21 / 11 / 12
——Head Lice Infestation: Developing Drugs for Topical Treatment（October 2016）
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page.
bind on是to force sb to do sth by making them promise to do it or by making it their duty to do it 约束；迫使
statute是a law that is passed by a parliament, council, etc. and formally written down 成文法；法令；法规
The purpose of this guidance is to assist sponsors in the clinical development of drugs for the treatment of head lice infestation. Specifically, this guidance addresses the Agency's current thinking regarding the overall development program and clinical trial designs of drugs to support approval of an indication for topical treatment of head lice infestation. The information presented will help sponsors plan clinical trials, design clinical protocols, and conduct and appropriately monitor clinical trials. Development plans should be discussed with the review division before initiating trials to ensure that the trial design meets defined objectives.
and conduct and appropriately monitor，此处的逻辑层级关系很有意思
review division，可以理解为评审部门
In general, FDA's guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.
legally enforceable responsibilities，有人译为“法律强制性职责”，但感觉表达上似乎不妥，暂时考虑“具有法律约束力的...”
Head lice infestation is characterized by infestation of the scalp and scalp hair by a wingless parasitic insect, the human head louse, Pediculus humanus capitis. Head lice live onthe hair and feed on the scalp by consuming a blood meal.
be characterized by，特征系列表达结构
live on，这里似乎可以考虑“寄生”
consume，这词用的实在不赖。参考“Cambridge Advanced Learner's Dictionary”，这个词的意思是“formal. to eat or drink, especially a lot of something ”
There are many FDA-approved drugs (including prescription and nonprescription drugs) for the treatment of head lice infestation, but genetic resistance of lice to lindane and to the most commonly used treatments, pyrethroids, is not uncommon in the United States; thus development of additional drugs for this indication is encouraged.
prescription and nonprescription drugs，处方与非处方药的一个替代表达get
genetic resistance of lice to，genetic resistance一般考虑遗传抗性或者遗传耐药性；resistance of A to B，结构get；第二个to感觉或可省略？暂且全收。
In early phase clinical development the components of the investigational drug should be defined and all active moieties identified. If two or more active components are identified, it should be demonstrated that each active component makes a contribution to the claimed effects and the dosage of each active component is such that the combination is safe and effective for the intended patient population (see 21 CFR 300.50).
moiety，1. a half. 2. an indefinite portion, part, or share.
contribution，“贡献”？似乎可以进一步优化
Head lice infestation is primarily a pediatric disease. Sponsors are encouraged to discuss pediatric drug development with the FDA early in the course of clinical development, including appropriate pharmacokinetic (PK) trials in pediatric subjects to support dose selection and the recommended size of the preapproval safety database in children. Under PREA, a waiver to provide a pediatric assessment may be granted if certain criteria are met. Historically, studies in patients younger than 6 months of age for the treatment of head lice infestation have been waived most often because the studies were impossible or highly impracticable. Under certain circumstances, there may be other reasons for waiver (e.g., there was evidence of lack of meaningful therapeutic benefit over existing treatments and was not likely to be used by a substantial number of patients in that age group or there was strong evidence suggesting the drug is ineffective or unsafe in that age group). If studies for any pediatric age group are waived for safety concerns, the safety concern must be included in product labeling. Sponsors are required to submit an initial pediatric study plan no later than 60 days after an end-of-phase 2 meeting. See the draft guidance for industry Pediatric Study Plans: Content of and Process for Submitting Initial Pediatric Study Plans and Amended Initial Pediatric Study Plans for information regarding the content of and process for submission of an initial pediatric study plan.
in the course of，考虑和during的替换
safety concern
Trials to identify an appropriate (safe and effective) dose are an important component of phase 2 development for topical treatment of head lice infestation. A dose-response trial conducted during early phase clinical development to assess safety and efficacy can help ensure that the most appropriate dose regimen is selected for phase 3 development. For additional information on the FDA's current thinking regarding dose response, see the ICH guidance for industry E4 Dose-Response Information to Support Drug Registration and the guidances for industry Providing Clinical Evidence of Effectiveness for Human Drug and Biological Products and Exposure-Response Relationships — Study Design, Data Analysis, and Regulatory Applications.
help，常见错误之一；用作“帮助”解的时候，help 后面接不定式或宾语和不定式，不可接动名词，如可以说 This book will help to improve your English 和 This book will help you to improve your English。不可说 This book will help improving your English。那不定式的 to 往往省去，如 This book will help improve your English 和 This book will help you improve your English。这种省略在美国比在英国普通。但当 helped 用在被动语态的时候，后面的不定式的 to 不可省去。 例如：You will be helped to improve your English. （参考：《葛传椝英语惯用法词典》）
information，常见表达优化点；on/about sb/sth
Although head lice infestation (P. capitis) is primarily a disease of the pediatric population, it may be appropriate to obtain safety and efficacy data in adults before proceeding with studies in the pediatric population. See the ICH guidance for industry E11 Clinical Investigation of Medicinal Products in the Pediatric Population.
proceeding，涉及逻辑主语相关语法点
If the sponsor plans to conduct trials outside of the United States, the sponsor should consider factors that may affect the acceptability of such data for drug approval in the United States. Sufficient information should be provided to demonstrate that data from clinical trials conducted outside of the United States are applicable to and will predict the clinical outcomes in U.S. patients (see 21 CFR 314.106). See the ICH guidance for industry E5 Ethnic Factors in the Acceptability of Foreign Clinical Data and the guidance for industry Collection of Race and Ethnicity Data in Clinical Trials.
the sponsor，同样考虑到逻辑主语，似乎可以进一步简化
outcomes in U.S. patients，这里的in，值得学习
Both local and systemic safety information (e.g., adverse events and laboratory data) should be collected during clinical trials. All subjects should be evaluated for safety at the time of each trial visit or assessment, regardless of whether the investigational drug has been discontinued for safety. Generally, all adverse events should be followed until resolution, even if time on clinical trial would otherwise have been completed.
at the time of each trial visit or assessment，过往似乎更可能会直接考虑at each trial visit or assessment，此处照单全收
resolution，(Medicine) the disappearance of inflammation, or of any symptom or condition (医)（炎症或其他症状的）消散，消退
Local safety assessment of the skin/scalp (with careful attention to the adjacent skin such as the forehead, neck, and ears) and eyes should include evaluation for the presence of erythema, edema, pustules, excoriation, and a query for pruritus (at baseline and post-treatment visits). This evaluation should occur at intervals most likely to capture any safety signal. The timing of evaluation may be affected by factors such as the type of drug** being studied** and the type of reaction that is expected.
capture，这个词很传神
being study和that is expected两个限定，表达优化
Neurotoxicity: The treatment may achieve efficacy through effects on the insect's nervous system. Systemic absorption of the drug could raise concern about effects on the human nervous system.
A could raise concern about B
Teratogenicity: The risk of teratogenicity should be evaluated. See ICH M3(R2). Measures to reduce the risk for pregnancy exposure should be employed for both caregivers, who administer the investigational drug to pediatric subjects, and subjects who are of reproductive potential.
caregiver，A caregiver is someone who is responsible for looking after another person, for example, a person who is disabled, ill, or very young.
be of adj. potential
For topical drugs, dermal safety studies with the to-be-marketed drug may be needed to provide information regarding cumulative irritancy, contact sensitization, photoxicity, and photo-contact allergic potential.
to-be-marketed drug，总比before/prior to后面balabala强太多了
PK trials to assess systemic absorption may be needed unless there is a waiver of in vivo bioavailability studies, which is rarely granted. Because of the variable dosing nature of topical drugs, the FDA recommends that trials of the in vivo assessment of systemic exposure be done under so-called maximal use conditions. The recommended elements of such a maximal use PK trial are as follows:
这里面的recommend配be，是一个有趣的语法点。
recommend 后面可以接以 that 引导的从句，从句里用虚拟现在式。例如：I recommend that the reader be（不用is）on the lookout for idioms.和 I recommended that the reader be（不用 was）on the lookout for idioms.
The objective of this trial is to maximize those elements affecting dermal penetration to assess systemic bioavailability and systemic safety of the drug. The FDA recommends, when possible, that the resulting PK data be analyzed using standard PK metrics (e.g., area under the concentration versus time curve, maximum concentration (Cmax), time at which Cmax occurs, half-life). It is also recommended that the trial protocols incorporate evaluations for cutaneous safety.
time at which Cmax occurs，替换表达get
Presentation at the treatment site with visible skin/scalp condition(s) that are not** attributable** to head lice infestation and that in the opinion of the investigative personnel will interfere with safety and/or efficacy evaluations
attributable，[not before noun] ~ to sb/sth probably caused by the thing mentioned 可归因于；可能由于
The primary efficacy endpoint should be dichotomized to success or failure with success defined as the absence of live lice and failure defined as the presence of live lice. Specifically, success should be defined as follows:
be dichotomized，一分为二，表达get
the presence/absence of，常见套路
The assessment of presence or absence of live lice should be performed by a trained evaluator, with a minimum agreed-upon time for lice examination in the event that lice are not immediately identified. The actual time spent in examination should be documented on the case report form.
in the event that，if替换词
The use of drugs for the treatment of head lice infestation occurs within the context of an overall lice management program. Trial design should include appropriate instructions to subjects such as:
within the context of，表达get