Perceptions of Regulatory Decision-Making for New Drugs From the Viewpoints of the Manufacturers in South Korea.

Regulatory decisions for new drugs approval present high uncertainty, low reversibility, the avoidance of observable errors, and high political stakes. However, research on the behavior of regulatory agencies is scarce, particularly in the context of more open decision-making processes. We aimed to evaluate the perceptions of regulatory decision-making for new drugs approval from the viewpoints of the manufacturers in South Korea. In 2019, employees in domestic (n = 5) and foreign (n = 7) manufacturers with expertise in regulatory affairs were invited to participate in a questionnaire survey and semi-structured group interview. We asked about the relevance of various criteria in regulatory decision-making, the participation of various stakeholders, and the degree of consent for new drug approval with uncertainty. The domestic and foreign manufacturers perceived that a regulatory decision made by the MFDS was solely based on technical merit within a closed decision-making system. They responded that safety, efficacy, and benefit-to-harm ratio were the most relevant criteria and the most prioritized criteria in regulatory decision-making. They also perceived that the MFDS was the sole relevant member in a regulatory decision. However, the foreign manufacturers disagreed that the regulatory agency and the advisory committee were independent of conflicts of interest, which might imply that regulatory decisions were occasionally determined by the agency given the political benefits and/or costs within a more open system. The role of an advisory committee in terms of deliberation and participatory democracy were requested to make politically legitimate regulatory decisions from the viewpoints of the manufacturers. However, their perceptions toward public involvement in regulatory decision-making is still at the early stage.

Easy cuts, easy rebound: Drug expenditures with massive price cuts in Korea.

BACKGROUNDS: Since 2012, the Korean government has introduced 46.5% price cut for off-patent medicines in order to reign everescalating drug expenditure. This study sought to appraise the impact of the price cut measure (in the context of Korean National Health Insurance system). METHODS: We employed Korean National Health Insurance database from January 2007 until December 2016 for 120 month period. An interrupted time series analysis with segmented regression analysis was conducted to estimate the impact of price cut on overall drug spending. RESULTS: Drug spending significantly dropped with the price cut by 186.22 billlion Korean Won (KRW) (p < 0.0001) and the trend after the price cut has also significantly decreased by 1.33 billion KRW (p = 0.002). However, it was predicted that total expenditures showed an increasing trend and bounced back to the original level. Quantity prescribed had no significance with the price cut. Unit price had a substantial drop (ß = -41.68, p < 0.0001) with the price-cut, but the trend after the intervention has increased (ß = 0.16, p = 0.656) with no significance. CONCLUSIONS: Although the price cut has successfully countered the everescalating pharmaceutical expenditures in Korea, the impact was temporary. A lack of demand-side measures resulted in an ineffectiveness and unsustainability of policy effect. Thus, more aggressive demand-side measures should be introduced in the Korean context,and both the demand and supply-sides should be balanced.

Do Physicians Change Prescription Practice in Response to Financial Incentives?

We assessed the impact on physician prescription behaviors of an outpatient prescription incentive program providing financial rewards to primary care physicians for saving prescription costs in South Korea. A 10% sample of clinics (N = 1,625) was randomly selected from all clinics in the National Health Insurance claims database for the years 2009-2012, and all claims with the primary diagnosis of peptic ulcer or gastro-esophageal reflux diseases were extracted from those clinics' data. A clinic-level random-effects model was used. After the program, clinics in general medicine showed a lower prescription rate (by 0.8 percentage points), lower number of medicines prescribed (by 0.02), lower prescription duration (by 0.15 days), and lower drug expenditure per claim (by 740 won). Small clinics on the <25th percentile of a regional sum of monthly drug expenditure had shorter prescription duration (by 0.76 days), while large clinics on the ≥75th percentile and clinics in group practice had a higher prescription rate (by 1.5 and 2.5 percentage points, respectively) and a higher number of medicines prescribed (by 0.03 for group practice only) after the program. The outpatient prescription incentive program worked as intended only in certain subgroup clinics for the target medicines.

Improved Administration of Antibiotics in the Emergency Department: A Practice Improvement Project.

PROBLEM: Although consensus exists among experts that early intravenous antibiotic therapy has an impact on patient mortality, the medical literature includes little information about ensuring that the patient receives the complete dose. At our emergency department, it had become standard clinical practice to administer antibiotics with primary pump tubing and an infusion pump. Clinical pharmacy staff identified this practice as a cause for concern, because at least 20 mL (up to 40%) of the dose volume remains in the tubing. This practice improvement project was aimed at improving the administration of antibiotics by programming a secondary infusion to ensure the complete dose would be administered. METHODS: A multidisciplinary educational intervention was initiated consisting of one-on-one instruction with each emergency nurse (n = 103) at the department's annual Skills Sessions, distribution of educational tip sheets, and reinforcement of the proper procedure at the patient's bedside. Emergency nurses were educated via simulation regarding correct secondary pump programming, using smart pump technology. RESULTS: Surveys indicated that 8% of emergency nurses used secondary tubing along with a smart pump to administer antibiotics before the intervention, compared with 96% after the intervention (P < .0001). IMPLICATIONS FOR PRACTICE: This project demonstrates that our educational intervention improved awareness of the need to administer the entire antibiotic dose and adherence to the use of secondary tubing along with smart pump technology to administer antibiotics.

Effects of pharmaceutical cost containment policies on doctors' prescribing behavior: Focus on antibiotics.

OBJECTIVES: We analyzed the effect of the outpatient prescription incentive program and price cuts of listed medicines in South Korea on prescription drug expenditures and prescription behaviors, focusing on antibiotics for the most common infectious diseases. METHODS: We used the National Health Insurance claims data from January 1, 2009 through December 31, 2012. For 1625 primary clinics randomly sampled, we included all claims with principal diagnoses of acute upper respiratory tract infections (URTIs, J00-J06), acute lower respiratory tract infections (LRTIs, J20-J22), or otitis media (H65, H66). An interrupted time-series analysis was conducted. RESULTS: Pharmaceutical spending per claim dropped immediately after the outpatient prescription incentive program only for otitis media (adults), but the secular trend shifted downward after the incentive program for all target diseases. The incentive program lowered the trend of antibiotic prescribing rate in otitis media (adults). The program was associated with an increase of the number of antibiotics prescribed in URTI (adults) and LRTI (children) and decrease in otitis media (adults). The broad markdown of drug prices reduced pharmaceutical expenditures immediately for all diseases, but without lasting effect. CONCLUSION: The direct financial incentives to physicians to reduce in prescription spending had the intended effect over time and can be an important tool to improve pharmaceutical spending management.

Use of injectable drugs with oral-formulation alternatives for outpatients in South Korea.

This study analyzed the use of injectable drugs with oral-formulation alternatives in the outpatient setting in South Korea. We conducted a retrospective cross-sectional data analysis using 2008 National Health Insurance claims data. All active ingredients were categorized into dual-formulation ingredients (DFIs) and single formulation ingredients (SFIs), and were identified by the type of healthcare service provider (HSP) and anatomical therapeutic chemical (ATC) group. 14.6 % (102/701) of total drugs were extracted as DFIs at about the same rate as that for drugs in the World Health Organization database (14.45 %), showing similar patterns by ATC group. The rate of injectable drug use varied more substantially for DFIs (range 0.94-4.54 %) than for SFIs (range 0.27-1.12 %) by the type of HSP. For DFIs, the highest proportion of injectable drug use was observed in group H (all hormonal preparations, 22.74 %) and group M (anti-inflammatory and anti-rheumatic preparations, 10.23 %) among ATC groups. The proportion of injectable drug use was higher in clinics and small hospitals than in tertiary hospitals and general hospitals where patients with more severe cases tend to visit. The results imply the potentially inappropriate or excessive use of injectable drugs and suggest the need to develop standard guidelines for injectable drug use and strategies to promote high-quality healthcare including education on rational prescribing.

Sociodemographic factors influencing the use of injections in South Korean outpatient care.

PURPOSE: This study explored the relationship between sociodemographic factors and injection utilization in South Korea. METHODS: We conducted a retrospective cross-sectional analysis using 2009 prescription claims for Korean National Health Insurance beneficiaries. We analyzed the utilization, costs, and proportion of injections in the insured market for oral-injection dual-dose-form ingredients (DFIs). We included outpatients who were prescribed DFIs with no age limits. Descriptive analysis and multivariate logistic regression were performed to evaluate the predictive factors of injection use. RESULTS: Injections accounted for about 5% of outpatient utilization and costs of the study drugs. The odds of having injections were 1.3-1.6 times higher among those patients who are 70 years and older compared with those in the 20s, in smaller-sized hospitals and clinics than that in larger, and among medical institutions in rural areas than those in the capital area. The odds of having injections were increased stepwise for the age groups of 30-69 years. Injections were more likely to be prescribed for systematic hormonal preparations and drugs for the musculoskeletal system. CONCLUSIONS: The use of injections was higher among older groups, among smaller medical institutions, and among institutions in rural areas in Korean outpatient care. The difference between prescribing defined daily doses and prescribing rate for injections of the audit reports implies that Korean doctors prescribed injections often, but small doses for momentary effects in outpatient settings. Further studies are required to uncover the underlying causes of the high prevalence of injection use in older or rural populations and smaller institutions.

Unique perception of clinical trials by Korean cancer patients.

BACKGROUND: In the past few years, the number of clinical trials has increased rapidly in East Asia, especially for gastric and hepatobiliary cancer that are prevalent in Asian populations. However, the actual degree of understanding or perceptions of clinical trials by cancer patients in East Asian countries have seldom been studied. METHODS: Between July 1st and November 30th of 2011, we conducted a prospective study to survey cancer patients regarding their awareness of, and willingness to participate in, a clinical trial. Patients with gastrointestinal/hepatobiliary cancer who visited the Hematology-Oncology outpatient clinic at Samsung Medical Center (SMC) were enrolled. A total of 21 questions were asked including four questions which used the Visual analogue scale (VAS) score. RESULTS: In this survey study, 1,000 patients were asked to participate and 675 patients consented to participate (67.5%). The awareness of clinical trials was substantially higher in patients who had a higher level of education (p<0.001), were married (p=0.004), and had a higher economic status (p=0.001). However, the willingness to participate in a clinical trial was not affected by the level of education or economic status of patients. The most influential factors for patient willingness to participate were a physician recommendation (n=181, 26.8%), limited treatment options (n=178, 26.4%), and expectations of effectiveness of new anti-cancer drugs (n=142, 21.0%). Patients with previous experience in clinical trials had a greater willingness to participate in clinical trials compared to patients without previous experience (p<0.001). CONCLUSIONS: This large patient cohort survey study showed that Korean cancer patients are more aware of clinical trials, but awareness did not translate into willingness to participate.

Effect of switching antipsychotics on antiparkinsonian medication use in schizophrenia: population-based study.

BACKGROUND: The extent to which atypical antipsychotics have a lower incidence of extrapyramidal symptoms than typical antipsychotics has not been well-evaluated in community practice. AIMS: To examine the effects of switching antipsychotics on antiparkinsonian medication use among individuals with schizophrenia in UK general practices. METHOD: We included those switched from typical to atypical antipsychotics (n=209) or from one typical antipsychotic to another (n=261) from 1994 to 1998. RESULTS: Antiparkinsonian drug prescribing dropped by 9.2% after switching to atypical antipsychotics (P<0.0001). Switching to olanzapine decreased the rate by 19.2% (P<0.0001), but switching to risperidone had no impact. After switching from one typical antipsychotic to another, antiparkinsonian drug prescribing increased by 12.9% (P<0.0001). CONCLUSIONS: Reduction in antiparkinsonian medication use after switching to atypical antipsychotics was substantial in community practice but not as large as in randomised controlled trials. The rate of reduction varied according to the type of medication.

Antibiotic use following a Korean national policy to prohibit medication dispensing by physicians.

This study investigated whether a Korean national policy prohibiting doctors from dispensing drugs as of 2000 selectively reduced inappropriate antibiotic prescribing in viral illness compared with bacterial illness. We assessed the proportions of episodes prescribed an antibiotic and the number of different antibiotics prescribed for patients with viral and bacterial illness episodes before and after the policy. The nationally representative sample consisted of 50,999 episodes (18,656 viral and 7758 bacterial pre-policy, 16,736 viral and 7849 bacterial post-policy) from 1372 primary care clinics. We used generalized estimating equations to investigate changes in antibiotic prescribing after the policy, and multiple linear regression to determine provider factors associated with reductions in inappropriate antibiotic prescribing for viral illness. After the dispensing restriction, antibiotic prescribing declined substantially for patients with viral illness (from 80.8 to 72.8%, relative risk (RR) = 0.89, [95% confidence interval: 0.86, 0.91], p<0.001), and only minimally for patients with bacterial illness (from 91.6 to 89.7%, RR = 0.98, [0.97, 0.99], p = 0.017). Reductions in antibiotic prescribing were significantly larger (RR = 0.90, [0.87, 0.93], p<0.001) for patients with viral illness. The number of different antibiotics prescribed per episode also decreased significantly after the policy, but there were no significant differences in these reductions between viral and bacterial illness. The dispensing restriction also reduced prescribing of non-antibiotic drugs, with no difference by diagnosis. Provider factors found to be associated with reduced inappropriate antibiotic prescribing were younger age and practice location in an urban area. Prohibiting doctors from dispensing drugs reduced prescribing overall, both of antibiotics and other drugs, and selectively reduced inappropriate antibiotic prescribing in viral illness.

Knowledge and beliefs of primary care physicians, pharmacists, and parents on antibiotic use for the pediatric common cold.

The aim of this study is to investigate knowledge and beliefs of primary care physicians (e.g. family practitioners and pediatricians), pharmacists, and parents regarding the use of antibiotics for the pediatric common cold, using a self-administered questionnaire for physicians and pharmacists and a telephone interview for parents. This article suggests that parents' expectation for antibiotics is a minor factor, and health care providers' unfounded beliefs in the effectiveness of antibiotics and exaggeration of parents' demand for antibiotics may be the major contributing factor underlying antibiotic over-prescription for the pediatric common cold in Korea. Most physicians and pharmacists knew the correct cause of the pediatric common cold, but majorities of the physicians and pharmacists believed that antibiotics could treat and reduce its complications. On the other hand, 34% of the parents believed that antibiotics could prevent complications. Seventy three per cent of the physicians reported that they perceived expectations for antibiotics from parents, but only 2% of the parents reported asking their physicians for antibiotics. In summary, this study suggests that physicians' knowledge and faulty beliefs can be more important factors for inappropriate antibiotic prescription.

A network of rice genes associated with stress response and seed development.

We used a systematic approach to build a network of genes associated with developmental and stress responses in rice by identifying interaction domains for 200 proteins from stressed and developing tissues, by measuring the associated gene expression changes in different tissues exposed to a variety of environmental, biological, and chemical stress treatments, and by localizing the cognate genes to regions of stress-tolerance trait genetic loci. The integrated data set suggests that similar genes respond to environmental cues and stresses, and some may also regulate development. We demonstrate that the data can be used to correctly predict gene function in monocots and dicots. As a result, we have identified five genes that contribute to disease resistance in Arabidopsis.

Identification of rice (Oryza sativa) proteins linked to the cyclin-mediated regulation of the cell cycle.

Yeast two-hybrid assays were used to identify rice proteins interacting with two rice cyclins and other proteins potentially involved in cell cycling. The DNA sequences encoding 119 protein fragments identified were then compared by BLAST against proteins in GenBank. The proteins found include myosin-like proteins, transcription factors, kinesins, centromere proteins and undefined proteins. Based on interactions with cyclins and other elements required for cycling, we believe the undefined proteins may be involved in associated cycling processes. The identification of proteins involved in cell cycle regulation in rice may allow for the control of agronomic traits involving plant growth or development.

A draft sequence of the rice genome (Oryza sativa L. ssp. japonica).

The genome of the japonica subspecies of rice, an important cereal and model monocot, was sequenced and assembled by whole-genome shotgun sequencing. The assembled sequence covers 93% of the 420-megabase genome. Gene predictions on the assembled sequence suggest that the genome contains 32,000 to 50,000 genes. Homologs of 98% of the known maize, wheat, and barley proteins are found in rice. Synteny and gene homology between rice and the other cereal genomes are extensive, whereas synteny with Arabidopsis is limited. Assignment of candidate rice orthologs to Arabidopsis genes is possible in many cases. The rice genome sequence provides a foundation for the improvement of cereals, our most important crops.