Generic drug approval: A US perspective

Abstract

Objective:

Generic drugs are identical or bioequivalent versions of the brand name drugs. They are the economic alternative of the costlier brand name drugs. This article presents a general overview of the procedure and regulatory aspects relating to generic drug approval in the US.     

Addressing the health technology assessment of biosimilar pharmaceuticals

Abstract

The growing number of biosimilars presents challenges to regulatory and health technology assessment (HTA) systems. This paper illustrates these challenges by focusing on biosimilars used in the oncological setting. In particular, discordances between data required by regulatory and HTA authorities potentially deprive patients of effective treatments and hinder optimal resource allocation. Regulatory and HTA authorities need to harmonize requirements to foster the development and widespread use of biosimilars, which potentially release considerable resources. The authors believe that often-inappropriate methodology creates a very real chance that HTA authorities will reject some biosimilars. This would effectively extend patent protection and, in the absence of competitor pressure from biosimilars, result in prices remaining unnecessarily high. The authors propose that HTA organizations should accept pharmacokinetic and pharmacodynamic equivalence between the brand and the biosimilar as a proxy of biological comparability. HTA organizations should then adopt, in the absence of compelling reasons otherwise, cost-minimization analysis (CMA) as the basis of the cost-effectiveness deliberations. In the absence of adequate studies demonstrating equivalent efficacy, a prerequisite of CMA, HTA organizations should require threshold analysis. Once approved, biosimilar manufacturers and regulators should maintain rigorous pharmacovigilance to exclude immunoreactivity or other rare adverse events. Furthermore, cancer centres and trusts should regularly audit and publish the impact of biosimilars on clinical outcomes and resource use. When appropriate, regulatory and HTA authorities should demand revised cost-effectiveness analyses from biosimilar manufacturers. This approach would hone the accuracy of the cost-effectiveness analyses, protect patients and allow health services rapid access to low cost treatments.     

门诊实名制预约挂号的实践与对策初探

目的 探讨门诊实名制预约挂号的实践意义,为患者就医提供方便.方法 2011年10月开始对本院门诊挂号实施实名制预约挂号方式,为患者提供电话专线、网络预订等多种预约门诊挂号途径,并细化、合理安排专家门诊类型.通过发放问卷,调查2011年10月～2012年10月的患者对实名制预约挂号的了解以及受益情况.结果 ①1年中各季度预约门诊量逐渐提高,201 1年10～12月预约量占总门诊量的14.2％,2012年7～10月初则达到26.1％,预约量明显提高（P＜0.05）,复诊患者的人数占总预约门诊人数的10.1％;②患者对实名制预约挂号和普通挂号区别的认知情况较差,认知度为30.0％,预约方式中患者首选诊间预约（38.3％）,而网络预约选择较少,患者对实名制预约挂号的满意度达71.7％.结论 门诊实名制预约挂号是突破顽固思想的新举动,充分发挥信息时代的优势,解决患者就诊的基本问题,社会效益良好.     

Effectiveness and tolerability of dolutegravir and abacavir/lamivudine administered as two separate pills compared to their equivalent single‐tablet regimen in a multicentre cohort in Spain

IntroductionWe aimed to assess the effectiveness and tolerability of dolutegravir (DTG), abacavir (ABC) and lamivudine (3TC) administered as branded STR (DTG/ABC/3TC) or as two separate pills (DTG and either branded ABC/3TC [DTG+(ABC/3TC)b] or generic ABC/3TC [DTG+(ABC/3TC)g]).MethodsWe included individuals from the multicentre cohort of the Spanish HIV/AIDS Research Network (CoRIS) who received DTG/ABC/3TC, DTG+(ABC/3TC)b or DTG+(ABC/3TC)g during 2015 to 2018. We used multivariable logistic regression to compare the proportion of antiretroviral‐naïve individuals who achieved viral suppression (VS) (viral load ≤50 copies/mL) at 24 weeks of initiating with DTG+(ABC/3TC)b or DTG+(ABC/3TC)g versus DTG/ABC/3TC. We also calculated the proportion of virologically suppressed individuals who maintained VS at 24 weeks after switching from DTG/ABC/3TC to DTG+(ABC/3TC)g.ResultsDuring the study period, 829, 68 and 47 treatment‐naïve individuals started treatment with DTG/ABC/3TC, DTG+(ABC/3TC)b or DTG+(ABC/3TC)g respectively. The proportions of individuals who changed their regimens due to side effects during the first 24 weeks were 3.7%, 4.4% and 6.4% respectively (p = 0.646). We did not find significant differences in VS at 24 weeks among individuals starting with DTG+(ABC/3TC)b or DTG+(ABC/3TC)g compared to those initiating with DTG/ABC/3TC. Among 177 virologically suppressed individuals who switched from DTG/ABC/3TC to DTG+(ABC/3TC)g, 170 (96.0%) maintained VS at 24 weeks.ConclusionsIn naïve individuals, the effectiveness and tolerability at 24 weeks of DTG plus ABC/3TC administered as two separate pills, either as branded or generic ABC/3TC, was similar to the STR DTG/ABC/3TC. Switching the STR DTG/ABC/3TC to its separate components DTG+(ABC/3TC)g in virologically suppressed individuals did not seem to impair its effectiveness.     

The role of the slope of oxygen consumption and EMG activity on freely chosen pedal rate selection

The objective of this study was to verify the following hypothesis: the pedal rate that minimizes root mean square (RMS) slope and the slow component amplitude of oxygen consumption could be close to the freely chosen pedal rate (FCPR) used by well-trained cyclists. Nine male competitive cyclists performed a 21 min submaximal exercise on a cycle ergometer at a workload of 65% of their respective peak aerobic power. For each session, the subject's pedal rate was freely chosen or assigned to 60, 75, 90 or 105 rev min(-1). When pedal rates were imposed, the electromyographic root mean square slope, the oxygen uptake during the third minute and the 20th min, and the slow component amplitude of oxygen consumption were used in the analysis. In order to determine the optimal pedal rate (OPR), a quadratic function was fitted to the data by regression, for each variable measured. The mean values of OPR relative to oxygen uptake during the third min (71+/-9 rev min(-1)) were lower than the mean values of the OPR relative to the slow component amplitude of oxygen consumption (82+/-8 rev min(-1)), the electromyographic root mean square slope (80+/-7 rev min(-1)) and freely chosen pedal rate (86+/-13 rev min(-1)). Freely chosen pedal rate was not significantly different from the OPR in reference to the amplitude of the slow component of oxygen consumption, electromyographic root mean square slope, and oxygen uptake during the 20th min. OPR for RMS slope was correlated (R=0.72) to FCPR. Expert cyclists were likely to use a spontaneous pedal rate that minimizes neuromuscular fatigue.     

高海拔地区官兵实名和匿名心理状况调查结果的差异

目的探讨实名和匿名调查方法测试高海拔地区官兵心理健康状况的准确性。方法采用症状自评量表（SCL-90）对驻守在高海拔地区的两部边防官兵进行实名和匿名心理测试,两部官兵测试结果进行比较,并分别与成人常模比较。结果采用实名心理测试的甲部官兵与成人常模比较,除躯体化因子分值差异无统计学意义（P〉0．05）外,余各项因子分值均明显低于成人常模,差异有统计学意义（P〈0．01）。采用匿名心理测试的乙部官兵与成人常模比较,躯体化、抑郁、焦虑、敌对、恐怖、精神病因子分值明显高于成人常模,人际关系敏感因子分值低于成人常模,差异有统计学意义（P〈0．01,P〈0．05）。采用实名心理测试的甲部官兵SCL-90各项因子所得分值均明显低于采用匿名心理测试的乙部官兵,差异有统计学意义（P〈0．01）。结论对官兵进行实名心理测试可能影响测试准确性,建议高海拔地区官兵采用匿名方法进行心理测试。     

Embolic protection in carotid artery stenting: new options

Carotid artery stenting (CAS) has emerged as an attractive alternative to carotid endarterectomy (CEA) in patients with carotid disease who are at high risk for CEA. With increasing experience and improved technique, results in CAS patients have improved consistently over time in several clinical trials. Carotid stenting is clearly not inferior to CEA in appropriately selected high-CEA-risk patients treated by experienced operators. With improving results, CAS now has the potential to be considered "front-line therapy" even in standard-risk CEA patients, as demonstrated in CREST and as being studied in ongoing trials, such as the ACT I trial. Successful, low-risk CAS can only be performed if distal embolization is minimized during this procedure. This can be accomplished only with appropriate patient and case selection, adequate operator training and experience, and meticulous attention to procedural detail. Embolic protection devices (EPDs) are an important cornerstone of low-risk CAS. There are well-established, study-validated embolic protection systems available for CAS. Four new EPD options have been introduced in the United States over the past 3 years. Results with these newer devices appear to be extremely promising, with low event rates seen in high-risk clinical patients. This article will offer a practical review of techniques to decrease distal embolization during CAS. We will review patient selection and provide a "cookbook" approach to procedural technique, emphasizing techniques unique to each of the various EPD systems currently available. We will also introduce the newer options in EPDs, provide practical tips on their use, and contrast their use and results with that of the existing EPD systems. We will provide practical procedural techniques that incorporate the use of various EPDs into strategies that will reduce distal embolization during CAS and also provide pertinent data referencing results of these devices seen in clinical trials.