• 응용통계연구
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• 제24권3호
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• pp.495-503
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• 2011

When a patent of an innovative (brand-name) small-molecule drug expires, generic copies of the innovative drug may be marketed if their therapeutic equivalence to the innovative drug has been shown. The small-molecule drugs are considered therapeutically equivalent and can be used interchangeably if two drugs are shown to be pharmaceutically equivalent with identical active substance and bioequivalent with comparable pharmacokinetics in a crossover clinical trial. However, the therapeutic equivalence paradigm cannot be applied to biosimilars since the active ingredients of biosimilars are huge molecules with complex and heterogeneous structures, and these molecules are difficult to replicate in every detail. The European Medicine Agency(EMEA) has introduced a regulatory biosimilar pathway which mandates clinical trials to show therapeutic equivalence. In this paper, we discuss statistical considerations in the design and analysis of biosimilar cancer clinical trials.

• 한국임상약학회지
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• 제27권2호
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• pp.105-112
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• 2017

Background: Generic medications are approved on the basis of bioequivalence with brand medications in healthy volunteers rather than the target population, there remains a substantial uncertainty regarding their clinical effectiveness and safety. The object of this paper is to compare the clinical equivalence of generic statin drugs in patients. Methods: Literature published before September 2016, which is indexed in PubMed, EMBASE, RISS, comparing generic to brand products in statins. Outcomes included blood lipid level, proportion of days covered (adherence), hospitalization and mortality. Results: 511 citations were screened, of which 11 studies met eligibility criteria (6 randomized clinical trials, 5 observational studies). Generic atorvastatin was clinical equivalent with brand drugs in blood lipid level (3 RCTs) and generic simvastatin was also clinical equivalent with brand drugs (2 RCTs). 2 of 3 studies reported no significant difference in proportion of days covered except 1 study which reported generic statin significantly enhance proportion of days covered (p<0.001). Hospitalization was no significant difference in all studies (p>0.05). 1 study reported that all cause of mortality was significantly low in generic drugs (p<0.0001). Conclusion: Published data on comparing clinical efficacy of generic and brand statins were insufficient in both quantity and quality. This systematic review suggests that additional studies on clinical equivalence and safety of generic medications in patients would be needed.

• 한국임상약학회지
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• 제16권2호
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• pp.96-100
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• 2006

Korea Food and Drug Administration (KFDA) has been expediting the Biological Equivalence Examination (BEE) project to encourage generic substitution without expense of inappropriate therapeutic outcome. However, little is known about which considerations are most important in making the decision to prescribe a drug among many generic drugs. The purpose of this survey was to identify how strongly the KFDA certification of BEE influenced doctors when they make a choice between brand and generics of glimepiride preparations. Telephone survey was performed towards doctors working at local clinics by using a questionnaire. Most influential factor to doctors' decision was drug cost followed by pharmaceutical representatives, therapeutic efficacy, and review guideline for reimbursement. Advertisement of the drug was the least influential followed by KFDA certification of BEE. The meaning of BEE was best understood by relatively young doctors with specialty in surgical parts. This survey result further indicated that the doctors considered the therapeutic equivalence examination a preferred measure to expedite generic substitution.

• 한국임상약학회:학술대회논문집
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• 한국임상약학회 2007년도 추계학술대회
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• pp.170-170
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• 2007

• Communications for Statistical Applications and Methods
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• 제22권4호
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• pp.389-399
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• 2015

It is important not to overcalculate sample sizes for clinical trials due to economic, ethical, and scientific reasons. Kang and Kim (2014) investigated the accuracy of a well-known sample size calculation formula based on the approximate power for continuous endpoints in equivalence trials, which has been widely used for Development of Biosimilar Products. They concluded that this formula is overly conservative and that sample size should be calculated based on an exact power. This paper extends these results to binary endpoints for three popular metrics: the risk difference, the log of the relative risk, and the log of the odds ratio. We conclude that the sample size formulae based on the approximate power for binary endpoints in equivalence trials are overly conservative. In many cases, sample sizes to achieve 80% power based on approximate powers have 90% exact power. We propose that sample size should be computed numerically based on the exact power.

• 한국임상약학회지
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• 제16권2호
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• pp.139-146
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• 2006

Objectives: Bio-equivalence(BE) test is important not only to ensure the quality of generic drugs, but also to promote drug substitution under the separation of prescribing and dispensing practice(SPD). This study was intended to investigate the perception of consumers, doctors, and pharmacists on the confidence of bio-equivalence(BE) assured drugs. Methods: Nation-wide telephone interview survey was conducted for 1,018 consumers, 800 doctors, and 806 pharmacists from September to October in 2003. Descriptive analysis and ${\chi}^2$ analysis were conducted. Results: Even though people showed higher confidence level for the Bioequivalent drugs compared with Bio-inequivalent drugs, the confidence was generally low. Among those asked about the therapeutic substitutability of original drugs by BE versions, 95.78% of pharmacists responded "positive", while only 39.33% of consumers and 31.13% of doctors said so. The elderly, the less educated, who takes chronic disease medicine, pays high cost of prescription drugs, and are in the low income responded less aware of that. Also most consumers got information such as effect of drugs from either media or doctors. Conclusions: In order for people to believe that BE drugs and original drugs are equivalent, we need to strengthen health education, and to clarify any misunderstanding. It is also necessary for the national policy to provide accurate information about drugs to the public.

• 응용통계연구
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• 제21권5호
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• pp.867-873
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• 2008

임상시험의 자료에 대하여 통계적 검정을 실시하는 경우 유의수준 5%를 사용하는 것이 관례이다. 하지만 동등성 시험을 신뢰구간을 사용하여 검정하는 경우, 신뢰도 90%인 신뢰구간이 사용되고 있다. 흔히 신뢰도 $1-{\alpha}$인 신뢰구간을 검정에 사용하는 경우, 그 검정법의 유의수준은 ${\alpha}$이다. 이 때문에 동등성 검정에서 신뢰도 90%인 신뢰구간을 사용하게 되면, 유의수준은 10%가 되는 것이 아닌가 하는 혼란을 일으켰다. 본 논문에서는 이와 관련된 이슈들을 관련 문헌의 검토와 시뮬레이션을 통하여 명확하게 하여, 제약회사, CRO, 대학병원 등에 종사하는 통계전문가들에게 도움을 주고자 한다.

• 한국전문물리치료학회지
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• 제22권4호
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• pp.51-61
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• 2015

The purpose of this study were to translate the Fullerton Advanced Balance (FAB) scale into Korean and to verify the content validity by utilizing a back-translation method with a view to assessing balance function and the risk of falling in a clinical research setting. This research was conducted in six steps. First, three Korean physical therapists translated the FAB scale into Korean. Second, two bilingual professors of physical therapy and a physical therapist evaluated translation conformity of Korean-translated FAB scale. In the third and fourth steps, twelve physical therapists evaluated the degree of translation comprehension, and a translator back-translated the Korean FAB scale into the original language. Fifth, a bilingual professor of physical therapy and two native speakers evaluated the technical and conceptual equivalence between the original and translation versions. In this process, inappropriate translated items were revised using recommended substitute words or sentences, and all items were evaluated on the basis of three points or more on a rating scale in terms of translation comprehension, and the technical and conceptual equivalence of the back-translation. In the sixth and last step, the translation verification committee completed the final Korean version. The above process indicated that the content validity of the Korean-translated FAB scale was established by means of systematic translation methods, and it can therefore be used to assess balance function and the risk of falls in a clinical research setting.

• 한국임상약학회지
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• 제15권2호
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• pp.82-88
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• 2005

A new medical system was started in Korea in 2000 and pharmaceutical affairs law was revised in 2001. According to the revised law, generic substitution is permitted only to therapeutically equivalent generic product. Bioequivalence studies are usually used to demonstrate therapeutic equivalence between reference listed drugs and generic drugs. The issues that are recently heating up in Korea are to increase bioequivalent drug products and at the same time to ensure the credibility of the therapeutic equivalence of generic drugs. Sometimes food can change the bioavailability (BA) of a drug and influence the bioequivalence (BE) between test and reference products as well. Food effects on BA can have clinically significant consequences. Food can alter BA by various means including delaying gastric emptying, stimulating bile flow and changing gastointestinal pH. This paper provides the recently published Korean guideline on food-effect BA and fed BE studies.

• 응용통계연구
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• 제25권1호
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• pp.125-138
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• 2012

최근 들어 바이오시밀러에 대한 국내외 관심이 매우 증가하고 있다. 바이오시밀러가 오리지널 생물의약품과 효능과 안전성이 유사함을 보이기 위해서는 최종적으로 임상시험을 수행하여야 한다. 본 논문에서는 이러한 임상시험의 수행과 통계적 분석에 필요한 여러 방법들과 외국의 사례 그리고 관련된 가이드라인들을 살펴볼 것이다.