Do Cost-Effectiveness Analyses Account for Drug Genericization? A Literature Review and Assessment of Implications

ObjectivesWe investigated how health technology assessment (HTA) organizations around the world have handled drug genericization (an allowance for future generic drug entry and subsequent drug price declines) in their guidelines for cost-effectiveness analyses (CEAs). We also analyzed a large sample of published CEAs to examine prevailing practices in the field.MethodsWe reviewed 43 HTA guidelines to determine whether and how they addressed drug genericization in their CEAs. We also selected a sample of 270 US-based CEAs from the Tufts Medical Center’s CEA Registry, restricting the sample to studies on pharmaceuticals published from 1991 to 2019 and to analyses taking a lifetime time horizon. We determined whether each CEA examined genericization (and if so, whether in base case or sensitivity analyses), and how inclusion of genericization influenced the estimated incremental cost-effectiveness ratios.ResultsFourteen (33%) of the 43 HTA guidelines mention genericization for CEAs and 4 (9%) recommend that base case analyses include assumptions about future drug price changes due to genericization. Most published CEAs (95%) do not include assumptions about future generic prices for intervention drugs. Only 2% include such assumptions about comparator drugs. Most studies (72%) conduct sensitivity analyses on drug prices unrelated to genericization.ConclusionsThe omission of assumptions about genericization means that CEAs may misrepresent the long run opportunity costs for drugs. The field needs clearer guidance for when CEAs should account for genericization, and for the inclusion of other price dynamics that might influence a drug’s cost-effectiveness.     

对建立我国仿制药注册审批管理配套制度的探讨

为配合新版《药品注册管理办法》的有效实施，有效借鉴国际上仿制药的审批管理经验，提出了我国仿制药注册审批管理亟需建立的配套制度，并对建立的方式进行了讨论。     

Differing attitudes of industry and academia towards controlled clinical trials

A consensus conference was held in 1984 on controversial issues concerning controlled clinical trials. Thirty-six individuals working in academic institutions, forty-six in industry and twelve in regulatory authorities participated. Academics accepted and industrial representatives rejected the following: existing regulations cannot cope with the rate at which new treatments develop; drug companies may be reluctant to undertake surveillance programmes because sales will fall if adverse reactions are detected; novel remedies should not be promoted before extensive post-marketing surveillance; third parties should finance trials promising to reduce the costs of illness and trialists should be separated from sponsors in data analysis and interpretation, the investigator owning the data unless stated otherwise. Industrial representatives supported and academics rejected the following: government price control inhibits drug development and a multicentre trial can be justified simply by the wish to speed drug registration.     

对建立我国仿制药注册审批管理配套制度的探讨

为配合新版《药品注册管理办法》的有效实施,有效借鉴国际上仿制药的审批管理经验,提出了我国仿制药注册审批管理亟需建立的配套制度,并对建立的方式进行了讨论。     

Biosimilars: it's not as simple as cost alone

Background: Biosimilars or follow‐on biologics (FoB) are biopharmaceuticals that, unlike small molecule generic products, are copies of larger, much more complex proteins. As such, data generated from one biopharmaceutical cannot be extrapolated to another. Unlike small molecule generics, FoB require a full developmental programme, albeit smaller than for an originator product. This has been recognized by European regulatory authorities and it is becoming clear that accelerated processes for FoB marketing approval are not feasible. Objective: To determine the balance between costs surrounding FoB (including relatively extensive developmental programmes and subsequent price to the market) and the necessity to ensure efficacy and safety. Principal findings: It is important that FoB are sufficiently tested to ensure patient safety is not compromised. Conducting such a development programme followed by sound pharmacovigilance is very challenging and costly. Conclusions: Cost‐savings associated with FoB may be limited.     

In vitro disintegration studies of weekly generic and branded risedronate sodium formulations available in Canada

Abstract

Objective:

The aim of this study was to evaluate the in vitro disintegration of the five newly available Canadian generic risedronate 35?mg tablets compared to the innovator (branded) product, ACTONEL (risedronate sodium) 35?mg.     

速释口服固体制剂人体生物等效性试验豁免药学研究的要求

随着科学认知的不断深入,为缩短药品的批准上市时间,不同药品监管机构相继出台了人体生物等效性豁免的相关法规及技术文件,旨在通过体外研究来替代体内试验。总结和比较国内外相关指导原则对速释口服固体剂型的仿制药药学研究的要求,重点关注存在的差异之处,探讨背后的科学原因,并在最终经国际人用药品注册技术协调委员会协调一致的过程中得到思考和启示,以期增加仿制药被豁免体内试验的成功率、进而降低仿制药的开发成本,但同时亦能保证其质量和疗效与参比制剂一致,真正实现其临床可替代性。     

On assessing bioequivalence and interchangeability between generics based on indirect comparisons

As more and more generics become available in the market place, the safety/efficacy concerns may arise as the result of interchangeably use of approved generics. However, bioequivalence assessment for regulatory approval among generics of the innovative drug product is not required. In practice, approved generics are often used interchangeably without any mechanism of safety monitoring. In this article, based on indirect comparisons, we proposed several methods to assessing bioequivalence and interchangeability between generics. The applicability of the methods and the similarity assumptions were discussed, as well as the inappropriateness of directly adopting adjusted indirect comparison to the field of generics' comparison. Besides, some extensions were given to take into consideration the important topics in clinical trials for bioequivalence assessments, for example, multiple comparisons and simultaneously testing bioequivalence among three generics. Extensive simulation studies were conducted to investigate the performances of the proposed methods. The studies of malaria generics and HIV/AIDS generics prequalified by the WHO were used as real examples to demonstrate the use of the methods. Copyright © 2017 John Wiley & Sons, Ltd.     

Pharmaceutical Pricing in Emerging Markets: Effects of Income,Competition, and Procurement

This paper analyzes determinants of ex‐manufacturer prices for originator and generic drugs across countries. We focus on drugs to treat HIV/AIDS, TB, and malaria in middle and low‐income countries (MLICs), with robustness checks to other therapeutic categories and the full income range of countries. We examine the effects of per capita income, income dispersion, competition from originator and generic substitutes, and whether the drugs are sold to retail pharmacies versus tendered procurement by non‐government organizations. The cross‐national income elasticity of prices is 0.27 across the full income range of countries but is 0.0–0.10 between MLICs, implying that drugs are least affordable relative to income in the lowest income countries. Within‐country income inequality contributes to relatively high prices in MLICs. Although generics are priced roughly 30% lower than originators on average, the variance is large. Additional generic competitors only weakly affect prices, plausibly because generic quality uncertainty leads to competition on brand rather than price. Tendered procurement that imposes quality standards attracts multinational generic suppliers and significantly reduces prices of originator and generic drugs, compared with their respective prices to retail pharmacies. ©2013 The Authors. Health Economics Published by John Wiley & Sons Ltd.