also encompasses clinicians who consider available evidence about drug safety and effectiveness as they care for children. Parents have a role, too, including in drug research when they administer test drugs or placebos at home and keep diaries or other records necessary for the assessment of safety and efficacy outcomes.

This chapter discusses selected aspects of FDA’s assessments of the safety and efficacy of drugs and biologics based on data from pediatric studies requested under BPCA or required under PREA. For safety, these aspects include reviewer conclusions about overall safety signals, risk-benefit assessments, and extrapolation of safety and findings of the 1-year safety reviews first required in BPCA of 2002. For efficacy, the discussion focuses on the use of alternative endpoints and extrapolation.


The most comprehensive perspective on the pediatric study data submitted by sponsors and evaluated by FDA is provided in the clinical reviews prepared by staff of the Center for Drug Evaluation and Research (CDER) or the Center for Biologics Evaluation and Research (CBER). For this report, these reviews were the primary source of information on the characteristics and findings of pediatric studies conducted under BPCA or PREA. The committee also consulted clinical pharmacology and statistical reviews (if any), product labeling, and letters describing FDA’s approval action and any further requirements (e.g., further pediatric studies). FDA managers may prepare memoranda that provide additional context for decisions or explain why a reviewer’s recommendations were not accepted. For some labeling changes, the committee consulted minutes from FDA advisory committee meetings.

Following congressional directives described in Chapter 3, CDER and CBER now post the reviews for products approved on or after September 27, 2007.1 For products approved earlier, clinical and other reviews are posted for a few products, but the committee had to request that FDA make public the reviews for most products approved before September 2007. (Appendix A describes how the committee selected the sample of requests, studies, and labeling changes assessed in this report.)

As described by CDER, the clinical review (sometimes called the medical review) is a “comprehensive summary and analysis of the clinical data


1 For CDER and CBER respectively, the reviews posted after September 26, 2007, are at and

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