title: European Union pediatric legislation jeopardizes worldwide, timely future advances in the care of children with cancer.
abstract: BACKGROUND
  Diagnosis of childhood cancer is no longer an automatic death sentence, but it has not lost all of its horror. Drugs, surgery, radiation, and clinical trials have advanced our capacity to handle these cancers, but pediatric cancers still face challenges. Pediatric pharmaceutical legislation was introduced in the United States in 1997 and has triggered many clinical trials that have helped us better understand what drugs do to a child's body and vice versa. Following the US precedence, the European Union introduced its own legislation. The US legislation was designed to generate additional pediatric data and balances between mandatory requirements and voluntary incentives. The US legislation was designed to mandate full registration of all new drugs for children whenever there is any potential pediatric use.
  
  
  OBJECTIVE
  The purpose of this article is to discuss unintended negative consequences of the legislation of the European Medicines Agency (EMA).
  
  
  METHODS
  We analyzed the effects of the EU pediatric legislation with respect to the history of the emergence of modern drugs, pediatric clinical pharmacology, and the development of drugs for pediatric malignancies.
  
  
  RESULTS
  No new drug can be registered in the European Union without a detailed pediatric investigation plan (PIP) approved by the EMA's Pediatric Committee (PDCO). This has moved the discussion of the pediatric aspects of drug development to an earlier stage and has increased public awareness. It also has brought industry and pediatric oncologists closer together. However, in a review of >100 PDCO PIP decisions in childhood cancer, we found a lack of balance between the legitimate desire to include children in drug development and the common sense needed in the complex worlds of drug development and pediatric oncology. Many decisions appeared to have been based on both exaggerated assumptions about the frequency of childhood malignancies and the feasibility of the clinical trials proposed.
  
  
  CONCLUSIONS
  Pharmaceutical companies are being forced into long-term commitments to clinical trials before efficacy in adults has been demonstrated. Pediatric clinical oncology trials are being driven by regulatory "tunnel vision" and not by therapeutic benevolence, epidemiologic data, or feasibility. As a result, children with cancer are being monopolized for PDCO-triggered, often unfeasible trials that are not always in their best interests and seldom produce useful therapies. Because clinical trials are global, this affects children with cancer worldwide. Until now, carefully worded concerns about these negative consequences have been published in specialty journals. It is time to start a broader debate on how to move forward.
authors: klausrose Consulting, Pediatric Drug Development & More, Riehen, Switzerland. Electronic address: Klaus.rose@klausrose.net.
authors: Klaus
authors: K
authors: Rose
mesh_terms: D002626:Chemistry, Pharmaceutical; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000331:legislation & jurisprudence; D004345:Drug Industry / Q000191:economics / Q000331:legislation & jurisprudence*; D005062:European Union / Q000458:organization & administration*; D006801:Humans; D009369:Neoplasms / Q000191:economics / Q000628:therapy; D010372:Pediatrics / Q000331:legislation & jurisprudence* / Q000639:trends; D014481:United States
keywords: European Union; childhood cancer treatments; clinical trial regulations; oncologic drug development; pediatric oncology; pediatric trials