figure prior to 2017 when Tagrisso was listed for reimbursement. Out of all four EGFR-TKIs, Tagrisso’s outpatient prescription takes 48.0 percent of the pie. During the same period, the prescription volume of first generation EGFR targeted therapies—AstraZeneca’s Iressa and Roche’s Tarceva—has been falling. Iressa’s outpatient prescription volume last year reached 17.5 billion won, or 18.3 percent less than the year before. Tarceva’s volume reached 3.6 billion won with 0.4 percent decrease. Boehringer Ingelheim’s second generation EGFR targeted therapy Giotrif’s outpatient prescription volume last year has doubled from the year before and made 10.3 billion won. Apparently, it was the highest figure the targeted therapy has reached since its release in Korea. Major EGFR targeted therapy’s outpatient prescription trend by month (Unit: KRW 1 million) Source: UBIST The pharmaceutical industry predicts the EGFR targeted therapy prescription landscape would take a sharp turn if Tagrisso successfully expands reimbursement on to the new indication as first-line treatment for lung cancer. The market experts expect that the prescription of first-line treatment for NSCLC would skyrocket, if AstraZeneca, which built a strong sales network in lung cancer for long period of time with Iressa, is to concentrate on marketing Tagrisso by differentiating it from other first and second generation drug. It also means Giotrif that just surpassed the ten-billion-won line last year for the first time could bounce back down. AstraZeneca is in the process of applying reimbursement on Tagrisso’s indication as first-line treatment for NSCLC patient. Recently, the company has reportedly applied for reimbursement expansion to Health Insurance Review and Assessment Service (HIRA) based on the findings of Phase 3 clinical study FLAURA that confirmed overall survival of patients with NSCLC, who were treated with Tagrisso as a fist-line treatment.
- Policy
- Korea-Switzerland promulgated an AMR on GMP
- by Lee, Jeong-Hwan Jan 29, 2020 06:26am
- The AMR (Agreement on Mutual Reliance) on GMP (Good Manufacturing Practice) between Korea and Switzerland was promulgated on the 23rd. It is a follow-up after the MFDS (Ministry of Food and Drug Safety) signed a GMP agreement with the SWISSMEDIC (Swiss Drug Agency) on December 18 last year. The agreement promulgated the mutual recognition that strengthening cooperation between Korea and Switzerland would mitigate trade barriers and create mutual benefits. Above all, it reaffirmed its importance in promoting international trade between the Republic of Korea and Switzerland and ensuring the global supply chain integrity of pharmaceuticals and the production of high quality pharmaceuticals. In conclusion, the results of the GMP survey between the MFDS and the SWISSMEDIC can be replaced by a GMP certificate issued in the country. Trust article in the GMP agreement between Korea &Switzerland This shortens the registration period for domestic pharmaceutical and bio companies by exempting GMP evaluation from the SWISSMEDIC. The GMP requirements apply to all human medicines, including investigational medicinal products (IMPs), active pharmaceutical ingredients (APIs), chemicals, biologics (including biologicals) or herbal preparations. Switzerland is one of the strongest pharmaceutical groups in A7 countries, and Korea's GMP system and management level is equivalent to that of Switzerland, which means that Korea's regulatory capacity and pharmaceutical industry are internationally recognized. The A7 countries are the United States, the United Kingdom, France, Germany, Italy, Switzerland, and Japan, which are advanced pharmaceutical countries that are used when deciding or reassessing domestic drug prices. As the ratification takes effect, Korean pharmaceutical companies are exempt from GMP due diligence when exported to Switzerland, and it is expected that market entry will be easier due to cost reduction and shortening of the permit period. In particular, as pharmaceutical quality management and regulatory levels are recognized by Switzerland, the possibility of equal treatment in the European market increases. so it will be a good opportunity for Korean pharmaceuticals to enter the European market.
- Company
- Eylea biosimilar by SCD applies for Phase 3 global IND
- by Lee, Seok-Jun Jan 29, 2020 06:25am
- Samchundang Pharm (SCD) plans to have Phase 3 global clinical trial protocol approved for Eylea’s biosimilar ‘SCD411’ within the first quarter of the year. The protocol approval would be reviewed for 90 days at longest, and green light the company to start the Phase 3 trial by the coming second quarter. The multiregional study is planned to be conducted in the U.S., Europe and Japan with a set number of participants. When the trial in Japan starts, SCD would receive USD 3 million (about 3.4 billion won) as a milestone payment stated on the substance license-out deal. According to pharmaceutical industry on Jan. 23, SCD is submitting an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) in the first quarter to obtain approval on a Phase 3 global clinical trial testing a biosimilar product of anti-vascular endothelial growth factor (VEGF) medication Eylea (aflibercept). When FDA clears the Phase 3 IND application, clinical trial in each region would be carried out with respective set number of participants. The approval would be reviewed within 90 days. SCD official stated, “Clinical trials in respective regions are ready to start immediately when the IND application is passed. The protocol review takes 90 days at most, but it could be a month at earliest. We are compiling a flawless application. The target schedule is to submit the IND application within the first quarter.” Initiating the study in Japan after the IND application approval would grant SCD three million dollars. In last March, SCD has signed a deal on SCD411 with Japan-based SENJU Pharmaceutical for 50 billion won. The deal gives exclusive sales rights of the drug in Japan. The Japanese company has paid upfront payment of 2.5 billion won, and agreed to pay out 47.5 billion won for achieving each clinical milestone. The Korean company has received total of 11.5 billion won from the upfront payment (2.5 billion won) and CRO deal related to global clinical trials (nine billion won). Preparation for IND approval has already been completed. In last August, SCD announced the company had a successful pre-IND meeting with the U.S. FDA as a preparation process prior to IND application submission. The company explained, at the meeting, the U.S. health authority generally reviewed the SCD 411’s quality equivalence test outcome and clinical protocol and confirmed the candidate medicine would not have an issue proceeding with IND application. Moreover, the company elaborated about the U.S. FDA recommending execution of Phase 3 trial straight without Phase 1, as recommended by European Medicine Agency (EMA) and Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Basically, the company can simultaneously process the marketing approval in the U.S., Europe and Japan and other major global markets with the Phase 3 global clinical trial. The VEGF treatment has relatively high marketability due to rarity of the treatment option. At the moment, the only options available are Bayer’s Elyea (aflibercept) and Novartis’ Lucentis (ranibizumab). The market volume is expected to grow from seven trillion won in 2017 to 13 trillion won by 2026.
- Policy
- Hanmi’s salt-modifying drug for Galvus was approved
- by Lee, Tak-Sun Jan 29, 2020 06:25am
- A salt alteration drug of Galvus(Vildagliptin) by Hanmi, a DPP-4 inhibitor for diabetes was approved. But one indication in the original drug is excluded. It is understood as a strategy to avoid patent The Ministry of Food and Drug Safety approved the generic product (50mg) for Galvus by Hanmi. Unlike the original galvus, this generic has the HCl of the main ingredient, Vildagliptin. There are four efficacy and effectivess (indications) of Vildagle tablet 50mg including ▲monotherapy as an adjunct to diet and exercise therapy to improve glycemic control in patients with type II diabetes, ▲combination with Metformin if no prior diabetes medication has been received and monotherapy is not enough to control blood sugar, ▲concomitant use with Vildagle if Sulfonylureas and Metformin combinations do not provide sufficient glycemic control, ▲and combination with Vildagle when Insulin (Insulin alone or with Metformin) therapy does not provide sufficient glycemic control. One indication, which is concomitant use in case of Sulfonylurea, Metformin or Thiazolidinediones monotherapy does not provide sufficient blood sugar control, is missing compared to the original Galvus 50 mg. This is due to the fact that the Galvus’ Material Patent received an extension of its duration (2 years 2 months 23 days). One of the indications is excluded that Concomitant use is possible for insulin-independent diabetic patients (type II), if diet and exercise therapy are not sufficient to control glycemic control with Metformin, Sulfonylurea, or Thiazolidinedione alone. In other words, with the exception of the indication, it seems to be a strategy to circumvent the scope of rights of the extended patent for material and to release the product at the time of expiration of the material patent (December 9 2019). Hanmi requested a passive judgment on the scope of the rights of Galvus in December last year. If the claim is quoted, the reimbursement process can be used to bring the product to market immediately. This is a different strategy from Ahn-gook Pharm, which was previously approved for the same ingredient. Ahn-gook obtained the same indication as the original Galvus 50mg with Ahn-gook’s generic drug. Instead, due to the problem of extending the life of the material patent, it succeeded to invalidate 187 days of the extended 2 years 2 months 23 days. Thus, it became the sales base from August 30 2021. In addition, the company obtained a successful patent challenge and a generic monopoly 'generic exclusivity' granted to the first applicant. In order for Hanmi to release its products earlier than Ahn-gook, it must be cited by the passive jurisdiction checker who claimed at the end of last year. Hanmi also co-sold Galvus with Novartis in 2014. It is important to note whether the company will compete as a competitor in the former peer market through patent evasion.
- Company
- General hospitals clear Norvasc for pediatric use
- by Eo, Yun-Ho Jan 28, 2020 11:18am
- More general hospitals are reportedly listing Norvasc on their drug codes for pediatric treatment. Pharmaceutical industry on Jan. 28 said respective Drug Committees in Seoul National University Hospital, Severance Hospital and Korea University Guro Hospital cleared Norvasc (Amlodipine) 2.5 mg for prescription from the release in last year to now. The 2.5 mg dose of high blood pressure medicine Norvasc is newly approved dose of the drug and the only calcium channel blocker (CCB) in Korea approved by Ministry of Food and Drug Safety (MFDS) for treating pediatric high blood pressure patients aged six to 17. The pediatric indication allows administrating minimum 2.5 mg or maximum 5 mg of the drug once daily. From 2013 to 2017, the number of child and adolescent patients treated in a hospital for high blood pressure has been increased from 4,500 to 6,497, respectively. A clinical study confirmed the drug’s effect in 268 high blood pressure patients ages six to 17, randomized to be administered 2.5 mg or 5 mg of the drug once daily for first four weeks of treatment. The study outcome found, the 2.5 mg and 5 mg arms demonstrated significantly lower systolic blood pressure than the placebo group. In particular, the study reported 5 mmHg systolic on the 5 mg dose and 3.3 mmHg systolic on the 2.5 mg dose. Pfizer Upjohn Korea has diversified the original amlodipine item’s dose and formulation into Norvasc, Norvasc T, and in lower doses to keep the high market share of the off-patent drug. According to UBIST, Norvasc in last year has generated 58.9 billion won from outpatient prescription and defended its title of top single antihypertensive drug. The drug is the first prescribed drug to have made 100 billion won in 2001. Other pharmaceutical companies in Korea have released products with the same active ingredient, and S-amlodipine drugs that maintain the equivalent effect with lowered dose are also available in the market.
- Policy
- Tarlige, pain reliever & Smyraf, RA treatment approved
- by Lee, Tak-Sun Jan 28, 2020 06:13am
- New drugs such as Tarlige (Mirogabalin besylate by Daiichi Sankyo, Korea) used for the treatment of peripheral neuropathic pain and Smyraf (Peficitinib hydrobromide, Korea Astellas Pharmaceutical) for rheumatoid arthritis received domestic permission at the same time . They are expected to compete with existing products of the same family. The Ministry of Food and Drug Safety approved two new drugs on the 23rd, including 2.5mg, 5mg, 10mg, 15mg and 50mg of Tarlige, & 100mg of Smyraf. Both drugs were made by Japanese global pharmaceutical companies. Tarlige has the efficacy(indication) of treatment of peripheral neuropathic pain. The dosage and dose is usually administered orally 5mg/day twice daily for adults. Multi-national trials showed that 824 patients with diabetic peripheral neuropathy (DPNP) had double-blind, phase III trials performed in Asia for 14 weeks (1 to 2 weeks of dosing and 12 to 13 weeks of fixed dose). In the clinical trials, the group of 30 mg of Mirogabalin/day (15mg twice daily) showed a statistically significant improvement in the pain score at week 14 compared to the placebo group. The main ingredient, Mirogabalin, is a Gabapentinoid-based drug that acts on the calcium channel apa2-delta ligand and reduces the secretion of neurotransmitters involved in pain. Pfizer's Neurontin capsules (Gabapentin) and Lyrica capsules (Pregabalin) have the same mechanism. As a result, Mirogabalin is likely to compete with them. However, it is expected in the medical field for new drugs, since both Neurontin and Lyrica are patent expired drugs. According to the drug market researcher UBIST, in 2019, Neurotin recorded ₩ 19.5 billion and Lyrica recorded ₩62.7 billion in outpatient prescriptions. Smyraf is a JAK inhibitor, such as Pfizer's Xeljanz (Tofacitinib). JAK inhibitor is a drug that blocks the arthritis molecule and improves symptoms by inhibiting the enzyme neurons, Januskinase (JAK), and it is an oral rather than injection as a treatment for rheumatoid arthritis. Currently, there are two items in the same category, including Xeljanz and Lilly's Olumiant (Baricitinib). Smyraf is used to treat moderate to severe active rheumatoid arthritis in adults who do not adequately respond or tolerate one or more anti-rheumatic agents (DMARDs) and may be co-administered with Methotrexate or other abiotic rheumatic agents (DMARDs). However, it should not be combined with potent immunosuppressive agents (except topical therapies) such as biological antirheumatic agents or other Janukinase (JAK) inhibitors. It has a recommended dose of 100mg once a day after meals, and it seems to be more competitive than Xeljanz administered twice a day. However, Lilly's Olumiantis is also once daily use. In a multi-regional phase III trial in 500 patients with rheumatoid arthritis that did not respond properly to existing anti-rheumatic (cDMARDs) formulations including Methotrexate, Smyraf had a higher treatment rate compared to placebo and a statistically significant difference. According to last year's JAK inhibitors, Xeljanz recorded outpatient prescriptions of ₩4.3 billion based on UBIST and ₩500 million of Olumiantis. However, due to the rapid growth of this category of drugs, the market size is expected to expand further with the emergence of Smyraf.
- Company
- Repatha’s options for ultra high risk patients extended
- by Eo, Yun-Ho Jan 28, 2020 06:13am
- Professor Hyeon Cheol Gwon Since statins, the coverage of the PCK9 inhibitor Repatha, an option for managing dyslipidemia, is expected to increase utilization. Amgen Korea(the CEO Noh) held a press conference at the Westin Chosun Hotel in Seoul on the 22nd to commemorate the reinforcement of health insurance benefits for Repatha’s atherosclerotic cardiovascular disease (ASCVD). Repatha has been applied to the treatment of patients with atherosclerotic cardiovascular disease at very high risk and patients with heterozygous familial hypercholesterolemia with hypercholesterolemia and statin intolerance patients from January 1 this year. The press conference centered on atherosclerotic cardiovascular disease among them. Professor Hyeon Cheol Gwon, Director of circulatory internal medicine dept., Samsung Medical Center, who presented as the first speaker at the meeting, announced the theme of 'the latest knowledge on the treatment of atherosclerotic cardiovascular disease with ultra high risk group using PCSK9 inhibitor'. Atherosclerotic cardiovascular disease, known as myocardial infarction, stroke, or peripheral artery disease, is a type of atherosclerosis caused by the accumulation of cholesterol in the vascular lining. Patients who have experienced at least one atherosclerotic cardiovascular disease have a high risk of clinical recurrence and a poor prognosis, with a mortality rate of up to 85%. Professor Hyeon Cheol Gwon said, "A patient who has experienced atherosclerotic cardiovascular disease is a serious disease whose mortality rate increases rapidly with the second and third recurrences, and LDL-C, a major risk factor for the ultra high risk group, must be thoroughly managed". He said, “Statin and Ezetimibe are already standard treatment regimens, but some patients with ultra high risk group are still unable to reach their treatment goals because the LDL-C baseline is high and the target is low in the ultra high risk group. We look forward to lowering LDL-C to prevent recurrence of cardiovascular disease in more patients. And, the indication expansion is expected to lower the LDL-C in the high-risk group to prevent recurrence of cardiovascular disease in more patients”. Meanwhile, domestic treatment guidelines recommend that patients with atherosclerotic cardiovascular disease should be adjusted to less than 70 mg / dL of LDL-C to prevent recurrence of cardiovascular disease. However, in 2019, the European Heart Association lowered the target LDL-C level of the ultrahigh risk group to less than 55 mg/dL. Accordingly, there is increasing interest in the field of PCSK9 inhibitors that are useful for patients at very high risk who do not reach target levels with existing treatment regimens.
- Company
- Last year, Tamiflu sales fell by half
- by Jung, Hye-Jin Jan 28, 2020 06:13am
- Last year, the flu treatment Tamiflu market dropped sharply. The size of the market has shrunk as the number of flu patients has decreased significantly from 2018. The share of generics in the market has been expanding. Outpatient prescription performance of Oseltamivir were down ₩17.2 billion, down 50.4% from last year, according to UBIST, a drug research agency. This is the result of a survey of 37 products with recent prescriptions. Oseltamivir is a drug used to treat flu, and Roche's Tamiflu is the original medicine. Prescriptions for 37 items from 2017 to 2018 rose 103% from ₩17 billion to ₩34.6 billion, but fell back to ₩17.2 billion last year. In the winter of 2018, the flu was a very common epidemic. According to the KCDC(Korea Centers for Disease Control & Prevention), the number of influenza patients per 1,000 outpatients last year were 19.5 at 49 weeks, 28.5 at 50 weeks, 37.8 at 51 weeks, and decreased by more than 30% less than 49.8 at 52 weeks. 34.1, 48.7, 71.9, and 73.3 in the week 49-52 of 2018. In the prescriptions for Oseltamivir ingredients, Tamiflu, the original drug, was still ranked first last year. Tamiflu's prescription amount was ₩5.2 billion. Hanmiflu followed with ₩4.1 billion. After that, Comyflu came in third with ₩1.5 billion in earnings. Tamiflu and Hanmiflu, both of which ranked top in prescription performance, also saw a sharp decline. Both original and generic prescriptions declined, but Tamiflu was the largest among the top five. Tamiflu's prescriptions for 2019 decreased 58.4% year-on-year, while Hanmiflu also decreased 54.2%. Kolon's Comyflu decreased 31%, Yuhan's Yuhan N Flu decreased 50.6%, and Arlico's Tamipro decreased 20.8%. In particular, Tamiflu's share in the overall market of Oseltamivir is decreasing. Tamiflu's 2017 market share continued to decline from 51.3% to 36.2% in 2018 and 30.4% in 2019. The share of generics in the Oseltamivir market soared to around 70%. Generics such as Hanmiflu are interpreted as a competitive effect. However, as this winter is not over yet, it is necessary to observe the first quarter 2020 results. In 2018, the most common cases of influenza were in December, while in 2019, the number of patients has increased since the end of December, and the number of patients continues in January. The KCDC announced that the number of suspected influenza patients increased sharply in late December and January this year after the influenza watch warning was issued on last November 15. Last year, the number of suspected influenza patients per 1,000 outpatients fell 53.1 per week, down sharply from last December, but this week increased to 49.1 per week.
- Policy
- Finally a complete revision of PE guideline after 8 years?
- by Lee, Hye-Kyung Jan 28, 2020 06:12am
- After long eight years, the Korean health authority seems to finally accept the pharmaceutical industry’s demand to amend the pharmacoeconomic analysis guideline. Health Insurance Review and Assessment Service (HIRA) recently unveiled a final report on the cosigned research regarding ‘Pharmacoeconomic (PE) Analysis Guideline Revision Plan (Principal investigator: Professor Lee Tae-jin of Seoul National University Health Science Department and Professor Bae Eun Young of Gyeongsang National University College of Pharmacy).’ Aiming for a ‘complete revision’ of the PE analysis, HIRA has started the research from last year. The research report, disclosed on Jan. 22, found countries the Korean PE analysis guideline refers to, such as the U.K., Australia and Canada, have entirely amended their guidelines after 2011. And it claimed the Korean PE analysis guideline should also reflect the developed PE analysis methodology and precedents that the other countries have based since 2011. The research team conducted a survey on stakeholders like pharmaceutical industry organization, patient and civic group, and related scholars, from July to September last year. The team convened consultative meeting with Korean Research-based Pharmaceutical Industry Association (KRPIA), Korea Pharmaceutical and Bio-pharma Manufacturers Association (KPBMA), Korea Biomedicine Industry Association (KoBIA), Korea National Council of Consumer Organization, National Council of the Green Consumers Network, Korea Consumer Agency, National Health Insurance Policyholder Forum, Korean Association of Health Technology Assessment (KAHTA) and other experts. The survey helped the research team to limit the scope of guideline revision down to perspective of revision, analysis period, analysis subject and population group, analytic techniques, comparison subject selection, data source (indirect comparison), items of cost, utility (health related quality of life), discount rate, model construction, and uncertainty. The team recommended the guideline to remove ‘financial impact’ article, but to add ‘statistical consideration (estimated long-term effect, treatment switching (cross over) and etc.)’ and ‘analysis guideline for laboratory test drug.’ ◆ Cost: As the article of cost in PE analysis depends on the perspective, the researchers recommended using healthcare perspective instead of the existing limited societal perspective, as well as only including direct medical expense and excluding non-medical expense (transportation cost, time cost, nursing guardian cost and etc.) for the basic analysis. In the PE analysis material submitted to this date, expert’s opinion takes up the majority of data source with seven cases (14 percent) in diagnostic cost and five cases (ten percent) in treatment cost. Compared to data-focused referential material, expert opinion or cost and resource use quoted from hospital investigation have limited credibility or consistency. Therefore, referencing expert opinion should require official statement of an academic society, or stipulated minimum number of expert panel to improve credibility and consistency. Although the existing guideline does not mention drug wastage, the researchers suggested stating the cost of wastage volume, because it generates noticeable amount of expense. ◆ Utility, the healthcare related quality of life: Rounding up the recommendations made by HIRA, pharmaceutical companies, and civic groups, the researchers said following articles in the guideline about ‘utility’ should be revised; prioritization of utility measuring techniques; Health-related quality of life (HRQL) indicating tool and reviewing tariff selection; detailed guideline on mapping; detailed guideline of direct measuring; and additional review on minimal clinically important difference of utility. Recommending the revised guideline to clarify preference of indirect measurement based on the Health Technology Assessment (HTA) of many other countries, the researchers also suggested using health state vignette-based direct measuring, calculating weighted value of quality of life via mapping, or quoting a value proposed in a published literature, as an option when lacking or having limited data quoted from preference-based measuring tool. About reviewing and selecting HRQL tool and tariff, they argued the health authority should select a single set of tool and tariff to ensure consistency in policy-making process. ‘Tariff’ means the value that converts utility value in foreign country to fit the Korean landscape. The primary recommendation is to select EQ-5D-3L, a tool used the most home and abroad so far, as a single tool and to select tariff developed in the most recent study ‘Lee et al. (2009)’ with the largest sample as a standard tariff. However, the team also proposed keeping the existing guideline as a secondary option, because a proper comparison study or qualitative evaluation on HRQL tool and tariff in Korea has not been conducted, yet, and related empirical data are insufficient. ◆ Discount rate: According to 50 cases of PE analysis material submitted to HIRA, 45 cases (90 percent) have been discounted and five cases (10 percent) have not been discounted. The analysis period of the five cases was apparently under a year. The researchers stated the discount rate for PE analysis should be reduced as well, because the social discount rate continues to descend due to changes in socio-economic conditions. Hence, the report suggested the revised guideline should set 4.5 percent as an adequate level of discount rate, equivalent to the discount rate applied on preliminary feasibility assessment. About applying the same discount rate on the cost and result, the report tried to persuade applying the unchanged rate, but applying either zero percent for no discount or three percent discount rate to analyze sensitivity. Applying the discount rate of 4.5 percent for the entire period of basic analysis was suggested in case the period of PE analysis for the healthcare sector is longer than three decades. But also as a sensitivity analysis, 3.5 percent could be applied after 30 years in case the applicant drug is essential for pediatric treatment. ◆ Perspective: Taking in account the state and realistic environment of reimbursement decision making, the researchers argued the analytic perspective should be amended. Keeping in mind the interest of reimbursement listing reviewer is on the impact on the healthcare sector, the research team first recommended shifting the perspective from limited societal perspective to healthcare perspective and excluding items applicable for direct medical cost from the basic analysis. So the cost should cover items centering the direct medical expense, but it should include nursing if the cost is reimbursed from long-term nursing insurance, whereas the effect should reflect benefit of health on the patient. The secondary proposal suggested was maintaining the current guideline. ◆ Analysis period: The current guideline recommends the analysis to be conducted long enough to confirm major clinical endpoints. The research team studied deliberation cases of similar diseases and contemplated on patient age (cohort joining age), expected life expectancy of general population group, patient’s survival rate, analysis period of similar drugs, clinical trial outcome (median OS), monitoring period, clinical consulting, and uncertainty for calculating analysis period. The team advised to maintain the principal approach of the existing guideline, but to consider validity of calculated analysis period. Also the team elaborated the revision, when comparing with other countries’ guidelines, should take in account the age of applicable population, life expectancy, survival rate based on epidemiological data, median OS observed from clinical trial, difference in survival rate between cohorts, monitoring period, numerous uncertainties inserted in model, similar drug evaluation case or cases in referential countries and expert consulting. ◆ Analytic techniques: The current guideline recommends using cost-utility analysis when quality of life is a crucial aspect or the health outcome is demonstrated in various indicators. But the research team claims the guideline should provide more specific standard or analytic techniques to distinguish equivalence of effect. They first advised offering more detailed guideline on selecting subject for cost-minimization analysis, expense item and submission data to be considered when conducting the cost-minimization analysis. Regarding subject for cost-minimization analysis, the researchers recommended clarifying the cases of the drug effect is non-inferior (or superior) and recognizing the non-inferiority of the applicant drug in safety profile. As for the cost estimation, the guideline should set equi-effective doses and provide cost of comparing options’, as well as other costs estimated from monitoring, adverse reaction relief, and others. The secondary recommendation is to exclude cost-minimization analysis from the analytic techniques. The researchers explained it would theoretically eliminate the issues of effect equivalence and uncertainty. ◆ Subject of comparison: The existing guideline stipulates selecting alternative treatment option with the highest market share as a reference. When there are multiple drugs with similar market share, multiple options can be selected for comparison, and other therapy and surgery can be used as reference if there is no other alternative option. The referential option selection has been an issue raised by the pharmaceutical industry for a long while. The Korean guideline clearly states to select a substitutable option with the highest market share, but many of other countries’ guideline does not specify “the highest market share.” As a primary recommendation, the researchers suggested keeping the basic principal of selecting the ‘most used’ drug for comparison, but to loosen the description of ‘highest market share’ to prioritize replaceability when selecting a referential treatment option. The majority of the researchers were negative about providing a range of options like in Australia or limiting the option to reimbursed treatment, but they agreed on having government committee to discuss or negotiate with pharmaceutical companies based on submitted PE analysis material and market status. However, the team put down a precondition that comparing with existing treatment option, which fails to treat health condition but has no other option, is ‘not automatically neglected from referential candidate list.’ ◆ Data source: The HIRA’s guideline barely mentions of indirect comparison, but a separate indirect comparison guideline is used to accommodate, and the government agency has already opened up about possibly accepting simple comparison of drugs as they reflected stakeholders’ demands, since the 2014 revision. The researchers elaborated “It could be seen that it was actually more lenient than other countries’ guidelines,” and advised that the revised guideline should edit the detailed guideline and supplementary explanation in a wider sense.
