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Vol. 7, No. 8, August 2011 “Can You Handle the Truth?” EMA Pediatric Trial Results Due August 31, 2011
By Barbara Godlew
In March 2011, the European Medicines Agency (EMA) unveiled the EU Clinical Trials Register (www.clinicaltrialsregister.eu) for protocol-related information from ongoing trials in pediatric and adult populations. On May 20, 2011, the EMA further required the submission of clinical trial results from pediatric trials for release to the public. It referenced Article 45 Regulation No 1901/20061 when it sent a notification letter to pharmaceutical and medical device companies setting a deadline of August 31, 2011. This new requirement may be in response to calls for greater transparency. It also follows on the heels of a recent article in the British Medical Journal that criticizes the EMA’s apparent lack of transparency.2 EMA has given industry and academia less than four months to submit the data. Some may not be aware of the urgency of the situation. The European Commission may authorize EMA assess fines for delinquent submissions. Since the enactment of the European Clinical Trials Directive (Directive 2001/20/EC)3 in 2001, which governs public access to clinical trial information in the European Community, researchers and patient advocacy groups have stepped up requests for increased transparency of clinical trial data. In many cases, this data has not been available from the EMA because of its concerns. Further, it often has been locked up in complex industry and academic software systems and databases that are not conducive to data export. Indeed, a recent article in the British Medical Journal detailed two Danish researchers’ three-year dialogue with the EMA to obtain access to the clinical study reports and corresponding protocols for 15 placebo-controlled trials of two anti-obesity drugs.4 In the article, Peter Gøtzsche and Anders Jørgensen describe the challenges they faced in getting access to unpublished trial reports from the EMA for the drugs rimonabant and orlistat. Rimonabant (Acomplia, Sanofi-aventis) encountered numerous regulatory hurdles in the United States prior to Sanofi-aventis withdrawing the associated new drug application. It was withdrawn from the European market in 2008 following disclosure of information related to the risk of psychiatric adverse events, including suicidality.5 Orlistat (Xenical, Roche; alli, GlaxoSmithKline) has also faced post-approval challenges, with patient advocacy groups calling for its withdrawal from the market.6 Gøtzsche and Jørgensen suggested that allowing public access to unpublished trial data would benefit public health and that regulators should promote access to full information. Although the British Medical Journal article focused on the lack of transparency for drugs targeted for an adult population, the current push from the EMA is for data from clinical trials in pediatric populations. Enforcement of regulations pertaining to data from adult-oriented clinical trials will start in the next year or two.7 Accompanying the European Clinical Trials Directive are a number of corresponding regulations regarding the disclosure of clinical trial information: Article 57 of Regulation (EC) No. 726/2004,8 which pertains to clinical trials in adults; Article 41 of Regulation (EC) No. 1901/2006,9 which pertains to clinical trials in pediatric populations; and Article 45 of Regulation No. 1901/2006,10 which required pharmaceutical and medical device companies to submit to the EMA a “line listing” of clinical trials completed in children as of January 2008. 2011 First Clinical Research and the Author(s) Figure 1. Minimum Data Requirements
for Pediatric Clinical Trial Results in
Spreadsheet Submission
 A spreadsheet containing trial result  A synopsis in accordance with the ICH Participants of the trial: Inclusion criteria Participants of the trial: Exclusion criteria All pediatric clinical trial results data for nationally and EMA (“centrally authorized”) active substances will become available to the general public through the EMA's website as part of an interim publication before the release of the results database (EudraCT Version 9), which might occur in late 2012. The EMA will not validate the results-related responsibility of the marketing authorization nationally authorized products. For further (konstantina.makrogianneli@ema.europa.eu). Conclusion
Industry and academia had been waiting for EMA to provide guidance on the format of
clinical trial results submissions. The EMA has now provided this guidance but has given
industry and academia less than four months to submit the data, creating a resource challenge, to say the least. Although identification of most pediatric trials conducted in the European Community should be accounted for in the 2008 line listings already submitted to the EMA, sponsors should immediately identify both adult trial results and post-2008 pediatric trial results for submission to the EMA clinical trial results database. References
1. Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12
December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004. Off J Eur Union. 2006;378:1-19. 2011 First Clinical Research and the Author(s) 2. Gøtzsche PC, Jørgensen AW. Opening up data at the European Medicines Agency. BMJ 3. European Commission. Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Off J Eur Commun. 4. Gøtzsche PC, Jørgensen AW. Opening up data at the European Medicines Agency. BMJ 5. Christensen R, Kristensen PK, Bartels EM, Bliddal H, Astrup A. Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials. Lancet. 6. Letter from Public Citizen to Margaret Hamburg, MD, Commissioner of the United States Food and Drug Administration. April 14, 2011. http://www.citizen.org/documents/1942.pdf. 7. Sweeney F. European Medicines Agency. Presentation at the European Drug Information Association Clinical Trials Registry conference. May 23-24, 2011. Basel, CH. 8. European Commission. Communication from the commission regarding the guideline on the data fields contained in the clinical trials database provided for in Article 11 of Directive 2001/20/EC to be included in the database on medicinal products provided for in Article 57 of Regulation (EC) No 726/2004 (2008/C 168/ 02). Off J Eur Union. 2008;51:3–4. 9. European Commission. Communication from the commission—guidance on the information concerning paediatric clinical trials to be entered into the EU Database on Clinical Trials (EudraCT) and on the information to be made public by the European Medicines Agency (EMEA), in accordance with Article 41 of Regulation (EC) No 1901/2006. Off J Eur Union. 2009;28:1–4. 10. Regulation (EC) No 1901/2006 of the European Parliament and of the Council of 12 December 2006 on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004. Off J Eur Union. 2006;378:1-19. Author
Barbara Godlew is a Director with Huron Life Sciences. Contact her at 1.312.880.0451 or
2011 First Clinical Research and the Author(s)

Source: http://firstclinical.com/journal/2011/1108_EMA_Pediatric.pdf