• The Regulation mandated the establishment of the European Medicines Agency (EMA)’s Paediatric Committee (PDCO), coordinating the Agency’s work on the development of medicines for children and agreeing to the studies that pharmaceutical companies must carry out as part of Paediatric Investigation Plans (PIPs).

 • The Regulation comprises a system of requirements, obligations, incentives and rewards for completed PIPs, and also waivers and deferrals which provide the framework for either obviating or postponing the institution or completion of studies in some or all of the paediatric population (age < 18 years).

 • The Clinical Trials Regulation (EU) No 536/2014 has further improved the environment for clinical research in the paediatric population, now legally recognising their assent or agreement to clinical trial participation at the European level [25]. This is amongst other provisions to facilitate international research and to ensure quicker access to new, innovative treatments [26].

 • The possibility for PIP requirements beyond studies proposed by companies is limited by the adult condition (cancer type), and cannot be mandated on the basis of the drug’s-MoA. However, as PIPs must specify how research and development is done in patients from all age cohorts < 18 years, sponsors usually include adolescents 12–17 years in paediatric separate studies, rather than including them in relevant adult trials (which cannot be mandated). Adult studies generally recruit patients ≥ 18 years, while paediatric studies often cease recruitment at 18–21 years.

 • As paediatric studies generally start later than studies in adults, there are delays in evaluating new drugs for adolescents, and adult patients with ‘typical paediatric cancers’ are not included in disease-specific ‘paediatric’ trials. Such studies can be proposed by companies, and some have been agreed as part of PIPs (e.g. lenvatinib in an osteosarcoma phase II trial, NCT02432274), while others are executed without being part of a PIP (e.g. ruxolitinib phase III trial in GVHD, NCT02913261).

 • The Regulation mandated the establishment of the European Medicines Agency (EMA)’s Paediatric Committee (PDCO), coordinating the Agency’s work on the development of medicines for children and agreeing to the studies that pharmaceutical companies must carry out as part of Paediatric Investigation Plans (PIPs).

 • The Regulation comprises a system of requirements, obligations, incentives and rewards for completed PIPs, and also waivers and deferrals which provide the framework for either obviating or postponing the institution or completion of studies in some or all of the paediatric population (age < 18 years).

 • The Clinical Trials Regulation (EU) No 536/2014 has further improved the environment for clinical research in the paediatric population, now legally recognising their assent or agreement to clinical trial participation at the European level [25]. This is amongst other provisions to facilitate international research and to ensure quicker access to new, innovative treatments [26].

 • The possibility for PIP requirements beyond studies proposed by companies is limited by the adult condition (cancer type), and cannot be mandated on the basis of the drug’s-MoA. However, as PIPs must specify how research and development is done in patients from all age cohorts < 18 years, sponsors usually include adolescents 12–17 years in paediatric separate studies, rather than including them in relevant adult trials (which cannot be mandated). Adult studies generally recruit patients ≥ 18 years, while paediatric studies often cease recruitment at 18–21 years.

 • As paediatric studies generally start later than studies in adults, there are delays in evaluating new drugs for adolescents, and adult patients with ‘typical paediatric cancers’ are not included in disease-specific ‘paediatric’ trials. Such studies can be proposed by companies, and some have been agreed as part of PIPs (e.g. lenvatinib in an osteosarcoma phase II trial, NCT02432274), while others are executed without being part of a PIP (e.g. ruxolitinib phase III trial in GVHD, NCT02913261).

 •该法规要求建立欧洲药品管理局（EMA）的儿科委员会（PDCO），协调该机构在开发用于儿童的药物方面的工作，并同意制药公司必须将其作为儿科调查计划的一部分进行的研究（PIP）。

 •该法规包括对已完成的PIP的要求，义务，激励和奖励制度，以及豁免和延期制度，这些制度为避免或推迟部分或全部儿科人口（年龄<18岁）的研究或完成研究提供了框架年）。

 •第536/2014号临床试验条例（EU）进一步改善了儿科人群的临床研究环境，目前在法律上承认他们同意或同意在欧洲进行临床试验[25]。这是促进国际研究并确保更快地获得新的，创新的治疗方法的其他规定之一[26]。

 •公司提出的超出研究范围的PIP要求的可能性受到成人状况（癌症类型）的限制，并且不能基于药物的MoA强制规定。但是，由于PIP必须指定在18岁以下的所有年龄组的患者中如何进行研究和开发，因此申办者通常将12-17岁的青少年纳入儿科单独研究中，而不是将其纳入相关的成人试验中（这不是强制性的）。成人研究通常招募≥18岁的患者，而儿科研究通常在18-21岁时停止招募。

 •由于儿科研究通常开始于成人研究，因此对青少年的新药评估存在延迟，并且患有“典型儿科癌症”的成年患者不包括在特定疾病的“儿科”试验中。此类研究可以由公司提出，一些已经作为PIP的一部分达成了共识（例如，骨肉瘤II期试验中的lenvatinib，NCT02432274），而其他一些研究却没有成为PIP的一部分（例如，GVHD中的鲁索替尼III期试验，NCT02913261）。 ）。

 •该法规要求建立欧洲药品管理局（EMA）的儿科委员会（PDCO），协调该机构在开发用于儿童的药物方面的工作，并同意制药公司必须将其作为儿科调查计划的一部分进行的研究（PIP）。

 •该法规包括对已完成的PIP的要求，义务，激励和奖励制度，以及豁免和延期制度，这些制度为避免或推迟部分或全部儿科人口（年龄<18岁）的研究或完成研究提供了框架年）。

 •第536/2014号临床试验条例（EU）进一步改善了儿科人群的临床研究环境，目前在法律上承认他们同意或同意在欧洲进行临床试验[25]。这是促进国际研究并确保更快地获得新的，创新的治疗方法的其他规定之一[26]。

 •公司提出的超出研究范围的PIP要求的可能性受到成人状况（癌症类型）的限制，并且不能基于药物的MoA强制规定。但是，由于PIP必须指定在18岁以下的所有年龄组的患者中如何进行研究和开发，因此申办者通常将12-17岁的青少年纳入儿科单独研究中，而不是将其纳入相关的成人试验中（这不是强制性的）。成人研究通常招募≥18岁的患者，而儿科研究通常在18-21岁时停止招募。

 •由于儿科研究通常开始于成人研究，因此对青少年的新药评估存在延迟，并且患有“典型儿科癌症”的成年患者不包括在特定疾病的“儿科”试验中。此类研究可以由公司提出，一些已经作为PIP的一部分达成了共识（例如，骨肉瘤II期试验中的lenvatinib，NCT02432274），而其他一些研究却没有成为PIP的一部分（例如，GVHD中的鲁索替尼III期试验，NCT02913261）。 ）。