1. Drug approval and early benefit assessment in Germany
1. 德国药品审批和早期效益评估

If a pharmaceutical company wants to market a new prescription drug in Germany, the drug is subject to two procedures:
如果一家制药公司想在德国销售新处方药，该药物将经历两个程序：

• drug approval (also called marketing authorization) in order to be allowed to sell the drug in Germany, with coverage of costs by the statutory health insurance (SHI) funds, and
  药品审批（也称为市场授权），以便在德国销售该药物，并由法定健康保险（SHI）基金承担费用，
• early benefit assessment, which is used to determine the extent of coverage by the SHI funds after the first six months.
  以及早期效益评估，用于确定 SHI 基金在头六个月后的覆盖范围。

If a pharmaceutical company or a group of researchers wishes to market a drug or make it available to the public, it must first apply for approval, i.e. a regulatory permit to place this drug on the market. Approval is not required if the product belongs to one of the following groups (see 4. Particular therapeutic systems and traditional drugs):
如果一家制药公司或一组研究人员希望将药物推向市场或向公众提供，他们必须首先申请批准，即获得将此药物投放市场的监管许可。如果产品属于以下任何一类（见第 4 部分：特定的治疗系统和传统药物），则无需批准：

• food and dietary supplements,
  食品和膳食补充剂
• cosmetic products or   化妆品产品
• homeopathic and other remedies of so-called "particular therapeutic systems"
  家 opathic 和其他所谓的“特定治疗系统”的补救措施

Depending on where the drug is to be marketed, there are four procedural routes within the EU to apply for approval:
根据药物的市场定位，欧盟内部有四种程序途径可以申请批准：

• the national procedure - to market a drug only in Germany,
  国家程序 - 仅在德国上市药物
• two decentralized procedures - to market a drug in some EU countries, and
  两个分散的程序——在欧盟一些国家销售药物，和
• the centralized procedure - to market a drug in all countries of the European Economic Area (EEA).
  欧洲经济区（EEA）所有国家集中审批程序——在所有 EEA 国家上市药品。

Until 1995, national procedures were the most common ways to market a drug in a country. Since the introduction of the centralized EU procedure, however, they have played a less important role. In addition, if a new drug belongs to a certain group of drugs, the centralized route is mandatory. This applies to new drugs for cancer, neurodegenerative diseases, diabetes, HIV, viral diseases in general, autoimmune diseases, other immune deficiencies, and rare diseases.
直到 1995 年，国家程序是该国上市药品最常见的方式。然而，自从引入集中欧盟程序以来，它们的作用已经降低。此外，如果一种新药属于某些药物类别，则必须采用集中途径。这适用于针对癌症、神经退行性疾病、糖尿病、HIV、病毒性疾病、自身免疫性疾病、其他免疫缺陷和罕见疾病的新药。

If a company wishes to market a drug that does not belong to the above group only in Germany, it submits the documents supporting approval to the corresponding national authority, the Federal Institute for Drugs and Medical Devices (BfArM) or the Paul Ehrlich Institute (see "5. The institutions").
如果一家公司希望仅在德国上市不属于上述类别的药品，它应将支持批准的文件提交给相应的国家机构，即联邦药品和医疗器械研究所（BfArM）或保罗·埃里希研究所（见“5. 机构”）。

If, besides in Germany, a pharmaceutical company wants to market its drug in some other countries within the EU, one of two decentralized procedures apply: the Decentralized Procedure (DCP) if the drug has not yet been approved in any EU country or the Mutual Recognition Procedure (MRP) if the drug has already been approved in an EU country.
如果除了德国之外，一家制药公司希望在欧盟的其他国家销售其药物，则适用两种分权程序之一：如果药物尚未在任何欧盟国家获得批准，则适用分权程序（DCP）；如果药物已在欧盟国家获得批准，则适用相互认可程序（MRP）。

In the DCP, an application for approval is submitted in the target countries with an identical dossier. In the MRP, the regulatory authorities of the other countries review the regulatory dossier of the country that has already granted approval and grant approval on this basis.
在 DCP 中，在目标国家提交一个相同的档案的申请以获得批准。在 MRP 中，其他国家的监管机构审查已获得批准的国家提交的监管档案，并据此批准。

If a pharmaceutical company wants to market its drug in the whole EU and the other countries of the EEA (Liechtenstein, Iceland, Norway), it contacts the European Medicines Agency (EMA) with regard to the central authorization procedure.
如果一家制药公司希望在欧盟以及欧洲经济区（列支敦士登、冰岛、挪威）的其他国家销售其药物，它将联系欧洲药品管理局（EMA）以获取中央授权程序。

Beyond these regular approval procedures, there are alternative pathways for faster approvals (e.g. emergency approvals) or approvals for special circumstances (e.g. for rare diseases).
除了这些常规的批准程序之外，还有针对更快批准（例如紧急批准）或针对特殊情况的批准（例如罕见疾病）的替代途径。

What is examined? In the approval process, the drug has to pass three hurdles, as the following features of a drug are examined:
审查内容有哪些？在审批过程中，药物必须通过三个关卡，以下是对药物特征的审查：

• pharmaceutical quality  药品质量
• safety  安全
• efficacy and tolerability.
  效力和耐受性。

Mandatory tests must be performed to verify pharmaceutical quality. Safety, efficacy and tolerability are determined in studies, ranging from simple laboratory tests in a test tube, to animal experiments, to clinical trials with initially only a few participants, and finally to large clinical trials with many hundreds or thousands of participants in test and control groups (phases 1 to 3).
必须进行强制性测试以验证药品质量。安全性、效力和耐受性通过研究确定，研究范围从试管中的简单实验室测试，到动物实验，再到最初只有少数参与者的临床试验，最后到测试组和对照组有数百或数千名参与者的大型临床试验（第 1 至 3 期）。

The definition of safety is inconsistent in the various national and international laws and regulations. In the context described here, we understand "safety" to mean the elimination of harmful drugs in preclinical testing and call the acceptability of side effects shown in clinical trials "tolerability".
在各种国家和国际法律法规中，安全性的定义并不一致。在此所述的背景下，我们将“安全性”理解为在临床前试验中消除有害药物，并将临床试验中显示的副作用的可接受性称为“耐受性”。

If the studies show that the benefits outweigh the risks, approval is granted. Whether a drug is more effective or, for example, has fewer side effects than other drugs already on the market plays no role in the approval process. It is sufficient if the drug is better than a placebo (a dummy drug) in controlled trials, or at least is no worse than a standard drug that has been shown to be better than placebo. The extent of benefit only becomes important in the second step, the early benefit assessment. Then, in Germany, it is examined whether the new drug helps patients better than the standard treatment, i.e. whether it has an added benefit.
如果研究显示益处大于风险，则授予批准。药物是否比市场上已有的其他药物更有效，或者例如副作用更少，在审批过程中不起作用。只要药物在对照试验中比安慰剂（一种假药）更有效，或者至少与已被证明比安慰剂更有效的标准药物相当，就足够了。益处的程度只有在第二步，即早期益处评估中才变得重要。那时，在德国，将检查新药是否比标准治疗更好地帮助患者，即它是否具有额外的益处。

A drug that passes the approval procedure is approved for five years. After that, the pharmaceutical company can apply for an extension, which is unlimited, provided there are no safety concerns. The cost of the drug is covered by the SHI funds from the time of approval. For the first six months, the price of the drug is set by the pharmaceutical company alone.
通过审批程序的药品获得五年批准。之后，制药公司可以申请延期，延期无限期，前提是没有安全担忧。药品费用从批准时起由 SHI 基金承担。在前六个月内，药品价格由制药公司单独设定。

New drugs are usually more expensive than drugs already established on the market; pharmaceutical companies usually justify this with the high development costs and better performance of these new drugs compared to the existing ones. However, the budgets of health care systems are limited and there have always been reasonable doubts as to whether new drugs are per se better than those on the market. Therefore, on 1 January 2011, a procedure was introduced in Germany based on the Act on the Reform of the Market for Medicinal Products (AMNOG), in which the actual patient-relevant benefit of a new drug is compared with that of an established drug or treatment strategy.
新药通常比市场上已经确立的药物更贵；制药公司通常用这些新药与现有药物相比的高开发成本和更好的性能来为其辩护。然而，卫生保健系统的预算是有限的，并且始终存在合理的怀疑，即新药本身是否比市场上的药物更好。因此，2011 年 1 月 1 日，德国根据《药品市场改革法》（AMNOG）引入了一项程序，该程序将新药的实际患者相关效益与已确立的药物或治疗方案进行比较。

On the basis of this comparison, a decision is then made as to which price will be covered by the SHI funds. This benefit assessment is referred to as an "early" benefit assessment because it is conducted immediately after market launch in Germany.
在此比较的基础上，然后决定由 SHI 基金承担的价格。这种效益评估被称为“早期”效益评估，因为它是在德国上市后立即进行的。

For the early benefit assessment, the pharmaceutical company must submit a comprehensive dossier to the Federal Joint Committee (G-BA) no later than the time of first marketing in Germany. In this dossier, the pharmaceutical company must demonstrate the patient-relevant added benefit of the new drug in comparison with an established drug. This is done based on data from published and unpublished clinical trials on the new drug. In addition, the dossier contains estimates on the annual number of patients potentially benefiting from the new drug as well as the projected annual drug costs.
对于早期效益评估，制药公司必须在德国首次上市时最迟向联邦联合委员会（G-BA）提交一份全面的文件。在该文件中，制药公司必须证明与已上市药物相比，新药对患者相关的额外益处。这是基于新药已发表和未发表的临床试验数据进行的。此外，该文件还包含对新药可能受益的年度患者数量的估计以及预计的年度药物成本。

The G-BA transfers the dossier to IQWiG, which uses these documents to conduct a comparison between the new and established drug. The entire process follows a strict timetable; the process must be completed after one year, or after 15 months at the latest.
G-BA 将文件转交给 IQWiG，IQWiG 使用这些文件对新药与已上市药物进行比较。整个过程遵循严格的日程安排；整个过程必须在一年内完成，最迟在 15 个月内完成。

Depending on which added benefit the G-BA assigns to the new drug (e.g. reduced mortality or improved quality of life), the cost of a new drug in Germany that will be covered by the SHI funds is then determined in price negotiations between the SHI bodies and the pharmaceutical company. The extent of the added benefit is graded in ascending order by
根据 G-BA 为新药分配的附加效益（例如，降低死亡率或提高生活质量），德国将由 SHI 基金支付的新药成本将在 SHI 机构和制药公司之间的价格谈判中确定。附加效益的程度按升序分级，

• minor (lowest extent),   微小（最低程度）
• considerable (medium extent) and
  重大（中等程度）和
• major (highest possible extent).
  重大（最高可能程度）。

If the assessment does not show an added benefit (either because it is not proven in the studies or because the data are insufficient for a meaningful comparison), the drug can remain on the market. However, the cost will only be covered at the reference price set for this group of drugs or at a cost (for one year of treatment) that is not allowed to be higher than the cost of standard treatment. In general, therefore, a new drug with no added benefit is not allowed to cost more than standard treatment.
如果评估未显示额外益处（无论是由于研究未证明，还是因为数据不足以进行有意义的比较），该药物可以继续在市场上销售。然而，其费用只能按照为该类药物设定的参考价格或不超过标准治疗费用的费用（一年治疗费用）来报销。因此，通常情况下，没有额外益处的药物不允许比标准治疗费用更高。

The fact that no added benefit has been proven does not necessarily mean that the new price is necessarily lower than the price previously set by the pharmaceutical company if the comparator drug was already able to achieve a high price due to patent protection.
事实表明没有证明额外的益处并不一定意味着新价格必然低于制药公司之前设定的价格，如果比较药物由于专利保护已经能够实现高价。

Current and past benefit assessments are documented on the G-BA website.
当前和过去的效益评估在 G-BA 网站上均有记录。